Canada Introduction ‘Personalized medicine’, in its broadest aspects, is essentially the tailoring of treatments to individual characteristics, needs, and preferences. More commonly, however, the term is used to refer to the tailoring of treatments to an individual based on his personal genetic makeup and prior treatment history.
Current therapies that treat conditions without considering a patient’s genetic background show a lack of efficacy ranging from 38 per cent (for anti-depressants) up to 75 per cent (for anti-cancer drugs).1
With the completion of the human genome project and the identification of increasing numbers of biomarkers, an entire new sector of research has opened, looking at how best to target new and current therapies and re-purpose older drugs in order to improve these statistics. As a result, an increasing proportion of the innovations within the medical industry are in the personalized medicine area.
The development of technologies that assist with targeted diagnosis and treatment of patients involves much time, effort, and expense. It is, therefore, understandable that there is a strong interest to protect innovations in these areas in a meaningful way in order to attract investment and establish a potential commercial position.
The patent system is designed to help companies develop a foothold in the industry while, at the same time, encourage developments by others within the technology arena. This dynamic tension, of protecting innovations so that others are excluded from the domain of the invention and encouraging others to make developments based on the publicly disclosed invention, is at the base of the ongoing debate and development of acceptable practices within various countries.
The questions being considered involve determining how broad the exclusion defined by the claims of a patent may be, what information is required to be described in the patent in order to support the claims, what developments within the life science field are patentable, and why.
Innovations in personalized medicine may focus on the targeted treatment of patients, identified, for example, by the presence or absence of a particular biomarker, and on diagnostic methods for identifying such patients (ie, ‘companion diagnostics’). Patent claims are typically directed to methods of using a specific drug or drug combination, potentially at a defined dosage, to treat a specified sub-population of patients, and to methods of identifying such patients. Related claims may include claims to the biomarker itself and/or to reagents (such as primers) for identifying the biomarker.
In the following, the authors briefly summarize the approach being taken by the courts and Patent Offices in Canada and Europe with respect to claims directed to personalized medicine.
Methods of medical treatment are not considered to be patentable subject matter in Canada. The original Supreme Court decision that excluded methods of medical treatment from patentability, Tennessee Eastman Company v Commissioner of Patents,2 pre-dated revisions to the Patent Act that removed the prohibition on patenting of drugs; however, the revisions did not result in the inclusion in the new Act of any statutory prohibition on patenting methods of medical treatment.
As a result, exclusion of these methods in Canada is entirely case law driven and is based essentially on the rationale that Canadian patents ought not to interfere with the ability of physicians to exercise their skill and judgment.
Protection for therapeutic methods nevertheless can be obtained in Canada, provided that claims are drafted in a medical-use format, which may be traditional-use format, purpose-limited product format, or ‘Swiss style’ format. New uses of known compounds, ie, second or subsequent medical uses, also are considered patentable, provided that the new use also meets the other requirements of the Patent Act and Rules.3 Diagnostic methods also are considered to be patentable in Canada.4
Care needs to be given the exact wording of medical use and diagnostic method claims, however, to ensure that they cannot in some way be equated to a method of medical treatment, such as by including a medical or surgical step, or a step or aspect that may be construed as requiring the skill and judgment of a physician.
For example, a method that includes removing a sample of blood and assaying the components in the sample may be objected to as comprising a medical or surgical step if not appropriately worded. As noted in the Manual of Patent Office Practice, ‘[t]he removal of fluids from the body such as by needle or cannula is not of itself surgery’;5 however, ‘[a] method to remove fluids may nevertheless be proscribed if it otherwise involves surgery, such as in the placement of a cannula or stent in the body . . .’.6 The possibility that the requirement for a physician’s skill may be read into a claim has the potential to impact the ability to obtain personalized medicine patents in Canada.
Statutory Subject Matter
The Canadian Intellectual Property Office (Canadian Intellectual Property Office) recently revised its practice for determining whether or not claimed subject matter is statutory, and several Practice Notices that impact computer-related and life science technologies have been published.
The approach identified in the Practice Notices is influenced by the jurisprudence pertaining to Amazon’s ‘one-click’ patent application (CA 2,246,933). While the technology in the ‘one-click’ application is computer-related, many of the principles established in this jurisprudence are broadly applicable across technologies.7
The ‘one-click’ application was originally rejected by the Patent Appeal Board as being directed to non-patentable subject matter. This conclusion was reached by determining the ‘inventive concept’ by analyzing the ‘form’ and the ‘substance’ of the claims:
Form of the Claims
 . . . These claims, on their face, are directed at a method for the purchase of goods, and as such, are claiming a method of doing business [and] are directed to excluded subject matter.
 If the substance of the claimed invention is not ‘an act or series of acts performed by some physical agent upon some physical object and producing in. such object some change either of character or of condition’, it is not an art under Section 2 of the Patent Act.8
The Federal Court, however, subsequently determined that the ‘form and substance’ analysis of the claims used by the Patent Office was incorrect and that claims should be analyzed using a ‘purposive construction’as set forth by the Supreme Court both inWhirlpool9 and Free World Trust.10 Based on a purposive construction approach, the Federal Court concluded that the claims in question were directed to statutory subject matter:
‘. . . Although the Commissioners attempt to confine this analysis to patentable subject matter, a return to ‘form and substance’ language, no matter what the context, is confusing and unnecessary. Further, it represents a departure from the clear distinction of the Supreme Court to apply purposive construction universally.
 . . . It is thus not wrong to speak of ‘what has been invented’ so long as this is determined with reference to the essential elements as disclosed through purposive construction of the claims, rather than through a subjective secondary consideration by the Patent Office as the to the ‘substance of the invention’.11
Furthermore, the Federal Court noted that an approach that involves parsing the elements of the claim and analyzing the elements in isolation is incorrect:
 The rejection of purposive construction and in essence a holistic consideration of the claims, also allowed the Commissioner to parse the claims into their novel and non-novel components in order to evaluate patentability. As discussed above, it is problematic to suggest that ‘what has been discovered’ stands apart from the claims as a whole . . .
 . . . the Commissioner clearly erred by ‘parsing’ the claims into their novel and obvious elements in order to assess patentability. When viewed as a whole it is clear that the claimed invention is a process which uses stored information and ‘cookies’ to enable customers to order items over the Internet . . .
On appeal, the conclusion reached by the Federal Court was upheld by the Federal Court of Appeal:12
 However, it seems to me that the jurisprudence of the Supreme Court of Canada, in particular Free World Trust and Whirlpool, requires the Commissioner’s identification of the actual invention to be grounded in a purposive construction of the patent claims. It cannot be determined solely on the basis of a literal reading of the patent claims, or a determination of the ‘substance of the invention’ within the meaning of that phrase as used by Justice Binnie, writing for the Supreme Court of Canada in Free World Trust, at paragraph 46.
 In my view, there is nothing in the cases cited by the Attorney General of Canada that casts any doubt on the proposition that the Commissioner’s determination of subject matter must be based on a purposive construction of the patent claims. Therefore, on the question of analytical framework, I agree with Justice Phelan that in determining subject matter solely on the basis of the inventive concept, the Commissioner adopted an analysis that is incorrect in law.
Canadian Intellectual Property Office Practice Notices
The Canadian Intellectual Property Office has published three Practice Notices that impact all technology areas, including personalized medicine. The most relevant is Practice Notice 2013-04 ‘Examination Practice Respecting Medical Uses’.13 However, as this Practice Notice is based on the purposive construction approach set out in Practice Notice 2013-02 ‘Examination Practice Respecting Purposive Construction’,14 both of these Practice Notices are discussed below.
Practice Notice 2013-02, Examination Practice Respecting Purposive Construction
In this Practice Notice, the Canadian Intellectual Property Office acknowledges that claim construction is determined using a purposive construction as set out in Free World Trustand Whirlpool. However, a technical argument is presented to excuse the Canadian Intellectual Property Office from following the approach mandated by the Supreme Court.
The Patent Office suggests that, while Free World Trust and Whirlpool guide the courts, which have the benefit of expert testimony and cross-examination to construe the claims, this approach is ‘not directed to patent examiners in the course of examinations to determine whether applications for patents should be granted’and that ‘examination of a patent application must take into account the role of the patent examiner and the purpose and context of examination’.
On this basis, the Practice Notice sets out the Canadian Intellectual Property Office’s approach to purposive construction. Briefly, this involves:
- Using a fair, balanced approach — ‘. . . in order to arrive at a fair, balanced and informed understanding of the subject matter of a claim, it is critical that a purposive construction of the claim be performed considering the specification as a whole as read through the eyes of the person skilled in the art, against the background of the common general knowledge in the field or fields relevant to the invention at the time the application became available to the public’.
- Identifying the problemand solution—‘. . . recognizing that a patentable invention is an inventive solution to a practical problem, it follows that an invention must be disclosed (and ultimately claimed) so as to provide the person skilled in the art with an operable solution.’ (footnote omitted)
- Considering the context of the application as a whole — The purposive construction considers the application as a whole, with the claims interpreted in light of the description. Furthermore, ‘The examiner must be “alive to the possibility that a patent claim may be expressed in language that is deliberately or inadvertently deceptive”, thus recognizing that, for example, what appears on its face to be a claim for an “art” or a “process” may, on a proper construction, be a claim for a mathematical formula and therefore not patentable subject matter’. (footnote omitted)
- Determining which elements of the claim solve the identified problem — Following identification of the problem and solution as described in the specification, the essential elements of the claims are to be identified. An element is non-essential if at the date of publication of the patent, the skilled person would appreciate that the element could be substituted without affecting working of the invention. The Practice Notice then states that ‘. . . some element or combination of elements defined in the claim must provide the “inventive solution”. . . [s]ome elements of a claim merely define the context or the environment of a specific working embodiment, but do not actually change the nature of the solution to the problem.’15
- Focusing on one solution to a problem — A claim may provide solutions to more than one problem. The choice of the solution should be guided with reference to the description.
This approach, however, diverges in several respects from the guiding case law. Under the second point, above, the Practice Notice indicates that the problem and solution is used to inform the purposive construction of the claims and is to be determined with reference to the description ‘and not by reference to the closest prior art’. The Practice Notice further indicates that identifying the problem and solution occurs when the examiner determines the ‘promise of the invention (ie, its utility).’
However, the problem-solution approach as set out in the Practice Notice is not in keeping with Canadian jurisprudence as set out in the Supreme Court decision in Shell Oil16 and summarized in Progressive Games:
 Accordingly, the definition of the term ‘art’ as provided by the Supreme Court [in Tennessee Eastman] includes a process that:
- is not a disembodied idea but has a method of practical application;
- is a new and innovative method of applying skill or knowledge; and
- has a result or effect that is commercially useful.17
In the Practice Notice, there is no consideration as to whether or not the invention is a disembodied idea, has a practical application, is an innovative method, and has a commercially useful result. The approach set out in the Practice Notice is, in fact, reminiscent of the determination of the ‘pith and substance’ or ‘contribution’ after the ‘promise of the invention’ is determined, which has been specifically rejected by the Supreme Court in Free World Trust.18
Additionally, the approach to determine whether an element is essential as set out under the third point, above, of the Practice Notice is not in keeping with Canadian jurisprudence as set out in the Supreme Court decision of Free World Trust:
 . . . (e) The claims language will, on a purposive construction, show that some elements of the claimed invention are essential while others are non-essential. The identification of elements as essential or non-essential is made:
(i) on the basis of the common knowledge of the worker skilled in the art to which the patent relates;
(ii) as of the date the patent is published;
(iii) having regard to whether or not it was obvious to the skilled reader at the time the patent was published that a variant of a particular element would not make a difference to the way in which the invention works; or
(iv) according to the intent of the inventor, expressed or inferred from the claims, that a particular element is essential irrespective of its practical effect; and
(v) without resort to extrinsic evidence of the inventor’s intention.
The Free World Trust test, to determine essentiality, requires that ‘the words chosen by the inventor will be read in the sense the inventor is presumed to have intended and in a way that is sympathetic to the accomplishment of the inventor’s purpose expressed or implicit in the text of the claims’.
Furthermore, current examination practice emphasizes the function of a specific claim element, without regard to whether the element is correctly essential, ie, would the variant of the claimed element perform the same function in the same way as per step (e)(iii) of theFree World Trust test outlined above.
There is no mention in Practice Notice 2013-02 that, in order to substitute a variant without altering the function of the element, the variant must have been obvious on the publication date to one of skill in the art, and the analysis does not take into account the intent of the inventor (steps (e)(i) and (ii).
A Markush group19 of elements may indicate that the inventor intended the elements to be non-essential and that variants of the element may be substituted. However, if the members of the Markush group share a specific property, the specific property is a unifying feature of the Markush group, and this feature would, therefore, be intended by the inventor.
However, the Practice Notice fails to take into account the intent of the inventor in determining whether an element is essential. The result being that the determination as to whether or not an element is essential is made subjectively by the examiner. For example, if it is determined that a diagnostic method requires a surgical step (or other step requiring professional skill), even if the step is not recited in the claim, the examiner may interpret this step as being essential within the claim resulting in the claim being rejected as being directed to non-patentable subject matter.
Practice Notice 2013-04: Examination Practice Respecting Medical Uses
The Practice Notice expands on the guidance provided in the Manual of Patent Office Practice (section 17.02.03),20 and is directed to claims of the general form: ‘. . . use of product X for the manufacture of a medicament for treating disease Y’ (Swiss style claim), or ‘a product X for use in treating disease Y . . .’.
The Practice Notice also is directed to claims that recite dosage regimens or dosage ranges. As noted above, in Canada, methods of medical treatment and surgical step performed on a body are not statutory subject matter.21 For example, a method of treating diabetes that comprises a step of injecting insulin into a patient is considered non-statutory since the step of injecting is performed by a medical professional and the step provides a therapeutic benefit. However, a ‘use’of insulin to treat diabetes in a patient in need thereof is considered patentable.
Practice Notice 2013-04 makes reference to Practice Notice 2013-03 (Purposive Construction) as a basis for determining whether a claim is statutory, especially if the claims include reference to a dosage regimen or dosage range. However, the mere inclusion of a dosage regimen or dosage range does not mean that the claim is non-statutory. If the dosage regimen, dosage range, or dosing schedule is an essential element, the claim may be considered a method of medical treatment. Practice Notice 2013-04 states:
Where an essential element only serves to instruct amedical professional ‘how’ to treat a patient, rather than ‘what’ to use to treat the patient, this will lead to the conclusion that the claimed use encompasses a method of medical treatment. (footnote omitted)
The Canadian Intellectual Property Office considers that, if the problem relates to a ‘what’, and the solution is provided by an element or elements, or a tool (a composition, formulation, or dosage form), the claim is generally acceptable. However, if the emphasis of the claim is directed to the ‘how’, for example, how to administer, or how to refine a treatment, this may place a limit on a professional’s skill or the judgement of a physician and is considered non-statutory. The rejection of a claim directed to ‘how’to administer is controversial since, if no professional skill is required to determine this step, such a claim is arguably statutory.
Support for the interpretation in Practice Notice 2013-04 that a claim directed to the ‘how’(or ‘when’) is not statutory is referenced to the Supreme Court decision ofApotex.22 Interestingly, the use claim considered in Apotex does not refer to ‘how’ or ‘when’ a drug is administered, but rather defines a dosage form, which was determined to be statutory. Apotex does not state that a claim directed to the ‘how’ or ‘when’ is a basis for considering a claim non-statutory, rather the court stated:
 The AZT patent does not seek to ‘fence in’ an area of medical treatment. It seeks the exclusive right to provide AZTas a commercial offering. How and when, if at all, AZT is employed is left to the professional skill and judgment of the medical profession.
An alternate interpretation of Apotex also is available. Since a dosage form, if essential, and defined explicitly in a claim, is acceptable, other elements if defined explicitly should also be permitted. For example, if the route of administration (eg, ‘for oral administration’, ie, the ‘how’) or the timing of administration (eg, ‘to be administered once weekly’, ie, the ‘when’) is an essential element and defined explicitly within the claim so that no professional skill is required to determine these parameters, in a manner analogous to providing a dosage form within a claim, the claim should be acceptable. Practice Notice 2013-04 appears to simplify the determination of the requirements for patentability by suggesting that any claim directed to providing an invention based in the ‘how’ (or ‘when’) is not statutory.
In this context, the Practice Notice states that essential elements ‘that narrow treatment to a patient sub-population (rather than bring treatment to a new population) or administration site’also are considered a limitation of a physician’s professional skill or judgment and are currently considered non-statutory.
The fact that a treatment of a sub-population is deemed non-statutory is problematic as many developments in personalized medicine are directed to optimizing effectiveness of a treatment by understanding the patient population to whom the treatment is administered. For example, reducing negative side effects within patients with a characterized physiological background or genetic makeup may be key in many personalized medicine developments, and these developments clearly have utility. However, claims that are directed to sub-populations are considered non-statutory under current Canadian practice, even though this determination is not based on any Canadian jurisprudence.
It is of interest to note that Japan has amended its practice pertaining to patentability of ‘how’a patient is treated. In the case of administering a known compound to treat a known disease, and the only difference is ‘how’ to administer the compound (eg, a new dosage regimen of 30 to 40 micrograms/kg body weight every three months), the new practice provides that the dosage regimen (and administration mode) is treated as medical use and imparts novelty, provided that the method is not obvious (eg, provides substantial advantages or the prior art teaches away).23 This example also is of significance in that dosage regimens at the point of invention are considered acceptable in Japan.
Practice Notice 2013-04 provides an accompanying set of examples24 to help understand the Patent Office’s position in interpreting medical use claims. For example, a claim directed to a new compound, and the use of the new compound to treat a disease (Example 1) is statutory. If a dosage regime is provided in the claim, the claim is still considered statutory since the solution is the new compound (the ‘what’) and the dosage regimen is not an essential element of the claim.
The second example relates to the new use of a known compound to treat a disease. In this case, if a dosage regime is provided, the claimis considered statutory since the solution is the newuse (which is considered the ‘what’), and not the dosage regimen. Similarly, a new fixed dosage form (the ‘what’) of a known compound for a known use (Example 3) is statutory.
However, a new dosage range (eg, between X to Ymg/kg/day; Example 4) or a new dosage regimen (eg, X mg/kg/day for three days followed by Y mg/kg/day for one week; Example 5.1), for a known drug and for a known use, is considered to be directed to ‘how’ the drug is used. The use of a new unit dosage form at a regular defined interval (eg, X mg once a week) may be considered a dosage regimen, but this claim is considered statutory (Example 5.2) since the essential element is the new dosage form (eg, a higher dosage formulation).
A new formulation of a compound for a known use also is acceptable (Example 6.1) if the new formulation addresses a problem, for example, that prior art formulations were not effective when administered orally while the new formulation permits effective oral administration. The use of the same formulation for the same use but administration of the formulation in a different way is not considered statutory (Example 6.2). Thus, the use of the formulation in a different way is considered ‘how’ the formulation is used (eg, placement of a transdermal patch on the leg instead of the arm).
As noted above, this interpretation appears in contrast to the general finding as set out inApotex, where a new use of a specific dosage form was found to be patentable. If the patch comprised a different formulation for its use in a new location, then the claim may be directed to ‘what’ is being delivered (the new formulation under Example 6.1).
Example 7.1 pertains to treatment of a ‘sub-population’ of patients that would previously be treated using the same drug, but now it has been determined that due to their genetic make-up, they respond more efficiently to treatment with compound X. Thus, some members of the patient ‘population’ are now excluded from treatment based on a genetic analysis of the population prior to treatment. The Practice Notice states that invention is not considered a ‘selection because, in a selection, all of the range claimed must be novel’.
While it is not clear at this time if a sub-population may be considered a selection, the position as set out in Example 7.1 of the Practice Notice is debatable. It is well established in Canadian jurisprudence, as stated by the Supreme Court of Canada in Sanofi, that a selection patent ‘. . . is one whose subject matter (compounds) is a fraction of a larger known class of compounds which was the subject matter of a prior patent’.25 Sanofioutlines the test for determining a selection patent as follows:
 The locus classicus describing selection patents is the decision of Maugham J in In re IG Farbenindustrie A.G.’s Patents, (1930), 47RPC289 (Ch D.), at p 321, he explained that in the field of chemical patents (which would of course include pharmaceutical compounds), there are often two ‘sharply divided classes’. The first class of patents, which he called originating patents, are based on an originating invention, namely, the discovery of a new reaction or a new compound. The second class comprises patents based on a selection of compounds from those described in general terms and claimed in the originating patent.MaughamJ cautioned that the selected compounds cannot have been made before, or the selection patent ‘would fail for want of novelty’. But if the selected compound is ‘novel’and ‘possess[es] a special property of an unexpected character’, the required ‘inventive’ step would be satisfied (at page 321). At page 322, Maugham J stated that a selection patent ‘does not in its nature differ from any other patent’.
 While not exhaustively defining a selection patent, he set out (at pp. 322 and 323) three conditions that must be satisfied for a selection patent to be valid.
1. There must be a substantial advantage to be secured or disadvantage to be avoided by the use of the selected members.
2. The whole of the selected members (subject to ‘a few exceptions here and there’) possess the advantage in question.
3. The selection must be in respect of a quality of a special character peculiar to the selected group. If further research revealed a small number of unselected compounds possessing the same advantage, that would not invalidate the selection patent. However, if research showed that a larger number of unselected compounds possessed the same advantage, the quality of the compound claimed in the selection patent would not be of a special character.
The features that define a selection patent, therefore, include having an advantage (or disadvantage), the whole of the group possesses the advantage, and the selection is in respect of a quality or character peculiar to the group. This definition has been provided with respect to selecting one or more compounds from those that have been described in general terms and claimed in the originating patent. However, the compounds of the selection cannot have been made before.
Of interest is that, in Sanofi, the selected compound was a stereoisomer with beneficial properties when compared to a mixture comprising both D and L isomers. Therefore, the beneficial isomer was previously administered to a patient, in the form of a mixture of isomers. However, the court still determined that the specific isomer was not anticipated, not obvious, and statutory.
The Canadian Intellectual Property Office has interpreted the test of a proper selection to mean that ‘all of the claimed range must be novel’, while selectively ignoring the other requirement for consideration (having an advantage, the whole of the selected members possess the advantage, the selection is of a special character) that may permit the selection of a sub-population. The Canadian Intellectual Property Office position is that, since the population as a whole has already been treated, ‘all of the range’ of the sub-population is not novel. This position appears to be controversial, not based in case law, and may be inconsistent with the conclusion arrived at in Sanofi.
In the example directed to a sub-population (Example 7.1), the identification of a patient that is suitable for treatment would be a result of a genetic test carried out on one patient. In many instances, there is no identification of a ‘population’ of patients. Rather, the method would involve a diagnostic test to determine, for example, if an individual patient carried the mutation and, if they did, a specific treatment may be proposed. Even under these circumstances, the treatment of a specific patient would still be considered by the Canadian Intellectual Property Office to be a treatment of a ‘sub-population’unless it can be shown that the population being treated was not previously treated.
A possible way to address a rejection directed to a claim that is interpreted as including a sub-population is to amend the claim into a diagnostic claim, such as a diagnostic method for determining if a population is suitable for treatment for compound X, involving a diagnostic screen to identify a specific gene mutation.
The last example (Example 7.2), provided in the accompanying examples to Practice Notice 2013-04, is directed to a ‘distinct population’, which is acceptable and analogous to saying that a new use (ie, a treatment of a new population) is acceptable under Canadian practice.
It is of interest that there is no mention of well-established case law that pertains to the requirements for statutory subject matter, as laid out by the Supreme Court of Canada inShell Oil, in Practice Notice 2013-04. As acknowledged by the Federal Court of Appeal inAmazon, the leading case for the definition of patentable art is Shell Oil,26 which focuses the inquiry on whether there is a practical application of the discovery or idea:
What then is the ‘invention’ under section 2? I believe it is the application of this new knowledge to effect a desired result which has an undisputed commercial value and that it falls within the words ‘any new and useful art’. I think the word ‘art’ in the context of the definition must be given its general connotation of ‘learning’or ‘knowledge’as commonly used in expressions such as ‘the state of the art’or ‘the prior art’. The appellant’s discovery in this case has added to the cumulative wisdom on the subject of these compounds by a recognition of their hitherto unrecognized properties and it has established the method whereby these properties may be realized through practical application. In my view, this constitutes a ‘new and useful art’ and the compositions are the practical embodiment of the new knowledge.
In many instances, methods directed to personalized medicine are a result of ‘cumulative wisdom’, the ‘recognition of hitherto unrecognized properties’, and to establishing methods ‘whereby the properties may be realized’. It is, therefore, anticipated that developments within personalized medicine may be seen as constituting a new and useful art.
Treatment — Sub-Populations and Dosage Regimens
In contrast to Canada, as well as the United States, where many claims relating to personalized medicine are being questioned on the basis of patentable subject matter, the main challenges for such claims in Europe tend to relate to novelty and inventive step.
In Europe, methods of medical treatment are specifically excluded from patentability by article 53(c) of the European Patent Convention. Article 53(c), however, also explicitly states that the use of a substance or composition in such methods is not covered by this exclusion.27 As such, therapeutic methods may be claimed in Europe by way of purpose-limited product claims. Provided that claims are drafted in this format, therefore, the assumption is that the claims are directed to patentable subject matter, and the question that needs to be addressed then becomes whether or not the other requirements of the European Patent Convention are met, in particular novelty and inventive step (obviousness).
Novelty in Europe is governed by article 54 of the European Patent Convention, which expressly acknowledges that both the first medical use of a substance or composition, as well as second (and subsequent) medical uses of a substance or composition, can be novel even though the substance or composition is already known.
The patentability of second medical uses was first formally confirmed by the Enlarged Board of Appeal in Decision Number G5/83. The conclusion reached in G5/83 was that ‘Swiss-style’claims protecting second (and subsequent) medical indications did not conflict with the requirements for patentable subject matter and industrial applicability under the European Patent Convention.28 The Enlarged Board of Appeal recognized, however, that in such cases ‘there may be a problem concerning the novelty of the invention’, since the medicament resulting from the claimed use is no different from a known medicament, leading the Board to conclude that the basis for novelty for this type of claim is the new pharmaceutical use, rather than the medicament itself.
The subsequent revision of the European Patent Convention by the Act Revising the Convention on the Grant of European Patents of 29 November 2000 formally provided for the patentability of second and subsequent medical uses by introducing new article 54(5) (which had no counterpart in the earlier version of the European Patent Convention) into the European Patent Convention 2000.29 The language of this new provision reflects the principle set out inDecision Number G5/83 by confirming the novelty of any substance or composition comprised in the state of the art ‘for any specific use in a method referred to in article 53(c) (ie, a method for treatment by surgery or therapy), provided that such use is not comprised in the state of the art’.
Treatment-based personalized medicine claims are, by definition, second medical use claims in that they relate to the use of a known therapeutic. A further complication is that such claims also typically relate to a use of a known therapeutic to treat the same disease as previously treated, differing only in one or more of the population being treated, the route of administration, the dosage amount, and/or the dosage regimen.
Several Technical Board of Appeal decisions have considered this issue. In one of the earliest, Decision Number T19/86, the Board considered the question of whether application of a known therapeutic for prophylactic treatment of the same disease in an immunologically different population of animals (sero-negative rather than sero-positive piglets) was a new therapeutic use in the context of Decision Number G5/83. The Board concluded that the concept of patentability of a second medical use as determined by Decision Number G5/83 should be broadly construed and that:
. . . such a use is not only valuable in cases where a novel area of therapeutic use, ie, a novel medical indication, is provided, but also in those cases where a novel class of animals, which previously did not respond to a medicament, is cured or protected against a disease.
The Board thus determined that the question of whether a new therapeutic use is in accordance with Decision Number G5/83 should be answered not only on the basis of the ailment to be treated, but also on the basis of the subject or patient to be treated.
Subsequent Technical Board of Appeal Decisions have followed similar lines of reasoning. In Decision Number T893/90, for example, claims directed to treatment of non-haemophiliac patients with a therapeutic previously used for the treatment of haemophiliac patients were considered novel as controlling bleeding in the two sub-populations of patients (haemophiliac and non-haemophiliac) was based on different physiological effects.
In Decision Number T0233/96, the Board considered these two preceding decisions and interpreted them as indicating that novelty of a use of a known compound to treat the same disease in a sub-group of patients required that:
- The sub-group could be distinguished in respect of its physiological or pathological status and did not overlap with the group previously treated; and
- The choice of the new group was not arbitrary, but rather a functional relationship existed between the physiological or pathological status of the sub-group and the therapeutic effect obtained.
In the case before the Board in Decision Number T0233/96, it was determined that the selection of the claimed sub-group (patients who were unable to exercise adequately) was arbitrary in that there was no difference in the treatment effect expected between this sub-group and the known population of patients able to exercise adequately, nor was any such difference shown in the patent.
In Decision Number T1399/04, the Board considered claims relating to treatment of an anti-viral naïve patient having hepatitis C infection with a viral load higher than a specified amount with a known combination therapy for a specified duration of time. The Board considered whether the claims were anticipated by a prior disclosure of treatment of HCV patients with the same combination therapy for a length of time that encompassed the period specified in the claims, given that some of the patients in the previously treated group would have been anti-viral naïve and have viral titers within the claimed range.
The Board determined that the claimed treatment was novel despite this potential overlap as the claims defined a sub-group with a previously undisclosed pathological and physiological status, and that the selection of this sub-groupwas not arbitrary; rather, there was a functional relationship between the claimed sub-group and the improved effect of the claimed treatment.
Subsequent to these Decisions, the Enlarged Board of Appeal again considered second medical use claims in Decision Number G2/08, specifically with reference to European Patent Convention 2000 and what is encompassed by the ‘specified new and inventive therapeutic application’ of article 54(5). The conclusion reached in Decision Number G2/08 was that permitted second medical uses encompass not only the use of a known therapeutic to treat a different disease, but also the use of a known therapeutic in a different treatment of the same disease.
In Decision Number G2/08, the Enlarged Board of Appeal was considering specifically a treatment that differed from a known treatment by dosage regimen. Importantly, however, the Enlarged Board of Appeal also noted several earlier Technical Board of Appeal Decisions which pre-dated European Patent Convention 2000, including Decision Number T19/86, Decision Number T893/90, and Decision Number T0233/96, that addressed the questions of whether treatment of a sub-population, treatment by a new route or mode of administration, and treatment relating to a new technical effect, fall within the principle set out in Decision Number G5/83.
In this regard, the Enlarged Board of Appeal expressed the opinion that ‘the principles established by this case law still hold true’.30 Decision Number G2/08 thus essentially established that second medical use claims may validly be based on a different treatment of the same disease with the same therapeutic where the difference resides in a new population, a new route of administration, and/or a new technical effect.31
This general principle is reflected in the more recent Technical Board of Appeal Decision Number T0734/12, which considered second medical use claims specifying a different sub-population for treatment. In this case, the claims were directed to a use of a known therapeutic to treat the same disease following a particular dosage regimen in a specified sub-population of patients (patient refractory to TNF-inhibitors).
The claims were held to be novel even though the dosage regimen was known for a different population and this population overlapped with the claimed sub-population. The Board held that although the populations overlapped, the claimed sub-population had a different physiological and pathological status, thus rendering the claimed use novel.
However, on further consideration, the use was found to lack an inventive step. Specifically, as the patent did not include any data demonstrating an improvement over the prior art treatment, the Board considered that the problem addressed by the patent was simply to provide an alternative treatment and that this alternative was obvious from the prior art.
In general, treatment-based personalized medicine claims appear to be faring better in Europe than in Canada or the United States, with both the Enlarged Board of Appeal and the Technical Board of Appeal taking a relatively open-minded approach to the potential patentability of such claims. As illustrated by the recent Decision Number T0734/12, however, and given that personalized medicine treatment claims will always be second medical uses, the importance of supporting data in an application has to be emphasized, as this is key to establishing that selection of any claimed sub-population/dosage regimen/ route of administration is not arbitrary, but based on a functional relationship between this claimed feature and an improved effect of the claimed treatment.
Also worth noting is the fact that the European Patent Office appears to be adopting a more limited approach to personalized medicine claims, particularly in relation to sub-populations. In a summary of a meeting between the European Patent Office and the biotech committee of the European Patent Institute, published in the June 2012 issue of EPI Information, the European Patent Office indicated that it is of the opinion that in inventions in the area of pharmacogenomics, such as those involving a new patient group defined by a biomarker, claims often lack novelty.
More specifically, the European Patent Office is taking the position that, in such cases, it is assumed that at least one patient with the biomarker will inevitably have been previously treated, even if the article does not explicitly say so, and that the claim is, therefore, anticipated.
Thus, a second medical-use claim, drafted in standard purpose-limited product format, claiming a use of a known therapeutic to treat the same disease in a patient with a specified biomarker may face novelty objections from the European Patent Office if it can be established that the biomarker is present in a significant proportion of patients.
However, there is some indication from the European Patent Office that, if the claim is drafted as a diagnostic-style ‘identify and treat’ claim reciting an active step of determining whether or not a patient has a particular biomarker and then treating the patient accordingly, it may be considered novel, since the step of determining whether the patient has the biomarker is new.
The novelty of this type of claim will be dependent on whether a link has been established between the presence/absence of the biomarker and an improvement in the treatment (eg, improved efficacy or decreased side-effects), again highlighting the importance of having supporting data in hand when the application is filed.
Like claims to methods of medical treatment, subject matter eligibility of diagnostic method claims is governed by article 53(c) of the European Patent Convention,32 which explicitly excludes from patentability any diagnostic methods performed on a human or animal body.
The scope of this exclusion was considered by the Enlarged Board of Appeal in Decision Number G1/04. The Enlarged Board of Appeal concluded that the exclusion should be interpreted narrowly and that in order to fall under this exclusion, a diagnostic method claim must include all of the following essential characteristics:
- Examination phase including the collection of data;
- Comparison of these data with standard values;
- Identification of a deviation from the normal or desired state;
- Attribution of the observed deviation to a particular clinical picture; and
- Any steps of a technical nature (usually the first step, above) must satisfy the criterion ‘practised on a human or animal body’.
Thus, any claimed diagnostic method that stops short of including all steps, for example, by relating only to the data-gathering stage, is likely to fall outside this exclusion. However, in Decision Number G1/04, the Enlarged Board of Appeal also indicated that a multi-step method will fall under the exclusion in article 53(c) of the European Patent Convention if it includes just one step that constitutes ‘a method of treatment by surgery’.33 An example provided in Decision Number G1/04 was the step of performing a lumbar puncture.
The question of what constitutes ‘treatment by surgery’, particularly in the context of diagnostic methods, was looked at more closely by the Enlarged Board of Appeal in Decision Number G1/07. In this Decision, however, the Enlarged Board of Appeal declined to provide an authoritative definition of the term, indicating rather that the boundaries of this term are best decided on a case-by-case basis.34
Nonetheless, the Enlarged Board of Appeal provided some guidance for future decisions, indicating that diagnostic methods that encompass an invasive step that requires professional medical expertise to be carried out and which entails substantial health risk are excluded under article 53(c) of the European Patent Convention as a method for treatment.35
While Decision Number G1/07 may have left interpretation of diagnostic methods somewhat open, there also was a clear indication that if claims to diagnostic methods were drafted such that it was clear no invasive steps are encompassed, for example, by use of language such as ‘pre-implanted’ or ‘pre-delivered’, such claims would not be excluded under article 53(c) of the European Patent Convention.
Moreover, many diagnostic methods associated with personalized medicine rely on in vitrotesting of a previously obtained sample and, as such, need not include any steps that may trigger an exclusion under article 53(c) of the European Patent Convention.
No clear trend emerges from this overview as to how Canada and Europe interpret claims relating to personalized medicine inventions. Rather, both Canada and Europe are developing unique ways as to how this subject matter should be protected, as based on jurisprudence, stakeholder involvement, and evolving Patent Office practices.
Personalized medicine is a rapidly growing field and it is clear from various initiatives that governments have recognized its importance, both in driving innovation and in providing dramatic improvements in health care. In Canada, for example, the government funded Canadian Institute of Health Research established the ‘Personalized Medicine Initiative’ in 201236 to encourage innovations in this area and to assist in integrating these into public health policy.
This overview suggests, however, that there is a disconnect between these types of government initiatives and the approaches being taken by the Canadian Intellectual Property Office. The Practice Notices currently in use at the Canadian Patent Office lend uncertainty to an innovator’s ability to protect developments in the personalized medicine area; in Europe, the situation also is somewhat uncertain, given the European Patent Office’s current approach to inventions in the area of pharmacogenomics.
Nonetheless, despite the challenges presented by current Patent Office practices, it also appears from this overview that there is sufficient leeway in these practices for meaningful protection to still be obtained for personalized medicine inventions with a creative use of claim language.
In addition, one commonality between the current approaches being adopted by the Canadian Intellectual Property Office and the European Patent Office is that these approaches are not necessarily in line with the relevant case law.
Given that innovator companies are continuing to invest large amounts of capital into the personalized medicine space and to file patent applications for their innovations, it appears inevitable that the current Patent Office approaches will be challenged and it is hoped that more consistent case law and Patent Office practice will emerge as a result, as it has in more traditional practice areas.