Merck Sharp & Dohme Corp. v. Wyeth LLC

Merck Sharp & Dohme Corp. v. Wyeth LLC
Court (s) Database
Federal Court Decisions
Date
2021-04-30
Neutral citation
2021 FC 317
File numbers
T-1184-17
Decision Content
Date: 20210430
Docket: T-1184-17
Citation: 2021 FC 317
Ottawa, Ontario, April 30, 2021
PRESENT: The Associate Chief Justice Gagné
BETWEEN:
MERCK SHARP & DOHME CORP. and MERCK CANADA INC.
Plaintiffs
and
WYETH LLC
Defendant
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons issued April 14, 2021)
TABLE OF CONTENTS
I. Overview 3
II. The Composition Patent 4
A. The Story of the Composition Patent 4
B. The Issues for the 363 Patent 8
C. The 363 Patent Experts 8
(1) Merck’s Experts 9
(2) Wyeth’s Experts 10
D. The Person of Skill in the Art [PSA] 12
E. Claims Construction – Legal Principles 12
F. Claims Construction – Are The Impugned Claims Limited to 13 serotypes 13
G. Claims Construction – meaning of “Immunogenic” 19
H. Validity of the 363 Patent 23
(1) Novelty/Anticipation 23
(2) Claim 1 of the 363 Patent vs Peña 2004 24
(a) Disclosure 24
(b) Enablement 29
(3) Obviousness of the 363 Patent 33
(4) Obviousness of the Composition Claims 34
(a) Inventive Concept of the Composition Claims (Claims 1 to 6, 17 to 19, and 22 to 30) 34
(b) The Common General Knowledge 35
(c) Bridging the Gap 41
(d) Obvious to Try to Make a 13 Serotype Conjugate to CRM197 42
(5) Obviousness of the Method/Process Claims 47
I. Overbreadth/Inutility 48
III. The Formulation Patents 48
A. The Issues for the Formulation Patents 49
B. The Formulation Patents’ Witnesses 49
(1) The Story of the Formulation Patents 49
(2) Merck’s Expert 51
(3) Wyeth’s Expert 52
C. The Skilled Person of the Formulation Patents 52
D. The Formulation Patents – Claims Construction 54
(1) The 056 Patent 56
(2) The 111 Patent 59
E. Anticipation: The Formulation Patents v Chiron 61
(1) The Chiron Patent 61
(2) Disclosure 62
(a) Use of Surfactants/Aluminum Salt in the Chiron Patent 62
(b) Siliconized Container Means 65
(3) Enablement 66
F. Obviousness 67
(1) The Common General Knowledge and State of the Art 68
(a) Buffers 69
(b) Aluminum Salts 70
(c) Siliconized Containers 71
(d) Surfactants 71
(e) Serotype Selection 75
(2) State of the Art vs Inventive Concept 76
(3) The Inventors’ Course of Conduct 77
G. Double Patenting 79
IV. Conclusion 80
V. Costs 81
I. Overview
[1] Merck Canada Inc. and Merck Sharp & Dohme Corp. [together Merck], seek to impeach three Canadian patents, one composition patent and two formulation patents, property of Wyeth LLC [Wyeth], pertaining to a 13-valent pneumococcal polysaccharide protein conjugate vaccine commercialized under the name Prevnar® 13.
[2] Merck states that Prevnar® 13 lacks inventiveness and that it was not worthy of patent protection. Merck takes its position despite the fact that it took years of research and clinical testing to develop Prevnar® 13; that Wyeth succeeded where several competitors had failed; and, that Wyeth has immunized over 1.5 billion people around the world during the decade when Prevnar® 13 benefited from a monopoly.
[3] If Wyeth invented anything – and Merck submits that Wyeth did not, owing to anticipation and obviousness – the invention is at most a 13-serotype vaccine. To the extent that any of the claims are not limited to those 13 serotypes, Merck contends they are overbroad and one could not soundly predict them.
[4] Wyeth, on the other hand, states that its patents disclosed to the world a platform to make polysaccharide conjugate vaccines comprising 13 or more serotypes of pneumococcus. According to Wyeth, Prevnar® 13 is the result of years of experimental work by teams of scientists, and it is the gold standard of the industry to this day. It argues that its monopoly is not limited to 13 serotypes, and that it would cover any pneumococcal polysaccharide conjugate vaccines that contain the 13 serotypes recited in the claims of its patents, plus any other known serotypes or clinically relevant serotypes.
[5] At the onset of the trial, Merck’s standing to take action was a live issue. Wyeth now concedes it is no longer an issue since during the trial Merck Canada Inc. filed a New Drug Submission for approval to sell a 15-valent pneumococcal polysaccharide protein conjugate vaccine [V114] in Canada. Since the parties are both innovative pharmaceutical companies that have been competing to make newer and better pneumococcal vaccines since the early 1980s, Merck believes that Wyeth will try to use its patents to block V114 from entering the Canadian market.
[6] That said, Wyeth’s patents are deemed valid. Merck bears the burden to proof otherwise.
II. The Composition Patent
A. The Story of the Composition Patent
[7] Dr. Peter R. Paradiso, formerly responsible for research and development at Wyeth, is one of the named inventors of Canadian Patent No. 2,604,363 [the 363 Patent or Composition Patent]. He testified to Wyeth’s history of conjugate vaccine development and the story behind the invention of the 363 Patent.
[8] During his professional career with Wyeth, he engaged in the discovery, development and clinical research that led to the licensure of various conjugate vaccine products, including:
HibTITER® (Haemophilus influenzae serotype b (Hib) conjugate vaccine);
Tetramune® (combined diphtheria, tetanus, and pertussis and HibTITER);
Meningitec® (Neisseria meningitidis group C conjugate vaccine);
Prevnar® (7-valent Streptococcus pneumoniae conjugate vaccine); and,
Prevnar® 13 (13-valent Streptococcus pneumoniae conjugate vaccine).
[9] All of these vaccines are either monovalent (comprising a single serotype) or multivalent (comprising multiple serotypes) and conjugated with Wyeth’s preferred protein carrier, CRM197, a cross-reactive derivative of the diphtheria toxoid.
[10] Beginning in the 1980s and throughout the 1990s, at the same time that Wyeth was developing HibTITER®, Tetramune® and Meningitec®, it was also working on developing its first pneumococcal polysaccharide protein conjugate vaccine [PCV].
[11] Streptococcus pneumoniae (also referred to as S. pneumoniae) is a bacteria that causes many pneumococcal infections including serious diseases such as meningitis, pneumonia, and bacteraemia, as well as milder infections such as sinusitis and otitis media. Infants and young children are especially susceptible to S. pneumoniae and are at serious risk for pneumococcal infections. S. pneumoniae is classified into different serotypes (i.e. strains) depending on the polysaccharide that encapsulates the bacteria.
[12] When Wyeth was developing its first PCV, some 90 serotypes were known, and some were part of a same serogroup. Each serotype is identified by a number, and where more than one is known in the same serogroup, they are also given a letter.
[13] Despite the successful use of bacterial polysaccharides to immunize adults and older children, polysaccharides were not very immunogenic in children under the age of two. Previously, immunization of that age group took place with bacterial proteins, also with moderate success.
[14] However, it had been shown that, by conjugating polysaccharides to carrier proteins, the immune response to the polysaccharide could be enhanced. Studies performed in the 1980s and 1990s showed that such conjugation resulted in vaccines that had a better immune response (than polysaccharides alone) in children under two years of age.
[15] Wyeth was thus working to create a multivalent conjugate formulation to protect against multiple serotypes of the S. pneumoniae bacteria in a single vaccine.
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[17] In 2000, Prevnar® [Prevnar 7] became the first licensed PCV in the world. It contained coverage for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F.
[18] Wyeth never sought a patent for its invention and never disclosed the serotype-specific methodology used to make the conjugates found in Prevnar 7.
[19] Although Prevnar 7 was a successful vaccine, there remained a global need for increased serotype coverage, particularly in the developing world. Wyeth thus developed a 9-valent vaccine for sub-Saharan Africa, which included serotypes 1 and 5 (PCV-9).
[20] However, by year 2000, GSK and Aventis Pasteur were developing 11-valent PCVs covering additional serotypes 3 and 7F (PCV-11). PCV-11 was expected to protect against 90% of invasive pneumococcal disease worldwide.
[21] As a result, Wyeth determined that it had to develop a new product to expand protection and remain competitive. It decided to pursue PCV-13, adding serotypes 6A and 19A to the PCV-11, all conjugated to CRM197. While CRM197 was Wyeth’s carrier protein of choice, Wyeth had concerns about immune interference. |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| but chose to use CRM197 after the data described in the 363 Patent became available.
[22] The immunogenicity data obtained showed that Wyeth’s PCV-13 was dozens to hundreds of times more immunogenic than the corresponding free polysaccharides. The data made Dr. Paradiso confident that Wyeth could develop even higher-valency PCVs using CRM197 as the sole carrier protein, and the data made Wyeth affirm that it invented a 13-valent “platform”.
B. The Issues for the 363 Patent
[23] Merck argues that each of claims 1 to 6, 13, 14, 17 to 19, 22 to 30 and 36 to 38 of the 363 Patent [the Impugned Claims] are invalid.
[24] The 363 Patent was filed on March 31, 2006 and claims priority to US 60/669,605 dated April 8, 2005. The 363 Patent was issued on June 16, 2015 and has not expired.
[25] Merck raises three main issues regarding the 363 Patent:
(1) Are the Impugned Claims limited to compositions made from 13 serotypes?
(2) In any event, are the Impugned Claims invalid because:
(a) They are anticipated by Peña (Claim 1 only)?
(b) They are obvious (all Impugned Claims)?
(3) To the extent that the Claims cover compositions made from more than 13 serotypes, are they invalid for overbreadth and/or lack of utility?
C. The 363 Patent Experts
[26] Both parties tendered evidence from two experts on the 363 Patent. Dr. James Cleland Paton and Dr. Dennis Kasper testified on behalf of Merck. Dr. Neil Ravenscroft and Dr. Ron Dagan testified on behalf of Wyeth.
[27] All experts heard at trial are well-respected scientists that have extensive knowledge and experience with encapsulated bacteria and, to varying degrees, with conjugation methods. They all are prolific authors of numerous articles and papers published in the most prestigious scientific publications around the world. Unfortunately, perhaps with the exception of Dr. Kasper, the experts all lost some of their objectivity during cross-examination and, at times, became argumentative and non-responsive.
(1) Merck’s Experts
[28] Dr. Paton is Merck’s pneumococcal expert. He is a professor of Microbiology and Director of the Research Center for Infectious Disease at the University of Adelaide in Australia.
[29] Merck presents him as having had benchtop experience making a polysaccharide-protein conjugate before 2005. On the other hand, in addition to listing several omissions, admissions and inconsistencies in his testimony, Wyeth submits that Dr. Paton has never worked on a multivalent conjugate vaccine and has mainly focused his work on protein alone vaccines. Indeed, Dr. Paton admitted he never worked on the development of a multivalent conjugate vaccine, but stated that he had made a polysaccharide-protein conjugate in the 1990s.
[30] Dr. Kasper is Merck’s polysaccharide-protein conjugate expert and immune interference expert. He is a physician-scientist and currently holds the positions of William Ellery Channing Professor of Medicine and Professor of Immunology at Harvard Medical School.
[31] His testimony focussed on the Method/Process claims of the 363 Patent. Merck rightly notes that Dr. Kasper made concessions where fair, and digressed less in cross-examination than others did.
[32] Without attacking Dr. Kasper’s credibility, Wyeth states that all but four pages of his report are irrelevant to this case. Dr. Kasper opines that general steps set out in the Method/Process claims were known at the relevant time, without considering whether these claims were inventive because of the new 13-valent immunogenic composition.
[33] In addition, Wyeth notes that Dr. Kasper is not an expert in pneumococcus and that no more than 10 of the 400 papers he has authored deal with pneumococcus.
(2) Wyeth’s Experts
[34] Dr. Ravenscroft is Wyeth’s expert in multivalent pneumococcal conjugate vaccines. He currently is Associate Professor and Deputy Head of the Department of Chemistry at the University of Cape Town in South Africa.
[35] Wyeth points to the fact that he is the only expert who has actually worked to develop a licensed pneumococcal conjugate vaccine.
[36] Wyeth concedes that while Dr. Ravenscroft’s testimony was difficult to reconcile at times, his testimony was forthright and it was not argumentative, despite having been unnerved during cross-examination and asked to adopt assumptions that were opposite to his actual views.
[37] On the other hand, Merck argues that Dr. Ravenscroft made fatal concessions in cross-examination and that he was unable to defend his initial tortured construction of the claims of the 363 Patent, just as he was unable to support his initial position on anticipation and obviousness.
[38] Dr. Dagan is Wyeth’s expert on the development of pneumococcal vaccines, including serotype selection and immune interference. He is currently a Distinguished Professor of Pediatrics and Infectious Diseases of the Ben-Gurion University of the Negev, and Emeritus Director of the Pediatric Infectious Disease Unit at the Soroka University Medical Center, both in Israel.
[39] Wyeth suggests that his expertise is unparalleled in the scientific community, and that the Court should entirely accept his evidence. Wyeth acknowledges that his cross-examination became heated on occasion but Wyeth blames Merck’s counsel for putting propositions to Dr. Dagan that rephrased his prior statements.
[40] Merck notes that Dr. Dagan is a clinician with no experience making conjugate vaccines himself. As the father of the doctrine of immune interference, Merck warns the Court that Dr. Dagan’s knowledge on the subject well-exceeds that of the skilled person at the relevant time. Merck also points to the fact that Dr. Dagan openly disagreed with Dr. Ravenscroft, Wyeth’s other expert, on an important issue. Finally, Merck says that Dr. Dagan’s testimony was generally evasive and that he was unwilling to concede even basic points where fair.
D. The Person of Skill in the Art [PSA]
[41] The parties’ experts generally agree that the 363 Patent is directed to the following person or team of persons possessing the ordinary skill and knowledge of the particular art to which the 363 patent relates (Free World Trust v Électro Santé Inc, 2000 SCC 66 at para 44 [Free World]):
One or more vaccinologists with an interest in the development of pneumococcal conjugate vaccines, having relevant experience in chemistry, microbiology, immunology, epidemiology, and clinical infectious disease. The intended audience would have had an M.D., M.Sc., and/or Ph.D., as well as applied expertise in the context of pneumococcal conjugate vaccine development. In particular, the PSA would have had actual experience in carbohydrate chemistry and the preparation of polysaccharide-protein conjugates and conjugate vaccines.
E. Claims Construction – Legal Principles
[42] Subsection 27(4) of the Patent Act, RSC 1985, c P-4 [Patent Act] requires that claims define “distinctly and in explicit terms the subject-matter of the invention for which an exclusive privilege or property is claimed.”
[43] As stated in Free World at paragraph 14, citing from Minerals Separation North American Corp v Moranda Mines, Ltd, [1947] Ex CR 306 at 352, the claims must not be flexible, but rather must provide a “bright line demarcation” of the monopoly claimed:
By his claims the inventor puts fences around the fields of his monopoly and warns the public against trespassing on his property. His fences must be clearly placed in order to give the necessary warning and he must not fence in any property that is not his own. The terms of a claim must be free from avoidable ambiguity or obscurity and must not be flexible; they must be clear and precise so that the public will be able to know not only where it must not trespass but also where it may safely go.
[44] The words of the claims must be read through the eyes of the PSA, in light of that person’s common general knowledge, in an informed and purposive way, and with a mind willing to understand (Free World at paras 31(c) and 44; Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 49 [Whirlpool]).
[45] Construction of a patent is a question of law left to the Court to decide (Whirlpool at para 61). However, expert evidence provides the technical knowledge that enables the Court to step into the shoes of the PSA faced with the claims as of the publication date (October 19, 2006 for the 363 Patent).
[46] The PSA will appreciate the nature and description of the invention on a technical level, making sense of the words used in the claims in light of the common general knowledge (Whirlpool at para 53).
F. Claims Construction – Are The Impugned Claims Limited to 13 serotypes
[47] Five of the Impugned Claims are independent claims: Claims 1, 13, 17, 36 and 38.
[48] The 363 Patent includes three groups of claims: (i) Composition Claims; (ii) Use Claims; and (iii) Method/Process Claims:
The Composition Claims: The 363 Patent has claims to compositions with 13 or more serotypes (according to Wyeth), or it has claims to compositions with exactly 13 serotypes (according to Merck).
Claim 1 claims a multivalent immunogenic composition comprising 13 distinct polysaccharide serotypes conjugated to CRM197.
Claims 2-5 add adjuvants.
Claim 17 claims a 13-valent immunogenic composition conjugated to CRM197 using reductive amination.
Claims 18 and 19 add adjuvants.
The Use Claims: The 363 Patent has claims for the use of the composition as a medicament and as a vaccine.
Claim 6 is a medicament claim relating to a conjugate composition of 13 (Merck) or more serotypes (Wyeth).
Claims 22-30 claim the use of a conjugate composition of 13 serotypes for vaccination.
The Method/Process Claims: Claims 13-14 and 36-38 claim the general methods and processes to arrive at compositions containing conjugates of the 13 serotypes.
[49] Claim 1 is the only claim for which Wyeth contends that its scope exceeds the 13 specific serotypes listed in the 363 Patent. Claim 1 describes a multivalent immunogenic composition comprising 13 distinct conjugates prepared from 13 serotypes each individually conjugated to CRM197:
A multivalent immunogenic composition, comprising 13 distinct polysaccharide-protein conjugates, together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of Streptococcus pneumonia conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, wherein the carrier protein is CRM197.
[50] Merck asserts that all experts agreed that Claim 1 is limited to 13 serotypes.
[51] Wyeth responds that the Court should be very prudent in relying on the admissions obtained by Merck’s counsel in cross-examination of its experts, as counsel used an approach that should be rejected: an approach that focused on “excessive literalism”. Wyeth reminds the Court that patent specifications are not to be read using a “dictionary approach” nor are they addressed to grammarians, etymologists or laypeople (Whirlpool at paras 52-53).
[52] Based on their general knowledge at the time, Wyeth argues that the PSA would have appreciated that the 363 Patent was about expanding coverage while retaining the key benefits of conjugation: increasing immunogenicity. The PSA would have understood that the 363 Patent describes the “next generation” of Wyeth’s conjugate development program and that Wyeth had managed to exceed the known limits of serotype coverage with its PCV-13. Finally, the PSA would have understood that the 363 Patent describes a “platform” technology; it discloses the details of Wyeth’s conjugation technology that were needed in order to replicate its success. The PSA would have used the platform to add other serotypes in a future vaccine, just as Merck did with its V114.
[53] As to the number of additional serotypes that this “platform” covers, Wyeth’s position is somewhat elastic. Dr. Ravenscroft first stated in his report that it should include all 50 serotypes of known structure; he later suggested that it be limited to clinically relevant serotype. Finally, he landed on the 23 serotypes contained in Pneumovax® 23 (a polysaccharide only pneumococcal vaccine).
[54] Wyeth’s notion of a “platform” basically comes from the use of the word “comprising” in Claim 1, which Wyeth asks the court to replace with “including but not limited to”. Claim 1 would then read as follows:
A multivalent immunogenic composition, [including but not limited to] 13 distinct polysaccharide-protein conjugates, together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of Streptococcus pneumonia conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, wherein the carrier protein is CRM197.
[55] On the other hand, Merck asserts that the word “comprising” allows for more elements in the composition, such as acceptable physiological vehicles and/or adjuvants, and that the two “wherein” clauses limit both the serotypes and carrier protein that can be used:
A multivalent immunogenic composition, comprising 13 distinct polysaccharide-protein conjugates, together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of Streptococcus pneumonia conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, wherein the carrier protein is CRM197.
[Emphasis added by Merck.]
[56] For several reasons, I prefer Merck’s proposed construction. I find that a purposive interpretation of both Claim 1 and the 363 Patent in its entirety supports the view that Claim 1 is limited to 13 serotypes.
[57] In Purdue Pharma v Canada (Attorney General), 2011 FCA 132 at para 22 [Purdue Pharma], the Federal Court of Appeal held that even if the word “comprising” used in claim language could be regarded as open-ended, the inclusion of other elements requires some justification. The basis for such an inclusion must be found within the confines of the patent. No such basis existed in Purdue Pharma, and none can be found in the 363 Patent.
[58] When one reads the patent as a whole, one finds sufficient bases for adding adjuvants, buffers and other excipients. However, there is no basis to go beyond 13 serotypes.
[59] First, the Summary of the Invention describes the invention as providing a 13-valent pneumococcal conjugate composition comprising the seven serotypes contained in Prevnar 7 (4, 6B, 9V, 14, 18C, 19F and 23F), plus six additional serotypes (1, 3, 5, 6A, 7F and 19A). This is very specific and limited.
[60] Second, in the Detailed Description of the Invention, a rationale is provided for the inclusion of the original seven serotypes: they were responsible for 82% of the invasive pneumococcal diseases in children under the age of two. A very detailed rationale is also provided for the inclusion of each of the additional six serotypes. For example, serotypes 6A and 19A account for more invasive pneumococcal disease in US children under two than serotypes 1, 3, 5 and 7F combined, in addition to being commonly associated with antibiotic resistance. There is no mention in the 363 Patent of a need, a desire, or a basis for adding any other serotype. Again, some 90 serotypes were known at the time.
[61] Third, all of the 16 examples provided in the 363 Patent, which contain instructions needed by the PSA, refer only to the specific 13 serotypes recited in the claims, no others.
[62] Fourth, I find that Dr. Ravenscroft’s reference to Figure 1 of the 363 Patent to support his view that the inventors also contemplated serotype 12F and others is misplaced. Figure 1 conveys information that was publically available in April 2005; it shows the increase of invasive pneumococcal disease rates in US children under the age of two, from baseline (1998/99) to 2001. As admitted by Dr. Ravenscroft on cross-examination, this figure was added for the sole purpose of making a point: to address prevalence/antibiotic resistance and justify the addition of serotypes 6A and 19A. Serotype 12F being entirely penicillin sensitive, Dr. Ravenscroft admitted that Figure 1 cannot be used as a rationale to add it to the invention disclosed in the 363 Patent.
[63] Fifth, Wyeth’s argument that the wording of Claim 17 supports its construction of Claim 1 should also fail. Claim 17 reads as follows:
A multivalent immunogenic composition, comprising polysaccharide-protein conjugates together with a physiologically acceptable vehicle, wherein said polysaccharide-protein conjugates consist of 13 distinct polysaccharide-protein conjugates, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of Streptococcus pneumoniae conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, wherein the carrier protein is CRM197 and wherein conjugation is effected by reductive amination.
[64] Wyeth admits that Claim 17 is limited to 13 serotypes but argues that in order to differentiate it from Claim 1, Claim 1 must not be limited to 13 serotypes. Dr. Ravenscroft’s interpretation of Claim 1 is grounded in the fact that “in claims drafting, when different terms are used, they are presumed to have different meanings. Consequently, the use of ‘consist of’ in claim 17 would have indicated to the PSA that ‘comprising’ must have a different—and broader—meaning” (Ravenscroft Report at para 246).
[65] I disagree. The word “comprising” along with a few “wherein” clauses (that have the same limiting effect as for Claim 1) are also used in Claim 17. Moreover, Claim 17 is not without purpose if both claims are limited to 13 serotypes. Dr. Ravenscroft acknowledges that unlike Claim 1, which allows for the use of any conjugation technology, Claim 17 excludes conjugates made using any approach other than reductive amination. Thus, Claim 17 is different from Claim 1. They each have a different scope, and they are not redundant (MIPS AB v Bauer Hockey Ltd, 2018 FC 485 at para 134).
[66] Finally, if the Court were to side with Wyeth on the construction of Claim 1, the Court would have to choose a cap on the number of serotypes covered by the invention or that could be added using Wyeth’s so-called “platform”. It would also mean that the ambit of Wyeth’s monopoly could grow over the life of the 363 Patent as new serotypes – or their structure – are discovered. This would be contrary to the fundamental principles of claims construction (Free World at para 57).
[67] For these reasons, I find that Claim 1 of the 363 Patent is limited to 13 serotypes and does not disclose any “platform” for making a vaccine with greater coverage.
G. Claims Construction – meaning of “Immunogenic”
[68] Antibodies may be measured in an enzyme-linked immunosorbent [ELISA] assay, which is a common assay technique designed for detecting and quantifying antibodies to an antigen. On the other hand, an opsonophagocytic activity [OPA] assay measures whether the antibodies elicited by a vaccine are functional; that is, that they are shown to efficiently kill the bacteria.
[69] According to Merck, the PSA would read “immunogenic” in the claims of the 363 Patent to mean that the composition generates “an immune response” or that it elicits antibodies for each of the serotypes, without any particular level of antibody response. Merck emphasizes the fact that Dr. Ravenscroft conceded on cross-examination that the ordinary meaning of “immunogenic” in the art is that the composition elicits an immune response, and most studies at the time demonstrated immunogenicity based on IgG responses in ELISA assays alone.
[70] Wyeth responds that this definition is nonsensical. As stated by Dr. Dagan, the body produces an immune response to almost all stimuli: “If I drink milk, I get antibodies to milk… eating elicits antibodies. Living, breathing, everything else, it is antibodies” (Trial Transcript Vol 9, page 1229, lines 23-27).
[71] Wyeth contends that the PSA would understand the term “immunogenic” to mean that each conjugate elicits an immune response greater than the polysaccharide alone. That is the whole purpose of conjugating. That is what the data tables in the 363 Patent demonstrate: the 13-valent conjugate composition is more immunogenic than the polysaccharide alone, and the antibodies elicited are functional.
[72] At paragraph 249 of his report, Dr. Ravenscroft, Wyeth’s expert in multivalent pneumococcal conjugate vaccines, states the following:
The [PSA] would have also understood that the compositions were “immunogenic”. At the most basic level, the [PSA] would have understood that the term “immunogenic” referred to the fact that the compositions generate an immune response when administered. The [PSA] would have recognised that the polysaccharides themselves are classified as antigens (i.e., antibody generators). Further, such polysaccharides can be conjugated to a carrier protein to achieve a greater immune response. In other words, for a composition of “polysaccharide-protein conjugates”, the [PSA] would have understood “immunogenic” to mean that each conjugate would have been expected to elicit an immune response that was greater than the polysaccharide alone. The 363 Patent itself recognises that the conjugates of the composition produce “higher serum IgG titers and overall greater functional antibody activity than seen with the free polysaccharide alone or mixed with unconjugated CRM197.” As of the relevant date, the accepted means of measuring the immunogenicity of pneumococcal conjugates were (1) serotype-specific ELISA to detect serum IgG titers and (2) OPA to detect functional (i.e., opsonophagocytic) antibodies.
[Footnotes Omitted.]
[73] I must first say that Dr. Dagan’s analogy with milk (which Wyeth took up in its closing argument) does not convince me. Drinking milk, eating, living, and breathing will not elicit antibodies to the pathogens a vaccine aims at protecting against, hence the research for a vaccine. This argument says nothing about the quantity (ELISA assay) or quality (OPA assay) of the immune reaction the 363 Patent is referring to, and in that sense, it does not advance the debate on the issue.
[74] I also have to consider the fact that the Impugned Claims themselves do not state any particular level of immunogenicity or any particular assays for measuring immunogenicity.
[75] I therefore have to turn to other information convened by the 363 Patent and to the common general knowledge of the PSA to determine whether the term “immunogenic” means that the invention claims an immune response for each of the 13 serotypes that is greater than the polysaccharide alone (ELISA), and that the antibodies elicited are functional (OPA).
[76] I am willing to accept that, at the time, the PSA would have known that the purpose of conjugating was to elicit an improved immune response, especially in children under the age of two. Additionally, the PSA would have known that since 2003, the World Health Organization required functional antibodies in immunogenic compositions.
[77] The PSA would have understood that the data illustrated in Tables 5 and 6 of the 363 Patent was consistent with the inventors’ conclusion “that conjugation of the 13-valent pneumococcal vaccine polysaccharides produces higher serum IgG titers and overall greater functional antibody activity than seen with free polysaccharide alone or mixed with unconjugated CRM197” (363 Patent, Trial Exhibit [TX] 3 at 47, lines 6-9). The inventors say “overall” because the serotype 14 admittedly fell short of demonstrating that it generated functional antibodies in pre-clinical immunogenicity studies.
[78] Having considered all of the evidence, I am of the view that Wyeth confuses what the inventors sought with what the 363 Patent claims. The 363 Patent claims a “multivalent immunogenic composition” without further qualification. Although the PSA would have known that the whole purpose of conjugating is to improve immunogenicity, particularly in young children, Dr. Ravenscroft also admitted that the PSA would understand the word “immunogenic” to mean “elicits an immune response” and that a common way of measuring immunogenicity is with ELISA assays.
[79] In my view, if Wyeth wanted to claim a specific level of immunogenicity, or define immunogenicity otherwise than to illicit an immune response, it could have done so in so many words. It could have used language similar to that used by GSK in its patent WO 00/56358 where it claimed:
1. An antigenic composition comprising one or more Streptococcus pneumoniae capsular polysaccharide conjugates adjuvanted with 3D-MPL and substantially devoid of aluminium-based adjuvants, wherein at least one of the Streptococcus pneumoniae polysaccharide conjugates is significantly more immunogenic in compositions comprising 3D-MPL in comparison with compositions comprising 3D-MPL in conjunction with an aluminium-based adjuvant.
[Emphasis added.]
[80] In my view, those words should not be read in Claim 1 of the 363 Patent.
H. Validity of the 363 Patent
(1) Novelty/Anticipation
[81] Subsection 28.2(1) of the Patent Act requires that, for a patent to be valid, its subject matter cannot have been previously disclosed. If the subject of the Patent’s claims was made available to the public in a single enabling disclosure prior to the claim date, it was anticipated. The two-part test for anticipation is set out in Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61 [Sanofi]:
1. The prior art reference must disclose the claimed invention such that, if performed, it would necessarily result in infringement of the patent; and,
2. The prior art reference must be sufficiently detailed to enable a PSA to perform the claimed invention without the exercise of inventive ingenuity or undue experimentation.
[82] Anticipation requires the prior publication to contain clear and unmistakable directions to do what the patentee claims to have invented (Sanofi at para 21 and Free World at para 26). The enablement element is satisfied where there is enough information to allow the subsequently claimed invention to be performed without undue burden (Sanofi at para 37).
[83] Disclosure and enablement are two distinct requirements; if disclosure is not proven, enablement does not need to be considered (Sanofi at para 42).
(2) Claim 1 of the 363 Patent vs Peña 2004
(a) Disclosure
[84] Merck contends that all essential elements of Claim 1 of the 363 Patent were publically disclosed in a 2004 publication by C. de la Peña entitled “Present and future of the vaccination against pneumonia” [Peña 2004], published in Pediátrika, a Spanish journal. It is uncontested that Peña 2004 is a Wyeth publication, written by Wyeth’s employees. It discusses the incidence of S. pneumoniae related diseases in various groups of young Spanish children. For example, it discusses:
Ÿ Pneumococcal disease as a significant cause of morbidity, hospitalization and mortality, where 40% of all deaths due to pneumonia are children under five years of age;
Ÿ The impact of antibiotic resistance when prevention of the infection is not possible, and the known relationship between serotypes and resistance;
Ÿ The fact that the 23-valent polysaccharide only vaccine is not immunogenic in children under two;
Ÿ The fact that conjugation with “an appropriate protein” improves immunogenicity, as demonstrated with the vaccine Haemophilus influenza type b.
Ÿ Several statistics comparing the incidence of S. pneumoniae related diseases among regions in Spain and between Spain and other European countries and the United States;
Ÿ The fact that in February 2000, the United States authorized the use of a pneumococcal conjugate vaccine against seven serotypes of S. pneumoniae (Prevnar 7), and its observed efficacy;
Ÿ The introduction of Prevnar 7 in the Spanish market in June 2001, and its observed efficacy;
[85] What Merck views as disclosure of the elements of Claim 1 are the following excerpts of Peña 2004 at 52-53:
Other pneumococcal vaccines
As we know, there are currently two vaccines available for the prevention of invasive pneumococcal disease: the 23-valent polysaccharide (VNP-23V) and the 7-valent conjugate vaccine (VNC-7V).
There are other pneumococcal conjugates that have not yet been marketed and that are in advanced phases of study:
Ÿ The 9-serotype vaccine (adds 1 and 5), which increases the coverage up to 87% in children less than two years of age and in children between two and five years of age.
Ÿ The 11-serotype vaccine (adds 3 and 7F). Serotype 3 is the most likely to cause invasive disease in adults in Spain; therefore, the use of these vaccines could have a favourable impact on the incidence of the infection by this serotype.
Ÿ The 13-serotype vaccine (adds 6A and 19A)”
…
The future of pneumococcal vaccination
The 23-valent polysaccharide vaccine was the first step in the fight against pneumococcal disease, and the heptavalent conjugate vaccine has drastically reduced the disease in the youngest of children. Thus, in terms of future pneumococcal vaccinations, we should keep in mind several issues: serotypes and age and geographic distribution, combination with other vaccines, new routes of administration and other strategies.
The geographic variability of pneumococcal serotypes represents a problem when developing a vaccine with worldwide coverage. We would almost have to design a specific vaccine for each geographic area, conducting a prior epidemiological study of the most common serotypes, which would only be possible in developed countries.
Furthermore, we know that the spectrum of serotypes widens with advancing age, which complicates the acquisition of vaccines for age groups other than children, although children are the group at greatest risk and for whom the current vaccine is most effective. In this respect, work is being conducted to incorporate new serotypes to the 7-valent conjugate vaccine, with the 9-valent (which incorporates the serotypes 1 and 5), 11-valent (adding 3 and 7F) and 13-valent (6A and 19a) vaccines in various stages of research. This could broaden the spectrum of ages and countries, although we will continue to have much diversity in coverage. In addition, attempts are being made to incorporate the pneumococci that show the greatest resistance to antibiotics.
[Emphasis added.]
[86] It is uncontested that Peña 2004 is silent on the carrier protein used to conjugate the different serotypes that are listed and that are said to compose the 9-valent, 11-valent and 13-valent vaccines, although