Meda AB v. Canada (Health)

Meda AB v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2016-12-09
Neutral citation
2016 FC 1362
File numbers
T-200-15
Decision Content
Date: 20161209
Docket: T-200-15
Citation: 2016 FC 1362
Ottawa, Ontario, December 9, 2016
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
MEDA AB, MEDA PHARMACEUTICALS LTD. AND VALEANT CANADA LP/VALEANT CANADA S.E.C.
Applicants
and
THE MINISTER OF HEALTH AND PHARMASCIENCE INC.
Respondents
and
OREXO AB
Respondent/Patentee
PUBLIC JUDGMENT AND REASONS
Table of Contents
I. Background. 3
A. The Underlying Application. 3
B. The Notice of Allegation (“NOA”) 4
II. Issues. 6
A. Summary of Decision. 6
B. Preliminary Issues. 7
(1) The Affidavits of Drs. Fassihi and Davé. 7
(2) Alleged “ambush evidence” of Pharmascience. 8
(3) Conclusion of the Preliminary Issues. 16
III. Burden of Proof. 17
IV. Applicants’ Expert Witnesses. 17
A. Dr. Loyd Allen, Jr. 17
B. Dr. Patrick J. Sinko. 18
V. Pharmascience’s Expert Witnesses. 19
A. Dr. Yuriy Ososkov. 19
B. Dr. Reza Fassihi 20
C. Dr. John D. Smart 21
D. Dr. Rajesh Davé. 21
VI. The ‘988 Patent 22
A. The Person Skilled in the Art (POSITA) 24
B. Common general knowledge. 24
(1) Acute disorders and insomnia. 27
(2) Dosage form development 27
(3) Rapidly disintegrating or dissolving tablets. 28
(4) Sublingual Tablets. 28
(5) Ordered Mixtures. 29
(6) [redacted] 30
C. Claim Construction. 30
(1) Relevant Date. 30
(2) Claim terms that need construction. 32
VII. Prior Art 36
VIII. Anticipation of the ‘988 Patent by the ‘725 Patent 38
IX. Obviousness. 41
X. Claims Overbroad. 46
XI. Utility. 50
XII. Infringement 53
XIII. The Gillette Defence. 57
XIV. Conclusion. 57
XV. Costs. 57
I. Background A. The Underlying Application [1] Meda AB, Meda Pharmaceuticals, and Valeant Canada LP (“Valeant”) (together, the “Applicants”) are “first persons” as defined in the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, subsections 2(1) and 4(1) (PM(NOC) Regulations).
[2] The Applicants filed New Drug Submissions with the Minister of Health (the “Minister”) for 10 and 5 mg zolpidem tartrate sublingual orally disintegrating tablets (the “SUBLINOX® Tablets”) for which Notices of Compliance (“NOC”) for Submissions (Submissions 140675 and 153453) were issued on July 19, 2011 and February 15, 2012, respectively.
[3] On January 16, 2014, the Applicants (Meda AB and Meda Pharmaceuticals), licensees of the Canadian Patent No. 2,629,988 (the “‘988 Patent”), requested the listing of the ‘988 Patent on the Patent Register in respect of the above submissions and the SUBLINOX® Tablets. The Minister found the ‘988 Patent eligible for listing in respect of these submissions and added it to the Patent Register on January 28, 2014. On January 8, 2015, the Patent Register was updated to reflect Valeant, a sublicensee under the ‘988 Patent, as the current holder of the NOCs and Drug Identification Numbers for the SUBLINOX® Tablets.
[4] Orexo AB owns the ‘988 Patent (issued in Canada January 7, 2014, based on a Patent Cooperation Treaty (“PCT”) application dated September 24, 1999) and is party to the prohibition application under subsection 6(4) of the PM(NOC) Regulations.
[5] On May 30, 2014, the respondent, Pharmascience Inc. (“Pharmascience”), filed an Abbreviated New Drug Submission (“ANDS”) seeking a NOC for 5 and 10 mg zolpidem tartrate sublingual orally disintegrating tablets (“PMS-Zolpidem”) and compared its proposed tablets to the SUBLINOX® Tablets.
B. The Notice of Allegation (“NOA”) [6] On December 23, 2014, Pharmascience served the Applicants with a letter, purporting to be a NOA pursuant to subsections 5(1)(b)(iii) and 5(1)(b)(iv) of the PM(NOC) Regulations in respect to the ‘988 Patent and the medicinal ingredient zolpidem in Pharmascience’s PMS-Zolpidem compared to the Applicants’ SUBLINOX® Tablets.
[7] The NOA is 87 pages and lists over 200 documents in its attached Schedule B. It raises numerous arguments on the issues of patent and claim construction, non-infringement and validity of the ‘988 Patent (including a “Gillette Defence”, anticipation, obviousness, insufficiency, inutility, overbreadth, ambiguity and improper patent listing).
[8] At the hearing, Pharmascience abandoned the invalidity allegations of insufficiency, ambiguity and improper patent listing.
[9] The Applicants commenced this prohibition application on February 12, 2015, seeking an order that the Minister be prohibited from issuing a NOC to Pharmascience for PMS-Zolpidem until the ‘988 Patent expires on September 24, 2019.
[10] On September 11, 2015, the Applicants served their evidence on Pharmascience consisting of three affidavits:
a) Dr. Patrick J. Sinko;
b) Dr. Loyd V. Allen Jr.;
c) Ms. Sonica Soares (law clerk at Lenczner Slaght Royce Smith Griffin LLP).
[11] On December 11, 2015, Pharmascience served its responding affidavits:
a) Dr. Reza Fassihi ;
b) Dr. John David Smart (served December 14, 2015);
c) Dr. Rajesh N. Davé;
d) Dr. Yuriy Ososkov.
[12] Reply affidavits of the Applicants were served in March, 2016:
a) Reply affidavit of Dr. Allen;
b) Reply affidavit of Dr. Sinko.
[13] Sur-Reply affidavits of Pharmascience were served in March, 2016:
a) Sur-Reply affidavit of Dr. Fassihi;
b) Sur-Reply affidavit of Dr. Smart.
[14] Cross-examinations of Drs. Allen, Sinko, Fassihi, Smart and Davé on their affidavits were conducted in March and April, 2016.
[15] The Applicants seek not only the order prohibiting the Minister from issuing a NOC to Pharmascience for its proposed PMS-Zolpidem tablets until expiry of the ‘988 Patent, but as well as an order striking the affidavits of Dr. Fassihi and Dr. Davé, on the basis that Pharmascience’s counsel obstructed the cross-examinations of these affiants to the extent that the conduct was abusive and frustrated the process such that their evidence should be rejected.
[16] Further, the Applicants claim that only approximately half of the over 200 references listed in Schedule B are discussed in the NOA, many without pinpoints, and the other half are not referenced in relation to any propositions raised in the NOA.
[17] Therefore, the Applicants challenge Pharmascience’s evidence as listed in Schedule “A” to this decision on the basis that the evidence in Schedule “A” exceeds the NOA.
II. Issues [18] The issues are:
Preliminary Issues:
Should the affidavits of Dr. Fassihi and Dr. Davé be struck? Is Pharmascience’s evidence in Schedule A beyond the facts alleged in the NOA and therefore, improper?
Validity
i. Is the Pharmascience allegation of anticipation justified?
ii. Is the Pharmascience allegation of obviousness justified?
iii. Is the Pharmascience allegation of inutility justified?
iv. Is the Pharmascience allegation of overbreadth justified?
Infringement
Is the Pharmascience allegation of non-infringement justified, and/or does the Gillette Defence apply?
A. Summary of Decision
The affidavits of Dr. Fassihi and Dr. Davé are not struck.
The evidence in Schedule A is not improper.
Pharmascience’s allegation of:
anticipation is not justified; obviousness is not justified; inutility is not justified; overbreadth of claim 1 is justified; otherwise, the allegation is not justified.
Pharmascience’s allegation of non-infringement is justified.
B. Preliminary Issues (1) The Affidavits of Drs. Fassihi and Davé [19] The Applicants argued that both Dr. Fassihi and Dr. Davé were shielded against meaningful cross-examination by abusive conduct by Pharmascience’s counsel. They cite Federal Courts Rules, SOR/98-106, Rule 97(c), which states that “[w]here a person fails to…answer a proper question…the Court may strike all or part of the person’s evidence, including an affidavit made by the person”. Moreover, the Applicants rely on the Court’s inherent jurisdiction to redress abuses of its process.
[20] I agree with Pharmascience that the alleged “abusive conduct” in the cross-examination of Dr. Fassihi in fact consisted of assisting counsel for the Applicants who confused Schedule A with Schedule B to the NOA; ensuring that the witness understood the question; advising that the NOA document numbers had been inserted to assist with cross-examinations; assisting counsel in the pronunciation of benzodiazepines; and raising an objection when the question related to what the inventors were doing. As to the complaint that counsel suggested answers, the examples in the Applicants’ factum consist of asking for clarification of a question; objecting when the question was misleading the witness; objecting to questions based on erroneous facts; advising as to the NOA document number; advising the witness to look at the document which was the subject of questioning; and objecting to questions on the ultimate issue of infringement.
[21] As to the three refusals which are the focus of the allegation of abusive conduct in the Applicants’ factum, counsel for the Applicants admit on the transcript that it was not necessary to enter the Remington text as an exhibit since the question was already answered by Dr. Fassihi. Further, Dr. Fassihi did answer questions on Ativan.
[22] With respect to the cross-examination of Dr. Fassihi, there were five objections in a transcript of 165 pages. With respect to the cross-examination of Dr. Davé, there were three objections in a transcript of 165 pages. The Applicants chose not to bring a motion to compel answers to the questions that were the subject of the eight objections. Nor did the Applicants bring a motion to strike the evidence of Dr. Fassihi and Dr. Davé, but instead have relied upon their evidence in their factum.
[23] Therefore, while these interruptions and objections by counsel for Pharmascience were not always necessary or useful, they were not abusive.
(2) Alleged “ambush evidence” of Pharmascience [24] The Applicants pointed out that the NOA filed by Pharmascience lists some 200 documents—which comprise more than 10,000 pages, not including text books—in Schedule B to the NOA, and that of these documents, only approximately 95 were described within the text of the NOA.
[25] Pharmascience’s experts relied on approximately one third of the documents listed in Schedule B, and 31 of these citations refer to documents that were not discussed in the text of the NOA (the “Table 1 Documents”) (listed in Schedule A, Table 1 to the Applicants’ factum). Further, the Applicants pointed to three instances where the Pharmascience’s experts allegedly cited documents for propositions that were different from the propositions set out in the NOA (the “Impugned Propositions”) (listed in Schedule A, Table 2 to the Applicants’ factum).
[26] The Applicants contended that both the Table 1 Documents and the Impugned Propositions are improper evidence that should be struck from the record. They argued that including this evidence would be allowing Pharmascience to stray from its NOA, causing the Applicants irreparable prejudice. Additionally, they claimed that, because many of the documents in Schedule B were not fully discussed, the NOA did not give them proper notice of the case to be met, and that Pharmascience had split its case.
[27] The Applicants stated that, at the motion to strike hearing in February 2016 (the “Motion to Strike”), they reserved the right to challenge Pharmascience’s evidence to the full extent that it exceeded the NOA. They argued that the Table 1 Documents and the Impugned Propositions were “ambush evidence”, which expanded the legal and factual basis detailed in the NOA, and which should be found to be inadmissible.
[28] Pharmascience contended that the Table 1 Documents could not be “ambush evidence” because they were all listed in the NOA, and they all related to facts covered in the NOA. Further, they asserted that the Impugned Propositions did not actually introduce new facts into the application before this Court, because the propositions all related to facts discussed in the NOA.
[29] As stated in the Amended Confidential Reasons and Order, dated March 8, 2016, issued as a result of the Motion to Strike, striking evidence is an extraordinary remedy, to be exercised rarely; and where an applicant will not be prejudiced in a manner that cannot be compensated for by costs, evidence is best left for the hearing judge based on the full record (Meda v Pharmascience, 2016 FC 219, citing Proctor & Gamble Pharmaceuticals Canada Inc v Canada (Minister of Health), 2009 FC 113 [Proctor & Gamble] and Janssen-Ortho Inc v Apotex Inc, 2010 FC 81).
[30] However, both the Federal Court and the Federal Court of Appeal have consistently held that the NOA must raise all legal and factual arguments, which the party crafting the NOA will rely on, and that subsequently introducing new arguments and facts is improper, no matter how draconian this may seem (Bayer Inc v Cobalt Pharmaceuticals Co, 2013 FC 1061 at para 37 [Cobalt], aff’d in 2015 FCA 116; Aventis Pharma Inc v Mayne Pharma (Canada Inc), 2005 FCA 50 at para 25 [Aventis]; AB Hassle v Canada (Minister of Health and Welfare), [2000] FCJ No 855 (FCA) at paras 19, 21, 23 [AB Hassle]).
[31] Factual and legal arguments must be raised in the NOA in a manner that is sufficient to meet the requirement of section 5(3)(b)(ii) of the PM(NOC)Regulations: “A second person who makes an allegation under paragraph (1)(b) or (2)(b) shall include in the notice of allegation … a detailed statement of the legal and factual basis for the allegation”. The intent of this section is that the entire factual basis be set forth in the statement, rather than revealed piecemeal when some need happens to arise in the proceeding (AB Hassle, above, at para 23)
[32] The NOA must contain a detailed statement of the legal and factual basis for every allegation raised because of the unusual scheme established by the PM(NOC) Regulations, where the allegations are framed by the second person, but the application for prohibition is brought by the patent holder, who frames their arguments to deal with the allegations made in the NOA (Aventis, above, at para 20). Enough information needs to be included to allow the patent holder to make an informed decision as to whether to respond to the NOA by commencing an application for a prohibition order (AB Hassle v Apotex Inc, 2006 FCA 51 at para 4).
[33] Proceedings under the PM(NOC) Regulations are designed to be expeditious. The patent holder only has 45 days to assess its course of action in response to the NOA (subsection 6(1)), and the question of whether the Minister is free to issue the requested NOC, should be resolved within 24 months of the patent holder filing their NOA. Therefore, sufficiency of information must be assessed with the NOC scheme’s time constraints in mind (Cobalt, above, at para 32).
[34] However, there is a key distinction between the facts in a document and the document itself. A document cannot be assimilated to a factual basis; therefore, it is not that a second person is precluded from relying on any document not cited in the NOA, but rather that the second person may not rely on facts not cited in the NOA (Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC, 2015 FC 178 at para 137; Proctor & Gamble, above, at para 12).
[35] Finally, the lack of an affidavit, describing how the patent holder had not been able to decide whether to challenge an NOA because of the lack of specificity in the NOA, has been found to be a relevant factor in determining whether the patent holder has been prejudiced by new issues that were not raised in the NOA (Alcon Canada Inc v Apotex Inc, 2014 FC 791 at paras 80 and 82). The Federal Court of Appeal has confirmed that a lack of an affidavit on the part of the patent holder can be considered “to be telling” in a determination of the sufficiency of the NOA (Alcon, above, at para 81).
(a) The Table 1 Documents [36] There was no argument that the Table 1 Documents were introduced in the NOA. The real question was whether the experts cited those documents in a manner that introduced facts not raised in the NOA. A related question was whether facts in those documents, but not stated in the body of the NOA, were raised in the NOA in a manner that was sufficient to meet the requirement of subsection 5(3)(b)(ii) of the PM(NOC) Regulations.
[37] If merely attaching the document was all that was required for sufficient citation of a factual basis in an NOA, it would place an undue burden on a patent holder, who would have to assess all of the possible facts for which a Schedule B-type document could be evidence. This goes against the objective of the scheme set out in the PM(NOC) Regulations.
[38] It is not appropriate for a document that is merely attached to the NOA, and not discussed in any way, to stand for all of the facts that could be teased out of that document. Attachment in a list or table is not sufficient to meet the requirement of section 5(3)(b)(ii) of the PM(NOC) Regulations. However, as stated above the prohibition against raising new facts does not mean that experts cannot rely upon documents not discussed in the NOA to support facts clearly in the NOA.
[39] The Pharmascience experts, particularly Dr. Fassihi, gave very generic, high-level descriptions of the contents of each document. For example, regarding Schedule B, Document #35 (“NOA #35”), Dr. Fassihi stated (paras 150 to 151 of his affidavit):
This is a paper on order mixtures from 1983 discusses [sic] terminology for power mixing including ordered mixture, random mixture, degree of homogeneity and interactive powder.
In this article, the authors discuss the nomenclature for ordered mixture suggesting that “interactive” instead of ordered more closely reflects the interaction mechanism, i.e., the cohesive aspects between find drug particles and the carrier.
[40] Pharmascience, in their Response to Schedule A to the Applicants’ factum (the “RSA”), stated that these facts proffered by Dr. Fassihi related to the following facts in the NOA: (1) ordered mixtures were known; (2) ordered mixing is different from random mixing; and (3) there is a difference between obtaining homogeneity through [redacted] versus an ordered mixture. His statement is clearly related to the fact that ordered mixtures were known, and while it is unclear from his synopsis whether NOA #35 also stands for the facts that ordered mixing is different from random mixing, and/or that different amounts homogeneity is obtained via [redacted] versus an ordered mixture, he was not adding new facts.
[41] I am not convinced that any of the expert statements relating to the Table 1 Documents stand for new facts. Accordingly, I did not think that it was appropriate for these statements to be struck. In the few instances where any statement by one of the Pharmascience experts did raise a fact that was broader than what is in the NOA, it was given no weight in the decision, as it would have been inappropriate for Pharmascience to use the Table 1 Documents for facts beyond the factual statements made explicitly in the body of NOA.
(b) The Impugned Propositions [42] The key issue with regards to the Impugned Propositions was whether by discussing the underlying documents (listed as NOA #17, 54, and 128) in the body NOA, Pharmascience had sufficiently raised all of the facts within each document, and whether those facts could be used to support any/or all of the legal arguments made in the NOA.
[43] In the NOA, most of the Schedule B documents are discussed under the heading “Relevant Common General Knowledge of the Person Skilled in the Art”. This is a broad category, which suggests that all of the documents could support any of the validity attacks raised. In Eli Lilly Inc v Apotex Inc, 2007 FC 455 at paragraph 109, Justice Johanne Gauthier writes:
It is obviously important for a first person to know exactly on what basis the validity of the patent is challenged for this will have a major impact on the type of evidence it will be required to put forward. The analysis and evidential concerns that arise in response to allegations of invalidity based on anticipation or obviousness are very different from those that would arise in response to a challenge of validity based on insufficiency or lack of utility.
[44] However, the heading “Relevant Common General Knowledge of the Person Skilled in the Art” is located between two headings that have to do with the obviousness analysis: “Obviousness” and “The Test for Obviousness”. Therefore, it was reasonable to infer that the facts contained within these documents, except if the document was explicitly referenced in another section of the NOA, were all directed to an allegation of obviousness. To the extent that one of Pharmascience’s experts cited a proposition that was different from what was stated in the NOA, but which was used in an obviousness analysis, it was allowed. The way that the documents were disclosed in the body of the NOA was sufficient notice to the Applicants that any of the facts in each document, including the Impugned Propositions, would be put forward in an obviousness analysis.
[45] Under the headings “Anticipation”, “Insufficiency of the Description”, and “Lack of Utility and Lack of Sound Prediction”, Pharmascience has referenced specific documents, out of the Schedule B documents, in support of their arguments. It was appropriate to consider the whole of those specific documents, in the analysis under which each is listed. However, if Pharmascience used any one of documents NOA #17, 54, and 128 outside of a section where the document is explicitly listed, for a fact not explicitly stated in that section of the NOA (e.g., the document is listed in the section “Anticipation”, but not in the section “Lack of Utility”, and Pharmascience references it for a fact not explicitly stated in “Lack of Utility”), I gave that evidence no weight, because the NOA did not give sufficient notice that this was a fact that would be relied upon for that particular analysis. Therefore, it was not appropriate to strike the Impugned Propositions.
(c) Prejudice and Abuse of Process [46] There was no evidence that the Applicants were prejudiced because the NOA lacked particulars. Specifically, it was “telling” that they did not raise more vigorous objections to the Schedule B evidence during the Motion to Strike, nor had they filed any evidence suggesting that they would not have brought the application or that they had difficulty deciding whether to bring the application. However, it is clear that a NOA of this sort—that is one where there is a very long list of prior art references attached but not discussed in the body of the NOA—could lead to real prejudice in other cases. Given the scheme of the PM(NOC) Regulations, it is important that the NOA contain sufficient information to enable a patent holder to make an informed decision quickly. An overwhelming amount of information that has to be processed in a short time period can be just at stymying as an absence of information.
[47] Having carefully reviewed the NOA, I am not satisfied there was an abuse of process.
(3) Conclusion of the Preliminary Issues [48] The cross-examinations of Drs. Fassihi and Smart had interruptions and objections by counsel for Pharmascience which were not always necessary or useful, and which created a less than ideal situation. However, these interruptions did not rise to the level of shielding Pharmascience’s experts from meaningful cross-examination, and I find that they were not abusive.
[49] Regarding the Table 1 Documents, I find that these documents do relate facts that are laid out in the NOA. Further, the experts’ statements regarding these documents largely repeat facts that are raised in the NOA, as laid out Pharmascience’s RSA. To the extent that the experts’ statements go beyond the facts that are explicitly raised in the NOA, as highlighted in the RSA by Pharmascience, I give those specific facts no weight.
[50] Finally, although the Pharmascience experts did raise slightly different propositions in their expert affidavits than were raised in the NOA, these Impugned Propositions appear to be directed to same analysis in both the NOA and the expert affidavits. Because the underlying documents were raised in detail in the NOA, I find that the Applicants were given enough information for all of the facts in the documents to be considered sufficiently raised to meet the requirement of subsection 5(3)(b)(ii) of the PM(NOC) Regulations.
III. Burden of Proof [51] The burden of proof for infringement of a patent lies with the party alleging infringement (Monsanto Canada Inc v Schmeiser, 2004 SCC 34 at para 29; Eli Lilly v Apotex, 2009 FC 991 at para 211, aff’d 2010 FCA 240 [Eli Lilly]; Merck & Co Inc v Apotex, 2010 FC 1265 at para 135, aff’d 2011 FCA 363).
[52] The presumption of validity in subsection 43(2) of the Patent Act, RSC, 1985, c P-4, is weak and once Pharmascience adduced evidence that has an “air of reality” to rebut that presumption, the legal burden shifted to the Applicants to establish on a balance of probabilities that all the allegations of invalidity asserted are not justified (Abbott Laboratories v Canada (Minister of Health), 2007 FCA 153 at paras 9 to 10; Hoffman-La Roche Ltd v Apotex Inc, 2013 FC 718 at paras 58 to 61).
IV. Applicants’ Expert Witnesses A. Dr. Loyd Allen, Jr. [53] Dr. Loyd V. Allen, Jr. obtained a B.Sc. and M.S. in Pharmacy from the University of Oklahoma College of Pharmacy in 1966 and 1970, respectively. He completed a residency in hospital pharmacy at the US Public Health Service Hospital in Boston, MA in 1967; and he received a Ph.D. in Pharmaceutics from the University of Texas at Austin in 1972.
[54] Dr. Allen is currently the CEO of the Midwest Institute of Research and Technology, and a Professor Emeritus of the University of Oklahoma College of Pharmacy. He is a named inventor on 13 US patents in the field of drug formulations, and is widely published (i.e., over 200 experimental publications; 25 books, chapters and monographs; and over 500 professional publications, including two text books). He is also the founder and current Editor-in-Chief of the International Journal of Pharmaceutical Compounding, and has held or currently holds many distinguished fellowships and/or committee positions.
[55] Dr. Allen is an expert in the areas of pharmaceutical formulation and pharmaceutical compounding.
B. Dr. Patrick J. Sinko [56] Dr. Patrick J. Sinko received a B.Sc. in Pharmacy from the College of Pharmacy, Rutgers University, New Brunswick, New Jersey in 1982; and a Ph.D. in Pharmaceutics from the College of Pharmacy, the University of Michigan, in 1988.
[57] He is currently the Associate Vice President for Research at Rutgers University, and a Distinguished Professor of Pharmaceutics in the Ernest Mario School of Pharmacy. He is also appointed to the Parke-Davis Endowed Chair in Pharmaceutics and Drug Delivery, which is a distinguished professorship. He teaches biopharmaceutics, pharmaceutics, physical pharmacy, and drug delivery systems.
[58] He was the editor and principal author of the Fifth (2005) and Sixth (2010) Editions of Martin’s Physical Pharmacy and Pharmaceutical Sciences. He has published 159 articles in scientific journals; and 282 books, reviews, and contributed chapters. He has served as a reviewer for numerous scientific journals, and has held or holds many distinguished fellowships and/or committee positions.
[59] Dr. Sinko is an expert in the areas of pharmaceutical science and formulation.
V. Pharmascience’s Expert Witnesses A. Dr. Yuriy Ososkov [60] Dr. Yuriy Ososkov received a combined Bachelor’s and Master’s degree in Engineering from the Moscow Institute of Steel and Alloys in 1991; and a Ph.D. in Materials Engineering from the Warsaw University of Technology in 1997. He holds the designation of Professional Engineer, certified by the Professional Engineers of Ontario.
[61] From 2006 to 2015, Dr. Ososkov was employed by Exova Canada Inc., where he was the Manager, until February 2014, and then the Senior Materials Scientist, Physical Characterization in the Health Sciences Division. As the Senior Materials Scientist, he acted as the technical lead in implementing materials services, such as X-Ray Diffraction, Scanning Electron Microscopy (“SEM”), and Energy-dispersive X-ray Spectroscopy.
[62] [redacted]
B. Dr. Reza Fassihi [63] Dr. Reza Fassihi received a B.Sc. in Pharmacy from Punjab University, in India, in 1974; and a Ph.D. in Pharmaceutics from Brighton University, in England, in 1978.
[64] He is currently a Professor of Biopharmaceutics and Industrial Pharmacy at Temple University, School of Pharmacy in Philadelphia, and the Co-Chair of the Philadelphia Pharmaceutical Forum. He is a named author on more than 130 publications in peer-reviewed journals, and a named inventor on 9 US patents. He is also a Fellow of the American Association of Pharmaceutical Sciences, and a member of the American Association of Colleges of Pharmacy.
[65] Dr. Fassihi is an expert in the area of pharmaceutical formulation, and has experience in biopharmaceutics and pharmacokinetics.
C. Dr. John D. Smart [66] Dr. John D. Smart received a B.Sc. in Pharmacy from Brighton Polytechnic (now University of Brighton) in 1979; and a Ph.D. in Pharmacy from the Welsh School of Pharmacy (now the University of Wales, College of Cardiff) in 1983.
[67] He is currently a Professor of Pharmaceutical Sciences and Academic Director of Pharmacy at the School of Pharmacy and Biomolecular Sciences at the University of Brighton. He is the co-author of 65 peer-reviewed research articles, and a named author/co-author of six book chapters. He is a founding member of the Pharmacy Schools Council, and is a member of the Royal Society of Chemistry, the Royal Pharmaceutical Society, and the Royal Society’s Expert Advisory Panel.
[68] He is an expert in the area of pharmaceutical formulation and in particular the area of bioadhesive agents.
D. Dr. Rajesh Davé [69] Dr. Rajesh Davé received a B.Tech. in Mechanical Engineering from the Indian Institute of Technology, Bombay, in 1978; a M.S. in Mechanical Engineering from Utah State University in 1981; and a Ph.D. in Mechanical Engineering from Utah State University in 1983.
[70] He is currently a Distinguished Professor of Chemical, Biological, and Pharmaceutical Engineering at the New Jersey Institute of Technology. He is the founding director of the Research and Development Excellence Center, New Jersey Center for Engineered Particulates, and a New Jersey Institute of Technology Site-Leader, Thrust Leader and Test-bed Leader of the National Science Foundation Engineering Research Center on Structured Organic Particular Systems. He is a Senior Member of the American Institute of Chemical Engineers, and a Member of the American Association of Pharmaceutical Sciences. He is a named author on over 100 peer-reviewed papers.
[71] Dr. Davé is an expert in engineered formulations, including micronization and other methods for formulating poorly soluble drugs.
VI. The ‘988 Patent [72] The ‘988 Patent has an International Filing Date of September 24, 1999; was published on March 30, 2000; and will expire on September 24, 2019. Orexo AB owns the ‘988 Patent, and consented to listing it on the Patent Register against the innovative drug, SUBLINOX, which is marketed by the Applicants.
[73] The ‘988 Patent relates to novel rapid-onset sublingual pharmaceutical compositions for treating the acute disorder insomnia, involving ordered mixtures—of microparticles of the active pharmaceutical ingredient (“API”) and water-soluble carrier particles—and bio/mucoadhesives, a method for making such compositions, and their use in the manufacture of a medicament.
[74] The ‘988 Patent has one independent claim, and 21 dependent claims. Independent claim 1 states:
Claim 1:
A pharmaceutical composition for the treatment of insomnia by sublingual administration, comprising an ordered mixture of microparticles of at least one pharmaceutically active agent selected from diazepam, oxazepam, zopiclone, zolpidem, propiomazin, valeriana, leomepromazin or a sleep inducing peptide, which agent is adhered to the surfaces of carrier particles, said particles being larger than said microparticles and being water-soluble, and a bioadhesion and/or mucoadhesion promoting agent.
[75] The ‘988 Patent abstract describes the invention as follows:
A pharmaceutical composition for the treatment of an acute disorder is described. The composition comprises an essentially water-free, ordered mixture of at least one pharmaceutically active agent in the form of microparticles which are adhered to the surfaces of carrier particles which are substantially larger than the particles of the active agent or agents, and are essentially water-soluble, in combination with the bioadhesion and/or mucoadhesion promoting agent. The invention also relates to a method for preparing the composition and to the use of the composition for the treatment of acute disorders.
[76] Accordingly, the essential elements of claim 1 are:
a pharmaceutical composition for the treatment of insomnia by sublingual administration; comprising an ordered mixture of microparticles; of at least one API selected from diazepam, oxazepam, zopiclone, zolpidem, propiomozin, valeriana, leomepromazin or a sleep inducing peptide; which is adhered to the surfaces of carrier particles; said particles being larger than the API microparticles and being water-soluble; and a bioadhesion and/or mucoadhesion promoting agent.
[77] The parties agreed that each of these elements was known in the prior art, but the Applicants argued that the combination of these elements is novel, unobvious and useful.
[78] Particularly, the Applicants said that sublingual administration and use of an ordered mixture of API adhered to the surfaces of carrier particles, in combination with a bioadhesion and/or mucoadhesion promoting agent, was both novel and unobvious. Not surprisingly, Pharmascience took a contrary view.
A. The Person Skilled in the Art (POSITA) [79] The experts generally agreed that a POSITA for the ‘988 Patent would be (1) an individual with a Ph.D. in Pharmaceutical Sciences, or an equivalent field, and one to two years of experience in the development of oral pharmaceutical formulations; or (2) an individual with an advanced degree in a field other than Pharmaceutical Sciences (i.e., a Ph.D. in chemical engineering, physical chemistry, or similar) and three to five years of experience in development of oral pharmaceutical formulations.
B. Common general knowledge [80] The Applicants’ experts disagreed that the list of statements found at paragraph 108 of the NOA represented an accurate picture of what would comprise a POSITA’s common general knowledge at the relevant time.
[81] Dr. Sinko explained that, while NOA paragraph 108 points (a) to (m) are general concepts that would have been known to a POSITA at the relevant time, it would not have been part of the common general knowledge that these concepts would apply to the issues addressed by the ‘988 Patent. Additionally, he stated that paragraph 108 points (n) to (cc) would not have been interconnected in the common general knowledge at the relevant time, and criticized the list as being collected via hindsight.
[82] Dr. Allen addressed all of the articles and patents listed in the NOA as forming a part of the common general knowledge, individually, and commented that this was a disjointed list, without an obvious relationship between the different articles cited.
[83] Drs. Allen and Sinko agreed that the general information in Lieberman et al., Pharmaceutical Dosage Forms, Second Edition, 1989 (the “Lieberman Text”) would have been part of the common general knowledge at the relevant time. However, they were of the opinion that there would have been no reason for a POSITA to combine the 16 specific references listed in the NOA. Further, they pointed out that the Lieberman Text contains a lot of material that is either completely irrelevant to the ‘988 Patent, or teaches away from the ‘988 Patent. Dr. Sinko stated that what is evident from the Lieberman Text is that sublingual administration was rare, and there was little known about sublingual administration at the relevant time.
[84] Dr. Fassihi, Dr. Smart, and Dr. Davé approached their assessments of what would comprise the common general knowledge differently than Drs. Allen and Sinko, basing their answers upon the questions posed to them by counsel for Pharmascience rather than the information presented in the NOA.
[85] Dr. Fassihi stated that by 1998 orally disintegrating tablets were known, and that Ativan (lorazepam) was a sublingual, orally disintegrating tablet on the market at that time and, because Ativan was on the market, it would have been part of the common general knowledge that orally disintegrating tablets would have to dissolve quickly (less than three minutes). He believed that standard excipients, at the time, would have included water soluble fillers and powerful disintegrates, and that known bio/mucoadhesive excipients included hydrophilic polymers such as hydroxypropyl cellulose, carboxymethyl cellulose, carbomers and trangacanth gum or gelatin. Additionally, he asserted that a POSITA would have been familiar with ordered mixtures and how to make them.
[86] Dr. Smart claimed that sublingual tablets for nitroglycerin were known decades before the relevant date. He stated that the transmucosal formulations that were known had mannitol, with “super disintegrants” such as Ac-Di-Sol, and were made by normal tableting procedures using wet granulation, dry granulation, or direct compression. A POSITA would have known about nitroglycerin sublingual and buccal, slow release tablets; and Ativan (lorazepam) fast dissolving sublingual tablets. He also believed that a POSITA would be aware of how to make an ordered mixture.
[87] Dr. Davé opined that the process for making an ordered mixture, and the benefits of ordered mixtures would have been part of the common general knowledge at the relevant time.
[88] Based upon consideration of the expert evidence, what does form part of the prior art and common general knowledge is as follows.
(1) Acute disorders and insomnia [89] A POSITA would have known about acute disorders. An acute disorder is a disorder that is treated through emergency medical, general medical and surgical treatment rather than through long-term care for chronic conditions. Acute disorders can include pain and insomnia. Insomnia is the inability to sleep, in the absence of external impediments (e.g., noise, bright light, etc.) during the period when sleep should normally occur. There are two broad classes of treatment for insomnia: psychologic and pharmacologic.
[90] At the relevant time, there were multiple drug products listed for insomnia, including Diazepam (Valium); Lorazepam (Ativan); Zolpidem (Ambien); and Phenobarbital (Luminal). Dosage forms for insomnia included tablets and capsules, elixirs and syrups, suppositories, and transdermal gels and/or creams.
(2) Dosage form development [91] Drug substances, at the relevant time and continuing to the present, are generally given as part of a formulation, which is a combination of the API and one or more excipients, which are non-medicinal and which serve varied pharmaceutical functions (e.g., solubilize, thicken, dilute, emulsify, stabilize, preserve, etc.). Excipients are added to produce efficacious and appealing dosage forms.
[92] If the medication is intended for systemic use and oral administration is appropriate, tablets or capsules are usually prepared because they are easy to handle and convenient for patients to self-administer. The vast majority of the tablets on the market, at the relevant time, were taken orally, to be swallowed whole, for the active drug to be absorbed in the gastrointestinal tract. Other methods of adm