Hoffman-La Roche Limited v. Apotex Inc.

Hoffman-La Roche Limited v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2013-07-12
Neutral citation
2013 FC 718
File numbers
T-1247-11
Decision Content
Date: 20130712
Docket: T-1247-11
Citation: 2013 FC 718
Ottawa, Ontario, July 12, 2013
PRESENT: The Honourable Madam Justice Kane
BETWEEN:
HOFFMAN-LA ROCHE LIMITED
Applicant
and
APOTEX INC.
and
THE MINISTER OF HEALTH
Respondents
and
F. HOFFMAN-LA ROCHE AG
Respondent Patentee
PUBLIC REASONS FOR JUDGMENT AND JUDGMENT
(Confidential Reasons for Judgment and Judgment Issued June 27, 2013)
INDEX PARA
INTRODUCTION.............................................................................................................. 4
THE PARTIES.................................................................................................................. 12
THE ‘721 PATENT GENERALLY................................................................................. 19
THE EVIDENCE.............................................................................................................. 26
ISSUES............................................................................................................................. 28
THE NOTICE OF ALLEGATION.................................................................................. 44
BURDEN.......................................................................................................................... 57
PERSON SKILLED IN THE ART.................................................................................. 65
THE ‘721 PATENT IN DETAIL...................................................................................... 71
CONSTRUCTION OF THE CLAIMS............................................................................ 90
THE INVENTION ........................................................................................................... 99
IS IT A SELECTION PATENT?................................................................................... 133
ANTICIPATION............................................................................................................ 179
OBVIOUSNESS............................................................................................................. 243
CLAIMS BROADER THAN THE INVENTION MADE OR DISCLOSED............. 355
INFRINGEMENT.......................................................................................................... 365
CONCLUSIONS AND COSTS..................................................................................... 400
[1] This is an application brought under the provisions of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133, as amended [NOC Regulations] to prohibit the Minister of Health from issuing a Notice of Compliance to Apotex in respect of its valganciclovir hydrochloride 450mg tablets (the Apotex product) until the expiry of Canadian Letters Patent No 2154721 (the '721 Patent) on July 26, 2015.
[2] For the reasons that follow, I find that the allegations with respect to invalidity are justified and the allegation with respect to non-infringement of claim 4 is justified.
[3] The application is dismissed with costs to Apotex.
INTRODUCTION
[4] In the 1990s, ganciclovir was recognized as the leading drug for the treatment of certain herpes viruses, particularly cytomegalovirus [CMV], a type of herpes virus. The parties and the experts described ganciclovir as an antiviral nucleoside, which is a compound that disrupts DNA synthesis in, for example, virally-infected cells. Disrupting viral replication induces the death of the infected cell. A nucleoside is a compound formed by joining a base moiety with a sugar moiety. A disadvantage of ganciclovir was its limited oral bioavailability. Although it could be more effective when administered intravenously [IV], this mode had other disadvantages including inconvenience for patients and potential infections, particularly in immunocompromised patients. An improvement in the bioavailability of ganciclovir for oral administration was, therefore, desired.
[5] Acyclovir and penciclovir were other antiviral nucleosides that were also effective against various strains of the herpes virus. However, they also shared the disadvantage, when orally administered, of poor absorption across the gut (small intestine) into the blood stream. These drugs were, therefore, also generally administered by IV (directly into the bloodstream). Several research groups were seeking to improve the oral bioavailability of these compounds in the 1980s and 90s. As explained by the experts, one of the several possible approaches for improving the bioavailability of a drug like ganciclovir was to link the molecule to another compound, referred to as a pro-moiety, (often an amino acid) and to thereby create a prodrug. A prodrug is a compound that has improved absorption and is metabolized to the active drug after absorption (valganciclovir is a prodrug formed by the molecular combination of ganciclovir with the amino acid, mono-L-valine).
[6] The intended mechanism of action of a prodrug is that the pro-moiety will help deliver the active medicine more effectively to the site of action. Prodrugs are designed such that the pro-moiety (in this case, the amino acid ester) is hydrolyzed, or cleaved, from the active drug compound at an appropriate point after absorption into the body.
[7] Doctor McGuigan, an expert for Apotex, noted at paragraph 54 of his affidavit that by 1994 it was well known that prodrugs are often used where a drug has suboptimal bioavailability. He described a prodrug as a molecular derivative of the parent drug which requires structural transformation to the active drug in vivo (in the body). Once activated in the body it can then exert its pharmacological action. A prodrug often results in improved tissue penetration by altering the lipophilicity and/or the water solubility of the drug. Prodrugs can also take advantage of the various active transport mechanisms available in the body, in particular when the prodrug resembles natural metabolites, such as with amino acid esters. The prodrug form is better absorbed, and after biotransformation, results in a greater exposure to the active drug that would have occurred had the parent drug form been administered.
[8] He also noted that the majority of produgs are esters (para 55). An ester is a compound produced through the reaction of an acid (with a -COOH functional group) with a compound having a hydroxyl group (-OH).
[9] Dr McGuigan indicated that in order to be suitable, a nucleoside prodrug would need improved bioavailability (assuming that the desired improvement is higher oral bioavailability) and would have to be: soluble enough to be dissolved in the stomach; stable enough to survive the acidic environment of the stomach; have the ability to pass through the gut; reach the blood stream; and, release the active agent. Additionally, a suitable prodrug would have to be acceptable for use as a pharmaceutical.
[10] Roche holds the patent for valganciclovir, which is more fully described below, and which the inventors claim meets these desired characteristics.
[11] In GlaxoSmithKline Inc v Pharmascience Inc, 2011 FC 239, [2011] FCJ 287, Justice Hughes explained the nomenclature of NOC proceedings and the requirements of the Notice of Allegation [NOA] as follows:
[38] The NOC Regulations identify two groups of persons, a “first person”, commonly called the “brand”, who is the person owning or licensed under a patent and who has received permission to sell a drug somehow relating to that patent in Canada (section 4(1)). A “second person”, commonly called a “generic” is a drug company wanting to take advantage of much of the material submitted by the first person in order to obtain approval itself to sell the drug. The second person must notify the first person providing particulars of its application to secure approval and to state that the patent will not be infringed or is invalid or that the second person will wait for the patent to expire. That notification takes the form of a “Notice of Allegation” (NOA).
[39] That Notice of Allegation (NOA) is required by subsection 5(3)(b)(ii) of the NOC Regulations to include “a detailed statement of the legal and factual basis for the allegations”… .
THE PARTIES
[12] The applicant, Roche, is a “first person” as described in the NOC Regulations. It has listed the '721 Patent in accordance with those Regulations. Roche has obtained a Notice of Compliance [NOC] to sell valganciclovir hydrochloride, which it does under the brand name Valcyte, from the Minister of Health.
[13] The applicant, Roche, claims to be the owner of the '721 Patent and this is not contested in these proceedings.
[14] The respondent, Apotex, is a “second person” as described in the NOC Regulations. It seeks to sell a generic version of Roche’s valganciclovir drug. To do so, it must receive a NOC from the Minister of Health. In accordance with the NOC Regulations, Apotex served Roche with a Notice of Allegation [NOA] dated June 14, 2011.
[15] In the NOA, Apotex alleges that claims 4-8 and 10 of the ‘721 Patent would not be infringed, and that the patent is invalid on the grounds of anticipation, obviousness, and overbreadth or claims broader than the invention made or disclosed. Apotex also alleges that it does not infringe any valid claim in making, constructing, using or selling its Apotex product.
[16] The respondent, the Minister of Health, who has various responsibilities under the NOC Regulations, including the issuance of an NOC to a “second person” such as Apotex, took no active role in these proceedings.
[17] The respondent, Apotex, submits that the applicant, Roche, has not honored its part of the bargain upon which the ‘721 Patent is based. The nature of this bargain was described in Apotex Inc v H Lundbeck A/S, 2013 FC 192, [2013] FCJ 274 by Justice Harrington, as follows:
[7] A patent represents a bargain between the inventor and the state. In consideration of the grant of a monopoly, the inventor must fully and properly disclose the invention so that when the monopoly expires, others may reproduce the product or process involved without undue difficulty. The Patent Act requires the applicant to provide a specification which discloses what has been invented and how to replicate it. The specification ends with a claim or series of claims over which a monopoly is asserted. According to Apotex, the specification is fatally defective.
[18] In the present case, Apotex makes this same allegation.
THE '721 PATENT GENERALLY
[19] Canadian Letters Patent 2,154,721 (the ‘721 Patent) was applied for by an application deemed to be filed with the Canadian Patent Office on July 26, 1995. The Patent is therefore governed by the provisions of the new Patent Act, RSC 1985 c P-4, that governs patents applied for after October 1, 1989.
[20] The application was filed under the provisions of the Patent Cooperation Treaty [PCT] and claims priority from a first application filed in the United States Patent Office on July 28, 1994. This is the date upon which the issues of anticipation and obviousness will be determined.
[21] The publication date, i.e. the date at which the public could inspect the patent, was January 29, 1996. This is the date that is to be used for the purposes of the construction of the claims.
[22] The ‘721 Patent lists the inventors as John J Nestor, Scott W Womble and Hans Maag, all of the United States of America. None of the inventors provided evidence in these proceedings.
[23] The ‘721 Patent was issued to F Hoffman-LaRoche AG, CH.
[24] The term of the ‘721 Patent, unless declared as invalid, will expire 20 years from the date of the filing of the application in Canada, which is July 26, 2015.
[25] There are 17 claims in the ‘721 Patent, 14 of which are at issue in this proceeding. The construction of the claims and the inventive concept of the patent are addressed below.
THE EVIDENCE
[26] The evidence in this proceeding was provided in the form of affidavits and transcripts of cross-examinations of experts along with their exhibits. All of the experts were cross-examined. Each party also submitted as evidence the affidavits of law clerks to place documents on the record and attest to facts and specific communications between the parties.
[27] The evidence on the record includes the following:
For the applicant (Roche)
i) Dr Ronald Sawchuk
Dr Sawchuk is a Professor of Pharmaceutics, Emeritus, and Morse Alumni Distinguished Teaching Professor and the Director of the Bioanalytic and Pharmacokinetic Services Laboratory at the University of Minnesota. Dr Sawchuk was called on by the applicants for his extensive experience in the areas of pharmaceutical research, pharmacokinetics, and drug development. Dr Sawchuk was asked to review Apotex’s Notice of Allegation and provide an opinion as to the content of the ‘721 Patent, and the validity of the ‘721 Patent.
ii) Dr Youla S Tsantrizos
Dr Tsantrizos is a Professor of Chemistry at the Faculty of Science at McGill University and an Associate Member of the Biochemistry Department at the Faculty of Medicine at McGill University. Dr Tsantrizos spent 10 years at the Medicinal Chemistry Department of the pharmaceutical company Boehringer Ingelheim where she participated in pre-development and development committees that moved compounds through the different stages of drug discovery, pre-clinical and clinical development. She was called by the applicant for her expertise in human pharmaceuticals for the treatment of viral infections.
Dr. Tsantrizos was asked to comment on the claims of the ‘721 Patent and explain what is understood as the subject matter involved; to review and consider the allegations in the NOA; including anticipation, obviousness, the proper scope of the invention, and non-infringement.
iii) Dr Jeffrey Manthorpe
Dr Manthorpe is a Professor of Chemistry at Carleton University. His current academic research interests include synthetic chemistry and particularly synthetic organic chemistry, the development of new synthetic chemistry techniques and their application to biologically relevant molecules. Dr Manthorpe was asked to design and perform an experiment to determine whether the Apotex crystallization process produces amorphous or crystalline material.
iv) Dr Ilia Korobkov
Dr Korobkov is an X-ray diffraction scientist, crystallographer, and supervisor at the X-ray Core Facility of the Faculty of Science at the University of Ottawa. His work is focused on single crystal X-ray diffraction, but he has also conducted analyses using other instruments such as powder X-ray and fluorescence. Dr Korobkov was called by the applicant to analyze Dr Manthorpe’s experiment and to provide an opinion whether some samples were crystalline or amorphous.
v) Richard Killworth
Richard Killworth is a Partner at Dinsmore & Shohl LLP in Dayton, Ohio, USA. Mr Killworth was called as an expert by the applicant as a US patent attorney and because of his extensive knowledge of US patent law and the United States Patent Office [“USPTO”] practices, requirements, and procedures.
vi) Erin McIntomny
Erin McIntomny is a law clerk for the office of the applicant’s solicitors, Gowling Lafleur Henderson LLP, and was asked to attest to the truth of various procedural facts relating to motions, orders, letters, and email correspondence between Apotex and Roche.
For the respondent (Apotex)
i) Dr Chris McGuigan
Dr McGuigan is a Professor of Medicinal Chemistry and Deputy Pro-Vice Chancellor (Research) at the Cardiff School of Pharmacy & Pharmaceutical Sciences at Cardiff University. Dr McGuigan has an extensive research background in new drug discovery and development, particularly for the treatment of viral and retroviral diseases, for diseases associated with viruses, and for osteoarthritis. Dr McGuigan was asked to explain the state of the art in the pharmaceutical treatment of herpes virus infections, including cytomegalovirus infections [HCMV], from the perspective of an ordinary medicinal chemist.
Dr McGuigan was asked to comment on the ‘721 Patent, to address its scope, the allegations of invalidity, the inventive concept and related issues.
Dr McGuigan was also asked to provide comments on the statements in the affidavits of Dr Ronald Sawchuk and Dr Youla Tsantrizos.
ii) Dr George G Zhanel
Dr Zhanel is a Professor of Medicinal Microbiology/Infectious Diseases at the Faculty of Medicine at the University of Manitoba, and is the Coordinator of the antimicrobial resistance program in the Departments of Medicine (Section of Infection Control) and Clinical Microbiology at the Health Sciences Center in Winnipeg, Manitoba. Dr Zhanel is also the Research Director of the Canadian Antimicrobial Resistance Alliance [CARA] in Winnipeg, Manitoba.
Dr Zhanel was asked by Apotex to state what a skilled pharmacologist would have known about acyclovir and ganciclovir, and their use in treating herpes viruses, as of July 28, 1994.
Dr Zhanel was also asked to comment on the ‘721 Patent to address its scope, the allegations of invalidity, the inventive concept and related issues and to address several questions from the perspective of a skilled pharmacologist.
Dr Zhanel was also asked to provide comments on the opinions of Dr Ronald Sawchuk and Dr Youla Tsantrizos in their affidavits.
iii) Dr Siddegowda
Dr Siddegowda has a PhD in organic chemistry from the University of Mysore. Since April 2010, Dr Siddegowda has worked as Team Leader of Quality Assurance and Regulatory Affairs for Apotex Pharmachem India Private Limited [APIPL], in the City of Bangalore, India. Before that, he was the Group Leader II of Process Development R&D at APIPL, and from 2004 to 2009 was the Assistant Manager. Dr Siddegowda was called by Apotex to explain specific terminology, statements and passages within APIPL’s Drug Master File [DMF] for valganciclovir.
iv) Dr Robert K Boeckman, Jr
Dr Boeckman is the Marshall D Gates Jr Professor of Chemistry and the Chair of the Chemistry Department at the University of Rochester. Dr Boeckman is an active researcher in the area of synthetic chemistry applied to medicinal chemistry, and is also a trained X-ray crystallographer.
Dr Boeckman was asked to provide his opinion on what the EP 329 patent taught and disclosed to the synthetic chemist reading it as of July 28, 1994.
Dr Boeckman was asked to comment on the ‘721 Patent to address its scope, the allegations of invalidity, the inventive concept, crystallinity, and related issues and to address several questions from the perspective of a synthetic chemist.
Dr Boeckman was also asked to review and comment on the affidavits of Dr Tsantrizos and Dr Manthorpe.
v) Dr Jonathan Steed
Dr Steed is a Professor of Chemistry at Durham University, with considerable expertise in crystallography, crystallization, solid-state chemistry, coordination chemistry and intermolecular interactions in solids. Dr Steed established and ran the first X-ray crystallographic facility in the UK to be based on a particular new area detector technology. He was called by Apotex as an expert in the structures and solid state behavior of organic and molecular solids, and in the methods and techniques used to study and characterize them. He was also asked to comment on the ‘721 Patent and answer several questions from the perspective of the solid state chemist including the scope, allegations of invalidity, inventive concept and the allegations of infringement, particularly regarding whether the product was crystalline.
Dr Steed was also asked to review and comment on the affidavits of Dr Tsantrizos, Dr Manthorpe and Dr Korobkov.
vi) Dr Richard Christian Moreton
Dr Moreton is a pharmaceutical formulation scientist, and Vice-President of FinnBrit Consulting, a pharmaceutical consulting company. Dr Moreton has over 30 years experience in the pharmaceutical industry and throughout his industrial career has worked in formulation, pre-formulation, formulation development and scale-up, drug development and optimization, including the study and design of prodrug strategies, and the technical transfer of products into commercial manufacture. He also has experience with antiviral drugs, including antiviral drug formulations and prodrugs.
Dr Moreton was asked to review the ‘721 Patent and answer several questions from the perspective of the pharmaceutical formulator including the scope, allegations of invalidity, inventive concept and the allegations of infringement, particularly regarding whether the product was crystalline.
Dr Moreton was also asked to review and comment on the affidavits of Dr Tsantrizos and Dr Sawchuk.
vii) Duane Terrill
Duane Terrill is a long time employee of Apotex and is currently Associate Director of Regulatory Affairs. From 2005 until 2012, Mr Terrill was Manager for Apotex’s Regulatory Affairs Department, which regulates all of Apotex’s interactions with Health Canada regarding Apotex’s submissions for approval to promote and sell new drugs as well as its compliance obligations.
Mr Terrill was called by Apotex to comment on Health Canada’s requirements for regulatory approval of new drugs in Canada, and to provide specifications on the procedure followed by Apotex while seeking approval for the sale of Apo-Valganciclovir tablets. He was also asked to comment on the contents of the tablets.
viii) Lisa Ebdon
Lisa Ebdon is a law clerk at the office of the respondent’s solicitors, Goodmans LLP. She was called to testify as to the truth of various documents sent by Apotex to the applicant, specifically those relating to Apotex’s drug submissions and filings.
THE ISSUES
[28] The principal issue is whether to grant an Order prohibiting the Minister of Health from granting a Notice of Compliance to Apotex for its generic valganciclovir until the expiry of the '721 Patent. This determination depends upon whether the allegations raised by Apotex as to the invalidity of the '721 Patent and non-infringement are justified.
[29] Apotex alleges that the ’721 Patent is invalid on the basis of anticipation, obviousness and overbreadth (insufficiency of claims or claims broader than the invention made or disclosed).
[30] Apotex also claims in the alternative, that if the patent is valid, they do not infringe the patent because their product is non-crystalline (it is amorphous). This flows from the submission by Apotex that the invention of the ‘721 is its crystallinity.
[31] The key area of disagreement between the applicant and respondent (and from which many issues depend) is the meaning of the patent – i.e. what is the invention or what is the inventive step.
[32] The applicant, Roche, asserts that the invention of the ‘721 Patent is the identification that the mono-L-valine ester of ganciclovir (referred to as “L-valganciclovir” or simply “valganciclovir”) has unexpectedly better bioavailability over the previously known esters of ganciclovir, most importantly the bis-valine ester. This improvement is not only over the closest prior art (i.e. the bis-ester of EP 329), but also over other known ganciclovir esters and over ganciclovir itself. Roche notes that the bioavailabilities of the invention are specifically compared with EP 329 and other esters and ganciclovir in the ‘721 Patent.
[33] The applicant also asserts that the ‘721 Patent is probably, likely, or is definitely a selection patent from the genus of EP 329.
[34] The applicant asserts that the allegations of invalidity due to anticipation and obviousness are not justified. The applicant argues that the respondent, Apotex, did not provide any evidence whether it was obvious that L-valganciclovir would have improved bioavailability over the other known ganciclovir esters, and, in particular, the bis-valine ester and the bis-propyl ester.
[35] With respect to overbreadth, Roche submits that the ‘721 Patent teaches and claims both amorphous and crystalline valganciclovir (and that crystallinity is merely an additional advantage).
[36] With respect to infringement, Roche submits that there is evidence to establish that the Apotex product is not limited to amorphous (i.e. non-crystalline) valganciclovir. As a result, Roche submits that Apotex infringes all claims.
[37] The respondent, Apotex, asserts that the applicant’s position is based on a flawed construction of the ‘721 Patent. Apotex maintains that the ‘721 Patent neither claims nor indicates in its disclosure that its invention is “the identification that the mono-L-valine ester of ganciclovir … has unexpectedly better bioavailability over the previously known esters of ganciclovir, most importantly the bis-valine ester”, as indicated by Roche in their memorandum. Apotex argues that no witness stated that this was the inventive concept of any of the claims of the ‘721 Patent.
[38] Apotex submits that the invention relates to valganciclovir, a prodrug of ganciclovir, and its pharmaceutically acceptable salts, methods and intermediates used to prepare these compounds, and compositions of these compounds for use to treat viral diseases in humans. Apotex’s position is that the invention is the crystalline compound and submits that the patent distinguishes its invention from the prior knowledge by identifying its compounds as crystalline, which it says provides a “decisive advantage” in characterization and processing.
[39] With respect to anticipation, Apotex submits that EP 329 disclosed the subject matter of the claims of the ‘721 Patent, including valganciclovir, as a medicine to treat herpes virus infections with improved oral bioavailability over ganciclovir.
[40] With respect to obviousness, and to the extent that EP 329 did not explicitly make crystalline valganciclovir, Apotex submits that this was obvious from the art.
[41] With respect to overbreadth, Apotex submits that most of the claims in the ‘721 Patent cover all solid forms of valganciclovir hydrochloride rather than being limited to the crystalline form (which Apotex submits is the inventive concept). In its written argument, Apotex also argued that other claims are overbroad for claiming the use of valganciclovir to treat all viral diseases, rather than being limited to those diseases against which ganciclovir had been shown to be effective.
[42] Apotex also asserts that it will not infringe any claim of the ‘721 Patent because all of the claims are invalid.
[43] Alternatively, Apotex submits that it does not infringe claims 4 to 8 and 10 of the ‘721 Patent. All of the details of the preparation and testing of Apo-Valganciclovir are included in its abbreviated new drug submission [“ANDS”] and its supplier’s drug master file [“DMF”]. These documents establish that Apotex’s valganciclovir is never crystalline and contains a mixture of the (R) and (S) forms of the compound. Apotex notes that it produced all of these details to the applicant.
NOTICE OF ALLEGATION
[44] As a preliminary issue, the applicant, Roche, asserts that the respondent raised new issues in its argument that it had not set out in the Notice of Allegation [NOA].
[45] The applicant notes that the respondent is limited to the factual and legal basis set out in its NOA and that any new non-infringement and invalidity allegations cannot be considered. The applicant further notes that the NOA does not assert or suggest that the advantages set out or information provided in the ‘721 Patent are not true.
[46] More particularly, the applicant asserts that Apotex in its NOA indicated that the question to be answered was whether “making the mono-ester instead of the diester (bis-ester) would have been obvious” but then “shifted ground” and changed the question, which is central to the allegation of obviousness, to whether the mono-ester was obvious over ganciclovir.
[47] Roche asserts that the NOA is deficient because it fails to make any allegations relating to whether Apotex’s supplier makes crystalline valganciclovir during the manufacturing process.
[48] Roche also asserts that because the respondent did not raise an allegation pursuant to section 53 of the Patent Act, its witnesses could not question whether the statements in the Patent were true, particularly with respect to Examples 9 and 10.
Jurisprudence / Principles regarding NOA
[49] In GlaxoSmithKline Inc v Pharmascience Inc, 2011 FC 239, [2011] FCJ 287, Justice Hughes summarized the requirements of subsection 5(3)(b)(ii) of the NOC Regulations governing the contents of the NOA which must include “a detailed statement of the legal and factual basis for the allegations”. He noted at para 40:
[40] Without comment as to whether they are right or wrong as a matter of “fairness”, certain principles have emerged as a result of judicial interpretation as to an NOA, including:
i. The NOA cannot be amended once legal proceedings have
commenced except that certain allegations made can be omitted or no longer relied upon (e.g. Hoffmann-La Roche Ltd v. Canada (Minister of National Health and Welfare) (1996), 70 C.P.R. (3d) 1, (FCA); Bayer A/G v. Novopharm Ltd. (2006), 48 C.P.R. (4th) 46 (FC) at paras 72 to 84).
ii. The Notice of Allegation must be sufficient so as to make the
“first person” fully aware of the grounds raised as to invalidity or non-infringement (Mayne Pharma (Canada) Inc. v. Aventis Pharma Inc. (2005), 38 C.P.R. (4th) 1 (FCA), at paras. 19-21).
iii. A second person cannot, in proceedings taken in Court, present argument and evidence relating to an issue that is outside the scope of its NOA (e.g. Ratiopharm Inc. v. Canada (Minister of Health) (2007), 58 C.P.R. (4th) 97 (FCA), at para. 25.
iv. The second party may not shift ground or raise a new ground during the legal proceedings that has not been raised in its NOA (Pfizer Canada Inc. v. Canada (Minister of Health) (2006), 54 C.P.R. (4th) 279 (FC), at paras 70 – 71).
Conclusion re NOA
[50] I have considered these principles and do not agree that there was any deficiency in the NOA.
[51] The NOA sufficiently set out the allegations of invalidity and non-infringement to make Roche fully aware and to permit Roche to respond. Apotex did not raise any new ground or new argument or lead any evidence that was beyond the NOA or that was not responsive to arguments raised by the applicant. In addition, as noted by Apotex, the applicant did not bring any earlier motions, except for the production order as noted below, to resolve any concerns it had about the NOA.
[52] Apotex served the NOA alleging that the ‘721 Patent and each of its relevant claims are invalid and will not be infringed by Apotex’s making, constructing, using or selling of Apotex’s Apo-Valganciclovir product. Apotex noted that the details of its valganciclovir and its formulation would be provided once a confidentiality order was in place. The applicant, Roche, obtained a Court Order requiring Apotex to produce those portions of its ANDS and associated DMF that provide information on the solid state form of Apotex’s valganciclovir at each stage of its manufacture and formulation into tablets.
[53] Apotex’s NOA gave sufficient notice that its allegation of non-infringement was not limited to the fact that Apotex’s valganciclovir hydrochloride will not be crystalline when sold. Apotex’s NOA states that Apotex will not infringe the ‘721 Patent in its “making” or “using” of its product. The applicant, Roche, was aware of how to seek Apotex’s process information and pursued the production order. Moreover, the experts for Roche considered whether Apotex’s product might become crystalline at any point in its processing, handling or subsequent storage.
[54] With respect to Roche’s assertion that Apotex changed the key question on obviousness, from whether “making the mono-ester instead of the diester (bis-ester) would have been obvious” to whether making the mono-ester instead of ganciclovir would have been obvious, I find that the words quoted are taken out of the context of the full sentence and the part of the NOA in which they are found.
[55] This issue relates to the inventive concept of the ‘721 Patent which is a significant point of disagreement between the parties. It was fully addressed in argument by both parties.
[56] With respect to the concern that section 53 was not raised, I agree with Apotex that its submissions with respect to the data set out in Examples 9 and 10 respond to evidence on the record submitted by the applicant.
BURDEN
[57] There is extensive jurisprudence with respect to who bears the burden of proof of the allegations and there is no dispute on this issue.
[58] Where the validity of a patent is at issue, the patent will be presumed to be valid. However, where a generic manufacturer (a second person), in this case Apotex, raises allegations of invalidity and adduces some evidence capable of establishing the invalidity of the patent, the generic is said to put the issue “into play”. This puts the burden on the brand or applicant (first person), in this case, Roche, to establish on a balance of probabilities that all of the allegations of invalidity are not justified: see Lundbeck Canada Inc v Ratiopharm Inc, 2009 FC 1102, [2009] FCJ 1466; Abbott Laboratories v Canada (Minister of Health), 2007 FCA 153, 59 C.P.R. (4th) 30 at paras 9-10; Pfizer v Canada (Minister of Health), 2007 FCA 209, 60 C.P.R. (4th) 81 at para 109 (FCA); Pfizer v Canada (Minister of Health), 2012 FC 767 at para 42 affirmed in the result 2012 FCA 308; Pfizer Canada Inc v Pharmascience Inc, 2013 FC 120, [2013] FCJ 111 at paras 24-27.
[59] If the generic (second person) does not adduce any evidence with respect to a ground of invalidity alleged, then the presumption is not rebutted.
[60] The burden is also on the brand (first person), Roche, with respect to allegations of non- infringement. The generic manufacturer, Apotex, has alleged non-infringement of specific claims in its NOA. These statements are presumed to be true. The onus is on the brand, Roche, to demonstrate, on a balance of probabilities, that the allegations of non-infringement are not justified. The applicant cannot simply raise the possibility of infringement: see Novopharm Limited v Pfizer Canada Inc, 2005 FCA 270, 42 CPR (4th) 97, at paras 19-20 and 24.
[61] In Pfizer Canada Inc v Apotex Inc, 2007 FC 26, 59 CPR (4th) 183 (aff’d 2007 FCA 195, leave to appeal refused [2007] SCCA No. 371) Justice O’Reilly set out the approach to be followed with respect to the burden of proof at paragraphs 9 and 12:
9 In my view, the burden on a respondent under the Regulations is an "evidential burden" -- a burden merely to adduce evidence of invalidity. Once it has discharged this burden, the presumption of validity dissolves and the Court must then determine whether the applicant has discharged its legal burden of proof. I believe this is what is meant in those cases where the Court has stated that the respondent must put its allegations "into play". It must present sufficient evidence to give its allegations of invalidity an air of reality.
. . .
12 To summarize, Pfizer bears the legal burden of proving on a balance of probabilities that Apotex's allegations of invalidity are unjustified. Apotex merely has an evidentiary burden to put its case "into play" by presenting sufficient evidence to give its allegations of invalidity an air of reality. If it meets that burden, then it has rebutted the presumption of validity. I must then determine whether Pfizer has established that Apotex's allegations of invalidity are unjustified. If Apotex does not meet its evidential burden, then Pfizer can simply rely on the presumption of validity to obtain its prohibition order.
[62] As noted above, Justice Hughes summarized the requirements of subsection 5(3)(b)(ii) of the NOC Regulations governing the contents of the Notice of Allegation [NOA] in GlaxoSmithKline Inc v Pharmascience, 2011 FC 239, [2011] FCJ 287, and also noted at para 41:
[41] In the Court proceedings, a first person is required to demonstrate, in accordance with subsection 6(2) of the NOC Regulations, that “none of those allegations is justified”. Thus, the object of the proceedings is to look at the allegations, consider the evidence, apply the law, and determine whether an allegation made in the NOA is justified. Such a determination, for instance, whether an allegation as to invalidity is justified or not, does not preclude that issue from being litigated in an ordinary action respecting the patent, in other words, there is no res judicata (Aventis Pharma Inc. v. Apotex Inc. (2006), 46 C.P.R. (4th) 401(FCA), at para. 7).
[63] In the present case, Apotex has raised allegations in its NOA and has led evidence as to the invalidity of the Patent on the basis of anticipation, obviousness and overbreadth which is sufficient to put those issues into play. As a result, the applicant, Roche bears the burden of establishing, on a balance of probabilities, that these allegations are not justified.
[64] Apotex also alleges that it will not infringe claims 4-8 and claim 10. As noted above at paragraph 60, the law is well-settled that where a generic has alleged non-infringement, the statements that it makes in that regard in its NOA are presumed to be true. The applicant, Roche, therefore bears the burden of proof, on a balance of probabilities, to satisfy the Court that the allegations of non-infringement are not justified; merely to raise the possibility of infringement is insufficient.
PERSON SKILLED IN THE ART
[65] The person skilled in the art (or person of ordinary skill in the art – a “POSITA”) provides the lens through which the patent is construed and many other issues are assessed. As described by Justice Hughes in Pfizer Canada Inc v Pharmascience Inc, 2013 FC 120, [2013] FCJ 111:
28 The person skilled in the art, or as sometimes described, the person of ordinary skill in the art (POSITA) is the notional person, which may include a team of persons, through whose eyes a patent is to be construed, the prior art is to be considered. This notional person may be pertinent to other issues that arise in respect of a patent under consideration by the Court.
[66] In Apotex Inc v Sanofi-Aventis, 2011 FC 1486, [2011] FCJ 1813, Justice Boivin noted:
[64] In assessing the hypothetical POSITA, the Court must define the person or group to whom the ‘777 Patent is addressed. This person is obviously not a real person. As explained by Justice Hughes in Merck & Co v Pharmascience Inc., 2010 FC 510, 85 CPR (4th) 179, at para 42: “[T]hat person is to be unimaginative, but that does not mean that the person is slow-witted or graduated (if at all) at the bottom of the class. Nor is the person the gold medalist who graduated at the top of the class. That person is the average person in the group. Just as a “reasonable man” is expected to be reasonable, the POSITA is expected to possess the ordinary skill in the art”.
[65] The Supreme Court of Canada considered such a person in Whirlpool, above, at para 74, where Justice Binnie for the Court wrote that the POSITA refers to the hypothetical “ordinary worker” who is reasonably diligent in keeping up with advances in the field to which the patent relates.
[67] In my view, it is difficult to characterize the POSITA as an ordinary person possessing ordinary skill in the art given the expertise, experience and educational qualifications of the scientists engaged in this research; even if they are considered ordinary vis–à-vis their peers, they are far from ordinary. In this case, these highly qualified experts were in disagreement on most issues, but there was general agreement on the POSITA.
[68] The experts called by both parties expressed their opinions on the qualifications of the proposed person skilled in the art and why such qualifications and experience would be necessary. There is no significant difference among the experts about the attributes