Zoetis Services LLC v Boehringer Ingelheim Vetmedica GmbH
[2024] APO 4
•8 February 2024
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Zoetis Services LLC v Boehringer Ingelheim Vetmedica GmbH [2024] APO 4
Patent Application: 2017245601 and
Innovation Patent: 2020102685
Title:Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease
Patent Applicant: Boehringer Ingelheim Vetmedica GmbH
Opponent: Zoetis Services LLC
Delegate: L. F. McCaffery
Decision Date: 8 February 2024
Hearing Date: 18 and 19 July 2023, in Canberra.
Catchwords: PATENTS – opposition to the grant of a patent under section 59 to a standard application – opposition under section 101M to an Innovation Patent – treatment of a patient group with a known pharmaceutical – novelty – prior use – inventive step – bonus effect – support – clarity – clear enough and complete enough disclosure – utility – manner of manufacture – opposition successful on inventive step – other grounds of opposition unsuccessful – costs – opposition under section 101M is concluded – applicant given the opportunity to propose amendments to the standard application.
Representation: Counsel for the applicant: Clare Cunliffe
Patent attorney for the applicant: Marcus Caulfield of FB Rice Pty Ltd
Counsel for the opponent: Patrick Flynn SC and Ben Mee
Patent attorney for the opponent: Duncan Longstaff and Andrew Rankine of Spruson & Ferguson Lawyers
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2017245601 and
Innovation Patent: 2020102685
Title:Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease
Patent Applicant: Boehringer Ingelheim Vetmedica GmbH
Date of Decision: 8 February 2024
DECISION
The opposition is successful on the standard application (AU 2017245601). The claims lack inventive step in view of the information provided in the EPIC Press Release. However, the other grounds of opposition are unsuccessful (novelty, support, clarity, sufficiency and manner of manufacture).
The standard application may contain patentable subject matter. I give the applicant 2 (two) months from the date of this decision to propose amendments to overcome the issues identified above.
The opposition is unsuccessful on the Innovation Patent (AU 2020102685). The opposition to this Patent is concluded.
REASONS FOR DECISION
Background
This matter involves oppositions by Zoetis Services LLC (the opponent) to the grant of Application 2017245601 (the standard application or ‘601) and to Innovation Patent 2020102685 (the Innovation Patent or ‘685), both in the name of Boehringer Ingelheim Vetmedica GmbH (the applicant).[1] The invention in question relates to the use of pimobendan. Pimobendan is a known pharmaceutical used for the treatment of congestive heart failure (CHF) originating, for example, from dilated cardiomyopathy (DCM) or mitral valve disease (MVD) in animals, especially dogs. Pimobendan is also approved for cardiovascular treatment of humans in Japan.[2]
[1] Note: with the exception of page 1, the descriptions for ‘601 and ‘685 are much the same. Reference in the decision to the specification applies to both ‘601 and ‘685.
[2] Specification at page 2, lines 31 to 34.
The standard application was filed on 4 April 2017 and claims an earliest priority date of 6 April 2016. The Innovation Patent is a divisional of the standard application. The claims of the standard application and the Innovation Patent have significant overlap, and the evidence for both oppositions is essentially the same. I have therefore combined the consideration of the two oppositions for most grounds, except for obviousness and innovative step where clearly the two grounds, and the consequential tests, are different.
The oppositions have been the subject of a previous decision by the Commissioner (hereinafter Zoetis v Boehringer No. 1).[3] That decision provides a useful background leading up to the evidence in reply (EIR) in the present oppositions, including:
Evidence in support (EIS) consists of declarations by Stephen Joel Ettinger (Ettinger 1 and exhibits SJE-1 to SJE-17) and Frazer Donald McLennan (McLennan and exhibits FDM-1 to FDM-18).
Evidence in answer (EIA) consists of declarations by Adrian Boswood (Boswood 1 and exhibits AB-1 to AB-28), Sonya G Gordon (Gordon and exhibits SGG-1 to SGG-3), Jens Häggström (Häggström and exhibits JH-1 to JH-4) and Christoph Schummer (Schummer 1 and exhibits CS-1 to CS-26).
Evidence in reply (EIR) consists of declarations by Bruce William Keene (Keene and exhibits BWH-1 to BWK-12), Christopher Butler (Butler and exhibits CB-1 and CB-2) and Stephen Joel Ettinger (Ettinger 2 and exhibits SJE-10 to SJE-38).
[3] Zoetis Services LLC v Boehringer Ingelheim Vetmedica GmbH [2022] APO 72.
In Zoetis v Boehringer No. 1, the delegate determined that paragraphs [31] to [85] of Keene and exhibits BWK-5 to BWK-12 are not properly in reply. However, they considered it appropriate to invoke regulation 5.23 to consult this material. The applicant was given 2 months to file evidence in response. On 1 February 2023, the applicant filed declarations by Adrian Boswood (Boswood 2, together with exhibits AB-29 to AB-34), and Christoph Schummer (Schummer 2, together with exhibits CS-27 to CS-35).
On 13 February 2023, the opponent sought a direction from the Commissioner that the applicant not be allowed to rely on the following evidence:
· Declaration of Adrian Boswood dated 31 January 2023 and exhibits thereto
Paragraph 8
In the third sentence, the words “As with all EPIC study investigators including Dr Ettinger”
In the fourth sentence, the words “and (ii) Dr Stephen Ettinger”
In the fifth sentence, the words “and Dr Ettinger”
Exhibit AB-29(ii)
The whole of the four-page document titled “Mutual Confidentiality Agreement” dated “4/23/2010”
· Declaration of Christoph Schummer dated 31 January 2023 and exhibits thereto
Paragraph 9
In the third sentence, the words “and ii) Dr Stephen Ettinger”
Paragraph 10
In the quotation, the words “Steve Ettinger”
Paragraph 11
The words “Steven Ettinger”
Exhibit CS-27(ii)
The whole of the four-page document titled “Mutual Confidentiality Agreement” dated “4/23/2010”
Exhibit CS-28
The words “Steve Ettinger”
A delegate sought submissions from the parties on this issue. The applicant requested that if the above material was struck out, that it be considered pursuant to regulation 5.23. On 16 March 2023, the delegate struck out the above material from Boswood 2 and Schummer 2. They also did not invoke regulation 5.23, advising the parties that any further consideration under regulation 5.23 of the material could be considered at the substantive hearing. The applicant did not pursue this at the hearing.
Finally, several days prior to the hearing, the applicant filed amendments to the claims of the standard application (the proposed amendments). My understanding is that the opponent does not intend to oppose the amendments. Few significant issues turn on the features they incorporate, and even though they have yet to be allowed, I have included a discussion of the proposed amendments where relevant.
The Expert Witnesses
As indicated above, the opponent adduced evidence from the following witnesses:
Dr Stephen Ettinger: Dr Ettinger graduated as a Doctor of Veterinary Medicine in 1964 and completed specialist post-graduate training in veterinary internal medicine and cardiology in 1973 and 1974. He has over 45 years of experience in clinical and academic practice, is the editor of the leading textbook of veterinary internal medicine practice and has served as an investigator on multiple clinical trials.[4]
Professor Bruce Keene: Professor Keene is said to be a global leader in the field of veterinary cardiology. He has over 35 years’ experience in clinical practice and academia and completed specialist post-graduate specialisation in internal medicine and cardiology in 1983. In 1989 he was appointed to the faculty of the North Carolina State University College of Veterinary Medicine (NCSU) where he continues to work today.
[4] Opponent’s written submissions (OS) at [24] to [31].
Declarations were also provided by Mr Frazer McLennan, a patent information specialist at Spruson & Ferguson, and Mr Christopher Butler, an office manager at the Internet Archive. This evidence related to the publication dates of some documents referred to in evidence. This evidence does not appear to be in dispute, and therefore is not further discussed in this decision.
10. The applicant provided evidence from the following witnesses:
Professor Adrian Boswood: Professor Boswood was appointed to the Royal Veterinary College, University of London in 1990 and is currently Professor of Veterinary Cardiology. He has over 30 years’ experience specialising in veterinary cardiology of dogs, having worked in private practice, research and teaching roles.
Dr Christoph Schummer: Dr Schummer is Global Technical Director with the applicant, where his main therapeutic areas are animal cardiology, pain and inflammation, renal disease and diabetes. He stated that he has 20 years’ experience in veterinary medicine. Dr Schummer is named as an inventor on the standard application and Innovation Patent.
Professor Jens Häggström: Professor Häggström is Professor of Internal Medicine in the Faculty of Veterinary Medicine at the Swedish University of Agricultural Sciences. Professor Häggström’s evidence related to the 2009 ACVIM[5] “Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease” (the 2009 ACVIM guidelines).
Professor Sonya Gordon: Professor Gordon is Professor of Cardiology in the College of Veterinary Medicine and Biomedical Science at Texas A&M University. Her evidence also related to the 2009 ACVIM guidelines.
[5] The American College of Veterinary Internal Medicine.
11. The opponent submitted that, where there is a conflict, the evidence of Dr Ettinger and Professor Keene should be preferred.[6] They argued that Professor Boswood has provided opinions for the applicant in other matters not related to the present matter, and has received funding from the applicant and the opponent.[7] The opponent also submitted that Dr Schummer is an employee of the applicant and a named inventor, and therefore cannot be regarded as an independent witness.[8] The opponent submitted that Dr Schummer also does not appear to have any clinical veterinary experience, having spent his career in the pharmaceutical industry, and holds no professional qualifications in veterinary cardiology. The opponent argued that he, therefore, cannot be considered a person skilled in the present technical field.
[6] OS at [60] to [61].
[7] OS at [46].
[8] OS at [59].
12. The applicant submitted that Dr Ettinger’s evidence as to what was known at the priority date is idiosyncratic and not supported by the other experts or contemporaneous documents. The applicant also submitted that, despite his prolific publication history, Dr Ettinger did not publish any of the theories on pimobendan that he set out in evidence and has no material to corroborate his assertions as to its use before the priority date.[9] The applicant also noted that Dr Ettinger failed to disclose his involvement in the EPIC[10] clinical trial (the EPIC Trial) in his evidence in support. For example, when addressing the issue in his evidence in reply, Dr Ettinger stated that:
“Until reading the Boswood declaration, I did not recall attending the meeting referred to in paragraph 247 of that declaration.[11] I now recall that, at some time during 2010, I attended a gathering of veterinary cardiologists at which a presentation was given concerning the EPIC trial (2010 meeting). To my recollection, that meeting occurred on the side-lines of an ACVIM conference held in the United States. Over the course of my career, I have attended many such events, which provide me with an opportunity to connect with my professional colleagues, including colleagues from other countries.
To my current recollection, the 2010 Meeting was directed to veterinary cardiologists who may be interested in participating in the conduct of the EPIC trial. I note, in this regard, that in paragraph 143 of his declaration, Professor Boswood refers to attendees at the 2010 Meeting as ‘potential investigators’. By contrast, in paragraph 108 of his declaration, Dr Schummer describes the 2010 meeting as a ‘confidential investigator meeting’ and suggests that attendees were provided with ‘the detailed EPIC study plan, case report forms, clinical parameters including efficacy and safety… and were provided with specific training’. I have no recollection of receiving such materials nor do I recall participating in any training in relation to the EPIC trial.” [original emphasis].[12]
[9] I note that the lack of corroborative evidence led the opponent to file evidence Professor Keene’s evidence, which required the determination in Zoetis v Boehringer No. 1.
[10] EPIC - Evaluation of Pimobendan In dogs with Cardiomegaly caused by preclinical mitral valve disease.
[11] Professor Boswood had referred to a confidential planning meeting in 2010 (hereinafter the 2010 meeting) that discussed trial protocol options, took feedback from the potential investigators and decided on the study protocol – see Boswood 1 at [247]. Dr Schummer similarly stated that the meeting included a discussion of inclusion criteria, interim analysis criteria and exclusion criteria – see Schummer 1 at [60].
[12] Ettinger 2 at [158] to [159].
13. In response to Dr Schummer’s statement that attendees at the 2010 meeting signed confidentiality agreements,[13] Dr Ettinger stated, “I have no recollection of signing or not signing such an agreement (that is I have no recollection either way)”.[14] He went on to state that his instructions were to have regard only to the EPIC March 2015 Press Release, together with any matters that were generally known and accepted in his field when discussing how the press release influenced his prescribing practices before the priority date.[15] As to his being acknowledged in the 2016 publication of the final results of the EPIC Trial, Dr Ettinger stated:
“As Medical Director, my responsibilities included giving approval for patients of the hospital to be enrolled in clinical trials (with the consent of their owners) and for staff of the hospital to participate in the conduct of clinical trials in the course of their work. I recall that at least one of the veterinary cardiologists at the California Animal Hospital, Dr Kirstie Barrett, was involved in the care of dogs enrolled in the EPIC trial in the course of her clinical work at the hospital (Dr Barrett was subsequently named as a co-author on the EPIC 2016 Publication).
In accordance with my usual practice and the scope of my responsibilities as Medical Director at the California Animal Hospital in the period up to 2010, I expect that I gave approval for dogs receiving care at the hospital to be enrolled in the EPIC trial and for staff members including Dr Barrett to participate in the EPIC trial in the course of their work. While I do not have any specific recollection of giving that approval, I have no reason to doubt that I did so. It is possible that my consent was given verbally rather than in writing. On the other hand, to my current recollection I was not personally involved in the conduct of the EPIC trial in the course of my clinical duties at the California Animal Hospital. In 2010, I left the California Animal Hospital and was not involved in the conduct of the EPIC trial after that time.”[16]
[13] Schummer 1 at [60].
[14] Ettinger 2 at [160]. I note that the delegate determined not to consult a copy of a confidentiality agreement signed by Dr Ettinger (Exhibit AB-29) as Dr Ettinger's involvement was sufficiently covered by the existing evidence.
[15] Ettinger 2 at [162].
[16] Ettinger 2 at [164] to [165].
14. The opponent did not rely on much of Dr Ettinger’s evidence, and most of the background material was not in dispute, but I share the concerns of the applicant in relation to Dr Ettinger’s evidence. Nevertheless, Dr Ettinger was provided with a copy of the Federal Court of Australia Expert Evidence Practice Note, and I have no reason to conclude that he has not acted in accordance with those guidelines. However, I am led to approach his evidence with caution where statements are not supported by corroborative evidence.
15. The applicant also noted that all of the expert witnesses were all involved in the EPIC Trial which forms the basis of the present invention and is incorporated by reference in the present standard application and Innovation Patent. Professors Boswood, Häggström and Gordon were lead investigators, Dr Schummer was the clinical study manager, and Professor Keene and Dr Ettinger were investigators in the EPIC Trial. Professors Boswood, Häggström, Gordon and Keene are named as authors on the paper describing the final results of the trial (the 2016 EPIC paper).[17] Dr Ettinger is acknowledged for assistance in management and recruitment of cases. Professor Keene’s veterinary clinic was one of the major recruiting sites for the EPIC Trial, and he also received the interim results of the trial and the manuscript of the trial before their publication.[18]
[17] Boswood et al., “Effect of Pimobendan in Dogs with Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study – A Randomized Clinical Trial, J Vet Intern Med 2016; 30: 1765-1779 (Exhibit SJE-12).
[18] Exhibit AB-31.
16. It is unusual that the expert witnesses on both sides of a matter would have such first-hand knowledge of the work leading up to an invention. This brings into question whether the practices used in Professor Keene’s clinic were based solely on publicly available information or whether they would have been influenced in some way by their involvement in the EPIC Trial.[19] Furthermore, given the close association of all the experts with the EPIC Trial, it is arguable whether their knowledge would be truly representative of the person skilled in the art at the relevant time, and whether they would have viewed publications about the EPIC Trial in the same way as a veterinarian with no direct knowledge or experience of the trial.
[19] AS at [7].
17. Notwithstanding my concerns on this point, I do not consider it necessary to entirely disregard any evidence on this basis alone. Issues such as those identified above are simply relevant factors that should be taken into account when determining the weight that can be given to any evidence provided in the matter by any of the experts, noting that the Commissioner is not bound by the rules of evidence. However, I consider the nature of the evidence also constrains how it can be used. For example, Professor Keene’s evidence concerns a single issue (whether his clinic treated dogs in stage B2 with pimobendan prior to the priority date of the present application). Similarly, Professors Häggström and Gordon provide evidence only on events related to the 2009 ACVIM guidelines. I do not consider that evidence specific to a single issue can be extrapolated beyond the specific question it relates to and the statements made by the expert in that regard. Where necessary I have discussed such issues in greater detail below.
The person skilled in the art (PSA)
18. The task of construing the specification is undertaken from the viewpoint of a person skilled in the art and the prevailing common general knowledge at the priority date. The person skilled in the art is a hypothetical non-inventive person or team likely to have a practical interest in the subject matter of the invention:
“He is the person to whom the patent is addressed and who must construe it. He is the person whose knowledge will determine whether a patent is novel. He is the person who will judge whether a patent is obvious.”[20]
[20] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70]-[72].
19. The parties differed in their characterisation of the skilled person and particularly whether the skilled person would have specialist qualifications and experience in cardiology and internal medicine, or whether it would include veterinarians working in the field of developing new treatments for veterinary cardiological diseases. The parties’ respective experts clearly reflect their differing characterisations of the skilled person.
20. On balance, I do not consider that the person having an interest in the patent would necessarily be limited to specialist cardiologists. From a practical point of view, the skilled addressee may be a veterinarian with a working knowledge of cardiac conditions in dogs and their treatment, probably as part of a team that includes suitably qualified technicians (for example, radiographers) assisting in the diagnosis of the underlying condition. Given this characterisation of the skilled person, I consider that all of the experts have knowledge and experience relevant to the present consideration.
21. I also note that several of the experts are leaders in the field of veterinary cardiology, and it could reasonably be asked whether they are truly representative of a person of ordinary skill in the art. But that is not determinative of whether they are suitable candidates to provide evidence in the present matter. The key consideration is whether the evidence and the opinions they provide reflect the common general knowledge in the art rather than their own.
22. Finally, the claims of the standard application presently extend to treatment of human patients, and the opponent provided some submissions on the treatment of humans. All of the experts are veterinarians and I consider the evidence provided in relation to the treatment of dogs is of little assistance as to the common general knowledge in the treatment of humans. In any case, the proposed amendments would render this issue moot.
The common general knowledge
23. The task of construing the specification is undertaken in the context of the common general knowledge as it existed at the priority date:
“The notion of common general knowledge itself involves the use of that which is known or used by those in the relevant trade. It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.”[21]
[21] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; 144 CLR 253 at 292.
24. It is not sufficient that a document is publicly available for it to be considered part of the common general knowledge in the art. There must be evidence of its general acceptance and assimilation by the person skilled in the art.[22] However, common general knowledge is not limited to information that the skilled person has committed to memory, and also includes material in the field in which he is working which he knows exists and to which he would refer as a matter of course.[23] I have attempted to provide a background to the invention and the material which I understand constitutes common general knowledge in the following sections.
Basic heart structure and function
[22] Aktiebolaget Hassle v Alphapharm Pty Ltd supra at [31].
[23] ICI Chemicals and Polymers Ltd v Lubrizol Corporation Inc 1999 FCA 345 at [111].
25. In mammals, including dogs, the heart is divided into four chambers, as shown in the diagram below. The upper chambers are known as the left atrium and right atrium, while the lower chambers are known as the left and right ventricles.[24] The right side of the heart receives blood from the body and pumps it to the lungs, via the pulmonary blood vessels, where carbon dioxide is excreted, and oxygen is absorbed. The left side of the heart receives oxygenated blood from the lungs and pumps it to the rest of the body.[25] Within the left side, the main pumping chamber is the left ventricle. The left atrium receives oxygenated blood that arrives from the lungs.
[24] Ettinger 1 at [40].
[25] Ettinger 1 at [39].
26. The mitral valve is situated in the left side of the heart, between the left atrium and the left ventricle. The normal function of the mitral valve is to ensure that blood flows in the correct direction. It acts as a one-way valve, allowing blood to move from the left atrium to the left ventricle and, when the left ventricle contracts, the mitral valve also ensures that blood is pumped forwards to the body by blocking any movement backwards into the left atrium.[26]
Myxomatous mitral valve disease
[26] Boswood 1 at [28] to [29].
27. Valvular heart disease is the most common cause of heart disease and heart failure in the canine population. The disease most commonly affects the mitral valve, and the associated disease is referred to more commonly as mitral valve disease (MVD) or myxomatous mitral valve disease (MMVD).[27] The latter term will be used in this decision. MMVD typically develops in adult small breed dogs as they age and is a common cause of morbidity and mortality in the ageing dog population, accounting for about 75 to 85% of all cases of heart disease diagnosed in dogs in developed countries. Some breeds of dog are very strongly predisposed to the development of the disease, such as the Cavalier King Charles Spaniel.[28]
[27] Note: the term MVD is broader than MMVD. For example, there are congenital diseases of the mitral valve, or instances where mitral valve degeneration can be caused by an infection. These are not captured in the term MMVD. However, these are relatively rare and if what is being considered is an acquired mitral valve disease that a dog has developed in later life then it would be considered MMVD. See Boswood 1 at [35] to [37].
[28] Boswood 1 at [26]-[27], Ettinger 1 at [73] to [75].
28. MMVD causes the valve tissue to degenerate, becoming distorted and unable to fully close. When the left ventricle contracts, blood leaks backwards through the misshapen valve and into the left atrium (referred to as mitral valve regurgitation). Once blood is pumped from the left ventricle, the heart relaxes, and the leaked blood goes back from the atrium to the ventricle. This results in the heart needing to pump a larger than normal amount of blood.
29. MMVD is progressive, but not all animals will develop further symptoms. In the early stages of the disease, the leak is relatively small and has negligible consequences for the heart. As leakage increases it can be detected as an audible murmur in clinical examination, which is generally the earliest clinical sign of MMVD.[29] As the disease progresses, mitral regurgitation results in blood leaking back into the left atrium at a relatively high pressure.[30] In dogs with severe MMVD, more than 75% of the left ventricular stroke volume may be ejected back into the left atrium. This blood would potentially enter the pulmonary venous circulation, which normally operates at low pressure, and result in the development of pulmonary congestion and pulmonary oedema (accumulation of an abnormal amount of serous fluid in the lung tissues).[31]
[29] Boswood 1 at [30] to [32].
[30] Ettinger 1 at [85].
[31] Ettinger 1 at [87].
30. However, compensatory mechanisms are activated to protect the pulmonary circulatory system against the effects of mitral regurgitation, as well as assisting the heart to maintain adequate forward stroke volume. These compensatory mechanisms, while initially beneficial, contribute to progressive deterioration of cardiac structure and function.[32] There may be secondary changes in the shape, size, and function of the heart (cardiac remodelling). Dogs may go on to develop heart failure and eventually die because of the condition.[33]
Classification systems used to characterise and treat the different stages of MMVD
[32] Ettinger 1 at [86].
[33] Boswood 1 at [34].
31. Several classification systems have been developed to identify the stage to which MMVD has progressed in an animal and the treatments that are appropriate at each stage. The American College of Veterinary Internal Medicine (ACVIM) has developed a classification system for the diagnosis of MMVD (the ACVIM classification system).[34] Other classification systems include the New York Heart Association and International Small Animal Cardiac Health Council classification systems (the NYHA and ISACHC systems respectively).[35] These systems are apparently used less frequently than the ACVIM classification system.
[34] Exhibit SJE-3.
[35] Ettinger 1 at [123].
32. In each system a distinction is drawn in each of the schemes between patients that do, and patients that do not, display clinical signs caused by heart failure.[36] For example, in the ACVIM classification scheme, Stage B is distinguished from Stages C and D by presence or absence of clinical signs of heart failure.[37] This is relevant to the present determination as Claim 1 of the Innovation Patent and Claim 2 of the standard application define the invention with reference to the ACVIM and ISACHC systems. Most of the submissions focussed on the ACVIM system and, as a consequence, the present determination refers for the most part on the guidance provided by that system unless specifically indicated.
Heart disease and heart failure
[36] OS at [153].
[37] Ettinger 1 at [125], Boswood 1 at [62]; Schummer 1 at [22].
33. Heart disease is not synonymous with heart failure. Heart disease refers to any pathological change in the structure and/or function of the heart that is outside the limits of normality. Heart failure is a pathophysiological state in which the heart’s ability to eject or receive blood becomes severe enough to overwhelm the compensatory mechanisms of the cardiovascular system. A normally functioning heart must eject blood into the aorta and pulmonary artery with sufficient force to provide adequate perfusion of the systemic and pulmonary capillary beds. It must also receive returning blood so as to provide adequate drainage of those beds and ensure an appropriate distribution of blood throughout the circulatory system. Either or both of those functions may be impaired in heart failure.[38]
[38] Ettinger 1 at [111].
34. Heart failure commences when there is insufficient blood ejected by the heart. When the body senses that insufficient blood is circulating, one response is the upregulation of sympathetic nervous system to increase the circulating concentrations of adrenaline and other stimulating hormones. Like the remodelling of the heart that occurs to deal with mitral regurgitation, neurohormonal activation is initially a compensatory response. Neurohormonal activation leads to the retention of fluid and an increase in blood pressure (and “pre-load) via the renin-angiotensin-aldosterone system (RAAS).[39] However, when some of those responses are chronically stimulated, they eventually lead to a damaging effect on the heart and circulation (decompensation), ultimately causing the development of heart failure.
[39] Boswood 1 at [67].
35. As noted above, a key distinction between the various stages of MMVD is the presence of clinical signs of heart failure. This appears to involve a subjective evaluation by the practitioner. Typical signs of heart failure secondary to MMVD include: elevated breathing rate and respiratory distress, coughing, anxiousness and restlessness, weakness and reduced stamina, reduced exercise tolerance, abnormal respiratory sounds including crackles and wheezing, pleural effusions[40] and/or ascites[41], loss of appetite and significant loss of bodyweight, additional abnormal heart sounds such as a “cardiac gallop” or an extremely loud third heart sound, arrhythmias (irregularities of heart rhythm), and syncope (fainting). [42]
[40] Accumulation of serous fluid in the pleural sac that lies between the lung and the chest wall.
[41] Accumulation of serous fluid in the peritoneal sac that lies between the abdominal organs and the abdominal wall.
[42] Ettinger 1 at [127].
36. Coughing may be observed when a dog is in heart failure as fluid builds up in the lungs. However, while it was common ground between the experts that coughing is a non-specific sign that may be observed in dogs in Stage B2 as a result of compression of the left mainstem bronchus by the enlarged left atrium, other broncho-pulmonary diseases such as “collapsing trachea”, or pathologies unrelated to the dog’s heart disease can also result in coughing. [43] This has implications for the interpretation of the patient records provided by Professor Keene, as further discussed below.
Management and treatment of MMVD
[43] Boswood 1 at [118], Ettinger 1 at [133].
37. In human patients, treatment of valvular diseases generally involves surgical valve repair or replacement. However, surgical treatment has not been considered appropriate in the overwhelming majority of canine patients affected by MMVD, and drug treatment has been the mainstay of treatment.[44] A knowledge of the pathophysiology and staging of MMVD is critical for the optimal management of the disease. The ACVIM classification was required because of important clinical implications for prognosis and treatment based on the different stages of MMVD.[45]
[44] Ettinger 1 at [150].
[45] Boswood 1 at [71] to [72].
38. At the early stages of MMVD, no drug treatment is recommended. In Stage A (that is, dogs who are at risk of developing MMVD), regular checks for the development of a heart murmur are performed as part of routine veterinary care. Drug therapy was universally not recommended for Stage A dogs.[46] For dogs in Stage B1 (that is, having a heart murmur, without detectable heart enlargement), agreement on a potential treatment has been difficult to reach because there is little evidence to suggest that drug therapies provide any benefits. The 2009 ACVIM consensus statement therefore recommended no drug therapies for MMVD Stage B1 patients.[47]
[46] Boswood 1 at [76].
[47] Boswood 1 at [81] to [83].
39. In the case of dogs at MMVD Stage B2 (that is, dogs that show heart enlargement but do not display clinical signs of heart failure), there was no consensus pharmacological or dietary treatment.[48] The 2009 ACVIM Guidelines stated that:
“No other pharmacologic treatments were recommended in Stage B2 by a majority of panelists. A few panelists considered the use of the following medications for patients in Stage B2 under specific circumstances: pimobendan, digoxin, amlodipine, and spironolactone. The panel felt in general that these treatment strategies needed additional investigation into their efficacy and safety in this patient population before a consensus recommendation could be made.”[49]
[48] Boswood 1 at [84] to [85].
[49] Exhibit AB-5 at p.1145.
40. Administration of ACE inhibitors (ACEi)[50], such as enalapril and benazepril, was (and remains) one line of therapy used by cardiologists. ACEi are vasodilators and also inhibit fluid retention, and the theory is that they should reduce both pre-load (the volume of blood entering the heart) and after-load (resistance from the vascular bed to the blood being ejected from the heart) on the heart.[51] That is consistent with the evidence of Dr Ettinger, who stated that he, and other cardiologists with whom he interacted, routinely prescribed ACEi to dogs with MMVD.[52] On the other hand, Professor Boswood stated that the theoretical benefit of ACEi administration was not substantiated by clinical studies.[53] He noted that the administration of ACEi was generally favoured in the United States more than in most of Europe, but fortunately ACEi did not appear to cause any detrimental effects to the heart.[54] Nevertheless, in the preparation of the 2009 ACVIM Guidelines, the majority of ACVIM panellists suggested ACEi therapy for Stage B2 dogs, despite admitting that clinical trials showed mixed results and noting that it was not a consensus recommendation.[55]
[50] Angiotensin converting enzyme inhibitors.
[51] Ettinger 1 at [165].
[52] Ettinger 1 at [166] to [167].
[53] Boswood 1 at [87].
[54] Boswood 1 at [90].
[55] Boswood 1 at [92].
41. Once a dog reaches heart failure (Stage C), several treatments are available to improve quality of life, and in some cases, prolong life. These target different abnormalities in heart function:
· Preload: this is predominantly determined by the pressure with which the blood returns to the heart from venous circulation. As noted above, heart failure is often accompanied by increased fluid retention which causes an increase in preload. Treatment is aimed at reducing the circulating fluid volume using diuretics such as furosemide, or dilating veins using venodilators.
· Afterload: compensatory responses to heart failure includes several mechanisms that increase afterload, thereby increasing the resistance in the vascular bed into which blood is ejected by the heart. Vasodilators are used to reduce systemic or pulmonary vascular resistance and modify afterload.
· Myocardial contractility: this is one of the main determinants of cardiac output. Positive inotropic drugs increase contractility of the heart. Pimobendan has both inotropic and vasodilatory properties.
· Cardiac filling: to fill adequately, the heart must have enough time to fill, and the myocardium must be sufficiently flexible to allow adequate venous return to enter the ventricles during diastole. Drugs that directly influence the myocardium to relax are referred to as lusitropic drugs and include sympathomimetic agents and calcium channel blockers.[56]
[56] Boswood 1 at [97].
42. Professor Boswood stated that treatment of patients in Stage C depended on client preference and the feasibility of administering multiple medications in these patients. The optimum treatment would consist of up to four medications, but administration of furosemide (a diuretic) was necessary in patients with congestive heart failure.[57] Typical therapies included:
Furosemide plus pimobendan
Furosemide plus pimobendan plus ACEi
Furosemide plus pimobendan plus ACEi plus spironolactone.[58]
[57] Boswood 1 at [104].
[58] Spironolactone has diuretic properties, but acts on the effects of aldosterone, a hormone that forms part of the RAAS. See Ettinger 1 at [160] to [161].
43. Similarly, Dr Ettinger stated that he, and other veterinarians he interacted with, generally prescribed a triple therapy of a diuretic (usually furosemide), and ACEi (enalapril or benazepril) and pimobendan.[59] In some cases other drugs would be prescribed, including spironolactone and hydralazine (a vasodilator).[60]
[59] Ettinger 1 at [176].
[60] Ettinger 1 at [186].
44. Once optimal therapeutic treatment of a dog at Stage C has been achieved, there is generally a period of several months where the patient is stable and compensates for their heart failure. However, for most dogs, there is a point where clinical signs return, and a modification of treatment is required (Stage D). Professor Boswood referred to the aim at this stage being to decrease clinical signs of congestive heart failure, delay death due to cardiac reasons and reduce the distress of the dog.[61] Some of the modifications included:
Changing the treatment regime to include all four of furosemide, pimobendan, ACEi and spironolactone (if this regime was not already being used);
Addition to the combination of further diuretics, vasodilators and/or digoxin (where the patient has atrial fibrillation);
Increase the furosemide dose and frequency, maximise the spironolactone dose, and double the frequency of the ACEi administration.
[61] Boswood at [108] to [109].
45. While the optimal treatments are generally guided by the classification that a patient falls into, Professor Boswood stated that difficulties can arise with dogs hovering on the boundaries between categories. He considered that there is an artificial level of certainty associated with a patient either having or not having signs of heart failure. For example, it can be difficult to judge in patients with moderate to marked intolerance to exercise, or radiographic evidence of a mild interstitial lung pattern, whether the patient is in heart failure or not. These questions remain difficult, and in such cases decisions about therapy were made on a case-by-case basis.[62] This case-by-case approach at the boundaries of classification would seem consistent with Dr Ettinger’s evidence that an “increasing rate of enlargement of the left atrium and left ventricle on successive echocardiograms was one of the key findings that indicated to me that a dog with MMVD in ACVIM Stage B2 was at risk of progressing to ACVIM Stage C in the near term and required pharmacological treatment, including with pimobendan”.[63]
The EPIC Trial
[62] Boswood 1 at [116] to [117].
[63] Ettinger 2 at [104].
46. The present invention is based on the results of the EPIC Trial and the 2016 EPIC paper is incorporated by reference.[64]
[64] See Example 2 and page 5, lines 35 to 38.
47. Professor Boswood stated that prior to 6 April 2016, the only clinical evidence for benefit of the use of pimobendan in MMVD was in relation to the treatment of dogs with clinical signs of heart failure (Stage C). The ability of pimobendan to improve cardiac contraction made it suitable for treating diseases characterised by primary failure of the heart to contract normally, such as dilated cardiomyopathy. However, its use may be counter-intuitive for the treatment of MMVD where the heart muscle is not the source of the primary disease in MMVD. Some cardiologists were extremely sceptical about the application of pimobendan in MMVD, and its use was therefore limited mainly to refractory treatment of dogs with heart failure. These concerns were addressed by the QUEST clinical trial which convincingly showed the benefits of pimobendan in treating dogs in Stage C of MMVD.[65]
[65] Boswood 1 at [120] to [124].
48. The use of pimobendan with dogs at Stage B2 was apparently even more contentious. Some studies had suggested a potentially detrimental effect in dogs at the early stages MMVD. For example, a study by Chetboul et al.,[66] suggested that pimobendan exacerbated mitral regurgitation in dogs receiving pimobendan.[67] Toxicological studies at the time demonstrated that when administered intravenously at high doses, pimobendan can cause changes in the endocardium, valve and myocardium.[68]
[66] Exhibit AB-9.
[67] Boswood 1 at [127].
[68] Boswood 1at [128].
49. It was against this background that the EPIC Trial commenced to determine whether there was any benefit in the use of pimobendan in treating dogs with MMVD in Stage B2. The blinded randomised study commenced planning in 2009. Clinical investigators were recruited from 36 different centres internationally. Dogs were enrolled in the study based on very strict inclusion criteria, and around 1000 dogs were screened to select the 360 that were eventually recruited.[69] Data acquisition was not finished until March 2015 and analysis continued until 2016 to obtain the final results. An interim analysis was planned at about 75 to 80% through the study. At this stage the lead investigators were advised that the results of the interim analysis were positive, and the decision was made to stop the study. This was announced in the EPIC Press Release[70] on 16 March 2015. The full results of the trial were first presented at the 2016 ACVIM meeting in Denver Colorado on 11 June 2016, and subsequently published in the 2016 EPIC paper on 28 September 2016.[71]
[69] Boswood 1 at [141] to [145].
[70] Exhibit SJE-26.
[71] Boswood 1 at [159] to [163].
50. It was a matter of some dispute in the opposition whether the EPIC Trial, and specifically the information contained in press releases about the trial, was common general knowledge. The opponent submitted that a substantial amount of information concerning the trial was made publicly available and widely publicised among veterinary cardiologists. Key results of the EPIC Trial were made available in the EPIC Press Release, as well as in press releases by Professor Boswood’s and Professor Gordon’s universities. Those press releases were subsequently disseminated by media organisations. As a result of these activities, there was a high awareness of the EPIC Trial amongst veterinary cardiologists before the priority date.[72]
[72] OS at [113(?)].
51. The applicant noted that all of the expert witnesses in the present matter were involved in the EPIC Trial. No evidence has been adduced from anyone who was not involved in the trial but was aware of it.[73] Instead the opponent relied on the evidence of Dr Ettinger, who stated that he was aware of the EPIC Trial and that he read both the announcement and the EPIC Press Release at around the time of their publication.[74] He went on to state that he and other veterinary cardiologists with whom he interacted at the time were very familiar with the EPIC Trial and regarded it to be an important clinical trial in the field of veterinary medicine.[75]
[73] AS at [89].
[74] Ettinger 1 at [309] and [317].
[75] Ettinger 1 at [217], [218] and [319].
52. However, in response to Professor Boswood and Dr Schummer pointing out that he had failed to disclose his early involvement in the EPIC Trial, Dr Ettinger stated that he did not recall attending the meeting, receiving any materials relating to the trial parameters or receiving any training. I find it difficult to reconcile that Dr Ettinger recalled discussions with other cardiologists concerning a clinical trial that he regarded as so important but failed to recall his own direct involvement in that same trial. On balance, I prefer the evidence of Professor Boswood, who stated that:
“At the onset of the study, some cardiologists held the view that we (the investigators) were irresponsible for administering pimobendan, which they regarded as potentially harmful to the dogs, and we were criticised for administering it too early in the disease. According to many people skilled in our field, the only acceptable use of pimobendan – where the benefit would outweigh its alleged harm – was administration to dogs with clinical signs of heart failure (stage C dogs), or dogs who have clinical signs of heart failure and are refractory to standard therapies (stage D dogs), as a salvage agent.
Opposition to our study was further strengthened when, as the study was ongoing in 2015, publications were coming out which claimed that there was no benefit associated with a number of drugs including pimobendan in stage B disease. Further, a paper came out by a respected cardiologist stating that there was no evidence to support administering pimobendan in stage B2.
So the question about the benefit of pimobendan administration to dogs with MMVD but without clinical signs of heart failure was very contentious, and continued to be so until after the publication of the full results of the EPIC study in September 2016.”[76]
[76] Boswood 1 at [134] to [136].
53. Common general knowledge requires that information be generally assimilated and accepted without question by persons skilled in the art. The evidence suggests that the existence of the EPIC Trial, and even the hypothesis that was being tested, formed part of the public knowledge of veterinary cardiologists. However, the technical information relating to the EPIC Trial appears to have been more contentious, and less well-accepted, in the art. I am satisfied that the existence of the EPIC Trial may well have been widely known amongst veterinary cardiologists. However, I do not consider that the EPIC Trial or any of the information provided in the various press releases and announcements can be considered common general knowledge as of the priority date of the application.
Principles of Construction
54. The legal principles applicable to the construction of patent specifications are well established.[77] The Full Court in Airco Fasteners Pty Ltd v Illinois Tool Works Inc.,[78] recently reiterated the principle that experts can give evidence on the meaning which those skilled in the art would give to technical or scientific terms and phrases and on any unusual or special meanings that would be given by skilled addressees to words which might otherwise bear their ordinary meaning.[79] The Court is to place itself in the position of some person acquainted with the surrounding circumstances as to the state of the art and manufacture at the time.[80] However, it is for the Court, not for any witness however expert, to construe the specification.[81] A similar approach is taken in matters before the Commissioner. I also note the guidance of Middleton J in Eli Lilly and Company Limited v Apotex Pty Ltd:
“It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date.”[82]
[77] Jupiters Ltd v Neurizon Pty Ltd (2005) 65 IPR 86; [2005] FCAFC 90 at IPR 99-100 [67].
[78] [2023] FCAFC 7 at [48].
[79] Sartas No 1 Pty Ltd v Koukourou & Partners Pty Ltd [1994] FCA 1529 (Sartas No. 1); (1994) 30 IPR 479 at [485]-[486].
[80] Kimberley-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8; 207 CLR 1 at [24].
[81] Sartas No 1, supra at [485]-[486].
[82] [2013] FCA 214; 100 IPR 451 at [139].
55. A key consideration in the present case is the construction that should be given to the independent claims defining methods of treatment. The parties respectively drew my attention to the approaches taken in Otsuka v Generic Health,[83] and Apotex v Sanofi-Aventis.[84] These were said to provide guidance as to the construction that the present claims should be given, albeit in a manner that best suited the respective cases forwarded in the opposition.
[83] Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) (2015) 13 IPR 191, [2015] FCA 634.
[84] Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (No 2) [2012] FCAFC 102; (2012) 204 FCR 494; 290 ALR 1; 96 IPR 185.
56. I agree that it can be useful to draw analogies between previous decisions and the claims under consideration. However, the principles of construction, while often referred to as rules, are perhaps better characterised as guidelines or aids to construction rather than strict rules. The cases referred to by the parties serve to illustrate how the Courts have applied those principles to the specific circumstances of each case. Thus, while I have had regard to the cases identified by the parties, I have attempted to construe the claims consistent with the general principles of construction according to the specific facts of the case and understanding of a skilled person in this field of technology.
The claims
57. The specifications of ‘601 and ‘685 are essentially the same. The claims of ‘601 are given in Attachment A, and ‘685 in Attachment B. The key difference lies in the first claim of each, as indicated below.
Claim 1 of the standard application (‘601)
A method for treating a patient with asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD), the method comprising administering to the patient an effective amount of a pharmaceutical composition comprising pimobendan so as to effect a reduction of the heart size of an already pathologically enlarged heart of the patient in combination with delaying the onset of clinical symptoms of heart failure in the patient.
(Claim 2: The method of claim 1, wherein the asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD) is of a stage selected from the group consisting of: stage ISACHC Class IB and ACVIM stage B2.)
Claim 1 of the Innovation Patent (‘685)
A method for treating a dog with asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD), the method comprising administering to the dog an effective amount of a pharmaceutical composition comprising pimobendan so as to effect a reduction of the heart size of an already pathologically enlarged heart of the dog in combination with delaying the onset of clinical symptoms of heart failure in the dog;
wherein the asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD) is of a stage ISACHC Class IB or ACVIM stage B2.
58. As indicated above, claim 1 of ‘685 is more specific than ‘601 as to the treatment group (a dog, as opposed to a patient), and also identifies the stage of MMVD by its ISACHC and ACVIM category. The latter feature is separately defined in claim 2 of ‘601. The proposed amendments to ‘601 dated 11 July 2023 limit the claims to the treatment of dogs. But in any case, I do not consider this greatly affects the consideration since the evidence adduced in the opposition was primarily directed to the treatment of MMVD in dogs.
59. The issues of construction are essentially the same between ‘685 and ‘601 so most of the discussion of the following issues applies equally to each. The opponent’s submissions on construction were grouped into two themes: the patient characteristics and the steps of the method versus the outcomes. A number of specific issues were covered in each theme. I will deal with each of these in turn.
Patient species
60. As it currently stands, Claim 1 of the ‘601 is directed to a patient. The specification states that:
“The term ‘patient’ embraces mammals such as primates including humans. In addition to primates, a variety of other mammals can be treated according to the method of the present invention. For instance, mammals, including but not limited to, horses, dogs, cats, or equine, canine, feline species can be treated. Preferred are human patients, dogs, cats and horses … Most preferred are dogs.”
61. This is consistent with the definition currently provided in Claim 5 of ‘601, wherein the patient is selected from the group consisting of a human, a dog and a horse.
62. As noted above, the proposed amendments to the claims of ‘601 limits the patient group to dogs. This would have the effect of the patient group in each of the standard application and Innovation Patent both being limited to dogs.
A method for treating an individual patient
63. There was no apparent dispute between the parties in their submissions that the method defined by Claim 1 is directed to the treatment of an individual patient, as distinct from, say, a method of treating a population of patients or a method for conducting a clinical trial. In this regard the opponent noted the use of the singular noun (a patient, the patient) at four points in the claim.[85] However they also noted that the specification states that:
“…as used herein and in the appended claims, the singular forms ‘a’, ‘an’, and ‘the’ include plural references unless the context clearly indicates otherwise.”
[85] OS at [145].
64. The opponent submitted that the context of the claims “clearly indicates otherwise” and that the method is directed to the treatment of an individual. Several dependent claims refer to outcomes in terms of quantitative terms (for example, claims 10, 11, and 13 of ‘601 define prolongation of the time of survival of “at least about 5 months”, “at least about 7 months”, or “at least about 30 days”), but the terminology is not suitable for specifying quantitative outcomes across a population of patients. For example, there is no reference made to “mean” or “median” values. In this regard, the opponent noted that Professor Boswood and Dr Schummer emphasise the results of the EPIC Trial as being related to “average” or “median” results obtained across a “population” of dogs.[86] They argued it is not clear whether this evidence should be taken to suggest that the claims are directed to a population of dogs. This has implications for whether the claims comply with section 40.
[86] Boswood 1 at [373], [377], [381], Schummer 1 at [165], [168], [169], [171].
65. I do not share the concerns of the opponent in this regard. The invention, and the act which ultimately would constitute an infringement of a granted claim, is the administration of pimobendan to an individual patient. The evidence of Dr Schummer and Professor Boswood referred to by the opponent related to comments made by Dr Ettinger concerning the extent to which the results of the EPIC Trial could be extrapolated to the treatment of an individual dog. It would seem to me that the purpose of carrying out any clinical trial is to determine whether or not a drug provides an appreciable benefit to an individual patient. This is consistent with the evidence of Professor Boswood, who stated that:
“At paragraphs 423-427 of the Ettinger Declaration, the effect of the methods claimed in the Patent Application is being questioned in relation to an individual patient. To explain, while a change in an individual measurement is actually quite difficult to attribute to the administration of a drug, a clinical trial provides the opportunity to determine a distinct and detectable change attributable to the drug by comparing the change in the two studied groups on average. In this way, a change due to administration of the drug, such as a reduction in heart size, can be described in a population. Obtaining an average effect allows one to predict the extent to which any dog in the population is likely to benefit from the studied drug” [original emphasis].[87]
[87] Boswood 1 at [371].
66. In short, I take the claims to define a method of treating an individual patient (or in the case of the claims as proposed to be amended and the claims of the Innovation Patent, an individual dog). To the extent that the defined features are based on a population of dogs rather than an individual dog, I am satisfied that the results of a clinical trial would be understood by a skilled person as providing a basis for extrapolation to individual patients within a patient population. A similar construction applies to the claims of the Innovation Patent.
Asymptomatic (occult, preclinical) myxomatous mitral valve disease
67. There was no apparent dispute between the parties as to the meaning of this term, though the parties differed on whether the patients in specific case studies would be considered asymptomatic. In short, the term refers to a specific stage of a specific cardiovascular disease, namely MMVD prior to the development of clinical signs caused by heart failure.[88]
[88] OS at [151].
Already pathologically enlarged heart and ACVIM Class B2/ISACHC Class IB
68. The opponent provided separate submissions on these two features, but I consider they relate to the same issue of construction. The gist of the opponent’s submissions, which the applicant did not dispute, is that the claims are directed to a method for treating a patient with MMVD that falls within ACVIM Stage B2 and ISAHC Class IB. As Claim 1 of the standard application does not explicitly define the invention using these classifications, I consider it worth some explanation.
69. Both Dr Ettinger and Professor Boswood understood the claims to be limited to a method for treating a patient (or dog) that, at baseline, exhibits pathological enlargement of the heart.[89] Their statements were said to accord with the disclosure in the specification that:
“… pimobendan treatment effects a reduction of the heart size of the already pathologically enlarged heart of the patient. In other words, such patient suffers from asymptomatic (occult, preclinical) heart failure due to mitral valve disease (MVD) of ISACHC Class I (Class IA and/or Class IB), NYHA Class I and ACVIM stage B2 and already has pathologically enlarged heart (e.g. visible by means of echocardiography), but does not yet show any clinical symptoms of heart failure, preferably congestive heart failure”.[90]
[89] OS at [166], referencing Ettinger 1 at [415]-[419], Ettinger 2 at [200], Boswood 1 at [225], [237].
[90] Specification at page 7, lines 21 to 27.
70. Thus Claim 1 of the standard application is directed to a method for treating a patient with MMVD that satisfies two criteria: first, a pathologically enlarged heart;[91] second, the absence of clinical signs caused by heart failure. The opponent submitted that these criteria necessarily limit the scope of the claims to a patient group having MMVD corresponding to ACVIM Stage B2 and ISAHC Class IB.[92] The applicant appears to agree with this conclusion.[93] The opponent went on to say that, pursuant to this construction, the features defined in Claim 2 of the standard application do not add anything of substance over Claim 1.[94] I note this does not apply to Claim 1 of the Innovation Patent as it includes the specific classifications.
[91] The parties did not provide an explicit definition for the term “pathologically enlarged heart”, but I understand it to mean that enlargement is due to the heart disease (MMVD), in contrast to a physiological enlargement due to other causes such as high blood pressure.
[92] OS at [170].
[93] AS at [15].
[94] OS at [173].
71. On balance, I am satisfied that the definition of an already pathologically enlarged heart includes dogs which would fall within ACVIM Stage B2 and ISAHC Class IB. However, I note that the 2009 ACVIM consensus statement defined stage B2 as consisting of asymptomatic patients having hemodynamically significant valve regurgitation as evidenced by radiographic or echocardiographic findings of left-sided heart enlargement.[95] The consensus goes on to define hemodynamically significant mitral regurgitation as clearly enlarged LA, LV or both. Stage B1 is characterised by hemodynamically insignificant mitral regurgitation, in which these measures are normal or equivocal. While no direct evidence on this point was provided by the experts, the terms “pathologically enlarged heart” as used in the claims and “hemodynamically significant valve regurgitation” as used in the classification appear to be different, though substantially overlapping, in meaning. That is, it appears that a heart may be enlarged as a result of MMVD, but not yet hemodynamically “significant” enough to be considered as falling within stage B2. I therefore do not consider, to the extent that it matters in the present determination, that the scope of Claims 1 and 2 of the standard application are identical. However, even if this is not the case, “where the plain meaning of a claim has the effect that one or more dependent claims are redundant, then the consequence of redundancy would not drive the construction of the claim itself.”[96]
[95] Exhibit SJE-3.
[96] Sandoz AG v Bayer Intellectual Property GmbH [2023] FCA 1321 at [153]
72. As an aside I note that the 2019 Updated ACVIM Guidelines[97] define Stage B2 as referring to asymptomatic dogs that have more advanced mitral valve regurgitation that is hemodynamically severe and long-standing enough to have caused radiographic and echocardiographic findings of left atrial and ventricular enlargement that meet clinical trial criteria used to identify dogs that clearly should benefit from initiating pharmacologic treatment to delay the onset of heart failure. The specific criteria are a murmur intensity of ≥3/6, LA:Ao ratio of ≥1.6, LVIDDN ≥1.7 and VHS >10.5.[98] Ideally all criteria should be met because treatment is a lifelong commitment. This appears to indicate that the criteria for Stage B2 under the 2019 Guidelines are more refined than the 2009 Guidelines and, in effect, relate to a more specific patient group within the previous definition. This potentially impacts on the interpretation of claims using the ACVIM classification to characterize the invention, but I am satisfied that references in the specification and claims can be taken to refer to the ACVIM classification as it applied under the 2009 Guidelines, which is specifically set out in the description.
[97] Exhibit AB-14.
[98] These appear to also be the criteria used for the selection of dogs for the EPIC trial. See Exhibit SJE-12 at page 1777, “Generalizability of the Study”.
Steps of the claimed method versus outcomes
73. One of the key issues in the opposition related to the “claim outcomes” (that is, the clinical outcomes provided by the method of treatment). In short, my understanding of the opponent’s submissions is that the defined clinical outcomes should not be considered to be “standalone” features of the claim, but rather as the effects obtained by the administration of pimobendan regardless of the purpose for which the drug is being administered. This interpretation has consequences for the determination of novelty, inventive step and innovative step since any prior art administration of pimobendan to dogs in stage B2 would anticipate the claims.
74. The opponent drew my attention to the approach taken in Otsuka v Generic Health by Yates J,[99] which was upheld by the Full Court on appeal.[100] The claims at issue in that case were directed to the use of the anti-psychotic drug aripiprazole in the treatment of “disorders of the central nervous system associated with the 5-HT1A receptor subtype” selected from cognitive impairment caused by treatment-resistant, inveterate, or chronic schizophrenia which fails to respond to other antipsychotic drugs. The consideration of the court related to whether the association of the particular conditions with the 5-HT1A receptor subtype was a separate essential feature that a prior art document must disclose in order for it to constitute an anticipation. This impacted on the consideration of novelty and inventive step. Yates J stated that:
“I do not accept that the words ‘disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …’ define a free-standing essential feature of the invention that adds, meaningfully, to the identification of the specific forms of cognitive impairment already referred to. The specification does not suggest, for example, that the identified forms of cognitive impairment can be further divided into disorders of the central nervous system that are associated with the 5-HT1A receptor, and those that are not. The claims treat the nominated forms of cognitive impairment as disorders that are associated with the 5-HT1A receptor. It follows that, for the purposes of the claims, and importantly for the question of infringement, use of the compound to produce a medicament for (claim 1), or use of the compound as a method of treating (claim 7), one of those forms of cognitive impairment is use of the medicament or the method to treat a disorder of the central nervous system that is associated with the 5-HT1A receptor” [opponent’s emphasis].[101]
[99] Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) (2015) 13 IPR 191, [2015] FCA 634.
[100] Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 2) [2016] FCAFC 111.
[101] Otsuka v Generic Health (FCA) at IPR 216, [146].
75. Consistent with the approach taken by Yates J, the opponent submitted that the method defined by Claim 1 comprises a single step of administering an effective amount of a pharmaceutical composition comprising pimobendan to a patient with asymptomatic (occult, preclinical) MMVD that has an already pathologically enlarged heart. The claim identifies no other action or step to be performed or any other limitation on the characteristics of the patient to be treated. They argued that the balance of the integers of Claim 1 are directed to outcomes, in the sense of effects or results (namely the reduction of the heart size in combination with delaying the onset of clinical symptoms of heart failure) rather than the purpose for which pimobendan is administered. The fact that the specification teaches that the single step defined by the claim achieves the claim outcomes means that, were the claim to be granted, it would be infringed, and conversely, anticipated, by the administration of an effective amount of pimobendan to a patient with an already enlarged heart who has not reached the onset of clinical signs of heart failure.[102] I understand this argument to be in line with the opponent’s submissions on novelty, to the extent that treatment with pimobendan of any dog in Stage B2 of MMVD, regardless of the purpose for which pimobendan has been administered, would anticipate the present claims.
[102] OS at [183].
76. On the other hand, the applicant disputed that the claim in Otsuka v Generic Health is analogous to the present claims, and instead drew analogies with the claims in Apotex v Sanofi-Aventis,[103] which was appealed to the High Court but not on the ground of novelty.[104] The claim in that case was directed to a “method of preventing or treating a skin disorder, wherein the skin disorder is psoriasis, which comprises administering to a recipient an effective amount of pharmaceutical composition” containing leflunomide. Relevantly the Court found that:
“The claim in the patent is not for the use of leflunomide in a manner that treats or prevents psoriasis. The claim is not for the discovery of whatever happens in the human body after the drug is administered. Rather, the claim is for a method of preventing or treating psoriasis. The claim is for a method of treatment of a human ailment. That method necessarily presupposes a deliberate exercise of diagnosis and prescription by a medical practitioner. The treatment or prevention of psoriasis by the use of the claimed method presupposes a diagnosis of psoriasis and the consequent prescription of the application of leflunomide. That this is so is hardly controversial: as is apparent from all the potential constructions of the patent advanced by the parties, the claim in the patent involves the application of leflunomide by a medical practitioner.”[105]
[103] Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (No 2) [2012] FCAFC 102.
[104] Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50; 253 CLR 284; 88 ALJR 261; 304 ALR 1; 103 IPR 217.
[105] Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (No 2) [2012] FCAFC 102 at [37].
77. The applicant submitted that the claim outcomes cannot be read out of the claim as the opponent seeks to do. Contrary to the opponent’s submissions, pimobendan can be administered for multiple purposes, some of which would infringe the claim and some of which would not. It is too simplistic to say that administration of pimobendan to a dog with stage B2 MMVD for any purpose would infringe the claim.[106]
[106] AS at [17].
78. On balance I prefer the interpretation suggested by the applicant. As an initial point, I do not consider that Otsuka v Generic Health necessarily supports the opponent’s case. Based on the facts of the case before him, Yates J determined that the separate features (the association with 5-HT1A and the cognitive impairment) were so intrinsically linked as to constitute the “same” feature:
“Further, and importantly, the reference in the claims to the association between the disorders and the 5-HT1A receptor is immediately followed by, and qualified by, the words “which disorder is selected from …”. The claims then list specific disorders, namely certain nominated forms of cognitive impairment. The focus of each claim then becomes the treatment of these forms of cognitive impairment. It does not matter, therefore, that different medical or scientific views might be held about the involvement of the 5-HT1A receptor in the identified forms of cognitive impairment or their treatment. The claims take those forms of cognitive impairment as being “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype”.
In this way, it can be seen that, as used in the claims, the words “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …” are but part of the description of an essential feature—the disorders to be treated. The other part of the description is the identification of the forms of cognitive impairment to be treated. Both parts of the description—defining the one essential feature—must be read together, not treated as separate integers.”[107]
[107] Otsuka v Generic Health (FCA) at [144] to [145].
79. The present claims are not linked to a specific receptor but are clinical outcomes of the treatment of a particular patient population. My understanding of the evidence is that different compensatory mechanisms are initiated at different stages, and the treatments used at each stage are aimed at the clinical conditions resulting from those mechanisms. There is nothing in the specification or common general knowledge that would lead to the conclusion that treatment of MMVD (at any stage of development) would necessarily result in a single outcome to the extent that the claimed outcomes would not be considered as “separate, or free-standing” essential features.
80. The opponent’s submissions linking the construction to infringement and anticipation seems to be more in line with a consideration of whether the purported prior art use of pimobendan inherently provides the defined outcomes. That is also indicated by their submissions that the claim outcomes are merely information about effects of, or mechanisms of, prior art treatments of MMVD, or, alternatively, an instance of parameteritis.[108] But even if the prior art does teach the use of pimobendan in a patient group in Stage B2 of MMVD, I do not consider that this would necessarily lead me to approach the interpretation of the claims in a different way. Having construed the claims in light of the common general knowledge, that construction is used in the subsequent determinations. The consideration of whether the claims suffer parameteritis or the prior art inherently discloses certain features of the invention is part of that subsequent determination. To constrain the interpretation of the claims with considerations of infringement and anticipation would, in my opinion, risk inappropriately expanding the interpretation of the claims beyond the use of the common general knowledge to include public knowledge. Moreover, it is well established that issues of construction are approached without regard to the alleged infringement. As noted by Heerey J in Welcome Real-Time SA v Catuity Inc.,
“All that needs be added is the perhaps trite observation that the alleged infringement is to be ignored when construing the patent. Although the forensic contest will throw up the particular construction issues to be resolved, a patent must, as the saying goes, be construed as if the infringer had never been born.”[109]
[108] OS at [13].
[109] [2001] FCA 445; (2001) 51 IPR 327 at [21].
81. In short, I consider the clinical outcomes to be essential features of the present claims. The opponent made similar submissions in relation to the dependent claims and a similar conclusion applies to those. It also follows that the same construction applies to the claims of the Innovation Patent.
Concomitant administration of other APIs
82. The opponent noted that the claims prior to incorporation of the amendments to both ‘601 and ‘685 dated 14 October 2021 included dependent claims that were directed to a method in which pimobendan is administered concomitantly with one or more additional active pharmaceutical ingredients, including an ACE inhibitor and/or a diuretic. While these claims were deleted in the amendments, the opponent submitted, and the applicant did not dispute, that the inclusive language used in Claim 1 (and particularly the step of “administering to the patient an effective amount of a pharmaceutical composition comprising pimobendan) does not exclude the use of additional pharmaceutical agents in the method of treatment. I agree with this interpretation of the claims.
An effective amount.
83. The opponent submitted that the reference in claim 1 of the standard application to “an effective amount”, adds nothing to the scope of the claim.[110] They referred to the definition in the specification:[111]
“The term ‘effective amount’ as used herein means an amount sufficient to achieve a reduction of the heart size in patients with asymptomatic (occult, preclinical) heart failure (HF) due to mitral valve disease (MVD) and/or to achieve the delay of onset of clinical symptoms in patients with asymptomatic (occult, preclinical) HF due to MVD …”
[110] OS at [184].
[111] Specification at page 7, lines 8-12.
84. They argued that the reference to an effective amount is circular since the composition is administered in an effective amount so as to effect the claim outcomes, wherein an effective amount means the amount that will achieve those outcomes. Even if this might be considered circular, I do not see it as a significant issue that impacts on the scope of the claim. In this regard, I prefer the interpretation of the applicant, who submitted that the words “an effective amount” simply reinforces that the purpose of the method of treatment is to achieve the claim outcomes.[112]
[112] AS at [18].
Conclusion on construction
85. One of the key issues of dispute in the opposition was whether the clinical outcomes of reduction of the heart size of an already pathologically enlarged heart in combination with delaying the onset of clinical symptoms of heart failure in the patient represented “standalone” features of the claims. I have interpreted these to be essential (standalone) features of the claim. It follows that claims define methods of treatment comprising the administration of pimobendan to individuals in a particular patient group (that is, suffering asymptomatic (occult, preclinical) MMVD and having a pathologically enlarged heart with no clinical signs of heart failure) in order to achieve the defined clinical outcomes.
86. This is the construction that I will apply in the following determinations.
Novelty
General principles
87. An invention is taken to be novel when compared with the prior art base unless it is not novel in light of certain types of prior art information, each of which must be considered separately.[113] For the purposes of the present consideration, the following kinds of information are relevant:
Prior art information made publicly available in a single document or through doing a single act;
Prior art information made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art would treat them as a single source of that information.
[113] Subsection 7(1) of the Patents Act.
88. It is well-established that the general test for anticipation is the reverse infringement test as articulated by Aickin J in Meyers Taylor v Vicarr Industries:
“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement.”[114]
[114] Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; 137 CLR 228 at [235].
89. Thus, the test is satisfied if the alleged anticipation discloses all of the essential features of the invention as claimed. Furthermore, as stated by the Full Court in AstraZeneca v Apotex:
“… for a prior art document to be anticipatory, there must be … a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent.”
90. A classic formulation of this principle was given in General Tire v Firestone, which stated that the prior art “must contain clear and unmistakable directions to do what the patentee claims to have invented… a signpost, however clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.”[115]
On balance I do not consider this issue results in a lack of clarity in the claim. In my opinion, the claim can be given a sensible meaning. In particular, the preamble of the claim defines that “the daily pimobendan dose is administered as two doses”. While the body of the claim suggests that “two doses” are administered every 12 hours, it would seem to me that that administration in this manner would not be regarded as “two doses” but as a single dose. Under the circumstances, and in the context of the claim as a whole, I consider that the person skilled in the art would understand the claim to define the use of a divided dose providing the total daily amount defined in the preamble.
In summary, I do not consider the claims lack clarity under section 40(3).
Lack of utility
Section 18(1)(c) of the Act requires that the claimed invention be useful. A summary of relevant principles was provided by the Full Court of the Federal Court in Artcraft Urban Group v Streetworx:
“It is ‘no objection’ to the validity of an innovation patent granted under the Act that it is ‘commercially impracticable’. The utility of the patent depends upon whether, by following the teaching of the specification, the result claimed is produced.
The ‘basic principle’ of inutility is that if an invention ‘does what it is intended by the patentee to do, and the end attained is itself useful, the invention is a useful invention’ … What the invention is intended to do is a matter to be gathered from the ‘title and the whole of the specification.
Put another way, the two questions are: first, what is the promise of the invention derived from the whole of the specification?; second, by following the teaching of the specification, does the invention, as claimed in the patent, attain the result promised for it by the patentee? … Further, ‘everything’ that is within the scope of a claim must be useful, that is, attain the result promised for the invention by the patentee.”[204] [citations omitted]
[204] Artcraft Urban Group Pty Ltd v Streetworx Pty Ltd [2016] FCAFC 29 at [118]-[121].
Section 7A also requires that an invention is taken to not be useful unless a specific, substantial and credible use for the invention (so far as claimed) is disclosed in the complete specification. The Explanatory Memorandum to the Raising the Bar Act explained that:
“specific” means a use specific to the subject matter claimed so as to “provide a well-defined and particular benefit to the public”;
“substantial” means the claimed invention does not require further research to identify or reasonably confirm a “real world use”; “an application must show that an invention is useful to the public as disclosed in its current form, not that it prove useful at some future date after further research”;
an asserted use will be “credible” “unless there is evidence that the invention is inoperative (i.e., does not operate to produce the results claimed by the patent application) or there is reason to doubt the objective truth of the statements in the specification.[205]
[205] Explanatory Memorandum, Intellectual Property Laws Amendment (Raising the Bar) Bill 2011 (Cth), pages 44-45.
The opponent submitted that:
(a)The promise of the specification to reduce the risk of reaching heart failure is not attained.
(b)The treatment of the claimed outcomes will not be achieved in (“a non-trivial proportion of”) species other than dogs. There is no credible evidence of any beneficial effect of treatment of pimobendan of these species.
(c)One or more of the claim outcomes are incapable of being ascertained in an individual patient.
(d)The claim outcomes will not be achieved in a non-trivial proportion of patients.
(e)The claims define outcomes for which no comparator is identified.
I have dealt with last four of these submissions previously under the grounds of sufficiency, support and/or clarity. I do not see that a different consideration or outcome applies under this ground. The invention described in the specification clearly provides a specific, substantial and credible use for the invention inasmuch as the treatment provides the clinical outcomes defined in Claim 1. The opponent’s assertions are contrary to the accepted purpose of clinical trials and contemporaneous evidence that the EPIC Trial has led to changes in the way that the broader veterinary community approaches. No evidence has been adduced by the opponent that would establish that the invention does not produce the results claimed by the patent specification.
I consider a similar conclusion applies to the first argument raised by the opponent. The gist of the opponent’s arguments appears to be that dogs treated with pimobendan will still develop heart failure. To this end Dr Ettinger stated that:
“As I explained in paragraphs 359 to 362 of my First Declaration, the EPIC 2016 Publication (incorporated into the Specification by reference) makes clear that, although pimobendan treatment was associated with an increase in the median time to the onset of clinical signs of heart failure in the group of dogs treated with pimobendan, the proportion of dogs that ultimately developed heart failure was not significantly different between the pimobendan group and the placebo group in the EPIC trial. On that basis, the Specification provides no evidence that pimobendan treatment ‘reduces the risk of reaching heart failure’. On the contrary, the EPIC 2016 Publication (incorporated by reference into the Specification) demonstrates that pimobendan does not alter the risk of MMVD Stage B2 dogs reaching heart failure (although it does prolong the time taken to do so)”.[206]
[206] Ettinger 2 at [230].
My understanding of Dr Ettinger’s evidence on this point is that pimobendan does not reduce the risk of developing heart failure – as a degenerative disease, an animal suffering MMVD will inevitably progress to heart failure, unless of course it dies of another cause first. In effect only a curative treatment would provide a different risk ratio between the treatment and placebo groups. This appears to be a different approach from that of Dr Schummer, who stated that:
“[T]he results presented in the Opposed patent application and the 2016 EPIC paper (Exhibit CS-5) showed an absolute risk reduction. See for example, page 9 of the 2016 EPIC paper under the heading Discussion, where it is stated:
“The EPIC study has shown, for the first time, convincing evidence of benefit of a treatment before the onset of CHF in dogs with cardiac enlargement secondary to MMVD (stage B2). Dogs receiving pimobendan had approximately two-thirds the risk of reaching the primary endpoint compared with dogs on placebo. This resulted in a 60% prolongation of the preclinical period with dogs receiving pimobendan taking, on average, an additional 462 days, or approximately 15 months, to develop CHF or die as a consequence of MMVD.” [emphasis added]
The data is presented in the EPIC paper as a hazard analysis, as shown in Table 5 of the paper. The hazard ratio of the pimobendan group compared to the placebo group to reach congestive heart failure is 0.58 (0.42-0.82). This means that the risk of developing congestive heart failure was 0.58 in the pimobendan group compared to the placebo group at any time point. As further stated in the EPIC paper, dogs receiving pimobendan had approximately two-thirds the risk of reaching the primary end-point compared with dogs on placebo.”[207]
[207] Schummer 1 at [126] to [127].
Professor Boswood further explained that the results of the EPIC study were expressed as hazard ratios and went on to explain:
“Proportional hazards analysis is a standard statistical method applied to ‘time to event’ studies such as the EPIC study. In this analysis, a period of time is defined over which the risk is measured, and the risk is quantified as at a given point in time. It appears from the comments of the Ettinger Declaration[208] that Dr Ettinger has misinterpreted the concept of a hazard ratio …
…
However, risk reduction and prolongation of the time to the onset of clinical signs are interrelated, and the only way to prolong the time is by reducing the risk. Thus, the evidence is actually provided in the 2016 EPIC publication… as the calculated hazard ratios, hazard and risk being essentially the same thing. For example, the paper describes hazard ratios of 0.5-0.6 in the multivariable analysis, which is the same as saying that the risk is reduced by about one third to a half.”[209]
[208] This is a reference to comments in Ettinger 1, but Dr Ettinger reiterated those views in his subsequent declaration.
[209] Boswood 1 at [346] to [348].
Professor Boswood also used a simple analogy to help explain the concept:
“Take two groups of 100 people, wherein in the first group people die at the rate of one per day, and in the second group people die at the rate of two per day. After 150 days, all the people in both groups will be dead. However, people in the second group were dying at twice the rate of the first group, and therefore the risk of death was higher in the second group, even though all the people ultimately reached the same endpoint (death). There was clearly a difference in risk between the two groups over time. Clearly, even though the number of patients who succumb to an endpoint in both groups is the same, the risk of death per unit time is not equal between the two groups.”[210]
[210] Boswood 1 at [351].
On balance I am not satisfied that the specification has failed to meet the promise in relation to providing a risk reduction of reaching congestive heart failure. The evidence suggests that there may be some dispute as to the terminology used, but I am satisfied that the specification shows a reduction in the point in time risk of reaching heart failure.
In summary, the opposition is unsuccessful on the ground of utility.
Manner of manufacture
Section 18(1)(a) requires that an invention be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. This requires asking “is this a proper subject of letters patent according to the principles which have been developed for the application of section 6 of the Statute of Monopolies”.[211]
[211] National Research Development Corporation (NRDC) v Commissioner of Patents (1959) 102 CLR 252 at 269.
While the claimed invention is characterised “by reference to the terms of the specification having regard to the substance of the claim and in light of the common general knowledge”,[212] the determination is made on the face of the specification. As stated by the High Court in NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd:
“if it is apparent on the face of the specification, when properly construed, that the quality of inventiveness necessary for there to be a proper subject of letters patent under the Statute of Monopolies is absent, one need go no further.”[213]
[212] Aristocrat Technologies Australia Pty Ltd v Commissioner of Patents [2022] HCA 29 at [73].
[213] [1995] HCA 15, (1995) 183 CLR 655 at [9].
In Microcell, the High Court stated that a claim for nothing more than the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable did not constitute a manner of manufacture.[214] The High Court in Apotex v Sanofi determined that a method claim for the administration of a known pharmaceutical for a hitherto unknown therapeutic use can be a patentable invention.[215] However, the opponent noted that a distinction was drawn between a method of medical treatment which involves a hitherto unknown therapeutic use, and the activities or procedures of doctors (and other medical staff) when physically treating patients.[216]
[214] Commissioner of Patents v Microcell Ltd [1959] HCA 71 at [15].
[215] Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (2013) 253 CLR 284; [2013] HCA 50 at CLR 354 [177].
[216] Ibid at CLR 384 [287].
The opponent submitted that the following matters are acknowledged on the face of the specification, and before the priority date:
Pimobendan was a known pharmaceutically active compound;
Pimobendan was well-known for the treatment of MMVD, including in dogs;
Several publications had disclosed the use of pimobendan in the treatment of dogs with MMVD that had progressed to the stage of exhibiting clinical signs of heart failure.
The use of PDE-III inhibitors such as pimobendan for the treatment of “asymptomatic (also known as occult or preclinical) heart failure” was known.
The EPIC Trial was being conducted to investigate “the effects of pimobendan in the delay of onset of clinical symptoms of congestive heart failure due to” MMVD;
Determining an appropriate dose of pimobendan required to prevent, counter, delay or arrest the progress of MMVD was within the skill of the relevant art.
The opponent forwarded several alternative positions in relation to whether the methods of treatment defined by the present claims are a manner of manufacture:
The specification discloses that the alleged invention is not a method of treatment involving an unknown therapeutic use of a pharmaceutical with prior therapeutic uses, but rather the validation in a large-scale clinical trial of the use of pimobendan for MMVD, carried out on ACVIM Stage B2 dogs, a population for which there was (as alleged on the face of the specification) previously no clinical trial data available. There is no new product, composition, method, or use, and therefore the threshold requirement of invention has not been met.
Alternatively, the claims are to no more than the exploitation of a known property of the known drug pimobendan in an allegedly new class of MMVD patients. The specification discloses that the EPIC Trial itself was known, but that the results of the trial were not publicly known as at the priority date. The alleged invention is “new results”.
Each claim is in substance a claim to the activities or procedures of doctors and veterinarians (and other medical staff) when treating patients, which is outside of the concept of manner of manufacture.
On balance I do not find the opponent’s submissions persuasive. As an initial point, most of the matters acknowledged in the specification relate to the treatment of heart failure secondary to MMVD, or to the treatment of preclinical dilated cardiomyopathy (DCM) where heart enlargement does not involve the mitral valve. None of these relate to the treatment of dogs in MMVD Stage B2, and, more specifically, the treatment to achieve the combination of clinical outcomes defined in the present claims. In this regard, the present invention does not relate to the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable. The present claims relate to treatment at a particular stage in the progress, which involves different compensatory actions in the body. This is not merely information about an existing treatment.
To the extent that the claims relate to a method of treatment, the opponent sought to characterise the present invention as impermissibly constraining the activities or procedures of medical staff when treating patients. The present claims certainly require the actions of a practitioner to diagnose a patient and to prescribe pimobendan. However, that is an activity required of most therapeutic methods, including some that the High Court has considered patentable. The key distinction lies with whether the claims are directed to a therapeutic use or whether they are directed at the actions of medical practitioners when physically treating a patient. In my opinion the present claims relate to the former.
In summary, I consider the invention is a manner of manufacture.
Conclusion
The opposition is successful on the standard application (AU 2017245601). The claims lack inventive step in view of the information provided in the EPIC Press Release. However, the other grounds of opposition are unsuccessful (novelty, support, clarity, sufficiency and manner of manufacture).
The standard application may contain patentable subject matter. I give the applicant 2 (two) months from the date of this decision to propose amendments to overcome the issues identified above.
I note that the amendments proposed on 11 July 2023 have yet to be advertised for opposition purposes. Given that further amendments to overcome the present determination would supersede the current proposed amendments, I do not consider there is any value in processing the current amendments separately from any further amendments filed by the applicant. If the present decision is appealed, then the Commissioner will refuse the proposed amendments pursuant to section 112A(a) of the Act.
The opposition is unsuccessful on the Innovation Patent (AU 2020102685). The opposition to this patent is concluded.
Costs
Costs generally follow the event.
The opposition has been successful for one of the cases and not for the other. I therefore consider it appropriate that each party bears its own costs in the matters.
Dr Leslie. F. McCaffery
Delegate of the Commissioner of Patents
Attachment A: Claims of the Standard Application (as accepted)
A method for treating a patient with asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD), the method comprising administering to the patient an effective amount of a pharmaceutical composition comprising pimobendan so as to effect a reduction of the heart size of an already pathologically enlarged heart of the patient in combination with delaying the onset of clinical symptoms of heart failure in the patient.
The method of claim 1, wherein the asymptomatic (occult, preclinical) myxomatous mitral valve disease (MMVD) is of a stage selected from the group consisting of: stage ISACHC Class IB and ACVIM stage B2.
The method of claim 1, wherein the administration of pimobendan results in a reduction of the heart size of the already pathologically enlarged heart of the patient of up to about 5%, as compared to a baseline prior to pimobendan treatment.
The method of claim 1, wherein the administration of pimobendan results in one or more of the following in the patient selected from the group consisting of: increases the survival time of the treated patient as compared to placebo treatment, improves the quality of life of the treated patient, improves cardiac function/output in the treated patient, reduces sudden cardiac death/euthanasia of the patient due to cardiac reasons, and reduces the risk of reaching heart failure.
The method claim 1, wherein the patient is a mammal selected from the group consisting of: a human, a dog, and a horse.
The method of claim 1, wherein pimobendan is administered in a daily dose of 0.2 mg/kg to 0.6 mg/kg bodyweight.
The method of claim 6, wherein the daily pimobendan dose is administered as two doses of 0.1 mg/kg to 0.3 mg/kg bodyweight, wherein two doses of 0.1 mg/kg to 0.3 mg/kg bodyweight are administered every 12 hours, or two doses of 0.25 mg/kg bodyweight are administered every 12 hours.
The method of claim 1, wherein pimobendan is administered orally or parenterally.
The method of claim 1, wherein pimobendan is administered orally in the form of a tablet or a capsule.
10.The method of claim 1, wherein the administration of pimobendan effects a prolongation of the time of survival of the patient as compared to placebo treatment or non-pimobendan treatment, of at least about 5 months.
11.The method of claim 1, wherein the administration of pimobendan effects a prolongation of the time of survival of the patient as compared to placebo treatment or non-pimobendan treatment, of at least about 7 months.
12.The method of claim 1, wherein the delaying the onset of clinical symptoms of heart failure in the patient or the reduction in heart size of the patient in combination with delaying the onset of clinical symptoms of heart failure in the patient is for a period of at least about 12 months.
13.The method of claim 1, wherein the administration of pimobendan further effects a prolongation of the time of survival of the patient, as compared to placebo treatment or non-pimobendan treatment, of at least about 30 days.
Attachment B: Claims of the Innovation Patent
A method for treating a dog suffering from asymptomatic (occult, preclinical) heart failure due to mitral valve disease (MVD) or myxomatous mitral valve disease (MMVD), the method comprising administering to the dog an effective amount of a pharmaceutical composition comprising pimobendan so as to effect a reduction of the heart size of an already pathologically enlarged heart of the dog in combination with delaying the onset of clinical symptoms of heart failure in the dog; wherein one or both of the asymptomatic (occult, preclinical) heart failure due to mitral valve disease (MVD) and asymptomatic (occult, preclinical) heart failure due to myxomatous mitral valve disease (MMVD) is/are of a stage ISACHC Class IB or ACVIM stage B2.
The method of claim 1, wherein pimobendan is administered orally in the form of a tablet or a capsule; and wherein pimobendan is administered in a daily dose of 0.2 mg/kg to 0.6 mg/kg bodyweight; and wherein the daily pimobendan dose is administered as two doses of 0.1 mg/kg to 0.3 mg/kg bodyweight, wherein two doses of 0.1 mg/kg to 0.3 mg/kg bodyweight are administered every 12 hours, or two doses of 0.25 mg/kg bodyweight are administered every 12 hours.
The method of claim 1 or claim 2, wherein the administration of pimobendan results in a reduction of the heart size of the already pathologically enlarged heart of the dog of at least 5%, at least 20%, or at least 30%, as compared to a baseline prior to pimobendan treatment.
The method of any one of the preceding claims, wherein the administration of pimobendan results in one or more of the following in the dog selected from the group consisting of: effects a prolongation of the preclinical phase without exhibiting clinical symptoms of heart failure, effects a delay of onset of (clinical symptoms of) heart failure, increases the survival time of the treated dog as compared to placebo treatment, improves the quality of life of the treated dog, a reduction of heart size of the treated dog as compared to baseline (before start of treatment), improves cardiac function/output in the treated dog, reduces sudden cardiac death/euthanasia of the dog due to cardiac reasons, and reduces the risk of reaching heart failure.
The method of any one of the preceding claims, wherein pimobendan is administered concomitantly with benazepril and/or furosemide.
Attachment C
The ACVIM Classification System[217]
[217] Boswood 1 at [62] and SJE-3.
| Stage | Definition | |
| A (‘At risk’) | In stage A dogs are considered predisposed to the disease but do not yet have it. | |
| B (‘Asymptomatic’) | This is the ‘asymptomatic’ (preclinical) stage of MMVD. In stage B dogs have evidence of valvular disease (e.g., the murmur is present) but have not developed signs of heart failure. The stage is subcategorised into B1 and B2. | Stage B1: No radiographic or echocardiographic evidence of cardiac remodelling in response to MMVD |
| Stage B2: Hemodynamically significant valve regurgitation, as evidenced by radiographic or echocardiographic findings of left-sided cardiac enlargement | ||
| C (‘Clinical signs of heart failure’) | In stage C dogs are showing, or have previously shown, clinical signs of heart failure. | |
| D (‘Refractory’) | In stage D dogs have clinical signs of heart failure that are refractory to standard therapies. | |
The ISACHC classification system[218]
[218] Specification at page 1, line 20.
| Class I | Asymptomatic (also known as occult or preclinical) | Class IA: no evidence of compensation for underlying heart disease (no volume overload or pressure overload detected radiographically or echocardiographically) |
| Class IB: clinical signs of compensation for underlying heart disease (volume overload or pressure overload detected radiographically or echocardiographically) | ||
| Class II | Mild to moderate heart failure with clinical signs at rest or with mild exercise (treatment required) | |
| Class III | Advanced heart failure; clinical signs of severe congestive heart failure | Class IIIA: home treatment possible |
| Class IIIB: requires hospitalization | ||
The NYHA classification system[219]
[219] Specification at page 1, line 32.
| Class I | describes patients with asymptomatic heart disease (e.g., chronic valvular heart disease (CVHD) is present, but no clinical signs are evident even with exercise). |
| Class II | describes patients with heart disease that causes clinical signs only during strenuous exercise. |
| Class III | describes patients with heart disease that causes clinical signs with routine daily activities or mild exercise. |
| Class IV | describes patients with heart disease that causes severe clinical signs even at rest. |
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