Apotex Inc v. Shire LLC

Apotex Inc v. Shire LLC
Court (s) Database
Federal Court Decisions
Date
2018-06-29
Neutral citation
2018 FC 637
File numbers
T-1056-16, T-998-16
Decision Content
Date: 20180629
Dockets: T-1056-16
T-998-16
Citation: 2018 FC 637
Ottawa, Ontario, June 29, 2018
PRESENT: The Honourable Mr. Justice Fothergill
Docket: T-1056-16
BETWEEN:
APOTEX INC.
Plaintiff
(Defendant by Counterclaim)
and
SHIRE LLC AND SHIRE PHARMA CANADA ULC
Defendants
(Plaintiffs by Counterclaim)
Docket: T-998-16
AND BETWEEN:
SHIRE PHARMA CANADA ULC
Applicant
and
APOTEX INC. AND THE MINISTER OF HEALTH
Respondents
and
SHIRE LLC
Respondent/Patentee
PUBLIC JUDGMENT AND REASONS
(Identical to the Confidential Judgment and Reasons issued on June 21, 2018)
Table of Contents
I. Overview 4
II. Background 7
A. Parties 7
B. Pleadings and History of the Proceedings 7
C. Foreign Proceedings 9
III. The 646 Patent 11
IV. Claims in Issue 13
V. Issues 16
A. Validity 16
B. Infringement 17
C. Prohibition Application 17
VI. Evidence 17
A. Fact and Expert Witnesses 17
(1) Apotex’s Witnesses 17
(2) Shire’s Witnesses 18
B. Observations Regarding the Evidence 19
VII. Claims Construction 20
A. Legal Principles and Relevant Dates 20
B. Person of Ordinary Skill in the Art 22
C. Common General Knowledge of the PSIA 22
D. Claim Term Needing Construction 28
VIII. Validity 30
A. Developments Leading to the Patent 30
B. Selection Patents 32
(1) Legal Principles 32
(2) Analysis 34
C. Anticipation 37
(1) Legal Principles 37
(2) Analysis 38
D. Obviousness 41
(1) Legal Principles 41
(2) The PSIA and Common General Knowledge 43
(3) Inventive Concept of the Patent 43
(4) Differences between the Prior Art and the Invention 45
(5) Whether the Differences were Obvious or Required Invention 51
(6) Whether the Invention was Obvious to Try 53
E. Overbreadth 56
(1) Legal Principles 56
(2) Analysis 56
F. Insufficiency of Specification 56
(1) Legal Principles 56
(2) Analysis 57
IX. Infringement 58
A. Legal Principles 58
B. Experimental and Regulatory Use Exception 59
C. Analysis 59
X. Prohibition Application 61
A. Legal Principles 61
B. Analysis 61
XI. Conclusion 62
I.
Overview
[1] Attention Deficit and Hyperactivity Disorder [ADHD] is a common neurobehavioural condition in both children and adults that is characterized by a persistent pattern of hyperactivity, impulsivity and inattention. For many years, physicians have treated the symptoms of ADHD with stimulants, such as amphetamine.
[2] Amphetamine products are available as immediate and sustained release formulations, each of which produces different durations of action. In sustained release formulations, also known as controlled release, extended release and slow release, the dosage form is designed to release the drug at a continuous and controlled rate for a longer period than would normally be achieved using its conventional, non‐sustained counterpart (i.e., immediate release).
[3] One significant drawback of both immediate and sustained release formulations of amphetamine is their potential for abuse. The dosage forms may be ground into a powder that is snorted or inhaled intranasally. The powder may be dissolved in water and the recovered drug may be injected intravenously. The intact or pulverized dosage forms may be ingested to produce an oral overdose.
[4] Canadian Patent 2,527,646 [646 Patent] is titled “Abuse Resistant Amphetamine Compounds”, and relates generally to the compound lisdexamfetamine [LDX], its compositions, methods of delivery and use. The application for the 646 Patent was filed on June 1, 2004, and claimed priority from United States Patents US60/567,801 dated May 5, 2004 and US60/473,929 dated May 29, 2003.
[5] According to the 646 Patent, rendering amphetamines resistant to abuse, particularly by parenteral routes such as snorting or injecting, adds considerable value to this otherwise effective and beneficial prescription medication. Although formulations exist that provide sustained release, they have several shortcomings, including uneven release and the potential for abuse. There is therefore a need for an abuse-resistant dosage form of amphetamine which is therapeutically effective. There is also a need for an amphetamine dosage form which provides sustained release and sustained therapeutic effect.
[6] The 646 Patent claims to address both of these needs with the invention LDX. This is a compound that comprises amphetamine covalently bound to a chemical moiety in a manner that diminishes or eliminates the pharmacological activity of amphetamine until it is released. LDX is a prodrug, i.e., a molecule which is converted into its active form in the body by normal metabolic processes.
[7] Release of amphetamine following the oral administration of LDX occurs gradually over an extended period of time, thereby eliminating the spiking of drug levels. When taken at doses above the intended prescription, the bioavailability of amphetamine, including peak levels and the total amount of drug absorbed, is substantially decreased, thereby decreasing the potential for oral overdose. LDX is also resistant to tampering, and to abuse by parenteral routes of administration. LDX therefore provides a stimulant-based treatment for ADHD with substantially decreased abuse liability compared to other stimulant treatments.
[8] The issues raised in these proceedings are whether the specified claims of the 646 Patent are valid; if so, whether they are infringed by the Plaintiff’s/Respondent’s generic product; and whether the Minister of Health should be prohibited from issuing a Notice of Compliance [NOC] to the Plaintiff/Respondent for its generic product under the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [PM(NOC) Regulations], promulgated under the Patent Act, RSC 1985, c P-4.
[9] For the reasons that follow, I conclude that the specified claims of the 646 Patent are not invalid on any of the asserted grounds of anticipation, obviousness, overbreadth, or insufficiency of specification. However, the 646 Patent has not been infringed by the Plaintiff’s/Respondent’s manufacture and retention of its generic product for experimental or regulatory use. Finally, the Minister of Health should be prohibited from issuing a NOC to the Plaintiff/Respondent for its generic product.
II. Background
A. Parties
[10] Apotex Inc [Apotex] is a generic pharmaceutical company incorporated under the laws of Ontario.
[11] Shire LLC is a company incorporated in the United States of America, and the owner of the 646 Patent. Shire Pharma Canada ULC is authorized to sell LDX capsules in Canada under the trade name Vyvanse.
[12] Shire Pharma Canada ULC is a company incorporated under the laws of Canada. Shire LLC and Shire Pharma Canada ULC are wholly-owned subsidiaries of Shire PLC, a company with its head office in Ireland. Only Shire LLC and Shire Pharma Canada ULC are named as parties in the present action and application. I shall refer to them collectively as Shire.
[13] The Minister of Health is named as a Respondent in Court File No. T-998-16, but has not participated in these proceedings.
B. Pleadings and History of the Proceedings
[14] On February 11, 2016, Apotex filed an abbreviated new drug submission with Health Canada seeking a NOC to manufacture and sell Apo-Lisdexamfetamine, a generic version of Vyvanse.
[15] On March 24, 2016, Apotex served a first Notice of Allegation [NOA] upon Shire pursuant to s 5(3) of the PM(NOC) Regulations. Shire responded to the NOA by filing an application in this Court pursuant to s 6(1) of the PM(NOC) Regulations for an order prohibiting the Minister of Health from granting a NOC to Apotex until the expiry of the 646 Patent (Court File No. T-723-16). Apotex served a second NOA on Shire on April 7, 2016. Shire again responded with a prohibition application (Court File No. T-816-16). On June 20, 2016, these proceedings were dismissed as moot following Apotex’s withdrawal of both NOAs.
[16] Apotex served Shire with a third NOA on May 13, 2016. Shire responded with the prohibition application that forms a part of these proceedings [T-998-16, or the Prohibition Application].
[17] On February 27, 2018, Apotex served Shire with a fourth NOA, pertaining to 10 mg capsules of Apo-Lisdexamfetamine.
[18] Shire initially claimed that Apotex’s service of multiple NOAs, causing Shire to respond with numerous prohibition applications and potentially extending the timeframe for the assessment of damages pursuant to s 8 of the PM(NOC) Regulations, amounted to an abuse of process. Shire subsequently resiled from this position, while reserving its right to address the procedural history in its submissions on costs.
[19] On July 4, 2016, Apotex commenced an action against Shire pursuant to s 60 of the Patent Act for declarations that the 646 Patent is invalid and, in any event, Apotex’s proposed generic product will not infringe any valid claim of the 646 Patent [T-1056-16, or the Impeachment Action].
[20] The Impeachment Action and the Prohibition Application were consolidated pursuant to the order of Prothonotary Mireille Tabib dated October 3, 2016. Prothonotary Tabib directed that T-998-16 and T-1056-16 be heard together, and that T-998-16 be decided on the basis of the evidence adduced in T-1056-16, subject to relevance. Apotex appealed the consolidation order, which was upheld by Justice Cecily Strickland on February 6, 2017.
[21] The present proceedings are governed by the NOA dated May 12, 2016; the Prohibition Application dated June 24, 2016; the Second Further Amended Statement of Claim dated March 22, 2018; the Further Amended Statement of Defence and Counterclaim dated April 6, 2018; the Second Further Amended Reply and Defence to Counterclaim dated April 12, 2018; and the Further Amended Reply to Defence of Counterclaim dated December 11, 2017.
C. Foreign Proceedings
[22] Courts and tribunals in other countries have considered counterparts of the 646 Patent, and have consistently affirmed their validity: Shire LLC v Amneal Pharmaceuticals, LLC, 2015 US App LEXIS 16908 (NJ Dist Ct); Shire LLC v Amneal Pharmaceuticals, LCC (2015), 802 F.3d 1301 (Dist Ct App); Shire LLC v Generics [UK] Limited (2014), App No 04 753 925.9 (EPO (Opp Div)); Generics [UK] Limited v Shire LLC (2016), Case No T 2277/14 - 3.3.07 (EPO (App Board)). Shire notes that the proceedings in other countries were concerned with questions of novelty and obviousness, and an Australian patent relied upon by Apotex in these proceedings, “Amino Carboxylic Acid Amides and Process for the Manufacture Thereof,” AU Patent No 54168/65 (20 January 1965) [AU 168], figured prominently in the foreign proceedings as well.
[23] Shire acknowledges that the factual records and applicable law may have differed in the foreign proceedings, but nevertheless argues that this Court should regard them as “instructive”. Shire cites Harvard College v Canada, 2002 SCC 76 at paragraph 13 [Harvard College] for the proposition that “[t]he mobility of capital and technology makes it desirable that comparable jurisdictions with comparable intellectual property legislation arrive (to the extent permitted by the specifics of their own laws) at similar legal results”.
[24] Apotex responds that in Harvard College, the Supreme Court of Canada ultimately endorsed the “discordant note” sounded by the Commissioner of Patents in refusing a patent for a higher life form, specifically a genetically-altered mouse useful for cancer research. Consistent with that decision, this Court must decide the legal issues raised by these proceedings in accordance with the factual record and Canada’s own laws.
[25] I agree with Apotex. In reaching the conclusions below, I have placed no reliance on the decisions of foreign jurisdictions regarding patents that are said to be comparable to the 646 Patent.
III. The 646 Patent
[26] The 646 Patent describes the field of invention as follows:
[002] The invention relates to amphetamine compounds, compositions and methods of delivery and use comprising amphetamine covalently bound to a chemical moiety.
[003] The invention relates to compounds comprised of amphetamine covalently bound to a chemical moiety in a manner that diminishes or eliminates pharmacological activity of amphetamine until released. The conjugates are stable in tests that simulate procedures likely to be used by illicit chemists in attempts to release amphetamine. The invention further provides for methods of therapeutic delivery of amphetamine compositions by oral administration. Additionally, release of amphetamine following oral administration occurs gradually over an extended period of time thereby eliminating spiking of drug levels. When taken at doses above the intended prescription, the bioavailability of amphetamine, including peak levels and total amount of drug absorbed, is substantially decreased. This decreases the potential for amphetamine abuse which often entails the use of extreme doses (1 g or more a day). The compositions are also resistant to abuse by parenteral routes of administration, such as intravenous · “shooting”, intranasal “snorting”, or inhalation “smoking”, that are often employed in illicit use. The invention thus provides a stimulant based treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), which is commonly treated with amphetamine. Treatment of ADHD with compositions of the invention results in substantially decreased abuse liability as compared to existing stimulant treatments.
[27] According to the Background of the Invention, the invention is directed to an anti-abuse/sustained release formulation of amphetamine which maintains its therapeutic effectiveness when administered orally. The invention further relates to formulations which diminish or reduce the euphoric effect of amphetamine while maintaining therapeutically effective blood concentrations following oral administration.
[28] The Background of the Invention notes that potent central nervous system [CNS] stimulants have been used for decades to treat children with ADHD. However, the potential for abuse is a major drawback. This has earned amphetamines Schedule II status under the United States Controlled Substances Act, a classification that is reserved for drugs that have an accepted medical use but the highest potential for abuse. Adderall XR, another amphetamine-based ADHD medication manufactured and sold by Shire, is a product with increased abuse liability relative to single dose tablets. This is due to the higher concentration of amphetamine in the extended release formulation, and the potential for release of the full amount of the active pharmaceutical ingredient upon crushing. It may be possible for substance abusers to obtain a high dose of the pharmaceutical with rapid onset by snorting the powder or dissolving it in water and injecting it.
[29] The Background of the Invention asserts that rendering amphetamines resistant to abuse, particularly by parenteral routes such as snorting or injecting, would provide considerable value to this otherwise effective and beneficial prescription medication. Although formulations have been successfully used to manufacture dosage forms which demonstrate sustained release properties, these formulations are subject to several shortcomings, including uneven release, and are subject to abuse. The need therefore exists for an abuse-resistant dosage form of amphetamine which is therapeutically effective. Further, the need exists for an amphetamine dosage form which provides sustained release and sustained therapeutic effect.
[30] The Summary of the Invention states that the invention provides covalent attachment of amphetamine and derivatives or analogs thereof to a variety of chemical moieties. The chemical moieties may include any substance which results in a prodrug form. The chemical moieties may be amino acids, peptides, glycopeptides, carbohydrates, nucleosides, or vitamins. The chemical moiety is covalently attached either directly or indirectly through a linker to the amphetamine. The site of attachment is typically determined by the functional group(s) available on the amphetamine.
[31] Covalent attachment of a chemical moiety to amphetamine can decrease its pharmacological activity when administered through injection or intranasally. Compositions of the invention provide amphetamine covalently attached to a chemical moiety which remains orally bioavailable. The bioavailability is a result of the hydrolysis of the covalent linkage following oral administration. Hydrolysis is time-dependent, thereby allowing amphetamine to become available in its active form over an extended period of time. In one embodiment, the composition provides oral bioavailability which resembles the pharmacokinetics observed for extended release formulations. In another embodiment, release of amphetamine is diminished or eliminated when delivered by parenteral routes. Other embodiments are also described.
[32] The 646 Patent then provides a Detailed Description of the Invention and accompanying drawings. The claims of the 646 Patent, which number 51 in total, follow.
IV. Claims in Issue
[33] Shire alleges infringement of claims 1 to 5, 8, 10 to 12, 22, 24 to 30, 33 to 36, and 43 of the 646 Patent. Apotex challenges the validity of only these claims.
[34] Claims 1 to 5 describe compounds:
1. A compound selected from the group consisting of L-lysine-d- amphetamine and a pharmaceutically acceptable salt thereof.
2. The compound of claim 1, wherein the compound is L-lysine-d-amphetamine.
3. The compound of claim 1, wherein the compound is L-lysine-d-amphetamine mesylate.
4. The compound of claim 1, wherein the compound is L-lysine-d-amphetamine hydrochloride.
5. The compound of any one of claims 1 to 4 wherein the L-lysine-d-amphetamine is defined by:
[35] Claim 8 describes a composition:
8. A pharmaceutical composition comprising L-lysine-d-amphetamine mesylate and one or more pharmaceutically acceptable additives.
[36] Claims 10 to 12 describe compositions:
10. The pharmaceutical composition according to any one of claims 6-9, wherein the composition provides release of amphetamine as an active from the compound following oral administration.
11. The pharmaceutical composition according to any one of claims 6-9, wherein the L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof provides a therapeutically effective amount of amphetamine.
12. The pharmaceutical composition of claim 11, wherein the L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof provides a reduced Cmax of amphetamine as compared to amphetamine alone.
[37] Claim 22 describes a composition:
22. The pharmaceutical composition of any one of claims 7 to 21 wherein the L-lysine-d-amphetamine is defined by:
[38] Claims 24 to 30 describe compositions:
24. The pharmaceutical composition of any one of claims 6-15, wherein said compound is present in an amount of from 10 to 250 mg.
25. The pharmaceutical composition of any one of claims 6-15, wherein said compound is present in an amount of 20 mg.
26. The pharmaceutical composition of any one of claims 6-21, wherein said compound is present in an amount of 30 mg.
27. The pharmaceutical composition of any one of claims 6-21, wherein said compound is present in an amount of 40 mg.
28. The pharmaceutical composition of any one of claims 6-21, wherein said compound is present in an amount of 50 mg.
29. The pharmaceutical composition of any one of claims 6-21, wherein said compound is present in an amount of 60 mg.
30. The pharmaceutical composition of any one of claims 6-21, wherein said compound is present in an amount of 70 mg.
[39] Claims 33 to 36 describe uses:
33. Use of the compound of any one of claims 1-5 for the preparation of a medicament for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in a subject.
34. Use of the compound of any one of claims 1-5 for the treatment of ADHD in a subject.
35. The use according to claim 33 or 34, wherein the subject is an adult.
36. The use according to claims 33 or 34, wherein the subject is a human.
[40] Claim 43 describes a use:
43. The use according to any one of claims 33-42, wherein the compound is for administration once daily.
V. Issues
[41] The issues raised in these proceedings are whether the specified claims of the 646 Patent are valid; if so, whether they are infringed by Apotex’s generic product; and whether the Minister of Health should be prohibited from issuing a NOC to Apotex for its generic product.
A. Validity
[42] Apotex alleges that the specified claims of the 646 Patent are invalid based on four grounds: obviousness, anticipation, overbreadth, and insufficiency of specification.
B. Infringement
[43] Shire alleges that Apotex has infringed the specified claims of the 646 Patent by manufacturing and/or retaining between 918,707 and 3,409,337 capsules of its generic product. In response, Apotex relies on the experimental and regulatory use exception recognized in ss 55.2(1) and (6) of the Patent Act and at common law.
C. Prohibition Application
[44] Shire seeks an order prohibiting the Minister of Health from issuing a NOC to Apotex, pursuant to s 6(1) of the PM(NOC) Regulations, on the ground that Apo-Lisdexamfetamine infringes the specified claims of the 646 Patent.
VI. Evidence
A. Fact and Expert Witnesses
(1) Apotex’s Witnesses
[45] Apotex called the following witnesses to testify in these proceedings.
[46] Dr. Robert Langer. Dr. Langer is a David H. Koch Institute Professor at the Massachusetts Institute of Technology [MIT]. He holds appointments at the Department of Chemical Engineering at MIT, Whitaker College of Health Sciences Technology and Management, and the MIT Cancer Institute. He is also affiliated with the Children’s Hospital Medical Center at Harvard Medical School. Dr. Langer was qualified as an expert in chemical and biomedical engineering, pharmaceutical chemistry, drug design and formulation and drug delivery systems, including targeted drug delivery and controlled release applications.
[47] Dr. Brian Marron. Dr. Marron is the President and Owner of Brian Marron Drug Discovery Consulting LLC. He was qualified as an expert in synthetic organic chemistry, medicinal chemistry and the discovery, design and development of drugs.
[48] Mr. Gordon Fahner. Mr. Fahner is the Senior Vice President, Global Finance at Apotex. He was called as a fact witness.
(2) Shire’s Witnesses
[49] Shire called the following witnesses to testify in these proceedings.
[50] Dr. Travis Mickle. Dr. Mickle is listed as a named inventor on the 646 Patent. He is currently the President, Chief Executive Officer and Chairman of the Board of KemPharm, a publicly-traded pharmaceutical company with its headquarters in Coralville, Iowa. He was called as a fact witness.
[51] Dr. Scott Moncrief. Dr. Moncrief is listed as a named inventor on the 646 Patent. He is a biologist who was formerly the head of animal testing at New River Pharmaceuticals [New River]. He was called as a fact witness.
[52] Dr. Michael Eldon. Dr. Eldon is a consultant specializing in pre-clinical and clinical pharmacology, pharmacokinetics and pharmacodynamics. He is also the Principal Scientific Fellow at Nektar Therapeutics, a publicly-traded pharmaceutical company with its headquarters in San Francisco, California. Dr. Eldon was qualified as an expert in pre-clinical and clinical pharmacology, pharmacokinetics and pharmacodynamics, drug discovery, drug development, translational sciences, and the design and evaluation of drugs with reduced-abuse potential.
[53] Dr. Bernd Clement. Dr. Clement is Professor of Pharmaceutical and Medicinal Chemistry, and one of the Directors of the Pharmaceutical Institute at the University of Kiel, Germany. He was qualified as an expert in pharmaceutical and medicinal chemistry, including organic chemistry, synthetic chemistry, pharmacokinetics and pharmaceutics, and also drug discovery and development, and prodrugs.
B. Observations Regarding the Evidence
[54] To their credit, the parties largely agreed upon the qualifications of the witnesses who were called to give expert opinion evidence. However, Apotex questioned the depth of Dr. Eldon’s expertise in the design and development of abuse-resistant drugs, and the depth of Dr. Clement’s expertise in organic and synthetic chemistry, pharmacokinetics, pharmaceutics and drug development. I ultimately agreed to qualify Drs. Eldon and Clement in the manner proposed by Shire, with only minor adjustment to the description of qualifications tendered for Dr. Clement. In accepting the expertise of Drs. Eldon and Clement, I applied the test for expert opinion evidence articulated by the Supreme Court of Canada in White Burgess Langille Inman v Abbott and Haliburton Co, 2015 SCC 23 at paragraph 19: (1) relevance; (2) necessity in assisting the trier of fact; (3) absence of an exclusionary rule; and (4) a properly qualified expert. With respect to the last of these points, I observed that the threshold for establishing expertise is relatively low: the capacity to provide information “which is likely to be outside the experience and knowledge of a judge or jury” (R v Mohan, [1994] 2 SCR 9 at 23). Once qualified, the depth of a particular witness’ expertise, particularly in comparison to that of a competing expert witness, is a matter of weight.
[55] I found all of the witnesses called in these proceedings to be generally credible. The experts presented impressive qualifications, and all witnesses provided useful information. Unfortunately, the experts called by both parties sometimes exhibited a tendency to provide short, direct answers in examination in chief, and considerably longer, less direct answers in cross-examination. While this did not detract from their credibility, it did sometimes raise questions regarding their impartiality.
[56] Despite these reservations, I am not prepared to wholly reject or discount the evidence of any witness who was called to testify in these proceedings. My reasons for preferring some witnesses’ evidence over that of others are explained in the analysis that follows.
VII. Claims Construction
A. Legal Principles and Relevant Dates
[57] The first step in a patent suit is to construe the claims in order to give them meaning and determine their scope (Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 43 [Whirlpool]). The relevant date for construing the claims is the date of publication of the patent application: January 6, 2005 (Whirlpool at paras 54-55). The Court must examine the description contained in the patent to identify its “essential elements”, and may be aided by expert evidence regarding the meaning of specific terms (Whirlpool at paras 43, 45, 57).
[58] The canons of claims construction may be found in the Supreme Court of Canada’s decisions in Whirlpool at paragraphs 49 to 55 and Free World Trust v Électro Santé Inc, 2000 SCC 66 [Free World Trust] at paragraphs 44 to 54. They are the following:
(a) claims are to be read in an informed and purposive way with a mind willing to understand, viewed through the eyes of the person skilled in the art as of the date of publication having regard to the common general knowledge;
(b) adherence to the language of the claims allows them to be read in the manner the inventor is presumed to have intended, and in a way that is sympathetic to accomplishing the inventor’s purpose, which promotes both fairness and predictability; and
(c) the whole of the specification should be considered to ascertain the nature of the invention, and the construction of claims must be neither benevolent nor harsh, but should instead be reasonable and fair to both the patentee and the public.
B. Person of Ordinary Skill in the Art
[59] In order to construe the claims in issue, the Court must define the Person of Ordinary Skill in the Art [PSIA]. This is “the person to whom the patent is said to be addressed, through whose eyes the Court is to read the patent, and who stands as the criterion for determination of obviousness” (Amgen Canada Inc v Apotex Inc, 2015 FC 1261 at para 42).
[60] The expert witnesses called by both parties were in substantial agreement that the PSIA is a drug development team with expertise in medicinal chemistry, pharmacology, pharmaceutical formulation and medicine. Shire described the members of the team as having “knowledge of (a) medicinal chemistry; (b) pharmaceutical formulation; (c) pharmacology; and (d) the treatment of ADHD.” Each of the team members would have an advanced degree such as a PhD or MD, and would have approximately three to five years of work experience.
C. Common General Knowledge of the PSIA
[61] The patent must be construed taking into account the “common general knowledge” shared by persons skilled in the art (Free World Trust at para 44; Whirlpool at para 53). This is the knowledge possessed by the PSIA at the relevant time, and includes what the PSIA would reasonably be expected to know (Sanofi-Synthelabo Canada Inc v Apotex Inc, 2008 SCC 61 at para 70 [Sanofi-Synthelabo]; Whirlpool at para 74). The common general knowledge of the PSIA must be established on a balance of probabilities, and cannot be assumed (Uponor AB v Heatlink Group Inc, 2016 FC 320 at para 47 [Uponor AB]).
[62] The assessment of common general knowledge is governed by the principles found in Eli Lilly & Co v Apotex Inc, 2009 FC 991 at paragraph 97 and General Tire & Rubber Co v Firestone Tyre & Rubber Co, [1972] RPC 457 (UKHL) at pages 482 to 483:
(a) the common general knowledge imputed to the PSIA must be carefully distinguished from what in patent law is regarded as public knowledge;
(b) common general knowledge is a different concept derived from a common sense approach to the practical question of what would in fact be known to an appropriately skilled addressee – the sort of person, good at his or her job, who could be found in real life;
(c) individual patent specifications and their contents do not normally form part of the relevant common general knowledge, although there may be specifications which are so well known that they do form part of the common general knowledge, particularly in certain industries; and
(d) regarding scientific papers generally:
it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, or in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates;
a piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated;
such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art; and
it is difficult to appreciate how the use of something which has in fact never been used in a particular art can ever be held to be common general knowledge in the art.
[63] Shire argues that prior art in an unrelated field does not form part of the common general knowledge unless it is proven to be something the PSIA would consider. Hindsight is prohibited. Shire relies on Justice Michael Manson’s recent decision in Frac Shack Inc v AFD Petroleum Ltd, 2017 FC 104 at paragraph 146:
[…] Public knowledge is theoretical and includes each and every patent specification published, however unlikely to be looked at and in whatever language it is written. Common general knowledge, in contrast, is derived from a common sense approach to the question of what would be known, in fact, to an appropriately skilled person that could be found in real life, who is good at his or her job.
[64] Apotex accepts that the patent specifications it relies upon as prior art in support of its arguments regarding anticipation and obviousness do not form a part of the PSIA’s common general knowledge. It does, however, rely on the discussions of prodrugs contained in scientific papers published prior to May 2003.
[65] Both parties assessed the common general knowledge as of May 2003, the relevant date for the assessment of obviousness. In its closing submissions, Shire commented in a footnote that “[t]he same teachings would have been applicable as of June 1, 2004 (the filing date) and January 6, 2005 (the publication date, the relevant date for claims construction)”.
[66] The expert witnesses who testified in these proceedings were in substantial agreement that the common general knowledge of the PSIA would include the following:
(a) ADHD is a common neurobehavioural disorder in both children and adults that is characterized by a persistent pattern of hyperactivity, impulsivity and inattention.
(b) Physicians could treat the symptoms of ADHD with stimulants, including amphetamine.
(c) Amphetamine products were available as immediate and sustained release formulations, each of which produced different durations of action.
(d) In sustained release formulations, the dosage form was designed to release the drug at a continuous and controlled rate for a longer period than would normally be achieved using an immediate release formulation.
(e) One significant drawback of both immediate and sustained release formulations of amphetamine was their potential for abuse. Those who abused amphetamine wished to attain the euphoria that results from exposure to a rapid and elevated dose. In pharmacokinetic terms, abusers were seeking a short time to maximum plasma concentration [Tmax] and a high peak plasma concentration [Cmax] of amphetamine.
(f) As of May 2003, the PSIA would have recognized the need for an amphetamine product that could not be abused by crushing and snorting, dissolving and injecting, or taking an oral overdose.
(g) The PSIA would have understood that one of the known strategies to reduce the abuse of amphetamine was to reduce its Cmax and extend its Tmax.
(h) As of May 2003, no known formulation could address all principal routes of abuse of amphetamine (i.e., crushing and snorting, dissolving and injection, oral overdose). Adderall XR was an extended release formulation which reduced Cmax and extended Tmax, but did not provide a means to prevent abusers from circumventing the extended release mechanism, either by crushing or dissolution.
(i) Concerta was a known methylphenidate composition that was designed to form a paste when crushed so it could not be snorted. However, Concerta would dissolve in water and release its active ingredient for injection or swallowing, and thus its abuse protection was limited. Further, the extended release mechanism in Concerta could be undone by crushing or chewing the tablet.
(j) An irritant could be added to a formulation that was intended to sting if snorted or injected. However, the irritant would do nothing to alter the pharmacokinetics of amphetamine, or stop someone from dissolving the drug and ingesting it orally. No formulation containing an irritant to discourage abuse had ever reached the market.
[67] The principal area of dispute is whether the PSIA’s common general knowledge would encompass prodrugs and, if so, to what extent.
[68] According to Apotex, as of May 2003, prodrugs were an established concept extensively discussed in the literature as a way of developing a product with better properties to overcome barriers to a drug’s usefulness, including its pharmacokinetic limitations. The field matured in the 1970s, when a number of comprehensive reviews appeared and presented the rational basis for prodrug design as applied to many drugs. Specific applications for prodrugs included controlling the release rate by reducing the Cmax, optimizing the pharmacokinetics, and extending the duration of action of a wide range of different drug types.
[69] Shire says that, based on the scientific literature of the time, the use of prodrugs to achieve sustained release or deter abuse would not form a part of the common general knowledge of those who were engaged in the art to which the disclosure of the 646 Patent relates; namely, a compound that provides sustained release of a therapeutic quantity of amphetamine and is also resistant to abuse. A more detailed discussion of the relevant scientific literature may be found under the heading Differences between the Prior Art and the Invention, below. While prodrugs were a known concept in May 2003, using prodrugs to control release was understood to be difficult and unpredictable, and was generally avoided. There was no known use of a prodrug to render a drug less susceptible to abuse.
[70] I generally prefer the articulation of the common general knowledge proposed by Shire, which in my view is better supported by the scientific literature cited by the parties. I therefore conclude that the common general knowledge of the PSIA is as described in paragraph 66, above. However, I also accept Apotex’s assertion that the PSIA’s common general knowledge would include an awareness of the development of prodrugs to overcome barriers to a drug’s usefulness, including its pharmacokinetic limitations. This is consistent with Shire’s acknowledgment that prodrugs were an established concept as of May 2003.
D. Claim Term Needing Construction
[71] Patent construction is a matter of law for the judge. Expert evidence is necessary only where the meaning of a term is not apparent based on a reading of the patent specification (Johnson & Johnson Inc v Boston Scientific Ltd, 2008 FC 552 at para 92).
[72] The parties both maintain that the claims in issue are clear and unambiguous. However, they disagree about the meaning of the term “L-lysine-d-amphetamine”. Paragraph 95 of the 646 Patent defines “amphetamine” as “any of the sympathomimetic phenethylamine derivatives which has central nervous system stimulant activity”. Apotex argues that, with the exception of claims 5 and 22 (which show LDX in picture form), the claims of the 646 Patent that refer to “L-lysine-d-amphetamine” include a group of conjugates of L‐lysine bound to any sympathomimetic phenethylamine derivative, as defined in paragraph 95.
[73] Apotex says its proposed construction of “L-lysine-d-amphetamine” avoids the redundancy of claims 5 and 22. This construction is also consistent with paragraph 105 of the 646 Patent, which states: “[f]or each of the recited embodiments, the amphetamine may be any of the above discussed stimulants. In one embodiment, the amphetamine is dextroamphetamine or methylphenidate”.
[74] Shire responds that “amphetamine” when used alone is given the expanded definition in paragraph 95 of the 646 Patent. However, “L-lysine-d-amphetamine” is defined in paragraph 100 to exclude the various sympathomimetic phenethylamine derivatives described in paragraph 95. Moreover, Dr. Langer acknowledged that all other references to “L-lysine-d-amphetamine” in the 646 Patent specify the compound LDX. Importantly, Dr. Langer admitted that it does not make sense from a chemical perspective to have “L-lysine-d-” followed by any and all of the amphetamine variations found in paragraph 95. Apotex’s proposed construction includes some compounds that cannot exist. Furthermore, Example 2 of the 646 Patent discusses the synthesis of “L-lysine-d-amphetamine” and refers the reader to Figure 2, which clearly shows LDX as having the structure of L-lysine bound to d-amphetamine, rather than any other sympathomimetic phenethylamine derivative.
[75] I prefer the construction advocated by Shire. As a general rule, claims should be construed to avoid redundancy. However, claims may be repeated, and courts may even read claims as redundant when it is reasonable