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These guidelines set out the practice within the Intellectual Property Office as it relates to patent applications for medical inventions. The relevant legislation is the Patents Act 1977, as amended by subsequent legislation, and the Patents Rules 2007. The interpretation of this legislation has been informed by case law in the UK courts. It has also reflected the fact that judicial notice must be taken of international conventions (such as the European Patent Convention) and of decisions and opinions made under these conventions by the appropriate bodies. Accordingly, decisions taken by the UK courts relating to the 1977 Patents Act are binding on our practice, whilst EPO Board of Appeal decisions are strongly persuasive. UK court decisions under previous legislation may also be persuasive, depending on the extent to which that aspect of patent law had been changed by the 1977 Act. Existing Office practice, as set out in the Manual of Patent Practice (MoPP) and in decisions taken in Office hearings, has not been changed without good reason.

2.

The Patents Act 2004, which received royal assent on 22 July 2004, amended the Patents Act 1977 in respect of medical inventions, to implement the European Patent Convention as revised in 2000 (EPC 2000). The Convention (and therefore the medical provisions of the Patents Act 2004) took effect on 13 December 2007. The Patents Act 2004 introduced a new Section 4A to the 1977 Act which states in Section 4A(1) that the invention of a method of treatment of the human or animal body by surgery or therapy, or a method of diagnosis practised on the human or animal body, is not patentable. This replaced the former Section 4(2), and thereby removed the “legal fiction” that such methods lack industrial application – they are regarded as unpatentable in their own right.

3.

In addition, Section 4A states that patents may be granted for a known substance or composition for use in medicine (Section 4A(3)), or for a specific medical use (Section 4A(4)). These provisions therefore explicitly allow patent protection for the first medical use of a known substance or composition (as previously, under the former Section 2(6)) and a second or further medical use. Prior to 13 December 2007, inventions relating to second medical uses could only be protected using the “Swiss-type” claim form of “the use of substance X for the manufacture of a medicament to treat disease Y”. Section 4A(4) allows a simpler and more direct second medical use claim, of the form “substance X for use in the treatment of disease Y”. Following the issue of a Practice Notice on second medical use claims on 26 May 2010, inventions relating to second medical uses may only be protected this way; the Office no longer accepts “Swiss-type” claims ().

4.

It is very important to note that the changes introduced by the Patents Act 2004 have not led to any substantive change in what is and is not patentable in this field. Previous case law under the repealed Section 4(2) (or the equivalent Article 54(2) of the EPC) relating to the exclusions of methods of treatment by surgery or therapy, or methods of diagnosis practised on the human or animal body, continues to govern our practice under Section 4A(1). Similarly, case law relating to first medical use under the repealed Section 2(6) (or the equivalent Article 54(5) of the EPC) governs our practice under Section 4A(3). Moreover, the body of case law relating to Swiss-type second medical use claims remains relevant to our practice in relation to the current form of second medical use claim under Section 4A(4). Throughout these Guidelines, reference is made to decisions under the law as it stood before 13 December 2007; these decisions (other than where explicitly noted) are considered to be directly relevant to the law under the amended Patents Act.

5.

Any comments or questions arising from these Guidelines should be addressed to: Vanessa Luu [email protected] or Sophie Brown [email protected] Intellectual Property Office

Intellectual Property Office Concept House Cardiff Road Newport South Wales NP10 8QQ

Basic principles

6.

Patent applications in the medical field must meet the same requirements as applications in all other fields of technology; that is, they must be new, inventive and capable of industrial application, and the claims must clearly define the scope of the invention and be supported by the description. The invention must not fall wholly within the excluded categories defined in Section 1(2), and its commercial exploitation must not be contrary to public policy or morality.

7.

In addition, patenting in the medical field is constrained by the exclusion from patentability of methods of treatment of the human or animal body by therapy or surgery, or methods of diagnosis performed on the human or animal body, under Section 4A(1) of the Patents Act 1977 (as amended), which states that such methods are not patentable. This exclusion applies only to methods of treatment and diagnosis and not to the materials used in such methods, as explicitly stated in Section 4A(2).

8.

In addition, the definition of novelty for substances or compositions used in methods of treatment is addressed by Sections 4A(3) and (4). Section 4A(3) states that a substance or composition which is itself already known is regarded as novel “for use in” any method of treatment or diagnosis prohibited by Section 4A(1), provided that the substance or composition has not been known to be used in any such method before (“first medical use”). Section 4A(4) states that a substance or composition for a specific use in any such prohibited method is regarded as novel, provided that the substance or composition has not been known for that specific use before (“second medical use”).

9.

Much of the case law relating to patenting in the medical field has focussed on boundaries between, on the one hand, the exclusion of methods of treatment from patents, and on the other hand the patentability of the materials used in such treatments, and in particular the first or subsequent medical uses of substances or compositions.

“[The exclusion] has the limited purpose of ensuring that the actual use, by practitioners, of methods of medical treatment when treating patients should not be the subject of restraint or restriction by patent monopolies. The difficulty is to decide whether the restraint concerns a method of treatment as opposed to that which is available for treatment”.

Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414 [2001] RPC 1 (Court of Appeal)

10.

There are an increasing number of patent applications in the medical field which relate to the use of biotechnological inventions for medical purposes, for example through gene therapy. Any such applications will also need to meet the requirements of Schedule A2 to the Act. The Examination Guidelines for Patent Applications relating to Biotechnological Inventions in the Intellectual Property Office set out the practice of the UK Intellectual Property Office in these areas. There are also an increasing number of patent applications which include the use of Artificial Intelligence. Guidance on our practice, as well as practical illustration in the form of several scenarios, are set out by Examining patent applications relating to artificial intelligence (AI) inventions. Scenario 6 is of particular relevance to these Medical Guidelines. Our practice in relation to chemical inventions, including those relating to pharmaceuticals, is set out in the Examination Guidelines for Patent Applications relating to Chemical Inventions in the Intellectual Property Office.

Methods of treatment or diagnosis

11.

Methods of treatment by therapy or surgery or methods of diagnosis performed directly on the human or animal body are unpatentable, as set out in Section 4A(1) of the Patents Act 1977 (as amended):

“A patent shall not be granted for the invention of-

(a) a method of treatment of the human or animal body by surgery or therapy, or

(b) a method of diagnosis practised on the human or animal body.”

Section 4A(1) of the Patents Act 1977 (as amended by the Patents Act 2004)

12.

Section 4A(1) replaced the previous Section 4(2), now repealed, which stated that such methods “shall not be taken to be capable of industrial application”. Similarly, the equivalent Article 53(c) of the EPC 2000 replaced the repealed Article 52(4), which also related to industrial application. It had been clearly stated that the purpose of Section 4(2) (and Article 52(4)) was to prevent medical or veterinary practitioners being restrained or hampered in their practice by patent legislation.

13.

The exclusion of medical methods on grounds of lack of industrial applicability under Section 4(2) was therefore a “legal fiction” designed to achieve a public policy objective, as medical and veterinary activities are clearly industries. Section 4A(1) removes this legal fiction and simply states that these methods cannot be patented.

14.

Section 4A(1) does not prevent the patenting of materials or compositions used in such methods, as explicitly stated in Section 4A(2):

Subsection (1) above does not apply to an invention consisting of a substance or composition for use in any such method.

Section 4A(2) of the Patents Act 1977 (as amended by the Patents Act 2004)

This replaced the repealed Section 4(3), which stated that substances and compositions for use in medical and veterinary methods are capable of industrial application.

15.

Not all methods of treatments of the human or animal body are excluded; only those that fall within the scope of the terms “therapy” or “surgery”. In addition, claims to methods of diagnosis are only objectionable if they are performed directly on the human or animal body. This is discussed in more detail in the subsequent sections.

Therapy

Definition of “therapy”

16.

The definition of therapy used by both the UK courts (Unilever (Davis’s) Application [1983] RPC 219) and the EPO (T 19/86 (Pigs II)) includes both treatments to cure or prevent disease, and so methods of, for example, vaccination of healthy individuals are considered to be methods of treatment by therapy and thus unpatentable. In Unilever (Davis’s) Application it was stated that therapy should be construed as the medical treatment of disease, including preventative treatment as well as curative treatment. Moreover, therapy encompasses methods of alleviating symptoms as well as curative treatments for a disease (T 81/84 (Dysmenorrhea)), Schultz’s Application BL O/174/86, and T 1599/09 COVIDIEN). In deciding whether a treatment can be considered to be “therapy”, the broad definition applied by the EPO in T 24/91 (Cornea) and T 58/87 (Pigs III) should be used:

“…any treatment which is designed to cure, alleviate, remove or lessen the symptoms of, or prevent or reduce the possibility of contracting any disorder or malfunction of the animal body”

T 24/91 (Cornea)

17.

Veterinary treatment of a diseased or injured animal is regarded as therapy and it was pointed out in Unilever (Davis’s) Application [1983] RPC 21 (at pages 229-230) that therapy cannot have a different meaning for humans and animals. Similarly, the EPO Board of Appeal in T 116/85 (Pigs I) held that therapeutic methods practised on farm animals are not patentable, and this applies regardless of who performs the method.

Therapeutic methods: form of claims

18.

The following formats of claim are all considered to define methods of treatment by therapy, and are thus unpatentable under Section 4A(1):

9. The treatment of (medical condition Y) with (substance X).

ii) The use of (substance X) to treat (medical condition Y).

iii) (Substance X) when used to treat (medical condition Y).

iv) The use of (substance X) as a pharmaceutical.

In G 05/83 (Second medical indication), the Enlarged Board of Appeal of the EPO decided that claims to “the use of X to treat Y” were indistinguishable from claims to “the treatment of Y with X”, and this was upheld by the Patents Court in John Wyeth’s and Schering’s Applications [1985] RPC 545. These cases established that “Swiss-type” second medical use claims of the format “the use of X in manufacture of a medicament to treat Y” were acceptable. However, since the implementation of the medical provisions of the Patents Act 2004, second medical use inventions can be protected by claims of the form “substance X for use in the treatment of disease Y”, and following the decision of the EPO Enlarged Board of Appeal in G 02/08 (Dosage regime/ABBOTT RESPIRATORY) and the release of our Practice Notice on 26 May 2010, “Swiss-type” claims are no longer allowable (see below, ).

19.

A claim to the use of a substance “as a pharmaceutical” (claim (iv) above) is interpreted as a method claim to the use of the substance in therapeutic treatment, rather than simply a claim to its use in a pharmaceutical formulation. This is in accordance with the general rules for construction of claims in this format, as described in . Where appropriate, amendment to acceptable first or second medical use claims should be sought for claims of this type. The use of a substance as an adjuvant or immunostimulant may be acceptable if restricted to non-therapeutic uses, as adjuvants are often used to produce antibodies in animals for experimental use, as well as in therapy.

Guidelines for determining whether a method is “treatment by therapy”

20.

It is useful to consider whether the method would normally be carried out by a medical professional such as a doctor or vet. Section 4A(1) is intended to prevent medical or veterinary practitioners being restrained or hampered in exercising their professional skills by patent rights, and so a claimed method which does not impact on a practitioner’s medical discretion is likely to fall outside the scope of Section 4A(1) T 245/87 (Flow measurement) and T 426/89 (Pacemaker). This principle was also applied (in relation to both therapy and surgery) in Virulite’s Application BL O/058/10, where the Hearing Officer held that the “fundamental test” for inventions in this field is whether the patent, if granted, would interfere with the work of a medical or veterinary practitioner in their treatment of patients. A method in which a laser was used to modify a synthetic lenticule implanted on the cornea, on the other hand, was considered to be unpatentable, in part because it would be performed by or under the supervision of a medical practitioner due to the health risks concerned (T 24/91 (Cornea)).

“The intention underlying [Article 52(4)] is to ensure that nobody who wants to use the methods specified in this Article as part of the medical treatment of humans or animals should be prevented from this by patents. Such medical treatments need not necessarily be carried out by physicians…However, where, in view of the health risks connected with such a treatment, a claimed method of treatment has to be performed by a physician or under his supervision, it will normally fall within the exclusion…”

T 24/91 (Cornea)

21.

However, this consideration is not decisive, and the purpose and inevitable effect of the invention are more important. If a method has no therapeutic purpose or effect (for example in methods for collecting bodily fluids for analysis etc), then the fact that it may be carried out by a doctor does not render it unpatentable (T 329/94 (Blood extraction method) and T 1165/97 (Feminine hygiene device/ULTRAFEM INC.). Conversely, methods for treating diseases in farm animals are excluded, even if the method may routinely be carried out by the farmer rather than the vet.

“…if a claimed method requires the treatment of an animal body by therapy, it is a method which falls within the prohibition on patentability set out in Article 52(4) EPC. It is not possible as a matter of law to draw a distinction between such a method as carried out by a farmer and the same method as carried out by a veterinarian, and to say that the method when carried out by a farmer is an industrial activity and therefore patentable… and when carried out by a veterinarian is a therapeutic treatment not patentable under Article 52(4)”.

T 116/85 (Pigs I)

Furthermore, the fact that a method may be carried out by patients on themselves does not render a therapeutic method patentable (T 1599/09 COVIDIEN). This is consistent with the view of the Enlarged Board of Appeal in G 01/07 (Treatment by surgery/MEDI-PHYSICS) that the exclusions under Art.53(c) EPC (and therefore s.4A(1)) are not solely limited to methods which might hinder a doctor or vet in their practice:

“There is, however, no term in Article 53(c) EPC which would allow concluding that hampering of the practitioner’s freedom is a prerequisite for the exclusion to apply in the individual case considered. The only condition defined in Article 53(c) EPC for a claim to be excluded from patentability is that it contains subject-matter being a method for treatment of the human or animal body by surgery or therapy or a diagnostic method.”

G 01/07 (Treatment by surgery/MEDI-PHYSICS)

In view of this clear statement from the Enlarged Board of Appeal, the question of whether a claimed method would hamper a medical or veterinary practitioner’s freedom can only be considered an important guide in determining whether a method is excluded under s.4A(1), rather than a “fundamental test” as suggested in Virulite’s Application BL O/058/10.

22.

Although both prevention and cure of diseases are considered to be therapeutic, there must be a direct link between the treatment and the condition to be treated or prevented. Methods of hygiene are not considered therapeutic even though they may result in a reduced incidence of infection, except for certain methods of oral care . In Commonwealth Scientific & Industrial Research Organization’s Application BL O/248/04, the Hearing Officer held that a method for the destruction of wool follicles in the skin of a wool-bearing animal was not directly linked to a disease state to be cured or prevented, even though it could have the indirect effect of reducing parasite infestation. In addition, methods of sterilising non-living surfaces (such as surgical devices) are not considered to be methods of treatment by therapy. In T 611/09 ASH ACCESS TECHNOLOGY the use of an anti-bacterial citrate solution inside a catheter was not considered to constitute a method of treatment by therapy as - even when the catheter was inserted - the citrate could not exert its anti-bacterial effect in the patient’s body, as the citrate would be inactivated on contact with blood.

23.

The Board of Appeal in T 699/12 NILSSON distinguished between methods that are therapeutic or surgical treatments of the body, and methods that are used in therapeutic or surgical treatments - it is only the former that are excluded. In this case, a method of verifying and quantitating the dose delivered to a patient in radiotherapy was allowed, on the grounds that the quantitation of the dose had no therapeutic effects in itself, and did not have any direct impact on the dose received by the patient; the medical practitioner would be free to choose what to do with the information obtained in this way.

Claims to both therapeutic and non-therapeutic methods

24.

There are many instances where claims may potentially include within their scope both patentable and non-patentable methods. For example, a claim to “a method for inhibiting the coagulation of blood by contacting the blood with a carrier containing compounds X and Y” could include a method of treating the blood in a patient as part of a therapeutic method (not patentable), and also a method of treating stored blood in a bottle (patentable). In cases where it is unambiguously clear from the specification that the claims relate only to patentable methods, then no amendment is required.

25.

If it is apparent from the specification that the claims could cover non-patentable embodiments of the method then amendment is required to clearly limit the claim to methods which are patentable, and if necessary to amend the description to clarify that therapeutic methods do not form part of the invention.

26.

The EPO Enlarged Board of Appeal in G 01/03 (Disclaimer/PPG) considered whether, and under what circumstances, an “undisclosed disclaimer” - that is, one where neither the disclaimer nor the subject matter excluded by it were disclosed in the application as filed - may be allowable. The Enlarged Board held that an undisclosed disclaimer to exclude unpatentable subject material, including methods of treatment by therapy or surgery, or methods of diagnosis practised on the human or animal body, is in principle allowable and does not necessarily constitute added matter. This principle was applied in the specific medical context by the Enlarged Board in (G 01/07 (Treatment by surgery/MEDI-PHYSICS) and subsequent decisions T 385/09 LELY ENTERPRISES and T 266/07 (WISCONSIN ALUMNI RESEARCH FOUNDATION). The Enlarged Board’s later decision in G 02/10 (Disclaimer/SCRIPPS) confirmed that the subject matter remaining in the claim after the introduction of the disclaimer must be disclosed in the application as filed, whether or not the disclaimer itself is disclosed in the application. This is in accordance with UK Office practice, which is explained in more detail in . Therefore if claims are limited, either by disclaimer or otherwise, to patentable methods, there must be support in the description for a non-therapeutic method - if there is not, then the amended claim will constitute added matter, as well as being objectionable through lack of support. In ICI (Richardson’s) Application [1981] FSR 609 a claim was made to a method of producing an anti-oestrogenic effect in a human, but excluding any method of treatment by therapy. It was considered that the specification did not describe any application of the method other than in the treatment of breast cancer or infertility, and so the claim was rejected. The words “cosmetic” or “non-therapeutic” in a claim to a method of treatment are generally acceptable as sufficient limitation (T 36/83 (Thenoyl peroxide)); the use of the phrase “preimplanted”, to disclaim a surgical method step in an otherwise patentable method, is also allowable G 01/07 (Treatment by surgery/MEDI-PHYSICS). Of course, if a claim is amended to “cosmetic methods”, there must be disclosure of such methods in the application as filed. If there is not, then the amended claim will constitute added matter, as well as being objectionable through lack of support. Any disclaimer needs to exclude therapeutic methods and leave the scope of the remaining monopoly clear. A disclaimer which merely uses the words of the Act is considered to leave the scope of the monopoly unclear (ICI (Richardson’s) Application).

27.

Moreover, it must be possible to distinguish the therapeutic and non-therapeutic effects of a claimed method. If the non-therapeutic effect is inseparable from the therapeutic effect, or if it is merely a secondary consequence of the therapy, then the invention is unpatentable, regardless of the wording used. For example, it has been held in both the UK courts and the EPO that it is not possible to claim a cosmetic method for the removal of plaque from teeth, as such a method will inevitably have therapeutic benefits in preventing tooth decay and gum disease.

“…the claimed use of a lanthanum-containing composition for cleaning plaque and/or stains from human teeth…will always inevitably have a therapeutic effect (at least in the prophylactic sense) as well as a cosmetic effect. Thus the invention as here claimed is not directed solely to a cosmetic effect, but is also necessarily defining ‘a treatment of the human body by therapy’ as well”

T 290/86 (Cleaning plaque)

The EPO Technical Boards of Appeal have applied these criteria in, for example, T 1680/08 BÖHM, where it was held that a method of optimising an artificial respiration system (performed while the system was in use) was inextricably linked to the therapeutic use of the respiration system in keeping the patient alive, and so the claim was not allowable.

28.

On the other hand, if the effects are separable, then the existence of a possible therapeutic use should not prevent a cosmetic or other non-therapeutic method from being patentable. For example, a treatment may be therapeutic or cosmetic depending on the subject being treated. This distinction was accepted in the case of an appetite suppressant (T 144/83 (Appetite suppressant)) and an antibacterial skin treatment (T 36/83 (Thenoyl peroxide)). Similarly, in T 1916/19 UNILEVER , the Board of Appeal found that non-therapeutic methods of “providing an anti-microbial effect to skin” could be separated from therapeutic prophylactic treatments, in view of the patent’s demonstration of clearly cosmetic realisations (e.g., removing non-pathogenic bacteria responsible for body odour, such as through applying a deodorant composition). A distinction between therapeutic and non-therapeutic uses of the same method was also made in T 584/88 (Anti-snoring means/REICHART), wherein a treatment of snoring was regarded as either therapeutic in cases where the snoring was harmful to health, or non-therapeutic if the snoring was merely troublesome. In this case it was accepted that it was difficult to draw a precise boundary between harmful or merely troublesome snoring, but this did not prevent a method claim from being accepted for the latter (and a second medical use claim for the former).

29.

The way these general principles have been applied by the courts and the EPO Boards of Appeal to specific, contentious areas is discussed below.

Therapeutic and non-therapeutic methods: specific examples

i) Cosmetic treatments

30.

Purely cosmetic treatments of the skin and hair are patentable. These may include cosmetic methods of strengthening hair and nails (following Joos v. Commissioner of Patents [1973] RPC 59), and cosmetic methods to prevent hair loss (T 453/95 REDKEN). In Virulite’s Application BL O/058/10 the Hearing Officer observed that the removal of wrinkles caused by ageing had no conceivable therapeutic benefit, and so a cosmetic method claim for removing wrinkles by phototherapy was allowed. Methods of protecting the skin by simply blocking UV radiation are not considered to be therapy, but where a method includes physiological protective effects against UV-associated damage then it is considered to be therapeutic (T 1077/93 L’OREAL /Protection against UV [1997] EPOR 546). In this case the Technical Board decided that the cosmetic and therapeutic aspects of the claimed method of protecting skin were “inevitably linked, such that each one necessarily develops together with the other and such that it is impossible to separate them”. The argument that the treatment was effectively directed towards natural ageing of the skin, and was therefore not therapeutic, was rejected on the grounds that “a natural process of cell degeneration loses its physiological normality when it develops in an abnormal manner, and in particular faster than its normal process”. A similar view was taken by the Board of Appeal in T 67/02 BEIERSDORF, wherein a “non-therapeutic” method of prevention of skin ageing was held (on the facts of the case) to be inseparable from therapeutic effects acting on the skin. In the same case however, the use of the same agent to protect the lips (eg. from sunburn) was held to be a purely cosmetic application with no therapeutic benefit. The use of a composition for the local treatment of comedones (blackheads) was regarded as a cosmetic method of non medical body hygiene, although when applied for the treatment of acne this would be regarded as therapeutic (T 36/83 (Thenoyl peroxide)).

ii) Removal of parasites

31.

Methods of treating or preventing infestation of internal parasites are regarded as therapy; the argument that the host animal is unaffected and that it is only the parasites that are being killed and that therefore this is not therapy of the animal body, has been rejected (Ciba-Geigy’s Application BL O/35/85). Treatment of parasites residing on the skin of a human or animal is considered to be therapy (T 116/85 (Pigs I)). The Board of Appeal in this decision explicitly rejected the view that a treatment of an ectoparasite infection was therapeutic in the case of “permanent” ectoparasites residing in the skin, and not in the case of “temporary” ectoparasites residing on the skin. Treatment of, for example, head lice, is therefore considered therapeutic, despite the decision made under the 1949 Act in Stafford-Miller’s Application [1984] FSR 258.

32.

However, the procedure must be directly related to the treatment or prevention of parasite infestation to be excluded. A procedure to remove hairs from the skin of an animal, which had the indirect effect of reducing the incidence of blowfly strike, was held to be non-therapeutic (Commonwealth Scientific & Industrial Research Organization’s Application BL O/248/04).

iii) Oral care

33.

While methods of hygiene are generally regarded as non-therapeutic, methods for the removal of dental plaque, or preventing the formation of plaque are considered to be therapeutic and thus unpatentable. All such methods have the direct effect of treating or preventing dental caries, and have been refused on these grounds under the 1949 Act (Oral Health Products (Halstead’s) Application [1977] RPC 612 and Lee Pharmaceuticals’ Applications [1975] RPC 51) and under the previous Section 4(2) of the 1977 Act (ICI Ltd’s Application BL O/73/82). In EPO decision T 290/86 (Cleaning plaque) it was found that the inherent therapeutic effect of removing plaque could not be separated from the purely cosmetic effect of improved appearance of the teeth, and so restriction of such a claim to a cosmetic method is not possible. On the other hand, “treatment of halitosis” was not considered to be a method of treatment by therapy, as it could only in extreme cases be considered a disease (T 675/11 COLGATE-PALMOLIVE).

iv) Pain, fatigue and addiction

34.

The relief of pain is considered to be therapeutic, even where the pain has no pathological cause:

“Irrespective of the origin of pain, discomfort or incapacity, its relief, by the administration of an appropriate agent, is to be construed as ‘therapy’…”

T 81/84 (Dysmenorrhea)

35.

However, in T 385/09 LELY ENTERPRISES the Board of Appeal rejected the argument that any alleviation of discomfort is by definition therapeutic - in this case a claim to a non-therapeutic method of cooling farm animals (for example, to encourage them to enter a milking stall) was allowed. In addition, in T 469/94 MIT it was held that a method of reducing the perception of fatigue (for example, following exercise) was not comparable with the relief of pain, discomfort or incapacity, and could be considered to be non-therapeutic when carried out on healthy individuals, although there were clearly therapeutic uses of the treatment as well. In contrast, treatment of symptoms of biorhythm desynchronisation (e.g. from jet lag) was held to be necessarily therapeutic and a claimed method of non-therapeutic treatment of such symptoms was refused (T 767/12 SUNTORY).

36.

Methods of treatment of addiction or withdrawal symptoms, including methods to help stop smoking, are considered to be therapeutic.

v) Obesity, weight reduction and fitness

37.

Methods of weight reduction for purely cosmetic reasons, including the suppression of appetite, are patentable. In T 144/83 (Appetite suppressant) a claim to a “method of improving the bodily appearance of a non-opiate-addicted mammal” was considered allowed insofar as it related to cosmetic weight loss only. It was recognised that the method could also be used for therapeutic effects such as the treatment of obesity. Claims to such methods therefore need to clearly relate to cosmetic weight loss only. Similarly, a method for “enhancing skeletal muscle performance of normal healthy subjects” was considered to be non-therapeutic by virtue of its limitation to healthy subjects (T 1230/05 BIOENERGY).

vi) Contraception, abortion and fertility treatment

38.

Claims to methods of abortion, termination of pregnancy or induction of labour are considered to be unpatentable treatments, as they will always be carried out under medical supervision (see UpJohn (Kirton’s) Application [1976] RPC 324 - 1949 Act). This applies regardless of the reasons for performing these methods.

39.

Methods of contraception are not considered to be therapeutic, and may be patented (following the decision under the 1949 Act in Schering’s Application [1971] RPC 337). Pregnancy is not an illness or disorder, and so its prevention is not regarded as therapy. This has been confirmed in decisions of the EPO Boards of Appeal T 820/92 (Contraceptive method) and T 74/93 (Contraceptive method). However, contraceptive methods are excluded under Section 4A(1) if they contain a therapeutic element (T 820/92). In T 1635/09 (Composition contraceptive/BAYER SCHERING PHARMA AG), this principle was applied to a low dosage contraceptive, on the grounds that the improvement over the prior art was in the reduction of side effects, rather than any increase in efficacy, and the claim was refused as being a method of treatment by therapy. However, unlike in T 820/92, it was not alleged that any element of the composition served to actively reduce the side-effects; instead, the lower dosage resulted in reduced side effects compared to the prior art. This would appear to be simply a safer way of carrying out a non-therapeutic contraceptive method, and so we would not follow this approach. Methods of contraception are not considered to lack industrial application merely because they are for “private and personal use”. The private use of such a method would not constitute an infringement of a patent according to Section 60(5) of the Patents Act 1977, and so a patent to such a method is allowable (notwithstanding the EPO decision in T 74/93).

40.

Methods of treatment of infertility, including methods utilising in vitro fertilisation, are considered to be therapeutic. Moreover, the implantation of an in vitro fertilised embryo would, in most cases at least, be considered to be a surgical process and thus not patentable (as was the case in Occidental Petroleum’s Application BL O/35/84). In addition, the implantation of a human embryo would constitute a “commercial or industrial use” of such an embryo, and so would be unpatentable under Schedule A2 of the Patents Act.

vii) Methods concerning technical operation of technical devices

41.

If a claimed method produces or directly influences a therapeutic effect then it is unpatentable under Section 4A(1) even if the method is defined only in relation to a non-living technical object, such as an implanted device or a therapeutic treatment system. A method of operating a pacemaker in which its output to the heart was adjusted was rejected as being a method of treatment by therapy in T 82/93 (Cardiac pacing) because there was a functional link between the claimed method and the effects produced on the body by the device. The applicant’s argument that this was a “technical operation performed on a technical object” was considered to be irrelevant. On the other hand, a method of controlling the input energy to a pacemaker, which had the effect of minimising the energy requirements of the device but did not affect the output to the heart was accepted (T 789/96 (Therapeutic method/ELA MEDICAL)). Similarly, methods for measuring drug flow from an implant (T 245/87 (Flow measurement)), detecting downstream occlusion of a syringe pump (T 44/12 SMITHS MEDICAL ASD), and measuring delivered radiotherapy doses (T 699/12 NILSSON) were all held to be non-therapeutic – in each case, there was no “functional link” because the method would not control or directly influence the therapeutic dose delivery. In contrast, a data processing method for monitoring delivery of radiotherapy was considered a treatment method because, even though only passive computer-implemented monitoring steps were claimed, the disclosure as a whole taught that the purpose of the monitoring process was for automatically controlling patient positioning during dose delivery, so that the control of treatment delivery was considered essential to the invention and consequently could not be disclaimed (T 944/15 BRAINLAB). A method of calibrating an artificial ventilator during use on a patient was held to be treatment by therapy because the calibration involved adjusting airway pressure, thus directly influencing the artificial ventilation being delivered during calibration (T 1680/08 BÖHM). While these examples involve therapy, the same principle applies to surgery .

viii) Treatments performed outside the body

42.

A therapeutic treatment of the human or animal body is unpatentable under Section 4A(1) even if the actual treatment takes place outside the body, as in an extracorporeal blood dialysis or filtration method (Calmic Engineering’s Application [1973] RPC 684 -1949 Act - and Schultz’s Application BL O/174/86). In the latter case it was observed that the words “practised on the human or animal body” relate only to methods of diagnosis, and not methods of treatment by therapy or surgery. Similarly, the addition of anticoagulants in an ex vivo blood processing system, and the ex vivo removal of immunoglobulins using a binding agent, wherein the blood was returned to the patient were considered to be therapeutic by the EPO in T 1075/06 FENWAL and T 2003/08 EDWARDS LIFESCIENCES respectively. However, methods of treating blood removed from the body are only regarded as therapeutic where the method includes - explicitly or implicitly - the return of the blood to the patient. In particular, if the blood is returned to the same body in a continuous or “closed loop” process then the method will be regarded as therapeutic, whether or not the claim explicitly includes the re-infusion step. Where the blood treatment is separated from the subsequent use of the blood - for example where it is stored for use in treating another patient, or the same patient at later date, it may be patentable (T 144/04 ARUBA INTERNATIONAL). In addition, a method of preparing a dialysis solution which was carried out “on line” (i.e. while the patient was connected to the dialysis system) was not considered therapeutic as the solution in question did not ever come into contact with the patient’s blood - it was merely a component of the dialysis solution (T 794/06 GAMBRO LUNDIA).

ix) Treatment of stock animals

43.

The treatment of stock animals in order to improve their meat or other products, eg. milk yields, or to improve their growth by administration of substances or compositions in their food is not regarded as therapy, even if the substances concerned may have therapeutic benefits. However, where an increase in meat yield or other industrial benefit is merely an inevitable consequence of improved health through therapeutic treatment, then such a method is unpatentable. Claims have been rejected for this reason to methods involving general immunostimulation (T 780/89 (Immunostimulant)) or through a specific effect on a pathogen (T 438/91 MEIJI/Feeds [1999] EPOR 333).

44.

On the other hand, a claim to the non-therapeutic use of antibiotics may be acceptable if the effect on meat or milk production is not a mere consequence of improved health. The test used in T 774/89 (Efomycine als Leistungsförderer/BAYER) was that a non-therapeutic method would be expected to show an improvement on the normal condition of the subject, rather than merely restoring an animal to a normal, healthy condition. In such cases, the non-therapeutic effects must be distinguishable from the therapeutic benefit, and any therapeutic methods must be specifically disclaimed (see above).

Surgery

45.

Decisions of the UK courts, Intellectual Property Office Hearing Officers and EPO Boards of Appeal concerning the interpretation of the term “methods of surgery” in section 4A(1) of the Act and Article 53(c) have considered the nature of the procedure in question, its purpose, and by whom the method is carried out.

Methods of surgery: the nature of the procedure

46.

The dictionary (OED) definition of surgery is the treatment of the body by incision or manipulation. It is therefore not limited to cutting the body but includes manipulation such as the setting of broken bones or relocating dislocated joints (sometimes called “closed surgery”), and also dental surgery. Furthermore, in Occidental Petroleum’s Application BL O/35/84, it was observed that a method of implanting an embryo could still be viewed as surgery even if the method did not require incision. Similarly, a method comprising the insertion of devices into the respiratory cavities of the body (without incision) was also considered to be surgical by the EPO (T 05/04 CAMTECH).

47.

In T 35/99 (Pericardial access/GEORGETOWN UNIVERSITY) a very broad interpretation of the term “methods of surgery” was put forward, which included any physical interventions on the body in which maintaining the life and health of the subject was of paramount importance. This was distinguished from those interventions which result in the death of the subject (e.g. slaughter of farm animals or sacrifice of laboratory animals), which are not excluded. This followed the Technical Board of Appeal decision in T 182/90 (Blood flow), which stated that the definition of surgery includes (amongst other things) “endoscopy, puncture, injection, excision and catheterisation”. However, the Enlarged Board of Appeal in G 01/07 (Treatment by surgery/MEDI-PHYSICS) held that such a broad interpretation of “method of surgery” was unjustifiable, given the advances in medical techniques. Although the Enlarged Board did not provide an authoritative definition of the term “methods of surgery”, it did state that a method should be excluded if it constitutes a substantial physical intervention, which entails a significant health risk even when carried out by a medical professional, and subsequent Technical Board of Appeal decisions have followed this approach.

“A … method … which comprises or encompasses an invasive step representing a substantial physical intervention on the body which requires professional medical expertise to be carried out and which entails a substantial health risk even when carried out with the required professional care and expertise, is excluded from patentability as a method for treatment of the human or animal body by surgery pursuant to Article 53(c) EPC”

G 01/07 (Treatment by surgery/MEDI-PHYSICS)

48.

Therefore, in deciding whether a claimed method is objectionable under s.4A(1) on the grounds that it is a method of surgery, examiners should be satisfied that the method is invasive, requires professional skill and carried a potential risk. For example, a simple injection method, either for taking a small blood sample or introducing a composition would not be regarded as a method of surgery, as it would involve relatively low levels of technical expertise. A dental method of gum retraction (before taking a tooth impression for a crown) was held to be non-surgical in view of the low level of health risk involved (T 2699/17 COLTÈNE/WHALEDENT). On the other hand, a method which requires more specialist medical skills or carries a significant risk, such as a lumbar puncture to deliver epidural injections, puncturing veins and extracting significant volumes of blood for blood donation or blood processing (T 1075/06 FENWAL and T 1695/07 TRANSONIC SYSTEMS), or injecting material into a space between the prostate and rectum (T 1758/15 INCEPT) is unlikely to be patentable. In deciding whether a claimed method of introducing an agent (such as a pharmaceutical or contrast agent) is surgical in nature, it is the risk of the invasive procedure, and not the risk of any side effects of the agent, that should be considered (G 01/07 (Treatment by surgery/MEDI-PHYSICS)).

49.

Methods which define the implanting or insertion of devices by surgical means are clearly unpatentable – as in the cases considered in Allen’s Application BL O/59/92 and T 05/04 CAMTECH. The same applies for methods which control a surgical device, for example a surgical robot, in a manner which impacts on the body (T 2102/12 INTUITIVE SURGICAL OPERATIONS). However, methods of attaching exoprostheses to the skin using an adhesive were found to be patentable in T 635/08 DOW CORNING FRANCE. Claims to methods involving the internal operation of implanted devices, or the interaction between the implanted device and the operator or external control system, are not objectionable if they do not relate to the implantation of the device, and do not impact on the body. The fact that the device needs to have been implanted by surgical means prior to performing the claimed method does not render the claim unpatentable (T 09/04 KONINKLIJKE PHILIPS ELECTRONICS and T 1102/02 MAQUET CRITICAL CARE). On the other hand, where the claimed method necessarily encompasses a surgical step (even if this step is not explicitly claimed), then it will be objectionable - in T 429/12 DENTAL VISION it was held that a method of producing dental apparatus was unpatentable because the method encompassed an indispensable step of fixing a “reference element” (such as a screw) to the jaw bone by surgical means. Similarly, a method for producing tooth replacement parts using impressions taken from a patient’s teeth before and after a temporary surgical rebuild of the damaged area was considered to implicitly include this surgical step, even though it was not explicitly claimed (T 1631/17 MUEHLBAUER TECHNOLOGY).

50.

The Enlarged Board of Appeal in G 01/07 (Treatment by surgery/MEDI-PHYSICS) held that a method (such as an imaging method) which is not itself surgical but is useful for or during surgery, e.g. by allowing a surgeon to make a real-time decision during a surgical intervention, is not an excluded method of surgery. In addition, it was held that the surgical method exclusion could, in principle, be avoided by omitting the surgical step from a claim, for example by use of a disclaimer. Nevertheless, the claims must adequately define the invention, and so if a surgical step is an essential feature of the invention (rather than being simply a necessary prerequisite) then disclaiming or omitting the surgical step may lead to an objection under s.14(5) (T 1695/07 TRANSONIC SYSTEMS). In T 2102/12 INTUITIVE SURGICAL OPERATIONS it was held that a claimed imaging method was inextricably linked to the “unclaimed” surgical method, and so the claim was considered unclear. In T 1526/17 BRAINLAB, a claimed method of operating a surgical navigation system included a calculation step to be carried out when a bone is pivoted, so that the invasive step of pivoting the bone was held to form an essential part of the claimed method and thus excluded it from patentability as a surgical method. Furthermore, a disclaimer directed to “such uses that comprise or encompass an invasive step representing a substantial physical intervention on the body of a human or an animal which requires professional medical expertise to be carried out and which entail a substantial health risk even when carried out with the required professional care and expertise” (taking the wording from G 01/07) was considered unclear, as it would be require the skilled person to evaluate whether any such use met these conditions and so left the boundaries of the claim uncertain (T 1487/09 BIOLASE). A disclaimer of “any functional link between the [claimed method] and effects produced by the device on the patient’s body” (again based on wording from G 01/07) was similarly found unclear (T 944/15 BRAINLAB).

Methods of surgery: purpose

51.

The definition of surgery used in applying Section 4A(1) relates to the nature of the treatment, and not its purpose. The exclusion of methods of surgery is not limited to therapeutic surgery; methods of surgery for cosmetic purposes, or other non-therapeutic purposes such as sterilisation, are not patentable.

“…surgery can be curative of the disease or diseased conditions, or prophylactic, that is, preventative of diseased conditions, as for example, where an appendix or tonsils may be removed before any diseased condition starts up, and surgery may even be cosmetic without being curative or preventative. So that the subsection it seems to me is saying that any method of surgical treatment, whether it is curative, prophylactic or cosmetic, is not patentable.”

Unilever (Davis’s) Application [1983] RPC 219 (NB remarks on surgery were obiter)

52.

This remains the practice of the Intellectual Property Office with respect to cosmetic surgery, and is also in line with EPO practice following the Enlarged Board’s decision in G 01/07 (Treatment by surgery/MEDI-PHYSICS):

“Hence, the Enlarged Board concludes that the meaning of the term “treatment by surgery” is not to be interpreted as being confined to surgical methods pursuing a therapeutic purpose.”

G 01/07 (Treatment by surgery/MEDI-PHYSICS)

This overturned previous EPO practice as established in the decision by the Technical Board of Appeal in T 383/03 (Hair removal method/THE GENERAL HOSPITAL CORP), where it was decided that the only surgical methods which are excluded from patentability are those potentially suitable for “maintaining and restoring the health, the physical integrity, and the physical well-being of a human being or animal, and to prevent diseases.” In this case, a method of hair removal by optical radiation was held to be surgical in character, but nonetheless patentable as its purpose was purely cosmetic. This type of procedure would not in any case be considered to be surgical in nature under UK Office practice. (Indeed, it is very similar to the procedure in Commonwealth Scientific & Industrial Research Organization’s Application BL O/248/04, in which method claims were granted, although the question of whether this was a surgical method was not considered at the hearing). The EPO Technical Board of Appeal has applied the practice established in G 01/07 in, for example, T 1213/10 SONY. In this case a method of measuring in vivo enzymatic activity which included a surgical step of using a “penetration device” such as an endoscope to introduce a substrate to an organ in the body was excluded as being a method of surgery despite the applicant’s argument that the method was carried out for analytical rather than therapeutic purpose.

Methods of surgery: who carries out the method?

53.

The Enlarged Board in G 01/07 (Treatment by surgery/MEDI-PHYSICS) stated that whether a method is excluded or not as a “method of surgery” cannot depend on who carries it out, not least because of the changing medical roles in healthcare systems. Nevertheless, the Board did consider that the exclusion is intended to cover methods which require professional medical skills, and so the level of medical skill needed to perform a method can be a useful guide in determining whether a method is excluded or not. In general, any operation on the body which requires the skill or knowledge of a surgeon or other medical practitioner is regarded as being surgery, whether or not it is therapeutic. A method of embryo implantation which required the intervention of a surgeon or veterinary surgeon was held to be a surgical method, regardless of its purpose (Occidental Petroleum’s Application BL O/35/84). In this case, it was stated that “if a method requires a surgeon for its execution then it must be surgery.” However, in Allen’s Application BL O/59/92 (which related to a method of inserting implanted markers into the body for NMR or CT scans) it was held that this did not mean that a method which did not necessarily require a surgeon could not be considered to be surgery. A physical intervention which required the medical skills of, for example, a nurse, could still be regarded as surgery. Similarly, methods of dental surgery require specialist dental skills and so are not patentable. If a method does not require medical skills or knowledge, on the other hand, (such as, for example, a method for cosmetic ear-piercing, or a method of tattooing the body) then it would not be excluded as a method of surgery. In T 663/02 PRINCE it was held that tasks which are likely to be delegated or are carried out on such a routine basis as to be thought commonplace, with a low health risk, may be patentable. This case also reinforced the notion that consideration of the surgical aspect is separate from any possible therapeutic effects of what, exactly, is introduced.

54.

Similarly, the setting of bones is carried out by doctors and is considered to be surgical in nature, while making and applying a plaster cast is normally carried out by a technician and would not be regarded as surgery. A method of making a plaster cast would also not be treated as therapeutic, as the therapy resides in holding the bone in position while it heals, and this occurs after the method of making the cast is complete. Methods of making artificial limbs or taking measurements or making casts are therefore not regarded as surgery or therapy.

Methods of surgery: technical operation of technical devices

55.

A method which is only concerned with the operating of a device without any functional link between the claimed method and the effects produced by the device on the body is not excluded as a method of treatment. If, on the contrary, there is such a functional link then the method is excluded from patentability by Section 4A(1). This principle is well established by the EPO Boards of Appeal in the context of therapy (as set out in more detail in above) and in G 01/07 (Treatment by surgery/MEDI-PHYSICS), 134 the Enlarged Board of Appeal applied the same principle in the context of treatment by surgery, confirming also that is immaterial whether the surgery serves a therapeutic purpose.

Diagnosis

Definition of diagnosis

56.

Diagnosis is the determination of the nature of a medical condition, usually by investigating its history, aetiology and symptoms and by applying tests. Diagnosis in itself is an intellectual exercise which is not patentable in view of Section 1(2)(c). Section 4A(1) however relates to methods of diagnosis practised on the human or animal body. Diagnosis includes a negative finding that a particular condition can be ruled out, as well as a positive identification of a disease (T 807/98 ST JUDE). However, determination of the general physical state of an individual (for example, for a fitness test) is not considered to be diagnostic if it is not intended to identify or uncover a pathology.

The meaning of “methods of diagnosis”

57.

Typically, the process of diagnosis involves a number of steps leading towards identification of a condition. The EPO Enlarged Board of Appeal in G 01/04 (Diagnostic methods) characterised these steps as being;

(1) the examination and collection of data;

(2) comparison of the data with normal values;

(3) finding any deviation from the norm; and finally

(4) attributing the deviation to a particular clinical picture.

If a claimed method includes all these steps, and thereby makes it possible to identify a clinical state (e.g. identifying a disorder and/or enabling the doctor to decide on a particular course of treatment), it clearly constitutes a method of diagnosis. (In practice, if the method includes the first measurement step, and the final deductive step, then the intermediate steps may be implied.)

58.

Alternatively, claims may be directed towards methods which are of value in diagnosis, but which do not in isolation enable a full diagnosis to be made. Examples include methods of internal imaging or methods of taking samples for subsequent in vitro analysis. Where a claimed method does not encompass all the steps necessary to enable a diagnosis to be made, then it is not considered to be a “method of diagnosis” and is not excluded from patentability under Section 4A(1). In G 01/04 (Diagnostic methods) the EPO Enlarged Board of Appeal decided that the term “method of diagnosis” should be interpreted narrowly. Only a method which comprises all of the 4 steps listed above, and therefore allows the identification of a pathological condition, falls within this definition.

“The method steps to be carried out prior to making a diagnosis as an intellectual exercise… are related to examination, data gathering and comparison…. If only one of the preceding steps which are constitutive for making such a diagnosis is lacking, there is no diagnostic method, but at best a method of data acquisition or data processing that can be used in a diagnostic method…”

G 01/04 (Diagnostic methods)

59.

This decision led to a significant change in practice in this Office and the EPO. We had adopted a broader definition of a method of diagnosis, based on the decision of the EPO Technical Board of Appeal in T 964/99 (Device and method for sampling of substances using alternating polarity/CYGNUS, INC). In that case it was held that all methods practised on the human or animal body which related to diagnosis or which were of value for the purposes of diagnosis were excluded. Thus, a method of taking a sample from the body for the purpose of medical examination was held to be an unpatentable method of diagnosis. The Enlarged Board in G 01/04 (Diagnostic methods) overturned this interpretation, and instead endorsed a narrower definition more in line with the earlier decision T 385/86 (Non-invasive measurement), relating to a method of determining temperature and pH by magnetic resonance imaging. A method of taking a sample, or determining internal temperature or pH, does not in itself identify a condition, and so it is no longer considered to be a method of diagnosis. This is also consistent with the earlier UK Office practice prior to T 964/99, which followed T 385/86 and the decision under the 1949 Act in Bio-Digital Sciences’ Application [1973] RPC 668.

60.

A method performed on the body which does not enable a disease to be identified, but which may be of value in diagnosis is therefore not excluded under Section 4A(1). For example, a method of imaging using CT scanning (T 09/04 KONINKLIJKE PHILIPS ELECTRONICS), a method of measuring blood glucose (T 330/03 ABBOTT LABORATORIES) and a method of assessing tissue viability by measuring total haemoglobin, oxygen saturation and hydration (T 41/04 NATIONAL RESEARCH COUNCIL OF CANADA) were all considered to provide only intermediate results which did not enable a diagnosis to be made. In Aueon’s Application BL O/248/13 the Hearing Officer held that a method of analysing a sample from a tumour to determine the status of a plurality of markers and using this method to interrogate a database of drug treatment options, to identify and rank drug treatment options, was not a method of diagnosis as it did not include steps (3) and (4) as identified in G 1/04 (though the method would not have been excluded regardless under s.4A(1) as it was not practised on the body).

61.

A method practised on the body (see below) which includes all of the steps leading to a diagnosis should be objected to under Section 4A(1). This is usually clear-cut if the claim relates to the identification of a specific condition. In addition, it may be apparent from the description that a claimed method does in fact result in a diagnosis, even if the words of the claim do not specify a specific disease. In T 125/02 AEROCRINE, the measurement of nitrogen monoxide levels in exhaled air was used to identify “impaired respiratory function”. The technical board held that the objective of ascertaining the condition or function of a lung was constantly and repeatedly presented in the application as filed as the main object of the invention. Therefore, the indication of an impaired lung function represented the determination of the nature of a medical condition intended to identify or uncover a pathology, or the negative finding that a condition can be ruled out, i.e. the diagnosis as defined in G1/04. The description also noted that the method allowed a particular course of treatment to be selected. The claimed method was considered to encompass all the steps leading to a diagnosis.

62.

In T 1016/10 GENERAL HOSPITAL, it was argued that the detection of an “amyloidogenic disorder” was merely an intermediate finding as this term includes a range of disorders, and further tests would be needed to identify precisely which disorder. The Technical Board held that the term “particular clinical picture” used in G 01/04 (Diagnostic methods) to define step (4) was broader than identification of a single disease or determining the course of treatment, and so encompassed the identification of a class of disorders such as amyloidogenic disorders. The technical board in T143/04 BETH ISRAEL HOSPITAL also held that neither Art. 52(4) EPC nor G1/04 requires that only reliable diagnostic methods which themselves lead to an unambiguous result are excluded from patentability, therefore the question whether or not a diagnostic method is absolutely reliable is not relevant for the assessment of the exclusion.

63.

It should be noted that Section 14(5)(a) requires that the claims adequately define the matter for which the applicant seeks protection. If an essential step of the method is omitted (such as the initial examination or measurement step, or the final, deductive step) then it needs to be considered whether the claim adequately defines the invention (G 01/04 (Diagnostic methods)). In addition, if one of the steps is deleted by amendment, then it must be considered whether the amendment adds matter if the entire teaching of the application as filed related to the diagnostic method in its entirety (T 143/04 BETH ISRAEL HOSPITAL). However, this does not mean that the claim must explicitly refer to every detail of the process. In particular, a claim to a diagnostic method performed in vitro on a sample taken from the body does not need to explicitly include the step of obtaining the sample (unless the invention actually lies in the method of obtaining the sample from the body).

The meaning of “practised on the body”

64.

Section 4A(1) states that methods of diagnosis practised on the human or animal body cannot be patented. In vitro diagnostic tests, performed on blood or other samples removed from the body, are therefore patentable. Furthermore, to be excluded from patentability, diagnostic methods must be carried out on the living human or animal body. A method carried out on a dead body, for example to determine the cause of death, would not be objectionable.

65.

Moreover, diagnostic methods may encompass both in vivo and in vitro steps. If the claimed method includes new and inventive technical steps performed in vitro then the method as a whole is not considered to be practised on the body. The Enlarged Board in G 01/04 (Diagnostic methods) considered whether all, or just one of the steps leading to a diagnosis had to be performed on the body for a method to be excluded. It was concluded that a method is only excluded if all of the technical steps in a method are practised on the human or animal body.

“if… some or all of the method steps of a technical nature… are carried out by a device without implying any interaction with the human or animal body, for instance by using a specific software program, these steps may not be considered to satisfy the criterion “practised on the human or animal body”, because their performance does not necessitate the presence of the latter. By the same token, this criterion is neither complied with in respect of method steps carried out in vitro in a laboratory.”

G 01/04 (Diagnostic methods)

66.

In practice, the key question is whether the examination and collection of data is practised on the body. As discussed above, a method is only considered to be a “method of diagnosis” if it has all the steps (1) to (4) listed in leading to a diagnosis - i.e. examination and collection of data, comparison of the data with normal values, finding any deviation, and attributing the deviation to a particular clinical picture. If the method includes all these steps, and the examination stage - step (1) - is practised on the body, then an objection should be made under Section 4A(1).

67.

Formally, the practice set out in G 01/04 (Diagnostic methods) is that for each of these 4 steps, there are two questions. Firstly, is this a technical step? For each technical step, the 2nd question is to ask whether the step is practised on the body. The method is not patentable if all the technical steps are practised on the body, but is patentable if any of these 4 steps are technical in nature but are carried out away from the body. In practice, the first step of examination and collection of data is the only one that may be “practised on the body”, and is (in most cases at least) the only “technical” step. The final deductive step of determining the condition is a purely intellectual exercise carried out by the doctor or vet, and so is not considered to be a technical step. In most cases, the comparison of data with standard values and finding of any deviation (steps 2 and 3) are also not technical features, and so are irrelevant for deciding whether the claim is objectionable. Moreover, in T 1197/02 AUSTRALIAN NATIONAL UNIVERSITY it was held that any additional or preparatory steps (other than these 4) are irrelevant - the claim may still be objectionable even if these additional steps are both technical and in vitro. Thus in this case the claimed method for diagnosing glaucoma was held to be unpatentable despite the fact that it included a technical process of producing images prior to presenting them to the patient - i.e. preparatory to step (1) - and technical data analysis steps between steps (1) and (2), none of which were practised on the body. Similarly, in T 143/04 BETH ISRAEL HOSPITAL and T 1016/10 GENERAL HOSPITAL methods of diagnosing disorders such as Alzheimer’s disease which included automated data analysis or signal processing steps between steps (1) and (2) were held to be unpatentable as the initial measurement step was practised on the body.

68.

To decide whether a particular step in a method is “practised on the human or animal body”, the key test is whether the step requires the presence of the patient to perform it. It is irrelevant whether the procedure is invasive, or capable of causing harm to the patient (G 01/04 (Diagnostic methods)).

69.

If step (1), examining and collecting data, is not an essential method step of the invention, then it follows that it does not matter whether or not patient presence is required. For example, the claim at issue in Perspectum Diagnostics’ Application BL O/446/22 defined a method of obtaining a volumetric map of organ health from MRI scan data sets and calculating a liver-viability measure from said volumetric map. Although an MRI scan would necessarily have been performed at some point previously, this collection of data had been performed separately to the method. Therefore, the Hearing Officer held that none of the steps of the invention were performed via interaction with the human or animal body, given the details of the method in suit. There was no teaching in the specification which concerned taking the MRI data. In this case, the invention only included steps (2)-(4) and was not excluded as a method of diagnosis. However, if the measurement step (1) cannot be separated from the later analytical steps (2)-(4), (for example, in a method of real-time imaging or sonography, wherein the analysis is performed at the same time as capturing the image) then the exclusion could not be avoided by omitting the first step. At paragraph 3.2 of T 143/04 BETH ISRAEL HOSPITAL, the technical board held that it was not correct to artificially dissociate the examination phase into a measuring step involving capturing images and a processing step including measuring pupil diameter from those images. Consequently step (1) was practised on the human body even though later processing steps did not require patient presence. Furthermore, at paragraph 2.2 of T 125/02 AEROCRINE, the board similarly held that the presence of the human subject “during one or more exhalation phases” was necessary for data collection. Therefore, the condition “practiced on the human body” was satisfied, even if the measuring was to be performed on exhaled air removed from the body. Moreover, as discussed in , the claims must define the essential features of the invention and be properly supported by the description, and if the claims are amended to omit a step to avoid exclusion under s.4A(1) then it needs to be considered whether the amendment adds matter by omission.

Who performs the method?

70.

The question of whether a claimed method is excluded under Section 4A(1) depends on whether it falls within the definition of a “method of diagnosis” (), and whether it is “practised on the human or animal body” (). It is not dependent on who carries out the method, or whether a physician needs to be present.

“whether or not a method is a diagnostic method within the meaning of Article 52(4) EPC should neither depend on the participation of a medical or veterinary practitioner, by being present or by bearing the responsibility, nor on the fact that all method steps can also, or only, be practised by medicinal or non-medicinal support staff, the patient himself or herself or an automated system.”

G 01/04 (Diagnostic methods)

At most, if a doctor is required to be present for a given step then this would appear to imply that the step is performed on the body. However, the decision of the Enlarged Board in G 01/04 (Diagnostic methods) makes it clear that this is not a decisive factor in determining whether a method is excluded or not. This contrasts with the decision of the Technical Board in T 655/92 (Contrast agent for NMR imaging), where a method of NMR imaging included a step of injecting contrast agents into the body. These agents carried the risk of side effects, including potentially fatal anaphylactic shock, and so the method required the involvement of medical as well as technical staff. It was therefore held that this was a diagnostic method falling within the scope of the exclusion. In view of the clear direction given by the Enlarged Board in G 01/04, this reasoning is no longer relevant.

Diagnosis: summary of examination practice

71.

To determine whether to object that a claim defines an unpatentable method of diagnosis practised on the human or animal body, a simplified test based on the reasoning of G 01/04 (Diagnostic methods) and subsequent EPO decisions may be used, at least at first instance. First, the examiner must consider whether the method includes (explicitly or implicitly) both a measurement or examination step, and a deductive step of determining the disease or clinical picture (steps (1) and (4) as set out above). If this is the case, then the second question is whether the measurement or examination step is “practised on the body” - the simple test for this is whether the patient has to be present during this step. If (and only if) the answer to both questions is “yes”, an objection should be made.

Diagnostic methods and Section 1(2)

72.

Diagnostic methods typically include steps of data analysis and interpretation. This may include steps which fall into the excluded categories defined in Section 1(2); in particular mathematical methods (Section 1(2)(a)), or methods of performing a mental act or computer programs (Section 1(2)(c)). In such cases, the four-step approach set out by the Court of Appeal in Aerotel/Macrossan (Aerotel Ltd v Telco Holdings; Macrossan’s Application [2006] EWCA Civ 1371; [2007] RPC 7) should be followed to determine patentability;

(1) properly construe the claim;

(2) identify the actual contribution;

(3) ask whether it falls solely within the excluded subject matter; and

(4) check whether the actual or alleged contribution is actually technical in nature.

73.

This approach to assessing patentability under Section 1(2) should be taken regardless of whether the original diagnostic method is carried out in vitro or in vivo. In Aueon’s Application BL O/248/13, it was argued that a method of diagnosis could not be excluded under s.1(2) as G 01/04 (Diagnostic methods) made it clear that such methods are inventions (unlike the categories in s.1(2), which are considered not to be inventions), albeit inventions which are excluded under s.4A(1) if they are practised on the body. The Hearing Officer concluded that the method in question was not a method of diagnosis, and so did not need to come to a view on this question.

74.

Similar lines of argument were pursued in Clawson’s Application BL O/042/15 and Ventana’s Application BL O/209/18. In the former, the Hearing Officer considered that section 4A was of little assistance in determining whether an invention could be excluded under section 1(2) or not, as there was no category for inventions which were diagnostic methods in the sense of that section but that would remain patentable; if a method is not excluded under section 4A then it is not a method of diagnosis within the meaning of this section. In Ventana’s Application, the applicant suggested that the wording of the Act allows for methods which are diagnostic in the general sense rather than excluded under section 4A, such as those carried out on tissues or fluids, and which must therefore be inherently technical as they are regarded as “inventions”. It was considered that it was the contribution in the sense of step (3) of Aerotel/Macrossan (Aerotel Ltd v Telco Holdings; Macrossan’s Application [2006] EWCA Civ 1371; [2007] RPC 7) that was important, rather than the general sense of whether the invention was ‘diagnostic’. As the contribution in this case was an improved way of displaying virtual slides in a virtual microscope, this was not a method of diagnosis in the sense of the Act.

In vivo testing of drugs etc.

75.

In vivo methods of testing pharmacological efficacy or toxicity of drugs, or experimental methods of investigating diseases in animals are not considered to be methods of diagnosis as defined in Section 4A(1). However, if the method would cause suffering to the animal and the application does not disclose any potential medical use or medical research benefit, then objection may be made that the method is incapable of industrial application, and moreover that the commercial exploitation of such a method would be contrary to public policy or morality (Section 1(3)).

Multi-step methods involving a surgical, therapeutic or diagnostic step

76.

Section 4A(1) states that a patent shall not be granted for an invention of a method of treatment of the human or animal body by surgery or therapy or a method of diagnosis performed on the human or animal. Unlike section 1(2) of the Act, there is no proviso in s.4A(1) that methods are only excluded “to the extent that a patent or application for a patent relates to that thing as such”. The EPO Enlarged Board of Appeal in G 01/07 (Treatment by surgery/MEDI-PHYSICS), confirming a body of earlier EPO case law (e.g. T 820/92 (Contraceptive method) and T 35/99 (Pericardial access/GEORGETOWN UNIVERSITY), held that any multi-step method which includes a step comprising a method of surgery or therapy step is excluded from patentability. The claimed method in question in G 01/07 encompassed the step of injecting contrast media into the heart and as such was considered to fall within the exclusion. Nevertheless, the Board held that it could be possible to omit or disclaim a surgical or therapeutic step which necessarily takes place before or after the non-excluded steps, for example by using the phrase ‘pre-implanted’ or similar. This would only be possible if the omission of this step does not add matter and the excluded step is not essential for defining the invention. This was followed by the Technical Board in T 266/07 WISCONSIN ALUMNI RESEARCH FOUNDATION in allowing a claim to an imaging method which relied on the prior introduction of a contrast agent; as this introduction was not part of the claim it was irrelevant whether it was surgical in nature. However, if the claimed method inevitably encompasses a surgical or therapeutic step then this step may be considered implicit in the method even if it is not explicitly included in the claim (T 429/12 DENTAL VISION and T 1631/17 MUEHLBAUER TECHNOLOGY – see ).

77.

In view of this settled view of the EPO Boards of Appeal, where a claimed method involves a number of steps, one or more of which constitutes a method of therapy or surgery (as defined above), then objection should be raised under s.4A(1). This means that, for example, a claim to a method of manufacturing a pharmaceutical, and then using it to treat a disease, is objectionable as a method of treatment by therapy. In addition, a method of producing a transgenic animal which includes a surgical method of embryo transplantation is also objectionable under s.4A(1). This is consistent with Hearing Officer’s decision in Occidental Petroleum’s Application BL O/35/84, where amendment of a claim to a surgical embryo transplantation method to a claim to a “method of enhancing the production of thoroughbred mammalian animal stock” (which still encompassed the surgical step) did not save the application from refusal. The invention was held to be to a method of surgery, and thus unpatentable. If the claim includes an unpatentable surgical or therapeutic step, then it is considered unpatentable even if the technical contribution lies elsewhere in the method (T 1695/07 TRANSONIC SYSTEMS).

78.

The principle that one excluded step renders the whole claim unpatentable does not apply in the same way to methods of diagnosis practiced on the body, following the decision in G 01/04 (Diagnostic methods). As discussed above (see ) the Enlarged Board in this decision held that diagnostic methods are inherently multi-step methods, and claims are only excluded if they include all the steps necessary for making a diagnosis, and all the new and inventive technical steps of the diagnostic method are practised on the body.

Apparatus and devices for surgery, therapy or diagnosis

79.

Claims to medical apparatus or devices are allowable in the same way as claims to non-medical apparatus or devices. However, the exclusion of methods of surgery, therapy or diagnosis performed on the human body means that claims to such an apparatus or device “when used” in such a method are not patentable. In such cases, the invention is considered a method of treatment or diagnosis because the claim requires carrying out the excluded method of use. For example, a claim to a pacemaker, which was characterised in part by its method of use, was rejected in T 82/93 (Cardiac pacing).

80.

Moreover, apparatus or devices that are claimed “for use” in therapy, surgery, diagnosis, or a particular method thereof, are not entitled to the special claim construction afforded to first and second medical uses by Sections 4A(3) and 4A(4). In other words, the claimed apparatus or device cannot derive novelty from the way in which it is intended to be used. Sections 4A(3) and 4A(4) are restricted to substances and compositions, and cannot be used to protect apparatus or devices. This has been confirmed in respect of first medical use claims by the UK courts (National Research & Development Corporation’s Application BL O/117/85), and similarly it has been held in this decision and by EPO Boards of Appeal that second medical use claims are not allowable with respect to apparatus (T 227/91 (Second surgical use)) or prostheses (T 775/97 EXPANDABLE GRAFTS/Surgical device [2002] EPOR 24 and T 213/07 TAYSIDE FLOW TECHNOLOGIES). The rationale for this distinction given in T 227/91 was that compositions are expended in use, and so any new use is correlated with an expansion in the manufacture of the composition for this purpose. This does not apply to surgical apparatus, where there is the possibility of repeated and different uses of the same item. This practice was confirmed by the Technical Board of Appeal in T 1099/09 COLOPLAST and T 2369/10 CYBERONICS; in both cases a request to refer a question relating to the allowability of second medical use claims for medical devices to the Enlarged Board of Appeal was refused on the grounds that there was no ambiguity in the EPC or the case law to resolve. Apparatus or devices that are claimed in the style of a first or second medical use will typically be objected to under Section 14(5) because the method of use imposes an unclear limitation, if any, on the scope of the invention and does not confer novelty or inventive step.

81.

While in most cases it may be obvious whether a claimed product is a device, as opposed to a substance or composition, in some cases the distinction is less clear-cut. As discussed below in and , the EPO Technical Boards have held that the protection of first and second medical uses for “substances or compositions” applies only to their use as active agents; i.e. where the substance has a pharmaceutical, physiological or immunological effect. If the substance merely forms a physical barrier or filler, it is considered to be acting as a device, and so the interpretation of what constitutes a ‘device’ may be broader than expected. The Boards of Appeal in T 1758/15 INCEPT and T 2136/15 CARDIOPOLYMERS ruled that amorphous injectable materials - collagen and a self-gelling alginate respectively - were “initially viscous devices” rather than substances or compositions, and so new uses of these materials were not entitled to second medical use protection under Art. 54(5) of the EPC ().

82.

A method of assembling or manufacturing a device or system inside the body which requires surgical steps is not patentable, as held by the Technical Board of Appeal in T 775/97 EXPANDABLE GRAFTS/Surgical device [2002] EPOR 24. In this decision, the Board further held that this exclusion also applied to a product-by-process claim wherein the process of manufacture required a surgical step:

“…no European patent can be granted with claims directed to a new and even possibly inventive way of using devices, in particular endoprostheses, involving a treatment by surgery. This is equally true in the case of product claims defined by a construction which is only arrived at in the human or animal body following a surgical method step.”

T 775/97 EXPANDABLE GRAFTS/Surgical device [2002] EPOR 24

83.

However, more recent decisions (T 1695/07 TRANSONIC SYSTEMS and T 1407/08 BARONE) have held that product claims which do not define any method steps are not excluded under Art. 53(c) EPC (S.4A(1)), even where they define products which are only obtained in their completed form following surgical methods. In T 1407/08 the Board said that such product claims were patentable even if they were expressed as product-by-process claims, where the manufacturing process included one or more surgical steps, as the claim protected the product only and not the process used to manufacture it; this appears to be inconsistent with the second sentence of the quoted passage from T 775/97 EXPANDABLE GRAFTS/Surgical device [2002] EPOR 24. Pending clarification from the courts, it remains our practice that if a claimed product can only be manufactured by performing a method of surgery then it is objectionable under s.4A(1); in such a case it would not be possible to work the invention without performing an excluded method.

84.

While the use of a device in surgery, therapy or diagnosis performed on the human body is unpatentable, the existence of functional features (for example, defining a prosthesis in relation to the human anatomy) in a product claim does not in itself transform the claim into a method claim (T 712/93 JOINT MEDICAL PRODUCTS). However, such a claim may be open to objection on clarity grounds, as being defined by its desired result.

First medical use

Section 4A(3)

85.

In order to alleviate the effects of the Section 4A(1) prohibition on the claiming of methods of medical treatment, Section 4A(3) of the Patents Act 1977 (as amended by the Patents Act 2004) states that:

“In the case of an invention consisting of a substance or composition for use in any such method, the fact that the substance or composition forms part of the state of the art shall not prevent the invention from being taken to be new if the use of the substance or composition in any such method does not form part of the state of the art.”

Section 4A(3) of the Patents Act 1977

86.

This replaced the similarly worded Section 2(6) of the Patents Act 1977, which was repealed by the Patents Act 2004. The words “any such method” refers to any method rendered unpatentable by Section 4A(1); ie a method of treatment of the human or animal body by surgery or therapy, or a method of diagnosis practised on the human or animal body. Under this section, and the equivalent Article 54(4) of the EPC 2000, a substance or composition which is itself already known is regarded as novel “for use in” a method of treatment prohibited by Section 4A(1) provided that the substance or composition has not been known to be used in any such method before. This provides an exception to the general rule of anticipation that once a substance or composition is known for whatever purpose then it cannot be patented again for another purpose, because it is old.

87.

Section 4A(3) protects the first medical use only. However, Section 4A(4) allows further, specific medical uses for a known substance or composition to be claimed, using the same basic format. This is discussed in more detail in the next section. First medical use claims are normally used in cases where the substance is known. However, first (and second) medical use claims are acceptable for new compounds, for example, as a fall-back in the event of a prior disclosure of the compound coming to light after grant (T 09/81 (Cytostatic Combination)).

88.

The case law relating to first medical use under the repealed Section 2(6) (or the equivalent Article 54(5) of the EPC 1973) continues to govern our practice under Section 4A(3). The exception to this is the case law relating to the novelty of claims of the form “substance X, for use in treating disease Y”, which is now governed by Section 4A(4) as discussed below.

First medical use - forms of claim

89.

A claim to the first medical use of a known substance or composition may broadly claim any therapeutic use.

Such claims may have the wording:

9. (Substance X) for use in therapy; or

ii) (Substance X) for use as a medicament.

Obviously no single drug is suitable for treating all diseases. Nonetheless, this broad form of first medical use claim is allowable for the first medical use of a substance or composition, providing at least one medical use is made plausible by the application see (). The question of the allowability of this broad form of medical use claim was considered by the EPO Board of Appeal in T 128/82 (Pyrrolidine-Derivatives). It was decided that claims which did not state the specific therapeutic purpose were allowable if the substance in question had not been used in therapy, even if the specification only disclosed a single therapeutic use. It was argued that, as the inventor of a new chemical compound is granted absolute protection for all uses of the compound, an inventor who for the first time makes a known compound available for therapy should be able to gain protection over the whole field of therapy. This was confirmed much more recently by the Board of Appeal in T 424/21 ROCHE GLYCART.

90.

In addition, the first (or subsequent) medical use of a known substance or composition may be protected by a specific medical use claim of the form:

(Substance X) for use in the treatment of (medical condition Y).

Following the implementation of the EPC 2000 by the Patents Act 2004, claims of this form are treated as second medical use claims for the purpose of novelty, under Section 4A(4). In other words, they are only anticipated by the use of X for the specific purpose of treating disease Y. This represented a change in UK and European patent practice; formerly, a claim of this type was considered to be anticipated by any medical use of the substance or composition (John Wyeth’s and Schering’s Applications [1985] RPC 545 and Sopharma’s Application [1983] RPC 195). This type of claim is discussed in more detail in the next section. However, essentially the distinction between “first” and “second” medical use claims is artificial; both types of claim are considered to be limited in scope to the substance when prepared for the defined use (whether general or specific), and both types of claim are only anticipated by the use of the substance or composition for the purpose (whether general or specific) defined in the claim. Therefore much of the case law concerning the construction of medical use claims, the criteria for assessing novelty and inventive step, and the requirements for sufficiency and support, applies equally to first or second medical use claims. The vast majority of the case law has concerned second medical use claims, and so the detailed discussion of these issues is considered in the following section, but this case law and the practice derived from it may need to be considered in examining applications relating to the first medical use of a known substance or composition. Case law specifically relating to first medical use claims is highlighted in the present section.

91.

Claims of the form “the use of (substance X) in therapy” or “the use of (substance X) as a medicament” are not first medical use claims; these are unpatentable method of treatment claims, as discussed in .

First medical use and Section 4A(1)

92.

It is a general principle that a substance or composition cannot be protected by Section 4A(3) unless the method for which it is to be used is prohibited by Section 4A(1) (cf Articles 54(4) and 53(c) of the EPC 2000). The two Sections run hand-in-hand, and if the substance or composition is known in itself (but is not known for use in surgery, therapy or diagnosis) and the method falls foul of Section 4A(1), then a claim to the substance or composition for use in the method is protected by Section 4A(3) against an objection of lack of novelty. The meanings given to “surgery”, “therapy” and “diagnosis” in Section 4A(1) therefore apply equally to Section 4A(3). Since non-surgical, purely cosmetic methods are not considered to be therapeutic, a substance or composition for use in a cosmetic method cannot be protected by Section 4A(3). However, an application may include both claims to the first medical use of a compound for therapeutic purposes, and claims to cosmetic methods using the compound (as in T 36/83 (Thenoyl peroxide)). Moreover, known compositions or substances cannot derive novelty under Section 4A(3) in a claim worded as a first medical use claim where there is no disclosure of actual prophylactic or therapeutic effect achieved beyond, for example, the maintenance of a healthy diet (T 135/98 NORSK HYDRO [2004] EPOR 14).

93.

EPO case law in relation to both first (T 1758/07 BIOTEC PHARMACON) and second medical use claims (see below) indicates that protection for medical uses of known substances or compositions is only available for the use of a substance or composition as an active agent in medicine. The use of a known substance or composition as an inactive carrier or excipient for a therapeutic agent cannot therefore be protected by a first medical use claim.

Searching and assessing novelty and inventive step of first medical use claims

94.

A first medical use claim of the form “(substance X) for use in therapy” would be anticipated by any prior use of the substance in therapy. The search should nevertheless be focussed on the use(s) disclosed in the application, as amendment of the claim to the second medical use format is likely if any prior medical use is found.

95.

As discussed below in it has been established in the case law that a claim to a substance or composition “for use in treating disease Y” is construed as “suitable and intended for” the claimed treatment. It therefore follows that a first medical use claim to a substance or composition “for use in therapy” is construed as the substance or composition suitable and intended for a therapeutic use in humans or animals.

96.

The disclosure of the effective use of the claimed substance or composition in the therapeutic treatment or prophylaxis of any medical condition will therefore anticipate a claim to the substance or composition for use in therapy. The substance or composition does not need to cure the disease or treat all patients with it, but it must have some beneficial effect. A claim to the first medical use of a compound is anticipated by its prior use in therapy, even if the only previous use was in association with another compound. However, the EPO Technical Board of Appeal in T 1758/07 BIOTEC PHARMACON held that the prior use of a composition to simply improve the palatability of a therapeutic agent did not anticipate a first medical use claim for the same composition. This case indicates that first and second medical use claims are not anticipated by the prior use of the agent in question as an inactive carrier or excipient for a therapeutic agent.

97.

As medical use claims are construed as being limited to the intentional treatment of disease, the disclosure that the substance in question has previously been administered or ingested (for example, in a food product) would not anticipate a first medical use claim if there was nothing in the prior art to indicate any therapeutic benefit, even though this may have occurred inherently.

98.

As with other fields of technology, for a prior art document to anticipate a first medical use claim it must meet the two requirements of prior disclosure and enablement. The disclosure requirement was summarised by Lord Hoffmann in SmithKline Beecham’s (Paroxetine Methanesulfonate) Patent [2005] UKHL 59; [2006] RPC 10 (NB this case did not relate to medical use claims) as follows: “anticipation requires prior disclosure of subject-matter which, when performed, must necessarily infringe the patented invention”. For this reason, a research paper which discloses experiments which show an activity which would make the substance or composition suitable for use in therapy, or discloses in vitro testing for such a use, but does not explicitly or implicitly disclose such a use does not anticipate a first medical use claim. Such disclosures of experiments and tests might of course be used as a basis for an obviousness objection under Section 3. Furthermore, a general statement of the medical use of a large class of chemical substances does not necessarily anticipate a first medical use claim to a specific compound falling within the class (T 07/86 (Xanthines)).

99.

Where there is an explicit statement of a therapeutic use, it is not always necessary for this to be accompanied by actual clinical evidence of a therapeutic effect to meet the disclosure requirement, at least, for novelty. A document (typically a patent document) which states that the substance is used in therapy without describing actual clinical data may therefore be cited for novelty. It would then be open to the applicant to challenge whether such a statement constitutes an enabling disclosure, as discussed further in . The EPO Board of Appeal in T 1031/00 SEPRACOR rejected a first medical use claim on grounds of novelty, where the experimental data provided in the application was considered to be the same as that in a published research paper. It was not argued that the prior art paper explicitly disclosed the invention as claimed. Instead, it was argued that there was no new technical feature provided in the application - the only new feature was the assertion of a therapeutic use. However, it is not clear whether this prior art would have met the test for disclosure in UK law as set out in SmithKline Beecham’s (Paroxetine Methanesulfonate) Patent [2005] UKHL 59; [2006] RPC 10. In such a case, if a novelty objection could not be made due to a lack of explicit disclosure then the claim is likely to fall on grounds of either inventive step or support and/or sufficiency as discussed in relation to second medical use claims in .

100.

In Eli Lilly v Genentech [2019] EWHC 387 it was held that a broad first medical use claim of the form “for use in therapy” or similar could not be inventive if it would be obvious to try the product in question for any therapeutic use. This means that such claims are unlikely to be inventive if the product itself is not novel and inventive, unless it would not be expected to have any useful therapeutic effects. In this case the product was an antibody against a protein predicted to have some role in inflammation, and so a broad first medical use claim could not be inventive if the antibody itself was known.

Plurality

101.

If a substance or composition has not previously been used in medicine, a number of general and/or specific surgical, therapeutic or diagnostic uses may be independently claimed in the one application without objection to plurality of invention.

Combined therapies

102.

A first medical use claim to the use of two different agents (both of which are known in the prior art for therapeutic use separately) for simultaneous, separate or sequential use in therapy is considered novel, if there has been no disclosure of the use of the two agents together in therapy. However, it should be noted that the inventiveness of claims of this type needs to be scrutinised carefully, to determine whether the claim represents a mere collocation of known elements - below.

“The Board also takes the view that combined products intended under Article 54(5) EPC for therapeutic, surgical or diagnostic methods also include compositions in which the components are presented side by side and can therefore be applied simultaneously, separately or at intervals to one and the same human or animal body.”

T 09/81 ASTA/Cytostatic combination

First medical use, apparatus and devices

103.

Section 4A(3) is restricted to substances and compositions; apparatus and devices cannot be so protected (National Research & Development Corporation’s Application BL O/117/85).

First medical use claims: support and sufficiency

104.

The requirements for support and sufficiency of medical use claims are discussed in full at as the case law in this area primarily relates to second medical use claims to the treatment of specific diseases and conditions. Much of this case law is also directly applicable to first medical use claims. However, as discussed above, it has been established that where an invention relates to the first medical use of a known substance or composition, the inventor is entitled to a broad claim to the substance “for use in therapy”. Therefore no objection should be made that such a claim lacks support across its full scope, or is insufficient due to undue claim breadth, if the application provides credible evidence of the efficacy of the claimed agent or agents to treat any one or more diseases (though such an objection can of course be made if the claim is unduly broad in terms of the claimed substances or compositions).

105.

A claim to the first medical use of a known substance or composition should be supported by evidence of its likely efficacy in therapy, surgery or diagnosis. In the absence of any such evidence, the claim is merely speculative and objection should be raised under s.14(5)(c). This requirement for first medical use claims follows from the logic of the decision by the Patents Court in Prendergast’s Applications [2000] RPC 446. This case concerned support for Swiss-type second medical use claims. It was held that, as the claims are distinguished from the prior art by their use, this use must be supported by evidence. The Hearing Officer in F. Hoffmann - La Roche’s Application BL O/192/04 applied the same reasoning to claims in the first medical use format - the essential feature of such claims is the intended use and so there must be support for it. The form of evidence is not critical; the application may provide in vivo or in vitro data, and in silico modelling data may be sufficient if it is considered to provide a credible basis for support. In F. Hoffmann - La Roche’s Application, the evidence was in the form of sequence homology with related genes and proteins; on the facts of the case it was held that this provided credible support for a medical use for a nucleic acid, but not for the protein coded by it. The Hearing Officer in Lalvani et al’s Applications BL O/220/13 followed this reasoning and also concluded that first medical use claims require evidence to support them.

106.

Furthermore, if the application is not considered to render any medical use plausible, an objection of lack of sufficiency under s.14(3) may also be raised. The case law in relation to sufficiency of second medical use claims is discussed at . In particular, the requirements for plausibility established by the Supreme Court for second medical use claims in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 () were held to apply equally to first medical uses in Eli Lilly v Genentech [2019] EWHC 387. In addition, a lack of any evidence for a therapeutic utility for antibodies to a newly-discovered receptor (of unclear function) was held to render a first medical use claim in respect of such antibodies insufficient in T 604/04 GENENTECH. On the other hand, in T 424/21 ROCHE GLYCART it was confirmed that a first medical use claim to a substance or composition “for use as a medicament” is sufficient if there is at least one plausible therapeutic use; if a claim in this form is novel and inventive there is no requirement for the claim to be restricted to the specific use or uses disclosed in the application.

107.

It should be made clear in the examination report whether the objection (under either s.14(5)(c) or s.14(3)) relates to all or only some of the claimed agents. In the former case, the objection is likely to be fatal to the application, if the agents in question are already known. The evidence in support of medical use claims must be provided in the application as filed, and this objection cannot be overcome by later-filed results. A warning, e.g. in the form of an examination opinion, should therefore be provided at the search stage if the main claims relate to the first medical use of a known substance or composition, and no data is provided.

108.

Moreover, if the application claims priority from an earlier application which does not provide evidence to render any medical use plausible, then it should be assumed at search and examination stage that a claim to the medical use of a known substance or composition is not entitled to a priority date based on the earlier application - . If the examiner considers it inherently implausible that the claimed composition could possibly have any therapeutic activity, then an objection of lack of industrial applicability, in addition to lack of sufficiency, may be raised as discussed in .

109.

In cases where a first medical use claim is included as a subsidiary claim to a per se claim to the substance or composition, then - as a general rule - if the substance or composition claim is new, inventive and supported by the description, further consideration of support for the medical use claim(s) is not necessary as a matter of practicality. Of course attention should be paid to any claims which were filed later than the application to check that they are supported by the description ().

Second medical use

Section 4A(4)

110.

Section 4A(3) of the Patents Act 1977 allows patent protection for the first medical use of a known substance or composition, in the same way as the now-repealed Section 2(6). Section 4A(4), on the other hand, allows for the protection of further, specific uses of a known substances or compositions (“second medical use”), and has no equivalent in the Patents Act prior to implementation of the EPC 2000.

“In the case of an invention consisting of a substance or composition for a specific use in any such method, the fact that the substance or composition forms part of the state of the art shall not prevent the invention from being taken to be new if that specific use does not form part of the state of the art”

Section 4A(4) of the Patents Act 1977

111.

The effect of this section (and the equivalent Article 54(5) of the EPC 2000) is that a claim to a known substance or composition for a specific medical use is considered to be novel if the substance or composition has not previously been used for that specific purpose, even if it has been used for other medical methods. This section for the first time introduces a statutory mechanism for the protection of inventions relating to second or further medical uses, and allows them to be defined using the same direct claim format as first medical use claims. However, it is important to note that Section 4A(4) has not changed the boundaries of what is and is not patentable, as for many years previously second medical use inventions were patentable through the “Swiss-type” claim format. A large body of case law in both the UK courts and the EPO has helped to define the scope, requirements and limits of Swiss-type second medical use claims. It was the express intention of the legislators, in drawing up both the EPC 2000 and the 2004 Act, that the new provisions were not intended to lead to any change in what is and is not patentable, and so the case law concerning Swiss-type claims is considered (with very few exceptions which are highlighted below) to apply equally to the new form of second medical use claims.

Second medical use: claim format

112.

Before implementation of the EPC 2000, second or further medical uses of a known substance or composition could only be protected by a claim to the use of the substance for the manufacture of a medicament for a specified medical use. If the use of the compound for the specified medical purpose was new, then such a claim was considered to be novel even if the same substance had previously been used in medicine for a different purpose before. This type of claim is known as a “Swiss-type” claim, as they were first allowed by the Swiss Patent Office. The protection of second medical uses by Swiss-type claims was allowed by the Enlarged Board of Appeal in G 05/83 (Second medical indication), and this was followed by the Patents Court in John Wyeth’s and Schering’s Applications [1985] RPC 545.

113.

Since the implementation of the medical provisions of the EPC 2000 on 13 December 2007, applicants have been able to protect inventions relating to second medical uses through the simpler and more direct claim form “substance X for use in the treatment of disease Y”. This form of claim is referred to henceforth as the “EPC 2000” claim form, to distinguish it from the “Swiss-type” claim form where necessary. Initially, applicants were allowed to claim inventions relating to second medical uses using either the EPC 2000 format, the Swiss-type format, or both, pending guidance from the UK courts and/or the EPO Boards of Appeal. In 2010, the EPO Enlarged Board of Appeal issued its decision on G 02/08 (Dosage regime/ABBOTT RESPIRATORY): this addressed, amongst other questions concerning second medical use claims, whether there were any special considerations applicable when interpreting and applying Articles 53(c) and 54(5) of the EPC 2000 (equivalent to sections 4A(1) and 4A(4)). The Enlarged Board considered that Swiss-type claims were accepted in G 05/83 (Second medical indication) as the only possible means of protecting inventions relating to second medical uses in order to fill a loophole in the provisions of the EPC 1973. Article 54(5) of the EPC 2000 and section 4A(4) of the Act fill this loophole by explicitly allowing claims to the further specific use of a known drug, and so the Board held that the reason for this judge-made or “praetorian” law no longer exists. It was therefore decided that Swiss-type claims for the second or further medical use of a known substance or composition should no longer be allowed. However, the Board set out transitional provisions such that this only applies to new applications filed at the EPO more than 3 months after the publication of the decision in the Official Journal - the EPO therefore only reject Swiss-type claims in applications with an earliest priority date of 29 January 2011 or later. For applications with an earlier priority date, the EPO allow applications with both forms of second medical use claims, following the decision in T 1021/11 BOEHRINGER INGELHEIM, which reversed the earlier decision of T 1570/09 PROTISTA BIOTECHNOLOGY which held that applications could only include one or the other form of claim.

114.

Following the decision of the Enlarged Board in G 02/08 (Dosage regime/ABBOTT RESPIRATORY), the Office issued a Practice Notice on 26 May 2010, which sets out the Office practice on second medical use claims. In view of the desirability of maintaining conformity with EPO practice as established in Board of Appeal decisions in this field, the Office no longer allows claims in the Swiss format, and so any claims in this format must either be deleted or replaced by EPC 2000 claims of the form “substance X for use in the treatment of disease Y”. This applies to both new and pending applications, regardless of their filing or priority date. While it is recognised that this is inconsistent with the transitional provisions set out in G 02/08, there is no clear legal basis under UK patent law for treating new and pending applications differently following a change in the interpretation of the statutes.

115.

Examiners should therefore object to second medical use claims in the Swiss format on grounds of lack of clarity. Specifically, Swiss-type claims are considered to be unclear because, although they define a method of manufacturing a medicament, the invention does not in fact relate to the method of production but instead relates to the intended use of the medicament. As stated in G 02/08 (Dosage regime/ABBOTT RESPIRATORY), there is no functional relationship between the feature conferring novelty (the intended use) and the claimed manufacturing process. As s.4A(4) now allows a simpler and clearer form of second medical use claim, there is no longer a reason to allow the more ambiguous Swiss form of claim. Lack of clarity is not one of the grounds for revocation under s.72, and so this practice does not have any bearing on the validity of patents already granted and including Swiss-type claims.

116.

The only form of second medical use claim that is now allowable is the “EPC 2000” format:

9. “Substance X for use in the treatment of medical condition Y”.

Under Section 4A(4) this claim is only anticipated by the prior use of substance X to treat disease Y. Prior to implementation of the EPC 2000, this form of claim was held (in John Wyeth’s and Schering’s Applications [1985] RPC 545 and Sopharma’s Application [1983] RPC 195) to be anticipated by any medical use of the substance in question. Slight variations of the above format are also acceptable. For example, these include second medical use claims having the above format but where “in the treatment of” is substituted with “treating”; e.g. “Substance X for use in treating disease Y”, and those which claim substance X as part of a composition; e.g. “A composition comprising X for use in the treatment of medical condition Y”. A claim in the form “Substance X for use in a method of treating disease Y by (steps A, B and C)…” is also acceptable if novel and inventive as discussed below in ; as the claim is in the second medical use format this claim is not excluded under section 4A(1).

117.

The following types of claim are not acceptable second medical use claims:

ii) “The use of substance X in the manufacture of a medicament for the treatment of medical condition Y.” This is the usual form of Swiss-type claim.

iii) “The use of substance X in the preparation of an anti-Y agent in ready-to-use drug form for treating or preventing medical condition Y.” The expression “in ready-to-use drug form” was intended to mean “as presented for sale”, ie packaged, as explained in the Hearing Officer’s decisions in John Wyeth’s Application, cited in John Wyeth’s and Schering’s Applications.

iv) “The use of substance X in the manufacture of an anti-Y agent in a package together with instructions for its use in the treatment of medical condition Y.”

22. “A process for the manufacture of a medicament for use in the treatment of medical condition Y, characterised by the use of substance X.”

vi) “Substance X for the treatment of/treating disease Y.”

All of claim forms (ii) to (iv) were considered to be allowable by the Patents Court in John Wyeth’s and Schering’s Applications [1985] RPC 545, although claims (iii) and (iv) have rarely been used. Claims in any of these forms are objectionable on grounds of clarity as discussed above. The EPO Board of Appeal in T 958/94 (Anti-tumoral agent) considered that claim form (v) was an acceptable alternative to the Swiss form of claim. It is also now objectionable on grounds of clarity for the same reasons. Claim form (vi) is considered to be unacceptable because it lacks “for use” which is an essential feature of the “EPC 2000” second medical use claim format. The term “for use” must be included to ensure the claim is construed as a substance limited by the specified medical use, as opposed to a substance per se, which is suitable for that use.

118.

The following types of claim are also not acceptable as second medical use claims:

vi) “The use of substance X in the treatment of disease Y”. This is an unpatentable method of treatment claim.

vii) “Commercial package containing as an active pharmaceutical agent compound X together with instructions … for treating condition Y”. If the pharmaceutical use of X is already known, the claim is only distinguished from the prior art by the content of the instructions, and this represents a mere presentation of information and thus not a patentable invention under Section 1(2)(d).

The interpretation of claims (vi) and (vii) given above was set out by the Patents Court in John Wyeth’s and Schering’s Applications [1985] RPC 545 and remains current practice.

119.

The examples above all relate to situations where the applicant wishes to protect the use of a known substance X to treat a specified disease Y. However, claims written in the EPC 2000 second medical use format may be used in a variety of more complex scenarios. These are discussed at greater length in the following sections of these Guidelines, but examples are provided below of the types of claim that may occur with a reference to the detailed discussion of such instances:

viii) “Substance X for use in a cosmetic method of treating the skin.” This is not a second medical use claim as the new use is not excluded under s.4A(1), and so will not be novel if substance X is known - .

ix) “Substance X for use in the treatment of disease Y by administration of a dosage of 0.1-1mg.” / “Substance X for use in the treatment of disease Y by intravenous administration.” The drug is used to treat the same disease as in the prior art, but using a new dosage regime or method of administration - .

24. “Substance X for use in the treatment of disease Y in patients showing over-expression of receptor Q”. The drug has been used to treat the same disease as in the prior art, but the specific patient group is defined - .

xi) “Substance X for use in the treatment of disease Y by inhibiting the activity of receptor Q”. The new use is defined, at least in part, by the mechanism of action by which the disease is treated - .

xii) “Substance X for use in the treatment of disease Y with reduced immuno-suppression”. The new use is defined, at least in part, by an unexpected advantage such as reduced side-effects - .

xiii) “Substance X for use in the treatment of disease Y as measured by an increased time to progression of disease”. The new use is defined, at least in part, by the level of efficacy achieved and/or the method used to determine efficacy - .

xiv) “Substance X for use in the treatment of diseases associated with over-expression of receptor Q.” / “Substance X for use in inhibiting activity of receptor Q.” The disease to be treated, or the therapeutic use, is defined in mechanistic rather than clinical terms - .

xv) “Substance X for use in the treatment of disease Y by combined, sequential or separate administration with substance N.” The new use relates to the combined use of two or more agents - .

xvi) “Substance X for use in the extra-corporeal treatment of blood to treat disease Y.” The new use relates to a treatment performed on blood or tissue outside the body - .

xvii) “An inhibitor of receptor Z, for use in the treatment of disease Y”. The active agent is defined in functional rather than chemical terms - .

xviii) “A prosthetic device Z, for use the treatment of disease Y”. The “active agent” is a device or piece of apparatus - second medical use claims can only protect the new use of a substance or composition, and so this claim will not be novel if device Z is known - .

“Swiss-type” and “EPC 2000” claim forms: scope, conflict and added matter

120.

It was clearly stated, in both the preparations for the EPC 2000, and the passage of the 2004 Act, that the new provisions were not intended to lead to any change in what is and is not patentable. Nevertheless, Swiss-type and EPC 2000 second medical use claims are different in claim category and this has implications for their scope in relation to infringement. Specifically, Swiss-type claims are “purpose-limited” process claims - the Supreme Court (Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21) confirmed the finding of the Patents Court (in Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3) and the Court of Appeal (in the earlier interim decision of Warner-Lambert v Actavis [2015] EWCA Civ 556; [2015] RPC 24) that Swiss-type claims are process rather than product claims. EPC 2000 format claims, on the other hand, are “purpose-limited” product claims. This means that direct infringement of a Swiss-type claim would constitute an infringement under s.60(1)(b) or (c), whereas direct infringement of an EPC 2000 second medical use claim would constitute an infringement under s.60(1)(a). There are also likely to be differences in the scope of the claims in relation to indirect infringement under s.60(2) - these issues were considered in detail in relation to Swiss-type claims by the Supreme Court in Warner-Lambert v Generics and in the earlier Patents Court decision in the same case (Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3), but it was emphasised that the findings on infringement related to Swiss-type claims only - the scope of protection of EPC 2000 second medical use claims has not yet been tested in the courts. Such infringement issues fall outside the scope of these Guidelines, and are discussed further in . However, it is clear that the scope of the two forms of claims is not identical; it was suggested in G 02/08 (Dosage regime/ABBOTT RESPIRATORY) that the EPC 2000 form is likely to be broader in scope.

121.

Regardless of the wording or scope of the claim, the technical disclosure (i.e., a new medical use for a substance or composition) is the same, and so where an application is filed with Swiss-type claims, replacement of these claims with the corresponding medical use claims in the new format does not constitute added matter. However, in view of the potentially broader scope of the EPC 2000 form, a request to make a post-grant amendment to replace Swiss-type claims with EPC 2000 form claims is unlikely to succeed - in T 250/05 BRIGHAM AND WOMEN’S HOSPITAL it was held that a post-grant amendment from a Swiss-type claim to the EPC 2000 claim form would extend the scope of protection and thus would not be allowable under Art. 123(3) EPC (equivalent to s.76(3)(b)). However, this might be permissible if the granted patent includes a per se (or first medical use) claim to the product in addition to a Swiss-type claim to its use – in this instance the scope of any EPC 2000 second medical use claim would appear to fall wholly within the scope of the per se or first medical use claim.

122.

The Boards of Appeal in T 1780/12 UNIVERSITY OF TEXAS and T 879/12 GENENTECH highlighted this difference in scope and claim category between Swiss-type and EPC 2000 form second medical use claims. In both cases it was concluded that where a divisional application included the EPC 2000 claim form, and the granted parent claimed the same medical use in the Swiss form, this did not constitute “double-patenting”. No objection should therefore be raised under s.18(5) or s.73(2) to conflict between applications including EPC 2000 second medical use claims and granted GB or EP patents which protect the same medical use solely through Swiss-type claims.

Second medical use and Section 4A(1)

123.

Second medical use claims to substances or compositions can only derive novelty from their intended use if the use is in a medical method excluded under Section 4A(1).

“It is to be clearly understood that the application of this special approach to the derivation of novelty can only be applied to claims to the use of substances or compositions intended for use in a method referred to in Article 52(4) EPC.”

G 05/83 (Second medical indication)

124.

This means that the second medical use claim format cannot be used to protect the new use of a known substance in, for example, non-surgical cosmetic or hygiene methods (Commonwealth Scientific & Industrial Research Organization’s Application BL O/248/04), or sterilisation of non-living surfaces or liquids (T 611/09 ASH ACCESS TECHNOLOGY). A claim to “substance X for use in cosmetic method Y” is therefore not limited by its intended use, and will not be new if substance X is known. Similarly, a second medical use claim “for the treatment of halitosis” was refused on the grounds that this is not a pathological condition (T 675/11 COLGATE-PALMOLIVE), and the Hearing Officer in Lalvani et al’s Applications BL O/220/13 considered that “for lactation” and “for bone health maintenance” did not constitute therapeutic uses according to s.4A(1) and so interpreted the claims as being claims to the composition “suitable for” such a use.

125.

An application may include both claims to the second medical use of a compound for therapeutic purposes, and claims to cosmetic or other patentable methods using the compound, providing the therapeutic and non-therapeutic methods are supported and distinguishable (as in T 584/88 (Anti-snoring means/REICHART), relating to therapeutic and non-therapeutic treatments for snoring). On the other hand, where any non-therapeutic effects are inseparably linked to (or a consequence of) the therapeutic effects, then (as discussed in ) a method claim would be unpatentable under s.4A(1) and so a second medical use claim to a new use which encompasses both effects may be protected under s.4A(4) (T 495/10 K. U. LEUVEN).

126.

As discussed below, second medical use claims may be defined in part by their mode of administration, or the patients to whom they are administered. However, definition in these terms alone (e.g. “for enteral feeding”), without specifying any actual therapy, does not define a new medical use and so in such cases the claim would be construed as a substance or composition “suitable for” such a use (T 1278/12 N.V. NUTRICIA).

127.

Although the Enlarged Board of Appeal referred only to “therapeutic” methods in its decision in G 05/83 (Second medical indication), second medical use claims may be used to protect the use of a known substance or composition in any method falling within the exclusion of Section 4A(1). For example, in T 655/92 (Contrast agent for NMR imaging), a Swiss-type claim was allowed for the use of a compound, previously used for therapeutic treatment, as a reagent in a diagnostic method performed directly on the human body.

128.

Second medical use claims are acceptable whether or not the substance is known or has been used in therapy previously. There is no requirement for evidence concerning prior medical use to be included in the specification (T 143/94 (Trigonelline)).

129.

If an application includes unpatentable method of treatment claims, such as “the use of X to treat Y”, amendment of these claims to convert them into second medical use claims does not constitute added matter. However, in T 1635/09 (Composition contraceptive/BAYER SCHERING PHARMA AG), post grant amendment of a method claim (to contraception) to a second medical use claim was refused on the grounds that it would extend the scope of protection. This situation would only be likely to arise if (as in this case) a granted patent with method claims was held to be excluded under s.4A(1)/ Art.53(c) in post-grant proceedings.

130.

In decision of the Technical Board in T 1758/15 INCEPT confirmed the view taken in T 1099/09 COLOPLAST and T 2003/08 EDWARDS LIFESCIENCES that second medical use claims can only be used to protect the use of a known substance or composition as an active agent. The use of a known substance or composition as an inactive carrier or excipient for a therapeutic agent cannot therefore be protected by a second medical use claim. Similarly, if a substance is used in the body as a mere physical barrier or filler this use cannot be protected as a second medical use.

Determining novelty and inventiveness of second medical use claims

i) Construction of “for use in treating disease Y”

131.

The Court of Appeal in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 held that the words “for treating disease Y” should be construed as “suitable for trying to treat disease Y”, since the skilled person would realise that drugs which are suitable for treatment will not always have a 100% success rate. Similarly, the EPO Board of Appeal in T 799/16 ACORDA held that the existence of non-responders to a therapy did not render a medical use claim invalid. However, drugs which are perceived as being suitable for treatment, but actually have no effect, do not fall within the scope of the claim. Furthermore, the therapeutic effect must be discernible (Teva v Merck [2009] EWHC 2952; [2010] FSR 17), and it must be more than a mere placebo effect (Pfizer’s Patent [2000] EWHC 49; [2001] FSR 16). In Regeneron Pharmaceuticals v Genentech [2012] EWHC 657 the Patents Court followed the view of the EPO Technical Board of Appeal in T 609/02 SALK INSTITUTE, that “the actual achievement of the therapeutic effect is a functional technical feature of the claim, as opposed to a mere statement of purpose or intention”, and it was held that this applied to both Swiss-type and EPC 2000 form claims. This interpretation was endorsed on appeal (Regeneron Pharmaceuticals v Genentech [2013] EWCA Civ 93; [2013] RPC 28). Recent case law has indicated that the criteria for determining whether the therapeutic effect has in fact been achieved may vary depending on the nature of the condition and the disclosure of the specification; in Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737; [2014] RPC 1 it was held (on the facts of the case) that the primary criterion for efficacy was success in a Phase 2 clinical trial, whereas in Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3 it was held that animal models (as used in the Examples of the patent) would suffice; not least because the claim was not limited to treatment of humans. In Merck Sharp & Dohme v Shionogi [2016] EWHC 2989 it was held that “effective in the treatment of a viral disease” meant effective in the sense of having a beneficial therapeutic effect in preventing and treating the disease, and sufficiently well tolerated to be capable of clinical use.

132.

Moreover, the “for use” element of a medical use claim has a limitation beyond mere suitability for the treatment in question. In Hospira v Genentech [2014] EWHC 1094 Birss J held that “for” in a second medical use claim means “suitable and intended for” - in other words, second medical use claims have a mental element. The second part of this definition was further refined (in the context of infringement) by the Court of Appeal in Warner-Lambert v Actavis [2015] EWCA Civ 556; [2015] RPC 24 and Warner-Lambert v Generics [2016] EWCA Civ 1006; [2017] RPC 1 to mean that the manufacturer knows, or can reasonably foresee, that the drug will be intentionally used for the claimed therapeutic purpose - this interpretation was applied to the assessment of novelty and inventive step by the Patents Court in Hospira v Genentech [2015] EWHC 1796; [2016] RPC 1. However, on appeal the Supreme Court (Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 )) unanimously rejected the Court of Appeal’s interpretation of the scope of second medical use claims, and held that it was too broad an interpretation to say that such a claim encompassed any manufacture of the product where the manufacturer could “reasonably foresee” that the product would be used for the claimed therapeutic method. However, this question was only considered in relation to infringement of “Swiss-type” second medical use claims, and in any event this reasoning was obiter as the patent was found invalid.

ii) Novelty

133.

In light of this construction, what is needed to anticipate a second medical use claim to the use of a substance or composition to treat a specified condition? Clearly, the actual disclosure of the effective clinical treatment of the disorder by the agent in question will anticipate. In addition, experimental data showing that an animal with the condition in question was successfully treated with the specified agent would constitute anticipation, unless the claim was limited to treatment of humans. If the compound in question has been used in the treatment of the specified disease, then this will anticipate the claim even if the treatment was not effective for all patients (Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1). Moreover, the treatment does not need to cure the disease, or treat all aspects of the disease, but it must have some beneficial effect (Regeneron Pharmaceuticals v Genentech [2013] EWCA Civ 93; [2013] RPC 28). The claim would be anticipated by any prior use of the compound to treat the disease in question, even if the only previous use was in association with another compound (Pfizer’s Patent [2000] EWHC 49; [2001] FSR 16). However, the previous use of the compound purely as an inactive carrier or excipient for a therapeutic agent does not anticipate a second medical use claim, as held in T 1758/07 BIOTEC PHARMACON. Furthermore, if the claimed substance was only present in a prior art composition at such a quantity (e.g. as an impurity) that it could not have had a material effect on the treatment, then it will not anticipate (GlaxoSmithKline v Wyeth [2016] EWHC 1045).

134.

As second medical use claims are construed as being limited to the intentional treatment of the disease, the fact that the prior art use of the substance to treat a different condition may have inherently treated or prevented the claimed disease in some patients does not constitute an anticipation if the prior art does not disclose the new therapeutic use. As the Court of Appeal in Warner-Lambert v Actavis [2015] EWCA Civ 556; [2015] RPC 24 said, in relation to a second medical use claim to the use of a known drug to treat pain:

“The therapeutic treatment is of course new because, and only because, it is carried out with the intention of producing the new therapeutic effect. The prior use of the compound may have in fact produced the effect, for example if a patient taking it for GAD or epilepsy was at the time experiencing pain as well. This demonstrates, to my mind, that it is the intention for which the compound is administered which is at the heart of the invention.”

Warner-Lambert v Actavis [2015] EWCA Civ 556; [2015] RPC 24

135.

As with other fields of technology, there are two requirements for anticipation, prior disclosure and enablement, and the requirements for each must be met. In SmithKline Beecham’s (Paroxetine Methanesulfonate) Patent [2005] UKHL 59; [2006] RPC 10, Lord Hoffmann summarised the disclosure requirement as follows: “anticipation requires prior disclosure of subject-matter which, when performed, must necessarily infringe the patented invention”. For that reason, a research paper that merely discloses experiments which show an activity suggesting the specified use, or disclosing in vitro testing for such a use, but does not explicitly or implicitly disclose the actual use would not anticipate a second medical use claim for the specified medical use. However, where there is such a disclosure, it is not always necessary for this to be accompanied by actual clinical evidence of a therapeutic effect to meet the disclosure requirement, at least, for novelty. In T 241/95 (Serotonin receptor/ELI LILLY), it was stated that “a pharmacological effect or any other effect such as a behavioural effect observed either in vitro or in animal models is accepted as sufficient evidence of a therapeutic application if for the skilled person this observed effect directly and unambiguously reflects such a therapeutic application”. On the other hand, as held by the Patents Court in Regeneron Pharmaceuticals v Genentech [2012] EWHC 657, the disclosure that the agent in question might have the claimed therapeutic effect does not enable the skilled person to directly and unambiguously deduce that it will have the claimed effect and so this does not meet the disclosure requirement for anticipation.

136.

A document which states that the substance is used to treat the particular disease without describing actual clinical data may therefore be cited for novelty - such statements are common in patent documents, as discussed in T 1001/01 SMITHKLINE BEECHAM.

“…it is common practice that a patent literature document, in order to be an enabling disclosure of a medical indication for pharmaceutically active compounds … does not necessarily need to include either clinical tests (Phase I, II or even III) or in vivo human assays.”

T 1001/01 SmithKline Beecham

It would then be open to the applicant to challenge whether such a statement constitutes an enabling disclosure. In Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10 (a case concerning a second medical use claim to the use of a particular antibody to treat cancer) a prior art patent document included the disclosure of the antibody in question and claims to its use to treat cancer amongst other disorders, together with evidence of an immune-regulatory role in vitro and in vivo, but without any data or models relating specifically to cancer. It was held that this document met the disclosure requirement for novelty, but not the enablement requirement. The reason was that Birss J considered that plausibility is an aspect of enablement of medical use claims - in order to be an enabling disclosure, the prior art has to make the claimed effect plausible, and on the facts of the case he held that it did not. Nevertheless, at first instance at least, a novelty objection should be raised if there is a clear disclosure in a prior art document of the use of the agent to treat the disease in question, unless it is clear to the examiner that the disclosure is not enabling (for example, if the condition is only referred to as part of a long list of diseases with no evidence to make the use plausible).

137.

The EPO Board of Appeal in T 1031/00 SEPRACOR rejected both first and second medical use claims on grounds of novelty, where the experimental data provided in the application was considered to be the same as that in a published research paper. It was not argued that the prior art paper explicitly disclosed the invention as claimed, Instead, it was argued that there was no new technical feature provided in the application - the only new feature was the assertion of a therapeutic use. While this prior art would appear to meet the test for enablement, it is not clear whether it would have met the test for disclosure as set out in SmithKline Beecham’s (Paroxetine Methanesulfonate) Patent [2005] UKHL 59; [2006] RPC 10. In such a case, if a novelty objection cannot be made due to a lack of explicit disclosure then the application is likely to fall on grounds of either inventive step or support and/or sufficiency as discussed below in .

138.

It should be noted that the disclosure that an agent is being evaluated in clinical trials for a condition does not necessarily constitute evidence of therapeutic use (T 158/96 PFIZER/Sertraline [1999] EPOR 285). It was pointed out in T 715/03 PFIZER that successful completion of Phase I trials merely demonstrates an acceptable safety profile, and so the mere disclosure that a compound is undergoing Phase II trials does not indicate any therapeutic effect unless results are provided. Phase II trials are intended to investigate efficacy as well as safety, and so in many cases the disclosure that a drug has entered phase III trials may be considered to be implicit disclosure of therapeutic efficacy in phase II trials. However, this is not always the case - in Hospira v Genentech [2015] EWHC 1796; [2016] RPC 1, the claimed combination of drugs had not been tested in phase II trials, as both drugs had been shown to be effective individually in treating breast cancer. The disclosure (without providing results) that the combination had entered Phase III trials was therefore not considered novelty-destroying, both in the Patents Court in this case and at the EPO Technical Board of Appeal in T 1859/08 GENENTECH. In Hospira v Cubist [2016] EWHC 1285; [2017] RPC 10, Carr J did not accept that a Press Release stating that Phase III trials of the claimed dosage regime were to take place indicated that efficacy must have been demonstrated in Phase II trials, given that the Press Release was forward-looking and could not be taken as a statement that the trials had actually taken place. In T 239/16 NOVARTIS, the EPO Board of Appeal held that a patient information leaflet for participants in a clinical trial which gave details of the treatment and its purpose did not anticipate a second medical use claim as it gave no indication as to whether the treatment was in fact effective.

139.

Clearly, however, a disclosure that a drug has entered clinical trials for the specified use is likely to be relevant for inventiveness, and in fact the Patents Court in both Hospira v Genentech [2015] EWHC 1796; [2016] RPC 1 (upheld on appeal - [2016] EWCA Civ 1185; [2017] RPC 14[2016] EWCA Civ 1185; [2017] RPC 14) and Hospira v Cubist [2016] EWHC 1285; [2017] RPC 10, and the Board of Appeal in T 239/16 NOVARTIS, held that the claims in question were obvious (see ).

140.

The case law concerning anticipation by use in clinical trials is discussed in relation to per se product claims at . In the case of second medical use claims, there is a further consideration; that prior use can only anticipate if it constitutes a public disclosure that the agent does in fact have the claimed therapeutic effect. As clinical trials have multiple participants to help distinguish genuine effects of the treatment from chance or placebo effects, it would generally seem to be unlikely that an individual patient’s experience of using the agent in question would provide this information.

141.

As discussed in , a per se claim to a previously unrecognised metabolite of a known drug may be anticipated if the production of the metabolite is the inevitable result of carrying out directions to make and use the drug disclosed in a prior art publication, as established in Merrell Dow v H N Norton [1996] RPC 76. Following this logic, a claim to such a metabolite for use in the treatment of the same disease as the known use of drug from which it derives would also be anticipated. Anticipation of a medical use claim does not require knowledge of the exact composition of the active agent if it is in fact the same as in the prior art, though it does require knowledge of the therapeutic effect and intention to achieve this effect. However, if the metabolite is claimed as part of a pharmaceutical composition, or in purified or isolated form, for use in the treatment of a particular condition, then this would be novel.

iii) Inventive step

142.

As in all fields of technology, when determining inventive step the four step test set out in Windsurfing International v Tabur Marine [1985] RPC 59, as reformulated in Pozzoli v BDMO [2007] EWCA Civ 588 should be used. The four step approach of Windsurfing/Pozzoli is intended to address the concept of inventive step without the benefit of hindsight, by ensuring that the examiner assesses the invention through the eyes of the person skilled in the art, with the benefit of his common general knowledge. The inventive concept of the claim in question is then construed, and the differences between the state of the art and the inventive concept of the claim are identified. This then enables the examiner to approach the final step and ask “is it obvious”. Section 3 of MoPP discusses these steps in detail, and therefore each step of this test is not discussed in detail here. Instead this section will focus on the specific issues raised in determining whether there is inventiveness in a claim to a new medical use for a known substance or composition, in light of the construction of such claims as discussed above.

143.

Clearly, just as the new medical use can provide novelty to a claim to “substance X for use in treating disease Y”, it can also provide inventiveness, as is made explicit in Teva v Merck [2009] EWHC 2952; [2010] FSR 17:

144.

Furthermore, it was held in Teva v AstraZeneca [2014] EWHC 2873 that for the new use to be considered inventive, the specification must provide reasons - not previously known or recognised - why the agent is likely to be effective in the new use:

“Where, as here, a patent is sought in relation to a new use of an existing drug or combination of drugs, patent protection will only be justified if the patentee discloses sound reasons, not recognised or known before, for thinking that new use will be effective to secure the object for which it is put forward”

Teva v AstraZeneca [2014] EWHC 2873

In other words, the specification must provide a contribution to the art beyond a mere proposal to treat a new condition. As discussed below in , if the specification does not provide any such “sound reasons”, then it is objectionable on grounds of lack of support or sufficiency, and this is likely to be the primary objection in such cases. Nevertheless, the technical contribution of the specification is taken into account in assessing inventiveness of selection inventions as discussed in below.

145.

There is a body of EPO case law in which objections of obviousness are made on the basis that the application has made no technical contribution to the art. This so-called “AgrEvo obviousness” is derived from the decision in T 939/92 AGREVO/Triazoles and is based on the EPO’s problem/solution approach to assessing obviousness – see and the Examination Guidelines for Patent Applications relating to Chemical Inventions in the Intellectual Property Office. This objection has been considered alongside sufficiency in a number of UK court decisions concerning medical use claims (e.g. Sandoz v Teva [2022] EWHC 822 (Pat), on the basis that the claimed use was not made plausible by the specification. In such cases, objection should be made that the application lacks sufficiency and/or support as discussed in ; there is no need to consider AgrEvo obviousness.

146.

Very often in the case law relating to new medical uses of known substances or compositions, the final step in the Windsurfing/Pozzoli (Windsurfing International v Tabur Marine [1985] RPC 59 and Pozzoli v BDMO [2007] EWCA Civ 588) test - assessing whether the invention is obvious - is framed as a question as to whether it would be obvious to try to use the agent for the claimed purpose. As discussed in MedImmune v Novartis [2012] EWCA Civ 1234; [2013] RPC 27 (although this case did not relate to medical use claims), in pharmaceuticals and biotechnology there may be many possible avenues to explore with little indication which, if any, will prove fruitful. Nevertheless, particularly given the potential rewards of inventing a successful treatment, they are pursued, and this would plainly not happen if the prospects of success were so low as not to make them worthwhile. But denial of patent protection in all such cases would act as a significant deterrent to research. For this reason, obviousness in these circumstances is generally only found where it is considered obvious to try with a reasonable or fair expectation of success, and the Court of Appeal gave some general guidance as to how this might be assessed:

“Whether a route has a reasonable or fair prospect of success will depend upon all the circumstances including an ability rationally to predict a successful outcome, how long the project may take, the extent to which the field is unexplored, the complexity or otherwise of any necessary experiments, whether such experiments can be performed by routine means and whether the skilled person will have to make a series of correct decisions along the way.”

MedImmune v Novartis [2012] EWCA Civ 1234, [2013] RPC 27

147.

This approach was endorsed in relation to a second medical use claim by the Court of Appeal in Regeneron Pharmaceuticals v Genentech [2013] EWCA Civ 93; [2013] RPC 28, and has been applied by the courts in many decisions since then. In Actavis v Eli Lilly [2015] EWHC 3294; [2016] RPC 12, it was pointed out that logically the question of whether the new use is obvious to try should be addressed first, and then, if necessary, whether there would be a reasonable expectation of success. On the facts of the case it was decided that it was not obvious to try to use the agent in question for the new use at all, and had it been there would have been no expectation of success. “Success” in second medical use cases means achieving the claimed therapeutic effect - as discussed above in , the criteria by which this would be assessed may vary according to the disclosure in the specification, and so what exactly the skilled person is said to be “trying” may also vary. In some cases, such as Hospira v Genentech [2014] EWHC 1094, and Teva v AstraZeneca [2014] EWHC 2873 the question was whether it would be obvious to undertake a clinical trial with a fair expectation of success, whereas in Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3 and Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10 the question was whether it would be obvious to perform specified animal tests with a fair expectation of success. In Hospira v Genentech [2015] EWHC 1796; [2016] RPC 1, Arnold J considered some of the factors which would determine whether it was obvious to run a clinical trial with a reasonable expectation of success. These included: the level of motivation to find a new or improved treatment for the condition; whether the trial would be of routine design; whether it would be technically difficult (as opposed to merely time-consuming and expensive); what risk to patients it would present; the failure rate in such trials; whether the specification overcame any “lions in the path” that would have deterred the skilled person from carrying out the trial; and how promising the skilled person would consider the prior art disclosure to be in light of the common general knowledge. The Court of Appeal (Hospira v Genentech [2016] EWCA Civ 1185; [2017] RPC 14) upheld Arnold J’s conclusion that it would have been obvious to try such a trial with a reasonable expectation of success, even though there had not been earlier trials on the combination therapy in question. In particular, the argument that any third party would be dissuaded by the burden of needing to produce and trial the agent in question was rejected; if those steps were an undue burden the patent would be insufficient. In Hospira v Cubist [2016] EWHC 1285; [2017] RPC 10, phase II trials of the dosage regime in question had taken place and so some efficacy must have been established, and so the skilled person would have a reasonable expectation of success at Phase III trials. A similar reasoning was used by the Board of Appeal in T 239/16 NOVARTIS, where it was held that the inclusion of the claimed dosage regime as one of five study arms in a clinical trial was in itself enough to lead to an expectation of success, unless there was countervailing evidence from the prior art which would point towards failure of this arm. The Board held in this case there was no such evidence.

148.

The Supreme Court in Actavis v Icos [2019] UKSC 15; [2019] RPC 9 - a case relating to a second medical use distinguished by the dosage regime used - set out a number of general principles to consider when determining whether a new medical use is inventive:

9. Whether the invention was obvious to try with a reasonable prospect of success (referring to MedImmune v Novartis 2010 EWCA Civ 1234; [2013] RPC 27; with the proviso there is no requirement that it should be manifest that the trial ought to work, and some experiments are so routine they may be obvious to perform without expectation of success.

ii) Whether the research was routine in nature.

iii) The burden and cost of the research programme.

iv) The necessity for and nature of value judgements by the skilled team in the course of research.

22. The existence of multiple paths for research, as an indicator of non-obviousness;

vi) The motive of the skilled person.

vii) Whether the results of research were surprising; unexpected results may point towards inventiveness.

viii) Hindsight must not be used, but it may be obvious to take a series of steps without the benefit of hindsight if these are steps that the skilled person would undertake as a matter of course.

ix) Whether any advantageous effect is merely a “bonus effect” i.e. where an invention has an added benefit but is obvious for another purpose.

149.

In this case the Supreme Court (Actavis v Icos [2019] UKSC 15; [2019] RPC 9) upheld the Court of Appeal’s decision ([2017] EWCA Civ 1671; [2018] RPC 7) that the dosage regime in question was obvious even though the skilled person would not at the outset have an expectation of success at that specific dosage. It was sufficient that there was a general expectation of success in the effectiveness of the treatment, and that by following established dose-ranging steps the skilled person would be very likely to arrive at that specific dosage. Therefore, there may not be a requirement for a “reasonable expectation of success” of all the specific features of a claimed therapy if there is a general expectation of success, and by following routine and established steps the skilled person would be led to the invention as claimed. This has particular implications for second medical uses defined by dosage regime as discussed below.

150.

The general principle that an invention can only be considered “obvious to try” if there would have been a reasonable expectation of success applies regardless of the extent of experimental evidence supporting the new use. As discussed below (), second medical use claims must be supported by evidence of the likely effectiveness of the claimed treatment, and so in the absence of any such evidence the claim should be objected to as being speculative. However, providing this threshold test is met, the examiner should not apply a different test for obviousness depending on the amount of evidence provided in the specification, or determine the inventive concept on the basis of the supporting evidence rather than the claims. This follows from the decision of the House of Lords in Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49; [2008] RPC 28, which reversed the decision of the Patents Court (Angiotech Pharmaceuticals’ Patent [2006] EWHC 260; [2006] RPC 28) and the Court of Appeal (Angiotech Pharmaceuticals v Conor Medsystems [2007] EWCA Civ 5; [2007] RPC 20).

151.

This case concerned a drug-coated stent, and so was not a first or second medical use claim, but the case is relevant to medical use claims as it related to the choice of pharmaceutical agent used in the device, and the likely efficacy and safety of that drug for a specific therapeutic use. The case revolved around the question of whether it would be “obvious to try” to coat a stent with paclitaxel (TaxolRTM) to prevent restenosis (the proliferation of cells around the stent). The Patents Court (Angiotech Pharmaceuticals’ Patent [2006] EWHC 260; [2006] RPC 28 held that the technical contribution disclosed in the application was critical in determining the question to be asked; whether it was merely necessary to show that the substance was an obvious candidate for testing without any expectation of success, or whether it was necessary to show that the skilled person must have had an expectation of success sufficient to induce them to use it in practice. The House of Lords (Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49; [2008] RPC 28) rejected this distinction:

“But there is in my opinion no reason as a matter of principle why, if a specification passes the threshold test of disclosing enough to make the invention plausible, the question of obviousness should be subject to a different test according to the amount of evidence which the patentee presents to justify a conclusion that his patent will work.”

Lord Hoffmann, Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49; [2008] RPC 28

152.

In this case there was evidence provided in the application as filed that Taxol RTM was a particularly effective anti-angiogenic agent, and the invention was based on the principle that inhibition of angiogenesis could be used to prevent restenosis. The House of Lords accepted that the absence of any evidence to support a speculative claim could lead to an objection of lack of support or insufficiency (quoting the decision in Prendergast’s Applications [2000] RPC 446), but held that this requirement should not be confused with the requirement for inventiveness (Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49; [2008] RPC 28).

153.

Moreover, it cannot be argued that a prima facie obvious selection of a particular compound or treatment is rendered inventive by a surprising effect, in the absence of any evidence for or disclosure of that effect in the application as filed. In this respect, we would take a different view from that of the Technical Board of Appeal in T 36/04 UNIVERSITY OF TEXAS. In this case, a second medical use claim relating to the administration of two agents in a specified order was granted on the basis of information obtained after filing showing an unexpected benefit of administration in that sequence, even though the specification as filed gave no hint that the order of administration was of importance. In assessing the inventiveness of any such selection invention, the question to be asked is whether the invention makes a technical contribution or is merely an arbitrary selection. If it is merely an arbitrary selection then the invention is obvious. This reasoning follows the Court of Appeal’s decision in Dr Reddy’s Laboratories v Eli Lilly [2009] EWCA Civ 1362; [2010] RPC 9 and the EPO Board of Appeal decision in T 939/92 (Triazoles), and was applied in respect of a second medical use claim in Teva v AstraZeneca [2014] EWHC 2873.

154.

The examination of selection inventions is discussed in greater detail in and the Examination Guidelines for Patent Applications relating to Chemical Inventions in the Intellectual Property Office.

155.

If the experimental evidence provided in support of the specified use is essentially the same as that provided in the prior art, then the application is likely to fail on grounds of either inventiveness on the one hand or support and/or sufficiency on the other. As discussed above, in Teva v AstraZeneca [2014] EWHC 2873 the Patents Court held that the specification must provide reasons not previously known or recognised why the agent is likely to be effective in the new use. This is sometimes referred to as an obviousness/insufficiency “squeeze”. In Teva v Merck [2009] EWHC 2952; [2010] FSR 17, Hospira v Genentech [2014] EWHC 1094 and Accord Healthcare v Medac [2016] EWHC 24; [2016] RPC 17, the Patents Court held that the claims in question were not inventive, but had they been found inventive then they would have been invalid for insufficiency. In Hospira v Genentech (2014), Birss J held that if the evidence in the prior art was not enough to make it obvious for the skilled person to conduct a clinical trial of the claimed dosage regime, then the (very similar) experimental evidence in the patent would not be enough to render the claimed effect plausible and so the skilled person would again not conduct a trial. He also stated as a general principle:

“…the patentee can hardly argue, and the Court or Patent Office is unlikely to accept, that a mere prior proposal is not enough to invalidate the claim if all that is present in the specification of the patent is a mere proposal followed by a use claim.”

Hospira v Genentech [2014] EWHC 1094

156.

However, in Actavis v Eli Lilly [2015] EWHC 3294; [2016] RPC 12, Carr J held that the standard for “plausibility” in relation to sufficiency was different from, and lower than, the “reasonable expectation of success” test used in the context of obviousness, and so rejected an obviousness/insufficiency squeeze argument and held that the patent in question was valid. (NB since this decision, the requirement for plausibility have been clarified by the Supreme Court in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 - ). In Actavis v Eli Lilly (2015), unlike the cases referred to in the previous paragraph, there was no suggestion at all in the prior art that the substance in question might be useful for the claimed purpose i.e. treatment of attention deficit/hyperactivity disorder (ADHD), and so perhaps unsurprisingly it was not considered obvious without the benefit of hindsight. The rationale provided in the patent as to why the agent was likely to be effective to treat ADHD had not previously been recognised, and on the facts of the case it was considered to render the use plausible. In the later decision of Accord Healthcare v Medac [2016] EWHC 24; [2016] RPC 17, the patentee argued that a new dosage regime would not have been obvious because of the skilled person’s concern about possible side effects. Birss J held that if this was the case, the patent in suit contained neither experimental evidence nor any reasoning that would suggest that this concern was unwarranted, and this was distinguished from Actavis v Eli Lilly (2015) where the patent did at least include some reasoning. He therefore held that there was indeed a “squeeze” between plausibility for insufficiency and obviousness.

157.

In Eli Lilly v Genentech [2019] EWHC 387, Arnold J held that a claim to an antibody defined as binding to a class of receptors with a particular affinity was obvious, as there was no evidence that generation of the antibodies could not be achieved by obvious techniques, and if there was a requirement for ‘special, non-obvious techniques’ then it would be insufficient as the patent did not disclose any such techniques. This particular claim was not a medical use claim, but the assessment of later medical use claims for the treatment of rheumatoid arthritis and psoriasis gives an example of the balance between the inventive step and sufficiency arguments. The experimental examples of the patent disclosed the identification of a new member of a receptor family, the isolation of antibodies against it and evidence that the receptor played a role in inflammatory processes (as expected from the prior art relating to this family). There was no direct evidence relating to any specific condition. In respect of rheumatoid arthritis, the prior art and/or common general knowledge about this family of receptors was enough to render the use obvious. This was not the case for psoriasis, and so this claim was considered non-obvious, but given the lack of any evidence relating to psoriasis in either the prior art or the specification this use was considered insufficient. The requirements for sufficiency and support are discussed further in

158.

If the agent in question in a second medical use claim has been used to treat a related condition, then this disclosure may form the basis of an inventive step objection. This will obviously have to be dealt with on a case-by-case basis, but some guidance may be derived from the decision of the EPO Board of Appeal in T 913/94 EISAI/Medicament for gastritis [2001] EPOR 362. The first question to be asked is whether the diseases have a common origin, causative factors or mechanism. If this is the case, then this does not automatically mean that the claim lacks inventiveness. However, if the symptoms of the disease already treated in the prior art are shared with, and are more serious than, the claimed condition, then this strongly suggests that the agent will be effective in the latter case as well.

159.

In relation to cancer treatments, the Board of Appeal in T 385/07 PHARMA MAR argued that different types of cancer have very different causes and characteristics, and there are no “magic bullets” which successfully treat all cancers. The disclosure that a particular treatment is effective against one or more cancer types would not normally indicate a “reasonable expectation of success” in the treatment of an unrelated form of cancer. Nevertheless, this will need to be assessed on the facts of the case, as there are cancer treatments which exert their effect by targeting a mechanism common to many, if not all cancers - one such treatment was at issue in Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10.

160.

Following the decision of the Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26, second medical use claims which are defined by a new dosage regime (where the substance or composition, and the disease treated, are both known in the prior art) are in principle allowable. In this decision, Jacob LJ highlighted the fact that investigating dosage regimes is standard practice in the art, and so only in an unusual case (such as the existence of a technical prejudice pointing away from the claimed dosage regime) would a new dosage regime alone confer inventiveness to a claim.

“…nearly always such dosage regimes will be obvious – it is standard practice to investigate appropriate dosage regimes. Only in an unusual case such as the present (where… treatment for the condition with the substance had ceased to be worth investigating with any dosage regime) could specifying a dosage regime as part of the therapeutic use confer validity on an otherwise invalid claim.”

Jacob LJ, Actavis v Merck EWCA Civ 444; [2008] RPC 26

In a review of an Office Opinion, the Hearing Officer in InterMune’s Patent BL O/163/16 held that the above comments provided useful guidance on determining obviousness, rather than establishing a binding legal principle that there is a general presumption that there must be a clear technical prejudice pointing away from the claimed dosage regime to confer validity on such a claim. Nevertheless, on the facts of the case the Hearing Officer declined to overturn the Opinion that the patent lacked inventive step.

161.

The obviousness of a new dosage regime was considered by the Patents Court in Actavis v Icos [2016] EWHC 1955. This case concerned the identification of particularly advantageous doses of the drug tadalafil. The dose arrived at (5mg) was significantly lower than that suggested previously and had the advantage of (among other things) reducing side effects. Birss J held that the claim was inventive, in particular because the skilled person would have no expectation of success that this low dose would be effective, and indeed it would not even be tested in the first phase of a dose ranging study. However, his findings of fact were that the skilled person would consider it obvious to carry out a dose ranging study of tadalafil, and the results of an initial dose ranging study would make it “very likely” that lower doses, up to and including 5mg, would be tested and found to be effective and safe. Essentially, the skilled person is always trying to find the minimum effective dose. Based on these findings of fact, the Court of Appeal (Actavis v Icos [2017] EWCA Civ 1671; [2018] RPC 7) overturned his decision and revoked the patent, and this revocation was upheld by the Supreme Court ([2019] UKSC 15; [2019] RPC 9). Notwithstanding the initial lack of any expectation of success of that specific dose, it was observed that “…the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials’ process” (Kitchin LJ, Court of Appeal). The Supreme Court agreed with this reasoning:

“I am not persuaded that, in the context of a dosage patent, it is necessary for the skilled team to identify in advance … the specific dose which is the subject of the claim. … In my view, the MedImmune requirement is met if the step by step approach, without the benefit of hindsight, demonstrates that the skilled team would be very likely to pursue the tests to the point at which they would ascertain the product or process falling within the claims.”

Lord Hodge Actavis v Icos [2019] UKSC 15

Nevertheless, the Supreme Court did emphasise that novel and inventive dosage regimes should be patentable, and there was no general presumption that the product of well-established or routine enquiries could not be inventive.

162.

In Hospira v Genentech [2014] EWHC 1094 the inventiveness of a new dosage schedule for an anti-cancer drug was considered. Birss J rejected the argument that the skilled person would not consider the new schedule, pointing out that the skilled person would be aware that changes to dosage regimes were a routine aspect of the development of existing drug treatments. He also held that there was nothing in the prior art or the common general knowledge to suggest the new dosage regime should not be trialled, and so it would be obvious to run a small clinical trial of the new schedule - on the facts of the case he considered that it would have a reasonable expectation of success. This decision was upheld at the Court of Appeal (Hospira v Genentech [2015] EWCA Civ 57), where it was pointed out that it was not necessary for the skilled person to know the new dosage schedule would work - all that was required was that the prospects of success were sufficiently good to warrant a small clinical trial. Similarly, in Novartis v Focus [2015] EWHC 1068 and Accord Healthcare v Medac [2016] EWHC 24; [2016] RPC 17, it was considered obvious to conduct trials of the claimed dosage regimes and in both cases the patents were revoked for lack of inventive step. In Accord Healthcare v Medac, it was held that the skilled team would include a drug formulator as well as a clinician and it would be obvious to the formulator to investigate dosages to reduce undesirable effects (in this case, injection pain). Second medical use claims defined by dosage regime were also found invalid for obviousness in Hospira v Cubist [2016] EWHC 1285; [2017] RPC 10, Fujifilm v Abbvie [2017] EWHC 395; [2018] RPC 1 and Generics v Yeda [2017] EWHC 2629; [2018] RPC 2. In the latter case, the claim was distinguished by the dosing schedule rather than quantity. The claimed schedule was one of several options that would be considered by the skilled person, each of which had a fair expectation of success given the prior art, and moreover the claimed schedule had obvious advantages in terms of patient compliance. On the other hand, in T 799/16 ACORDA the Board of Appeal accepted that a report that a clinical trial was to take place - including testing the claimed dosage - might at first sight give rise to an expectation of success. However, in this case the Board accepted the applicant’s arguments that the difficulties of assessing response to treatment in multiple sclerosis patients meant that the skilled person would have failed to appreciate the effectiveness of the claimed dosage regime after performing the trial, and so (unlike in Actavis v Icos [2019] UKSC 15; [2019] RPC 9) there was no routine pathway leading to the invention.

163.

The decision of the Hearing Officer in Advance Biofactures of Curacao’s Application BL O/303/04 (issued before Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26) illustrates some of the other factors which might, exceptionally, lead to a new dosage form being considered both novel and inventive. The active agent was present at substantially higher concentration than the prior art, and it was impossible in practice to deliver the required dose with the prior art solutions. Moreover, the person skilled in the art would have considered this higher concentration to have unacceptable side effects, and the concentrated composition was successful in treating a group of patients who did not benefit from treatment with the prior art compositions. A new dosage regime was found to be inventive by the Technical Board of Appeal in T 2015/20 ALMIRALL on the grounds that the closest prior art was directed to lowering the dose of the agent in question and so pointed away from the claimed higher dose.

Second medical use claims - the new use

i) Treatment of a new disease or condition

164.

The decisions of the EPO Enlarged Board of Appeal in G 05/83 (Second medical indication) and the Patents Court in John Wyeth’s and Schering’s Applications [1985] RPC 545 established that the use of a substance for a “new and inventive therapeutic application” could (prior to G 02/08 (Dosage regime/ABBOTT RESPIRATORY) and the release of our Practice Notice on 26 May 2010) be protected by a Swiss-type claim, while Section 4A(4) allows such a use to be protected by the direct form of second medical use claim. Typically, second medical use claims are used to protect the use of a substance or composition in the treatment of a specified disease, where it had previously been used for the treatment of a different disease. Providing the use of the substance in the treatment of the specified disease is not known, such claims are considered to be novel.

165.

It may be more difficult to determine whether a second medical use claim is novel if the new use is the treatment of a specific form of a disease, where the prior art discloses (or appears to disclose) the treatment of a wider class of diseases. Examples considered by the EPO Boards of Appeal include the use for treating pancreatic cancer of an agent known for the treatment of a variety of other cancers (T 385/07 PHARMA MAR), adenocarcinoma of the ovary as opposed to ovarian cancer in general (T 1001/01 SMITHKLINE BEECHAM), and hormone refractory prostate cancer as opposed to prostate cancer in general (T 380/05 PRAECIS PHARMACEUTICALS). As a general principle, a general disclosure of a class does not anticipate a claim to a specific member of that class. Nonetheless, a novelty objection should be made if the prior art disease class appears to encompass the specific disease claimed, and, either the specific disease is referred to in the prior art document as being treatable with the substance in question, or it may reasonably be implied that the prior art does disclose the treatment of the specific disease (for example, where the specific disease is the predominant form of the disease class). It would then be for the applicant to argue whether the prior art constitutes an enabling disclosure for the disease in question - in the three cases referred to above, the EPO decided that the specific use was in fact novel. Nevertheless, it should be emphasised that the mere discovery that a treatment is particularly effective in one particular sub-group of disease patients, does not render a claim novel if the substance has clearly been used to treat this sub-group (amongst others) in the prior art.

ii) New method, time, frequency or dosage of administration

166.

Second medical use claims which are distinguished from the prior art solely by the dosage regime used, or the mode of administration, are considered to be patentable if the claimed use is both new and inventive. This follows from the decision of the Court of Appeal in Actavis v Merck [2008] EWCA Civ 444 [2008] RPC 26; which led to a significant change in Intellectual Property Office practice in this field.

167.

In this case, the disputed claim was as follows:

The use of [finasteride] for the preparation of a medicament for oral administration useful for the treatment of androgenic alopecia in a person and wherein the dosage amount is about 0.05 to 1.0 mg.

Finasteride was a known drug (used for treating prostate conditions), which had in the past been proposed as a treatment for alopecia, but at a dosage of at least 5mg - the only new feature of the claim was thus the reduced dosage. The Court of Appeal held that the claim was valid, as it was novel, inventive and not excluded as a method of treatment by therapy (Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26). This overturned the decision of the Patents Court (Actavis v Merck [2007] EWHC 1311) that this claim lacked novelty, and was a method of treatment excluded under Section 4(2) of the Patents Act 1977. These two grounds for invalidity both stemmed from the earlier decision of the Court of Appeal in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1, which had governed UK patent practice in relation to dosage regimes and similar second medical use claims prior to the more recent Court of Appeal decision in Actavis v Merck.

168.

The claim in question in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 had the wording:

Use of taxol and sufficient medications to prevent severe anaphylactic reactions, for manufacturing a medicamentation for simultaneous, separate, or sequential application for the administration of from 135 mg/m2 up to 175 mg/m2 taxol over a period of about 3 hours or less as a means for treating cancer and simultaneously reducing neutropenia.

The Court of Appeal held that this claim defined an improvement in the method of administering an existing treatment; it did not define a new and inventive therapeutic purpose (Taxol(RTM) was known to treat cancer). In particular, it was noted that all the claimed steps were in fact directed at actions taken by the doctor, tailored to the individual patient, rather than being directed at the manufacturer.

“The claim is an unsuccessful attempt to monopolise a new method of treatment by drafting it along the lines of a Swiss-type claim. When analysed it is directed step-by-step to the treatment. The premedication is chosen by the doctor, and administered prior to the taxol according to the directions of the doctor. The amount of taxol is selected by the doctor as is the time of administration. The actual medicament that is said to be suitable for treatment is produced in the patient under supervision of the medical team. It is not part of a manufacture.”

Aldous LJ, Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 14

169.

Following this decision, the practice of the Intellectual Property Office was to treat second medical use claims which defined the new use in terms of the mode of administration, or the quantity, frequency or timing of dosage, as being unpatentable methods of treatment, disguised by drafting in the second medical use format. Moreover, such claims were also considered to lack novelty over the prior use of the substance to treat the same disease at a different dosage or by a different method of administration.

170.

This interpretation of Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 was supported by the Patents Court in Merck’s Patents [Alendronate] [2003] EWHC 5; [2003] FSR 498 (upheld by the Court of Appeal - Merck’s Patents [Alendronate] [2003] EWCA Civ 1545; [2004] FSR 330). In this case, a Swiss-type claim based on a new dosage regime (a single weekly administration of 70 mg of alendronate as opposed to daily administration of 10mg) was considered to be an unpatentable method of treatment.

171.

However, the Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 took the view that Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 provided no clear ‘ratio decidendi’ that a second medical use claim lacks novelty if the only difference between it and the prior art is a new dosage regime. There was therefore no binding precedent to consider in respect of novelty, and the Court concluded that a second medical use claim solely distinguished by a new dosage regime is novel over the use of the substance to treat the same disease at a different dosage. Second medical use claims which define a new dosage regime or mode of administration should therefore be considered novel, even if this is the only new feature of the claim. This does not, of course, mean that such a claim will necessarily be inventive - see .

172.

The Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 accepted that there was a clear ‘ratio’ from Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 that the claim at issue defined an unpatentable method of treatment. However, the dosage-specific claim of Actavis v Merck was considered to be directed at the manufacturer, and so was distinguished from the claim in Bristol-Myers Squibb v Baker Norton Pharmaceuticals which defined a series of steps performed by the doctor.

“So Aldous LJ decided the method of treatment point on a very narrow ground indeed. It was that if in essence the claim is merely to a method of treatment it is bad. The claim in the present case is far from that. It is in its essence directed at the manufacturer. The doctor’s only involvement will be in prescribing for the treatment of aa the 1mg pill made by an alleged infringer. We do not regard Aldous LJ’s ratio as binding in its effect so far as the general case of dosage specific Swiss form claims or so far as this case is concerned.”

Jacob LJ, Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26

173.

In addition to distinguishing the facts of the case from Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1, the Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 decided (unusually) that it was not in any case bound to follow its own, earlier decision. The reason the Court of Appeal gave for departing from its own precedent was that Bristol-Myers Squibb v Baker Norton Pharmaceuticals was inconsistent with the “settled view” of European patent law as interpreted in EPO Board of Appeal decisions.

174.

The EPO had historically taken a more liberal view of what constitutes a “new therapeutic use” than the UK courts. For example, claims were accepted in which the prescription regime of the treatment was specified (T 570/92 BAYER) and where the distinguishing feature was mode of administration (T 51/93 SERONO). On the other hand, in T 56/97 EURO-CELTIQUE, a Swiss-type claim defined by an amount of thiazide diuretic “with the range of 7-25% by weight of the predetermined diuretic effective dose” was refused as a method of treatment. In this case, the Board noted that the pre-determination of the “diuretic-effective dose”, and the determination of the dosage for achieving the desired result, required the exercise by the medical practitioner of his professional skill. However, in the later decision T 1020/03 (Method of administration of IGF-I/GENENTECH INC.) it was held that the new therapeutic use may relate to any new and inventive use falling within Article 52(4) (equivalent to the now-repealed Section 4(2)). The claim in question was distinguished by the precise timing of an intermittent course of treatment over a period of several weeks, and this decision was followed in subsequent Technical Board of Appeal decisions.

175.

As a result of this, the Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 held that the approach taken in T 1020/03 (Method of administration of IGF-I/GENENTECH INC.) represented the “settled view” of the EPO on this issue. This was confirmed by the decision of Enlarged Board of Appeal in G 02/08 (Dosage regime/ABBOTT RESPIRATORY); which considered the following specific questions:

1. Where it is already known to use a particular medicament to treat a particular illness, can this known medicament be patented under the provisions of Articles 53(c) and 54(5) EPC 2000 for use in a different, new and inventive treatment by therapy of the same illness?
2. If the answer to question 1 is yes, is such patenting also possible where the only novel feature of the treatment is a new and inventive dosage regime?
3. Are any special considerations applicable when interpreting and applying Articles 53(c) and 54(5) EPC 2000?

176.

The Enlarged Board’s decision on the third question is discussed above (see ). In answer to the first two questions, the Board decided that a medicament could be protected under Art. 54(5) EPC for use in a different method of treating the same disease as the prior art, and this could include uses where the dosage regime is the only new feature.

177.

In view of the decisions in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 and G 02/08 (Dosage regime/ABBOTT RESPIRATORY), second medical use claims defined by a new dosage forms, or new modes of administration (for example, intramuscular as opposed to intravenous injection) should therefore not be objected to under Section 4A(1) as being an unpatentable method of treatment. It was pointed out in Actavis v Merck that manufacturers have to provide detailed information relating to uses and dosages with their medicines, and so such a claim can fairly be said to be directed at the manufacturer, rather than the doctor. Moreover, a new dosage regime may necessarily result in the use of a wholly different composition, for example, where the active agent is present at a different concentration compared with the prior art (Advance Biofactures of Curacao’s Application BL O/303/04).

178.

The Court of Appeal in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26 took care to identify the narrow ‘ratio’ in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1 and distinguish the claim in question (and typical dosage regime claims in general) from it, and so it is not clear that the Court considered that the ‘ratio’ in Bristol-Myers Squibb v Baker Norton Pharmaceuticals was no longer relevant. However, since the decisions in Actavis v Merck and G 02/08 (Dosage regime/ABBOTT RESPIRATORY) were issued in 2010, no subsequent decisions of the UK Courts have suggested that either form of second medical use claim can be construed as defining an unpatentable method of treatment by therapy - further UK court cases relating to new dosage regimes are discussed in . Moreover, in discussing the infringement scope of Swiss-type second medical use claims, Arnold J in Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3 held (at 683) that the invention defined in Swiss-type claims is, by definition, a process of manufacture (limited to the intended use) rather than a method of treatment. The infringement scope of EPC 2000 second medical use claims has not yet been tested, but as it is accepted that they are “purpose-limited” product claims rather than method claims it would appear less likely still that they could be construed as defining unpatentable methods.

179.

However, an objection may be raised if the claimed use includes a surgical, therapeutic or in vivo diagnostic step which is not in fact directly connected to the administration of the agent in question. In T 566/07 MELLES, the Technical Board of Appeal rejected a claim to the use of a dye “for staining a retinal membrane … in a method for performing retinal membrane removal” on the grounds that the claimed use of the dye solely related to staining the retina, and not to the surgical removal of the retina. This was considered to be an entirely separate surgical method step (even though it was worded as part of the second medical use) and so the claim was rejected under Art. 53(c) as defining a method of treatment by surgery. Similarly, in T 1075/09 LABORATOIRES SERONO a second medical use claim to a new use of LH (luteinising hormone) which included the words “and wherein folliculogenesis is induced by the administration of FSH [follicle stimulating hormone]” was considered to define both a second medical use for LH and a method step of administering FSH, and so included an unpatentable method of treatment. This objection was overcome by amending the claim to define a new use of FSH and LH, with defined steps of administering each hormone.

180.

The type of objection was raised in EOS Neuroscience’s Application BL O/579/18, to a claim to a recombinant nucleic acid for use in a method of relieving neuropathic pain, wherein the method comprised expressing the nucleic acid in a nerve cell and controlling its activity with a light beam - this latter step required a surgical implantation. Following T 566/07 MELLES, the examiner objected that this was a second medical use claim combined with a separate surgical step, and so was unpatentable under s.4A(1). However, the hearing officer found that, unlike in T 566/07, in this case the illumination with a light beam was an integral part of the claimed medical use as without this illumination there was no therapeutic effect, and so this objection was not upheld.

181.

In T 1819/13 ZOETIS, the argument was made that as the advantages of a new administration route for antibiotics in farm animals were not therapeutic (instead relating to ease of administration and a reduction in antibiotic residues in the animals after slaughter), a claim defined by this route of administration was not novel. The Board of Appeal rejected this argument; as the use was therapeutic and the mode of administration was novel and inventive, the invention could be protected by a second medical use claim. If a second medical use claim is distinguished from the prior art by a new and inventive mode of administration, the reason for the new mode does not matter. Notwithstanding the settled view of the EPO that a new use can relate to a new method of administering the same agent to treat the same disease, the Technical Board of Appeal in T 174/07 GENVEC held that a negative feature of the method of administration (that the substance be administered and nature left to take its course) did not provide novelty over prior art in which further steps were taken following administration.

iii) New patient group/Personalised medicine

182.

A second medical use claim may, in limited circumstances, rely for novelty and inventive step solely on the type of patient to be treated, despite the fact that the active agent and disease treated have already been associated in the prior art. This type of claim was first considered in T 19/86 (Pigs II). It was held that the use of a known vaccine for preventing a known disease constituted a second medical use which could be protected by a Swiss-type claim when the type of animal treated (sero-positive pigs) was different from that previously treated in the art (sero-negative pigs). Similarly, in T 893/90 QUEEN’S UNIVERSITY KINGSTON, the use of a composition to treat bleeding in non-haemophiliac humans was not anticipated by its use in treating bleeding in haemophiliac patients.

183.

The selection of patient groups has become increasingly important due to advances in genetic testing and the development of “personalised medicine”, wherein treatments are tailored to the individual patient. The Technical Board of Appeal in T 233/96 MEDCO RESEARCH set out a number of conditions for this type of second medical use claim. Firstly, the new patient group must be clearly distinct from the subjects treated in the prior art, and the two groups must not overlap. Secondly, the distinction must not be arbitrary, but must be based on a functional relationship between the physiological or pathological characteristics of the new group and the therapeutic effect. In T 108/09 ASTRAZENECA, the Technical Board of Appeal considered whether the feature that a cancer patient had been previously treated unsuccessfully with another agent could provide novelty. The Board noted that the development of resistance to anti-cancer agents leads to physiological changes in the tumour, and so the post-treatment patients would have a different pathology to the pre-treatment patients, and this was a genuine difference in the new patient group. The Board distinguished this from a mere presentation of information about the medical history of the patient. This implies that a feature of the patient group with no physiological or pathological relevance (for example, the mere fact that the patients have previously been the subject of a genetic test) could not form the basis of a valid patient group selection. If, for example, “for use in treating cancer in patients with genotype ABC” does not confer novelty because patients with that genotype (amongst others) have already been treated with the same agent, then a claim to the use of the agent “for use in treating cancer in patients with a positive result in a test for genotype ABC” would also not be novel.

184.

Notwithstanding the earlier decision in T 233/96 MEDCO RESEARCH, the EPO have held in other decisions that the new patient group can overlap with, or be a subset of, the patients treated in the prior art. In T 1399/04 SCHERING a known treatment for hepatitis C virus (HCV) was used to treat patients infected with a high titre of the HCV-1 subtype. This claim was considered new and inventive, despite the fact that over half of HCV-infected patients fell within this category. Similarly, a claim to the use of a known treatment for rheumatoid arthritis (RA) in patients defined as being refractory to treatment with TNF-alpha inhibitors (30-40% of all RA patients fall into this category) was held to be novel over a prior art treatment of over 100 patients in a clinical trial where the patients were selected on grounds of being refractory to a different treatment (T 734/12 GENENTECH). However, in this case the new patient group selection was found to be obvious as the skilled person would find it highly likely that at least some of the successfully treated patients were also refractory to treatment with TNF-alpha inhibitors. More recently, in T 694/16 N V NUTRICIA the Board of Appeal considered a novelty objection to a claim to the use of an agent to treat the same disease in a patient group characterised by certain markers; it was argued that it was statistically inevitable that at least some patients characterised by such markers would have been treated in the prior art. The Board rejected this “inherent” novelty argument, and held that where a claim specifies that the subject to be treated displays a clearly defined and detectable marker, which is not displayed by all subjects affected by or likely to develop that disease, then the purposive selection of the patients displaying the marker for the specified treatment is a functional feature characterising the claim. In rejecting the inherent novelty argument, the Board followed the reasoning relating to new uses of known substances in G 02/88 (Friction reducing additive), which held that a claim to the use of a known substance to achieve a new technical effect is novel if the technical effect has not previously been disclosed, even if it may have inherently taken place in a prior art method.

185.

UK Office practice is that a second medical use claim to an agent for use in the treatment of a disease in a specific patient group is not new if the agent has already been used to treat the same group of patients amongst others, with the same disease. Insofar as this may depart from EPO practice, this is based on the decision of the Patents Court in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [1998] EWHC 300; [1999] RPC 253, that a new piece of information about an advantage, or how a treatment worked, did not constitute an invention if it did not lead to a new use. This aspect of the decision was upheld at appeal (Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1) and was not challenged in Actavis v Merck [2008] EWCA Civ 444; [2008] RPC 26. Moreover, the UK courts have interpreted G 02/88 (Friction reducing additive) narrowly, such that a use claim based on a newly discovered technical effect can only be considered novel if it leads to a new use which is clearly different from the old use (see below). The discovery that the treatment works particularly well for a group of patients does not therefore render such a claim novel if that same group of patients has already in fact been treated for the disease with the same agent. This is merely the discovery of an advantageous property of a known treatment. Nonetheless, a general disclosure that an agent may be used to treat a disease does not necessarily anticipate a specific claim to the treatment of a subgroup of patients with the disease, unless it can be shown that treatment of this subgroup is explicitly or inherently disclosed in the prior art ().

186.

Furthermore, novelty could be established for the selection of a patient group if the “use” part of the claim specifies the actual selection (e.g. by identification of patients carrying a particular marker) of patients as a step in their treatment. As discussed above (see ), second medical use claims may be distinguished by details of the treatment method used, and so a claim of the following form could be accepted if novel and inventive:

Substance X for use in a method of treating a patient with disease Y, wherein the method comprises:

(i) determining whether an isolated sample from the patient comprises biomarker Z; and

(ii) if the test sample comprises biomarker Z, administering substance X

This form of claim would only be acceptable where the diagnostic test is directly related to the patients’ suitability for treatment with a specific agent or class of agents. If the invention is simply a new diagnostic method to identify a disease, then a claim to, for example, an “an anti-cancer agent, for use in treating cancer, wherein the method comprises diagnosing cancer by…” would be objectionable through lack of clarity (as the agent is not clearly defined) and potentially lack of support and/or sufficiency if the application provides no evidence in relation to any treatment – (see ). In addition, if the diagnostic method is practised on the body, then the claim as a whole may be objectionable on the grounds that it includes an in vivo diagnostic step which is not in fact directly connected to the administration of the agent in question – (see ).

187.

A related aspect to patient groups is a claim distinguished by the clinical circumstances in which the drug is administered. In Teva v AstraZeneca [2014] EWHC 2873 the use of an inhaled preparation to treat asthma in both regular maintenance therapy and “rescue” therapy for treating acute attacks was considered novel (but not inventive) over the previous use of the preparation in maintenance therapy only. Second medical use claims may therefore also be used to protect treatment of patients in a new and inventive clinical situation.

iv) New mechanism or technical effect

188.

Second medical use claims which relate to the same therapeutic purpose as the prior art, but are solely distinguished by claiming a different technical effect or mechanism of action, should be rejected as lacking novelty; how a treatment works is irrelevant.

189.

This question was considered by the Patents Court in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [1998] EWHC 300; [1999] RPC 253. It was held that a new piece of information about how a treatment worked did not constitute an invention if it did not lead to a new use; this aspect of the decision was upheld by the Court of Appeal (Bristol-Myers Squibb v Baker Norton Pharmaceuticals [2001] EWCA Civ 414; [2001] RPC 1).

This decision was followed by the Patents Court in El-Tawil’s Application [2012] EWHC 185, where a claim was considered to relate to a combination of newly discovered technical effects, and newly discovered advantages of a known treatment, neither of which conferred novelty. Furthermore in Actavis v Janssen Pharmaceutica [2008] EWHC 1422; [2008] FSR 35 the Patents Court held that a second medical use claim relating to the use of a substance for “potentiating the effects of [other] blood pressure reducing agents” was not novel because the agent had already been disclosed for use in treating hypertension in combination with other agents as defined in the claim, and the “potentiation” would have occurred inherently in the prior art use - this was merely more information about the mechanism of action of a known treatment.

190.

These decisions contrast with the decision in T 290/86 (Cleaning plaque) that a second medical use claim can derive novelty from a new technical effect (in this case, strengthening of tooth enamel as opposed to removal of plaque), even where the condition to be treated and the agent are the same. This was based on the decision of the Enlarged Board of Appeal in G 02/88 (Friction reducing additive), which held that a claim to the use of a known substance to achieve a new technical effect is novel if the technical effect has not previously been disclosed, even if it may have inherently taken place in a prior art method. The UK courts have interpreted G 02/88 narrowly, such that a use claim based on a newly discovered technical effect can only be considered novel if it leads to a new use which is clearly different from the old use. The Patents Court in Bristol-Myers Squibb v Baker Norton Pharmaceuticals [1998] EWHC 300; [1999] RPC 253 and in Actavis v Janssen Pharmaceutica [2008] EWHC 1422; [2008] FSR 35 considered both G 02/88 and T 290/86 and declined to follow the Technical Board’s approach in the latter case. Similarly, in a non-medical case, Tate & Lyle Technology v Roquette Frères [2009] EWHC 1312; [2010] FSR 1 (upheld at appeal, though this was solely concerned with the construction of the claim - [2010] EWCA Civ 1049), a claim to “the use of maltotriitol to modify or control the form of maltitol crystals”, was held to lack novelty over a number of prior art documents which disclosed crystallisation of maltitol in the presence of maltotriitol at levels at which it would control crystal formation, even though this effect was not recognised (see ). Our practice based on this case law is therefore that a newly-discovered technical effect cannot - on its own - confer novelty to a second medical use claim.

191.

Notwithstanding the decision in T 290/86 (Cleaning plaque), there are a number of EPO Board of Appeal decisions which establish that merely specifying a new mechanism of action is not enough to provide novelty if it does not lead to a genuinely new therapeutic use. In T 254/93 (Prevention of skin atrophy), the EPO Technical Board of Appeal held that a newly discovered mechanism (in this case, how a dermatological composition with reduced side-effects achieved this effect) could not confer novelty; the claimed “technical effect” related merely to an explanation of the mechanism behind the treatment.

“The Board considers that the mere explanation of an effect obtained when using a compound in a known composition…cannot confer novelty on a known process if the skilled person was already aware of the occurrence of the desired effect when applying the known process”

T 254/93 (Prevention of skin atrophy)

192.

This was reinforced by the EPO Board of Appeal in T 486/01 GENENTECH, which held that the discovery of an additional mechanism of action of the protein IGF-1 in treating neurological diseases did not give rise to any new use over the prior art.

“For a medicinal application to be construed as a ‘further medical use’ this new technical effect would have to lead to a truly new therapeutic application, such as the healing of a different pathology or the treatment of the same disease with the same compound, however, when carried out on a new group of subjects distinguishable from the previously suggested subjects for such treatment…”

T 486/01 GENENTECH

Similarly, in T 406/06 NOVO NORDISK, the “stimulation of beta cell proliferation” was considered merely to provide an explanation of the known anti-diabetic effects of GLP-1. In T 1972/14 NESTEC, the Board of Appeal distinguished between the therapeutic effect (in this case, reducing the risk of developing obesity) and the mechanism underlying it (reduction in level of the protein IGF-1). As the prior art disclosed the use of the same composition achieving the same therapeutic effect, the claim was considered to be anticipated, notwithstanding the lack of any disclosure of an effect on IGF-1 levels.

193.

However, in other EPO decisions, claims defining the use of an agent to treat the same disease as the prior art but defined in terms of a specific effect have been allowed. For example, in T 509/04 ALLERGAN, a claim relating to the use of botulinum toxin to promote normal muscle growth in juvenile cerebral palsy patients was held to be novel over the previous successful use of the toxin to treat the same disease, in the same patient group. The prior art document did not suggest any activity in promoting muscle growth - it was instead known to act as a muscle relaxant - but the Opposition Division held that the muscle promotion activity was inherent in the prior art treatment. Nonetheless, the claim was considered to be both new and inventive by the Board of Appeal on the basis that the claimed technical effect (promoting muscle growth) was not disclosed or suggested in the prior art. In T 836/01 YEDA, the use of a medicament to directly restrict the growth of tumour cells was held to be novel over its previous use in immunotherapy for cancer. In a similar case, the use of an agent to treat cancer by restricting the growth of new blood vessels was held to be novel over its previous use as a direct anti-tumour effect (T 1642/06 SPRUCE), and a treatment of bacterial infection by killing the bacteria as opposed to merely neutralising their toxins was also allowed (T 1955/09 OCTOPLUS SCIENCES). In these latter three cases it was held that the new technical effect either led to a different category of patients who would be suitable for treatment, and/or a treatment of a different clinical situation. As discussed above in , claims defined by a new and inventive patient group or the administration to patients in different clinical circumstances can be allowed in situations where this is not encompassed by the prior art treatment. A newly discovered technical effect may therefore lead to a new and inventive claim defined in part by the patient group, the clinical circumstances, the dosage or some other feature of the treatment which is clearly distinguishable from the prior art.

194.

In G W Pharma’s Application BL O/237/12, a claim solely distinguished on mechanistic grounds from the prior art was refused by the Hearing Officer under s.1(2) as being a discovery, rather than on grounds of novelty, and the non-medical use claim in Tate & Lyle Technology v Roquette Frères [2009] EWHC 1312; [2010] FSR 1 was also held to be a discovery in addition to lacking novelty. However, recent case law has confirmed that EPC 2000 second medical use claims (which are now the only allowable form) are construed as products, limited by their purpose, and so this objection should not be raised to claims in this format - if the only new feature is the discovery of the mechanism then the claim should be objected to as lacking novelty and any objection under s.1(2) would in any case be superfluous.

v) New advantage to known use

195

The discovery of an unexpected advantage in a known treatment does not constitute a new therapeutic use, although it may form the basis of such a use. In Bristol-Myers Squibb v Baker Norton Pharmaceuticals ([2001] EWCA Civ 414; [2001] RPC 1 and [1999] RPC 253), the claim was based partly on the unexpected discovery that a shorter infusion time for a chemotherapeutic agent led to a lessening of the harmful reduction in white blood cells (neutropenia). However, the shorter infusion time had already been disclosed - this was merely an additional piece of information about a known treatment.

Similarly, the identification of symptoms which are alleviated by a known treatment does not in itself confer novelty (El-Tawil’s Application [2012] EWHC 185).

vi) Level of efficacy of treatment

196.

In general, a claim solely distinguished by an improved level of efficacy in comparison to existing treatments would not be regarded as a new and inventive therapeutic application, and may also lack clarity as being defined by a desired result. For example the “hastened onset” of pain relief was not considered to be a new medical use when the substance in question was already known as an analgesic (T 315/98 STERLING/S(+) ibuprofen [2000] EPOR 401). However, the courts have accepted that the achievement of a specified level of efficacy may be a functional technical feature of a claim that can establish novelty over a prior art disclosure of treatment of the same disease with the same agent. In Hospira v Genentech [2015] EWHC 1796; [2016] RPC 1, the patent in dispute claimed the use of an antibody to treat breast cancer in combination with a taxoid (a class of anti-cancer compound) “to provide clinical benefit as measured by increased time to disease progression”. “Time to progression” (TTP) is one of a number of measures of the efficacy of anti-cancer treatments. On the facts of the case, Arnold J held that this meant that the claim required that the treatment be capable of providing increased TTP compared to treatment with a taxoid alone, although in the event this feature was not critical for the establishment of novelty as it could not be established that this combination of drugs had been used to treat cancer in the prior art, and the patent was revoked on inventive step grounds. It was accepted that an actual measurement of TTP may not be needed if the increased TTP could be inferred from another measurement - consistent with the finding in T 669/01 PHARMACIA that “a different test for the same medical condition cannot render a known process or use novel”. It was also accepted that the claim did not require any specific level of increase. Nevertheless, in this case the achievement of a defined level of therapeutic efficacy was considered to be a functional technical feature of the claim. This reasoning was upheld by the Court of Appeal (Hospira v Genentech [2016] EWCA Civ 1185; [2017] RPC 14). Of course, if a claim defines a certain level of efficacy and the prior art discloses actual treatment with the same agent for the same purpose in the same way, it would be reasonable to infer that the efficacy would be comparable in the absence of any contradictory evidence. In Generics v Yeda [2017] EWHC 2629; [2018] RPC 2, a specific reduction in side effects compared to a prior art dosing schedule was considered to be a functional technical feature of a dependent claim (where the main claim defined the schedule without this claimed feature). However, it was accepted that if the claimed dosing schedule had in fact been anticipated by the prior art, then this technical effect would inevitably be achieved. In the event both the main claim and this dependent claim were found to be novel but not inventive.

vii) Functional definition of the new medical use

197.

Section 4A(4) allows the protection of a specific new and inventive therapeutic application of a substance or composition. The scope of the claimed use must be clear to the person skilled in the art. In cases where the disease or diseases to be treated are clearly defined in the claim, then this requirement is met. However, this may not be the case where the use is only defined in mechanistic terms; and so if the examiner is in any doubt that the skilled person would know what the claimed use means in terms of the treatment of specific conditions then an objection of lack of clarity should be raised. It is then for the applicant to show that the skilled person would be able to determine the scope of the claim without an undue burden of research. As held in T 241/95 (Serotonin receptor/ELI LILLY), a second medical use claim in which the new use is defined in functional terms can only be regarded as clear if means (in the form of experimental tests or other testable criteria) for assessing whether or not a condition falls within the scope of the claim are available to the skilled person from the specification or the common general knowledge. In this decision the Board of Appeal rejected on grounds of clarity a Swiss-type claim for the use of a compound in the treatment of “a condition which can be improved or prevented by selective occupation of the 5-HTic receptor”.

“…the ‘selective occupation’ of a receptor, although being indisputably a pharmacological effect, cannot in itself be considered a therapeutic application. The discovery on which an invention is based, even if representing an important piece of scientific knowledge, still needs to find a practical application in the form of a defined, real treatment of any pathological condition in order to make a technical contribution to the art and be considered an invention eligible for patent protection.”

T 241/95 (Serotonin receptor/ELI LILLY)

Similarly, in G W Pharma’s Application BL O/237/12, it was held that the application did not teach how to determine whether or not a cancer fell within the mechanistic definition used in this application. Definitions of therapeutic uses based on molecular activities (such as inhibition of the activity of a receptor, as in T 241/95) may be particularly problematic from a clarity point of view. Although it may be relatively straightforward to determine whether an agent binds or inhibits a receptor, it is likely to be much more complex to definitively determine the role of the receptor in a given pathology.

198.

Nevertheless, functional or mechanistic definitions of the therapeutic use are not necessarily unclear. In Regeneron Pharmaceuticals v Genentech [2012] EWHC 657 the Patents Court considered whether a claimed use for the treatment of “a non-neoplastic disease or disorder characterised by undesirable excessive neovascularisation” was so ambiguous and unclear as to be insufficient. Floyd J rejected this allegation:

Although (being a post-grant revocation case) Floyd J was addressing sufficiency (s.14(3)) rather than clarity (s.14(5)(b)), this decision (upheld at appeal - Regeneron Pharmaceuticals v Genentech [2013] EWCA Civ 93; [2013] RPC 28) does show that mechanistically-defined uses are not considered to be inherently so unclear as to be insufficient by the UK courts.

199

In addition to considering clarity, the examiner should also consider whether a functional or mechanistic definition is merely the identification of a mechanism or additional advantage of a known treatment (see above, ). A novelty objection should be raised if the functional definition includes diseases which have already been treated by the drug in question in the prior art. A common mechanistic feature, if new and inventive, may nevertheless provide the common subject matter between second medical use claims for different diseases (see below, ).

viii) Use in association with another agent

200.

Second medical use claims to the use of a composition comprising two or more agents together for the treatment of a disease are allowable providing the combination has not previously been used for the specified purpose. The inventiveness of claims of this type needs to be scrutinised carefully, to determine whether the claim represents a mere collocation of known elements - below. A claim to the use of an agent for the manufacture of a medicament to reduce the side effects T 254/93 (Prevention of skin atrophy)), or to potentiate the effects (Actavis v Janssen Pharmaceutica [2008] EWHC 1422; [2008] FSR 35), of another agent in the treatment of a disease will not be considered novel if the two agents have been used together before for the treatment of that disease and these effects can be inferred. It is irrelevant whether the prior art discloses the specific effect that the agent has - this is merely the discovery of an additional advantage to a known treatment. For example, in Actavis v Janssen Pharmaceutica, the use of one stereoisomer to potentiate the blood-pressure reducing effects of other agents - including one of the other stereoisomers - was held to be anticipated by the use of a racemic mixture of the isomers for the treatment of hypertension. The fact that the synergistic effect of the isomers was not recognised in the prior art did not render the claim novel. In GlaxoSmithKline v Wyeth [2016] EWHC 1045, Carr J considered the construction of a claim to a combination of a newly identified antigen (the “2086 protein”) and a known protein (PorA) for vaccination against meningitis. Based on the teaching of the specification, he held that this did not encompass vaccines comprising a non-functional 2086 protein, where efficacy came from PorA alone; the entire teaching of the patent was that the combination gave an improvement over the acknowledged prior art vaccination with PorA alone.

201.

The absence of a synergistic effect between the two agents is likely to lead to an inventiveness objection, but providing some efficacy in the claimed treatment is shown then a lack of synergistic effect does not give rise to an objection on grounds of sufficiency or support (T 1616/09 SUPERGEN). However, if - as in T 677/11 DUPONT - the claim actually defines the synergistic effect as an essential feature, then the absence of any evidence in the application showing such synergy could lead to such an objection. In the case of combination vaccine products, then inventiveness may be demonstrated by complementary rather than synergistic effects, so that protection in the population (as opposed to an individual) is enhanced through targeting different subtypes of the pathogen (GlaxoSmithKline v Wyeth [2016] EWHC 1045).

202.

In T 1075/09 LABORATOIRES SERONO, a claim relating to the combined use of two hormones was worded in such a way that it was construed as being a second medical use claim to one, and a method of treatment claim to the other, as discussed above in . The wording of claims relating to combined treatments therefore needs to be checked to ensure that they do not define a method of treatment by therapy, separate from the definition of the new use.

ix) Use in treatments performed outside the body

203.

As discussed in , therapeutic treatments such as dialysis where blood or tissue is treated outside of the body and returned to the patient are considered to be methods of treatment by therapy and so are unpatentable under s.4A(1). It therefore follows that an invention relating to the use of a known substance or composition for such an ex vivo treatment method could be protected using a second medical use claim. This practice accords with the decision of the EPO in T 2003/08 EDWARDS LIFESCIENCES, where a second medical use claim to the use of an agent for the treatment of a condition by removing immunoglobulins from plasma ex vivo before reinfusing the blood was allowed. This reversed the EPO practice established in T 138/02 KANEGAFUCHI, where it was held that Swiss-type claims could only protect the use of the substance or compound as a “medicament” (based on the wording of the decision in G 05/83 (Second medical indication)), and it was an essential feature of a medicament that it was administered to the body. (NB s.4A(4) make no reference to “medicaments”, and so the reasoning in T 138/02 would not in any case appear to apply to EPC 2000 claims.) In view of T 2003/08, and the UK case law (Schultz’s Application BL O/174/86 and Calmic Engineering’s Application [1973] RPC 684) which establishes that such methods are excluded under s.4A(1), we would allow second medical use claims for new and inventive uses of substances in ex vivo treatments.

204.

As discussed in , this applies only to treatments where the blood or tissue is returned to the patient - treatment of stored blood is not regarded as therapy and so could not be protected by a second medical use claim.

Second medical use claims - the substance or composition

205.

In determining the scope of the claimed substance or composition in a medical use claim, the established principles of claim construction (as set out in ,, and 125.01 - 125.24) should be be followed. The Court of Appeal applied these principles to a second medical use claim in American Home Products v Novartis [2001] EWCA Civ 165; [2001] RPC 8, concerning Swiss type claims for the use of a known antibiotic (rapamycin) for inhibiting organ or tissue transplant rejection. The Court of Appeal held that the claim did not cover derivatives of rapamycin thus finding the claim not infringed by the use of a rapamycin derivative as an immunosuppressant. On the other hand, in Regeneron Pharmaceuticals v Genentech [2012] EWHC 657 (upheld at appeal - [2013] EWCA Civ 93; [2013] RPC 28), it was held, on interpreting the claims in light of the description, that the term “isolated hVEGF receptor” included fragments and variants of the naturally-occurring receptor which were capable of binding hVEGF and inhibiting its activity. In American Home Products v Novartis it was also held that the presence of the compound in question as an impurity in a medicament does not fall within the scope of a second medical use claim. In Actavis v Eli Lilly [2014] EWHC 1511; [2015] RPC 6 the Patent’s Court applied the “Protocol” questions to determine the scope of a second medical use claim to the use of “pemetrexed disodium” and concluded that it could not extend to other salts or the acid of pemetrexed, even though the choice of counter-ion made no difference physiologically. The Court of Appeal (Actavis v Eli Lilly [2015] EWCA 555; [2016] RPC 2) agreed on this point, but held that the claim did encompass a solution comprising at least twice as many sodium ions as pemetrexed ions. On appeal, the Supreme Court (Actavis v Eli Lilly [2014] EWHC 1511; [2015] RPC 6) held that a potassium salt did infringe the patent through application of the doctrine of equivalents. However, subsequent decisions have indicated that the doctrine of equivalents does not apply to the assessment of novelty - see .

206.

Claims are often made for the second medical use of a group of compounds defined functionally; for example, antagonists of a particular receptor. This type of claim was at issue in Pfizer’s Patent [2000] EWHC 49; [2001] FSR 16, which included claims to the second medical use of phosphodiesterase inhibitors. Such claims are not inherently objectionable, and in this case there was no suggestion that this form of claim was unduly broad and speculative. However, the support for such claims must be considered - this is considered further in below. Clearly, the mere fact that a member of a functional class of compounds can be used to treat a disease does not mean that all such compounds will, particularly if there is no evidence that the treatment is related to that specific activity. In Pfizer’s Patent it was held that a second medical use claim relating to, for example, the use of an inhibitor of A for the treatment of disease X, is anticipated by any disclosure of the use in treating disease X of a compound which is capable of inhibiting A, regardless of whether the treatment is explicitly stated as being caused by the inhibition of A. More recently, in Eli Lilly v Genentech [2019] EWHC 387, Arnold J construed a claim to “use of antagonist anti-IL-17A/F antibody… in the preparation of a medicament or the treatment of rheumatoid arthritis or psoriasis” as meaning:

(a) the antibody must have a discernible therapeutic effect, and

(b) inhibition of IL-17 A/F must make a significant contribution to the effect

In other words, where the agent is defined in mechanistic terms, it can be interpreted as requiring some activity through this mechanism. Nevertheless, it does not mean that this mechanism has to be disclosed in the prior art, and so examiners may infer any such activity if it can be established that a prior art compound can in fact act as an inhibitor or activator as appropriate.

207.

Claims of this type may give particular problems when searching. It is not feasible or economic for the examiner to identify all such agents and searching should be directed to the specific examples of the agents given in the application since finding these would produce the most relevant citations. In addition, keywords based on the functional class defined in the claim should be searched. An appropriate comment should be added to the search letter to indicate the extent to which the invention has been searched.

208.

A prior art citation showing the use of a substance produced by a chemical reaction from the compound in question does not anticipate a second medical use claim (though it may be relevant for inventiveness). This question was particularly relevant to Swiss-type claims: the wording of Swiss-type claims (but not the new form of second medical use claims) could suggest that they encompass derivatives produced from the substance in question. The Court of Appeal in Monsanto v Merck [1999] EWCA Civ 1946; [2000] RPC 77 considered whether a claim to “the use of compound X in the manufacture of a medicament for the treatment of disease Y” encompassed the use of X as a chemical intermediate in the production of the active agent in the medicament. It was held that it was at least arguable that it could, although it did not come to a final conclusion on the matter. However, the Court of Appeal in American Home Products v Novartis [2001] EWCA Civ 165; [2001] RPC 8 decided that if this was the case this would require a wide construction of the term “medicament” in the claim (that is, to mean a medicament not restricted to one comprising compound X), and this would leave the claim hopelessly broad. This question was also addressed in relation to infringement in Ranbaxy v AstraZeneca [2011] EWHC 1831. In this instance the Patents Court also held that a Swiss-type claim would be construed as being restricted to the use of the substance as a medicament, rather than as an intermediate in the production of a medicament, though Kitchin J emphasised that he had interpreted with reference to the description in this patent, rather than providing an absolute rule of construction of Swiss claims. The patent in question included both Swiss-type medical use claims and second medical use claims in the form “Substance X for use in the treatment of disease Y”. It was accepted by all parties that the latter claim clearly does not encompass any derivative produced from substance X, and so this ambiguity does not arise with the new format of second medical use claim. As we no longer allow Swiss-type claims, this issue of construction no longer arises in pre-grant patent applications at the Office.

209.

The novelty of a claim to a metabolite of a known substance, for use in treating the same condition as that known substance, is discussed at .

Plurality

210.

Where the substance is known to have a medical use, second medical use claims directed to a variety of different diseases may give rise to a plurality objection. A plurality objection may be avoided if the conditions are related (and unrelated to the known conditions), or if there is a common mechanism linking the treatments (see ).

Second medical use, apparatus and devices

211.

Second medical use claims, like first medical use claims, can only be used in relation to substances or compositions. Claims to a new use of surgical apparatus framed in the Swiss format were disallowed by the EPO in T 775/97 EXPANDABLE GRAFTS/Surgical device [2002] EPOR 24 and T 227/91 (Second surgical use), and by the Hearing Officer in National Research & Development Corporation’s Application BL O/117/85. Similarly, a purpose-limited product (EPC 2000) claim to a known device “for use in” a method of treating substance addiction was held to lack novelty over the previous disclosure of the device used for a different purpose in T 2369/10 CYBERONICS, and claims in both forms to the new use of a known implanted device for preventing incontinence were refused in T 1099/09 COLOPLAST.

212.

On the other hand, the EPO have allowed Swiss-type claims to the use of a substance in the manufacture of a “device” for intrapulmonary administration (T 138/95 GENENTECH) and the use a substance in the manufacture of a “column” for removing immunoglobulins from the blood ex vivo before re-infusing the blood to the patient (T 2003/08 EDWARDS LIFESCIENCES). The Swiss-type format used in these claims is no longer allowable, but these decisions raise the question of whether a second medical use claims to the use of a known substance or composition can be defined in part by the device or apparatus used to deliver the agent to the body (or to the bodily fluids as in T 2003/08). As discussed above at , second medical use claims may be distinguished from the prior art by the method used to administer the agent, and so in principle this may extend to the delivery device used. However, as discussed in , the decision in T 1278/12 N.V. NUTRICIA established that second medical use claims cannot be defined solely in terms of method of administration - they must define an actual therapeutic use. The claim at issue in T 138/95, which defined the use as being simply “intrapulmonary administration” by a particular device, would not seem to meet this criterion. Moreover, in general where a drug is known to be used in therapy by administration through a particular route (e.g. intra-pulmonary or intravenous) then the selection of a known device for administration of agents by that route would not be considered inventive in the absence of any strong reasons pointing away from its use. In addition, where the invention relates to a new device for administration of a substance into the body, then a second medical use claim of the form “a therapeutic agent for use in the treatment of [any disease] wherein the agent is administered using the device of claim 1” may be objectionable through lack of clarity (if the agent and/or condition treated is not clearly defined) and support and/or sufficiency if there is no teaching in the application relating to the administration of any specific agent or class of agents .

213.

In addition, in both T 1099/09 COLOPLAST and T 2003/08 EDWARDS LIFESCIENCES it was held that second medical use claims can only be used to protect the use of a known substance or composition as an active agent. The Technical Board in T 1758/15 INCEPT found support for this view from the Enlarged Board of Appeal’s reasoning in G 05/83 (Second medical indication) (responsible for establishing “Swiss-type” second medical use claims), where the term “active ingredient” was used interchangeably with “substance or composition” (see “Reasons” point 23 of G 5/83, for example). In T 1099/09, Swiss-type second medical use claims to the use of a “biocompatible material” in the manufacture of a device were refused as the therapeutic effect of treating incontinence did not result from the nature of the “biocompatible material”; instead it depended on the shape and dimensions of the implant. This indicates that a new method of using a known medical device cannot be protected merely by defining it as “material X for use in a method of treating disease Y by means of [device Z]”, wherein the material is not itself pharmacologically active and is merely a constituent of the device.

214.

In T 1758/15 INCEPT, an EPC 2000 second medical use claim to a “biocompatible, biodegradable filler material” such as collagen, for injection prior to radiotherapy to protect organs from off-target radiation was considered. The material was refused second medical use protection because its protective properties were said to be a result of its physical rather than active characteristics. The material was assessed to be an “initially viscous device” rather than a “substance or composition” within the meaning of EPC Article 54(5). In the later decision T 2136/15 CARDIOPOLYMERS, “a self-gelling alginate” for injection into the heart of a patient with cardiomyopathy was also considered to be a device. In this decision, the Board stated there was no need to seek clarification from the Enlarged Board of Appeal over what constituted a “substance or composition” within the meaning of EPC Article 54(5), since the existing settled case law had clearly established that its meaning was limited to “active ingredients” and that there was “no room for further opening” of this definition.

Second medical use claims: sufficiency, support, priority and industrial application

215.

There is now a considerable body of case law (from the UK Courts, EPO Boards of Appeal and IPO Hearing Officers) concerning the related questions of sufficiency (under s.14(3)/Art.83 EPC) and support for the claims (s.14(5)(c)) for inventions relating to second medical uses, as discussed below. There is also case law concerning the requirements for entitlement to priority under s.5. In Biogen v Medeva [1996] UKHL 18; [1997] RPC 1 (which did not concern medical use claims) Lord Hoffmann said that the requirements for sufficiency in s.14(3), for support in s.14(5)(b) and for entitlement to priority under s.5(2)(a) all related to the requirement for an enabling disclosure, and so case law in relation to sufficiency is persuasive (where relevant) on questions of support or entitlement to priority and vice versa. Lack of sufficiency - but not lack of support - is grounds for revocation under s.72(1)(c), and so all of the post-grant case law in this area relates to sufficiency. In rare instances, an insufficient application relating to medical uses may also be considered to lack industrial applicability under s.4 as discussed below.

i) Sufficiency

216.

As with inventions in all fields of technology, the application must disclose the invention in a manner which is clear enough and complete enough to be performed by the person skilled in the art. As discussed at greater length in , there are three types of insufficiency objection that have been established in the case law: “classical” insufficiency, insufficiency by excessive claim breadth and insufficiency by ambiguity, and there is case law relating to second medical use inventions for all of these objections.

217.

“Classical” insufficiency relates to a lack of a disclosure which would enable the skilled person to perform the invention without exercising inventiveness or an undue burden of research. In the case of invention relating to the medical use of a known substance or composition, the agent in question can generally be produced and formulated in a composition suitable for administration to the patient without undue burden or inventiveness. However, this is not the end of the story, as the UK Courts have followed the EPO Technical Board of Appeal’s decision in T 609/02 SALK INSTITUTE in holding that the claimed medical use is a “functional technical feature” of the claim. This means, firstly, that if the agent is not effective for the treatment of the disease, then the application or patent is insufficient. In Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737; [2014] RPC 1, evidence obtained after the filing date (the failure of subsequent clinical trials) was held to show that the teaching of the patent was insufficient. In Merck Sharp & Dohme v Shionogi [2016] EWHC 2989, evidence provided at the trial demonstrated that a significant proportion of the claimed compounds either did not possess antiviral activity or were unduly toxic for clinical use. In addition, the patent claimed the use of a vast range of compounds (of which the vast majority would not be effective) but gave no useful teaching to identify which would work, and the patent did not itself identify any such useful compounds. The patent was therefore found to be insufficient.

218.

Moreover, the Board of Appeal in T 609/02 SALK INSTITUTE held that the specification must disclose the suitability of the agent for the claimed therapeutic application. Absolute proof of efficacy, or clinical trials, was not necessary, but a simple assertion was not enough. In vitro tests could suffice if the skilled person would know from the prior art, or the specification demonstrates, that the in vitro effect shown has a direct bearing on the disease in question. In In T 1685/10 ARK THERAPEUTICS it was held that in vitro test conditions should be carefully selected and should correspond as closely as possible to in vivo conditions; in this case it was held that it did not, in particular through the selection of an inappropriate cell type. It was emphasised in T 609/02 that post-filed evidence could only be used to back up the findings provided in the patent application, and not in itself to establish sufficiency of disclosure.

“If the description of the patent specification, like in the present case, provides no more than a vague indication of a possible medical use for a chemical compound yet to be identified, later more detailed evidence cannot be used to remedy the fundamental insufficiency of such subject matter.”

T 609/02 SALK INSTITUTE

219.

The approach taken in T 609/02 SALK INSTITUTE was followed by the Patents Court ([2012] EWHC 657) and the Court of Appeal ([2013] EWCA Civ 93; [2013] RPC 28) in Regeneron Pharmaceuticals v Genentech. The Court of Appeal in this case held that the specification must make it “plausible” that the invention would work (i.e. be effective to treat the disease) across the claimed scope. This concept was summarised by Birss J in Hospira v Genentech [2014] EWHC 1094:

“…a rule which demanded clinical results could cause real difficulties. On the other hand, if all the patent contains is a mere proposal, then it has not made a contribution to the art in this example … Moreover it would be a recipe for abuse if all that was required in order to obtain a patent in this field was a proposal, without any basis, to use drug A to treat disease B. Patent law seeks to address these factors balancing the requirements for sufficiency of disclosure against the rules of novelty and inventive step. But the conventional sufficiency test of asking whether the claimed invention works, does not help. The treatment does work but what if the patent does not say so? For these reasons the idea of “plausibility” as part of the law of sufficiency of disclosure has been developed … The term “plausibility” has been coined to characterise what it is that a patent specification must provide in order to be sufficient, short of full clinical proof of efficacy.”

Hospira v Genentech [2014] EWHC 1094

220.

In Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10 it was emphasised that there is no standard test for plausibility and it must be determined on the facts of the case. As “plausible” is not a term used in either the Patents Act or the EPC 2000 there is no law of plausibility as such. In Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3 Arnold J held (at 344) that data which merely made it “obvious to try” to use the agent for the condition in question was not enough for sufficiency. On the other hand, in Actavis v Eli Lilly [2015] EWHC 3294; [2016] RPC 12, Carr J held that the standard for plausibility was lower than the “reasonable expectation of success” test in the context of obviousness (see above). He also held that there was no absolute requirement for experimental evidence to be provided in the specification for plausibility to be established - on the facts of the case it was held that a proposed mechanism based on prior art findings concerning the active agent rendered the claimed use plausible. In both Merck Sharp & Dohme v Ono and Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737; [2014] RPC 1 a claim was held to be plausible even though the active agent was not actually tested - in both cases, experimental evidence relating to active immunisation by a protein or peptide was held to render plausible a second medical use claim relating to an antibody against that protein or peptide for passive immunisation. In T 2015/20 ALMIRALL, evidence of effective treatment of chronic obstructive pulmonary disease (COPD) was considered to render plausible the use of the same composition to treat asthma; although the mechanisms underlying these conditions are not the same there were considered to be enough common features to render the claim plausible.

221.

The requirement for plausibility to render an application or patent relating to a second medical use sufficient has now been confirmed by the Supreme Court in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21. The Court unanimously rejected the view that the sole criterion of sufficiency is whether the specification enables the invention to be performed, and that plausibility is irrelevant. Lord Sumption argued that this “classical” definition of sufficiency is not adequate for second medical use claims as it allows wholly speculative patents to be granted: “…it would be possible to patent the manufacture of known compounds for the purpose of treating every conceivably relevant condition without having invented anything at all, in the hope that trial and error might in due course show that the product was efficacious in treating at least some of them.” Moreover, the majority view in this case (as set out by Lord Sumption) set out a number of principles which should be followed when determining the sufficiency of medical use claims:

9. The proposition that a product is effective for the treatment of a given condition must be plausible.

ii) It is not made plausible by a bare assertion to that effect, and the disclosure of a mere possibility that it will work is no better than a bare assertion.

iii) The claimed therapeutic effect may be rendered plausible by a specification showing that something is worth trying for a reason; i.e. not just because there is an abstract possibility that it would work but because reasonable scientific grounds are disclosed for expecting that it might well work. The disclosure of those grounds marks the difference between a speculation and a contribution to the art.

iv) Although the disclosure need not definitively prove the assertion that the product works for the designated purpose, there must be something that would cause the skilled person to think that there was a reasonable prospect that the assertion would prove to be true.

22. That reasonable prospect must be based on a direct effect on a mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the specification per se.

vi) This effect on the disease process need not necessarily be demonstrated by experimental data. It can also be demonstrated by a priori reasoning.

vii) This evidence or reasoning must appear in the specification. The disclosure may be supplemented or explained by the common general knowledge of the skilled person. However, it is not enough that the patentee can prove that the product can reasonably be expected to work in the designated use, if the skilled person would not derive this from the teaching of the patent.

222.

It was emphasised that the specification as filed must make the claimed use plausible; data filed after the filing date of the patent can only be used to confirm an effect made plausible in the specification or to refute a contention that the treatment does not actually work; it cannot be a substitute for sufficient disclosure in the specification. Lord Sumption, giving the majority view, considered a number of EPO Board of Appeal decisions relating to second medical use claims where the specification did not provide direct experimental evidence of the efficacy of the treatment, but the inventions were nevertheless held to be plausible. These included T 0578/06 IPSEN (where plausibility was considered in the context of inventive step), T 1437/07 ALLERGAN and T 950/13 BRISTOL-MYERS SQUIBB. While he accepted that experimental evidence was not always needed to demonstrate plausibility (point (vi) above) he did not consider that these decisions indicated that a patent or application could be sufficient if it provided neither evidence nor any reasoning in support of the claimed use. He also rejected the argument that such evidence or reasoning only needed to be provided in the specification when the claimed use was otherwise implausible.

223.

It should be emphasised that the common general knowledge does not form part of the contribution of the patent, and an application cannot demonstrate plausibility by relying exclusively on the common general knowledge. This is highlighted by Sandoz v Teva [2022] EWHC 822 (Pat), in which the patentees relied solely on the common general knowledge to argue plausibility for the efficacy of apixaban as a factor Xa inhibitor for treating clotting disorders. The ruling consolidates point (vii) of the criteria from Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 that the reasoning must be derived from the patent, and the common general knowledge must only supplement or aid explanations of teachings appearing in the specification. Interestingly, in Sandoz v Teva, the common general knowledge also acted to undermine the patentees’ case for plausibility: specifically, the skilled person’s expectation that nanomolar potencies would be required for effective therapeutic action when the patent did not demonstrate such values. This case highlights the importance of establishing the common general knowledge, as well as understanding its role and limitations in arguments for plausibility.

224.

In Epshtein’s Applications BL O/508/15 (a case involving both applications with per se composition claims and with second medical use claims), there was experimental evidence (both in vitro and in vivo) provided in the applications, and the Hearing Officer considered that this data would of itself render the claimed use plausible. However, he could not identify a plausible basis for these observed effects according to the conventional scientific view of therapeutic mechanisms, as a dose of any of the compositions would be statistically unlikely to contain any active agent due to the extremely low dilutions used, and the applications were held to be insufficient. However, on appeal to the Patents Court (Epshtein’s Applications [2016] EWHC 1511; [2017] RPC 11) it was held that if a claimed effect can be established to be plausible by evidence provided in the application, there is no need to establish a plausible theory to explain the effect. In T 0966/18 PROTHENA BIOSCIENCES (a case relating to an agent inducing an immunogenic response against α-synuclein, for use in the treatment of diseases characterized by Lewy bodies or α-synuclein aggregation in the brain such as Parkinson’s) the validity of the supporting tests in providing a plausible link was questioned. The mouse study of the key example was conducted using a small number of animals, and the results lacked assessment of their statistical significance. The Board considered that the lack of statistical information and the small number of animals would not have diminished the credibility of the results of the relevant example, because they build upon what the skilled person would have expected from the prior art, namely that a link existed between the reduction of α-synuclein aggregation and the treatment of Lewy body disease (see quality of evidence in the context of support at onwards). Clearly however, if the prior art or the common general knowledge would lead the skilled person to consider that a treatment will not work, then the application must provide some evidence to counter this view. In T 1592/12 GENENTECH, it was held that the skilled person would have serious doubts that a new dosage regime for a known antibody would be effective based on the prior art at the priority date; as the specification did not provide any evidence to overcome these doubts it was insufficient. Post-filed evidence of effectiveness could not be taken into account in this case as the plausibility of the treatment was not established in the application.

225.

Insufficiency by excessive claim breadth has been considered by the Courts in terms of both the breadth of the class of agents, and the range of conditions to be treated. In Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21, the Supreme Court agreed unanimously that sufficiency needs to be present across the breadth of the claim, and second medical use claims covering different conditions must be enabled across their full scope. The agent in second medical use claims may be broadly defined structurally (for example, by Markush formula for chemical compositions, or by reference to a defined level of sequence identity for proteins or nucleic acids) or defined in functional terms, or a combination of both. The Court of Appeal in American Home Products v Novartis [2001] EWCA Civ 165; [2001] RPC 8 (see above, ) concluded that, had the claim in question been construed as covering derivatives of rapamycin (or presumably, worded as covering derivatives), the patent would have been insufficient because there was no disclosure in the description enabling the skilled person to decide which of the many possible derivatives would have worked. Although there was a strong possibility that some of the large number of derivatives would work in the same way as rapamycin itself, it was impossible to say which would so work, unless the skilled person undertook the “vast and correspondingly burdensome” research task necessary. The bar for what constitutes an undue burden is discussed further in FibroGen v Akebia Therapeutics [2021] EWCA Civ 1279 below in ).

226.

However, if the specification discloses a principle capable of general application, a claim in correspondingly general terms may be acceptable - in Regeneron Pharmaceuticals v Genentech [2012] EWHC 657 (upheld at appeal - [2013] EWCA Civ 93; [2013] RPC 28), this test was applied and the claim to the use of antagonists of a particular receptor was considered to be a fair generalisation. In this case it was pointed out that in the pharmaceutical industry a period of trial and error, sometimes extending over months or even years, is entirely normal, and so the need for such experimentation does not render the claim insufficient. There is no need to show proof of its application in every individual possible instance which could fall within the scope of the claim. This principle is, of course, applicable to more than just second medical use claims, but is particularly important for such claims as they are defined by the purpose of the product.

“Thus if the patentee has hit upon a new product which has a beneficial effect but cannot demonstrate that there is a common principle by which that effect will be shared by other products in that class, he will be entitled to a patent for that product but not for the class, even though some may subsequently turn out to have the same beneficial effect… On the other hand, if he has disclosed a beneficial property which is common to the class, he will be entitled to a patent for all products of that class (assuming them to be new) even though he has not himself made more than one or two of them.”

Aldous LJ, American Home Products v Novartis [2001] EWCA Civ 165; [2001] RPC 8

227.

On the other hand, in Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737; [2014] RPC 1, a claim to the use of “antibodies against beta-amyloid peptide” for treating Alzheimer’s disease was not considered to be enabled across its full scope, in part because it was not considered plausible that antibodies targeting the mid-region or C-terminus of the peptide would have the desired effect.

228.

The sufficiency of second medical use claims to broad classes of compounds defined in both structural and functional terms should be assessed in light of the Court of Appeal’s decision in FibroGen v Akebia Therapeutics [2021] EWCA Civ 1279 . The claims in question related to heterocyclic carboxamides further defined by their functionality as hypoxia inducible factor prolyl hydroxylase (HIF-PH) inhibitors, for use in the treatment of anaemia. The Court of Appeal overturned the Patents Court’s ruling on insufficiency due to excessive claim breadth (Akebia Therapeutics v FibroGen [2020] EWHC 866 (Pat). Birss J remarked that the Patent’s Court had erred in its interpretation, particularly in failing to identify that the functional features as well as the structural features limited the scope of the claimed class of agents.

229.

In considerations of plausibility, Birrs LJ outlined a three-step approach for assessing the plausibility of claims of this type:

9. identifying what falls within the scope of the claimed class (i.e., compounds that satisfy not only the structural features, but also the functional requirements which may be determined via relevant testing);

ii) determining what it means to say the invention works (i.e., identifying those compounds that are effective in treating the condition); and,

iii) asking whether there is a reasonable prediction that the invention will work with substantially everything falling within the scope of the claim (i.e., will compounds satisfying both the structural and functional features have the claimed therapeutic efficacy?).

230.

Using this approach, the claims were found to have plausibility. Birss LJ also held that no issue arose from the claims’ scope encompassing compounds still yet to be invented, due to the inherent nature of functional language. He also made a distinction between a functional feature of the claimed agent (i.e. HIF-PF inhibition in this case) and the achievement of the therapeutic effect. The former, but not the latter, limits the scope of the claimed class of agent – it cannot be argued that the claim is sufficient because it is limited to compounds that “work” in the sense of treating the condition.

231.

The Patents Court (Akebia Therapeutics v FibroGen [2020] EWHC 866 (Pat)) also held that the claims were insufficient because the invention could not be performed across the full scope of the claims without an undue burden. The Appeal Court (FibroGen v Akebia Therapeutics [2021] EWCA Civ 1279) disagreed and held that it was not necessary to identify substantially all compounds covered by the claim, but to instead ask: firstly, whether the skilled person can identify further useful compounds beyond those named in the patent; and secondly, whether the skilled person can work substantially anywhere within the whole claim. Although the work required by the skilled person or team was likely to be relatively time-consuming, it was deemed to fall within routine and iterative procedures and thus was not considered to equate to an undue burden. It is worth noting that if a claim defines a functional parameter and tests to determine that parameter which are not either disclosed in the application or known from the prior art, then working the invention across the scope of the claim would require an undue burden of research.

232.

In Regeneron Pharmaceuticals v Genentech ([2012] EWHC 657 and [2013] EWCA Civ 93; [2013] RPC 28) it was argued that the claim was not sufficient due to the breadth of the conditions to be treated - a “non-neoplastic disease or disorder characterised by undesirable excessive neovascularisation”. Both the Patents Court and Court of Appeal considered that it was a fair prediction that an anti-angiogenic effect demonstrated in the specification in tumours would also extend to non-neoplastic diseases characterised by excessive angiogenesis (growth of new blood vessels into a tissue), due to the common underlying mechanism. Similarly, in in Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10, a broad claim to the “treatment of cancer” was considered to be a soundly based and reasonable prediction given the evidence provided in the patent - this did not mean that the invention would necessarily treat all cancers, but it was plausible that it treated a wide range of them and this was borne out by the evidence after the filing date. On the other hand, in Generics v Warner-Lambert [2015] EWHC 2548; 2016 RPC 3 Arnold J held that there was no common underlying mechanism which would allow extrapolation from an animal model of inflammatory pain to other types of pain; this conclusion was upheld by the Supreme Court (Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21). The Hearing Officer in 4D Pharma Research’s Application BL O/202/21 applied the reasoning of the Supreme Court in Warner Lambert v Generics to the question of whether an application which provided evidence of the effect of a bacterial strain on the inflammatory condition uveitis enabled a claim encompassing the use of other strains of the same species and in the treatment of other autoimmune disorders. He concluded that the claims were enabled across their breadth as it was plausible that the observed effects would extend to other strains and other autoimmune disorders, based on the prior art, the evidence provided in the application and the mechanism proposed in the application.

233.

An application is not considered insufficient through excessive claim breadth merely because it is not effective in every patient. In T 799/16 ACORDA it was argued that a new treatment for multiple sclerosis which had the effect of improving walking speed was insufficient because it was only effective in about a third of patients in a clinical trial. The Board held that the existence of a non-responding group of patients did not render the claim insufficient, and there was no need to disclaim the treatment of non-responders.

234.

In Regeneron Pharmaceuticals v Genentech [2012] EWHC 657 the Patents Court also considered whether the claimed use was insufficient due to ambiguity. It concluded that the skilled person would not have any difficulty determining whether a disease fell within the scope of “a non-neoplastic disease or disorder characterised by undesirable excessive neovascularisation”, and so rejected this attack on the patent.

ii) Support

235.

There is a body of UK case law which has consistently held that second medical use claims to the further medical use of a substance or composition must be supported by evidence in the specification that the agent is (or at least is likely to be) effective for the specified use. The absence of any such evidence in a patent application leads to an objection under s.14(5)(c) that the claims are not supported by the description. The Hearing Officer rejected second medical use claims for this reason in Hoerrmann’s Application [1996] RPC 341 and McManus’s Application [1994] FSR 558.

“…unless there is some indication in the description of applications of this type of tests, however rudimentary, demonstrating that the invention has been carried out in an effective manner then the application must fail for lack of support for the invention claimed.”

Hoerrmann’s Application [1996] RPC 341

In Consultant Suppliers’ Application [1996] RPC 348 it was emphasised that mere assertion that tests had been carried out was not sufficient. The decision of the Patents Court in Prendergast’s Applications [2000] RPC 446 confirmed that speculative second medical use claims are not allowable. It was emphasised that full clinical trials on humans are not needed to satisfy the requirements of section 14(5)(c), but there must be some evidence.

“…where you have a claim for the use of a known active ingredient in the preparation of a medicament for the treatment of a particular condition, the specification must provide, by way of description, enough material to enable the relevantly skilled man to say this medicament does treat the condition alleged…pure assertion is insufficient.”

Prendergast’s Applications [2000] RPC 446

It was clearly stated that this support must be found in the specification, implying that late-filed evidence cannot overcome the absence of any such support in the application as filed. The decision of the Patents Court in Prendergast’s Applications was acknowledged with approval by the House of Lords in Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49; [2008] RPC 28, and by the Supreme Court in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21, and the requirement for some evidence in the application to support second medical use claims was confirmed by the Patents Court decision in El-Tawil’s Application [2012] EWHC 185.

236.

The judgement in Prendergast’s Applications [2000] RPC 446 has been applied in a number of subsequent IPO hearing decisions. It was held in Advance Biofactures of Curacao’s Application BL O/303/04 that the evidence provided does not need to meet the standard required of, for example, a peer-reviewed journal. Furthermore, in F. Hoffmann - La Roche’s Application BL O/192/04 the Hearing Officer held that the claimed use could be supported by in silico modelling or - as in the case in question - through sequence homology comparisons. In this case, the evidence was only considered to support some of the claimed diseases or substances, and similarly in Commonwealth Scientific & Industrial Research Organization’s Application BL O/248/04 the application was not considered to provide support for the full range of claimed conditions.

237.

However, if the evidence in the application shows an effect on a common underlying mechanism behind a broader class of diseases, then a correspondingly broad claim may be considered supported. In Agency for Science, Technology and Research’s Application BL O/221/13 the Hearing Officer applied the case law on sufficiency from Regeneron Pharmaceuticals v Genentech ([2012] EWHC 657 and [2013] EWCA Civ 93; [2013] RPC 28) and T 609/02 SALK INSTITUTE to the question of support, using Lord Hoffmann’s remarks in Biogen v Medeva [1996] UKHL 18; [1997] RPC 1 (see above) as basis for doing so. He held that experiments performed solely on breast cancer cells made it plausible that the claimed agents could treat any cancer characterised by the over-expression of a particular protein. In this case he also made it clear that support must be ascertained from the point of view of the skilled person at the priority date. Similarly, in 4D Pharma Research’s Application BL O/202/21 the Hearing Officer found that the claim was supported across its breadth both in terms of the agent (a bacterial species, supported by evidence from a single strain) and conditions treated (autoimmune and inflammatory disorders, supported by evidence of effect against uveitis) - . In G W Pharma’s Application BL O/237/12 on the other hand, there was considered to be no disclosure in the application that the in vitro evidence provided in the application - that the agent blocked a particular receptor - related to a mechanism underlying prostate cancer (the claimed use), and the evidence from other sources available at the priority date did not clearly show such a link either.

238.

In Mollick’s Application BL O/1082/22, which pertained to a new use of thyme in the treatment of COVID-19, the applicant argued (with reference to Prendergast’s Applications [2000] RPC 446, Hoerrmann’s Application [1996] RPC 341 and McManus’s Application [1994] FSR 558) that the specification satisfied both support and sufficiency as it disclosed some experimental evidence and thus acted on more than mere assertion. However, the Hearing Officer did not agree that ‘some’ evidence is all that is required by Prendergast’s Applications, and instead found that the specification failed to reach the necessary threshold: of providing “enough material to enable the relevantly skilled man to say this medicament does treat the condition alleged”. In this case, the symptoms presented in the single case study were not specific to COVID-19 and the identity of the illness remained unverified either through qPCR testing or suitable medical consultation. It was therefore held that, on the balance of probabilities, there was not adequate diagnostic evidence in the specification to convince the skilled reader of the patient being infected with COVID-19. Ultimately, the specification did not provide evidence or a priori reasoning to suggest thyme has a mechanistic efficacy specific to targeting coronaviruses, and the application did not meet the requirements of either Sections 14(3) or 14(5)(c).

239.

All the case law relating to support under s.14(5)(c) relates to pre-grant hearings and appeals from Office decisions, as this is not grounds for revocation of a granted patent. In addition, EPO practice (eg in T 939/92 (Triazoles)) has generally been to consider issues of plausibility and claim breadth under either Art. 56 (inventive step) or Art. 83 (sufficiency) rather than Art. 84 EPC (the equivalent of s.14(5)). Nonetheless Prendergast’s Applications [2000] RPC 446 and other UK court decisions concerning support remain binding on our practice and should be followed.It is at present unclear whether the requirements for support for medical use claims based on these decisions is in any way different to the requirements for sufficiency following the criteria set out in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21. It is common ground between these decisions that mere assertion of efficacy is not enough. However, in Prendergast’s Applications it was not suggested that the “material to enable the relevantly skilled man to say this medicament does treat the condition alleged” could be anything other than experimental evidence (of at least rudimentary nature). On the other hand, in Warner Lambert v Generics it was explicitly stated that plausibility could instead be derived from a priori reasoning (point (vi), above). In view of the observation in Biogen v Medeva [1997] RPC 1 that the requirements for sufficiency in s.14(3) and for support in s.14(5)(b) both relate to the requirement for an enabling disclosure, it is likely that the Courts would consider these to be essentially the same requirement. How these decisions should be applied in practice is discussed below in ).

iii) Priority

240.

In order for a patent application for an invention relating to a medical use to validly claim priority from an earlier application, the earlier application must itself make the claimed use plausible - a mere assertion unsupported by any evidence is not enough. This was established by the Patents Court decision in Hospira v Genentech [2014] EWHC 1094:

“The establishment of priority includes a requirement for an enabling disclosure. In order to make an enabling disclosure of an invention it must be possible to make a reasonable prediction that the invention will work. In the context of an invention which includes the achievement of a therapeutic effect as one of its features, absolute proof is not required but the patentee must show that the therapeutic effect is plausible. It seems to me that this logic applies just as much to priority as it does to sufficiency of disclosure … I find that in law the test for priority includes the requirement for plausibility in a case like this one.”

Hospira v Genentech [2014] EWHC 1094

This principle was subsequently applied by the Patents Court in in Merck Sharp & Dohme v Ono [2015] EWHC 2973; [2016] RPC 10.

iv) Industrial application

241.

In Epshtein’s Applications BL O/508/15, the Hearing Officer considered a group of applications relating to compositions comprising ultra-low doses of antibodies, diluted such that statistically a single dose would be unlikely to contain any molecules of the antibody itself - the applications included both per se composition claims and second medical use claims. On the facts of the case, the Hearing Officer held that it was implausible that the compositions could have any therapeutic effect, and so refused the applications on grounds of industrial applicability as well as sufficiency. On appeal, the Patents Court (Epshtein’s Applications [2016] EWHC 1511; [2017] RPC 11) held that the invention was both sufficient () and industrially applicable, but did not contest the principle that if any use was implausible, the application could be rejected under Section 4. An objection of lack of industrial applicability in relation to medical use claims should only be made where (as was held to be the case by the Hearing Officer in this instance) it is considered implausible that the substance or composition could have any useful activity of any kind, or where the invention is otherwise considered contrary to established physical, chemical or biological principles.

v) Search and examination practice

242.

Second medical use claims must be supported by some evidence in the description of the likely efficacy of the substance or composition for the claimed medical use. The specification should therefore provide, in the description as filed, an indication that in vivo or in vitro tests have been conducted and that positive or encouraging results ensued (not necessarily quantified). Clinical or animal model data is not necessarily required, but if in vitro data is relied on then its relevance to the disease in question should either be known to the skilled person or demonstrated in the specification (as held in T 609/02 SALK INSTITUTE). It may also be possible for the application to rely on, for example, in silico modelling, or sequence homology (F. Hoffmann - La Roche’s Application BL O/192/04), if this is considered to provide a credible level of support (although if the new use is based solely on, for example, sequence homology with a known useful protein or nucleic acid then the inventiveness of the claim will clearly need to be considered carefully). Lack of any data, even rudimentary, in the description of an application which relates to a second medical use should be objected to under section 14(5)(c) as lacking support.

243.

In addition, if the specification is not considered to render the claimed medical use plausible, an objection of lack of sufficiency under s.14(3) may also be raised. It should be made clear in the examination report whether the objection (under either s.14(5)(c) or s.14(3)) relates to the entire scope of the claimed invention or only to some of the claimed agents and/or uses. In the former case, the objection is likely to be fatal to the application. There is established case law that “classical” insufficiency cannot be overcome by amendment, and the judgement in Prendergast’s Applications [2000] RPC 446 clearly stated that the specification must provide support for the claimed use. This objection cannot therefore be overcome by subsequent filing of evidence which supports the claim - the evidence must be provided in the application as filed. This objection is therefore fatal if the application relates solely to a further medical use of a known substance or composition. A warning, e.g. in the form of an examination opinion, should therefore be provided at the search stage if the main claims relate to a second medical use, and no or inadequate data is provided to support this use.

244.

If it is argued that the application meets the requirements for sufficiency and support by providing a priori reasoning in lieu of experimental evidence, the examiner will then need to consider the following points, based on Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 and Sandoz v Teva [2022] EWHC 822 (Pat):

i)Is this reasoning in the application as filed? ii) Does the application give rise to a reasonable prospect that the treatment will work as claimed, based on a direct effect on a mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the specification (points (iv) and (v), (). iii) Is there a contribution from the application beyond what was already part of the common general knowledge? (Point (vii) () and ()

245.

Moreover, if the application claims priority from an earlier application which discloses the claimed use but does not provide evidence to render it plausible, then it should be assumed at search and examination stage that the medical use claims in question are not entitled to a priority date based on the earlier application.

246.

It is common for second medical use claims to be included as subsidiary claims to a main claim or claims relating to a new compound. In such cases, if the substance or composition claim is new, inventive and supported by the description, further consideration of support for the medical use claim(s) may not be necessary as a matter of practicality. Of course attention should be paid to any claims which were filed later than the application to check that they are supported by the description (see ).

247.

If the examiner considers that it is implausible that the substance or composition of the claims could have any therapeutic effect, then an objection under s.4 of lack of industrial applicability may be raised, in addition to an objection of lack of sufficiency.

Claims to pharmaceutical substances and compositions

248.

This section covers specific medical considerations that may need to be considered in relation to per se product claims to substances and composition intended for medical use. Further guidance on chemical inventions, including those relating to pharmaceuticals, is set out in the Examination Guidelines for Patent Applications relating to Chemical Inventions in the Intellectual Property Office, while further guidance concerning substances and composition comprising biological molecules (such as antibodies) is provided in the Examination Guidelines for Patent Applications relating to Biotechnological Inventions in the Intellectual Property Office.

Anticipation by prior disclosure: metabolites

249.

The chemical composition of a product need not necessarily be known for it to form part of the start of the art. In Merrell Dow v H N Norton [1996] RPC 76 Lord Hoffmann held that section 2(2) does not confine the state of the art about products to knowledge of their chemical composition. The invention is part of the state of the art if the information which has been disclosed enables the public to know the product under a description sufficient to work the invention. In this case, the claim at issue defined a previously unknown substance which was produced in the liver following administration of the known drug terfenadine (i.e. it was a metabolite of terfenadine). The claim was held to be anticipated because it was the inevitable result of carrying out the directions to make and use terfenadine disclosed in an earlier patent. However, had the metabolite been claimed in isolated or purified form, or in a composition with excipients etc., then it would not have been anticipated as a composition comprising the metabolite, or an isolated metabolite, would not be produced by following the teaching of the prior art.

Anticipation by use in clinical trials

250.

The decision of the House of Lords in Merrell Dow v H N Norton [1996] RPC 76 established that the use of a product makes an invention part of the state of the art only so far as that use makes available the necessary information. In this case, the fact that volunteers in clinical trials had taken terfenadine and therefore had made the claimed metabolite in their livers, was held not to constitute anticipation by use. The volunteers had been given terfenadine capsules for the sole purpose of swallowing them; they took them without knowing their composition and produced within themselves a substance, which was not then readily capable of being identified and was only later known to be the metabolite.

251.

Evidence of a new composition’s use in a clinical trial prior to the priority date of an application does not necessarily constitute a public disclosure. However, such matters appear to be highly dependent on how the trial itself is conducted and to relate to the specific circumstances and relationship that participating patients enter into with the investigator.

252.

In T 07/07 BAYER, the investigators in a clinical trial were found to have lost control over the drugs handed out to participants; and participants were not bound by any particular secrecy or obligations relating to drug disposal, and thus were seen to be members of the public. This was therefore considered to be public prior use. However, this was not held to be the case in T 0670/20 DAIICHI SANKYO. This decision concerned a patent relating to a tablet form of the anti-blood clot medicine edoxaban, which was opposed on the grounds of lack of novelty, due to prior public use when the tablets were distributed to patients participating in phase IIa and IIb clinical trials for edoxaban. The Board ruled in the patentee’s favour, due to the restrictions imposed on participating patients owing to the design of the trials. The clinical trials were carried out in accordance with the EMEA Guidelines for Good Clinical Practice, and the investigators required drug accountability: where patients agreed to use the provided medication only according to instruction, or to return any unused medication. Hence, it was found that participating patients had entered into a special relationship with the investigators of the trials and were, with regard to the provided tablets, not members of the public that could freely dispose over these tablets.

253.

In T 0670/20, the Board noted that there was no duty of confidence with respect to the information regarding patients’ enrolment in the trials, and indeed patients were at liberty to discuss their participation with doctors, relatives, and friends; but this was not considered to affect the obligations owed by patients with respect to the stipulated use and return of tablets. The opponents further argued that in the absence of any legal sanction, full compliance to the return of any unused medication could not be ensured. However, the Board found that the provision of such an obligation, irrespective of any possible non-compliance or absence of an associated legal sanction, was adequate in demonstrating that the clinical trials and their associated documentation did not constitute a public disclosure.

Compositions adapted to a particular use

254.

The previous two sections have detailed the ways in which known substances can be protected for the first or subsequent medical uses, by the use of purpose-limited first or second medical use claims. In addition, known substances may be protected by per se product claims to pharmaceutical compositions containing them, if the composition is in a form which is novel and inventive over any known products. In particular, a claim may be made to a medicament having a form of administration which is novel and distinct from the previous use, where this implies a difference in the chemical or physical composition. For example, an anti-eczema ointment containing X would be regarded as clearly distinct from a tablet containing X for controlling blood pressure. The ointment is new because X has never been formulated in this form before, and it would be inventive if the previous use of X would not suggest its use in topical form. In general, the term “adapted to” is construed as being the same as “suitable for”, as held by the Patents Court in a non-medical case, Brundle v Perry [2014] EWHC 475. However, it was stated in this case that this was not an absolute rule of claim construction, and a contrary view was taken on the facts of the case by the Technical Board of Appeal in T 289/84 (3-Amino-pryazoline derivatives/WELLCOME). In this case, the Board of Appeal held that there was a difference in meaning between a claim to a composition adapted for topical use, as opposed to one suitable for such a use. Both eye drops and injectable formulations typically consist of sterile aqueous solutions, so either might be “suitable” for the other use. However, an eye-drop formulation was not “adapted” for use as an injectable solution or vice versa - injectable solutions had to be both sterile and pyrogen-free, whereas eye-drops do not need to be pyrogen-free but have a very narrow range of acceptable pH. However, a claim to a composition “adapted to” a specific use should be objected to on clarity grounds as being defined by its intended result, unless it would be clear to the person skilled in the art as to what is meant.

255.

In two cases where the main claims related to a contraceptive composition comprising compounds that were already known as pharmaceuticals, the EPO Technical Board of Appeal, in decisions T 303/90 (VICTORIA UNIVERSITY MANCHESTER) and T 401/90 (VICTORIA UNIVERSITY MANCHESTER)), was of the opinion that the words “contraceptive composition” were not sufficient to distinguish the claim from known pharmaceutical compositions. In these cases the claims were amended to Swiss-type second medical use claims, although this would not normally be appropriate for methods of contraception as they are not excluded under Section 4A(1).

256.

Claims to compositions with a novel physical characteristic, such as shaped forms or tablets with particular surface features, may be acceptable providing the feature relates to a genuine technical effect. For example, a claim to a tablet of a particular shape or structure would be acceptable if this resulted in a particularly favourable release profile for the active agent. However, if the new shape or form is merely presentational or conveys information (for example, by allowing blind patients to distinguish different types of pill), then it represents either an aesthetic creation or a mere presentation of information. As aesthetic creations and the presentation of information are not in themselves patentable, these features cannot impart novelty to the claim.

Clarity of composition claims

257.

Composition claims of the form “a pharmaceutical composition containing compound X together with a diluent, excipient or carrier” are considered to be clear; X being a medically active compound which characterises the composition, and the diluent, excipient or carrier being any material suitable for the purpose and being selectable by knowledge of the art or by non‑inventive experiment. There is no requirement for the diluent, excipient or carrier to be further characterised. However, a claim to the active ingredient “with an auxillary substance or substances”, was considered (in T 80/96 (L-carnitine)) to be so broad as to be meaningless, and this could not distinguish the claim from the prior art. In addition, a claim to a solution of the compound, where the compound was known to be water soluble, could not make a claim novel (T 80/96).

258.

Terms such as “therapeutically effective amount” of an active ingredient are generally considered to be clear. However, if such a term is used to distinguish the composition from the prior art, then this is open to objection unless the specification teaches how this is tested, or there is a standard test in the art (T 151/01 INSITE VISION). The purity of a product cannot be defined merely by defining the substance “as a pharmaceutical product” (T 226/98 (Famotidine/RICHTER GEDEON)). The Board of Appeal in T 1635/09 (Composition contraceptive/BAYER SCHERING PHARMA AG) held that if a composition claim is defined in terms of parameters which require testing to determine its scope, then it may be objectionable on grounds of clarity if it could be defined without the need for such tests, particularly where the tests may be burdensome and/or ethically questionable.

Composition claims: support, sufficiency and industrial application

259.

A per se claim to a pharmaceutical composition does not need to be supported by evidence of its suitability for its intended medical use in the same way as a medical use claim. In T 1616/09 SUPERGEN it was held that the requirements for sufficiency for a pharmaceutical composition claim were that the specification enables the skilled person to produce the composition, and there are no substantial doubts that it could be used in therapy; this was contrasted with the requirement for second medical use claims that the agent’s suitability for the claimed treatment is plausibly disclosed. On the other hand, if it is considered implausible that the composition could possibly have any therapeutic benefit (either because of toxicity or lack of any plausible activity) then an objection of insufficiency may arise, and if it is considered inherently implausible that it could have any useful properties at all then it may also be objected to under s.4 as lacking industrial applicability. In Epshtein’s Applications BL O/508/15, the Hearing Officer refused a group of applications relating to compositions comprising ultra-low doses of antibodies on grounds of both sufficiency and industrial applicability, as it was considered implausible that the compositions (in which a single dose would be statistically unlikely to contain any antibody molecules) could have any therapeutic effect. However, as discussed above () on appeal the Patents Court (Epshtein’s Applications [2016] EWHC 1511; [2017] RPC 11) held that the application did provide plausible evidence of activity, and so the decision was overturned.

260.

The criteria for sufficiency set out by Lord Sumption in Warner Lambert v Generics [2018] UKSC 56; [2018] RPC 21 () were specifically concerned with inventions relating a new medical use of a known substance or composition; there was no suggestion that they were more widely applicable. Nevertheless, the Patents Court in Sandoz v Teva [2022] EWHC 822 (Pat) applied these criteria to both medical use and per se claims to the novel compound apixaban. In his judgement, Meade J held that all the claims were invalid through lack of plausibility of any of its potential uses. He noted that lack of plausibility was not an objection in itself, but could give rise to revocation for insufficiency (as in Warner Lambert v Generics) or lack of inventive step, on the basis of there being no contribution to the art – so called “AgrEvo obviousness”. This latter objection is based on the EPO Board of Appeal decision in T 939/92 (Triazoles), and is based on the EPO’s problem/solution approach to assessing obviousness. AgrEvo obviousness arises when the technical effect is not made plausible for substantially all that is encompassed by the claim and as such the technical effect cannot form part of the technical problem against which obviousness is to be decided – see the Examination Guidelines for Patent Applications relating to Chemical Inventions in the Intellectual Property Office for further guidance. In Sandoz v Teva, Meade J considered that it was not necessary to decide which of the two objections applied, and simply held that it was invalid through lack of plausibility. In practice, as lack of plausibility is not an objection under the Act, an objection under sufficiency and/or support should be made, not AgrEvo obviousness.

Compositions with a new non-medical purpose or property

261.

Compositions which are allegedly distinguished from the same compositions in the prior art by the discovery of a new non-therapeutic property in one of the ingredients are not considered to be novel. This follows the general principle of novelty in UK law that once a substance or composition is known for whatever purpose then it cannot be patented again for another purpose - first and second medical use claims are the only accepted exception to this rule. Claims to the use of the agent in its non-therapeutic role are also not novel if the overall composition has previously been used in the same manner and the newly discovered property already put into effect, albeit unknowingly. Toothpastes with sodium bicarbonate as a cleaning/tingling agent are known, and so a claim to the use of sodium bicarbonate as a masking agent for bitter ingredients present in the known toothpaste formulations would not be novel. In this respect, the Intellectual Property Office has not followed the decision of the EPO Enlarged Board of Appeal in G 02/88 (Friction reducing additive), where it was held that novelty could be derived from a new technical effect ().

Claims to unit dosage forms

262.

A unit dosage form consists of a tablet, suppository, ampoule or other device, containing a definite amount of a drug, the whole of which is intended to be administered as a single dose. It is thus distinguished from a supply of an indefinite amount of a medicament, eg a bottle of medicine, from which a dose has to be measured out.

263.

It may be possible in cases where the required dosage for a new medical use is markedly different from that for the known use, to allow a claim to a unit dosage form containing the known active ingredient in such an amount that the unit dosage form is novel and not obvious to have been made up in that amount for the prior art use. Thus if the new medical use requires a dose of, for example, ten times that for the prior art use, then a claim to a unit dosage form might be judged to be novel and inventive and allowable. In assessing the inventiveness of such claims it should be remembered that dosages required are usually related to body weight so that children’s doses are smaller than those for adults. It is also well known in medicine for patients to be asked to take more than one tablet at a time and it is known for half tablets to be taken.

264.

In Actavis v Icos [2017] EWCA Civ 1671; [2018] RPC 7, the Court of Appeal held that a claim to unit dosage of 1-5mg of tadalafil was not limited in any way by the words “up to a maximum total dose of 5mg/day”; this was not a medical use claim and any tablet of 1-5mg would be suitable for such a dose. The Court also held that the claim was quite clearly obvious over the prior art which proposed a much higher daily dose, as multiple tablets could be taken, regardless of whether the medical use claims (which were limited to the use at the lower dose) were obvious or not. ( for discussion of the inventiveness of the medical use claims). On appeal, the Supreme Court (Actavis v Icos [2019] UKSC 15; [2019] RPC 9) agreed on this point.

265.

Claims to unit dosage forms must clearly define a specific amount of medicament. A claim specifying an amount of medicament per unit body weight of patient is unclear in scope. Moreover there must be clear support in the description for a unit dosage form containing a specific amount of active ingredient. Claims derived from dosages of x mg/kg bodyweight by calculations using an average patient’s body weight have been rejected as lacking in support, as have claims derived from the amounts of active ingredient fed to experimental animals.

Combined preparations and packs of medicaments

266.

It is common in the pharmaceutical field for inventions to relate to the combined use of two or more known medicaments. Such claims may be in the form of per se composition claims or first or second medical use claims, and may also define a kit of parts for simultaneous or sequential administration. Following the practice established by the House of Lords in SABAF v MFI Furniture Centres [2004] UKHL 45; [2005] RPC 10 the first question that must be addressed is whether - for the purpose of assessing inventive step - the claim in question relates to a single invention or plural inventions. If the two (or more) ingredients simply perform their usual function in the body, and there is no synergy between them, then the claim relates to two separate inventions, and there is no inventiveness in combining them. The Hearing Officer in Lalvani et al’s Applications BL O/220/13 applied this practice to dietary supplement compositions with multiple ingredients, with no evidence in the application of any synergy between them. On the facts of the case, he considered that each of the ingredients was either a known or obvious ingredient of compositions intended for the uses in question, and so the applications were refused on grounds of lack of an inventive step. Similarly, in Lalvani et al’s Application BL O/664/17, claims to a composition suitable for the treatment of hair loss comprising multiple ingredients - where the specification did not disclose any evidence of synergy between them – were held to be obvious in view of prior art documents showing that each of these components was separately known for use in hair loss compositions. In this latter case the claims also defined a particular weight ratio between three of the components; the Hearing Officer accepted that this ratio was not disclosed or suggested in the prior art, but as the specification did not implicitly or explicitly teach any technical advantage to this ratio it did not constitute an inventive selection.

267.

Moreover, synergistic effects between the components must be identified in the specification (Glaxo Group’s Patent [2004] EWHC 477; [2004] RPC 43). Evidence of synergy provided after the filing date cannot be used to demonstrate inventiveness, if there is no indication of such synergy in the specification as filed (Richardson-Vicks’ Patent [1995] RPC 568).

“If a synergistic effect is to be relied on, it must be possessed by everything covered by the claim, and it must be described in the specification. No effect is described in the present specification that is not the natural prediction from the properties of the two components of the combination.”

Glaxo Group’s Patent [2004] EWHC 477; [2004] RPC 43

268.

Moreover, evidence of unexpected synergy between the two components does not render a combination inventive if the combination would in any case be obvious to the skilled person. In particular, if it is known to combine two categories of active agent (such as an analgesic and a decongestant), it is unlikely to be inventive to merely substitute a newer, more effective agent of one or other category in the combined preparation - the patents in question in both Glaxo Group’s Patent [2004] EWHC 477; [2004] RPC 43 and Richardson-Vicks’ Patent [1995] RPC 568 were revoked on these grounds. If the synergy demonstrated by the new combination is no greater than the equivalent prior art combination, then it does not provide evidence of inventiveness (T 492/99 NIPRO). Although lack of evidence of synergy in a combined composition may give rise to an obviousness objection, it does not render the application insufficient (T 1616/09 SUPERGEN).

269.

In Richardson-Vicks’ Patent [1995] RPC 568 the argument was made that combined preparations faced particular difficulties in obtaining regulatory approval, and this would constitute a prejudice away from a new combination. This was rejected by the judge - any perceived regulatory difficulty is considered irrelevant for inventiveness. On the other hand, if there is a technical prejudice that would point away from the combination in question, then inventiveness may be acknowledged, even if the combination is superficially obvious (Norbrook Laboratories’ Patent [2005] EWHC 2532; [2006] FSR 18).

270.

Pack or “kit of parts” claims are sometimes used where the invention comprises the administration of two or more different drug compositions at particular time intervals, or merely simultaneously or sequentially. A claim of this form was considered by the EPO Board of Appeal in T 09/81 (Cytostatic Combination). It was held in this case that the combination was novel and inventive, but needed to be “purpose limited” - i.e. in the first or second medical use format to distinguish it from a medical kit, collection or package containing the two agents together for their known independent uses. This is in line with the practice of the Intellectual Property Office that such claims are allowable provided that the pack is stated to be for the method in which the invention really resides, and that the pack is novel and not obvious for any other application. In addition there must be clear support in the description for such a pack, and a claim for a kit or pack for carrying out a method must define all the essential elements for carrying out the method.

271.

Claims to a pack or container containing a known substance with instructions for the new use should be rejected on the grounds that the only novel feature - the instructions - is merely a presentation of information and thus not a patentable invention under Section 1(2)(d) (Bayer’s (Meyer’s) Application [1984] RPC 11). However, the acceptance of second medical use claims has now made such claims redundant in the medical fields.

272.

However, a new package may be new and inventive if there is some physical relationship between the new and inventive method and the package, which goes beyond merely presenting instructions for the new use. In Organon’s Application [1970] RPC 235, a claim was allowed under the 1949 Act to a pack containing two types of known contraceptive pill arranged in the order in which they were to be taken, the arrangement being novel and not obvious from the art. This was despite the fact that packs containing contraceptive pills in a given order were known - the particular order defined in this case was not obvious as it was based on a new and inventive method of contraception.