Teva Canada Innovation v. Pharmascience Inc

Date: 20210106

Dockets: T-2182-18

T-2183-18

Citation: 2020 FC 1158

Ottawa, Ontario, January 6, 2021

PRESENT: The Honourable Madam Justice Kane

BETWEEN:

TEVA CANADA INNOVATION AND

TEVA CANADA LIMITED

Plaintiffs

and

PHARMASCIENCE INC

and

Defendant

YEDA RESEARCH AND

DEVELOPMENT CO., LTD.

Patentee added pursuant to ss 6(2)

of the PM (NOC) Regulations and

ss 55(3) of the Patent Act

PUBLIC JUDGMENT AND REASONS

Page: 2

(The Confidential Judgment and Reasons were issued on December 16, 2020 and no redactions

are necessary)

Table of Contents

I. Overview ................................................................................................................................. 4

II. The Patents at Issue ............................................................................................................... 12

A.

B.

III.

A.

(1)

(2)

(3)

(4)

B.

(1)

(2)

(3)

(4)

The ‘437 Patent.................................................................................................................. 12

The ‘802 Patent.................................................................................................................. 14

The Witnesses and the Nature of their Evidence............................................................... 16

The ‘437 Patent.................................................................................................................. 16

Fact Witnesses for Teva ............................................................................................. 16

Expert Witnesses for Teva.......................................................................................... 17

Fact Witnesses for Pharmascience ............................................................................. 18

Expert Witnesses for Pharmascience.......................................................................... 18

The ‘802 Patent.................................................................................................................. 19

Fact Witnesses for Teva ............................................................................................. 19

Fact Witnesses for Pharmascience ............................................................................. 19

Expert Witnesses for Teva.......................................................................................... 20

Expert Witness for Pharmascience............................................................................. 20

IV. MS and its Diagnosis / Criteria............................................................................................. 21

A.

B.

C.

D.

E.

F.

Types of MS....................................................................................................................... 22

Clinically Isolated Syndrome............................................................................................. 23

Diagnosis of MS ................................................................................................................ 24

Use of MRI ........................................................................................................................ 27

The McDonald Criteria...................................................................................................... 28

The Difference between the Poser and McDonald Criteria vis-à-vis a CIS patient .......... 31

V. Overall Position of the Plaintiff Teva on the ‘437 Patent..................................................... 32

VI. Overall Position of the Defendant Pharmascience on the ‘437 Patent ................................. 34

VII. Overall Position of the Plaintiff Teva on the ‘802 Patent.................................................. 37

VIII. Overall Position of the Defendant Pharmascience on the ‘802 Patent .............................. 39

IX. Onus and Burden of Proof .................................................................................................... 40

X. The ‘437 Patent – Description and Disclosure ..................................................................... 40

XI. The ‘802 Patent – Description and Disclosure ..................................................................... 45

XII. The Structure of this Judgment.......................................................................................... 47

XIII. Overview of the Experts’ Evidence re the ‘437 Patent...................................................... 48

A.

B.

C.

D.

Pharmascience’s Expert, Dr. Green................................................................................... 48

Teva’s Expert, Dr. Morrow................................................................................................ 52

Teva’s Expert, Dr. Selchen ................................................................................................ 54

Teva’s Expert, Dr. Kreitman.............................................................................................. 56

XIV. The POSITA for the ‘437 Patent ....................................................................................... 57

A.

B.

The Principles from the Jurisprudence .............................................................................. 57

Who is the POSITA for the ‘437 Patent?........................................................................... 58

XV. The Construction of the Claims......................................................................................... 60

A.

B.

The Principles from the Jurisprudence .............................................................................. 60

The Claims of the ‘437 Patent ........................................................................................... 61

Page: 3

C.

The Dispute regarding the Patients Included in the Claims............................................... 64

Pharmascience’s Submissions.................................................................................... 64

Teva’s Submissions.................................................................................................... 66

What do the Experts Say regarding the Patients Included in the Claims?......................... 69

Dr. Green .................................................................................................................... 69

Dr. Morrow................................................................................................................. 71

Dr. Selchen ................................................................................................................. 73

The Patients Included in Claim 1 and Subsequent Claims ................................................ 76

(1)

(2)

D.

(1)

(2)

(3)

E.

XVI. Prior Art related to the ‘437 Patent.................................................................................... 84

A.

B.

C.

D.

Prior art on the use of glatiramer acetate in MS ................................................................ 85

Prior art on CIS progressing to MS.................................................................................... 85

Prior art on the use of interferons in CIS ........................................................................... 86

Prior art cited by Pharmascience as anticipatory references.............................................. 89

XVII. Common General Knowledge............................................................................................ 90

A.

B.

(1)

(2)

C.

Principles from the Jurisprudence...................................................................................... 90

What Do the Experts Say? ................................................................................................. 91

Dr. Green .................................................................................................................... 91

Dr. Selchen ................................................................................................................. 95

The Common General Knowledge regarding the ‘437 Patent........................................... 98

XVIII. Can Pharmascience rely on the Gillette Defence to the Allegations of Infringement of

the ‘437 Patent?........................................................................................................................... 101

A.

B.

C.

D.

Principles from the Jurisprudence.................................................................................... 101

Pharmascience’s Submissions ......................................................................................... 102

Teva’s Submissions ......................................................................................................... 103

The Gillette Defence Cannot Succeed ............................................................................. 104

XIX. Is the ‘437 Patent Anticipated?........................................................................................ 105

A.

B.

C.

D.

(1)

(2)

E.

Principles from the Jurisprudence.................................................................................... 105

Pharmascience’s Submissions ......................................................................................... 108

Teva’s Submissions ......................................................................................................... 111

What do the Experts Say?................................................................................................ 114

Dr. Green .................................................................................................................. 114

Dr. Selchen ............................................................................................................... 116

Karussis 2006 does Not Anticipate the Claims of the ‘437 Patent.................................. 118

XX. Is the ‘437 Patent Obvious? ............................................................................................. 129

A.

B.

C.

D.

(1)

(2)

E.

(1)

(2)

Principles from the Jurisprudence.................................................................................... 129

Pharmascience’s Submissions ......................................................................................... 134

Teva’s Submissions ......................................................................................................... 139

What do the Experts Say?................................................................................................ 143

Dr. Green .................................................................................................................. 143

Dr. Selchen ............................................................................................................... 146

The Claims of the ‘437 Patent are Obvious..................................................................... 150

The State of the Art .................................................................................................. 151

The Differences between the State of the Art and the Subject Matter of the Claims155

XXI. The ‘802 Patent................................................................................................................ 159

A.

B.

The POSITA for the ‘802 Patent ..................................................................................... 160

The Construction of the Claims of the ‘802 Patent.......................................................... 161

Page: 4

XXII. Prior Art and Common General Knowledge related to the ‘802 Patent .......................... 161

A.

B.

C.

D.

Prior art on glatiramer acetate 20 mg daily vs. every-other-day (alternate-day)............. 162

Prior art on glatiramer acetate 20 mg vs. 40 mg administered daily ............................... 165

Prior art on glatiramer acetate 40 mg every-other-day.................................................... 167

Prior art on injection site reaction and immediate post injection reaction....................... 167

XXIII. Overview of the Experts’ Evidence on the ‘802 Patent ............................................... 168

A.

B.

C.

Pharmascience’s Expert, Dr. Green................................................................................. 168

Teva’s Expert, Dr. Prat .................................................................................................... 169

Teva’s Expert, Dr. Day.................................................................................................... 171

XXIV. Is the ‘802 Patent Invalid due to Obviousness? ........................................................... 172

A.

B.

C.

(1)

(2)

D.

(1)

(2)

(3)

Teva’s Submissions ......................................................................................................... 172

Pharmascience’s Submissions ......................................................................................... 180

What do the Experts Say?................................................................................................ 186

Dr. Green .................................................................................................................. 186

Dr. Prat...................................................................................................................... 194

The ‘802 Patent is Not Obvious....................................................................................... 206

The State of the Art .................................................................................................. 216

Differences between the State of the Art and the Subject Matter of the Claims...... 218

Not Obvious to Try................................................................................................... 219

XXV. Is the ‘802 Patent Invalid due to Lack of Utility or Sound Prediction of Utility?........... 224

A.

B.

C.

D.

Teva’s Submissions ......................................................................................................... 224

Pharmascience’s Submissions ......................................................................................... 228

Principles from the Jurisprudence.................................................................................... 230

The ‘802 Patent is not Invalid due to Lack of Sound Prediction of Utility ..................... 235

XXVI. The Jurisdictional Issue – Can Teva rely on the Regulations to assert infringement by

Pharmascience of 20 mg Glatect?............................................................................................... 241

XXVII. Infringement by Pharmascience................................................................................... 245

XXVIII. Costs............................................................................................................................. 249

I.

Overview

[1]

These proceedings involve two patent infringement actions [the Action] pursuant to

subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133

[the Regulations].

[2]

At issue are medications that treat multiple sclerosis [MS]. The Teva Canada Innovation

and Teva Canada Limited [collectively, Teva] product is Copaxone® [Copaxone]. Copaxone 20

Page: 5

milligram [mg] has been on the market since the mid-90s. Copaxone 40 mg is a more recent

product.

[3]

The Pharmascience Inc. [Pharmascience] generic product is Glatect® [Glatect].

Pharmascience obtained a Notice of Compliance [NOC] from the Minister of Health [Minister]

for Glatect 20 mg, which is administered daily, in 2017 and has been marketing Glatect 20 mg

since that time. The Glatect Product Monograph, which, among other things, describes what

Glatect 20 mg is intended to treat, is described in more detail later in these Reasons. Teva has

confirmed that regardless of the outcome of this Action, the NOC issued to Pharmascience for

Glatect 20 mg daily will not be affected.

[4]

Pharmascience now seeks to expand its Glatect product to include a 40 mg strength to be

administered three times per week. Pharmascience submitted a Supplementary New Drug

Submission [SNDS] to do so and, in that context, identified Copaxone 40 mg as the reference

product. Pharmascience describes its SNDS as a line extension to its 20 mg product.

[5]

This Action arises from Pharmascience’s filing of the SNDS. Teva submits that Glatect

40 mg would be marketed in accordance with Pharmascience’s proposed Glatect Product

Monograph that is substantially identical to Teva’s Copaxone Product Monograph.

[6]

Teva argues that Pharmascience’s Glatect products will infringe the two patents at issue –

Canadian Patent Nos. 2,702,437 [the ‘437 Patent] and 2,760,802 [the ‘802 Patent]. Teva submits

that Pharmascience will manufacture, sell and induce the use of its products, which will be for

Page: 6

exactly the same patient population, in the same dosage strength, and with the same dosage

regimen to achieve the same outcomes. Teva submits that Pharmascience has not led any

evidence to demonstrate that it will not infringe. Pharmascience argues that the patents are

invalid.

[7]

The criteria for a diagnosis of MS is a point of contention between Teva and

Pharmascience as this has an impact on the scope of the claims of the ‘437 Patent and in turn the

allegations of infringement and invalidity. As described below, in the 1980s and 1990s, the

diagnosis of MS was based on criteria developed by Poser (Poser CM et al, “New Diagnostic

Criteria for Multiple Sclerosis: Guidelines for Research Protocols”, 1983 Ann Neurol 13(3): 227-

230 [the Poser criteria]) which required the demonstration of two clinical attacks. In 2001, new

criteria were developed by McDonald (McDonald et al, “Recommended diagnostic criteria for

multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis”,

2001 Ann Neurol 50: 121-127 [the McDonald criteria]) which relied more extensively on

magnetic resonance imaging [MRI] evidence to demonstrate the disease and its progression. The

McDonald criteria were updated in 2005, 2010 and 2017. The experts noted that while the

McDonald criteria gained wide acceptance, the Poser criteria and terminology remain within

their knowledge and some physicians continue to refer to the Poser criteria.

[8]

Teva submits that the claims of the ‘437 Patent are directed only to patients who have had

one clinical attack and have not yet been diagnosed with MS.

Page: 7

[9]

Teva does not dispute that Copaxone 20 mg was known as an effective therapy for

patients diagnosed with relapsing-remitting multiple sclerosis [RRMS], a type of MS. Teva

argues that the ‘437 Patent was novel and inventive in identifying 20 mg of glatiramer acetate

daily for the early treatment of patients after their first clinical attack and before the onset of MS.

Teva argues that the prior art relied on by Pharmascience was obscure and only speculated that

glatiramer acetate administered daily would be effective for the early treatment of patients.

[10] Pharmascience argues that it will not infringe the ‘437 Patent because the patent is invalid

and because its Glatect 40 mg product is not intended for the single-attack patient but for patients

who meet the criteria for a diagnosis of MS or RRMS.

[11] Pharmascience asserts the Gillette defence in response to Teva’s allegations of

infringement. Pharmascience argues that it does not infringe the ‘437 Patent because its Glatect

product merely practices the teachings of the prior art. Pharmascience submits that the claims of

the ‘437 Patent include RRMS patients, and the prior art includes that glatiramer acetate was

well known to be an effective treatment for RRMS.

[12] Pharmascience also argues that the ‘437 Patent is neither novel nor inventive and, as a

result, is invalid due to anticipation and obviousness.

[13] Pharmascience submits that, although the claims of the ‘437 Patent reflect the Poser

criteria, the claims include some patients who meet the McDonald criteria for MS. If

Pharmascience’s interpretation prevails, then those patients who have had only one clinical

Page: 8

attack but who meet the criteria for a diagnosis of MS (i.e., based on MRI evidence) would fall

within the claims of the ‘437 Patent. Argueably, these MS patients are no different from the

RRMS patients for which Copaxone 20 mg was a well-known treatment.

[14] Pharmascience also submits that if the claims of the ‘437 Patent are interpreted narrowly,

to single-attack patients (as Teva proposes), the claims are still anticipated by the prior art, which

recommended that glatiramer acetate should be considered for the early treatment of such

patients.

[15] Pharmascience argues that the claims are obvious because there was no difference

between the state of the art in November 2007 and the subject matter of the claims.

[16] Jurisdictional issues have been raised by Pharmascience regarding whether the scope of

the Regulations permits Teva to assert infringement of the ‘437 Patent with respect to Glatect

20 mg on a go-forward basis in these circumstances, given that Pharmascience has already

obtained a NOC. This issue is addressed later in these Reasons in Part XXVI.

[17] With respect to the ‘802 Patent, Teva argues that Pharmascience will infringe the patent

because Pharmascience’s Glatect product is indicated for the very same patient population,

primarily patients with RRMS, with the same dosing schedule of 40 mg three times weekly.

Teva disputes that the ‘802 Patent is invalid for obviousness or lack of sound prediction of

utility.

Page: 9

[18] Teva argues that there were material differences between the state of the art in August

2009 and the subject matter of the claims of the patent. Teva disputes that the prior art relied on

by Pharmascience was authoritative or known by the person skilled in the art [POSITA or skilled

person] or would be considered as a “mosaic” by the POSITA. Teva argues that the POSITA

would not reach the invention using their common general knowledge and routine work. Rather

inventiveness was required. Teva submits that there is no question that the 40 mg three times per

week invention is inventive and useful.

[19] Pharmascience submits that it will not infringe Teva’s ‘802 Patent because the ‘802

Patent is invalid due to obviousness.

[20] Pharmascience alternatively submits that if the ‘802 Patent is not obvious based on the

prior art, then Teva has neither demonstrated utility nor soundly predicted utility. Teva notes that

there are no results set out in the ‘802 Patent, but only a proposal for a study of the expected

results.

[21] Generally, the parties have mapped out different paths to lead to the findings they seek

and have pointed to excerpts in the evidence in support of their particular directional paths.

However, the role of the Court is to take the “high road” and to consider all the relevant evidence

in its proper context.

[22] Both Teva and Pharmascience raised objections to particular evidence of the other party.

Page: 10

[23] For example, Teva submits that Pharmascience has engaged in case splitting by

introducing new evidence, in particular, the international patent application WO 2007/081975

[Pinchasi 2007], noted in Dr. Ari Green’s responding report on non-infringement. Pharmascience

disputes this allegation and argues that it clearly pleaded the Gillette defence as an infringement

issue. Pharmascience explains that Dr. Green was given and asked to review the prior art product

monographs for Copaxone and Pinchasi 2007 and to describe how a skilled person would

understand them. He was also asked to review the Glatect Product Monograph and to provide his

opinion as to whether it followed the teachings of the prior art.

[24] Pharmascience explains that it does not rely on Dr. Green’s opinion on Pinchasi 2007 in

his responding non-infringement report for its anticipation arguments; rather it relies on this

evidence for the Gillette defence. Pharmascience notes that Teva did not provide any reply to Dr.

Green’s non-infringement report.

[25] Pharmascience also notes that it clearly cited Pinchasi 2007 as an anticipatory reference

and it can, therefore, be relied on to show anticipation.

[26] Teva also submits that Pharmascience sought to introduce additional evidence in its

closing arguments. Pharmascience responds that the additional 21-page compendium contains

only excerpts of documents already in evidence to more clearly point to the references Dr. Green

relied on in his validity opinion.

Page: 11

[27] More generally, each party seeks to diminish the expertise and evidence of their

opponents’ experts by, among other things: questioning their understanding of the legal tests and

instructions provided; suggesting that they are in the pockets of big pharmaceutical companies

due to past research grants and consulting fees; suggesting that they have exceeded their

mandates; suggesting that they have not published in certain top scientific journals; suggesting

that they have cited other experts in the field in their publications who they now seem to differ

with on specific points; and, challenging their specific expertise, such as not being part of a drug

development team.

[28] In my view, all the experts have established their particular expertise and all have offered

evidence that is helpful to the Court on the issues at play. All the experts are clearly committed

to improving the experience of persons with MS. I have considered the submissions of both

parties who seek to discount the evidence of the other party’s witnesses. I have considered all of

the evidence in its proper context and have weighed it. I have not discounted the evidence of any

expert because they have been paid by the parties in this or other litigation or in their research, or

because they have published more or less extensively than other experts. Clearly, they are all

experts in the diagnosis and treatment of MS and have been so qualified for the purpose of this

Action. However, the experts have provided different opinions on key issues that are not possible

to reconcile. Cross-examination has identified some inconsistencies and frailties in some of the

evidence. However, some of the questions posed to the experts on cross-examination were

detailed and specific and understandably sought to elicit support for particular arguments. In

some instances, the questions and answers were confusing and contrived and have required me to

Page: 12

very carefully consider the totality of the expert’s extensive evidence. The assessment of the

evidence is addressed in the context of the relevant issues.

[29] For the reasons that follow, I find that the ‘437 Patent is not anticipated by Karussis D et

al, “A recommended treatment algorithm in relapsing multiple sclerosis: report of an

international consensus meeting”, 2006 Eur J Neurol 13: 61-71 [Karussis 2006]. However, I find

that the ‘437 Patent is obvious.

[30] The jurisdictional issue regarding Teva’s reliance on the Regulations to allege

infringement with respect to the 20 mg Glatect product need not be addressed given my

conclusion that the ‘437 Patent is not valid.

[31] I find that the ‘802 Patent is valid; it is not obvious and it soundly predicted its utility.

[32] With respect to infringement, if Pharmascience proceeds to market Glatect 40 mg in

accordance with its proposed SNDS, it will infringe the ‘802 Patent.

II.

A.

The Patents at Issue

The ‘437 Patent

[33] Yeda Research and Development Co., Ltd. [Yeda] is the owner of the ‘437 Patent.

Page: 13

[34] Pursuant to section 42 of the Patent Act, RSC 1985, c P-4 [Patent Act], Yeda has the

exclusive right, privilege and liberty of making, constructing, using and selling to others to be

used, the invention claimed in the ‘437 Patent.

[35] Yeda is a corporation with a head office in Rehovot, Israel.

[36] Teva Canada Innovation is a corporation with a head office in Montreal Quebec, and an

office in Toronto, Ontario. Teva Canada Limited is a corporation with a head office in Toronto,

Ontario.

[37] The ‘437 Patent is listed on the Patent Register maintained by the Minister pursuant to

the Regulations in respect of Teva's 40 mg glatiramer acetate product marketed under the brand

name Copaxone in 40 mg/1 mL pre-filled syringes for subcutaneous injection. Teva’s 20 mg

strength glatiramer acetate is not listed on the Patent Register.

[38] Teva notes that it has obtained Yeda’s consent for the inclusion of the ‘437 Patent on the

Patent Register maintained by the Minister pursuant to the Regulations. Teva is authorized by

Yeda to sell, and sells, the drug Copaxone (glatiramer acetate) in Canada.

[39] The ‘437 Patent is titled, “Methods of Delaying the Onset of Clinically Definite Multiple

Sclerosis”. The ‘437 Patent issued on June 25, 2013 and has not expired.

Page: 14

[40] The parties agree that the relevant date for claims construction is the date of the

publication of the patent, June 4, 2009. For anticipation and obviousness, the relevant date is the

claim date, November 28, 2007.

[41] The ‘437 Patent contains 50 claims. The claims relate to glatiramer acetate, or

medicaments comprising glatiramer acetate, for use in treating human patients at risk of

developing MS. The claims at issue (Claims 1, 2, 3, 4, 13, 14, 15, 16, 19, 24, 33, 47 and 50) are

set out at Annex 1.

[42] On November 13, 2018, Teva was served with a Notice of Allegation [NOA] from

Pharmascience, a generic pharmaceutical company, in respect of Glatect 40 mg regarding the

‘437 Patent. The NOA alleges that the ‘437 Patent would not be infringed by Pharmascience

making, constructing, using or selling Glatect and that the ‘437 Patent is invalid.

B.

The ‘802 Patent

[43] Yeda is also the registered owner of the ‘802 Patent and is a party to this Action pursuant

to subsection 6(2) of the Regulations.

[44] Pursuant to section 42 of the Patent Act, Yeda has the exclusive right, privilege and

liberty of making, constructing, using and selling to others to be used, the invention claimed in

the ‘802 Patent.

Page: 15

[45] The ‘802 Patent is listed on the Patent Register maintained by the Minister pursuant to

the Regulations in respect of Teva’s glatiramer acetate product marketed under the brand name

Copaxone in 40 mg /1 mL pre-filled syringes for subcutaneous injection.

[46] Teva notes that it has obtained Yeda's consent for the inclusion of the ‘802 Patent on the

Patent Register maintained by the Minister pursuant to the Regulations. Teva asserts that it is

authorized by Yeda to sell, and sells, the drug Copaxone (glatiramer acetate) in Canada.

[47] The ‘802 Patent is titled, “Low Frequency Glatiramer Acetate Therapy”.

[48] The parties agree that the relevant date for construing the claims is the publication date of

the patent application, February 24, 2011. The relevant date for the allegations of obviousness is

the claim date, August 20, 2009. The relevant date to assess utility is the filing date, August 19,

2010.

[49] The ‘802 Patent contains 66 claims. All claims relate to glatiramer acetate, or

medicaments comprising glatiramer acetate, for use in treating human patients with, or at risk of

developing, MS. The claims at issue are Claims 1, 2, 3, 4, 22, 24, 25, 36-39, 47-57, 59, 60, 63-66

and are set out at Annex 2.

[50] On November 13, 2018, Teva was served with a NOA from Pharmascience in respect of

Glatect regarding the ‘802 Patent. The NOA alleges that the ‘802 Patent would not be infringed

by Pharmascience making, constructing, using or selling Glatect and the ‘802 Patent is invalid.

Page: 16

III.

The Witnesses and the Nature of their Evidence

[51] The parties presented their evidence in both written reports from fact and expert

witnesses and oral testimony from many of the witnesses. The witnesses and a brief synopsis of

the nature of their evidence is set out below.

A.

The ‘437 Patent

(1)

Fact Witnesses for Teva

[52] Ms. Sigalit Zecharia Daniel is the Senior Director, Head of Global Clinical Quality at

Teva Pharmaceutical Industries Ltd. Ms. Daniel attached to her affidavit documents related to

clinical studies that Teva had conducted, including the clinical study protocols and reports.

[53] Dr. Rivka Kreitman holds a Ph.D. in biochemistry and completed a post-doctoral

fellowship in molecular biology and genetics. She joined Teva in 1993 and left in 2018. During

her time at Teva, among other things, she and her team were responsible for the research,

development, regulatory filings and clinical studies of Copaxone. Dr. Kreitman provided

documents related to the development of Copaxone. Dr. Kreitman has also provided evidence in

proceedings in other jurisdictions regarding the patents at issue.

Page: 17

(2)

Expert Witnesses for Teva

[54] Dr. Sarah Morrow is a neurologist with expertise in neurological disorders, including the

diagnosis and treatment of MS. Dr. Morrow described the POSITA, the disclosure of the ‘437

Patent and the construction of the claims. Dr. Morrow’s evidence focussed on whether the using

or selling of Pharmascience’s Glatect products, as described in the Glatect Product Monograph,

would infringe the claims of the ‘437 Patent.

[55] Dr. Selchen is a neurologist with expertise in neurological disorders, including the

diagnosis and treatment of MS. Dr. Selchen responded to Dr. Green’s invalidity opinion.

Dr. Selchen addressed the POSITA, common general knowledge, construction of the claims and

the state of the art in relation to the ‘437 Patent.

[56] Mr. Neil Palmer is an expert on the Canadian pharmaceutical marketplace. He is the

Founder, Senior Adviser, and President Emeritus of PDCI Market Access Inc., an Ottawa-based

pricing and reimbursement consultancy. Mr. Palmer’s evidence addressed, among other things,

the public and private reimbursement regimes relevant to glatiramer acetate including Copaxone

and Glatect. The parties agreed that Mr. Palmer’s report be accepted without oral testimony.

[57] Dr. Gregory Grant is a biochemist and professor of developmental biology and

biochemistry in medicine. Dr. Grant’s evidence addressed a biochemist’s understanding of

“glatiramer acetate” relative to the ‘437 and ‘802 Patents and assessed whether Glatect contains

Page: 18

glatiramer acetate. The parties agreed that Dr. Grant’s evidence be accepted without oral

testimony.

(3)

Fact Witnesses for Pharmascience

[58] Mr. Graham McKinnon is a registered patent agent in Canada and the United States.

Mr. McKinnon attached to his affidavit documents related to the filing history of the U.S. Patent

Application No. 11/651,212 and Canadian Patent No. 2,191,088 [the ‘088 Patent].

[59] Mr. Deirdre Cozier is the Director of Global Regulatory Affairs at Pharmascience,

responsible for compiling information and data and making submissions related to

Pharmascience’s pharmaceutical products to regulatory authorities worldwide, including Health

Canada. Mr. Cozier attached to his affidavit documents related to the regulatory filings of

Glatect, including the product monograph and SNDS.

(4)

Expert Witnesses for Pharmascience

[60] Dr. Ari Green is a neurologist with expertise in neurological disorders, including the

diagnosis and treatment of MS. He provided two reports with respect to the ‘437 Patent.

Dr. Green first set out his opinion on the validity of the ‘437 Patent and addressed anticipation,

citing Karussis 2006, and obviousness with reference to the prior art and common general

knowledge. Dr. Green also provided a second report in response to Dr. Morrow’s infringement

report. In the second report, Dr. Green addressed product monographs, elaborated on the target

Page: 19

patient population and cited additional prior art. Dr. Green has also provided expert evidence in

proceedings in other jurisdictions regarding the patents at issue or their equivalents.

[61] Ms. Susanne Picard is a pharmacist and regulatory affairs consultant with expertise in the

regulatory approval of pharmaceutical products. Ms. Picard’s evidence addressed, among other

things, the requirements for New Drug Submissions [NDS] and SNDS, the use of product

monographs and, more particularly, the Glatect SNDS and Product Monograph.

B.

The ‘802 Patent

(1)

Fact Witnesses for Teva

[62] Ms. Sigalit Zecharia Daniel and Dr. Rivka Kreitman, described above, also provided

evidence for the ‘802 Patent.

(2)

Fact Witnesses for Pharmascience

[63] Mr. Graham McKinnon and Mr. Deirdre Cozier, described above, also provided evidence

for the ‘802 Patent.

Page: 20

(3)

Expert Witnesses for Teva

[64] Dr. Reza Vosoughi is a neurologist with expertise in neurological disorders, including the

diagnosis and treatment of multiple sclerosis. Dr.Vosoughi’s evidence addressed the POSITA,

construction of the claims and infringement of the claims of the 802 Patent.

[65] Dr. Alexandre Prat is a neurologist with expertise in neurological disorders, including the

diagnosis and treatment of multiple sclerosis. Dr. Prat responded to Dr. Green’s opinion on the

invalidity of the ‘802 Patent.

[66] Dr. Simon Day is a biostatistician with expertise in clinical trial design and interpretation.

Among other things, Dr. Day addressed how the POSITA would have regardedthe results of

clinincal studies and other abstracts relating to glatiramer acetate.

[67] Mr. Neil Palmer and Dr. Gregory Grant, described above, also provided evidence for the

‘802 Patent.

(4)

Expert Witness for Pharmascience

[68] Dr. Ari Green, described above, also provided his opinion on the validity of the ‘802

Patent.

Page: 21

IV.

MS and its Diagnosis/Criteria

[69] MS is a disease of the central nervous system [CNS], which includes the brain, optic

nerve and spinal cord. MS is considered to be an inflammatory or autoimmune disease in which

the patient’s own immune system attacks the myelin of the CNS.

[70] As explained by Teva’s witness Dr. Morrow, and reiterated by the other experts, the CNS

is composed of grey matter and white matter. Grey matter contains neuron cell bodies, while

white matter contains axons, which are the projecting portions of neurons. The axons of the CNS

white matter are wrapped in a fatty substance known as myelin. The myelin forms a sheath

(analogous to insulation) that enables rapid transmission of electrical signals generated in neuron

cell bodies that are propagated along the length of axons.

[71] With MS, the body’s immune system attacks elements of the CNS and leads to the

destruction of the myelin sheath in the brain, optic nerve and spinal cord (referred to as

“demyelination”) and axonal loss, which causes CNS damage, or lesions over time.

[72] Demyelination may occur at various sites within the CNS. The symptoms experienced by

an MS patient depend upon the site or sites within the CNS that are affected by demyelination

and by the size of the lesions.

[73] Pharmascience’s expert, Dr. Green, explained that MS is characterized early on by

intermittent but potentially debilitating inflammatory and demyelinating events (also called

Page: 22

“attacks”, “relapses”, “exacerbations”, and “episodes”). One of the common presenting clinical

attacks is optic neuritis (which manifests itself as a loss of vision and pain behind the eye). Other

common clinical attacks include episodes of numbness, tingling, muscle weakness and spasticity,

incoordination, loss of control of bowel and bladder, general fatigue, dizziness and depression.

A.

Types of MS

[74] The expert witnesses all described the categories of MS in a similar manner noting that

the categories are related to the course or progression of the disease.

[75] The experts explained that as of November 2007, with respect to the ‘437 Patent, and as

of August 2009, with respect to the ‘802 Patent, four distinct clinical courses or categories of MS

had been described:

a. RRMS is characterized by intermittent and clearly defined relapses with at least partial

recovery or remission of some symptoms over weeks to months;

b. Secondary progressive MS [SPMS], which follows a diagnosis of RRMS is characterized

by progressive worsening of symptoms over time with fewer or no intermittent relapses

interspersed with periods of partial recovery;

c. Primary progressive MS [PPMS] is characterized by a steady decline in neurological

function without distinct relapses or remissions; and,

Page: 23

d. Progressive-relapsing MS [PRMS] is characterized by a steady decline in neurological

function from onset overlaid with occasional relapses and periods of recovery during

which progressive worsening of symptoms continues.

[76] Several experts explained that RRMS remains the most common type of MS.

B.

Clinically Isolated Syndrome

[77] Teva’s witness, Dr. Selchen explained that, as of November 2007, patients presenting

with a single clinical attack having features typical of MS were diagnosed as having a clinically

isolated syndrome [CIS]. Dr. Selchen noted that when examining a patient presenting with a

possible CIS, it would be important for the clinician to consider whether the CIS is caused by

something other than MS. Dr. Selchen also noted that it was recognized that many, but not all,

cases of MS begin as a CIS.

[78] MRI could be used for patients who had a single clinical attack to determine if the attack

was suggestive or supportive of an MS diagnosis.

[79] Dr. Green also explained that the term CIS was generally applied to patients who had a

single episode of clinical neurological worsening that was suspicious for demyelination with

MRI evidence of other lesions (at least one or two). CIS with evidence of MRI lesion(s) was

often distinguished from an episode that was suspicious for inflammatory demyelination but did

Page: 24

not have MRI lesions by calling it “high risk” CIS. Dr. Green stated that most of these “high

risk” CIS patients go on to develop RRMS.

[80] Dr. Green added that the primary means of distinguishing who is at risk of developing

future attacks is evidence of prior episodes that preceded the clinical event (the CIS event). As of

November 2007, this risk was largely assessed via the identification of suspect lesions on MRI.

C.

Diagnosis of MS

[81] All the experts agreed that the diagnosis of MS has evolved over time.

[82] The experts also agreed that there is no single diagnostic test for any type of MS. The

diagnosis is based on a combination of findings from a patient’s history, physical exam, ancillary

diagnostic tests (such as MRIs of the brain and spinal cord) and examination of cerebrospinal

fluid through lumbar puncture.

[83] As Dr. Green elaborated, by November 2007, MS diagnosis depended upon (and still

depends upon) numerous objective and subjective analyses. Objective analyses include clinical

examination, formalized clinical evaluations scored to measure disability, MRI scans, extended

clinical assessments (e.g., neuropsychological assessments and neurovisual assessments) and

relapse frequency assessments. Subjective assessments include patient questionnaires targeting

measurement of clinical progression.

Page: 25

[84] Although MS was diagnosed long before the 1980s, the criteria of relevance to this

Action are the Poser and McDonald criteria.

[85] The “Poser criteria” were developed in the 1980s. The Poser criteria depended to a great

extent on clinical observation.

[86] The concepts or pillars of the criteria are “dissemination in space” [DIS], described as

evidence of lesions at multiple locations in the CNS, and “dissemination in time” [DIT],

described as the occurrence of distinct episodes separated in time.

[87] Dr. Green explained that DIT and DIS continue to be crucial characteristic features of

MS.

[88] Dr. Selchen also explained that a diagnosis of MS can be made only after demonstration

of both DIT and DIS.

[89] Under the Poser criteria, a diagnosis of MS (also referred to as “clinically definite MS” or

CDMS) required evidence of multiple CNS lesions. This could be demonstrated by neurological

examination (referred to as clinical signs of neurological dysfunction) or by tests and procedures

that demonstrate the existence of a lesion without the patient having reported or observed a

clinical sign (referred to as paraclinical signs of neurological dysfunction, e.g., relying on MRI).

Patients had to have evidence that there was more than one lesion separated in space (i.e., DIS)

and evidence of more than one prior episode or relapse (i.e., DIT).

Page: 26

[90] Under the Poser criteria, a diagnosis of CDMS required:

 Two attacks and clinical evidence of two separate lesions; or

 Two attacks and clinical evidence of one lesion and paraclinical evidence (i.e., MRI) of

another, separate lesion.

[91] In simpler terms, the diagnosis in accordance with the Poser criteria (and in accordance

with the McDonald criteria) requires that the disease is demonstrated to affect different parts of

the CNS and at different times.

[92] Dr. Green explained that the Poser criteria initially established that, to make out a

diagnosis of CDMS, it was necessary to demonstrate that the disease involved more than one

pathway (DIS) and was not “monophasic” (i.e., a single phase) (DIT). This depended on clinical

evaluation and typically required that a patient have two identified attacks (i.e., relapses) of more

than 24 hours duration separated by more than a one-month interval together with clinical

evidence of lesions in at least two different places within the CNS.

[93] Dr. Morrow explained that according to the Poser criteria, a patient that has only

experienced one attack and had clinical or paraclinical signs of at least one CNS lesion was

referred to as having CIS.

[94] Dr. Morrow stated that the majority of CIS patients progress to being diagnosed with

CDMS. Dr. Green agreed. Dr. Selchen also agreed but noted that some patients would need to be

followed for a longer period of time.

Page: 27

[95] Dr. Selchen explained that CIS has been called a “clinical event suggestive of MS”

because in many patients it precedes a diagnosis of MS.

D.

Use of MRI

[96] By the early 2000s, MRI was increasingly relied on in the MS clinical setting.

Dr. Morrow explained that MRI is a highly sensitive technique for detection of tissue changes in

patients with MS. MRI is used as a paraclinical measure for the diagnosis of MS and to monitor

both disease activity and progression in patients.

[97] The experts explained how MRI of the brain to identify lesions that are characteristic of

MS depicts the disease and its progression and can guide the management of the disease. The

two main types of images are “T1-weighted” and “T2-weighted” images.

[98] Dr. Vosoughi and the other experts noted that inflammation in the brain can be observed

with the injection of Gadolinium (referred to as Gd or GAD). This was described as an imaging

technique in which the patient is given an “enhancing agent”, like a dye, to increase the contrast

between healthy and damaged tissues. Dr. Morrow and Dr. Green similarly explained the

visualization using MRI T1-weighted images and T2-weighted images and the use of Gd on

post-contrast images.

[99] Dr. Vosoughi explained that in patients with MS, T1 lesions tend to increase in number

and volume over time. In addition, when the immune system attacks the brain (or spinal cord) in

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MS patients, new T2 lesions appear. Over time, the number of T2 lesions and their volume

increases. In addition to diagnosis and progression of the disease, the measurement of the

number and volume of T1 and T2 lesions is used in clinical trials to monitor the effects of what

is being tried.

E.

The McDonald Criteria

[100] In 2001, the International Panel on MS Diagnosis published a report proposing revised

diagnostic criteria for MS, known as the “McDonald criteria”. The McDonald criteria permitted

the diagnosis of “monosymptomatic” disease (i.e., one attack) suggestive of MS, which was not

previously treated as MS, but would have been diagnosed under the Poser criteria as CIS (i.e.,

patients who had only one confirmed attack). The McDonald criteria also relied on the concepts

of DIS and DIT and highlighted the use of MRI along with other diagnostic methods.

[101] Dr. Green noted that the McDonald criteria were developed in response to the need for

earlier diagnosis of MS and the increasing use of MRI. Dr. Selchen explained that the McDonald

criteria responded to the need to diagnose with specificity and sensitivity; in other words, to

identify for treatment those patients that had MS and to exclude from treatment those that did not

have MS. MRI provided a means to document DIS and to standardize how to document DIT.

[102] The experts agreed that, by November 2007, it was routine to use MRI findings to

confirm a diagnosis of MS.

Page: 29

[103] In accordance with the McDonald criteria, a patient could be diagnosed with MS after a

single attack where MRI results could be relied upon to show objective evidence of DIT and DIS

(i.e., even if there is no clinical evidence of a second attack or no reporting of a second attack by

the patient).

[104] An excerpt from the abstract from McDonald 2001 states:

The revised criteria facilitate the diagnosis of MS in patients with a

variety of presentations, including “monosymptomatic” disease

suggestive of MS, disease with a typical relapsing-remitting

course, and disease with insidious progression, without clear

attacks and remissions. Previously used terms such as “clinically

definite” and “probable MS” are no longer recommended. The

outcome of a diagnostic evaluation is either MS, “possible MS”

(for those at risk for MS, but for whom diagnostic evaluation is

equivocal), or “not MS.”

[105] The McDonald criteria permitted a diagnosis of MS based on one clinical attack as long

as additional evidence was available. Two scenarios were described:

1. One attack with objective evidence of two or more lesions, which required:



dissemination in time demonstrated by MRI or

a second clinical attack

2. One attack with objective clinical evidence of one lesion (monosymptomatic or

CIS), which required:



dissemination in space demonstrated by MRI, or

 two or more MRI detected lesions consistent with MS plus positive

cerebral spinal fluid, and

Page: 30



dissemination in time demonstrated by MRI.

[106] The experts agreed that the McDonald criteria result in a diagnosis of either “MS”,

“possible MS” (where the diagnostic evaluation is equivocal) or “not MS”.

[107] All the experts noted how the criteria for diagnosis have evolved and agreed that the

McDonald criteria gained general acceptance. The experts agreed that the term CDMS has given

way to simply MS. Dr. Morrow explained, however, that the McDonald criteria did not

immediately replace the Poser criteria and that practicing neurologists remain familiar with the

terms CDMS and CIS. All the experts noted that the POSITA would still be familiar with the

terms under the Poser criteria and the McDonald criteria.

[108] The McDonald criteria were refined in 2005, 2010 and 2017.

[109] Dr. Green explained that under the McDonald criteria (Polman et al, “Diagnostic criteria

for multiple sclerosis: 2005 Revisions to the “McDonald Criteria”, 2005 Ann Neurol 58: 840-

846”), in addition to characteristic symptoms and signs on neurological examination, patients

could be diagnosed based on characteristic findings on MRI of the brain and spinal cord. For

example, where a patient presented with a history of two episodes or attacks characteristic of MS

but only one lesion was confirmed by objective clinical evidence, the McDonald criteria

permitted MRI findings to be relied upon to establish that the disease had affected more than one

area of the CNS and to support a diagnosis of MS. Alternatively, where neurological

examination revealed objective clinical evidence of two or more lesions in the CNS, but the

Page: 31

patient history suggested only one attack, the McDonald criteria permitted MRI findings to be

relied upon to establish that the disease was sufficiently disseminated in time to make a diagnosis

of MS.

[110] The experts noted that with the introduction of the 2005 McDonald criteria, relatively

more CIS patients were diagnosed as having MS (typically RRMS) on the sole basis of

appearance of new MRI lesions, regardless of whether new clinical symptoms developed or

whether the lesions were “clinically silent”.

F.

The Difference between the Poser and McDonald Criteria vis-à-vis a CIS patient

[111] A point of contention in this Action is whether the claims of the ‘437 Patent are directed

to a single attack (or CIS) patient, i.e., a patient who has had a single attack without more, or are

also directed to a single attack patient who meets the McDonald criteria for a diagnosis of MS,

but has not yet had a second clinical attack. Teva submits that the claims are clearly directed to

administering glatiramer acetate to a CIS patient who has not yet had a second clinical attack

and, as a result, has not been diagnosed with CDMS. Teva submits that the claims are not

directed at patients who have been or could be diagnosed with MS pursuant to the McDonald

criteria.

[112] Pharmascience argues that the McDonald criteria were the applicable diagnostic criteria

in 2007 and that some single attack (or CIS) patients that are diagnosed pursuant to the

Page: 32

McDonald criteria with MS and who have not yet had a second attack would also fall within the

claims of the ‘437 Patent.

[113] This issue is addressed below in the context of the construction of the claims.

V.

Overall Position of the Plaintiff Teva on the ‘437 Patent

[114] Teva notes that its glatiramer acetate product, Copaxone, is a therapy effective for the

treatment of patients in the relapsing-remitting phase of MS (i.e., RRMS) to reduce the

frequency of clinical relapses.

[115] Teva explains that after the initial approval of Copaxone in the 1990s, it spent over 10

years engaged in research and development to improve its product. Teva notes that it had failures

but also successes, notably the invention of the ‘437 and ‘802 Patents.

[116] Teva submits that Pharmascience seeks to benefit from Teva’s hard work, investment and

inventiveness.

[117] Teva disputes Pharmascience’s allegation or suggestion that it is seeking to extend the

life of its patents, referred to as “evergreening”. Teva acknowledges that its 20 mg Copaxone

product has been available for many years. The 40 mg Copaxone product was approved for sale

in Canada in 2016. Teva also acknowledges that Pharmascience already obtained a NOC to

market its 20 mg glatiramer acetate, Glatect.

Page: 33

[118] Teva explains that it designed and conducted a Phase III clinical trial in the early 2000s

(the PreCISe trial) to study the effect of glatiramer acetate in patients who had experienced a

single attack suggestive of MS and prior to development of CDMS.

[119] Teva characterizes patients who have experienced a single attack suggestive of MS, but

who have not yet been diagnosed with MS, as CIS patients.

[120] Teva filed and obtained the ‘437 Patent based on the results of the PreCISe trial. Teva

received regulatory approval for the new indication of CIS in its Product Monograph in 2009.

[121] Teva submits that the claims of the ‘437 Patent are directed to the use of glatiramer

acetate to treat CIS patients, including a claim specifying a reduction of at least 50% in new T2

lesions.

[122] Teva submits that Copaxone and Glatect will be used in the same manner if approved in

accordance with Pharmascience’s SNDS and draft combined Product Monograph. Teva also

submits that Glatect 40 mg would be marketed in accordance with a Product Monograph that is

substantially identical to Teva’s Copaxone Product Monograph.

[123] Teva notes that Pharmascience has not provided any evidence to establish

non-infringement.

Page: 34

[124] Teva submits that Pharmascience cannot rely on the Gillette defence to infringement.

Teva submits that Pharmascience is splitting its case and has taken Teva by surprise by seeking

to introduce new evidence in Dr. Green’s responding report to the report of Dr. Morrow, Teva’s

infringement expert. Teva further submits that the law and the facts do not support the Gillette

defence.

[125] Teva disputes that the ‘437 Patent is anticipated by the art cited by Pharmascience,

Karussis 2006, discussed more fully below.

[126] Teva also disputes that the ‘437 Patent is obvious. Teva submits that there are material

differences between the state of the art in 2007 – which, among other things, did not establish

with any evidence that glatiramer acetate would be effective for CIS patients – and the subject

matter of the claims. Teva argues that arriving at the invention required inventiveness.

[127] More generally, Teva alleges that the evidence of Pharmascience’s expert on validity,

Dr. Green, was inconsistent and should be approached with caution. Teva goes further in

challenging Dr. Green’s evidence suggesting that Dr. Green went beyond the role of an expert

witness and strayed into an advocate for Pharmascience’s position.

VI.

Overall Position of the Defendant Pharmascience on the ‘437 Patent

[128] Pharmascience notes that Teva’s Copaxone products have benefited from a 20-year

monopoly in the Canadian market.

Page: 35

[129] Pharmascience submits that Teva has attempted to extend its monopoly and “evergreen”

its invention of glatiramer acetate (Copaxone) through successive patents, which purport to add

old uninventive features.

[130] Pharmascience argues that its manufacture, marketing, sale and the overall use of its

Glatect products will not infringe the ‘437 Patent.

[131] Pharmascience raises the Gillette defence against Teva’s allegations of infringement of

the ‘437 Patent. Pharmascience submits that it is merely practising the teachings of the prior art

which recognized that glatiramer acetate was effective for RRMS and, as a result, Teva’s patent

is invalid. Alternatively, if Teva’s patent is valid it cannot be infringed by Pharmascience.

[132] Pharmascience also argues that the ‘437 Patent is invalid due to anticipation and

obviousness.

[133] Pharmascience submits that, as drafted, the claims of the ‘437 Patent would encompass

patients diagnosed pursuant to the modern and prevailing McDonald criteria. More specifically,

patients who have had a single attack but have not yet had a second clinical attack would be

included where they meet the criteria for MS pursuant to the McDonald criteria.

[134] Pharmascience notes that, by November 2007, glatiramer acetate was a first-line

treatment for patients with RRMS, which would include patients who had experienced a single

attack and met the McDonald criteria for MS.

Page: 36

[135] Pharmascience also argues that if the claims are interpreted narrowly, as advanced by

Teva, the claims are still anticipated and are obvious.

[136] Pharmascience disputes what it characterizes as Teva’s “extreme” position – i.e., that

until a Phase III clinical trial had been completed to demonstrate that early treatment of single

attack or CIS patients with glatiramer acetate was successful, the use of glatiramer acetate to

treat such patients remained novel and inventive.

[137] In support of its position that the ‘437 Patent is anticipated, Pharmascience points to

Karussis 2006. Pharmascience describes Karussis 2006 as the consensus of an international

group of 13 MS specialists [the Karussis Working Group] that indicates that glatiramer acetate

should be used to treat single-attack patients who meet the McDonald criteria and also those who

fall short of meeting the McDonald criteria.

[138] Pharmascience submits that Karussis 2006 indicated that glatiramer acetate “should

work” in the treatment of single-attack patients (including those who fell short of the McDonald

criteria for MS) and that it would be reasonable to use it to treat such patients.

[139] With respect to anticipation, Pharmascience submits that Karussis 2006 meets the

requirements of disclosure and enablement.

[140] Pharmascience further submits that claim 16 of the ‘437 Patent is anticipated by Pinchasi

2007 as it disclosed the use of 40 mg glatiramer acetate for the treatment of RRMS.

Page: 37

[141] Pharmascience also argues that there are no differences between the state of the art in

November 2007, which includes Karussis 2006, and the claims of the ‘437 Patent. As a result,

the ‘437 Patent was obvious. Pharmascience submits that, to the extent that there were any

differences, these would easily be bridged by the POSITA using the common general knowledge

and information found by conducting a reasonably diligent search.

[142] Pharmascience challenges Teva’s reliance on the Regulations to obtain declarations of

patent infringement in respect of both of Pharmascience’s products – Glatect 20 mg administered

daily and Glatect 40 mg administered three times per week – given that Pharmascience obtained

a NOC for Glatect 20 mg in 2017 and has been marketing it since that time.

VII. Overall Position of the Plaintiff Teva on the ‘802 Patent

[143] Teva reiterates that it worked over the years to improve its products, including to develop

an oral formulation, which proved unsuccessful in a Phase III clinical trial (CORAL), and to

develop a 40 mg daily dose of glatiramer acetate, which did not prove to be more effective than

the 20 mg dose in the Phase III clinical trial (FORTE).

[144] Teva notes that the ‘802 Patent was the result of a successful Phase III clinical trial

(GALA) that showed that 40 mg glatiramer acetate administered three times weekly was

effective for the treatment of RRMS.

Page: 38

[145] Teva argues that Pharmascience’s Glatect product will infringe the ‘802 Patent as

Pharmascience’s product will be used in exactly the same manner as Copaxone 40 mg if it is

approved in accordance with Pharmascience’s SNDS and proposed draft Product Monograph.

Teva notes that Pharmascience has not provided any evidence that it will not infringe, rather it

alleges only that the ‘802 Patent is invalid.

[146] Teva disputes that the ‘802 Patent is invalid due to obviousness or lack of sound

prediction of utility.

[147] Teva submits that Pharmascience has adopted a hindsight approach to obviousness and

has “cherry-picked” the prior art, some of which is obscure, to carve a path to show that the state

of the art was such that an every other day dose of 40 mg glatiramer acetate was known and that

it would be self-evident to simply change the administration to three times a week.

[148] Teva submits that the evidence of its experts should be preferred as it was more balanced.

Teva submits that without knowledge of the invention as claimed it would not have been obvious

to a POSITA to administer 40 mg glatiramer acetate three times per week to RRMS patients.

[149] Teva notes that Pharmascience has led no evidence to support its argument that the ‘802

Patent lacks utility. Teva notes that all that is required is a scintilla of utility and there is no doubt

that Copaxone 40 mg is useful.

Page: 39

[150] With respect to the allegations regarding lack of sound prediction of utility, Teva notes,

among other things, that the ‘802 Patent includes a detailed description of the GALA study, a

Phase III clinical trial, including efficacy and safety results of 40 mg glatiramer acetate three

times per week, and includes at least 18 references to support the invention.

VIII.

Overall Position of the Defendant Pharmascience on the ‘802 Patent

[151] Pharmascience submits that the ‘802 Patent is invalid due to obviousness. Alternatively,

it is invalid due to inutility or lack of sound prediction of utility.

[152] Pharmascience submits that Teva had already publicly disclosed an every-other-day

dosing regimen for 40 mg glatiramer acetate. Pharmascience relies on a mosaic of the prior art to

argue that the state of the art was that 40 mg glatiramer acetate was known to be effective (as

was 20 mg) on an alternate day basis. Pharmascience submits that the difference between the

state of the art and the claims of the ‘802 Patent is only the difference of one less 40 mg dose in a

two-week period. Pharmascience argues that it is easier for a patient to remember to take their

medication three times a week on fixed days rather than every other day. Pharmascience argues

that the difference between the state of the art and the claims would be easily bridged by the

POSITA who would move to the fixed day regime.

[153] Pharmascience also suggests that the Court’s determination of the validity of the ‘802

Patent should be informed by related proceedings. Pharmascience notes that the ‘802 Patent is

Page: 40

being examined by the Canadian Intellectual Property Office [CIPO], and that equivalent patents

have been found to be obvious in the U.K. and U.S.

[154] Pharmascience argues that if the ‘802 Patent is not obvious due to the state of the prior

art, then Teva cannot resort to the prior art that it discounts or rejects to support the utility or

sound prediction of utility of the ‘802 Patent.

[155] Pharmascience argues that the evidence of its experts should be preferred. Pharmascience

submits that Teva’s experts were misinstructed regarding the test for obviousness and, more

generally, are not of the same caliber as its expert Dr. Green who, among other expertise, is

experienced in clinical trial design.

IX.

Onus and Burden of Proof

[156] The burden is on the Defendant, Pharmascience, to prove each ground of invalidity on a

balance of probabilities. The burden is on the Plaintiff, Teva, to prove infringement on a balance

of probabilities. Where the validity of a patent is at issue, the starting point is that the patent is

presumed to be valid.

X.

The ‘437 Patent – Description and Disclosure

[157] The ‘437 Patent is titled, “Method of Delaying the Onset of Clinically Definite Multiple

Sclerosis”.

Page: 41

[158] The ‘437 Patent acknowledges that it cites various publications and that these

publications are incorporated by reference into the patent application “to more fully describe the

state of the art to which this invention pertains”. These references include: the Poser criteria;

Brex PA et al, “A longitudinal study of abnormalities on MRI and disability from multiple

sclerosis”, 2002 N Engl J Med 346(3): 158-164 [Brex 2002]; Frohman EM et al, “The utility of

MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of

the American Academy of Neurology”, 2003 Neurology 61(5): 602-611 [Frohman 2003];

Johnson KP et al, “Copolymer 1 reduces relapse rate and improves disability in relapsing-

remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled

trial. The Copolymer 1 Multiple Sclerosis Study Group”, 1995 Neurology 45: 1268-1276

[Johnson 1995]; Cohen JA et al., Rovaris, “9006 Study Group. Randomized, double-blind, dose-

comparison study of glatiramer acetate in relapsing–remitting MS”, Neurology, 2007, 68(12):

939-944 [Cohen 2007 or FORTE Phase II]; and, Comi G et al, “European/Canadian Multicenter,

Double-Blind, Randomized, Placebo-Controlled Study of the Effects of Glatiramer Acetate on

Magnetic Resonance Imaging-Measured Disease Activity and Burden in Patients with Relapsing

Multiple Sclerosis”, 2001 Ann Neurol 49: 290-297 [Comi 2001].

[159] In the Background of the Invention, the authors state that MS is “one of the more

common chronic neurological diseases in human adults” and that it is a “chronic, inflammatory

[CNS] disease characterized pathologically by demyelination” and “classified as an autoimmune

disease”.

Page: 42

[160] The ‘437 Patent states that “MS disease activity can be monitored by cranial scans,

including [MRI] of the brain, accumulation of disability, as well as rate and severity of relapses”.

[161] The ‘437 Patent further states that that the diagnosis of CDMS as determined by the

Poser criteria “requires at least two neurological events suggesting demyelination in the CNS

separated in time and in location”.

[162] The ‘437 Patent notes that a CIS is a single monosymptomatic attack suggestive of MS

such as optic neuritis, brain stem symptoms, and partial myelitis. It states that “[p]atients with

CIS that experience a second clinical attack are generally considered to have [CDMS]” and that

“[o]ver 80 percent of patients with a CIS and MRI lesions go on to develop MS, while

approximately 20 percent have a self-limited process”.

[163] The ‘437 Patent describes five types of MS: benign, RRMS, secondary progressive MS,

progressive relapsing MS and primary progressive MS.

[164] The ‘437 Patent describes glatiramer acetate and notes that it is marketed as Copaxone

which had been approved as a 20 mg glatiramer acetate injection for patients with RRMS.

[165] The ‘437 Patent also notes that the synthesis of Copaxone had been disclosed in several

U.S. patents and that the formulation of 40 mg Copaxone has been disclosed in a U.S. patent.

Page: 43

[166] The ‘437 Patent further states that the “efficacy of Copaxone® in reducing the frequency

of relapses in patients with RRMS is well established” and that both the 20 and 40 mg daily

subcutaneous dose have been shown to reduce the total number of enhancing lesions in MS

patients as measured by MRI (citing Cohen 2007).

[167] The ‘437 Patent notes that it was an open question whether Copaxone would be effective

in patients suffering from earlier stages of MS and that there was a debate in the medical and

scientific community as to the benefits of commencing MS therapy at the early stage. It states:

“[s]pecifically, questions exist regarding whether the benefits of early treatment outweigh the

inconvenience, cost, potential adverse effects of treatment, and the risk of submitting patients

that independently of treatment would not experience further events to unnecessary long-term

therapy”.

[168] The Summary of the Invention states that the invention “provides a method for delaying

the onset of [CDMS] in a patient at risk of developing [CDMS], the method comprising

periodically administering a pharmaceutical composition comprising a therapeutically effective

amount of glatiramer acetate to the patient, thereby delaying onset of [CDMS] in the patient”.

[169] The Summary adds, among other things, that the invention also provides a method to

reduce progression of MRI-monitored disease activity in a patient at risk of developing CDMS, a

method for reducing the progression of symptoms, and a method of delaying the progression to

CDMS. The Summary adds that the invention of the medicament of glatiramer acetate is for the

treatment of a patient who: “experienced a single demyelinating event and an active

Page: 44

inflammatory process, which are indicative of the patient being at high risk of developing

CDMS”; and, who “experienced a first clinical event suggestive of [MS] and is at risk of

developing [CDMS]”.

[170] The ‘437 Patent sets out definitions of the terms used therein. These definitions are noted

in the discussion in Part XV, Construction of the Claims.

[171] The ‘437 Patent includes five examples to illustrate the invention and to “aid in an

understanding of the invention” but not to “limit in any way the invention as set forth in the

claims”. The examples describe a clinical trial to assess the effect of treatment with daily

subcutaneous injections of 20 mg of glatiramer acetate compared to placebo on the time to

conversion to CDMS as determined by the Poser criteria. Examples 1, 2 and 5 specifically refer

to evaluating the effect of glatiramer acetate on patients presenting with CIS.

[172] The ‘437 Patent states that the results of the examples “show that early, pre-diagnosis i.e.,

pre-CDMS, [glatiramer acetate] treatment confers long-term benefits on MS symptoms and on

the progression of disability”.

[173] The ‘437 Patent further states that the results show that glatiramer acetate “delays the

development of [CDMS] when administered to patients presenting a single, clinically isolated

syndrome (CIS) suggestive of MS”.

Page: 45

XI.

The ‘802 Patent – Description and Disclosure

[174] The 802 Patent is entitled, “Low Frequency Glatiramer Acetate Therapy”.

[175] The ‘802 Patent acknowledges that “[t]hroughout this application various publications are

referenced by their full citations. The disclosures of these publications are referenced in this

application in order to more fully describe the state of the art”.

[176] In the Background of the Invention, MS is described, as are the various types of MS and

methods to monitor the disease. Glatiramer acetate is also described.

[177] The ‘802 Patent explains that patients suffering from RRMS “experience sporadic

exacerbations or relapses, as well as periods of remission” and that “[l]esions and evidence of

axonal loss may or may not be visible on MRI for patients with RRMS”.

[178] The ‘802 Patent notes that glatiramer acetate “is marketed under the tradename

Copaxone®” and that Copaxone as a 20 mg daily injection “is an approved therapy for patients

with [RRMS], including patients who have experienced a first clinical episode”.

[179] The ‘802 Patent also notes that “[t]he 20mg/day subcutaneous (s.c.) dose has been shown

to reduce the total number of enhancing lesions in MS patients as measured by MRI” and that

“[s]afety data accumulated for [glatiramer acetate] in clinical trials shows that the drug product is

safe and well tolerated”.

Page: 46

[180] The Summary of the Invention describes a “method of alleviating a symptom of [RRMS]

in a human patient suffering from [RRMS] or a patient who has experienced a first clinical

episode and is determined to be at high risk of developing [CDMS] comprising administering to

the human patient three subcutaneous injections of a therapeutically effective dose of glatiramer

acetate over a period of seven days with at least one day between every subcutaneous injection

so as to thereby alleviate the symptom of the patient”.

[181] The ‘802 Patent describes several embodiments including “the therapeutically effective

dose of glatiramer acetate is 40mg/ml”.

[182] Under the Detailed Description of the Invention, the ‘802 Patent again describes its goal

and sets out the several potential embodiments, including several different schedules of three

injections per week. Other embodiments describe means of alleviating the symptoms of RRMS,

for example, reducing the level of disability and reducing the number of different types of

lesions.

[183] The ‘802 Patent includes the following definitions:

Immediate post injection reaction (IRPR)” refers to “a reaction

such as, palpitations, feeling hot, flushing, hot flushes, tachycardia,

dyspnoea, chest discomfort, chest pain, and non-cardiac chest pain

that occurs immediately following injection.

Injection site reaction (ISR)” refers to “a reaction such as

erythema, hemorrhage, induration, inflammation, mass, pain,

pruritus, urticaria, and welt that occurs immediately around the site

of injection.

Tolerability” relates to “the level of discomfort associated with

[glatiramer acetate] treatment” and “is associated with the

frequency and severity of post injection reactions and injection site

Page: 47

reactions” and “influences the period that a patient can follow

[glatiramer acetate] treatment.

[184] Other definitions include, “clinically isolated syndrome”, “Gd-enhancing lesions”,

“single clinical attack”, and reference is made to the Poser criteria for a diagnosis of CDMS.

[185] The ‘802 Patent notes that the example section is set out to aid in understanding of the

invention but is not intended to “limit in any way the invention as set forth in the claims”.

[186] Experimental Details are set out over 16 pages.

[187] The Discussion notes that a “significant drawback to [glatiramer acetate] therapy is the

requirement of daily injections, which can be inconvenient”. It adds that “in all clinical trials,

injection-site reactions were seen to be the most frequent adverse reactions and were reported by

the majority of patients receiving [glatiramer acetate]” (as compared to placebo).

[188] The ‘802 Patent has 66 claims. The asserted claims are set out in Annex 2. Note that the

asserted claims all address the use of 40 mg glatiramer acetate for RRMS patients.

XII. The Structure of this Judgment

[189] As noted, Teva alleges infringement by Pharmascience of both the ‘437 and the ‘802

Patents. Pharmascience disputes that it will infringe and alleges that the ‘437 and ‘802 Patents

are invalid. The principles from the jurisprudence, set out below, apply to the determination of

Page: 48

the issues with respect to both patents. There is some evidence that applies to both patents,

including about the treatment of MS. However, other evidence is specific to the patent at issue.

The allegations regarding the ‘437 Patent are addressed first, followed by the allegations

regarding the ‘802 Patent.

XIII. Overview of the Experts’ Evidence re the ‘437 Patent

A.

Pharmascience’s Expert, Dr. Green

[190] Dr. Green described the POSITA as a medical professional (e.g., a neurologist), with

experience evaluating and diagnosing patients with MS and administering therapeutic agents for

the treatment of MS, who would also be a member of a drug development team.

[191] With respect to the common general knowledge as of November 28, 2007, Dr. Green

stated that the POSITA would be knowledgeable about MS and its characteristics, the

classification of MS, brain imaging (including the use of MRI), the evolution of diagnostic

criteria for MS, CIS, MS therapies (including glatiramer acetate) and CIS therapies (including

ongoing clinical studies of glatiramer acetate) and, more generally, the treatment of MS. Dr.

Green set out the sources of knowledge, including conferences, journals, online resources such as

PubMed and EMBASE (a subscription literature database) and the articles found therein. Dr.

Green referred to several reports of studies, suggesting that these were part of the common

general knowledge.

Page: 49

[192] Dr. Green stated that generally, the ‘437 Patent relates to the treatment of patients who do

not yet have CDMS to delay the onset of CDMS (and the progression of MS-related symptoms).

He stated that, more particularly, the ‘437 Patent relates to the use of glatiramer acetate, which

was a known treatment for patients suffering CDMS (in particular RRMS), to treat patients who

had not yet developed CDMS.

[193] In his written opinion, Dr. Green noted that while all the claims use slightly different

language to describe the patient groups, the POSITA would understand that the claimed patient

population for all claims is a CIS patient at risk of developing CDMS (and who has not yet

developed CDMS) and who presents with at least one lesion consistent with MS.

[194] In his written report in response to Dr. Morrow’s report on validity, and in his oral

evidence, Dr. Green opined that the claims also covered patients with MS in accordance with the

McDonald criteria.

[195] Dr. Green stated that the inventive concept of the claims of the ‘437 Patent is the same as

the subject matter defined by the claims. Other experts agreed.

[196] In Dr. Green’s opinion, the claims of the ‘437 Patent were anticipated. Dr. Green stated

that Karussis 2006 both disclosed and enabled the subject matter of all the claims of the ‘437

Patent.

Page: 50

[197] In Dr. Green’s opinion, the subject matter of the claims was also obvious. Dr. Green

stated that there was no difference between the state of the art in 2007 and the subject matter of

the claims disclosed in the ‘437 Patent.

[198] Dr. Green stated that, by November 2007, a large Phase III clinical study using glatiramer

acetate to treat CIS patients was underway (i.e., the PreCISe trial). He also stated that the

consensus of leaders in the field was that using glatiramer acetate to treat CIS patients was

reasonable and “should work”, and that the ongoing clinical study (i.e. the PreCISe trial) was

likely to show that early treatment at the time of the initial CIS would have enhanced efficacy

compared to later treatment of RRMS.

[199] Dr. Green added that, to the extent that there was any difference between the state of the

art and the inventive concept, it would have been easily bridged by the POSITA using the

common general knowledge. No inventive ingenuity was required.

[200] Dr. Green explained that the POSITA was aware of the concept of CIS. He added that

disease-modifying drugs or therapies [DMDs or DMTs] (e.g., interferons) used to treat MS

including RRMS had been shown to be effective in treating CIS patients by reducing the

likelihood of progression to CDMS and/or delaying the progression to CDMS. Dr. Green added

that the POSITA would be motivated to find new treatments, and glatiramer acetate was the

obvious choice.

Page: 51

[201] Dr. Green provided a second written opinion in response to the report on infringement by

Teva’s expert, Dr. Morrow. Dr. Green’s second report addresses several mandates.

[202] Dr. Green indicated that he generally agreed with Dr. Morrow’s opinions regarding the

scientific and clinical overview of RRMS, description of the POSITA and construction of the

claims.

[203] Dr. Green criticised Dr. Morrow’s use of the terms “CDMS” and “probable MS” given

her acknowledgement that these terms were not used after the McDonald criteria were adopted.

In Dr. Green’s opinion, the McDonald criteria had replaced the Poser criteria by 2005, at the

latest. However, Dr. Green agreed that practicing neurologists remain familiar with the terms

CDMS and CIS.

[204] Dr. Green acknowledged that in 2007 a CIS diagnosis would have been for patients who

had a single clinical event suggestive of MS.

[205] Dr. Green offered a revised opinion regarding the patients addressed by the claims. In his

responding report he stated that “by June 4, 2009, … at least some patients presenting with a

single clinical attack and at least one lesion would have been categorized as having MS pursuant

to the 2005 McDonald Criteria” and would be included within the claims.

[206] Dr. Green’s evidence on this issue is elaborated on in the discussion on the construction

of the claims in Part XV.

Page: 52

[207] In his second report, Dr. Green referred to Pinchasi 2007 (a patent application). Dr. Green

stated that, as read and understood shortly before November 28, 2007, Pinchasi 2007 directed

physicians to use glatiramer acetate to treat patients with RRMS, which would include some

patients who had only experienced a single clinical attack. On cross-examination, Dr. Green

agreed that a physician would not read Pinchasi 2007 to guide their prescribing practices in 2007

or now.

[208] Dr. Green also provided his opinion on product monographs in general and, more

specifically, on the Copaxone 2001 and 2006 product monographs.

[209] Dr. Green stated that, prior to November 2007, he and other physicians prescribed

Copaxone to treat CIS patients (i.e., patients who had only experienced a single clinical attack

but did not meet the 2005 McDonald criteria to confirm a diagnosis of MS). He acknowledged

that this was “off-label” use, meaning uses not approved and not indicated in the product

monograph.

[210] Dr. Green was challenged on his inconsistent testimony in proceedings in the U.K. where

he suggested that off-label use should only be done in the context of a research study.

B.

Teva’s Expert, Dr. Morrow

[211] Dr. Morrow provided an overview of the scientific and clinical history of MS, including

the criteria for its diagnosis, as it relates to the ‘437 Patent. Dr. Morrow explained that the Poser

Page: 53

criteria for diagnosing MS, which were introduced in the 1980s, used the term CIS for patients

who had experienced only a single clinical attack, and CDMS for patients who had experienced

at least two clinical attacks.

[212] Dr. Morrow noted that the Poser criteria were gradually replaced by the McDonald

criteria, which do not use the terms CIS or CDMS, and do not draw a clear distinction based

solely on the number of clinical attacks to make a diagnosis of MS.

[213] Dr. Morrow explained how MRI demonstrates DIT and DIS and that the increasing use

of MRI permits the diagnosis of MS without the demonstration of clinical attacks.

[214] Dr. Morrow stated that the POSITA would understand that the language in the claims

refers to terms that were used in relation to the Poser criteria (i.e., CDMS), which required the

confirmation of a second clinical attack. Dr. Morrow stated that the POSITA would understand

that the ‘437 Patent is directed to using glatiramer acetate to treat patients who have had one

clinical attack suggestive of MS but have not yet experienced a second clinical attack.

[215] With respect to infringement, Dr. Morrow stated that in her opinion, if Pharmascience’s

Glatect product is made, sold, used or constructed in accordance with the Glatect Product

Monograph she had reviewed, Glatect 20 mg and 40 mg will be used in the manner set out in the

asserted claims of the ‘437 Patent. Dr. Morrow noted the specific wording of the 20 mg product

and 40 mg product and the distinctions between them.

Page: 54

C.

Teva’s Expert, Dr. Selchen

[216] Dr. Selchen agreed with Dr. Morrow and with Dr. Green’s initial opinion regarding the

construction of the claims of the ‘437 Patent as focussed on the CIS patient.

[217] Dr. Selchen stated that in 2007, a patient presenting with the profile described in claim 1

was typically diagnosed as a patient with CIS. He explained that CIS was treated as distinct from

CDMS, which required the confirmation of a second clinical attack (and ruling out other possible

non-MS causes for the first attack).

[218] Dr. Selchen emphasized that the claims of the ’437 Patent are directed to the CIS patient

and not to a patient who could be diagnosed pursuant to the 2001 or 2005 McDonald criteria

with MS, including RRMS.

[219] Dr. Selchen noted that the claims of the ‘437 Patent sets out various modes of efficacy,

including: delaying the onset of CDMS; reducing progression of MRI-monitored disease activity

(including a reduction in the rate of accumulating new T2-weighted lesions, a measure of active

inflammatory process); reducing the progression of symptoms of MS; and, reducing the

frequency of relapse.

[220] Dr. Selchen also agreed that the inventive concept of the claims is the subject matter of

the claims asserted.

Page: 55

[221] Dr. Selchen did not fully agree with Dr. Green regarding the extent of the common

general knowledge, particularly articles from less known journals and those that reported on pilot

studies or case reports.

[222] With respect to the allegation of anticipation, Dr. Selchen opined that Karussis 2006

neither disclosed nor enabled a skilled person to practice the subject matter of the claims at issue.

[223] Dr. Selchen noted that the Karussis Working Group was tasked with developing

evidence-based recommendations. Karussis 2006 clearly stated that their proposed

recommendation for using glatiramer acetate (among other therapies) to treat patients with CIS

was not evidence-based. Dr. Selchen stated that the suggestion in Karussis 2006 that the

approved therapies “should” work did not single out glatiramer acetate. He stated that the

suggestions and opinions would not enable a skilled person to achieve the claimed outcomes of

the ‘437 Patent.

[224] Dr. Selchen acknowledged that in November 2007 the POSITA would have known only

that a clinical study had been commenced (i.e., the PreCISe trial). Dr. Selchen also noted that

several other clinical trials studying drugs for use in treating MS had failed to meet their

objectives and the POSITA would not have assumed the successful outcome of the PreCISe trial

simply because the trial had been started.

[225] Dr. Selchen stated that, in 2007, the POSITA would not and could not have treated CIS

patients with glatiramer acetate, noting that it was not approved for this use, it would not have

Page: 56

been covered by any drug plan and, more importantly, there was no evidence to support its

effectiveness.

[226] Dr. Selchen did not agree with Dr. Green that it would be obvious to the POSITA that

glatiramer acetate would be useful to treat CIS as claimed in the ‘437 Patent. Dr. Selchen again

noted that there was no evidence that glatiramer acetate had been used to treat patients with CIS,

and no evidence of any effect of that treatment, not even from uncontrolled studies or patient

case reports.

D.

Teva’s Expert, Dr. Kreitman

[227] Dr. Kreitman described the PreCISe trial, which demonstrated that 20 mg daily of

glatiramer acetate was efficacious in delaying the onset of CDMS in CIS patients. Dr. Kreitman

confirmed that the PreCISe trial did not test a 40 mg dose of glatiramer acetate.

[228] Dr. Kreitman also described Teva’ activities leading up to the development of Copaxone

40 mg three times a week and the ‘802 Patent.

[229] Dr. Kreitman noted other trials conducted by Teva, including to test a higher

concentration formulation of glatiramer (i.e., 20 mg/0.5 mL), which were abandoned or not

successful.

Page: 57

[230] Dr. Kreitman explained that around 2002 Teva began to explore the development of

glatiramer acetate 40 mg daily. Teva conducted a Phase III clinical trial, the FORTE trial, which

compared 40 mg daily to 20 mg daily of glatiramer acetate. The study failed to show that the

40 mg dose improved efficacy compared to the 20 mg dose.

XIV. The POSITA for the ‘437 Patent

A.

The Principles from the Jurisprudence

[231] The jurisprudence refers to this mythical person as the person of skill or the skilled

person or as noted above, the POSITA.

[232] The POSITA is not one real person, rather a fictitious person or team of persons with an

amalgamation of different skills. The POSITA provides the lens through which the patent is

construed, the prior art is considered, and other issues are assessed (Pfizer Canada Inc v

Pharmascience Inc, 2013 FC 120 at para 28; Teva Canada Limited v Janssen Inc, 2018 FC 754

at para 66, aff’d 2019 FCA 273).

[233] In Valeant Canada LP/Valeant Canada SEC v Generic Partners Canada Inc, 2019 FC

253 at para 44 [Valeant], Justice Fothergill described the POSITA as follows:

44.

The PSA is unimaginative and uninventive, but reasonably

diligent in keeping up with advances (Pfizer Canada Inc v Teva

Canada Ltd, 2017 FC 777 at para 185). The PSA is not

incompetent, and brings background knowledge and experience to

the workbench (AstraZeneca Canada Inc v Apotex Inc, 2015 FC

322 at para 276). The PSA is not stripped of the ability to pursue

Page: 58

reasonable and logical enquiries, and can make deductions based

on the information available (Jay-Lor International Inc v Penta

Farms Systems Ltd, 2007 FC 358 at para 75 [Jay-Lor], citing Beloit

Canada Ltd v Valmet Oy (1986), 8 CPR (3d) 289 at 294 (FCA)

[Beloit]).

B.

Who is the POSITA for the ‘437 Patent?

[234] Teva submits that the POSITA is a neurologist with experience in the diagnosis and

management of MS.

[235] Pharmascience submits that the POSITA would include a neurologist with several years

of experience, including direct experience evaluating and diagnosing patients with MS and

administering therapeutic agents for the treatment of MS (including familiarity with their dosing

schedules and frequencies of administration). Pharmascience adds that the POSITA would also

be part of a drug development team with experience developing clinical studies.

[236] Dr. Green described the POSITA as a medical professional, particularly a neurologist

with several years of experience, including direct experience evaluating and diagnosing patients

with MS and administering therapeutic agents for the treatment of MS. This would include

familiarity with the dosing schedules and frequencies of the different therapeutic agents available

for MS treatment, as well as side effects or adverse events that occur with these treatments. Dr.

Green added that the POSITA would also be part of a drug development team and have

experience with the design of clinical studies. Dr. Green disagreed with Dr. Morrow that the

POSITA would also include a biochemist, but agreed that a biochemist could be consulted by the

POSITA.

Page: 59

[237] Dr. Selchen agreed that the POSITA would be a medical professional such as a

neurologist, with at least a few years’ experience evaluating and diagnosing patients with MS

and administering therapeutic agents for the treatment of MS. Dr. Selchen did not agree with

Dr. Green that the POSITA or team should include a member of a drug development team, or

that the POSITA would have experience with the design of studies necessary for drug

development. Dr. Selchen opined that this would be too specialized.

[238] The experts all agree on the basic qualifications of the POSITA but disagree on the

additional special attributes argued by Pharmascience.

[239] Pharmascience appears to advocate for the POSITA to be part of a drug development

team and with experience in the design of clinical studies to later argue that the POSITA would

conduct patent searches and would have the skill to conduct clinical studies to the extent that this

would be “routine” work.

[240] In my view, the POSITA – through whose eyes the ‘437 Patent is understood and

directed – is a practicing neurologist with several years of experience evaluating, diagnosing and

treating patients with MS. This POSITA would be familiar with the therapeutic agents available

for the treatment of MS (i.e., the DMTs), their dosing schedules and side effects or adverse

events that occur with the various DMTs. The POSITA would have some knowledge of and

familiarity with clinical studies and their interpretation but would not be a member of a drug

development team. The POSITA is also referred to herein as a practicing neurologist.

Page: 60

XV.

A.

The Construction of the Claims

The Principles from the Jurisprudence

[241] Claims construction is for the court to determine guided by expert evidence if needed.

The construction of the claims precedes consideration of the allegations of invalidity. The claims

are construed as of the publication date; for the ‘437 Patent it is June 4, 2009 and for the ‘802

Patent it is February 24, 2011.

[242] In Biogen Canada Inc v Taro Pharmaceuticals Inc, 2020 FC 621 [Biogen], the Court

summarized the principles of claim construction at paras 76-78, noting at para 78:

[78] The principles of claim construction were laid out by the

Supreme Court of Canada in Whirlpool and Free World

Trust (Whirlpool at paras 49-55; Free World Trust v Électro Santé

Inc, 2000 SCC 66 at paras 44-54 [Free World Trust]). Claims are

to be read in an informed and purposive way, with a mind willing

to understand and viewed through the eyes of a POSITA having

regard to the common general knowledge. The entire patent

specification should be considered in order to ascertain the nature

of the invention, however adherence to the claim language allows

the claims to be read in the way in which the inventor is presumed

to have intended, promoting fairness and predictability.

[243] In Valeant, the Court reiterated the “canons of claim construction” at para 42:

[42] The canons of claims construction are 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

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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

I 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.

The Claims of the ‘437 Patent

[244] The ‘437 Patent includes definitions of some of the terms used in the patent and in the

claims.

[245] The ‘437 Patent defines a “patient at risk of developing MS (i.e. CDMS)” as a patient

presenting any of the known risk factors for MS. The risk factors noted include a CIS, a single

attack suggestive of MS without a lesion, the presence of a lesion without a clinical attack, and

environmental and genetic factors.

[246] CIS is defined as referring to “a single clinical attack (used interchangeably herein with

‘first clinical event’ and ‘first demyelinating event’) suggestive of MS, which, for example,

presents as an episode of optic neuritis, blurring of vision, … loss of balance, tremors…[and

several other indicators]”, and “at least one lesion suggestive of MS”.

Page: 62

[247] The ‘437 Patent states that “the criteria as defined by Poser … used to determine if a

subject meets the condition consistent with [CDMS] are:

 Two attacks and clinical evidence of two separate lesions or

 Two attacks; clinical evidence of one lesion and paraclinical evidence of another separate

lesion.”

[248] An “attack” or “exacerbation, flare, or relapse” are defined clinically as the sudden

appearance or worsening of a symptom or neurological dysfunction, with or without objective

confirmation.

[249] The ‘437 Patent defines both clinical and paraclinical evidence. Clinical evidence of a

lesion is defined as “signs of neurological dysfunction demonstrable by neurological

examination” and this includes signs that are no longer present if the sign was recorded by a

“competent examiner”. Paraclinical evidence of a lesion that has not produced clinical signs and

may or may not have caused symptoms includes evidence from various tests, including

neuroimaging.

[250] There are 50 claims in the ‘437 Patent of which 13 are asserted. As noted, the claims are

set out in full at Annex 1.

[251] Claim 1 provides:

A pharmaceutical composition comprising a pharmaceutically

acceptable carrier and a therapeutically effective amount of

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glatiramer acetate for use in delaying the onset of clinically

definite multiple sclerosis in a patient who experienced a single

clinical attack suggestive of multiple sclerosis, who presents with

at least one lesion consistent with multiple sclerosis and who is at

risk of developing clinically definite multiple sclerosis and prior to

development of clinically definite multiple sclerosis.

[252] The claim describes the pharmaceutical composition of glatiramer acetate. Subsequent

claims make it clear that this is administered as a subcutaneous injection, administered daily in a

20 mg or 40 mg dose.

[253] The claims that address the effects of treatment are not in dispute. These are claims 2

(reducing progression of… (MRI)-monitored disease activity), 3 (reducing the progression of

symptoms of [MS]), 4 (reducing the frequency of relapse), 19 and 24 (the relapse rate and the

mean number of new T2 lesions) and 33 (the reduction by at least 50% in the rate of

accumulating new T2-weighted lesions) and all relate to the patient population described in

claim 1.

[254] Claims that describe how glatiramer acetate is administered are also not in dispute:

claims 13 (use is once-a-day), 14 (use is subcutaneous), 15 (the therapeutically effective amount

of glatiramer acetate is 20 mg) and 16 (the therapeutically effective amount of glatiramer acetate

is 40 mg).

[255] Claims 47 and 50 relate to the use of glatiramer acetate in the manufacture of a

medicament for the treatment of the patient population set out in claim 1.

Page: 64

[256] The experts all construed the claims in a similar way noting the independent and

dependant claims and grouping them according to their similar features. Although all the experts

construed claim 1 in the same manner – basically, it means what it says. Teva and Pharmascience

interpret the scope of the patient population described in claim 1 differently, which in turn

impacts all the claims.

C.

The Dispute regarding the Patients Included in the Claims

(1)

Pharmascience’s Submissions

[257] Pharmascience submits that the ‘437 Patent is clear that its invention, defined in terms of

the Poser criteria, is the delay in onset of CDMS in a patient that has suffered a single clinical

attack and is at risk of having a second clinical attack (i.e., a CIS patient in accordance with the

definition of CIS provided in the ‘437 Patent).

[258] Pharmascience argues that the claims cover two groups of patients who have experienced

a single clinical attack:

 A patient who does not yet meet the MRI criteria to be diagnosed with MS under the

2005 McDonald criteria; and

 A patient who does meet the MRI criteria and is diagnosed or can be diagnosed with MS

under the 2005 McDonald criteria.

Page: 65

[259] Pharmascience argues that using the words of the claim and the definitions set out in the

‘437 Patent, the key terms are “single attack” and “prior to the onset of CDMS”, which is

specifically defined as a second clinical attack. Pharmascience relies on the McDonald criteria

which would result in a diagnosis of MS, based on MRI evidence demonstrating DIS and DIT of

lesions, for some patients who experienced only a single clinical attack.

[260] Pharmascience argues that CDMS as defined is not the same as MS or RRMS.

Pharmascience submits that a patient could be diagnosed with MS or RRMS pursuant to the

McDonald criteria after having only one clinical attack and that this “McDonald MS” patient

falls in the claims of the ‘437 Patent because the patient has not yet had a second clinical attack

and does not meet the definition of CDMS.

[261] Pharmascience submits that the experts agreed that, due to the use of the “out of date”

Poser criteria, the claims cover two groups of single attack patients.

[262] Pharmascience notes that, although its expert, Dr. Green, described the claimed patient

population for all claims as being a “CIS patient at risk of developing CDMS (and who has not

yet developed CDMS) and presenting with at least one lesion consistent with MS”, Dr. Green

repeatedly advised counsel to Teva on cross-examination that he was simply using the definition

offered by the patentee, Teva.

[263] Pharmascience also relies on the evidence of Teva’s expert, Dr. Morrow, who described

the claims of the ‘437 Patent as relating to “use in patients who meet the diagnostic criteria for

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CIS, but do not meet the Poser criteria for CDMS . . . in order to delay the onset of CDMS”.

Pharmascience suggests that Dr. Morrow’s description must be read in light of her opinion on

infringement where she stated that the indication for Glatect 40 mg includes within its scope

single-attack patients who meet the McDonald criteria.

[264] Pharmascience disputes Teva’s proposed narrow construction of the claims.

Pharmascience argues that Teva is bound by its choice to use the Poser criteria to draft the claims

of the ‘437 Patent despite that the McDonald criteria were widely accepted and used well before

2007. Pharmascience argues that Teva cannot seek to rewrite the claims with new definitions.

Pharmascience adds that if Teva intended to limit the claims it could have drafted the patent

clearly to do so.

[265] Pharmascience says that Teva’s narrow construction should be rejected as it relies on a

construction of the claim language that was rejected by Drs. Green, Selchen and Morrow when

they were “properly oriented”.

(2)

Teva’s Submissions

[266] Teva submits that claims 1-4 address the treatment of a patient who experienced a single

clinical attack suggestive of MS, presents with at least one lesion consistent with MS, and is at

risk of developing CDMS. Teva submits that this is a CIS patient – not a patient who has already

been diagnosed or met the criteria of CDMS. Nor is it a patient who has met the criteria of MS

pursuant to the application of the McDonald criteria.

Page: 67

[267] Teva submits that all the experts agree that the claims are directed to the treatment of a

CIS patient who experienced a single clinical attack suggestive of MS. Teva disputes

Pharmascience’s interpretation that this includes a CIS patient who meets the McDonald criteria

for MS but who has not yet experienced a second clinical attack.

[268] Teva submits that the claims should be construed through the eyes of the POSITA with

the common general knowledge as of the claim date, June 4, 2009, which included knowledge of

the criteria for diagnosing MS, pursuant to both the Poser criteria and the McDonald criteria.

[269] Teva notes that the McDonald criteria do not require two distinct clinical attacks for a

diagnosis of MS. Teva also notes that the experts agreed that reliance on the McDonald criteria

led to more CIS patients being diagnosed with MS (typically RRMS) based on the MRI evidence

of new lesions regardless of whether new clinical symptoms developed. Teva relies on the

evidence of Dr. Morrow who explained that the Poser terms continue to be used and that CIS is

understood to be a patient that does not yet meet the diagnostic criteria for MS.

[270] Teva also notes that Dr. Green stated (in his report on validity) that there are several

forms of CDMS, including RRMS and that the POSITA would understand that these do not

include CIS patients.

[271] Teva also points to Dr. Green’s opinion, which was echoed by Dr. Selchen, “[t]hough the

claims use slightly different language to describe the patient groups, the skilled person would

understand that the claimed patient population for all claims is a CIS patient at risk of developing

Page: 68

CDMS (and who has not yet developed CDMS) and presenting with at least one lesion consistent

with MS.”

[272] Teva notes that Dr. Selchen clearly explained that “a CIS patient by definition is different

than a McDonald patient” and that a single attack patient who meets the McDonald criteria does

not fall within the claims.

[273] Teva notes that Dr. Green revised his opinion in response to Dr. Morrow’s infringement

report but could not explain why he did not state this opinion in his validity report.

[274] Teva submits that Dr. Green’s revised opinion is inconsistent with his description of the

common general knowledge as reflecting that the patient population was “CIS patients at high

risk for developing MS”. Teva also notes that the papers cited by Dr. Green, including Comi

2001 and Kappos L et al, “Treatment with interferon beta-1b delays conversion to clinically

definite and McDonald MS in patients with clinically isolated syndromes” 2006 Neurology 67:

1242-1249 [Kappos 2006], distinguish CIS patients from patients diagnosed with MS under the

McDonald criteria. For example, Dr. Green cited Kappos 2006 which reported on the use of an

interferon (i.e., Betaseron® [Betaseron]) in CIS patients (at the time of the initial attack) to

prevent future relapses.

Page: 69

D.

What do the Experts Say regarding the Patients Included in the Claims?

(1)

Dr. Green

[275] Dr. Green explained that by 2001, pursuant to the McDonald criteria, there was no longer

the requirement for two attacks to confirm the diagnosis and the term CDMS was no longer

used – rather the term MS was used. A patient could have one attack yet meet the other

McDonald criteria for a diagnosis of MS. If the “one attack” patient did not meet that criteria,

they were considered to be a CIS patient.

[276] Dr. Green acknowledged that in 2007 a CIS diagnosis would have been for patients who

had a single clinical event suggestive of MS.

[277] He explained that MRI scans of CIS patients did not meet the McDonald criteria, at para

104 of his report:

MRI scans of such CIS patients, while consistent with MS, did not

fulfill the McDonald criteria to enable a confirmed diagnosis of

MS. CIS was defined somewhat differently depending on the

setting but was generally used to apply to patients who had a single

episode of clinical neurological worsening that was suspicious for

demyelination (i.e., subacute onset of neurological dysfunction,

especially in a young or middle-aged person) with MRI evidence

of other lesions (at least 1 or 2 depending on the investigator). Dr.

Green acknowledged that in 2007 a CIS diagnosis would have

been for patients who had a single clinical event suggestive of MS.

[278] In his validity report, Dr. Green explained that the Summary of the Invention set out in

the ‘437 Patent would be understood by the POSITA as the use of glatiramer acetate to treat CIS

Page: 70

patients and to produce various results, such as delaying the onset of CDMS, delaying

progression to CDMS, reducing the progression of MRI-monitored disease activity, reducing the

progression of MS symptoms, and reducing the frequency of relapses, among others.

[279] In his second report, which was for the purpose of responding to Dr. Morrow’s report on

infringement, Dr. Green stated that he generally agreed with Dr. Morrow’s interpretation of the

claims. Dr. Green then added “by June 2009 (and earlier), which is the date that I was instructed

to interpret the claims from the perspective of the skilled person, at least some patients

presenting with a single attack and at least one lesion would have been categorized as having MS

pursuant to the McDonald criteria”.

[280] Dr. Green reiterated this view in his oral testimony, to indicate that the POSITA would

understand that the claims include a McDonald MS patient, despite the definition of CIS

included in the ‘437 Patent.

[281] On cross-examination, Dr. Green was directed to para 269 of his validity opinion, where

he summarized the claims and stated that the “skilled person would understand that the claimed

patient population for all claims is a CIS patient at risk of developing CDMS and presenting with

at least one lesion consistent with MS”.

[282] Dr. Green acknowledged that he did not explicitly state that his reference to a CIS patient

means CIS patients plus “McDonald MS” patients because he had explained this in his opinion

on claims construction and he was working from the definitions in the patent. Dr. Green added

Page: 71

that the patent would be read in accordance with the common general knowledge of the time, i.e.,

the McDonald criteria.

[283] Counsel for Teva questioned why Dr. Green did not state in his validity report that

patients who met the McDonald criteria for MS would anticipate or render obvious the patent:

Are you suggesting to the Court that for the purpose of this validity

analysis you say in paragraph 269 it is a CIS patient and you do not

say anywhere in the report that McDonald MS patients with one

lesion would anticipate or render obvious the patent, treatment of

those patients, and it wasn’t on purpose?

[284] Dr. Green responded that this was not on purpose. Dr. Green noted that the clinical

terminology at the time was imprecise. He stated that he did not change his view, he merely

clarified it.

(2)

Dr. Morrow

[285] Dr. Morrow explained that the POSITA would understand that the language in claims of

the ‘437 Patent uses terminology in relation to the Poser criteria (e.g., CDMS, an MS diagnosis

which requires the confirmation of a second clinical attack). The POSITA would recognize that

the ‘437 Patent is directed to using glatiramer acetate to treat patients who have had one clinical

attack suggestive of MS but have not yet experienced a second clinical attack.

[286] With respect to the Poser criteria and CDMS, Dr. Morrow explained that, “to be

[CDMS], you needed to have two relapses separated in space, meaning in two different areas of

Page: 72

the CNS. . . . They had to really have two relapses separated by at least 30 days and separated in

areas of the brain to show that it was multiple, hence multiple sclerosis.”

[287] Dr. Morrow explained that the term CDMS is not used as often today given the

development of the McDonald criteria in 2001 and the subsequent iterations. Dr. Morrow

explained that when the McDonald criteria are applied, there does not necessarily need to be a

second clinical attack because there are other ways to make the diagnosis. She added that the

diagnosis would be either CIS or MS (or RRMS) and that the CDMS term has “fallen away”.

[288] In Dr. Morrow’s oral testimony, she noted that the ‘437 Patent and the claims use terms

derived from the Poser criteria:

So really we, a person skilled in the art, would understand this

means to those who have CIS or one clinical attack suggestive of

MS who have not yet met the diagnostic criteria for CDMS or not

yet had that second relapse. I guess one more point that is

important is under 67.5. Of course that specifically is referring to

those who are at risk of developing clinically definite MS. That is

where that one other lesion on the MRI becomes important, that

you want to see evidence of other inflammation, as well, and of

course prior to the development of CDMS, so of course at the CIS

stage.

[289] Dr. Morrow explained, as did the other experts, that the McDonald criteria allowed MRI

activity to help support a MS diagnosis, in particular by demonstrating DIS and DIT. She

explained that the refinements of the criteria have permitted the diagnosis to be made earlier

without as much clinical activity. With respect to the different diagnostic criteria, Dr. Morrow

explained that pursuant to the McDonald criteria:

You still need to show multiple areas of the brain and spinal cord

involved, as well as multiple over time, but that can now be met

Page: 73

with MRI criteria. So you can show one relapse and then have

areas involved on the MRI that show multiple areas involved in

certain areas, and the lesions must look typical for multiple

sclerosis. Then dissemination in time or multiple in time to

demonstrate that chronicity can be done at the time of the first

relapse if they have gad-enhancing lesions, so showing old and

new at the same time, or a repeat MRI done after the initial MRI,

which shows the development of new lesions, again showing that

chronicity, so development of new lesions or multiple over time.

(3)

Dr. Selchen

[290] Dr. Selchen did not agree that the claims of the ‘437 Patent included CIS patients who

met the McDonald criteria for MS.

[291] Dr. Selchen emphasized that CIS is a separate diagnosis that exists until the second attack

or relapse is demonstrated and that there are different implications for the treatment of CIS.

[292] Dr. Selchen stated that, in November 2007, CIS was considered to be distinct from MS.

The 2005 McDonald criteria maintained CIS as a separate syndrome. The prevailing view was

not simply that “CIS is a form of relapsing MS”, as Dr. Green stated.

[293] Dr. Selchen agreed that scientific publications indicated that many CIS patients and most

patients with additional brain lesions would go on to have further attacks. Dr. Selchen also

agreed that many patients who would previously have been diagnosed with CIS under the Poser

criteria would instead be diagnosed with RRMS according to the McDonald criteria (in 2007 and

today).

Page: 74

[294] Dr. Selchen acknowledged that with the advent of MRI evidence and the application of

the McDonald criteria, the proportion of patients that develop MS is probably 70-80% but this

estimate would depend on how long the patient was followed. Dr. Selchen also agreed with the

statement in the ‘437 Patent that by 2003, over 80% of CIS patients with CIS and MRI lesions

went on to develop MS. Dr. Selchen added that some CIS patients, for unknown reasons, do not

develop MS.

[295] Dr. Selchen noted that a goal of the McDonald criteria was to increase sensitivity without

sacrificing specificity in diagnosis. This means that you do not want to miss a patient nor do you

want to include a patient in a diagnostic category who does not have the condition.

[296] Dr. Selchen explained that T1 lesions are generally older lesions whereas T2 lesions

better represent new inflammatory activity. This made new T2 lesions a useful indicator of active

inflammation process (which may or may not be associated with a clinical relapse) and provided

a marker that is much more sensitive than clinical relapse as a surrogate for active clinical

disease activity.

[297] Dr. Selchen explained that the McDonald criteria allow a patient with a single attack to

be characterized as “McDonald positive MS” based on paraclinical, i.e., MRI evidence.

[298] Dr. Selchen stated that the POSITA would understand that CIS patients would not qualify

as “confirmed” MS, as this could only be established if and when there was a second attack or

the McDonald criteria were met.

Page: 75

[299] On cross-examination, counsel for Teva asked Dr. Selchen whether a patient who

presented in November 2007 with a single clinical attack and one or more lesions and met the

McDonald criteria for MS, more specifically RRMS, could be treated with glatiramer acetate to

delay a second attack and whether this patient would fall within the claims. Dr. Selchen agreed

that they could be so treated.

[300] Counsel for Teva described other scenarios, all with respect to the single attack patient

who met the McDonald criteria for MS, and asked Dr. Selchen whether this patient could be

treated with glatiramer acetate to reduce the progression of MRI-monitored disease activity, to

reduce disease progression, to reduce the frequency of relapse, or to address any of the other

outcomes set out in the claims. Dr. Selchen agreed that this patient could be so treated.

[301] On re-examination, Dr. Selchen reiterated the opinion set out in his report, which stated

that the claims use different language to refer to different patient groups, but that the POSITA

would understand that the claims are directed to a CIS patient, not a “McDonald positive” MS

patient. Dr. Selchen emphasized that a CIS patient is a patient who does not meet McDonald

criteria for MS, who has not yet had a further clinical episode and who has not had MRI lesions

showing DIT. Dr. Selchen clearly stated that the CIS and “McDonald positive” MS patients are

“totally different patients” by definition. One meets the criteria for a diagnosis of RRMS and the

other does not.

Page: 76

E.

The Patients Included in Claim 1 and Subsequent Claims

[302] The construction of the claims is for the Court to determine. As noted above, the Court

construes the claims through the eyes of the POSITA (the practicing neurologist) in a purposive

way, with reference to the whole of the specification and to the language used by the inventor,

and endeavours to interpret the claims to give effect to the intention of the inventor.

[303] I have considered the disclosure in the ‘437 Patent and the wording of the claims with

attention to the definitions in the patent. I have considered the expert evidence that explained the

diagnostic criteria for MS and opined on the definitions in the patent. While the common general

knowledge as of November 2007 included acceptance of the McDonald criteria to diagnose MS,

the experts agreed that the POSITA remained aware of the diagnostic criteria and the terms from

both Poser and McDonald. Moreover, the POSITA, being a neurologist with experience treating

MS patients, would certainly understand that the intention of the patent and the wording of the

claims were directed at early treatment before the onset of MS, regardless of how the diagnosis

was reached. The POSITA would be knowledgeable about how MRI (T1 and T2-weighted

images as described by the experts) demonstrate DIS and DIT, which are pillars of both the

Poser and McDonald diagnostic criteria. The POSITA would understand that CIS is not MS

according to the McDonald criteria and is not CDMS according to the Poser criteria. The

POSITA would understand that once a patient is diagnosed with, or meets, the criteria to be

diagnosed with MS, they are no longer “at risk” of CDMS nor are they “suggestive of MS” as

these criteria have been surpassed by the MS diagnosis. The window for the early treatment has

passed.

Page: 77

[304] Pharmascience focuses on the terms “single attack” and “before the onset of CDMS”.

Pharmascience argues that CDMS means only a second clinical attack and nothing else. Under

Pharmascience’s interpretation, a patient who experienced a single attack but has been diagnosed

with MS pursuant to McDonald criteria would be included in the claims of the ‘437 Patent.

However, this interpretation does not jive with the evidence of the experts who stated that under

the McDonald criteria there is no diagnosis of CDMS, just MS or not MS. Two attacks are not

needed for a diagnosis of MS pursuant to the McDonald criteria as would be required pursuant to

the Poser criteria, which did not rely on MRI evidence to the same extent. Pharmascience accepts

and relies on the ‘437 Patent’s use of the Poser criteria but seeks to superimpose the McDonald

criteria to expand the coverage of the claims without considering the disclosure in the patent and

the lack of logic in this interpretation.

[305] I acknowledge that glatiramer acetate was a known treatment for RRMS well before the

‘437 Patent. I understand that if the claims include MS and RRMS patients, the claims are not

novel. I understand that Pharmascience’s interpretation of the claims to include those single

attack patients who meet the criteria for MS pursuant to the McDonald criteria would pave the

way for a successful Gillette defence and other bases of invalidity. However, this interpretation

cannot succeed.

[306] In my view, far too much time and effort was devoted to debating the meaning of the

terms, the evolving diagnostic criteria and the scope of the patients covered by the claims.

Page: 78

[307] All the experts construed the claims in accordance with their plain language. The claims

mean what they say. Despite this general agreement, Pharmascience’s expert, Dr. Green, revised

his opinion in his responding report.

[308] I am not persuaded by Dr. Green’s revised view that the claims include both CIS patients

who do not meet the McDonald criteria and those CIS patients who do meet the McDonald

criteria. Dr. Green’s evolving evidence seemed to be tailored to support Pharmascience’s

invalidity arguments and the Gillette defence to infringement. Dr. Green provided confusing

responses when offered the opportunity to explain why he revised his opinion. Moreover, his

revised opinion discounts the knowledge base of the POSITA.

[309] As noted above, in Dr. Green’s report and opinions on validity, he noted the distinction

between CIS and CDMS in the patent and explained that the objective of the patent was to

determine whether glatiramer acetate would be effective in CIS patients.

[310] Dr. Green explained the importance of demonstrating DIS and DIT, which permit a

diagnosis of MS (and also of CDMS). Dr. Green noted the increasing use of MRI to identify the

earliest indication of the disease “meaning patients who had a single clinical attack and MRI

evidence suggestive of a MS diagnosis (referred to as “Clinically Isolated Syndrome” or “CIS”)”

and that “MRI scans of such CIS patients, while consistent with MS, did not fulfill the

McDonald criteria to enable a confirmed diagnosis of MS.”

Page: 79

[311] Dr. Green also stated, with respect to the disclosure of the ‘437 Patent that, “[t]he skilled

person would understand that RRMS, SPMS, PPMS and PRMS are all forms of CDMS and that

these do not include CIS patients.” [My emphasis]

[312] Dr. Green then modified his view of the claims in his second report in response to

Dr. Morrow’s infringement report and stated that the claims included some CIS patients who

also met the McDonald criteria for MS, usually RRMS.

[313] Dr. Green attempted to justify his change of opinion by explaining that he had relied on

the definitions in the patent in setting out his interpretation of claim 1 in his validity report.

Dr. Green’s response on cross-examination to his change of opinion was vague. He could not

effectively explain why he did not state in his first report on validity that the claims also included

some “McDonald MS” patients.

[314] Dr. Green also inconsistently stated that the concept of CIS was not part of the Poser

criteria. However, Dr. Green acknowledged that the ‘437 Patent used the Poser criteria and

defined several terms, including the term “clinically isolated syndrome” (and the definition notes

that the term is used interchangeably with a “single clinical attack” and “first demyelinating

event”). Dr. Green also claimed that he applied these definitions.

[315] On cross-examination, Dr. Green acknowledged that once the patient met the McDonald

criteria for MS, they were no longer “suggestive of MS” and they would not meet the criteria of

Page: 80

being “before the onset of CDMS”. Dr. Green stated, “once a patient has McDonald MS, they are

no longer a CIS patient”.

[316] Dr. Green also agreed that “single attack suggestive of MS” does not describe a patient

that has been diagnosed with MS.

[317] Contrary to Pharmascience’s submission, Dr. Morrow’s evidence does not support their

broader interpretation of the claims. Dr. Morrow’s opinion on the construction of the claims, as

noted above, is that the claims mean what they say. Her evidence with respect to infringement

and the Glatect product is based on the wording of the Glatect Product Monograph, not the

claims of the ‘437 Patent.

[318] In her explanation of the claims, Dr. Morrow noted that the POSITA would understand

them to be directed to those who have CIS and “of course prior to the development of CDMS, so

of course at the CIS stage”.

[319] Dr. Selchen clearly stated that the claims were directed to the CIS patient who did not

meet the McDonald criteria for MS. Dr. Selchen noted that a CIS patient is not a MS or a RRMS

or a CDMS patient (as also stated by Dr. Green). Dr. Selchen’s responses to various scenarios on

cross-examination addressed how the McDonald MS patient could be treated with glatiramer

acetate. The treatment of MS or RRMS patient is not in dispute. Dr. Selchen merely confirmed

that patients who had been so diagnosed would be treated with glatiramer acetate.

Page: 81

[320] Pharmascience seeks to superimpose the McDonald criteria on the wording of the claims.

However, pursuant to the McDonald criteria, a patient would never be diagnosed with CDMS, as

that term is not used. Rather, the patient would be diagnosed with MS or “not MS”. The experts

agree that a patient diagnosed with CDMS has MS. Dr. Green referred to a confirmed diagnosis

of MS where the Poser criteria are met. Dr. Green also agreed that RRMS is a form of CDMS

and that RRMS and CDMS are not CIS.

[321] All the experts explained that under the Poser criteria the diagnosis was based on clinical

observations and assessment. The second clinical attack demonstrated the DIT and DIS of

lesions. With the increased reliance on MRI, DIT and DIS could be demonstrated without the

observation of a second clinical attack.

[322] The MRI evidence is a surrogate or substitute for the second clinical attack to permit a

confirmed diagnosis as both demonstrate DIS and DIT. Under the Poser criteria, the second

clinical attack would permit a diagnosis of CDMS. Under the McDonald criteria, the MRI

evidence would permit a diagnosis of MS.

[323] The disclosure of the ‘437 Patent, as described above, acknowledges that 20 mg

glatiramer acetate is already approved and effectively used to treat patients with RRMS, which is

one of several types of MS. The patent notes that questions existed about the benefits of early

treatment. The examples in the patent focus on CIS patients – not those that already meet

diagnostic criteria for MS. It is apparent that the intention of the inventors was to focus on early

Page: 82

treatment, i.e., of CIS patient, with the goal of delaying the progress of the disease to CDMS

(which is MS).

[324] The plain wording of claim 1 provides that:

 the composition of glatiramer acetate is “for use in delaying the onset of clinically

definite multiple sclerosis”,

 the target patient population is the patient who:

o “experienced a single clinical attack suggestive of multiple sclerosis”, (CIS is

defined as including a single clinical attack and is used interchangeably with first

clinical event and first demyelinating event. “[s]uggestive of multiple sclerosis”

includes, for example, symptoms of optic neuritis and loss of balance, and means

not attributable to another condition.);

o “presents with at least one lesion consistent with multiple sclerosis”;

o “is at risk of developing clinically definite multiple sclerosis”; and,

o “presents with [the above] prior to development of clinically definite multiple

sclerosis”. (In other words, before a second clinical attack.)

[325] When the intention of the Patent and the plain words of the claims are read it would be

illogical to interpret the claims to suggest that the single attack is “suggestive of MS” once the

Page: 83

patient already meets the diagnostic criteria of MS. Once a patient is diagnosed with MS,

pursuant to the McDonald criteria, they are no longer “suggestive of MS” or of anything other

than MS. The patient at that point has MS. On cross-examination, Dr. Green agreed.

[326] Similarly, a patient who “is at risk of developing clinically definite multiple sclerosis” is

one that has not yet been diagnosed. Although the patent defines CDMS as two attacks, the

experts agreed that CDMS is MS. The POSITA would understand that CDMS is the same as a

diagnosis of MS. It would be illogical to characterize patients that have already been diagnosed

with MS as “at risk of CDMS”. Once diagnosed with MS, the “risk” has materialized.

[327] The claim also focuses on the use of glatiramer acetate in “delaying the onset” of CDMS

and “prior to development of [CDMS]”. Once CDMS, which is defined as a second clinical

attack, is diagnosed, the window for early treatment before its onset has closed. Similarly, once

diagnosed with MS, pursuant to the McDonald criteria, the window for early treatment is closed.

CDMS is MS and vice versa. What else would CDMS be if not MS?

[328] The POSITA in 2007, aware of both the McDonald and Poser diagnostic criteria, reading

the claims of the ‘437 Patent, would know that CDMS is MS and would deduce that the claims

are directed to treatment before the onset of the disease and, more particularly, at the CIS stage.

[329] In conclusion, the claims of the ‘437 Patent are directed to the patient who has had a

single clinical attack (or a first demyelinating event) suggestive of MS – a CIS patient – and

presents with the criteria set out in the claims before the development of CDMS (which means a

Page: 84

confirmed diagnosis of MS). This does not include patients who have had a single clinical attack

but already meet the McDonald criteria for a diagnosis of MS.

XVI.

Prior Art related to the ‘437 Patent

[330] Pharmascience set out 103 prior art references in its Statement of Defence. The experts

noted that there were thousands of articles on MS and the treatment for RRMS and CIS. A brief

description of the prior art cited and/or referred to is set out below.

[331] A special article published by Neurology (Goodin et al, “Disease modifying therapies in

multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council

for Clinical Practice Guidelines” 2002 Neurology 58: 169-178) established guidelines for the

treatment of MS. The article noted that “[t]he purpose of this assessment is to consider the

clinical utility of these disease-modifying agents including the anti-inflammatory,

immunomodulatory, and immunosuppressive treatments that are currently available.” The article

set out a comprehensive scheme for rating and evaluating data based on the study design, ranking

the studies in accordance with the quality of the design and the ability of a study to generate clear

and meaningful clinical conclusions. The guidelines noted that evidence based on controlled

studies have a higher rating while evidence based on uncontrolled studies, case series, case

reports, or expert opinion have a lower rating.

Page: 85

A.

Prior art on the use of glatiramer acetate in MS

[332] Bornstein et al, “A pilot trial of copolymer 1 in exacerbating-remitting multiple sclerosis”

1987 N Engl J Med 317: 408-414 [Bornstein 1987], was one of the first publications that

indicated the efficacy of glatiramer acetate as a treatment capable of reducing relapse rate in

patients with MS. Bornstein 1987 was published in the New England Journal of Medicine,

acknowledged to be one of the premier journals in the field of medicine.

[333] Johnson 1995 reported on a “pivotal” phase III clinical trial that evaluated the use of

glatiramer acetate 20 mg daily subcutaneous to treat RRMS and confirmed the conclusions in

Bornstein 1987. In particular, it found that relapses were reduced by approximately 30% in

RRMS patients who were treated with 20 mg of glatiramer acetate on a daily basis, compared to

placebo.

[334] Comi 2001 reported on a 9-month randomized, double-blind, placebo-controlled trial of

RRMS patients given 20 mg daily glatiramer acetate. In addition to the findings in Johnson 1995,

Comi 2001 found that RRMS patients treated with glatiramer acetate had a significant reduction

in the total number of MRI-measured lesions as compared to placebo.

B.

Prior art on CIS progressing to MS

[335] Filippi et al, “Quantitative brain MRI lesion load predicts the course of clinically isolated

syndromes suggestive of multiple sclerosis” 1994 Neur 44: 635-641 [Filippi 1994] reported on a

Page: 86

5-year study that assessed the likelihood of a CIS patient presenting with brain MRI

abnormalities to develop MS within 5 years. It demonstrated that, for patients who had a clinical

episode suggestive of a demyelinating attack with brain lesions (i.e. patients with a CIS

suggestive of MS), progression to MS occurred in 65% of those patients within 5 years.

[336] Brex 2002 documented a 14-year study following patients with CIS who were clinically

suggestive of MS based on MRI analysis. In the introduction, Brex 2002 noted that 90% of

patients with MS first present “with isolated syndromes that are clinically suggestive of multiple

sclerosis” and that, as of 2002, there were two trials of interferons (CHAMPS and ETOMS)

studying the use of “disease-modifying therapies aimed at delaying the onset of multiple

sclerosis.”

C.

Prior art on the use of interferons in CIS

[337] Jacobs L.D. et al., Intramuscular interferon beta-1a therapy initiated during a first

demyelinating event in multiple sclerosis (2000) N Engl J Med 343(13): 898-904 [Jacobs 2000]

reported on the CHAMPS trial. CHAMPS was a phase III (double-blind, placebo-controlled)

clinical trial that studied the use of 30 µg (microgram) subcutaneous interferon beta-1a (i.e.

AVONEX® [Avonex]) administered once weekly in CIS patients. The end point was the time

until the second clinical attack, which meant that patients who reach the end point would satisfy

the Poser criteria for CDMS. Among other things, the results of the trial showed a 58% reduction

in the mean number of T2 lesions between the treatment group and placebo.

Page: 87

[338] Comi G et al, “Effect of early interferon treatment on conversion to definite multiple

sclerosis: a randomized study”, 2001 Lancet 357: 1576-1582 [Comi 2001 Lancet] reported on the

ETOMS trial, which studied the effects of interferon beta-1a (i.e., Rebif® [Rebif]) in CIS

patients. ETOMS was a phase III (double-blind, placebo-controlled) clinical trial that studied the

subcutaneous use of 22 µg of Rebif administered once weekly in CIS patients. It found that

treatment with Rebif reduced the proportion of CIS patients who converted to CDMS as well as

reduced the frequency of relapses. Among other things, the results of the trial showed a 33%

reduction in the median number of T2 active lesions between the treatment group and placebo.

However, this point was disputed between the experts.

[339] Kappos 2006 reported the results of the BENEFIT trial, which was a phase III clinical

trial that studied the use of every other day of Betaseron administered by subcutaneous injection

in CIS patients. Among other things, the results of the trial showed a 50% risk reduction for

progression to CDMS for CIS patients treated with Betaseron compared to placebo. It also

showed a 33% reduction in the mean number of T2 lesions.

[340] Comi G and Martino G, “MS treatment: new perspectives”, 2006 Clin Neurol and

Neurosurg 108(3): 339-45 [Comi 2006] is a discussion paper that supported early treatment of

MS. Among other things, it discussed the CHAMPS and ETOMS trial results. In particular, in

comparing patients treated with Avonex in different clinical trials, the authors suggested that the

drug seemed to work better, earlier rather than later, in the disease course. Comi 2006 concluded

that “[the available] data suggest that early treatment of MS patients with immunomodulatory

drugs is advisable.”

Page: 88

[341] Karussis 2006, published in the European Journal of Neurology, is a report of an

International Working Group for Treatment Optimization in MS that discussed several

statements and refined them, resulting in 15 consensus statements on MS treatment.

[342] Frohman EM et al, “Most Patients with Multiple Sclerosis or a Clinically Isolated

Demyelinating Syndrome Should Be Treated at the Time of Diagnosis”, 2006 Arch Neurol 63:

614-619 [Frohman 2006] addressed the question of how early MS should be treated. Frohman

2006 noted the results of the ETOMS and CHAMPS trials and set out arguments in favour of

early treatment of MS, including for CIS patients.

[343] Pittock SJ et al, “Not every patient with multiple sclerosis should be treated at time of

diagnosis” 2006 Arch Neurol 63: 611-614 [Pittock 2006] was cited by Dr. Selchen for the

proposition that MRI findings of lesions and long-term disease prognosis in CIS patients

remained unclear, reflecting the other side of the debate regarding early treatment.

[344] Panitch H, “Do patients with clinically isolated syndrome benefit from treatment with

interferon β1b?” 2007 Nat Clin Prac Neurol 3(2): 81-81 [Panitch 2007] is a one page

commentary by Dr. Hillel Panitch on the BENEFIT trial. Dr. Panitch commented that the

BENEFIT trial represented the third trial (the others were CHAMPS and ETOMS) to show

“essentially the same outcome” in CIS patients. Panitch noted that “a similar large study of

glatiramer acetate versus placebo, given the acronym PRECISE, is currently in progress and is

likely to show a comparable magnitude of clinical efficacy.”

Page: 89

[345] Thrower BW, “Clinically isolated syndromes: predicting and delaying multiple

sclerosis.” 2007 Neurology 68(24 Suppl 4): S12-5 [Thrower 2007] reviewed the CHAMPS,

CHAMPIONS (an extension of CHAMPS), ETOMS, and BENEFIT clinical trials, all of which

investigated the use of DMTs in treating high-risk CIS patients. The author concluded that,

“initial trials of immunomodulatory therapies in patients with a CIS indicate that early treatment

can delay the second clinical event or new MRI lesion. Therefore, early treatment should be

considered for patients who have had a CIS and are at high risk for progression to CDMS.”

[346] Other less well known articles were Tintoré M, “Early MS treatment”, 2007 Int J MS 14:

5-10 [Tintoré 2007], Ruggieri M et al, “Glatiramer acetate in multiple sclerosis: a review”, 2007

CNS Drug Rev 13(2): 178-191 [Ruggieri 2007] and Coyle PK, “Evidence-based medicine and

clinical trials”, 2007 Neurology 68 (24 Suppl 4): S3-S7 [Coyle 2007], all of which noted that

Teva’s Phase III PreCISe trial was underway.

D.

Prior art cited by Pharmascience as anticipatory references

[347] Karussis 2006 is cited by Pharmascience as an anticipatory reference. It is described

above and below with respect to the allegation of anticipation and obviousness.

[348] Pinchasi 2007 is an international patent application, entitled “Method of treating multiple

sclerosis,” filed by Teva on January 9, 2007 and published on July 19, 2007. The patent

application describes the invention as “a method of alleviating a symptom of a patient suffering

from a relapsing form of multiple sclerosis which comprises periodically administering to the

Page: 90

patient by subcutaneous injection a single dose of a pharmaceutical composition comprising 40

mg of glatiramer acetate so as to thereby alleviate the symptom of the patient. . . . In [one]

embodiment, the periodic administration is daily and in another it is every other day.”

[349] The Copaxone® 2001 Package Insert and Copaxone® 2006 Product Monograph are cited

by Pharmascience. In November 2007, Copaxone was indicated for the treatment of RRMS. At

that time, the approved recommended dose for glatiramer acetate was 20 mg daily administered

subcutaneously.

XVII. Common General Knowledge

A.

Principles from the Jurisprudence

[350] As the Court noted in Valeant at paras 47-48, the jurisprudence establishes that a patent is

construed taking into account the common general knowledge of the POSITA. At para 48, the

Court elaborated, citing the principles set out in Eli Lilly & Co v Apotex Inc, 2009 FC 991 at para

97 [Eli Lilly], aff'd 2010 FCA 240, and General Tire & Rubber Co v Firestone Tyre & Rubber

Co, [1972] RPC 457 (UKHL) at pp 482-483 [General Tire]. The Court noted, among other

principles:

 common general knowledge is 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”;

Page: 91

 With respect to scientific papers:

. “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”; and,

. a particular piece of knowledge disclosed in a scientific paper “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”.

B.

What Do the Experts Say?

(1)

Dr. Green

[351] Dr. Green noted that as of November 28, 2007, the POSITA would be well versed

regarding MS and treatments for MS. The skilled person would have knowledge regarding MS,

the characteristics of MS, the classification of MS, brain imaging (including the use of MRI), the

evolution of diagnostic criteria for MS, CIS, MS therapies (including glatiramer acetate) and CIS

therapies (including ongoing clinical studies of glatiramer acetate). The other experts agreed.

Page: 92

[352] Dr. Green set out the sources of knowledge, including conferences, journals, online

resources such as PubMed and EMBASE (a subscription literature database) and the articles

found therein.

[353] Dr. Green agreed that, although the POSITA would identify many sources on PubMed

and EMBASE, and that he had identified thousands of documents about RRMS and CIS, only

some of which included therein would be part of the common general knowledge. Dr. Green

acknowledged that he did not refer to EMBASE as a source of common general knowledge in his

U.K. reports or in his U.S. reports. Dr. Green ultimately acknowledged that he did not use

EMBASE to conduct a search for the purpose of his opinion on the ‘437 Patent.

[354] Dr. Green noted, as did the other experts, that as of November 2007, the available DMTs

for MS were interferons (i.e., Avonex, Betaseron, Rebif) and glatiramer acetate (i.e., Copaxone).

He also noted Natalizumab and Mitoxantrone.

[355] Dr. Green stated that by November 2007, it was established that glatiramer acetate was

effective for RRMS patients in reducing relapses, increasing the time between relapses and

reducing MRI activity. In addition, a 40 mg dose had been shown to be equivalently efficacious

to the 20 mg dose with some possible advantages in terms of MRI activity.

[356] In Dr. Green’s opinion, by November 2007, it was becoming recognized that treatments

for CIS were identical to treatments for MS. Dr. Green cited reports of various studies, including:

Comi 2001 Lancet, Kappos 2006, Comi 2006 and Frohman 2006 in support.

Page: 93

[357] Dr. Green stated that Comi 2006 reported that treating early was the prevailing strategy,

although some in the field questioned this because of a small subset of patients who may not

require treatment.

[358] Dr. Green noted the results of Karussis 2006 and stated that Karussis concluded that

because interferons and glatiramer acetate had been shown to be effective in RRMS, and because

a CIS patient is highly likely to progress to MS, “it is reasonable to propose early treatment… at

the doses approved for MS, even though there is not yet evidence to support this approach.”

[359] Dr. Green also referred to Panitch 2007, which reported that the PreCISe trial was in

progress and that it was “likely to show a comparable magnitude of clinical efficacy” as the

BENEFIT trial, which showed a 50% risk reduction for progression to CDMS for CIS patients

treated with interferon beta-1b (i.e., Betaseron).

[360] Although Dr. Green cited Karussis 2006, Panitch 2007, Tintoré 2007, Ruggieri 2007 and

Coyle 2007 and suggested that these were part of the common general knowledge, he agreed that

these reports were not published in top journals.

[361] With respect to some of the papers cited, including Karussis 2006 and Panitch 2007,

Dr. Green acknowledged that he had not set these out as common general knowledge in his U.K.

opinion.

Page: 94

[362] Dr. Green acknowledged that he had identified different journals as part of the common

general knowledge in his opinion for the U.K. litigation than for the ‘437 Patent. Dr. Green noted

there was “overlap” between the common general knowledge in the U.K. and Canada.

[363] Dr. Green also agreed that not everything publicly available on the priority date is part of

the common general knowledge.

[364] Dr. Green agreed that Class 1 evidence comprised randomized, double-blind clinical

trials and were the “gold standard”. Dr. Green acknowledged that a case report would be a lower

classification than Class 3 evidence but stated that a case report still constitutes an important part

of the knowledge base.

[365] On cross-examination, Dr. Green appeared to acknowledge that Pinchasi 2007 and the

‘088 Patent (both of which were patent applications) did not turn up in the patent search

conducted with respect to the ‘437 Patent. Dr. Green noted that he did not personally conduct a

patent search related to the ‘437 Patent, but directed the search. Dr. Green stated that the

POSITA would know that there were patents on the topics but not the specific information.

[366] With respect to the role of product monographs (also referred to as product labels or

inserts) as common general knowledge, Dr. Green stated that physicians do not read or rely on

them. Dr. Green explained that the skilled person was aware of approved therapies for reasons

other than the product label, but they would know the pertinent facts on the product label.

Page: 95

(2)

Dr. Selchen

[367] Dr. Selchen agreed with Dr. Green regarding the common general knowledge about MS

and its treatment (as described above) and about many of the sources of that knowledge.

[368] Dr. Selchen agreed that the POSITA would have used online resources, including

PubMed, but expressed the view that most neurologists would not have consulted EMBASE or

other subscription-based literature searching services.

[369] Dr. Selchen noted that not all the references set out in the ‘437 Patent would have been

well known to the POSITA, as some are webpages and others are obscure journal articles or are

of limited interest, and that many internationally circulated journals would not have been

consulted regularly by neurologists in November 2007 because they were not considered leading

journals in the MS field. Dr. Selchen stated that information obtained from patent searches would

not be considered common general knowledge, unless the same information was also reported in

clinical studies.

[370] Dr. Selchen noted that it was extremely improbable that a clinical neurologist would

consult a patent application and that he had never done so. He added that a clinical neurologist

would not likely conduct a patent search or to request that this be done to guide clinical

decisions. However, he agreed that the skilled neurologist could read and understand patents

directed to the field of neurology.

Page: 96

[371] With respect to knowledge of treatment for RRMS, Dr. Selchen explained that “first-line

therapy” for RRMS in 2007 was typically interferons or glatiramer acetate.

[372] Dr. Selchen agreed with Dr. Green regarding the common general knowledge regarding

the effectiveness of treatments for RRMS, for example Comi 2001, which reported that RRMS

patients given 20 mg of glatiramer acetate daily had significant reduction in the total number of

MRI-measured lesions and relapse rates compared to placebo.

[373] Dr. Selchen also agreed that Cohen 2007, which stated that 40 mg of glatiramer acetate

daily was safe and potentially more effective than the 20 mg daily dose, was also known.

However, Dr. Selchen pointed out that this was not demonstrated and, as Cohen noted, a “larger,

longer study” would be needed.

[374] Dr. Selchen did not agree with Dr. Green that by 2007, it was recognized that CIS

treatments were identical to MS treatments.

[375] Dr. Selchen noted that for patients with CIS the tension was between early treatment,

given that there was evidence that early treatment may lead to improvements, and delayed

treatment, given that not all CIS patients progressed to MS and some did well without any

treatment.

[376] Dr. Selchen explained that, in 2007, opinions varied about whom to treat and when to

start treatment. One school of thought was that it was best to observe a period of no treatment

Page: 97

and monitor for disease activity for a year to establish whether the diagnosis could be made

based on the McDonald criteria (citing Panitch 2007).

[377] Dr. Selchen added that “the desire to begin therapy as soon as possible was not

universal”, noting that this had to be balanced against not providing treatment (due to its expense,

risk of adverse impacts and other considerations) to patients who would unlikely benefit from the

treatment, including the many CIS patients who never experience another clinical attack.

[378] Dr. Selchen explained that for those who advocated for early treatment, the standard of

care was “trending” toward using interferons for CIS upon diagnosis. He acknowledged the

existence of evidence in the treatment of CIS with interferons based on the ETOMS, CHAMPS,

and BENEFIT trials. However, he noted that there were neither reports nor evidence of the

effects of the use of glatiramer acetate in CIS patients.

[379] Dr. Selchen noted the need for caution when drawing inferences about glatiramer acetate

from the efficacy of treatment with interferons on CIS patients because the mechanism of action

for these treatments was not clear.

[380] Dr. Selchen also acknowledged that in “Early treatment” 2006 Neurol Sci 27: S8-S12,

Professor Comi reported some evidence that glatiramer acetate appeared to be more effective in

RRMS patients at earlier stages.

Page: 98

[381] Dr. Selchen took issue with Dr. Green’s statement that a number of trials had maintained

and even enhanced efficacy for reducing the relapse rate or delaying time to next relapse,

reducing evidence of new injury on MRI and reducing disability progression. Dr. Selchen noted

that Dr. Green did not identify the trials he relied on. Dr. Selchen also noted that any evidence

for reducing the progression of disability (for example with interferons) was short-term and, at

best, controversial.

[382] Dr. Selchen agreed that the relevant common general knowledge evolved between

November 28, 2007 and June 4, 2009 due to the publication of the results of the PreCISe trial

and the revision to the Copaxone product label to include an indication for patients who have

experienced a first clinical episode and have MRI features consistent with MS.

C.

The Common General Knowledge regarding the ‘437 Patent

[383] Pharmascience cited 103 pieces of art, but acknowledges that not all the prior art is

common general knowledge. Pharmascience submits, in the context of its submissions on

obviousness, noted below, and supported by the evidence of Dr. Green, that the POSITA was

aware of the treatments for MS, the prevailing view that early treatment of RRMS, in particular

CIS, was preferable and several studies supported this view, including the statements in Karussis

2006, if not Karussis itself.

Page: 99

[384] Teva agrees that the relevant common general knowledge included the approved

treatment therapies for MS (RRMS) available at that time, which were glatiramer acetate

(Copaxone) and interferons (Avonex, Rebif, and Betaseron).

[385] Teva notes that there were no test or approvals of glatiramer acetate for CIS, although it

was generally known that the PreCISe trial was underway.

[386] Teva submits that early treatment of patients was not part of the common general

knowledge. There was no “consensus”, rather the debate on whether, when and how to treat

continued.

[387] Teva acknowledges that as of November 2007 some interferon therapies were approved

for treatment of CIS, but notes that interferons are different compounds than glatiramer acetate.

[388] Teva submits that Karussis 2006 was not common general knowledge, as ultimately

acknowledged by Dr. Green.

[389] As noted above in Valeant at para 48 common general knowledge is that which would be

known to an “appropriately skilled addressed”, which means the average, real life POSITA. Not

all the articles and reports on studies cited, for example by Dr. Green, were well known or

generally accepted and were not part of the “common stock of knowledge”.

Page: 100

[390] The Court finds that the common general knowledge as of November 2007 reflected the

following:

 knowledge of the characteristics of MS, the classification of MS, brain imaging

(including the use of MRI), the evolution of diagnostic criteria for MS, the notion of CIS

and MS therapies (interferons and glatiramer acetate);

 for RRMS patients, glatiramer acetate was effective in reducing relapses, increasing the

time between relapses and reducing MRI activity, as demonstrated in clinical studies;

 there remained some debate regarding the benefits of early treatment of CIS patients.

Although there was a trend toward treating CIS patients with interferons, based on the

clinical trials of the interferons that had demonstrated the benefits of early treatment,

some experts continued to advocate to wait for a diagnosis of MS;

 interferons were different compounds than glatiramer acetate;

 glatiramer acetate had not been demonstrated to be effective for CIS patients;

 glatiramer acetate was not approved for use for CIS patients;

 it was generally known that the PreCISe trial was underway to determine the

effectiveness of glatiramer acetate in CIS patients; and

Page: 101

 Karussis 2006 was not part of the common general knowledge. As noted by Dr. Selchen

and acknowledged by Dr. Green, Karussis was not published in a well-known journal.

Dr. Green also acknowledged that Karussis was not part of the common general

knowledge, although some of the statements in Karussis were. I accept that statements in

Karussis 2006 that reflected the diagnostic criteria for MS pursuant to Poser and

McDonald and that noted the results of Phase III studies – e.g. of interferons for RRMS

and CIS patients and of glatiramer acetate for RRMS patients – would have been

common general knowledge. However, the recommendations or suggestions in Karussis

2006 to consider glatiramer acetate for CIS patients were not common general

knowledge.

XVIII. Can Pharmascience rely on the Gillette Defence to the Allegations of Infringement of the

‘437 Patent?

A.

Principles from the Jurisprudence

[391] The “Gillette defence” is so named due to its origins in Gillette Safety Razor Co v Anglo-

American Trading Co Ltd (1913), 30 RPR 465 (HL). The defence allows a defendant to deny

both the infringement and validity of the patent, and has been referred to as a short cut.

[392] The Gillette defence to a claim of infringement was described in AB Hassle v Apotex Inc,

2006 FCA 51 at para 15, as “made out when it is established that the alleged infringing product

is based on the teachings of a prior patent.”

Page: 102

[393] More recently, in Tensar Technologies, Limited v Enviro-Pro Geosynthetics Ltd, 2019 FC

277 at para 135, the Court explained:

[135] At trial, the Defendant abandoned anticipation as a validity

attack, except to the extent that anticipation relates to the Gillette

Defence. The Gillette Defence is made out when the alleged

infringer can establish that the allegedly infringing product is

based on the teachings of a prior art and therefore the alleged

infringer is merely doing something that is already known (Gillette

Safety Razor Co v Anglo-American Trading Co Ltd (1913), 30

RPR 465 (HL)).

B.

Pharmascience’s Submissions

[394] Pharmascience asserts the Gillette defence against the infringement allegations and

submits that it is practising the teachings of the prior art and, as a result, the ‘437 Patent is

invalid (as it claims what is in the prior art). Alternatively, if the ‘437 Patent is valid it cannot be

infringed by Pharmascience.

[395] Pharmascience submits that its Glatect product is indicated for the “treatment of

ambulatory patients with [RRMS]…to decrease the frequency of clinical exacerbations”, which

is the same indication that existed for Teva’s Copaxone prior to November 2007. Pharmascience

notes that 20 mg daily glatiramer acetate was a well-known treatment for RRMS well before

2007.

[396] Pharmascience’s reliance on the Gillette defence is based on its view that the target

patient population of the claims of the ‘437 Patent includes both CIS patients that do not meet

the McDonald criteria for MS and CIS patients who do meet the McDonald Criteria for MS.

Page: 103

Pharmascience submits that in 2007 glatiramer acetate was already the treatment for McDonald

MS patients, who typically have RRMS.

[397] Pharmascience also relies on Pinchasi 2007, which disclosed the use of 40 mg glatiramer

acetate for RRMS. Pharmascience submits that this includes the treatment of single-attack

patients who are diagnosed with MS under the 2005 McDonald Criteria.

[398] Pharmascience submits that Dr. Green referred to Pinchasi 2007 as a response to

Dr. Morrow’s infringement report. In addition, Pharmascience cited Pinchasi 2007 as an

anticipatory reference.

C.

Teva’s Submissions

[399] Teva argues that the law and the facts do not support Pharmascience’s Gillette defence.

[400] Teva submits that to establish the Gillette defence, the alleged infringer (Pharmascience)

must show that its activities are actually following the prior art and that the prior art anticipates

the claims of the patent.

[401] Teva argues that Pharmascience cannot rely on the Gillette defence to infringement

because Pharmascience’s proposed Glatect Product Monograph indicates that it is also for the

treatment of CIS patients (as does the Copaxone Product Monograph as of 2009). Prior to 2009,

Copaxone was not indicated for CIS. Teva points to Dr. Green’s evidence on cross-examination

Page: 104

where he acknowledged that the earlier Copaxone labels did not use the same language and did

not “call out” its use for CIS and that, at that time, there was no indication for CIS.

[402] Teva further submits that Pharmascience cannot rely on Pinchasi 2007 in support of a

Gillette defence. Teva first submits that Pinchasi should be disregarded as it was not referred to

in Dr. Green’s validity report. Teva also points to Dr. Green’s agreement that Pinchasi 2007 did

not guide physicians prescribing practices in 2007 or at all and that treating a CIS patient would

have been “off label” use in 2007.

D.

The Gillette Defence Cannot Succeed

[403] Based on the construction of the claims as found above, as targeting patients who have

had a single attack or CIS, (i.e., those who have not been diagnosed with CDMS in accordance

with the Poser criteria or have not been diagnosed with MS in accordance with the McDonald

criteria), the prior art did not teach the use of glatiramer acetate for CIS patients. The prior art

taught the use of glatiramer acetate for RRMS patients and this use was well known. The CIS

patient is not a MS or RRMS patient.

[404] Pinchasi 2007 was referred to by Dr. Green in response to Dr. Morrow’s opinion on

infringement and can be considered in the context of the Gillette defence. However, Pinchasi

2007 claims the use of glatiramer acetate 40 mg only for RRMS patients. There is absolutely no

mention in Pinchasi 2007 of a single attack patient or CIS. The test results referred to in Pinchasi

2007 are about RRMS patients. Pharmascience’s reliance on Pinchasi 2007 and Dr. Green’s

Page: 105

evidence that Pinchasi taught the use of 40 mg glatiramer acetate for some single attack or CIS

patients is based only on Pharmascience’s preferred construction of the claims, which the Court

has rejected.

[405] Pharmascience’s proposed combined Glatect Product Monograph provides that the 20 mg

product is indicated for RRMS patients and patients who have experienced a single

demyelinating event (i.e., a CIS patient). Pharmascience’s 40 mg product is for RRMS; there is

no mention of a CIS patient.

XIX.

A.

Is the ‘437 Patent Anticipated?

Principles from the Jurisprudence

[406] The test established in Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61

[Sanofi] governs the determination of anticipation. The Supreme Court of Canada reiterated that

anticipation requires disclosure and enablement and elaborated on both requirements. The Court,

at paras 25-26, referred to a U.K. decision, Synthon BV v SmithKline Beecham plc, [2006] 1 All

E.R. 685, [2005] UKHL 59 of Lord Hoffman:

[25] He explains that the requirement of prior disclosure means

that the prior patent must disclose subject matter which, if

performed, would necessarily result in infringement of that patent,

and states, at para. 22:

If I may summarize the effect of these two well-

known statements [from General Tire and Hills v.

Evans], the matter relied upon as prior art must

disclose subject matter which, if performed, would

necessarily result in an infringement of the patent. .

. . It follows that, whether or not it would be

Page: 106

apparent to anyone at the time, whenever subject

matter described in the prior disclosure is capable of

being performed and is such that, if performed, it

must result in the patent being infringed, the

disclosure condition is satisfied.

When considering the role of the person skilled in

the art in respect of disclosure, the skilled person is

“taken to be trying to understand what the author of

the description [in the prior patent] meant” (para.

32). At this stage, there is no room for trial and

error or experimentation by the skilled person. He is

simply reading the prior patent for the purposes of

understanding it.

[26] If the disclosure requirement is satisfied, the second

requirement to prove anticipation is “enablement” which means

that the person skilled in the art would have been able to perform

the invention (para. 26).

[407] The Supreme Court explained the requirements of enablement at para 27:

[27] Once the subject matter of the invention is disclosed by the,

prior patent, the person skilled in the art is assumed to be willing to

make trial and error experiments to get it to work. While trial and

error experimentation is permitted at the enablement stage, it is not

at the disclosure stage. For purposes of enablement, the question is

no longer what the skilled person would think the disclosure of the

prior patent meant, but whether he or she would be able to work

the invention.

[408] The Supreme Court set out a non-exhaustive list of factors to consider in making the

determination of enablement at para 37, including that the POSITA may rely on the common

general knowledge to supplement the information in the patent, and that routine trials are

acceptable, but prolonged or arduous trial and error would not be considered routine.

[409] In Tearlab Corporation v I-Med Pharma Inc, 2019 FCA 179 at paras 73 and 81, the

Court of Appeal noted the distinction between anticipation and obviousness, highlighting that

Page: 107

anticipation must be found in a single document, not in a mosaic, as is permitted for the

assessment of obviousness, and stated at para 73:

As noted by Donald MacOdrum in Fox on the Canadian Law of

Patents, 5^thed., looseleaf (Toronto, Ont.: Thomson Reuters

Canada, 2019), at pp. 4-6 and 4-7 [MacOdrum]:

There is a crucial difference in assessing the effect

of prior documents on the question of anticipation

and obviousness. When approaching an enquiry as

to the novelty of an alleged invention, anticipation

must be found in a single document. In other words,

it is not legitimate to read several documents

together and thus, as the cases put it, to make a

mosaic of extracts. In addition, that single document

must disclose the precise invention claimed in the

patent under attack. But, in considering invention

versus obviousness, the prior art should be reviewed

and its cumulative effect considered. [References

omitted.]

[410] In Hospira Healthcare Corporation v Kennedy Trust for Rheumatology Research, 2020

FCA 30 [Hospira], the Court of Appeal recently addressed the two requirements for anticipation

at paras 66-71, citing the Sanofi test.

[411] The Court of Appeal also found that the trial judge erred by conflating the elements of

disclosure and enablement and in so doing found that the prior art cited was speculative and, as a

result, not anticipatory. The Court of Appeal noted at para 73:

[73] Though the Judge acknowledged that the test for

anticipation has the two distinct requirements of disclosure and

enablement as identified in paragraph [66] above, his analysis of

the 1994 Kennedy Report and Higgins in the Reasons does not

address these requirements distinctly. The Judge appears to have

dismissed the appellants’ anticipation arguments concerning these

two references on the basis that they fail to meet the disclosure

requirement because they do not disclose results of the proposed

experiments. This approach appears to conflate disclosure and

Page: 108

enablement. The disclosure requirement is satisfied if performing

what is described in the prior art reference would necessarily result

in infringement. From a reading of the Reasons, it is not clear how

this requirement is not satisfied at least as regards the 1994

Kennedy Report. Even for Higgins, it is not clear how this

requirement is not satisfied for those claims that do not include

either infliximab or dosing or an administration schedule as an

essential element.

B.

Pharmascience’s Submissions

[412] Pharmascience argues that Karussis 2006 anticipates the ‘437 Patent (except claim 16)

regardless of how the claims are construed with respect to the single attack patient.

Pharmascience submits that Karussis 2006 satisfies both the disclosure and enablement

requirements of anticipation.

[413] Pharmascience notes that the Karussis Working Group reached consensus on several

statements and recommended that glatiramer acetate be used to treat single-attack patients who

satisfied the McDonald criteria. Pharmascience notes that Karussis 2006 also recommended that

glatiramer acetate be used to treat single-attack patients who fell short of satisfying the

McDonald criteria. Pharmascience submits that in November 2007, a POSITA could have easily

prescribed Copaxone 20 mg daily to treat both groups of patients.

[414] Pharmascience submits that it is beside the point that the 20 mg dosage was not approved

or indicated for single attack patients and that its use would be “off label”. Pharmascience

submits that physicians were not prohibited from prescribing Copaxone. Pharmascience adds that

Dr. Green indicated that he and others did so. Pharmascience submits that Teva’s experts

Page: 109

acknowledged that off label use occurred. Pharmascience submits that the only issue is whether

the POSITA could put the claims into practice based on the teaching of the prior art and clearly

they could.

[415] Pharmascience further submits, based on its preferred interpretation that the claims

include single attack patients who meet the McDonald criteria for MS, that all claims of the ‘437

Patent, including claim 16 (which claims 40 mg glatiramer acetate), are anticipated by Pinchasi

2007. Pharmascience also argues anticipation by Pinchasi because Pinchasi 2007 also disclosed

that a 20 mg dosage had been shown to reduce MRI-measured lesions in MS patients.

[416] Pharmascience notes that, regardless of how the claims are interpreted, the ‘437 Patent

states that the “formulation of 40 mg Copaxone® has been disclosed” and in doing so, the

POSITA must have been enabled to administer 40 mg glatiramer acetate. Pharmascience submits

that Teva is bound by this admission (i.e., regarding claim 16).

[417] Pharmascience disputes Teva’s submission – that because none of the benefits or

outcomes of early treatment with glatiramer acetate, as claimed in the ‘437 Patent, were

described in the prior art cited – the ‘437 Patent is novel. Pharmascience argues that as long as

performing the prior art would result in infringement of the claims, the disclosure requirement of

anticipation is met because the benefits or outcomes obtained simply flow from performing the

disclosure (Sanofi at paras 23-27).

Page: 110

[418] Pharmascience notes that the results of the PreCISe trial demonstrated that 20 mg

glatiramer acetate administered to single attack patients will result in all of the claimed benefits

(e.g., reducing progression of MRI-monitored disease activity; reducing the progression of

symptoms of MS; reducing the frequency of relapse; reducing the mean number of new T2

lesions; and the rate of accumulating new T2-weighted lesions is reduced by at least 50%).

[419] Pharmascience submits that although the POSITA may not have known that these

benefits would result, if the POSITA performed the disclosure in Karussis 2006 they would

obtain these benefits and they would infringe the claims of the ‘437 Patent.

[420] Pharmascience also disputes Teva’s submission that there is no anticipation when the

prior art sets out choices (e.g., the choice between interferons or glatiramer acetate).

Pharmascience submits that the issue is whether there is disclosure and enablement of the

essential elements of the claims.

[421] Pharmascience disputes Teva’s arguments that Karussis 2006 is not prior art for the

purpose of anticipation because it was speculative. Pharmascience submits that anticipation does

not require that the prior art be evidence-based; all that is required is that the prior art disclose

the invention and enable the POSITA to put it into practice. Pharmascience relies on Hospira at

para 73 where the Court of Appeal found that it was an error to discount prior art references

because they did not disclose the results of proposed experiments.

Page: 111

[422] Pharmascience also points to Biogen, where this Court dealt with an anticipatory

reference of a study protocol that did not include results. The Court applied Hospira, at paras

133-138, and found on the facts of that case that the lack of results from the ongoing study noted

in the anticipatory reference was not fatal to the anticipation allegation.

[423] By analogy, Pharmascience submits that the statements in Karussis 2006 and the

anticipated results from the PreCISe trial to support those statements are sufficient to meet the

disclosure requirement of anticipation.

[424] Pharmascience submits that Teva cannot be rewarded with a patent that took the ideas set

out in Karussis 2006. Even if Karussis 2006 did not pursue the recommendations, it disclosed the

recommendation.

C.

Teva’s Submissions

[425] Teva reiterates that the patient population addressed in the claims is a CIS patient and

does not include a patient who meets the McDonald criteria for MS.

[426] Teva submits that the claims of the ‘437 Patent are novel and were not anticipated by

Karussis 2006 or Pinchasi 2007. Teva submits that Karussis 2006 was a lesser-known article that

set out opinions without an evidence base. Teva submits that even if Karussis 2006 is a proper

prior art reference, it did not disclose or enable the claims of the ‘437 Patent as it does not

provide a clear direction that would inevitably lead the POSITA to the subject matter claimed in

Page: 112

the patent. Teva submits that Karussis 2006 did not specifically direct the use of glatiramer

acetate. Nor did Karussis 2006 provide any disclosure of the benefits or outcomes as claimed in

the ‘437 Patent. In addition, the POSITA could not practice the invention in November 2007.

[427] Teva submits that to establish anticipation, a single document must disclose the “precise

invention” and provide all information for an enabling disclosure. One document must “disclose

exactly and fully what the patentee has claimed” (Tearlab at para 81). Teva submits that this is a

high threshold to meet and that Karussis 2006 does not satisfy this threshold.

[428] Teva further submits that the benefits of glatiramer acetate to treat CIS patients were not

known or contemplated by the prior art cited by Pharmascience (Karussis 2006 or Pinchasi

2007). Teva submits that Karussis 2006 does not disclose the outcomes or benefits set out in the

subject matter of the claims. For example, Karussis 2006 does not disclose the therapeutic

efficacy of glatiramer acetate to: delay the onset of CDMS; reduce progression of MRI-

monitored disease activity; reduce the progression of symptoms of MS; or, reduce the frequency

of relapses. Nor does Karussis 2006 disclose a 40 mg dose of glatiramer acetate (claim 16). Teva

adds that Karussis 2006 does not disclose any specific therapeutic outcome. Teva notes that

claim 33 describes a 50% reduction in new T2 lesions, which was unexpected.

[429] Teva explains that the PreCISe trial was stopped prematurely due to its successful early

results that demonstrated “significant and pronounced effects for patients with MRI active

disease”. Teva relied on these results to gain approval for this new indication for treating CIS.

Page: 113

Teva relies on Sanofi, at para 41, and submits that the beneficial properties demonstrated in the

PreCISe trials were not disclosed in the prior art and, as a result, there is no anticipation.

[430] Teva submits that it cannot be said that if a POSITA practices the suggestions in Karussis

2006, it would work to effectively treat CIS patients because there was absolutely no such

evidence disclosed in Karussis 2006.

[431] Teva argues that the POSITA would not pursue the recommendations in Karussis 2006.

Teva points to the evidence of Dr. Selchen who clearly stated that the “skilled person would have

completely rejected this recommendation”.

[432] Teva further submits that the reference in Karussis 2006 to clinical trials in progress at

that time, cannot anticipate the ‘437 Patent as Teva’s experimental use in the course of the trial

does not constitute public disclosure or use.

[433] Teva also argues that Karussis did not enable the POSITA to practice the invention

because the use of glatiramer acetate for single attack patients was not approved in 2007.

[434] Teva submits that Dr. Green was inconsistent in his evidence regarding his use of

off-label drugs. Teva notes that in this litigation, Dr. Green stated that he prescribes off label and

that he and other physicians would have done so in 2007 for glatiramer acetate for CIS patients.

However, in the U.K. litigation, Dr. Green stated that he would not change his prescribing

Page: 114

practices even based on a Phase II clinical study; in other words, without evidence of

effectiveness.

[435] Teva further submits that Pinchasi 2007 does not anticipate the claims of the ‘437 Patent

because Pinchasi 2007 does not disclose the use of glatiramer acetate to treat CIS, rather it

discloses its use to treat RRMS. Teva also notes that Dr. Green admitted that a “physician

doesn’t read Pinchasi 2007 to guide their prescribing practices”.

D.

What do the Experts Say?

(1)

Dr. Green

[436] In Dr. Green’s opinion, the claims of the ‘437 Patent were disclosed and enabled by

Karussis 2006.

[437] Dr. Green noted that Karussis 2006 concluded that “there is evidence that early DMD

therapy in patients with a first acute clinical demyelinating event may provide long-term benefit

in delaying the progression of the disease and conversion to clinically definite MS”. Dr. Green

pointed to the Karussis Working Group’s conclusion that patients that “fall short” of the MS

diagnosis pursuant to the McDonald criteria “still warrant consideration for treatment”.

[438] Dr. Green referred to Karussis 2006, which concluded that because interferons and

glatiramer acetate had all been shown to be effective in RRMS, and because a CIS patient is

Page: 115

highly likely to progress to MS, “it is reasonable to propose early treatment with these DMDs at

the doses approved for MS, even though there is not yet evidence to support this approach”. In

his written opinion, Dr. Green stated that Karussis 2006 recommended “not just DMTs generally,

but glatiramer acetate specifically for use in CIS patients”.

[439] Dr. Green relied on the statement in Karussis 2006 – that the use of glatiramer acetate in

CIS patients (patients with a single attack suggestive of MS and evidence of lesions) “should

work” and would be “reasonable” – to support his opinion that Karussis 2006 discloses the

subject matter of the claims.

[440] Dr. Green added that Karussis 2006 also enabled the POSITA to implement the invention

by specifically indicating that it would be reasonable to treat a CIS patient with glatiramer

acetate “at the doses approved for MS”. The POSITA could easily implement this by

administering 20 mg glatiramer acetate to CIS patients (the dose approved for MS) and

monitoring their progress.

[441] In his oral evidence, Dr. Green stated that prior to November 2007, he and other

physicians prescribed Copaxone to treat RRMS patients who had only experienced a single

clinical attack. Dr. Green stated that he and other physicians also prescribed Copaxone 20 mg to

treat CIS patients (i.e., patients who had only experienced a single clinical attack but did not

meet the 2005 McDonald criteria to confirm a diagnosis of MS). Dr. Green acknowledged,

however, that he did not state this in his report on validity.

Page: 116

[442] Dr. Green noted that it is common for physicians to prescribe medicines for off-label

uses.

(2)

Dr. Selchen

[443] Dr. Selchen did not agree with Dr. Green that Karussis 2006 disclosed and enabled (i.e.,

anticipated) the claims of the ‘437 Patent.

[444] Dr. Selchen described Karussis 2006 as an opinion piece that reflected a consensus

among the Karussis Working Group on particular statements that were put to them for

discussion. He explained that the focus of Karussis 2006 was on treatment-switching strategies in

MS patients already undergoing therapy. Dr. Selchen noted that there was no study or collection

of data to underpin the statements or recommendations.

[445] Dr. Selchen acknowledged that the Karussis Working Group agreed that all approved

first-line treatments (i.e., interferons and glatiramer acetate) should also work in patients with

CIS and may be considered for use in such patients.

[446] Dr. Selchen agreed that in 2007, it was not controversial for the Karussis Working Group

to state that patients who fall short of the McDonald criteria “warrant consideration” for

treatment. However, the treatment at that time would have been with the tested and approved

interferons. Dr. Selchen did not agree that the Karussis Working Group recommended glatiramer

Page: 117

acetate for a CIS patient, rather that this be considered. He added that most POSITAs would have

disagreed with this recommendation in 2007 because it was not evidenced based.

[447] Dr. Selchen also noted that Karussis 2006 accepted that some CIS patients may choose

not to be treated and prefer to wait for a second attack before beginning treatment.

[448] Dr. Selchen emphasized that although the PreCISe trial was underway to study the use of

glatiramer acetate in CIS patients, glatiramer acetate had not been approved to treat CIS patients.

Dr. Selchen noted that nothing was known about the efficacy of glatiramer acetate for CIS

patients as there had been no previous studies.

[449] Dr. Selchen explained that a practicing clinician would not draw any inferences regarding

glatiramer acetate based on their awareness that the PreCISe trial was in progress and would not

draw an inference from the results of studies about interferons to recommend or commence off

label treatment of glatiramer acetate for CIS patients.

[450] Dr. Selchen added that Karussis 2006 did not disclose the therapeutic benefits or

outcomes set out in the claims of the ‘437 Patent. Dr. Selchen disagreed with Dr. Green that a

50% reduction in new T2 lesions was “typical” either of RRMS patients treated with glatiramer

acetate or of CIS patients treated with interferons.

[451] With respect to enablement, Dr. Selchen did not agree with Dr. Green that the POSITA

would “easily be able to implement” the disclosure of Karussis 2006 to arrive at the subject

Page: 118

matter of the claims. Dr. Selchen explained that the POSITA would not be able to administer

glatiramer acetate or determine whether the treatment was therapeutically effective as this would

require the conduct of a clinical trial, which is costly, time consuming and requires extensive

planning.

[452] Counsel for Pharmascience asked Dr. Selchen whether a physician who followed

statement #5 in Karussis 2006 would prescribe 20 mg glatiramer acetate to a CIS patient.

Dr. Selchen responded that this was “completely incorrect”. He stated that in the “real world”

doctors in Canada could not prescribe an unapproved drug: “absolutely, unequivocally no”. He

added that this would be untenable because there was no evidence to support its effectiveness, as

noted by Karussis 2006. Dr. Selchen acknowledged that there was no prohibition on prescribing

it off-label, and the drug was available, but that this would not be done in Canada.

E.

Karussis 2006 does Not Anticipate the Claims of the ‘437 Patent

[453] As noted, for anticipation, a single piece of prior art must both disclose and enable the

subject matter of the claims. Pharmascience relies on Karussis 2006 as the single piece of prior

art that anticipates all claims of the ‘437 Patent except claim 16. Pharmascience relies on

Pinchasi 2007, a patent application, as the single piece of prior art that anticipates claim 16.

[454] Pharmascience’s submission that claim 16 is disclosed and enabled by Pinchasi 2007 is

based on Pharmascience’s broader interpretation of the claims, which is rejected. Pinchasi

claimed the use of 40 mg glatiramer acetate only for RRMS patients and noted that 20 mg

Page: 119

glatiramer acetate had been disclosed previously for RRMS patients. Pinchasi disclosed test

results for RRMS only, not CIS.

[455] I find that Karussis 2006 does not disclose or enable the claims of the ‘437 Patent.

[456] Karussis 2006 and the key statements relied on by Pharmascience must be put in context.

[457] As mentioned above, Karussis 2006 was published in the European Journal of Neurology,

noted by Dr. Selchen as not one of the top journals and not well known by the POSITA.

Although Karussis 2006 is not common knowledge, some of the references cited are common

knowledge. Regardless, it is the prior art relied on.

[458] Karussis 2006 is a report of an International Working Group for Treatment Optimization

in MS that discussed several statements and refined them, resulting in 15 consensus statements

on MS treatment. The Karussis Working Group did not conduct or propose any experiments or

any study protocol. Rather, it considered what had already been studied and noted that other

studies were in progress.

[459] As noted by Dr. Selchen, the stated purpose of the Karussis Working Group was to

“recommend evidence-based therapeutic options for the management of suboptimal responses or

intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple

sclerosis (MS).”

Page: 120

[460] Statement #1 provides, “[c]andidates for initiation of DMD therapy should ideally meet

the McDonald criteria for the diagnosis of MS”. In the discussion regarding this statement, the

authors noted the criteria for a diagnosis of MS pursuant to McDonald. They also noted that

earlier clinical trials used the Poser criteria for diagnosis.

[461] In the discussion under statement #1, the authors noted “[w]hilst it is accepted that the

majority of patients recommended for initiation of DMD therapy should have MS (as described

by the McDonald criteria; Table 2), the Working Group agreed that some patients that fall short

of fulfilling the McDonald criteria still warrant consideration for treatment”. The authors

explained that those patients at high risk for developing MS should be considered. They also

noted that for those with ‘possible MS’ special care must be taken before any decisions are made

and advice must be sought from an experienced neurologist.

[462] The authors explained that the starting point is that the majority of patients to be treated

with DMDs (also referred to as DMTs) should be diagnosed with MS. A subset of patients, at

high risk, “warrant consideration for treatment”. This wording, noted by Dr. Selchen to be

conditional, conveys that it would be somewhat exceptional to treat a patient who falls short of

the MS diagnosis with a DMD.

[463] Karussis 2006 statement #4 provides that “[r]ecommendations related to the treatment

paradigm should be based on approved agents with proven efficacy in large, Phase III trials in

MS; experimental or ‘off-label’ treatments or combinations cannot be recommended as first line

therapies”. The authors then noted that three interferons and glatiramer acetate had been shown

Page: 121

to reduce disease activity in Phase III clinical trials in patients with RRMS and CDMS

(according to the Poser criteria). The references cited in Karussis 2006 include reports on several

Phase III clinical trials. This statement conveys that the authors agree that Phase III clinical trials

guide the use of DMDs.

[464] Statement #5, which is relied on by Pharmascience in support of its allegations of

invalidity based on anticipation and obviousness, provides that “[a]ll approved ﬁrst-line DMD

treatments can be considered for use after the ﬁrst demyelinating event in patients at high risk of

conversion to MS.”

[465] Karussis 2006 includes the following additional observations regarding Statement #5:

 “Whilst [the Karussis Working Group] agreed that all approved first-line treatments

([interferons] and glatiramer acetate…) should also work in patients with CIS and thus

may be considered for use in such patients, they accepted that this recommendation is not

evidence-based.”

 “There are no data with [Betaseron] or glatiramer acetate in patients with a CIS

suggestive of MS, although studies are ongoing.” The Working Group cited the

CHAMPS study, but did not specifically refer to the PreCISe study.

 “They [the Working Group] concluded that, as [interferons] and glatiramer acetate have

all been shown to be eﬀective in RRMS, and a patient with a CIS is highly likely to

Page: 122

progress to MS, it is reasonable to propose early treatment with these DMDs at the doses

approved for MS, even though there is not yet evidence to support this approach.”

[466] In the discussion, which follows the 15 statements, the authors note that “[a] patient with

CIS suggestive of MS may prefer to wait for a second attack before beginning treatment. Others

may reject treatment with IFN beta or glatiramer acetate because they do not wish to have

injections.”

[467] In my view, the POSITA would read Karussis 2006 in its entirety with the benefit of their

knowledge of MS and would draw distinctions between the statements that are based on

evidence and those that are not. The POSITA would understand Karussis 2006 statement #5 to

be a carefully worded opinion (“can be considered for use”) coupled with the caveat about the

lack of evidence about the early treatment of CIS patients and that the recommendations of the

Karussis Working Group are not prescriptive.

[468] Pharmascience’s position – that Karussis 2006 disclosed and enabled the claims of the

‘437 Patent because Karussis 2006 recommended that glatiramer acetate be used to treat single

attack (CIS) patients who fell short of the McDonald criteria for MS – is an over statement.

[469] Dr. Green’s evidence in support of this view also overstates some of the Karussis 2006

statements and recommendations and does not reflect the purpose of Karussis 2006 or the full

context in which the statements were made. Contrary to Dr. Green’s written opinion that

“Karussis recommended not just DMTs generally, but glatiramer acetate in particular for CIS

Page: 123

patients”, this is not what Karussis 2006 states. Dr. Green conceded on cross-examination that

Karussis 2006 does not specifically recommend glatiramer acetate, rather glatiramer acetate is

included as one of the approved therapies for MS and Karussis 2006 only suggested that such

therapies be considered.

[470] On cross examination, Dr. Green also acknowledged that there were no reports of the

effective use of glatiramer acetate in patients with CIS before November 2007; the studies done

to that date on glatiramer acetate were with respect to RRMS patients; the studies done to date

with respect to CIS patients were of interferons; the Karussis 2006 recommendation referred to

all therapies, not glatiramer acetate in particular; Karussis 2006 did not refer to 40 mg of

glatiramer acetate; and, Pinchasi 2007 claimed a 40 mg dose of glatiramer acetate for RRMS.

[471] As Dr. Selchen explained, there was no evidence anywhere at that time to support the

effectiveness of glatiramer acetate for CIS patients – no Phase II studies, pilot studies or even

case reports.

[472] Dr. Selchen noted that in 2007, the determination whether a given MS therapy is effective

was (and still is) based on scientific evidence from clinical studies. He explained that there are

“classes” of clinical studies, which guide the evaluation of the data presented (as noted in

Neurology). Class 1 would be a prospective study, randomized, controlled and blinded in a

representative population (such as the PreCISe trial). Other experts referred to this type of study

as the “gold standard”. Dr. Selchen noted that an expert opinion is not a study.

Page: 124

[473] I prefer the evidence of Dr. Selchen who characterized Karussis 2006 as disclosing only

the agreement of the thirteen members of the Karussis Working Group that DMTs, including

glatiramer acetate, “should” work, “may be considered” for use and that “it is reasonable to

propose early treatment”. Dr. Selchen regarded the statements in Karussis 2006 as proposals

based on a hypothesis and speculation, and not evidence-based as the report acknowledged.

[474] As mentioned above, Dr. Selchen agreed that it was not controversial for the Karussis

Working Group to state that patients who fall short of the McDonald criteria “warrant

consideration” for treatment, but in his view, the treatment considered at that time would have

been with the interferons that had been tested and were approved.

[475] I accept Dr. Selchen’s view that the POSITA would not have viewed Karussis 2006 as

disclosing glatiramer acetate 20 mg for CIS patients due to the wording of the report, its context

and purpose and the lack of any evidence about the efficacy of glatiramer acetate. Karussis 2006

did not disclose fully and exactly what the patent claims and would not lead the POSITA directly

to the claimed subject matter of the ‘437 Patent.

[476] With respect to Pharmascience’s submission that anticipation has never required the prior

art to be evidence based, the jurisprudence relied on by Pharmascience reflects factual findings

that the prior art at issue in those cases met the disclosure requirement (e.g., Eli Lilly Canada Inc

v Mylan Pharmaceuticals ULC, 2020 FC 816; Hoffman-La Roche Limited v Apotex Inc, 2013 FC

718; and Shire Biochem Inc v Canada (Health), 2008 FC 538). The jurisprudence relied on does

not set out any general proposition.

Page: 125

[477] As noted above, Pharmascience submits that as in Hospira and Biogen, it is an error to

ignore prior art that lacks test results where performing the idea described in the prior art would

result in infringement. Pharmascience submits that even if speculative, Karussis 2006 anticipates

the claims of the ‘437 Patent. Pharmascience submits that the statements in Karussis 2006, along

with the anticipated PreCISe results to support those statements, are sufficient to meet the

disclosure requirement of anticipation.

[478] First, the Court has not ignored Karussis 2006 as prior art; Karussis 2006 has been

carefully considered from beginning to end.

[479] Second, I accept the principle set out in Hospira, but find that Karussis 2006 is not in the

same category of speculative art noted in Hospira or Biogen.

[480] In Hospira, the prior art at issue was the 1994 Kennedy Report, which was intended to

“further investigate the tolerability and efficacy of repeated use of [infliximab]…” (at para 68)

and which noted that results would be available the following year. In Biogen, the anticipatory

art at issue was a study protocol, without any results. Karussis 2006 was not a study protocol nor

did it set out to investigate any of its suggestions or statements. Karussis 2006 was a report on

the discussions of a working group.

[481] In the present case, the idea described in Karussis 2006 is the very idea that Teva was in

the process of testing in the PreCISe trial. Karussis 2006 did not set out a study protocol or

describe any testing that was in progress or expected results. Karussis 2006 simply suggested

Page: 126

that CIS patients warranted consideration for early treatment. In my view, it would defeat the

purpose of clinical trials to support the patentability of an invention (and, of course, its safety and

efficacy) if a group of experts could note that a clinical trial conducted by others was in progress

and recommend or suggest that what is being tested be done. Moreover, Karussis 2006 did not

even recommend that glatiramer acetate be used for CIS patients – only that one of the DMTs

approved for RRMS be considered.

[482] I note that Karussis 2006 does not cite the PreCISe trial at all and does not speculate that

it would be successful. Statement #5 says only that “there are no data with [Betaseron] or

glatiramer acetate in patients with a CIS diagnosis suggestive of MS, although studies are

ongoing”. The study referred to in the relevant footnote is the CHAMPS study of the interferon

Avonex.

[483] Contrary to Pharmascience’s submission, Teva was not capitalizing on the Karussis

Working Group’s ideas, rather it was testing its own idea.

[484] In my view, if Karussis 2006 is anticipatory art, what would prevent a group of experts in

any field from having discussions and speculating on the positive outcome of a clinical trial in

progress, developed and implemented by others, in order to later argue that their speculation that

the trial in progress would be successful anticipated the claims of a patent that are based on such

clinical trials. This approach seems to be inconsistent with the objectives of the experimental use

exemption established in the common law.

Page: 127

[485] As noted by Teva, the law recognizes that there is no disclosure for the purposes of

anticipation where a prior use is experimental (Bayer Inc v Apotex Inc, 2016 FC 1013 at paras

157, 162). If a patent cannot be anticipated by its own clinical study, in my view, it cannot be

anticipated by the speculative recommendations of a group of experts who discuss the state of

MS treatment, note the lack of evidence, and note that trials are underway.

[486] With respect to enablement, I also find that on a balance of probabilities the POSITA

could not “work the invention” (Sanofi at para 27). While it may appear to be a simple matter to

prescribe 20 mg Copaxone for CIS patients given that 20 mg Copaxone was available and was

approved for RRMS patients, it was not that simple.

[487] Contrary to Pharmascience’s submission – that prescribing an off-label drug was not

prohibited and that is all that matters – the POSITA could not have easily prescribed glatiramer

acetate (Copoxone 20 mg) to treat a CIS patient.

[488] As noted above, in his oral evidence, Dr. Green stated that prior to November 2007, he

and other physicians had prescribed Copaxone 20 mg off-label to treat CIS patients. However,

Dr. Green acknowledged that he did not state this in his report on validity.

[489] Dr. Green added that it is common for physicians to prescribe medicines for off-label

uses and, in many instances, this may fall within the standard of care.

Page: 128

[490] Dr. Green’s evidence is not entirely consistent. His evidence of his own practice varied.

His reference to what other physicians did cannot be accepted. He stated that he prescribed

20 mg Copaxone off-label although it was not approved. However, he also stated that he would

not have prescribed 40 mg Copaxone based on Pinchasi 2007 because it was not approved. Dr.

Green also acknowledged that he was not well versed in the Canadian health system although he

had some awareness of national health systems.

[491] I have placed more reliance on Dr. Selchen’s opinion, that in his experience CIS patients

were not treated with a drug that was not approved for use to treat CIS. He emphasized that a

physician would not prescribe a drug for CIS patients in the absence of proof of efficacy.

Physicians would use what had a clear evidence base. Dr. Selchen also explained that,

practically, he would not have been able to use glatiramer acetate in 2007 as it was not approved

and it would not have been covered or reimbursed under any plan. He noted the very high cost of

the therapy, which would make it “untenable” to prescribe. Moreover, Dr. Selchen was not aware

of other doctors doing so outside of the clinical trial.

[492] I do not find that Dr. Selchen’s evidence regarding off-label drugs was inconsistent, as

alleged by Pharmascience. Dr. Selchen explained that the reference in a co-authored publication

to treating children with glatiramer acetate although off-label was not his area of expertise and

that was the input of other authors with expertise in pediatric MS. Dr. Prat later explained that

most drugs for children are considered to be off-label because clinical tests of drugs do not

engage children for obvious reasons.

Page: 129

[493] Dr. Morrow also stated that off-label drugs would not be prescribed. Contrary to

Pharmascience’s submission that Dr. Morrow said this could not be “ruled out”, her point was

that she could not speak for others, as Dr. Green purported to do.

XX.

A.

Is the ‘437 Patent Obvious?

Principles from the Jurisprudence

[494] The Supreme Court of Canada set out the law on obviousness in Sanofi. Subsequent

jurisprudence has provided additional guidance on its interpretation and application.

[495] In Sanofi, at paras 66-69, the Court followed the approach from Windsurfing

International Inc v Tabur Marine (Great Britain) Ltd, [1985] RPC 59 (UKCA) as updated in

Pozzoli SPA v BDMO SA, [2007] FSR 37, [2007] EWCA Civ 588 and described the four steps to

guide the analysis of allegations of obviousness:

1. Identify the notional “person skilled in the art” and the relevant common knowledge of the

skilled person as of the claim date;

2. Identify the inventive concept of the claim in question or if that cannot readily be done,

construe it;

Page: 130

3. Identify what, if any, differences exist between the matter cited as forming part of the state

of the art and the inventive concept of the claim or the claim as construed; and,

4. Determine whether these differences, viewed without any knowledge of the alleged

invention as claimed, constitute steps, which would have been obvious to the person

skilled in the art or would have required any degree of invention.

[496] The fourth step is referred to as the “obvious to try” test. The Court noted at para 66:

[66] For a finding that an invention was “obvious to try”, there

must be evidence to convince a judge on a balance of probabilities

that it was more or less self-evident to try to obtain the invention.

Mere possibility that something might turn up is not enough.

[497] The Court explained that where the obvious to try test is warranted, other factors may

assist and inform that step. The Court noted, at paras 69-71, that the relevant factors vary with

the circumstances and would include:

 “Is it more or less self-evident that what is being tried ought to

work? Are there a finite number of identified predictable

solutions known to persons skilled in the art?”

 “What is the extent, nature and amount of effort required to

achieve the invention? Are routine trials carried out or is the

experimentation prolonged and arduous, such that the trials

would not be considered routine?”

Page: 131

 “Is there a motive provided in the prior art to find the solution

the patent addresses?”

 The course of conduct leading to the invention, including the

history of the invention, whether the inventor arrived at the

invention quickly and easily based on the prior art and

common general knowledge, and the inventors’ particular

expertise compared to that of the POSITA.

[498] In Pfizer Canada Inc v Apotex Inc, 2009 FCA 8 at para 29, the Court of Appeal clarified

that “obvious” within the meaning of “obvious to try” means “very plain” and that possibility

and speculation is not the test, nor is “worth a try”; rather, the invention must be “more or less

self-evident”, as noted in Sanofi.

[499] In Ciba Specialty Chemicals Water Treatments Limited’s v SNF Inc, 2017 FCA 225 at

para 62 [Ciba], the Court of Appeal noted that, in bridging the differences between the invention

and the prior art, “[t]he Skilled Person can have recourse to their common general knowledge

supplemented by those pieces of prior art which could be discovered by a reasonably diligent

search”.

[500] In Hospira, the Court of Appeal clarified the distinction between the obvious to try test

(step 4) and the factors that inform it, at para 90:

[90] It should be noted that, whereas being “more or less self-

evident to try to obtain the invention” (per Sanofi at para. 66) is a

Page: 132

requirement for obviousness to try, being “more or less self-

evident that what is being tried ought to work” (per Sanofi at para.

69) is not a requirement but merely a factor to be considered

[501] In Hospira, the Court also considered the scope of the prior art that is relevant for the

obviousness analysis, noting that at the obvious to try step, the fact that a prior art reference

would not turn up or be part of a mosaic is relevant. The Court of Appeal noted at para 86:

[86] In light of section 28.3 of the Patent Act and the applicable

jurisprudence and commentaries, I conclude that it is an error to

exclude from consideration prior art that was available to the

public at the relevant date simply because it would not have been

located in a reasonably diligent search. The likelihood that a prior

art reference would not have been located by a PSA may be

relevant to consideration of step 4 of the obviousness analysis

(whether differences between the state of the art and the inventive

concept constitute steps which would have been obvious to the

PSA) in that the uninventive PSA might not have thought to

combine that prior art reference with other prior art to make the

claimed invention. However, excluding prior art simply because it

is difficult to find is problematic because it would result in the

possibility of a valid patent on an invention that had, but for some

non-inventive tweak, already been disclosed to the public. In my

view, that is not what Canada’s patent regime is intended to

permit.

[502] Unlike anticipation, the analysis required to determine obviousness does not focus on a

single piece of prior art. For obviousness, the question is whether the POSITA, relying on all the

relevant prior art and with the common general knowledge supplemented by information that

could be discovered by a reasonably diligent search, would reach the invention directly and

without difficulty or whether inventive ingenuity would be required.

[503] In Tearlab at paras 73 and 81, the Court of Appeal explained how prior art is used

differently in assessing allegations of anticipation and obviousness, noting at para 73:

Page: 133

[73] …There is nothing “contradictory” in finding that a prior

art reference, when considered alone, does not anticipate, but that

it can nonetheless render a claim obvious when combined with

another reference.

[504] At para 81, the Court of Appeal elaborated:

[81] . . . Every element of an obvious claim need not be found in

single prior art reference; that is the test for anticipation. The test is

rather whether a POSITA can bridge the gap between the state of

the art at the relevant time and the claim as construed, without

inventive ingenuity. Prior art will be used in the application of both

anticipation and obviousness, but in a different manner;

anticipation will be established if a single document can be found

which gives a POSITA all the information which is needed to

produce the claimed invention without the exercise of any

inventive skill, whereas for obviousness it is the cumulative effect

of the prior art that must be considered to determine whether the

skilled but unimaginative technician would have come to the

solution taught by the patent directly and without difficulty. As

stated by Harold G. Fox in his seminal book titled Canadian

Patent Law and Practice, 4^thed. (Toronto, Ontario: Carswell,

1969), at p. 137:

. . . Prior specifications are generally used to show

anticipation if they disclose exactly and fully what

the patentee has claimed. If such disclosure is not

made by the prior specification and it cannot be

used as an anticipation, it may be used as indicating

the state of the art at the time that the patentee made

his alleged invention and as showing that what the

patentee did was so slight a contribution to existing

knowledge as to lack the essential element of

invention and to be merely obvious…

Page: 134

B.

Pharmascience’s Submissions

[505] Pharmascience submits that the subject matter of the claims reflected the state of the art

in November 2007; there were no differences and no inventive ingenuity was required to reach

the subject matter of the claims.

[506] As repeatedly noted, Pharmascience interprets the claims of the ‘437 Patent more broadly

than the Court’s construction, but submits that regardless, the claims are obvious.

[507] Pharmascience argues that for single attack patients who have been diagnosed pursuant to

the McDonald criteria with MS, there are no differences between the state of the art and the

subject matter of the claims. As Pharmascience notes, Copaxone was being used to treat RRMS

patients well before November 2007. Pharmascience also points to Pinchasi 2007, which

disclosed the use of 40 mg glatiramer acetate for RRMS. If Pharmascience’s broader

interpretation of the claims had prevailed, the validity attack would succeed.

[508] Pharmascience also argues that if the claims are restricted to single attack patients who do

not meet the MS diagnosis based on the McDonald criteria (as the Court has construed the

claims), there are still no differences between the state of the art and the subject matter of the

claims. Pharmascience relies on the recommendations in Karussis 2006, other prior art, and the

common general knowledge, including the knowledge that the PreCISe trial of glatiramer acetate

for CIS patients was ongoing and expected to be successful. Pharmascience points to the

evidence of Teva’s witness, Dr. Day, in support of this expectation of success.

Page: 135

[509] Pharmascience submits that the following information was known and reflects that state

of the art as of November 2007:

 Over 80% of single-attack patients with MRI lesions go on to develop MS and that

single-attack patients with T2 lesions on MRI were considered to already have MS;

 Canadian and international guidelines noted the need to use DMTs early in the disease

course of RRMS;

 Karussis 2006 recommended that glatiramer acetate be used to treat single-attack patients

who satisfied the McDonald criteria for MS;

 The prevailing view of MS experts was that earlier treatment, at the time of the first

attack, was preferable;

 Four first-line DMTs were available for RRMS; three interferon products (Avonex,

Betaseron and Rebif) and glatiramer acetate (Copaxone);

 The interferon products (Avonex, Betaseron and Rebif) had been tested in Phase III

clinical trials (the CHAMPS, ETOMS and BENEFIT trials) and were demonstrated to be

effective in treating CIS patients;

Page: 136

 Karussis 2006 recommended that glatiramer acetate also be used to treat single-attack

patients who fell short of the McDonald criteria for a diagnosis of MS;

 It was known that the PreCISe trial – a phase III clinical trial assessing the effectiveness

of glatiramer acetate in treating CIS patients – was underway; and,

 Karussis 2006 reported that a clinical trial of glatiramer acetate in CIS patients was

underway and “should work”. Pharmascience suggests that this is a reference to the

PreCISe trial. Pharmascience also relies on Panitch 2007, a commentary reporting on the

BENEFIT trial of Betaseron, an interferon, where the author stated that the PreCISe trial

was “likely to show a comparable magnitude of clinical efficacy”.

[510] With respect to Teva’s argument that the ‘437 Patent disclosed results not expected and

not disclosed in any prior art, such as a 50% reduction in new T2-weighted lesions,

Pharmascience submits that even if this result was unexpected, the invention was still obvious.

Pharmascience submits that if it were obvious to try to use glatiramer acetate for single attack

patients, the “golden bonus” that this reduced lesions by 50% does not make it inventive

(Janssen Inc v Teva Canada Limited, 2015 FC 184 at para 100 [Janssen]).

[511] Pharmascience further argues that the claimed 50% reduction (in claim 33) was not an

unexpected result for the treatment of a single attack patient. Pharmascience relies on the results

of the use of glatiramer acetate in RRMS patients and the results of the ETOMS, CHAMPS and

Page: 137

BENEFIT trials regarding the use of interferons in CIS patients that showed significant

reductions in lesions.

[512] Pharmascience submits that the threshold of obviousness does not require the results of

clinical trials.

[513] Pharmascience argues that if there were any differences between the state of the art and

the subject matter of the claims, the gap could be bridged by the POSITA using their common

general knowledge and additional information found by way of a reasonably diligent search.

[514] Pharmascience submits that it was common general knowledge that interferons had been

demonstrated to be effective in treating CIS patients; Karussis 2006 recommended that

glatiramer acetate be considered and that it should be effective; and, the PreCISe trial was

underway and would not have been undertaken without an expectation of success.

[515] Pharmascience submits that the POSITA would be motivated to look for other treatments

and the only other treatment available at that time was glatiramer acetate for RRMS.

Pharmascience adds that even though treatment of CIS patients with glatiramer acetate was not

yet approved in 2007, some physicians prescribed it.

[516] Pharmascience submits that the evidence of Teva’s witness, Dr. Selchen, on obviousness

should be ignored for several reasons.

Page: 138

[517] Pharmascience first suggests that Dr. Selchen was misinstructed regarding the Sanofi test.

Pharmascience submits that Dr. Selchen erroneously opined on whether it was self evident that

what is being tried would succeed, which is a factor in the obvious to try test, not the test itself

(Hospira at para 90). Pharmascience also submits that Dr. Selchen erred by failing to consider

that any differences between the state of the art and the invention could be bridged, not only with

common knowledge, but with the results of information obtained by a reasonably diligent search.

[518] Second, Pharmascience characterizes Dr. Selchen as a sceptic who did not demonstrate a

mind willing to understand. Pharmascience points to Biogen at para 170, where the Court noted

“the prior art should be approached by a motivated POSITA with a mind willing to understand,

not one myopically focused on seeking out failure.”

[519] Third, Pharmascience suggests that Dr. Selchen’s evidence about off-label drugs was

inconsistent. Pharmascience points to Dr. Selchen’s acknowledgment that an article he

co-authored referred to the treatment of children with glatiramer acetate, which would be

off-label. Pharmascience suggests that if children could be treated off label, then there should

have been no reason not to treat CIS patients off-label with glatiramer acetate.

[520] Pharmascience also argues that the Court should draw an adverse inference from Teva’s

failure to provide any evidence from the inventors of the ‘437 Patent, who are still alive and

could have been contacted. Pharmascience submits that the evidence proffered by Teva from Dr.

Kreitman does not address the work involved in the invention. Pharmascience submits that the

Court should infer that Teva conducted the PreCISe trial only to confirm what was already

Page: 139

known and obvious – that glatiramer acetate would work better if administered earlier to CIS

patients.

C.

Teva’s Submissions

[521] Teva notes that obviousness is a difficult test to meet and submits that Pharmascience has

not established that the POSITA would have come directly and without difficulty to the subject

matter of the claims (citing Beloit v Valmet Oy (1986), 8 CPR (3d) 289 (FCA) at para 294).

[522] Teva submits that Pharmascience relies on hindsight analysis. What may appear to be

obvious today based on results later observed or demonstrated, such as in the PreCISe trial, is not

the issue, rather whether it was obvious in 2007.

[523] Teva does not fully agree with Pharmascience’s description of the state of the art or the

common general knowledge. Teva submits that, in November 2007, the early treatment of CIS

patients was not part of the common general knowledge. There remained a debate on whether

early treatment with any DMTs should be pursued. Teva notes that Dr. Green stated that there

was an “emerging consensus” for early treatment in 2007 but in the U.K. litigation, he

acknowledged that there were two schools of thought. Teva notes that Dr. Green failed to

mention that some experts in the field had reservations about treating patients that had not been

diagnosed with MS.

Page: 140

[524] Teva acknowledges that it was generally known that the PreCISe trial was underway.

However, Teva again notes that, as of November 2007, glatiramer acetate was not a viable

treatment option for CIS; there was no evidence of any type (i.e., no clinical studies with

reported class I, II, III or IV evidence) that glatiramer acetate would be therapeutically effective

for treatment of CIS. In addition, there was not even any speculation that it would be effective to

reduce progression of MRI-monitored disease activity, reduce progression of symptoms of MS

prior to the development of CDMS, reduce the frequency of relapse, or reduce new T2-weighted

lesions by at least 50%.

[525] Teva acknowledges that, as of November 2007, interferon therapies were known and

were approved for treating CIS patients but submits that interferons are different compounds.

[526] Teva submits that Karussis 2006 was not common general knowledge. Teva also cautions

against reliance on more obscure articles, which were not identified in the prior art, and on stray

references in footnotes from co-authored papers that were not directly referred to by the expert.

[527] Teva submits that Dr. Green relied on passages of Karussis 2006 without considering its

whole context, in particular that Karussis 2006 accepted that the recommendation for early

treatment of CIS patients was not evidence based. Teva submits that neither Karussis 2006 nor

Panitch 2007, relied on by Dr. Green, refer to any evidence that glatiramer acetate would be

effective for CIS patients.

Page: 141

[528] Teva acknowledges that Kappos 2006, referred to by Dr. Green and Dr. Selchen,

disclosed that earlier treatment is better than later treatment as the disease progresses. Teva

notes, however, that this disclosure is based on treatment with Betaseron and not with glatiramer

acetate. Teva submits that no inferences about glatiramer acetate can be drawn from interferons.

[529] Teva submits that there were substantial differences between the state of the art and the

subject matter of the claims.

[530] Teva argues that bridging the differences between the state of the art, which did not

support the use of glatiramer acetate for CIS patients, and the subject matter of the claims

required inventive ingenuity. Inventiveness was required because there was a debate about

whether to even treat CIS before a confirmed MS diagnosis; other proven and approved therapies

for CIS (e.g., interferons) were available and would have been the “go to” if treatment were

pursued; and, there was no evidence of the efficacy of glatiramer acetate to treat CIS.

[531] Teva submits that the invention was not obvious to try, noting that the “mere possibility

that something might turn up is not enough” (Sanofi at para 66).

[532] According to Teva, viewed without knowledge of the invention as disclosed and claimed

in the ‘437 Patent, the POSITA would not have expected the outcomes claimed, in particular,

that treating CIS patients with glatiramer acetate would lead to a 50% reduction in new T2

lesions, noting that this result was greater than any trial results of previous CIS therapies. Teva

adds that it was not self-evident that glatiramer acetate would be effective in treating CIS, or that

Page: 142

it would achieve this 50% reduction in new T2 lesions. Testing was required and had not been

completed. In addition, the POSITA would not expect the therapeutic benefits of the PreCISe

trial simply because the PreCISe trial was underway.

[533] Teva disputes Pharmascience’s characterization of Dr. Day’s evidence, noting that

Dr. Day did not say that it was more likely than not that a Phase III clinical trial would succeed.

Rather, Dr. Day stated that this would depend on the work done before Phase III. Teva notes that

there were no predecessor Phase II studies, pilot studies or even case reports for glatiramer

acetate for CIS patients.

[534] Teva also disputes that Dr. Selchen was not properly instructed with respect to the test for

obviousness, noting that he was guided by the Sanofi test. Teva submits that the excerpts of

Dr. Selchen’s testimony that Pharmascience relies on were Dr. Selchen’s comments in response

to Dr. Green, not Dr. Selchen’s full assessment of the obvious to try test.

[535] Teva argues that the POSITA would not have been motivated to use unapproved

therapies for CIS adding that off label use would not be possible.

[536] With respect to Pharmascience’s submissions on the “non-invention” story, Teva points

to its evidence regarding the trial protocols and the extensive planning and investment that are

required and to Dr. Kreitman’s evidence regarding the PreCISe trial in particular.

Page: 143

[537] Teva argues that it invested resources, expertise and ingenuity to bring about the

invention, noting that the clinical trial was a large Phase III study. Without the results of the

PreCISe trial, the POSITA would not be aware of the benefits of glatiramer acetate for CIS

patients.

D.

What do the Experts Say?

(1)

Dr. Green

[538] Dr. Green stated that there was no difference between the state of the art as of November

2007 (i.e., the starting point) and the subject matter of the claims of the ‘437 Patent (i.e., the end

point). He explained that the state of the art had already reached the point that glatiramer acetate

was being used to treat CIS patients in large clinical studies and that the “consensus view” was

that treating CIS patients with glatiramer acetate was a reasonable approach, glatiramer acetate

should work to treat CIS patients; and the PreCISe trial was likely to show that treatment at the

time of the initial CIS would have enhanced efficacy compared to later treatment of RRMS

(again relying on Karussis 2006).

[539] Dr. Green noted that the POSITA was well aware of the concept of CIS. In addition, the

POSITA knew that the interferons that had been effectively used to treat MS had been shown to

be effective in treating CIS patients. Dr. Green expressed the view that the POSITA would

understand that these drugs worked the same way in CIS patients as in MS patients, only they

were administered at an earlier stage. In Dr. Green’s view, this knowledge, along with the

Page: 144

knowledge of the prior art that showed the effectiveness of glatiramer acetate for RRMS, and

that the PreCISe trial was already in progress, would lead to the view that glatiramer acetate

would also be expected to work for CIS patients.

[540] Dr. Green noted that Phase III clinical trials are designed to provide clinically and

statistically significant evidence of efficacy and safety to regulatory authorities to obtain

marketing approval. He added that these studies, such as the PreCISe trial, are not undertaken by

pharmaceutical manufacturers without a confident expectation of success.

[541] Dr. Green stated that this would have been self-evident to the POSITA that this treatment

would be effective given the ongoing PreCISe trial, which was comparing the administration of

glatiramer acetate and a placebo to CIS patients. This knowledge would have been combined

with the conclusions from Karussis 2006 that glatiramer acetate should work and the other art

that supported early treatment of CIS patients.

[542] In Dr. Green’s view, the POSITA would have been familiar with the clinical study design

required to qualitatively and quantitatively assess and measure glatiramer acetate’s effect on

reducing the likelihood of progression to CDMS and/or delaying the progression to CDMS in

CIS patients.

[543] Dr. Green explained that the POSITA would have been motivated to find new therapies

for CIS for many reasons, including because the approved products were all interferons. If a

patient could not tolerate an interferon, an alternative therapy would be desirable. Dr. Green

Page: 145

explained that the natural choice would be the safe and well tolerated therapies that were used to

treat RRMS in the approved doses of 20 mg or 40 mg.

[544] Administering glatiramer acetate to CIS patients and confirming its efficacy would be a

matter of simply prescribing glatiramer acetate, which was an existing, approved medication

(Copaxone), to CIS patients and monitoring their progression. Doing so would not have required

any significant effort beyond the normal, routine work of a clinician.

[545] As noted above with respect to anticipation, on cross-examination, Dr. Green

acknowledged that Karussis 2006 referred to the available DMTs, not specifically glatiramer

acetate, that the clinical trials were underway but not completed, and that there was no data

regarding the effectiveness of glatiramer acetate for CIS, only for RRMS.

[546] With respect to Dr. Green’s view that in November 2007 there was an “emerging

consensus” regarding early treatment, on cross-examination, Dr. Green agreed that a subset of

experts questioned this approach.

[547] Counsel for Teva noted that in the U.K. litigation, Dr. Green referred to the two schools

of thought, not an emerging consensus, as he now states. Dr. Green explained that his statement

regarding the consensus view remains true and the debate was about who warranted early

treatment. Dr. Green added that early treatment was being recommended by the medical advisory

board of the National MS Society of the U.S. and others. He reiterated his opinion that “[i]t was

Page: 146

recognized that the benefits of early treatment generally would outweigh the costs and side

effects in the aggregate for patients who had a CIS”.

[548] Dr. Green acknowledged that the studies he relied on regarding glatiramer acetate were

with respect to MS or RRMS patients, not CIS patients. He noted that Comi 2001 studied RRMS

patients and reported a 31% reduction in new T2 lesions (not a 50% reduction as claimed in

claim 33 of the ‘437 Patent).

[549] Counsel for Teva sought to have Dr. Green acknowledge that no data existed in

November 2007 to show that any drug reduced new T2 lesions by at least 50%. Counsel pointed

Dr. Green to his own publication (2006) which reported that 20 mg glatiramer acetate decreased

the rate of relapses and new MRI lesions by approximately 30%. Dr. Green agreed that this was

consistent with the Comi 2001 study.

[550] With respect to the PreCISe trial, in progress in 2007, Dr. Green noted that it was well

known and well publicized by Teva and there was an “extraordinarily high likelihood that

[glatiramer acetate] was going to work”. He added that the “field” was anticipating a result that

would show efficacy similar to the therapies that existed to that date.

[551] On cross-examination, Dr. Green acknowledged that whether a treatment is effective is

not known on a patient-by-patient basis; rather that such knowledge is based on clinical trials in

populations of patients and from clinical experience.

(2)

Dr. Selchen

Page: 147

[552] In Dr. Selchen’s view, there were differences between the state of the art in 2007 and the

claims of the ‘437 Patent. He noted that while the claims of the ‘437 Patent are based on the

results of the PreCISe trial, which provided evidence that glatiramer acetate is effective to treat

CIS patients, the state of the art in 2007 did not include evidence that glatiramer acetate had been

used to treat CIS patients or that it was effective, even in uncontrolled studies or patient case

reports.

[553] Dr. Selchen agreed that the POSITA would understand that the Canadian and

international guidelines noted the need to start treatment with interferons or glatiramer acetate

early in the course of the disease for RRMS to treat “disease progression”, i.e., including the

reduction in frequency and relapse of MRI lesions. Dr. Selchen noted, however, that there was

some controversy about what “early” meant. As noted above with respect to anticipation,

Dr. Selchen noted the two schools of thought regarding early treatment.

[554] Dr. Selchen strongly disagreed that there was any consensus that treatment with

glatiramer acetate would show enhanced efficacy for CIS patients compared to RRMS. He noted

that Dr. Green’s reference to a “consensus view” was likely a reference to Karussis 2006; a

single paper that was not evidence based.

[555] Dr. Selchen agreed, as noted with respect to the allegations of anticipation, that it would

have been reasonable to consider glatiramer acetate as an option for CIS, but there were other

offsetting considerations, including the availability of approved alternative DMTs (i.e.,

Page: 148

interferons), the inability to prescribe glatiramer acetate due to the lack of regulatory approval

and reimbursement and the lack of any data on efficacy.

[556] Dr. Selchen agreed that Rebif, an interferon, which was approved for RRMS on a three

times per week dosage regimen, was shown to have delayed the onset of CDMS in the ETOMS

study. Dr. Selchen also agreed that the once-a-week Rebif drug had been shown to significantly

reduced disease activity in CIS patients, although it had no effect on RRMS.

[557] Dr. Selchen did not agree that Comi 2006 made any conclusions about early treatment for

CIS, only for RRMS. Dr. Selchen did not accept the proposition that Comi 2006 concluded that

there would be a greater benefit for treatment for CIS patients than RRMS patients.

[558] Dr. Selchen acknowledged that Kappos 2006, that reported on the BENEFIT study (of

Betaseron), concluded that treatment earlier in the disease is more effective than later. In

Dr. Selchen’s opinion, this was a general hypothesis based on only a trend in the data.

Dr. Selchen stated that he was “not suggesting that there is no merit in the argument that early

treatment is better than later treatment. In 2020 we know this is true”. However, he explained

that observing a trend is not evidence.

[559] Dr. Selchen also acknowledged that Panitch 2007 opined that the results of the PreCISe

trial were likely to be similar to the results of the BENEFIT trial, but noted that Panitch also

recommended waiting for the McDonald criteria to be established (i.e., a diagnosis of MS)

before commencing treatment.

Page: 149

[560] Dr. Selchen also disagreed with Dr. Green that it would have been self-evident to the

POSITA to look to glatiramer acetate to treat CIS because a clinical trial was underway.

[561] Dr. Selchen noted that predicting the outcome of a clinical study in progress is difficult.

He opined that the POSITA would not have had a high degree of confidence that glatiramer

acetate would be useful to treat CIS, nor confidence that it would be more effective than existing

therapies (the interferons) or more effective than glatiramer acetate in RRMS patients.

[562] Dr. Selchen explained that arriving at the claimed subject matter required a clinical trial –

which is not something that a POSITA could do. Dr. Selchen stated that the design and

successful conduct of the PreCISe trial (or a similar trial) would have required both expertise and

ingenuity that went beyond routine work and the capabilities of the POSITA.

[563] Dr. Selchen stated that, although a clinician could have considered glatiramer acetate for

their CIS patients, they would not have been motivated to do so, because there was no evidence

of any efficacy; other proven and approved therapies were available, which would have been

substantially reimbursed by most drug plans; there was debate within the field regarding whether

to treat CIS before a confirmed MS diagnosis; and, the success of the ongoing study was

uncertain. As a result, it would have been prudent to wait for the results and prescribe based on

scientific evidence.

Page: 150

E.

The Claims of the ‘437 Patent are Obvious

[564] As found above, the claims of the ‘437 Patent address a patient who has had a single

clinical attack, i.e., a CIS patient – not a patient who has been diagnosed with MS pursuant to the

McDonald criteria.

[565] The Sanofi test guides the analysis of whether the claims of the ‘437 Patent are obvious.

[566] As noted in Tearlab at para 73, it is not contradictory to find that a prior art reference,

such as Karussis 2006, when considered alone, does not anticipate, but when such a reference is

considered in combination with other references, it can make a claim obvious.

[567] The Court of Appeal noted, at para 81 that “the test [for obviousness] is rather whether a

POSITA can bridge the gap between the state of the art at the relevant time and the claim as

construed, without inventive ingenuity”. The Court added that, “for obviousness it is the

cumulative effect of the prior art that must be considered to determine whether the skilled but

unimaginative technician would have come to the solution taught by the patent directly and

without difficulty”.

[568] The POSITA is described above and, more generally, is a practicing neurologist with

knowledge of MS and experience treating MS patients.

Page: 151

[569] The inventive concept is the subject matter of the claims. The invention generally claims

the use of glatiramer acetate for use in delaying the onset of CDMS in CIS patents at risk of

developing CDMS and before its onset.

(1)

The State of the Art

[570] In some respsects, Pharmascience’s description overstates the state of the art. However,

Pharmascience’s overall characterization of the state of the art is supported by the evidence.

[571] There is no dispute that approximately 80% of CIS patients with lesions go on to develop

MS. Dr. Selchen initially stated that 30-70% do not, but ultimately agreed with the statement that

80% do develop MS, as the ‘437 Patent also states.

[572] While it is an exaggeration to state that there was a strong consensus that early treatment

of CIS patients should be pursued, the evidence supports that this was the prevailing view as of

November 2007. As Dr. Green indicated, while a subset of experts did not share this view, the

National MS Society in the U.S. recommended early treatment. Dr. Green’s opinion was that it

was recognized that the benefits of early treatment would outweigh the costs and side effects “in

the aggregate” for CIS patients.

[573] Although Dr. Selchen did not agree that this was the prevailing view, he did agree that

the statement in Karussis 2006 – that early treatment warranted consideration – was not

Page: 152

controversial. As noted above, while Karussis is not common general knowledge, the authors

referred to several studies that were prior art and/or common general knowledge.

[574] The preponderance of evidence supports the view that the state of the art recognized the

benefits of early treatment of CIS patients. In addition, the prior art that reports extensively on

the CHAMPS, ETOMS and BENEFIT Phase III clinical trials of the interferon DMTs all noted

positive results and recommended early treatment of CIS patients.

[575] The prior art notes the results of the use of DMTs for RRMS and the results of the use of

interferons for CIS. The reports regarding the studies of the interferons appear to make more

general statements about the benefits of early treatment. Clearly, the state of the art, even before

2007, was that early treatment was being considered and, in some cases, pursued for CIS

patients.

[576] For example, Filippi 1994 reported on a 5-year study that assessed the likelihood of a CIS

patient developing MS within 5 years. It demonstrated that, for patients who had a clinical

episode suggestive of a demyelinating attack with brain lesions (i.e., patients with a CIS

suggestive of MS), progression to MS occurred in 65% of those patients within 5 years. As noted

by the experts, the estimate in 2007 was that 80% of CIS patients developed MS, although the

length of time for this to occur was not specified.

Page: 153

[577] Comi 2001 noted that the ETOMS Phase III clinical trial reported that the use of Rebif

reduced the proportion of CIS patients who developed CDMS and reduced the frequency of

relapses.

[578] Comi 2006 supported early treatment of MS. Among other things, Comi 2006 discussed

the CHAMPS and ETOMS trial results and concluded that “[the available] data [with respect to

interferons] suggest that early treatment of MS patients with immunomodulatory drugs is

advisable.”

[579] Kappos 2006 reported the results of the BENEFIT trial that studied the use of Betaseron

every other day in CIS patients. Among other things, the results of the trial showed a 50% risk

reduction for progression to CDMS for CIS patients treated with Betaseron compared to placebo.

It also showed a 33% reduction in the mean number of T2 lesions. As noted above, Dr. Selchen

regarded Kappos’ findings as based only on a trend in the data. However, other reports on the

BENEFIT trial supported the conclusion that it showed the advantages of early treatment.

[580] Frohman 2006 also noted the results of the ETOMS and CHAMPS trials and set out

arguments in favour of early treatment of MS, including for CIS patients.

[581] Thrower 2007 reviewed the CHAMPS, CHAMPIONS (an extension of CHAMPS),

ETOMS, and BENEFIT clinical trials, all of which investigated the use of DMTs in treating

high-risk CIS patients. The author concluded that early treatment should be considered for CIS

patients who are at high risk for progression to CDMS.

Page: 154

[582] Panitch 2007 is a short commentary on the BENEFIT trial. Dr. Panitch commented that

the BENEFIT trial represented the third trial (the others being CHAMPS and ETOMS) to show

“essentially the same outcome” (i.e., effective treatment) of CIS patients. Panitch noted that “a

similar large study of glatiramer acetate versus placebo, given the acronym PRECISE, is

currently in progress and is likely to show a comparable magnitude of clinical efficacy.”

[583] Dr. Selchen expressed the view that Panitch’s comment about a “comparable magnitude

of clinical efficiency” related to the previous sentence where Panitch noted that an additional

feature of the BENEFIT trial showed a “clinically unimpressive result”, and that Panitch was

suggesting that PreCISe would also show a clinically unimpressive result. However,

Dr. Selchen’s interpretation is not borne out when the full paragraph is read. Panitch was

referring to the positive results of the BENEFIT study overall, noting that its primary outcome

was similar to that of CHAMPS and ETOMS.

[584] As noted above, Pharmascience and Dr. Green overstated Karussis 2006. Karussis did not

recommend glatiramer acetate specifically, nor did it point to any evidence of its efficacy.

However, Karussis 2006 did draw on the prior art to suggest that early treatment of CIS patients

warranted consideration.

[585] Karussis 2006 stated the approved DMTs should work based on studies for RRMS.

Karussis did not state that the PreCISe trial should work. The reference in Karussis 2006 to a

clinical trial in progress was a reference to CHAMPS. Although Dr. Selchen agreed on cross-

Page: 155

examination that “presumably” Karussis was referring to the PreCISe trial, this presumption is

not accurate as Dr. Selchen was not directed to the footnote for that statement.

[586] With respect to the reliance on the studies done on the treatment of CIS patients with

interferons, both Dr. Selchen and Dr. Prat stated that no inferences could be drawn from the

interferons with respect to glatiramer acetate due to their different mechanism of action. These

different mechanisms were not explained. However, all the experts agreed that interferons were

different compounds from glatiramer acetate.

[587] Dr. Green’s opinion was not based on an assumption that because interferons worked for

CIS patients, glatiramer acetate would also work. Dr. Green acknowledged that interferons were

different. Rather, his opinion was that if interferons worked for RRMS patients and also showed

positive results for CIS patients, a similar outcome would be expected for glatiramer acetate,

which had also been demonstrated to be effective for RRMS patients. The point is that the

glatiramer acetate treatment should begin earlier, not that it should work in the same way as the

interferons.

(2)

The Differences between the State of the Art and the Subject Matter of the Claims

[588] The state of the art in November 2007 was that DMTs (interferons and glatiramer acetate)

worked for RRMS; interferons had been demonstrated to be effective for CIS patients; there

remained a debate about early treatment, but the prevailing view was that early treatment was

Page: 156

preferable; and, there was no evidence that glatiramer acetate would be effective for CIS

patients, although it was known that the PreCISe trial was in progress.

[589] As noted, the invention generally claims the use of glatiramer acetate for use in delaying

the onset of CDMS in CIS patents at risk of developing CDMS and sets out more specific

outcomes and how it is administered (by injection, daily, 20 mg or 40 mg).

[590] The difference between the state of the art and the subject matter of the claims is that

state of the art did not include clinical studies to demonstrate that glatiramer acetate administered

to CIS patients was effective to delay the onset of CDMS (or MS) or to achieve the other

therapeutic benefits and specific outcomes.

(a)

Obvious to try

[591] The issue is whether it would have been obvious to the POSITA to administer glatiramer

acetate to CIS patients to delay the onset of CDMS (or MS). Would the unimaginative but skilled

POSITA come to the solution taught by the patent directly and without difficulty?

[592] In my view, the evidence shows that on a balance of probabilities it was obvious to try to

obtain the invention. It was more or less self-evident to do so. It would not have required much,

if any, imagination for the POSITA to look to glatiramer acetate for the treatment of CIS patients

to delay the onset of MS and reduce the frequency of relapses, among other benefits. It was more

than a mere possibility that this would be an effective treatment, given that approximately 80%

Page: 157

of CIS patients go on to develop MS and that glatiramer acetate was proven effective for RRMS.

It was more than simply “worth a try”.

[593] Dr. Selchen’s opinion that the invention was not self-evident appears to conflate the

obvious to try test with the factor or consideration that informs the test, i.e., whether it was

self-evident that it would work, in the sense of being effective for CIS patients to delay the onset

of MS and achieve the other claimed benefits. In any event, it is the Court that must determine

whether the invention was obvious to try. As with many legal tests guided by factors, it can be

somewhat circuitous to ask whether it is obvious to try to obtain the invention then to also

consider whether it was obvious that the invention would work. Regardless, the relevant factors

and the evidence supports that it was obvious to try.

[594] Teva’s submission – that the therapeutic benefits or outcomes of the ‘437 Patent were not

obvious or expected – does not diminish that the invention was obvious to try. In Janssen at para

100, the Court explained, that “if a patentee obtains a workable formulation, the later discovery

of one of its inherent characteristics does not add anything inventive to what had already been

discovered: see Alcon Canada Inc. v Apotex Inc., 2012 FC 410 at para 45, [2012] FCJ No 1707

(QL).” In the present circumstances, once the POSITA pursued the use of glatiramer acetate for

CIS patients, the claimed benefits would follow.

Page: 158

(b)

The relevant factors

[595] With respect to the relevant factors, it was not self-evident that treating CIS patients with

glatiramer acetate would work, in the sense of achieving reductions in relapses, reducing MRI

lesions and, more generally, delaying the onset of MS. However, as noted above, the results of

glatiramer acetate for RRMS patients had been demonstrated, early treatment was a prevailing or

trending view, there appeared to be no strong evidence suggesting that early treatment would be

harmful, and to the extent that the POSITA would be influenced by the results of the clinical

trials of the interferons, the administration of glatiramer acetate would be an option. The only

other solution to the treatment of CIS was, as noted, the administration of the approved

interferons. There is no evidence that other therapies – apart from glatiramer acetate – were

alternatives. Nor is there evidence of other approaches to treat CIS patients.

[596] It would not have required significant effort to achieve the invention because glatiramer

acetate (Copaxone) was well known, approved for the treatment of RRMS, and available.

Although the evidence is mixed regarding off-label use of drugs, it would be theoretically

possible for the POSITA to administer glatiramer acetate in the 20 mg dose and monitor the

patient regularly. While a clinical trial would not be routine for the POSITA, as it requires

planning, special expertise, funding and time, a clinical trial would not be otherwise arduous,

Copaxone was available and there was no need for further experiments with respect to its

formulation, administration or dosing regimen.

Page: 159

[597] There was also a motive to pursue glatiramer acetate for CIS patients. As noted by

Dr. Green, if the CIS patient cannot tolerate an interferon or experiences adverse side effects, the

only other option would be glatiramer acetate, which was a well-known DMT. More generally,

the state of the art supports an overall motive to pursue early treatment of CIS patients.

[598] With respect to the course of conduct of the inventors, there is no first hand evidence.

However, an adverse inference, as suggested by Pharmascience, that Teva was merely

confirming what was known, is not warranted. Dr. Kreitman described the phase III clinical trial

(the PreCISe trial) as a placebo-controlled, randomized, double-blind, multicenter trial with an

additional 2 year open-label phase during which all participants would receive Copaxone 20 mg

daily. There were 481 patients in the study, which occurred in 80 sites in 16 countries.

Dr. Kreitman stated that the study demonstrated that 20 mg daily glatiramer acetate was

efficacious in delaying the onset of CDMS in CIS patients.

[599] Teva was not simply confirming what was known, because it was not a certainty in 2007

that glatiramer acetate would be effective for CIS patients. Regardless, this factor is not

sufficient to overcome the other factors that support the conclusion that it was obvious to try.

[600] In conclusion, the ‘437 Patent is not anticipated by Karussis 2006, but is obvious.

XXI.

The ‘802 Patent

[601] The description of the ‘802 Patent is set out above in Part XI.

Page: 160

A.

The POSITA for the ‘802 Patent

[602] Teva submits that the experts agreed that the POSITA includes a neurologist with

experience understanding the results of clinical studies. Teva disputes Pharmascience’s

submission that the POSITA includes a member of a drug development team.

[603] Dr. Green described the POSITA in the same way as he did with respect to the ‘437

Patent.

[604] Dr. Prat described the POSITA as including a doctor who treats MS, likely a neurologist

with a specialty in MS. Dr. Prat generally agreed with Dr. Green regarding the attributes of the

POSITA. However, Dr. Prat did not share Dr. Green’s view that the POSITA would necessarily

have experience with the design of studies required for drug development. He noted that the

POSITA may have experience with participation in clinical studies focusing on MS but not in

their design, as that is typically the expertise of another type of specialist.

[605] Dr. Vosoughi described the POSITA as including a doctor specializing in neurology with

several years of experience treating patients with MS.

[606] In my view, the POSITA for the ‘802 Patent is the same as for the ‘437 Patent; a

practicing neurologist with several years of experience evaluating, diagnosing and treating

patients with MS. This POSITA would be familiar with therapeutic agents available for the

treatment of MS (i.e., DMTs), their dosing schedules and side effects or adverse events that

Page: 161

occur with the various DMTs. The POSITA would have some knowledge of and familiarity with

clinical studies and their interpretation, but would not be a member of a drug development team.

B.

The Construction of the Claims of the ‘802 Patent

[607] There is no dispute regarding the construction of the claims. All the experts agree that the

claims address the use of 40 mg of glatiramer acetate, administered by subcutaneous injection

three times per week (and with a day in between injections), for the treatment of patients with

RRMS.

[608] Claims 36 to 39, 48 and 53 claim treatment effects such as reducing the frequency of

relapses, the number of enhancing T1 lesions, the mean number of new T2 lesions and the level

of disability measured in different ways.

[609] Claims 47 and 54 to 57 specify tolerability effects compared to 20 mg daily, such as

reducing the frequency of immediate post injection reactions or of injection site reactions (claims

47, 54 and 55) and specific injection site reactions ( e.g., pain or welt) (claim 57).

XXII.

Prior Art and Common General Knowledge related to the ‘802 Patent

[610] The common general knowledge as of August 2009 builds on that set out above with

respect to the ‘437 Patent. There is no dispute that as of August 2009, the POSITA was aware of

the characteristics of MS, the types of MS, including RRMS, the diagnostic criteria, and the

Page: 162

DMTs (interferons and glatiramer acetate) available for MS. In addition, by August 2009,

Copaxone 20 mg administered by injection daily for CIS was available.

[611] However, not all the prior art relied on is part of the common general knowledge, as

noted above (Valeant at para 48, citing Eli Lilly and General Tire) and explained below.

[612] The parties disagree on the state of the art. Pharmascience cites several studies and

abstracts that it argues provide the mosaic of art to support that the claimed subject matter of the

‘802 Patent was obvious. Teva argues that much of this prior art was not well known, included

brief abstracts that reported on pilot or Phase II studies, would not turn up in a search (and that

some did not in fact turn up in Dr. Green’s own search), and/or that these references were not

part of the common general knowledge. Teva submits that Pharmascience and its expert, Dr.

Green, have cobbled together abstracts, lesser known articles, and patent applications in

hindsight to create a mosaic of art to argue that the POSITA would arrive at the invention with

ease. Teva submits that there is no justification for a POSITA to piece together this mosaic.

[613] The expert’s opinions on how the prior art cited would or would not guide the POSITA is

addressed in the discussion on obviousness.

[614] The key prior art that is relied on by Pharmascience is set out below.

A.

Prior art on glatiramer acetate 20 mg daily vs. every-other-day (alternate-day)

Page: 163

[615] Flechter et al, “Copolymer 1 (Glatiramer acetate) in relapsing forms of multiple sclerosis:

Open multicenter study of alternate-day administration”, 2002 Clin Neuropharm 25(1): 11-15

[Flechter 2002] is an open-label pilot study that compared the efficacy of glatiramer acetate

20 mg administered daily and on alternate days (i.e., every-other-day). In the study, 68 patients

with relapsing forms of MS received glatiramer acetate 20 mg every other day. The author then

compared the results of this study with the results of a previous study (i.e., Meiner 1997) that had

studied the efficacy of glatiramer acetate 20 mg administered daily. Based on the comparison,

the authors concluded that the results of this trial suggest that every-other-day treatment is “safe,

well-tolerated and probably as effective as daily [treatment] in reducing relapse rate and slowing

neurologic deterioration” in patients.

[616] Fletcher et al, “Comparison of glatiramer acetate (Copaxone®) and interferon β-1b

(Betaferon®) in multiple sclerosis patients: an open-label 2-year follow-up” 2002 J Neurological

Sci 197: 51-55, reported the results of a 2-year open-label follow-up study in the efficacy and

safety of glatiramer acetate 20 mg daily, glatiramer acetate 20 mg alternate-day, and Betaseron 8

MIU alternate-day administered to patients with relapsing forms of MS. Each treatment arm had

no more than 20 patients. The authors reported that the three treatment options showed equal

efficacy for the control of MS exacerbations and similar adverse event profiles.

[617] As noted above, Rebif is an interferon that was first approved in 2002 by the U.S. Food

and Drug Administration [FDA]. Rebif is indicated for treatment of patients with RRMS.

According to the 2005 product label and 2006 product monograph of Rebif, this interferon is

Page: 164

administered subcutaneously three times a week as a 22 µg or 44 µg dose. The doses are

administered at least 48 hours apart.

[618] Khan et al, “Randomized, prospective, rater-blinded, four-year, pilot study to compare

the effect of daily versus every-other-day glatiramer acetate subcutaneous injections in

relapsing-remitting multiple sclerosis”, 2008 Multiple Sclerosis 14:S296 (P902) [Khan 2008]

and Caon et al, “Randomized, prospective, rater-blinded, four year pilot study to compare the

effect of daily versus every-other-day glatiramer acetate 20 mg subcutaneous injections in

RRMS”, 2009 Neurol 72(11)(Suppl 3): A317 [Caon 2009] are both abstracts (less than a page

each) from a meeting/conference that described the results of the same 4-year, randomized,

prospective, rater-blinded study (i.e., where the assessors are not told which patients are in which

group) of patients who were treated with 20 mg glatiramer acetate administered daily or every-

other-day.

[619] Thirty RRMS patients were randomized to each treatment group and followed for two

years. Thereafter, patients in each group were given the option to continue or switch to the other

group and then they were followed for another two years. The authors reported that the study

revealed no difference in the relapse rate, disease progression, and change in T2-weighted lesion

volume or Gd enhancing lesions between the two groups after two years of study. At the

two-year mark, all patients in the daily group opted to switch to the every-other-day dosing

regimen. After four years, the authors reported no difference between the two treatment groups.

The authors concluded, “[t]his pilot study suggests that GA 20 mg [subcutaneous] administered

[daily] or [every-other-day] may be equally effective in RRMS.”

Page: 165

B.

Prior art on glatiramer acetate 20 mg vs. 40 mg administered daily

[620] Rovaris et al, “Results of a randomized, double-blind, parallel-group study assessing

safety and efficacy of 40mg vs 20mg of glatiramer acetate on MRI-measured disease activity in

relapsing-remitting multiple sclerosis”, 2006 J Neurology 253 (Suppl 2): P570 is an abstract (less

than a page) that described the results of a 9-month randomized, double-blind, parallel-group

study assessing the safety and efficacy of 40 mg vs. 20 mg of glatiramer acetate subcutaneous

administered daily. The authors concluded, “[o]ver a nine-month period of observation, GA 40

mg is safe, well-tolerated and more effective than the currently approved 20 mg dose in reducing

MRI activity and relapse rate in patients with RRMS.”

[621] Cohen 2007, as mentioned above, reported on the results of Teva’s FORTE Phase II

study, which was a randomized, double-blind, dose comparison study of glatiramer acetate 40

mg vs. 20 mg in patients with RRMS. Ninety patients were randomly assigned to the 20 mg or

40 mg daily regimens. The authors state that the primary efficacy endpoint “showed a trend

favoring the 40-mg group”. The authors concluded that the 40 mg daily regimen “was safe and

well tolerated,” and that “[t]he overall efficacy results suggested that a 40-mg dose of [glatiramer

acetate] may be more effective than the currently approved 20-mg daily dose in reducing MRI

activity and clinical relapses.”

[622] Teva’s press release, entitled “Data Published in Neurology Showed That Higher Dose of

Copaxone® Increased Efficacy in Relapsing-Remitting Multiple Sclerosis (Rms)”, dated April

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17, 2007 publicized the results of the phase II trial, as published in Neurology, and confirmed the

initiation of the phase III trial.

[623] Comi et al, “Results from a phase III, one-year, randomized, double-blind, parallel-group,

dose-comparison study with glatiramer acetate in relapsing-remitting multiple sclerosis”, 2008

Multiple Sclerosis 79(14): S299-301 [Comi 2008 or FORTE Phase III] is an abstract that

reported on the results of the Phase III clinical trial, which was done to confirm the results of the

phase II study. The study evaluated “the safety, tolerability, and efficacy of GA 40 mg compared

to the 20 mg dose” administered daily in patients with RRMS. The study was a 1-year,

multi-national, multi-centre, randomized, double-blind, parallel-group study that involved 1,155

patients. The authors reported that both the 40 mg and 20 mg group “showed a reduction in the

mean number of gadolinium-enhancing and new T2 lesions over time with a trend for a faster

reduction in the first trimester in the 40 mg dose compared with 20 mg dose.” It further reported

that “[b]oth doses were well-tolerated with a safety profile similar to that observed in previous

studies of 20 mg GA.” The authors concluded that “[i]n RRMS patients, both GA 40 mg and the

currently approved 20 mg doses were safe and well-tolerated, and were equally effective in

reducing clinical relapses and MRI activity.”

[624] Teva’s press release, entitled “Teva Provides Update on FORTE Trial”, dated July 7,

2008 stated, “[t]he 40 mg dose did not demonstrate increased efficacy in reducing the relapse

rate; however, the higher dose maintained the favorable safety and tolerability profile of

COPAXONE® 20 mg.”

Page: 167

C.

Prior art on glatiramer acetate 40 mg every-other-day

[625] As noted above at Part XVI, Pinchasi 2007 is an international patent application that was

not approved. The patent application describes “a method of alleviating a symptom of a patient

suffering from a relapsing form of multiple sclerosis which comprises periodically administering

to the patient by subcutaneous injection a single dose of a pharmaceutical composition

comprising 40 mg of glatiramer acetate so as to thereby alleviate the symptom of the

patient. . . .” In one embodiment, periodic administration is daily. In another embodiment, the

periodic administration is every other day. The patent application, in example 1, discloses the

trial data from the FORTE Phase II study (i.e., Cohen 2007 which studied 40 mg vs. 20 mg

daily).

[626] Pharmascience appears to suggest that the ‘437 Patent is prior art to the ‘802 Patent.

However, the’ 437 Patent, as construed above, is addressed to CIS patients, not RRMS, and

teaches the use of 20 mg glatiramer acetate daily, with one claim of 40 mg. The ‘437 Patent does

not refer to any other dosing regimen except daily.

D.

Prior art on injection site reaction and immediate post injection reaction

[627] Edgar et al, “Lipoatrophy in patients with multiple sclerosis on glatiramer acetate”, 2004

Can J Neurol Sci 31: 58-63 [Edgar 2004], reported the results of a study that examined the

relationship between lipoatrophy and patient characteristics in 76 RRMS patients using

glatiramer acetate. Over six months, during regular clinic appointments, physicians assessed

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these patients’ injection site areas through visual inspection and manual palpation. The study

reported that 45% had evidence of lipoatrophy in at least one injection site area, which was much

higher than expected.

[628] Devonshire et al, “The Global Adherence Project – A multicentre observational study on

adherence to disease-modifying therapies in patients suffering from relapsing-remitting multiple

sclerosis”, 2006 Multiple Sclerosis 12:S1 (P316) [Devonshire 2006], is an abstract published in

Multiple Sclerosis Journal. The Global Adherence Project is the largest global, observational

study that has evaluated real-world adherence rates to approved DMTs for RRMS. This study

retrospectively surveyed over 2,600 patients from 22 countries who were on one of the DMTs for

at least six months. The study found that 25.3% of patients reported non-adherence and that the

non-adherence rate was significantly lower for Avonex (administered once weekly) than for

Rebif, Betaferon/Betaseron, and Copaxone (administered daily). The most common reason for

non-adherence was forgetting to administer the injection.

XXIII.

A.

Overview of the Experts’ Evidence on the ‘802 Patent

Pharmascience’s Expert, Dr. Green

[629] In Dr. Green’s opinion, the claims of the ‘802 Patent were obvious. Dr. Green stated that

there were no material differences between the state of the art in August 2009 and the subject

matter of the claims.

Page: 169

[630] Dr. Green’s opinion is that the state of the art in August 2009 demonstrated at least that:

reduced-frequency dosage regimens of DMT were known; a 40 mg daily-dose of glatiramer

acetate was at least as safe and efficacious as a 20 mg daily-dose; reduced frequency of

injections would reasonably be presumed to result in reduced injection site irritation and

reaction; and, that Teva, based on its Pinchasi patent application, believed that the periodic

administration of 40 mg glatiramer acetate, including on an every-other-day basis, would be

effective to treat MS.

[631] Dr. Green added that the only possible difference would be between an every-other-day

dosage regimen of 40 mg of glatiramer acetate (as taught in Pinchasi 2007) and the claimed three

times per week dosage regimen of 40 mg of glatiramer acetate (with at least one day between

each injection).

[632] Dr. Green opined that the difference could have been easily bridged by the POSITA

using their common general knowledge and other information, which could have been located by

making a reasonably diligent search and making deductions. Dr. Green added that the POSITA

would be motivated to reduce injection frequency to reduce injection site reactions and a three

times weekly regimen would also be more convenient.

B.

Teva’s Expert, Dr. Prat

Page: 170

[633] In Dr. Prat’s opinion, the claims of the ‘802 Patent were not obvious; there were

differences between the state of the art and the subject matter of the claims and it would have

required inventive ingenuity to obtain the invention.

[634] Dr. Prat stated that some of the prior art cited by Dr. Green would not be known by the

POSITA or it would not be given much weight and would not be part of the common general

knowledge.

[635] With respect to the state of the art in August 2009, Dr. Prat explained that reduced

frequency of administration of 40 mg glatiramer acetate was not known by the POSITA. Dr. Prat

stated that there was no disclosure in the prior art cited by Dr. Green that glatiramer acetate

should be used for treating RRMS and/or CIS at a dose of 40 mg three times a week with at least

a day between each injection. There was also no disclosure of the claimed efficacy of such a

regimen.

[636] Dr. Prat concluded that there was nothing in the prior art that would point the POSITA

towards using 40 mg of glatiramer acetate three-times-a-week given that 40 mg daily was shown

to be about as effective as 20 mg daily but that 40 mg daily resulted in increased adverse events

and increased patient discontinuation of the therapy. Dr. Prat emphasized that 20 mg glatiramer

acetate daily was known to be optimal and a daily dosing regimen was easier to follow.

[637] In Dr. Prat’s opinion, the POSITA would not see any reason to increase the dosage to

achieve similar efficacy but have increased adverse events.

Page: 171

C.

Teva’s Expert, Dr. Day

[638] Dr. Day provided his opinion as a statistician with expertise in clinical trial design and

interpretation, on how the POSITA would regard the prior art relied on by Pharmascience.

Dr. Day explained, among other things, the purpose of a well-designed clinical trial and the

importance of sample size, randomization, blinding and statistical significance. Dr. Day assessed

the prior art cited and noted the features that inform the assessment of the results or the report.

[639] Dr. Day noted that Pinchasi 2007 was a patent application. Dr. Day explained that the

example in the application would be of most relevance to the POSITA. The example disclosed

trial data from the study comparing 40 mg and 20 mg glatiramer acetate administered daily (i.e.,

Cohen 2007). Dr. Day noted that Cohen 2007 was a well-designed trial, but the conclusions were

overstated. Dr. Day stated that the POSITA would be sceptical of the results that showed a faster

onset of action for the 40 mg dose at the three-month mark as this was a secondary endpoint and

not statistically significant. Dr. Day also noted that Cohen 2007 engaged only 90 patients, and 12

dropped out. Dr. Day noted that the statistical analysis of efficacy did not account for the drop-

outs which would raise a concern about the reliability of the conclusions.

[640] Dr. Day opined that, taking the disclosure of all of the prior art documents together, the

POSITA would conclude that 40 mg and 20 mg daily regimens are of similar efficacy, but that

the 40 mg dose did not demonstrate increased efficacy in reducing the relapse rate, as noted in

Teva’s press releases and confirmed in Professor Comi’s report (Comi 2008) and presentation

slides about the FORTE Phase III trial. Dr. Day added that the POSITA would also note that

Page: 172

there is conflicting evidence regarding the safety or tolerability of the two dosing regimens and

that Professor Comi’s slide 14 indicated that almost twice as many patients in the 40 mg group

withdrew because of adverse events.

[641] Dr. Day also opined that the POSITA would conclude that in 2009 there were no

well-designed trials about the relative efficacy of glatiramer acetate 20 mg every other day and

20 mg daily. He noted that a large, randomized, double-blinded, controlled trial would be needed

to draw a meaningful conclusion about the relative efficacy, safety and tolerability of the two

regimens.

XXIV.

A.

Is the ‘802 Patent Invalid due to Obviousness?

Teva’s Submissions

[642] According to Teva, as of August 2009, the common general knowledge was that daily

administration of Copaxone 20 mg was known to treat RRMS and CIS, and that glatiramer

acetate had a poorly understood mechanism of action, but that it differed from the interferons.

The common general knowledge also included some of the results from reliable clinical studies.

[643] Teva submits that Dr. Green’s presentation of the common general knowledge was not

balanced and not consistent with the manner in which he addressed common general knowledge

before the U.K. Court (as discussed above). Teva submits that Dr. Green attributed almost every

Page: 173

document he cited to the common general knowledge. Dr. Green pointed to abstracts, pilot

studies, and short papers in lesser-known journals.

[644] Teva notes that Dr. Green attached a 149-page list of articles and abstracts from PubMed

searches. Dr. Green’s search revealed over thirteen hundred articles, yet Dr. Green did not

explain why he relied on specific pieces of prior art to advocate that the patent is obvious.

Moreover, some of the prior art he relied on did not come up in the search he conducted. Teva

submits that Dr. Green used a results based and hindsight approach to identify minor abstracts

and articles to support Pharmascience’s argument and ignored articles that did not. Teva submits

that, although a mosaic of art can be relied on, the mosaic must be of the prior art that the

POSITA would have been led to combine.

[645] For example, Teva submits that Pinchasi 2007, a patent application, would not be looked

for by a POSITA and would only be found in hindsight. Teva notes that Dr. Green did not

conduct a patent search himself. Teva adds that the 1996 U.S. Federal Drug Administration

Summary Basis of Approval [FDA SBOA] document would not be sought or found, noting that

Dr. Green was not even aware of this until years after 2009.

[646] With respect to patient adherence, Dr. Green cited only one abstract (Devonshire 2006) to

support his characterization of the common general knowledge. Dr. Green admitted that the

skilled person may not have read Devonshire by August 2009 and contained minimal

information.

Page: 174

[647] Teva submits that the common general knowledge was that interferons, with reduced

frequency administration, did not have better adherence than Copaxone. Teva submits that

Dr. Green’s report omitted the information in the other articles that did not support his view,

although he had located them in his own PubMed search.

[648] With respect to the state of the art, Teva submits that there was no prior art that disclosed

the use of 40 mg glatiramer acetate three times a week.

[649] Teva acknowledges that Flechter 2002, Khan 2008 (and Caon 2009, which referred to the

same study) suggested that 20 mg could be used every other day; however, these short abstracts

reporting on pilot studies would not have guided the POSITA. Teva adds that Dr. Green

acknowledged the he was not aware of Flechter 2002 in 2009, but only later in the context of this

litigation.

[650] Teva also notes that Dr. Green agreed that he had never advised a patient to use 20 mg

every other day.

[651] Teva submits that other authors’ references to these studies does not increase their value.

Nor does the evidence of Dr. Selchen and Dr. Morrow who acknowledged that they had

considered the results of other, unrelated open label studies. Teva notes that there is no evidence

that the open label studies referred to by Dr. Selchen or Morrow were as poorly designed as

Khan 2008/Caon 2009 or Flechter 2002, how they differed, or how their results were interpreted

in relation to their design.

Page: 175

[652] With respect to Pharmascience’s reliance on the FDA SBOA for Copaxone in 1996, Teva

notes that this document would not be found or read by the POSITA. Moreover, the SBOA did

not disclose or suggest any particular dose or schedule, let alone 40 mg three times a week and

the reviewer’s questioning was based on an incorrect understanding of the drug. Teva also notes

that Dr. Green conceded that he was not aware of the SBOA in 2009, rather he only learned of it

at some point between 2012 and 2016.

[653] Teva submits that Cohen 2007 reported on 40 mg glatiramer acetate in a Phase II trial.

However, the subsequent Phase III trial, reported in Comi 2008, was not considered to be

successful as it demonstrated that 40 mg daily did not have better efficacy than 20 mg daily and

caused increased adverse reactions from injection site reactions which were “statistically

significant compared to GA 20mg”.

[654] Teva submits that Pinchasi 2007 was a patent application that the POSITA would not

look for or be aware of. Teva notes that Pinchasi 2007 was focussed on daily administration and

there was only a bare suggestion to administer 40 mg every other day.

[655] Teva notes that, as of 2009, there were several interferon therapies for RRMS, each with

different dosing schedules. For, example, Rebif was administered three times a week. Teva

submits that the POSITA would not be guided to consider a three times per week dosing

schedule for glatiramer acetate based on the interferons. Teva again notes that the interferons

differed in their mechanism of action.

Page: 176

[656] Teva acknowledges that patient adherence to DMTs was an issue, as mentioned in the

‘802 Patent. Teva submits that the prior art demonstrated that the interferons did not have better

patient adherence than Copaxone. Rather studies found that Copaxone 20 mg daily had equal or

better adherence than the interferons.

[657] Teva submits that the studies did not demonstrate that reducing injection frequency

would improve adherence.

[658] Teva argues that there was no reliable art pointing to an every other day administration of

any dose of glatiramer acetate. More particularly, Teva submits that no art pointed to three times

a week regimen for glatiramer acetate (at any dosage), or suggested that it would have the

claimed attributes of the ‘802 Patent. Teva notes that Dr. Green admitted on cross-examination

that the prior art did not disclose 40 mg three times per week. Teva adds that there is no evidence

to support Dr. Green’s “bald statement” that 40 mg three times a week is therapeutically

equivalent to 40 mg every other day.

[659] Teva submits that there were differences between the state of the art and the subject

matter of the claims. Teva adds that these differences existed even if Dr. Green’s mosaic of art

were relied on.

[660] Teva further submits that the differences would not be obvious to the POSITA;

inventiveness was required.

Page: 177

[661] Teva submits that Pharmascience has not met its burden of demonstrating that relevant

prior art existed or that the POSITA in 2009, even if they located the prior art, would have

combined the prior art to reach the subject matter of the claims (Laboratoires Servier, Adir, Oril

Industries, Servier Canada Inc v Apotex Inc, 2008 FC 825 at para 254 [Servier]; Biovail

Corporation v Canada (Health), 2010 FC 46 at para 84; Camso Inc v Soucy International Inc,

2019 FC 255 at para 125).

[662] Teva submits that it is only in hindsight that that the POSITA would use 40 mg

glatiramer acetate three times per week. Teva points to Free World Trust v Électro Santé Inc,

2000 SCC 66 at para 25, where the Supreme Court noted that, “it is all too easy after an

invention has been disclosed to find its antecedents in bits and pieces of earlier learning. It takes

little ingenuity to assemble a dossier of prior art with the benefit of 20-20 hindsight.”

[663] Teva points out that some of the references Dr. Green cited were not part of his PubMed

searches, including Pinchasi 2007, Khan 2008, Caon 2009, Devonshire 2006, and the FDA

SBOA. Teva adds that Dr. Green did not explain why the POSITA would find or combine the

cited references without having first reviewed the patent.

[664] Teva argues that the POSITA would not look for or review patent applications, such as

Pinchasi 2007. Teva further argues that the POSITA would not piece together the FDA SBOA or

Pinchasi 2007, even if they found these, with the other art relied on by Pharmascience.

Page: 178

[665] Teva submits that, although Dr. Khan was well regarded, the Khan 2008 abstract was

little known. Caon 2009 is also a short abstract reporting on the same study as Khan 2008. Teva

reiterates that the POSITA would not give these short abstracts any weight.

[666] Teva notes that Pharmascience directed Drs. Prat and Day to the GALA study protocol’s

reference to Khan 2008 and Flechter 2002. However, Pharmascience disregarded the subsequent

statement in the protocol which confirmed that the “studies were clearly too small and

underpowered to show a significant effect on clinical end-points”.

[667] Teva disputes Dr. Green’s opinion that 40 mg three times weekly fell within the weekly

dose ranges previously disclosed. Teva notes that Dr. Green acknowledged that it was not known

whether the same total weekly dose would be effective when administered differently.

[668] Teva adds that Dr. Green’s basis for the obviousness of three times weekly dosing is that

Rebif, an interferon, was administered three times weekly. Teva points to Dr. Prat, who stated

that the POSITA would “never consider that a specific dosing regimen of Rebif would equally

work for Copaxone”. Teva notes that the experts agreed that the interferons have different

mechanisms of action, different side effects and different pharmacokinetics. Teva adds that all

the interferons are administered at substantially different doses and frequency.

[669] Teva notes that its invention changed both the dose (20 to 40 mg) and the regimen (daily

to three times weekly). Teva submits that the POSITA “having no scintilla of inventiveness or

Page: 179

imagination” would not have “come directly and without difficulty to the solution taught by the

patent”.

[670] Teva notes that whether a piece of prior art would have been located by the skilled person

is relevant to the obvious to try step of the Sanofi test, including that the skilled person “might

not have thought to combine that prior art reference with other prior art to make the claimed

invention” (Hospira at para 86).

[671] Teva disputes that it was self-evident that 40 mg three times weekly would improve

adherence and compliance, as Dr. Green contended. Teva notes that many factors influence

adherence, as all the experts acknowledged.

[672] With respect to the effort required to achieve the invention, Teva disputes Dr. Green’s

evidence that it would be the normal or routine role of a clinician to discuss options with patients

and to advise them to self-administer 40 mg glatiramer acetate three times per week. Teva notes

Dr. Green’s inconsistent evidence regarding off-label use.

[673] Teva adds that there was no motivation to try 40 mg three times a week. As conceded by

Dr. Green, no prior art directed the skilled person to do so.

[674] Teva disputes that the side effects of frequent injection would motivate the POSITA to

look for less frequent injections. Dr. Green relied only on his view of common sense. However,

Page: 180

the prior art (found in Dr. Green’s literature search but omitted from his report) disclosed that

interferon therapies with reduced frequency administration did not result in improved adherence.

[675] Teva adds that if there was motivation to address the effects of injection, the POSITA

would look to non-injectable therapies.

[676] Teva explains that its actual course of conduct was not routine or straightforward. Teva

notes that there were several unsuccessful trials in its effort to improve Copaxone before

pursuing 40 mg three times per week.

[677] Teva disputes Pharmascience’s suggestion that this Court should be influenced by other

proceedings regarding the ‘802 Patent or equivalent patents. Teva notes that decisions of foreign

courts are not to be considered (Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC, 2015 FC 17

at para 66 [Mylan], citing Eli Lilly Canada Inc v Apotex Inc, 2007 FC 455 at para 244, aff’d 2008

FCA 44). Teva notes that there are differences in practice and procedure and differences in the

evidence presented.

B.

Pharmascience’s Submissions

[678] Pharmascience submits that the ‘802 Patent is obvious; there were no material differences

between the state of the art and the subject matter of the claims and any minor differences would

easily be bridged by the POSITA.

Page: 181

[679] Pharmascience submits that the state of the art as of August 2009 was that:

 reduced frequency of injections was associated with reduced injection-site

irritation and reaction and better tolerance (which led to improved patient

compliance and adherence);

 Flechter 2002, Khan 2008 and Caon 2009 described the safety and effectiveness

of every-other-day administration of 20 mg glatiramer acetate;

 Cohen 2007 and Comi 2008 described the safety and effectiveness of 40 mg

glatiramer acetate;

 Rebif, an interferon, used to treat patients with RRMS was administered three

times per week (and with a day in between injections);

 all of the interferons (Avonex, Rebif and Betaseron) were administered less

frequently than daily; and,

 Pinchasi 2007 described and claimed the use of 40 mg glatiramer acetate

every-other-day for the treatment of patients with RRMS.

[680] Pharmascience argues that moving from the state of the art, which in its view, taught the

every-other-day dosing regimen of 40 mg glatiramer acetate, to a fixed three times per week

Page: 182

dosing regimen of 40 mg glatiramer acetate (which only results in one less dose in a two week

period) would have been obvious to the POSITA to improve patient convenience and adherence.

Pharmascience suggests that fixed day dosing is easier to remember and that less frequent

injections would reduce injection site reactions and post injection reactions.

[681] Pharmascience submits that as of August 2009 it was known that daily administration of

glatiramer acetate by injection commonly caused injection site reactions including, erythema

(redness), pain, mass pruritus (itching), edema, inflammation and hypersensitivity.

[682] Pharmascience focuses on lipoatrophy, a side effect of frequent injection, and submits

that it has irreversible impact. Pharmascience submits that the lipoatrophy that occurred as a

result of daily Copaxone injections was permanent, disfiguring and relatively common.

[683] Pharmascience argues that common sense dictated that reducing the frequency of

injections also reduced injection site reactions and led to better tolerance and, in turn, improved

patient compliance and adherence. Pharmascience submits that some studies support this

assumption.

[684] Pharmascience points to Flechter 2002, Khan 2008 and Caon 2009 in support of its

submissions that every other day dosing of 20 mg glatiramer acetate was as effective as daily

administration. Pharmascience also points to a single line in Caon 2009 that injection site

lipoatrophy was significantly less in the every other day group of patients.

Page: 183

[685] Pharmascience submits that, as of August 2009, 40 mg glatiramer acetate was a known,

effective and safe dose for the treatment of patients with RRMS. Pharmascience points to Teva’s

Phase II and Phase III clinical trials (Cohen 2007 and Comi 2008), which compared daily

injection of 40 mg Copaxone and 20 mg Copaxone in RRMS patients. Pharmascience notes that

the studies found both doses to be well tolerated and equally effective in reducing clinical

relapses and MRI activity. Pharmascience also emphasizes that the studies found that the 40 mg

dose demonstrated a trend for faster results in the first few months with respect to the number of

lesions.

[686] Pharmascience submits that Pinchasi 2007 claimed 40 mg of glatiramer acetate, injected

periodically, including every-other-day, for the treatment of patients with RRMS.

[687] Pharmascience also relies on the interferon DMTs, in particular, Rebif, which was

injected three times per week. The other interferons Avonex and Betaseron had different

regimens but all were administered less frequently than daily. Pharmascience submits that,

among the interferons, the less frequent dosing regimens encouraged patient adherence and

compliance relative to the most-frequently administered product.

[688] Pharmascience alleges that Teva has taken a “scorched-earth” approach to the state of the

art by arguing that none or little of it taught anything. Pharmascience disputes Teva’s suggestion

that its own Comi 2008 clinical trial was a “failure” that would lead a POSITA to think that there

was no 40 mg product under development. Pharmascience disputes that the POSITA would be

unaware of Flechter 2002, Khan 2008 and Caon 2009 or would ignore these studies because they

Page: 184

were not Phase III clinical trials. Pharmascience also disputes that Pinchasi 2007 would not be

found or would be ignored because it did not disclose any clinical studies on a 40 mg dose

administered every-other-day and because it never issued as a patent. Pharmascience further

disputes that the Rebif three times a week regimen would be entirely ignored by the skilled

person because the mechanisms of action of interferon and glatiramer acetate were understood to

be different.

[689] Pharmascience adds that Teva’s conduct was inconsistent with its current approach. For

example, Teva’s 2008 press release regarding the FORTE Phase III study did not cast it as a

failure rather that “the higher dose maintained the favourable safety and tolerability profile of

Copaxone 20 mg”.

[690] Pharmascience submits that there are no material differences between the state of the art

and the subject matter of the claims. The only minor difference would be the use of 40 mg of

glatiramer acetate, by injection periodically, including “every-other-day” (Pinchasi 2007) and the

use of 40 mg of glatiramer acetate, by injection three times per week, with a day between

injections.

[691] Pharmascience submits that the common general knowledge, common sense and

motivation to address injection site reactions would lead to the invention. It was self-evident that

reducing the frequency of injections would improve tolerability and reduce injection site

reactions and irritation, without compromising efficacy.

Page: 185

[692] Pharmascience argues that moving to a three times weekly regimen on fixed days would

have been obvious to improve patient convenience as it is easier to remember and would avoid

weekend injections. Pharmascience submits that Teva’s expert, Dr. Prat, agreed that three times a

week is an improvement over Pinchasi 2007’s every other day regimen. Pharmascience adds that

Rebif provided an example as it was administered three times weekly.

[693] Pharmascience is critical of Dr. Prat’s suggestion that the POSITA would not be

motivated to develop a 40 mg dose but would instead look to an oral formulation. Pharmascience

notes that the oral formulation had been a failure.

[694] Pharmascience again submits that the Court should draw an adverse inference from the

lack of evidence from the inventors, who could have explained the course of conduct in the

invention.

[695] Pharmascience submits that the evidence of Teva’s expert, Dr. Kreitman, was unrelated

to the work leading to the ‘802 Patent. Dr. Kreitman stated that only a few meetings were held to

discuss a higher-dose, lower-frequency regimen for glatiramer acetate – one in November 2008

and one in June 2009, resulting in a decision to proceed with a Phase III clinical trial (i.e., the

eventual GALA trial).

[696] Pharmascience submits that Dr. Kreitman acknowledged that Teva’s work was aimed at

pursuing the 40 mg product because the patent for Teva’s 20 mg glatiramer acetate was soon

Page: 186

expiring and Teva was concerned that the generic version of 20 mg glatiramer acetate would be

used three times per week rather than the 40 mg product.

[697] Pharmascience also notes that Dr. Kreitman indicated that 40 mg three times per week

was among the first few higher-dose, lower-frequency dosing regimens that were considered by

Teva.

[698] Pharmascience suggests that the Court should infer that the GALA trial was undertaken

only to confirm what was obvious, i.e., that 40 mg three times per week would be just as safe and

effective as 20 mg daily, and would improve tolerability (e.g., fewer injection site reactions).

[699] Pharmascience argues that the evidence of Dr. Green should be relied on over that of

Teva’s experts. Pharmascience characterizes Drs. Day and Prat as sceptics and less qualified to

opine on the key issues than Dr. Green. Pharmascience suggests that Dr. Day’s evidence be

ignored completely because his perspective as a biostatistician is not relevant and he has a

history of criticising even highly reputable scientists.

[700] Pharmascience further argues that the Court should consider that patents equivalent to the

‘802 Patent have been found to be obvious, including in the U.K. and U.S. In addition,

Pharmascience notes that the CIPO is currently re-examining the ‘802 Patent.

C.

What do the Experts Say?

(1)

Dr. Green

Page: 187

[701] In Dr. Green’s opinion, the claims of the ‘802 Patent were obvious. Dr. Green stated that

there were no differences between the state of the art in August 2009 and the subject matter of

the claims.

[702] Dr. Green stated that, by August 2009, it was recognized that the 20 mg daily dose had

been arbitrarily selected as there had been no determinative study to establish the ideal dosage

regimen for glatiramer acetate. Dr. Green noted that less frequent dosing regimens of 20 mg

glatiramer acetate were also known and continued to be investigated. Dr. Green referred to Khan

2008, who built on the work of Flechter 2002.

[703] Dr. Green stated that the POSITA would know that other doses of glatiramer acetate were

being explored, including a 40 mg dose, based on the FORTE Phase II Study reported by Cohen

in 2007.

[704] Dr. Green added that the results of FORTE Phase III clinical trials were widely reported,

including by way of Teva’s July 2008 press release. Dr. Green noted that Comi 2008 reported on

the results of this Phase III clinical study and concluded that both the 40 mg and 20 mg doses

were safe and well tolerated in RRMS patients and equally effective in reducing clinical relapses

and MRI activity. Dr. Green noted that the abstract stated that both doses showed a reduction in

Gd-enhancing and new T2 lesions over time, but noted a trend for faster reduction in the first

three months with the 40 mg dose.

Page: 188

[705] In Dr. Green’s opinion, the combination of this knowledge was that the 20 mg dose was

not the necessary dose to achieve clinical efficacy; it could be achieved with alternate dosages

and dosing regimens.

[706] Dr. Green explained that because MS is a chronic condition, compliance and adherence

to long-term treatment is a concern. (Dr. Green explained that compliance refers to the degree to

which a patient takes the medication as prescribed. Adherence refers to the degree to which a

patient follows the physician’s instructions more broadly. He added that the terms are often used

interchangeably).

[707] Dr. Green stated that unpleasant side effects of injection were known to lead to issues

with patient compliance. Dr. Green opined that it would be common sense to the POSITA that

less frequent injections would result in increased compliance. Dr. Green cited the Global

Adherence Project (Devonshire 2006) in support of his view. He noted that, although there may

be other contributing factors, the prevailing trend was that increased injection was associated

with reduced compliance or adherence.

[708] Dr. Green also noted that the Johnson study (1995) found that 90% of patients taking

glatiramer acetate experienced injection site reactions. Dr. Green noted that injection site

reactions include pain, discomfort, skin change, “even lipoatrophy”, all of which are unpleasant

but not frightening.

Page: 189

[709] Dr. Green noted that Pinchasi 2007 relied on the Cohen 2007 Phase II study results in

stating that the 20 mg and 40 mg daily had been shown to reduce MRI measured enhancing

lesions in MS patients. Dr. Green stated that, if 20 mg is efficacious for this purpose, then a

POSITA would expect that 40 mg would also work as a treatment for patients at risk of

developing MS.

[710] Dr. Green stated in his report and in his oral evidence that there were three key messages

for the POSITA in Pinchasi 2007:

 40 mg daily glatiramer acetate significantly improved efficacy without an increase in

adverse reactions. Dr. Green is of the view that the POSITA would have this view

because they would read Pinchasi 2007 with the knowledge of Cohen 2007 and Comi

2008 and would have identified that there was good safety and tolerability for the 40 mg

glatiramer acetate. This would have reinforced that the FORTE trials were to be believed

– i.e., that there is an enhanced onset of action; that there was a suggestion that 40 mg

could be given every other day and would be equally or more efficacious.

 Pinchasi 2007 reported on the faster onset of action of the 40 mg dose compared to the

20 mg (based on Cohen 2007 and Professor Comi’s presentation of the FORTE Phase III

trial).

 The POSITA would be interested in Pinchasi 2007’s periodic administration and would

read this with the knowledge of Khan 2008.

Page: 190

[711] Dr. Green’s opinion is that the state of the art in August 2009 taught that:

 Reduced-frequency dosage regimens of DMTs, including 20 mg glatiramer

acetate, were known to be as effective in treating MS but better-tolerated than

daily-dosage regimens, leading to improved patient compliance and adherence;

 A 40 mg daily-dose of glatiramer acetate was at least as safe and efficacious as a

20 mg daily-dose and was well-tolerated by patients, with potentially an earlier

onset of action and increased effectiveness in reducing MRI activity and clinical

relapses;

 Reduced frequency of injections would reasonably be presumed to result in

reduced injection site irritation and reaction, especially for a medicine where the

injection site could remain inflamed or irritated in the period after injection; and,

 Teva believed that the periodic administration of 40 mg glatiramer acetate,

including on an every-other-day basis, would be effective to treat MS (based on

Pinchasi 2007).

[712] On cross-examination, Dr. Green acknowledged that his PubMed search regarding the

‘802 Patent, did not turn up the FDA SBOA document, Khan 2008, Caon 2009 or Devonshire

2006. Dr. Green acknowledged that in 2009, the POSITA would not likely have read Devonshire

2006.

[713] Dr. Green also acknowledged that in 2009, he was not aware of the 1996 FDA SBOA or

the questioning posed to the applicant. Dr. Green also acknowledged that in his deposition in

Page: 191

California in 2016, he stated that he became aware of the FDA SBOA sometime between 2012

and 2016.

[714] Dr. Green acknowledged that he was not aware of Flechter 2002 in 2009, but had

attached it to his report.

[715] Dr. Green further acknowledged that Pinchasi 2007 did not turn up in his search, but, on

re-examination, he was directed to a footnote in his report, which suggests that Pinchasi 2007

was part of the search he oversaw.

[716] With respect to Khan 2008, which Dr. Green stated taught that reducing frequency of

administration from daily to every other day can increase tolerability and compliance while

maintaining efficacy, Dr. Green acknowledged that he chose not to change his clinical practice

based on Khan 2008. He stated that prior to 2014 he did not advise a patient to take 20 mg

glatiramer acetate every other day.

[717] On cross-examination, Dr. Green agreed that there was no piece of prior art referred to in

the ‘802 Patent that teaches the administration of glatiramer acetate three times per week. Dr.

Green reiterated that, in his view, this was the common sense approach.

[718] Based on his view of the state of the art, Dr. Green’s opinion remained that there were no

material differences between the state of the art and the subject matter of the claims of the ’802

Patent.

Page: 192

[719] Dr. Green added that the only possible difference would be between an every-other-day

dosage regimen of 40 mg of glatiramer acetate (as taught in Pinchasi 2007) and the claimed three

times per week dosage regimen of 40 mg of glatiramer acetate (with at least one day between

each injection). Dr. Green acknowledged that the three times per week regimen had not been

exemplified in the prior art. Dr. Green stated that the dosage difference over 14 days would be

small and therapeutically equivalent.

[720] In Dr. Green’s opinion, this small difference could be bridged by the POSITA using their

common general knowledge and other information available from a reasonably diligent search

and making simple deductions.

[721] Dr. Green noted that the tolerability and compliance issues with daily injections would

have motivated the POSITA to seek a less frequent administration regimen.

[722] Dr. Green added that the POSITA would have known that three times a week dosing

regimens existed for Rebif and that it was more convenient to use a three times a week

“formulation” – i.e., the same days every week and that the dose difference over a week would

be minor. Dr. Green opined that it would also be well known that three times weekly on the same

days of the week would be more convenient and easier to remember.

[723] With respect to Dr. Green’s reliance on Devonshire 2006 on patient adherence, Dr. Green

agreed that Avonex, which had the best adherence rate (85%) was administered once a week.

Copaxone, which had the lowest rate (56.8%), was administered daily.

Page: 193

[724] With respect to Dr. Green’s view that it was common sense that reduced injections would

increase compliance and adherence and would be self-evident to do so, on cross-examination,

Dr. Green acknowledged that Khan 2008 did not recommend a three times weekly dosage

although Rebif, previously approved in 2002, had such a dosing schedule.

[725] Dr. Green also acknowledged that Pinchasi 2007, which relied on Cohen 2007 (FORTE

Phase II trial), noted that there was a 50% increase in the number of patients who had a potential

post injection reaction when given 40 mg. Dr. Green added that the type of reaction was

important and that the reactions that occurred with the 20 mg treatment were more concerning.

[726] Dr. Green stated that it would have been self-evident that the 40 mg three times weekly

dosing regimen would likely work to effectively treat MS and CIS patients, with increased

adherence and compliance, relative to a 20 mg daily dosing regimen. He added that advising MS

and CIS patients to self-administer 40 mg glatiramer acetate three times per week rather than

every-other-day would be a matter of simply discussing the available options for a dosing

schedule with patients, which is the normal, routine work of a clinician.

[727] On cross-examination, Dr. Green clarified that, although he was referring to the

administration of a 40 mg dosage as routine, only 20 mg was available in 2009. Dr. Green agreed

that, in 2009, a patient would have to inject two doses of 20 mg (two syringes). Dr. Green

speculated that the patient could transfer the dosage to another syringe to reduce the number of

injections, but appeared to agree that a patient would not be expected to do this.

Page: 194

[728] Dr. Green also agreed that, to evaluate whether 40 mg three times weekly would work, a

clinical study would be required. Counsel for Teva asked why it would be routine work to

administer 40 mg glatiramer acetate outside of a clinical study. Dr. Green responded that it

would “make sense” to posit the use of a three times per week schedule.

[729] Dr. Green acknowledged that in his report in the U.K. litigation, he had stated that the

POSITA would seek to conduct a Phase III clinical study with the 40 mg dose. Dr. Green

explained that his previous statement was made based on the assumption that the POSITA would

be motivated to investigate. Counsel for Teva noted that Dr. Green did not add this qualification

to his evidence regarding the ‘802 Patent. Dr. Green explained that while it would be routine

work to discuss and recommend a three times a week dosing schedule, it would not be routine

clinical work. To investigate it, a clinical study would be required. Dr. Green agreed that this

clarification was not in his report.

(2)

Dr. Prat

[730] Dr. Prat did not fully agree with Dr. Green regarding the common general knowledge or

the state of the art in 2009. Dr. Prat noted that not all prior art is common general knowledge.

Dr. Prat stated that he understood that common general knowledge refers to widely accepted

facts.

[731] With respect to clinical trials, Dr. Prat explained (as did Dr. Selchen and Dr. Day) the

differences between investigatory or pilot studies and Phase I, II and III trials.

Page: 195

[732] With respect to available therapies for MS in August 2009, Dr. Prat generally agreed with

Dr. Green. However, Dr. Prat stated that it was not common general knowledge that a 40 mg

dose of glatiramer acetate was under development. Dr. Prat explained that the results of Comi

2008 indicated that the 40 mg dose did not show increased efficacy.

[733] Dr. Prat agreed that Cohen 2007, an abstract on a Phase II clinical trial that compared 20

mg and 40 mg daily administration, showed a faster onset of action for the 40 mg dosage at the

three-month point, but explained that this was an exploratory endpoint and was not statistically

significant and that after 8-9 months, the results were the same.

[734] Dr. Prat also explained that Cohen 2007 noted that although the same number of patients

withdrew in both groups, more patients in the 40 mg group withdrew because of adverse events.

Dr. Prat noted that despite conclusions stated by Cohen 2007, the data does not suggest that 40

mg had less adverse reactions.

[735] Dr. Prat acknowledged that the results of Cohen 2007 did not point Teva away from

pursuing the Phase III study. However, Dr. Prat explained that the POSITA would not place

much, if any, weight on the Phase II results given that the results of the more robust FORTE

Phase III study, which investigated 20 mg daily compared to 40 mg daily, were available.

[736] Dr. Prat noted that the subsequent Phase III study and Teva’s press releases indicated that

“the 40mg dose did not demonstrate increased efficacy in reducing the relapse rate…” and that

“the study reaffirms that COPAXONE 20mg… remains the optimal treatment dose…”. Dr. Prat

Page: 196

noted that the FORTE Phase III trial reported that 40 mg daily seemed to have increased side

effects compared to 20 mg daily that were “statistically significant” and also reported “increased

treatment discontinuation due to injection site reactions with the higher [40mg] dose”. Dr. Prat

added that, at that time, the POSITA would assume that the 40 mg Copaxone was no longer in

development.

[737] Dr. Prat acknowledged that the Phase III trial results were presented by Professor Comi at

the World Congress on Treatment and Research in Multiple Sclerosis [World Congress] in 2008.

Dr. Prat noted that over 1,200 abstracts were presented. He noted that not every POSITA would

have attended Professor Comi’s presentation.

[738] Dr. Prat added that if Comi 2008 were part of the common general knowledge, it would

not support using 40 mg of Copaxone.

[739] Dr. Prat disagreed with Dr. Green that the results of the FORTE Phase II and Phase III

studies would be part of the common general knowledge, although they were prior art. Dr. Prat

stated that although these results were public, they did not form part of the common general

knowledge. Dr. Prat noted that not every widely reported clinical study becomes common

general knowledge.

[740] Dr. Prat did not share Dr. Green’s view that the 20 mg dose of glatiramer acetate was

arbitrarily selected, but he acknowledged that there had not been any dosing studies at the time

20 mg was approved. In Dr. Prat’s view, the results of FORTE Phase III would not lead the

Page: 197

POSITA to consider doubling the dose (20 mg to 40 mg daily) and the lack of a dosing study

early in the drug development would not change this.

[741] Dr. Prat stated that although Khan 2008 was available in 2009, it was not part of the

common general knowledge. Dr. Prat explained that it was improbable that the POSITA would

have seen this abstract or the related presentation, given that it was presented along with

approximately 83 oral presentations and at least 900 other abstracts during a 3-day meeting

hosting approximately 5,500 participants. He added that this abstract did not disclose

well-known principles and would not have been widely accepted.

[742] Dr. Prat added that, if the POSITA had reviewed Khan 2008, they would have given it

little, if any, weight because the short abstract described a small, pilot study involving only 30

patients. The study compared 20 mg daily against 20 mg every-other-day glatiramer acetate.

Dr. Prat explained that the results of such an insignificant study would not constitute common

general knowledge.

[743] With respect to compliance and adherence rates, Dr. Prat explained that the POSITA

would understand that adherence is complex and based on multiple factors. Dr. Prat referred to

different studies than Dr. Green.

[744] Dr. Prat explained that the pain of injections is not the sole contributor to

non-compliance. He noted that it is most often due to forgetting to take the medication. Dr. Prat

added that injections of glatiramer acetate are not as painful as for interferons.

Page: 198

[745] Dr. Prat noted that Devonshire 2006 on the Global Adherence Project was a retrospective

study. Dr. Prat noted the abstract described a higher non-adherence rate for the higher dose of

Rebif as compared to its lower dose. In Dr. Prat’s view, if a POSITA considered Rebif at all, this

information would point away from a higher dose. Dr. Prat stated that the Devonshire abstract

does not even suggest that frequency of administration is a possible cause of non-adherence. Dr.

Prat noted that Dr. Green relied on common sense to move to less frequent injections to improve

adherence, but this is contradicted by the prior art. Dr. Prat noted that Devonshire 2006 found

that forgetting was the main cause.

[746] Dr. Prat noted the article Treadaway, K, “Factors that influence adherence with

disease-modifying therapy in MS”, 2009 J Neurol 256: 568-576 [Treadaway 2009], which

pointed out the problem with comparing data across different dosing regimens, given that some

DMTs are administered daily and others weekly. Treadaway 2009 compared adherence rates for

Copaxone 20 mg (daily injection) and three interferons: Avonex (once weekly), Betaseron (twice

weekly), Rebif (three times weekly). Dr. Prat noted that the authors acknowledged that it was

“highly problematic” to compare adherence rates across such varied therapies and attempted to

adjust for the variations. Treadaway 2009 reported that Copaxone (daily injection) had slightly

better adherence than Avonex (once weekly injection) and had similar adherence to Rebif (three

injections per week). Dr. Prat added that Treadaway 2009 surveyed the patients to understand

what led to non-adherence and the highest cause indicated was forgetting to take the medication.

[747] With respect to the state of the art, Dr. Prat agreed that, in August 2009, glatiramer

acetate 20 mg daily was a known effective treatment for RRMS and CIS. Doctors had been

Page: 199

prescribing Copaxone 20 mg for at least 10 years for RRMS. Copaxone 20 mg had been recently

approved for CIS. He also agreed that the 40 mg dose of glatiramer acetate was at least as

effective as the 20 mg dose.

[748] Dr. Prat expressed the view that Dr. Green overstated the state of the art regarding the

efficacy of 40 mg daily. Dr. Prat noted that Cohen 2007 concluded that there is a suggestion that

40 mg may be more effective than 20 mg daily, but this was not supported by the results of the

study. Dr. Prat explained that after nine months, the 40 mg was not more effective. Dr. Prat

stated that given that there was no higher efficacy of the 40 mg dose, the potential for post

injection reactions and injection site reactions would point away from the 40 mg dose.

[749] Dr. Prat stated that neither he nor other doctors would have been aware of Pinchasi 2007

or patent applications more generally. Dr. Prat added that, even if a doctor were aware of and

read Pinchasi 2007, they would understand that its focus was the use of 40 mg of glatiramer

acetate daily.

[750] Dr. Prat stated that the POSITA would not view Pinchasi 2007 as providing any rational

basis for an every-other-day dosing regimen and, in the absence of any data to support 40 mg

every other day, the POSITA would give almost no weight to the mention of such a regimen.

[751] In considering whether the ‘802 Patent differed from the state of the art, Dr. Prat noted

that in 2009 there was no disclosure in the prior art that glatiramer acetate should be used to treat

Page: 200

RRMS or CIS at a dose of 40 mg either periodically or three times per week with at least a day

between.

[752] Dr. Prat disagreed with Dr. Green that it was known that three times per week and every

other day doses were therapeutically equivalent.

[753] With respect to reduced frequency dosing, Dr. Prat stated that, to his knowledge, there

was no publicly available information showing that a reduced-frequency dosing regimen of

glatiramer acetate promoted compliance and adherence.

[754] Dr. Prat noted that the FDA SBOA for Copaxone would not be the type of document a

doctor treating MS patients would find or review. Moreover, the author does not identify a

dosing schedule and misstates the nature of glatiramer acetate. In Dr. Prat’s view, the POSITA

would not give any weight to this document, if it were available to them.

[755] Dr. Prat explained that Flechter 2002 reported on an investigatory study. Dr. Prat

expressed the view that the suggestion in Flechter 2002 – that 20 mg glatiramer acetate

every-other-day is as effective as glatiramer acetate daily – was not supported by sufficient data.

Dr. Prat noted that there was no control group and patients self-reported. Dr. Prat also noted that

Flechter 2002 stated that, “these preliminary observations will have to be examined in larger

studies.” Dr. Prat stated that even if the POSITA were to consider Flechter 2002, it would not be

clear that alternate day injections represented an improvement over daily injections.

Page: 201

[756] Dr. Prat also noted concerns about Flechter 2002 because it compared 20 mg daily to 20

mg every other day and then compared those results to the results obtained by Meiner in 1997.

Dr. Prat noted concerns about cross-study comparisons and pointed out the need to adjust for

variabilities between the two cohorts.

[757] On cross-examination, Counsel for Teva posited that the data in Flechter 2002 included

an error regarding the relapse rate over two years for 20 mg administered every other day.

Counsel for Pharmascience recalculated the relapse rates recorded in Flechter 2002 to attempt to

demonstrate that the relapse rate noted was a mistake and that after two years, was highly similar

between the two groups and as set out in both Flechter 2002 and Meiner. Dr. Prat acknowledged

that, if there were errors in the data and if Counsel’s calculation were correct, it showed similar

efficacy in relapse rates.

[758] Dr. Prat disagreed with Dr. Green that the Rebif label supports reduced frequency to

improve compliance. Dr. Prat again noted that interferons differ from glatiramer acetate and the

POSITA would not consider that a specific dosing regimen for Rebif would work equally for

Copaxone. He explained that Rebif’s efficacy is related to the amount and the frequency of

dosing and this does not necessarily apply to Copaxone.

[759] Dr. Prat reiterated that the POSITA would not look at other DMTs, such as Rebif, to

arrive at the dosing regimen for glatiramer acetate. Dr. Prat noted several differences between

Rebif and glatiramer acetate.

Page: 202

[760] Dr. Prat noted that the mechanism of action of glatiramer acetate is complex and not fully

understood but differs from that of interferons. Among other things, Dr. Prat noted that the

POSITA understood that frequent administration was likely important for the efficacy of

glatiramer acetate because glatiramer acetate degrades quickly after injection.

[761] Dr. Prat also noted that the other interferons had different and unique dosing regimens;

Avonex was once per week, Betaseron, every other day and, Rebif, three times per week. There

was no reason to select Rebif’s dosing regimen for glatiramer acetate.

[762] Dr. Prat agreed that patient adherence was an issue for all DMTs regardless of dosing

schedule. Dr. Prat disagreed that one third of missed injections were due to the pain or side

effects of the injection. Dr. Prat reiterated that the most common reason cited in the literature

was forgetting to take the medication. In Dr. Prat’s opinion, it is easier to remember a daily

dosing regimen, as it becomes routine at the same time every day.

[763] On cross-examination, Dr. Prat acknowledged that the ‘802 Patent states that a drawback

to glatiramer acetate therapy is the requirement of daily injections, which can be inconvenient.

Dr. Prat also acknowledged that the 2009 Copaxone Product Monograph stated that commonly

observed adverse reactions were redness, pain, inflammation, itching or a lump at the injection

site.

Page: 203

[764] Dr. Prat agreed that fear, avoidance and anxiety were common reactions of some patients

regarding injections, but noted that this was usually only at the outset of treatment and did not

last.

[765] Dr. Prat also noted that if adverse reactions caused adherence issues, the POSITA would

not want to use a higher dose that had been shown to increase those adverse reactions.

[766] With respect to bridging the differences between the state of the art and the subject matter

of the claims, Dr. Prat stated that inventiveness would be required. Nothing in the prior art

pointed to 40 mg three times per week, FORTE Phase III did not demonstrate any benefit to the

higher dose. In Dr. Prat’s view, a POSITA would instead be interested in a lower daily dose.

[767] Dr. Prat noted that, even if the POSITA knew that 20 mg every-other-day was effective

based on the preliminary studies, such as Khan 2008 (which Dr. Prat noted was underpowered

and would not be known or guide), there was no prior art suggesting equivalence between 20 mg

every-other-day and 40 mg every-other-day, let alone 40 mg three-times-per-week.

[768] Dr. Prat disagreed with Dr. Green that the invention was obvious to try. In Dr. Prat’s

opinion, based on the state of the art and the common general knowledge, it would not be

self-evident to the POSITA to try a 40 mg three times weekly dosing regimen or self-evident that

it would “likely” work to effectively treat MS and CIS patients, with increased adherence and

compliance relative to a 20 mg daily dosing regimen.

Page: 204

[769] Dr. Prat explained his disagreement, noting, among other things, that adherence and

compliance depend on many factors. He also noted that the prior art taught that reduced

frequency would likely result in worse adherence and compliance. Dr. Prat repeatedly stated that

daily injections are more easily remembered.

[770] Counsel for Pharmascience suggested that Dr. Prat was not instructed that, in addition to

the common general knowledge, the skilled person could consider prior art or information

generated by a reasonably diligent search. Dr. Prat responded that a reasonably diligent search

would not have turned up pilot studies, Phase II studies or abstracts that are part of large abstract

books. If found, these would not have been influential.

[771] Dr. Prat added that the POSITA would also not recommend to a patient that they should

double their prescribed dose (20 mg to 40 mg) and simultaneously reduce the frequency of their

injections. Dr. Prat explained, among other reasons, that unless it will increase efficacy, patients

should be treated with the lowest dose.

[772] Dr. Prat agreed that there was general motivation to look for new treatments for MS,

including oral treatments. Dr. Prat agreed that he had not referred to the CORAL study in his

report, but he was aware of it. Dr. Prat acknowledged that oral treatments of glatiramer acetate

were explored in the CORAL study and were not successful. Dr. Prat explained that by

modifying glatiramer acetate and making it more stable, an oral dose may be possible and a

POSITA would be motivated to pursue this.

Page: 205

[773] Dr. Prat acknowledged that injection site related lipoatrophy was relatively common but

stated that it was an unusual and infrequent reason for discontinuing glatiramer acetate treatment.

He disagreed that lipoatrophy had a significant psychological impact, although agreed that for

some patients there would be some impact. Although the Copaxone label states that there is no

treatment for lipoatrophy, Dr. Prat noted that he was aware that plastic surgery was an option. He

did not say that he had recommended or resorted to plastic surgery for any patient.

[774] Dr. Prat acknowledged that injection site reactions are the most frequent adverse

reactions, but noted that this was true of all injectables, but it was much less so for glatiramer

acetate relative to the other DMTs. Dr. Prat stated that there was more concern about skin

reactions associated with interferon injections. Dr. Prat noted that he did not observe problematic

reactions to Copaxone in clinical practice. He also noted that Dr. Green’s footnote reference to

Edgar 2004 (in Dr. Green’s report) relied on by Pharmascience was derived from a paper about

acupuncture. Dr. Prat added that there was only a passing mention of lipoatrophy in Caon 2009.

[775] Dr. Prat explained that the prior art disclosed that daily injections were important for

maintaining sufficient anti-inflammatory cells activated and available to enter patients’ nervous

system. The POSITA would not be motivated to reduce injection frequency and potentially

counter this positive effect.

[776] Dr. Prat stated that it would be far more than the routine work of a clinician to arrive at

the invention. Dr. Prat explained that a doctor would not be able to advise a patient to take 40 mg

Page: 206

or to prescribe this until a 40 mg glatiramer acetate product was approved for use and, as of

2009, there was no such approval in Canada. To get approval, a clinical trial would be required.

[777] Dr. Prat stated that if a new dosing regimen were sought, there were many other solutions

to explore, which were not predictable based on the prior art. For example, to avoid injections, a

POSITA would look to a different active ingredient or to modify glatiramer acetate to allow oral

administration. To address lower frequency of glatiramer acetate, a patch or a sustained release

injectable formulation could be pursued.

[778] Dr. Prat noted that there was little motivation to find a new dosing cycle. He again noted

that in 2009 the POSITA was aware that 20 mg daily remained the optimal dose. However, to the

extent that the POSITA sought to vary the dosing cycle of glatiramer acetate, there were other

options – e.g., 30 mg, 50 mg, 75 mg and variations on the schedule. Nothing in the prior art

pointed to three times a week.

D.

The ‘802 Patent is Not Obvious

[779] The legal principles guiding the assessment of obviousness are set out above at Part XX

and have been applied.

[780] With respect to the evidence, contrary to Pharmascience’s submission, I do not find that

the evidence of Drs. Day and Prat should be disregarded or discounted and that the evidence of

Dr. Green should be determinative on the key issues.

Page: 207

[781] Pharmascience suggests that Dr. Prat is less qualified than Dr. Green because Dr. Prat

explained that he spends 70% of his time as a lab scientist and clinical neurologist and has not

focussed on clinical studies of humans. Pharmascience submits that, therefore, Dr. Prat’s

opinions on the clinical trials (e.g., Comi 2008, Khan 2008, Caon 2009, and Flechter 2002)

should be given less weight than those of Dr. Green, who is a specialized clinician.

[782] Pharmascience also submits that Dr. Prat’s opinion on obviousness should be given little

weight because he was misinstructed on the “obvious to try” test and he failed to consider that

the POSITA can bridge the differences using the common general knowledge and information

gathered as the result of a reasonably diligent search. Pharmascience also submits that Dr. Prat

erred in taking the approach that the only relevant prior art is a Phase III clinical trial.

[783] Neither Dr. Day nor Dr. Prat are sceptics. Dr. Day is a biostatistician and, of course, his

role was to assess the statistical significance of studies. His opinion does not make him a sceptic.

Dr. Prat’s evidence was candid and consistent. He took a balanced approach to his responses. He

offered context even when he was discouraged to do so. He provided explanations about why he

disagreed with Dr. Green and explained why some abstracts and reports would provide guidance

and others would not.

[784] Dr. Green also provided clarifications, explanations and additional context for his

opinions. Some of his opinions on key issues were more nuanced in his responses on

cross-examination.

Page: 208

[785] As noted above, all the experts provided helpful and relevant evidence. However, as is

typical, the experts do not agree on the key issues. As noted at the outset, I have considered all of

the expert and factual evidence in its full context.

[786] However, there are several examples of the parties seeking to extract responses from the

experts on specific points to support particular arguments. The arguments based on isolated

responses have glossed over the thrust of the evidence. As a result of this approach, I have been

required to very carefully review the evidence in its totality to determine if the experts were in

fact supporting the particular argument.

[787] For example, Pharmascience suggests that Teva’s expert, Dr. Morrow, agreed that the

‘437 Patent taught the use of 40 mg glatiramer acetate administered three times per week for the

treatment of MS (i.e., what is claimed in the ‘802 Patent). The evidence relied on by

Pharmascience relates to questions put to Dr. Morrow about the construction of the claims of the

‘437 Patent. Dr. Morrow agreed that claim 1 referred to periodic administration and that claim 13

added the essential element of daily administration. Dr. Morrow also agreed that the ‘437 Patent

included a claim for 40 mg (claim 16). On cross-examination, Dr. Morrow acknowledged that it

was possible that 40 mg three times per week would be covered by the claims of the ‘437 Patent.

However, Dr. Morrow repeatedly stated that her answer was based only on the wording of claim

1, which did not set out a dosing schedule. In my view, this evidence cannot be relied on to

suggest that the ‘437 Patent encompasses a three times weekly dosage of 40 mg of glatiramer

acetate. As noted above, the ‘437 Patent is directed at daily administration of 20 mg for CIS

patients. The examples do not address any other dosing regimen or the administration of 40 mg

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glatiramer acetate. The silence of claims 1-12 regarding a dosing schedule does not support the

argument that any possible schedule could work, particularly since the only schedule claimed is

daily.

[788] Pharmascience also submits that injection site lipoatrophy resulting from injection of

glatiramer acetate was so debilitating and irreversible that Dr. Prat’s patients resorted to plastic

surgery. Dr. Prat did not say that he had recommended plastic surgery to any patient. Dr. Prat’s

evidence was in response to the question of whether lipoatrophy was irreversible. Dr. Prat noted

that plastic surgery would be an option. Moreover, his evidence is that, although lipoatrophy did

occur in some patients, it was not a cause of lack of adherence to injections of glatiramer acetate.

[789] Pharmascience appears to put more emphasis on the “debilitating” effects of lipoatrophy

as an injection site reaction than its expert Dr. Green does. Dr. Green referred to lipoatrophy

once, noting that injection site reactions were “a component” of non-adherence. Pharmascience

repeatedly points to Caon 2009, but there is only one line in that very short abstract regarding

lipoatrophy.

[790] With respect to reduced frequency injections, contrary to Pharmascience’s submission,

Dr. Prat did not agree that a three times weekly dosing regimen of glatiramer acetate was

preferable. Dr. Prat reluctantly agreed that if the only two options available were every other day

or three fixed days a week, the three fixed days would be an improvement. Dr. Prat’s opinion,

which he clearly and repeatedly stated, was that daily administration was the better option for

remembering to take the medication.

Page: 210

[791] I have not considered the outcomes of proceedings in foreign jurisdictions or the interest

of the CIPO in the ‘802 Patent. As noted in Mylan at para 66:

There is no doubt that the Court is not bound by the decisions of

foreign courts dealing with corresponding patents, to say nothing

of different patents. As this Court stated in Eli Lilly v Apotex, 2007

FC 455, at para 244 (aff’d 2008 FCA 44):

This Court is not bound by the decisions of foreign

courts dealing with corresponding patents. In the

words of the Federal Court of Appeal: “Although

foreign patents may be practically identical, foreign

law is unlikely to be so and must, in any case, be

proved” (Lubrizol Corp. v Imperial Oil Ltd. (1992),

45 C.P.R.(3d) 449). These words are especially apt

in the present matter which can be differentiated

from what occurred in the United States on a

number of grounds, including the nature of the

proceedings, the evidence, and the burden of proof.

[792] The validity of the ‘802 Patent has been determined based on the jurisprudence and the

evidence before this Court and nothing else.

[793] As noted, Pharmascience relies on a mosaic of the prior art to argue that the state of the

art was that reduced frequency dosing regimens were known, 40 mg glatiramer acetate was

known to be effective, and potentially more effective than 20 mg, and that Pinchasi 2007

disclosed and taught an every other day dosing regimen of 40 mg of glatiramer acetate. On this

basis, Pharmascience submits that the small difference between the state of the art and the claims

of the ‘802 Patent would be easily bridged by the POSITA who would be motivated to use the

three times weekly dosing regimen to address injection site reactions and provide an easy to

remember regimen to improve patient adherence.

Page: 211

[794] I do not agree with Pharmascience’s depiction of the state of the art in 2009. The starting

point in assessing obviousness is not that 40 mg glatiramer acetate every other day was effective

to treat symptoms of MS.

[795] I find that Pharmascience and Dr. Green have overstated the teaching of the prior art they

rely on.

[796] First, the prior art relied on by Pharmascience would not all have been found by the

POSITA, as it was not all found by Dr. Green in his search. Notably, Dr. Green stated that he did

not turn up the FDA SBOA, Khan 2008, Caon 2009 or Devonshire 2006. Dr. Green noted that he

was not aware of the FDA SBOA or Flechter 2002 in 2009. Dr. Green also agreed that the

POSITA would not look at Devonshire 2006.

[797] Second, even if all this prior art were found by the POSITA, the POSITA would rely on

their expertise to read this art with a critical eye, make the distinction between small pilot

studies, Phase II studies and Phase III studies, and know that some clinical studies are more

reliable and informative than others.

[798] Dr. Day explained why certain studies teach more than others based on how they are

conducted and how the results are portrayed.

Page: 212

[799] Dr. Selchen also explained the classes of evidence ranging from case reports and opinion

pieces to Class 1 evidence of Phase III, double-blind clinical trials, noted to be the gold standard

by all the experts.

[800] Dr. Prat also noted the several classes of evidence. Dr. Prat explained that abstracts are

simply short summaries and that an abstract with a high number shows that it is one of at least

that many abstracts presented and, as a result, would not be at the top of a POSITA’s reading list.

[801] Third, I agree with Teva that Pharmascience has not explained how or why the POSITA

would regard these pieces of prior art together in a mosaic to lead to the invention. However,

even if the POSITA was handed this mosaic, it does not lead them directly to the subject matter

of the claims. Contrary to Dr. Green’s submission, it is not a matter of simple deduction to move

from 20 mg daily, or even 20 mg every other day, to 40 mg three times weekly.

[802] As noted in Servier at para 254:

As acknowledged by Servier, a mosaic of prior art may be

assembled in order to render a claim obvious. Even uninventive

skilled technicians would be presumed to read a number of

professional journals, attend different conferences and apply the

learnings from one source to another setting or even combine the

sources. However, in doing so, the party claiming obviousness

must be able to demonstrate not only that the prior art exists but

how the person of ordinary skill in the art would have been led to

combine the relevant components from the mosaic of prior art.

This case is a good example.

Page: 213

[803] With respect to reduced frequency administration, as Dr. Green acknowledged, he was

not even aware of the FDA SBOA in 2009. This document would not be found by the POSITA

and, if found, would not teach anything about the impact of reduced frequency injections.

[804] Flechter 2002 indicated that 20 mg every other day was “probably” as effective as daily.

Dr. Green admitted on cross-examination that he did not know about Flechter 2002 in 2009.

[805] Pharmascience was critical of Dr. Prat’s assessment of Flechter 2002, noting that it

exposed an error in Flechter 2002 regarding the calculation of the relapse rate reported for

every-other-day patients. Pharmascience submitted that once corrected, Dr. Prat’s criticism of

Flechter 2002 could not be maintained, nor could his criticism of the cross-study comparison.

However, Dr. Prat stated that he assessed the report as he found it. He acknowledged that if the

calculation of the two-year relapse rate was as stated by Pharmascience (after its recalculation)

the two relapse rates would be similar.

[806] Regardless, Dr. Prat’s key concern about Flechter 2002 was that it reported on an

investigatory study with insufficient data to support its “suggestion” that 20 mg glatiramer

acetate every-other-day is as effective as glatiramer acetate daily.

[807] With respect to Khan 2008, the experts agreed that Dr. Khan was a highly regarded

scientist. However, this does not automatically result in finding that every short article written by

Dr. Khan would be found, read, and/or guide the POSITA. The abstract was less than one page

long and reported on an investigatory study of only 30 patients comparing 20 mg daily and every

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other day. As Dr. Prat noted, Khan 2008 was one of at least 900 abstracts presented at a three day

conference of 5,500 participants and, as a result, would not have been brought to the attention of

all those in attendance. Dr. Prat added that Khan 2008 would not be common general knowledge

of the POSITA. Caon 2009 was also a less than one page abstract that reported on the same study

of 30 patients. Dr. Prat described both Khan 2008 and Coan 2009 as “underpowered”.

[808] Even assuming that the POSITA found these very short abstracts, they would read them

with a discerning eye to reveal that both reported on the same investigatory study of 30 patients.

[809] Comi 2008 was acknowledged by all the experts to be a well-designed Phase III study

conducted to confirm the results of the Phase II results (reported by Cohen 2007). All agree that

it showed that 20 mg daily and 40 mg daily were equally effective, including with respect to

safety and tolerability. All agree that Comi 2008 noted that there appeared to be a “trend” to

earlier onset of action for the 40 mg dosage in the first three months, but this did not endure in

the longer term. Dr. Green’s reliance on Comi 2008 to assert that the 40 mg is potentially more

effective ignores that after the three-month mark, the “trend” was not observed and, in the longer

term, the study shows that 40 mg is simply equally effective.

[810] Dr. Prat explained that the FORTE Phase III study showed that 40 mg daily resulted in an

increase of adverse effects compared to 20 mg daily. He noted that Professor Comi’s

presentation at the World Congress disclosed this increase in adverse events as “statistically

significant compared to GA 20mg” and “the difference [was] mainly due to Injection Site

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Reactions”. The presentation also disclosed that there were “increased treatment discontinuation

due to injection site reactions with the higher [40mg] dose”.

[811] The POSITA who reviewed Comi 2008 in its entirety would not conclude that 40 mg was

better than 20 mg, only that they were equally effective. The POSITA would also be alert to the

possibility of adverse side effects of the 40 mg dose.

[812] Pharmascience and Dr. Green heavily rely on Pinchasi 2007 as the state of the art and as

motivation for the subject matter of the claims of the ‘802 Patent.

[813] In my view, it is doubtful that the POSITA would look for patent applications. However,

if the POSITA did turn up Pinchasi 2007, the POSITA would assess its teachings based on the

fact that it was simply an application that was not approved.

[814] Dr. Green described three messages from Pinchasi 2007 (as noted above). I do not agree

that the POSITA would take away the same messages or weave the other art in the manner

suggested to bolster Pinchasi 2007.

[815] If the POSITA reviewed Pinchasi 2007 along with Cohen 2007 and Comi 2008 as

Dr. Green suggests, the POSITA would not likely conclude that it teaches that 40 mg could be

administered every other day and would be efficacious. If an unapproved patent application can

be regarded as teaching anything, Pinchasi 2007 did not teach – even given its reference to

Cohen 2007 – that 40 mg had increased efficacy over 20 mg. Nor did Pinchasi 2007 teach an

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every other day administration. Although Pinchasi 2007 noted the results of Cohen 2007, it did

not set out the additional results of Comi 2008 regarding the adverse side effects of 40 mg.

Moreover, if the POSITA read Pinchasi 2007, the POSITA would know that the focus was on

daily administration of 40 mg glatiramer acetate.

[816] As noted in the description of the prior art above, Pinchasi 2007 describes its invention as

“periodically administering” 40 mg of glatiramer acetate to alleviate the symptoms of RRMS. In

one embodiment, the periodic administration is daily. In another embodiment, the periodic

administration is every other day. In a further embodiment, the pharmaceutical composition is in

the form of a sterile solution for once daily administration. The claims include a claim for daily

administration and a claim for every other day administration. However, the only example is

based on the FORTE Phase II study, which compared 40 mg and 20 mg administered daily as

reported by Cohen 2007. There is no data in Pinchasi 2007 to support an every other day

administration of 40 mg glatiramer acetate.

(1)

The State of the Art

[817] Based on the review of the prior art, and all the expert evidence, I find that the state of the

art in 2009 was that:

 20 mg glatiramer acetate daily was used to treat RRMS and CIS;

 20 mg glatiramer acetate every other day had been explored in small, pilot

studies without reliable results, only suggestions based on a small sample size

(Flechter 2002, Khan 2008 and Caon 2009) which do not support any

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conclusion or teaching of the effectiveness of every-other-day administration

of glatiramer acetate;

 Comi 2008 (FORTE Phase III) demonstrated that 40 mg glatiramer acetate

was equally effective as 20 mg. A trend towards earlier onset of action was

“suggested” for 40 mg. An increase in adverse reactions, mainly due to

injection site reactions, was reported for 40 mg;

 Patient adherence to their DMT was a general concern for all DMTs and

dosing schedules;

 There were several factors at play regarding patient adherence, including

injection site reactions;

 The interferons were different compounds, all with different prescribed dosing

schedules; and,

 Pinchasi 2007 was a patent application – that was not approved – that

focussed on 40 mg daily for RRMS and relied on Cohen 2007 (FORTE Phase

II).

[818] The experts all agreed that not all prior art is common general knowledge.

[819] I accept Dr. Prat’s view that Flechter 2002, Khan 2008 and Caon 2009 were not part of

the common general knowledge.

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[820] I also accept Dr. Prat’s opinion that it was not common general knowledge that 40 mg

daily was potentially more effective than 20 mg daily. As noted, the Phase II and Phase III

results reported only a trend to faster onset of action at the three-month mark.

[821] Contrary to Pharmascience’s position, it was not common general knowledge that

decreasing the frequency of injections would increase patient compliance and adherence. All the

experts agreed that there were several factors at play regarding compliance and adherence.

[822] Dr. Green stated that “a component” of non-adherence and non-compliance was related

to frequency of injection. He stated that it is “just standard common sense” that if you give less

frequent administration of most drugs, enhanced compliance will result, especially if there is a

convenient dosing schedule that is easy for a patient to remember. However, Devonshire 2006

and Treadaway 2009 do not support this supposition. Dr. Prat repeatedly noted that forgetting to

take the DMT is the common reason for non-adherence.

(2)

Differences between the State of the Art and the Subject Matter of the Claims

[823] There were material differences between the state of the art and the subject matter of the

claims.

[824] As noted above, the starting point in assessing the differences is not 40 mg every other

day (Pinchasi 2007); rather, it is 20 mg daily as the optimal dosage. The POSITA would also be

aware that 40 mg had been demonstrated to be as effective as 20 mg.

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(3)

Not Obvious to Try

[825] The POSITA using the common general knowledge and information gathered from a

reasonably diligent search (Ciba at para 62) would not come directly and without difficulty to the

subject matter of the claims of the ‘802 Patent.

[826] As noted above, Pharmascience has not explained how or why the POSITA would

combine the prior art relied on. However, even if the POSITA did so, it would not point them to

try to obtain the invention (Hospira at para 86).

[827] As noted by Dr. Prat, even if the POSITA supplemented the common general knowledge

with the results of a reasonably diligent search, the POSITA would not turn up several of the

articles relied on or other articles not already identified by Dr. Green to support the view that 40

mg three times a week was the way to go. Dr. Green’s search revealed over 1,300 articles, of

which a handful were relied on and, as found above, several would not guide the POSITA and

would not create a mosaic for the POSITA to support Pharmascience’s position.

[828] Contrary to Pharmascience’s submission, Dr. Prat was not misinstructed on the test for

obviousness. But, even if he were, it is the Court’s task to determine if the test established in

Sanofi and elaborated on in subsequent jurisprudence has been met, based on the evidence. The

Court appreciates that the obvious to try test is informed by several factors, one of which is

whether it was self-evident that the invention would work (Hospira at para 90).

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[829] The evidence does not establish that it was more or less self-evident for the POSITA to

try to obtain the invention of 40 mg glatiramer acetate three times weekly, or that it was

self-evident that this would work to alleviate the symptoms of RRMS.

[830] Bridging the differences between the state of the art and the subject matter of the claims

required inventive ingenuity.

[831] As Dr. Prat emphasized, nothing taught that 40 mg administered periodically or three

times a week would be effective. In addition, the general approach is to not increase the dosage.

20 mg daily was considered to be the optimal dosage, despite no studies supporting how the

20 mg dosage was arrived at years ago.

[832] The art did not provide motivation to both change the dose and the frequency of

administration. Comi 2008 confirmed that 20 mg and 40 mg were equally effective. The

suggestion or trend to a faster onset of action for the 40 mg dose would not motivate the POSITA

given that these results did not continue for the longer term and there is no evidence or

suggestion that such a result would occur in an every other day dose.

[833] The concerns about injection site reactions were acknowledged by the experts, but are not

key motivating factors for reduced injection frequency. Dr. Prat noted that this concern would

motivate the POSITA to consider non-injectables. It would not motivate the POSITA to consider

a higher dose as a lower dose is always preferred if effective.

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[834] In addition, Dr. Prat noted that Comi 2008, which was more authoritative, reported

adverse reactions for 40 mg. Dr. Prat stated that a POSITA would not increase the dosage if it

would increase adverse reactions.

[835] Dr. Morrow had indicated that if a patient had a concern about needles, fewer injections

were not the solution, rather a different approach. Dr. Prat also noted that some patients have a

concern about self-injections but it is short lived.

[836] As noted above, Dr. Green also agreed that injection site reactions were “a component”

contributing to non-adherence.

[837] Dr. Prat acknowledged that the ‘802 Patent stated that in clinical trials “injection-site

reactions were seen to be the most frequent adverse reactions and were reported by the majority

of patients receiving [glatiramer acetate]”. However, this reaction was in comparison to

injections of placebo.

[838] The Rebif regimen of three times weekly would not motivate the POSITA given that all

agree that interferons are different – even if no one can explain how – and the other interferons

have different dosing regimens.

[839] Dr. Prat explained that if there were motivation to move away from injections, an oral

formulation could be explored. He acknowledged the failure of the CORAL study and noted that

glatiramer acetate could be modified to develop an oral formulation. Other approaches that could

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be pursued to avoid injections altogether included a sustained release injectable formulation or a

patch. Dr. Prat noted that there was little motivation to find a new dosing cycle.

[840] With respect to the effort required to obtain the invention, Dr. Green’s suggestion that it

would be a simple matter to discuss the dosing regimen with a patient is based on his view that

the starting point was 40 mg every other day. Dr. Green acknowledged that in 2009, a patient

would have to take two 20 mg injections in order to have a 40 mg dose every other day or three

times weekly because 40 mg was not available. In my view, two injections would clearly defeat

the purpose of reducing injection frequency. In addition, Dr. Green’s suggestion that a patient

could combine two 20 mg doses in a syringe appears to be beyond the skills or desire of a

patient.

[841] Dr. Green also agreed that a clinical study would be required to evaluate whether 40 mg

three times weekly would be effective. When asked why it would be routine work to administer

40 mg outside of a clinical study, Dr. Green responded that it would “make sense” to posit the

use of a three times per week schedule. Dr. Green drew a distinction between routine work and

routine clinical work.

[842] With respect to this off-label use, Dr. Green acknowledged that he had given a different

opinion in other proceedings, where he stated it would not be appropriate to prescribe 20 mg

every other day, as that would be off-label and only appropriate in clinical study (i.e., not routine

clinical work). Dr. Green also agreed that he would not advise his patients to skip doses and

would not advise patients to take Copaxone 40 mg three times a week until it was approved.

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[843] I place more reliance on the evidence of Dr. Prat who stated that a clinical trial would be

required and that a neurologist could and would not use 40 mg off-label, even if it were

available.

[844] With respect to the history of the invention, Teva did not provide evidence from the

inventors. Contrary to Pharmascience’s submission, the Court does not draw an adverse

inference from this. Dr. Kreitman explained the work undertaken by Teva.

[845] Dr. Kreitman stated that Teva conducted several studies to explore different possible

improvements to Copaxone. With respect to the higher dose, lower frequency administration

regimen which ultimately led to Copaxone 40 mg three times a week, Dr. Kreitman explained

that her team at Teva evaluated several dosing regimens (including 40 mg every other day, 40

mg three times per week, 35 mg three times per week, and 40 mg once or twice per week) before

the decision was made to proceed with the clinical trial of 40 mg three times a week (the GALA

trial).

[846] Dr. Kreitman acknowledged that Teva did not have supporting clinical evidence for the

contemplated reduced-frequency dosing regimens, but had pre-clinical evidence.

[847] Pharmascience suggests that Teva pursued the invention because its other patent was

soon expiring and because it feared that the generic version of 20 mg glatiramer acetate would be

used three times per week rather than the 40 mg product. Dr. Kreitman acknowledged that the

other patent would expire, but with respect to the possible generic use of 20 mg, she explained

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that she was copied on an email sent by another person who relayed a concern about use of the

generic product.

[848] Contrary to Pharmascience’s submission, I do not find that Teva pursued the GALA trial

only to confirm what was already known.

[849] In conclusion, the subject matter of the claims – 40 mg glatiramer acetate administered

three times a week to treat RRMS, and alleviate symptoms as measured in different ways – was

not obvious. The material differences between the state of the art and the subject matter of the

claims could not be easily bridged by the POSITA using their common general knowledge and

additional information gleaned from a reasonably diligent search. It was not self-evident to try

40 mg of glatiramer acetate three times weekly or that the 40 mg three times weekly dose would

work; there were other possible solutions to address patient adherence if that were a motivating

concern; and, there was no motivation to simultaneously increase the dose, given that the

increased dose had not been shown to be more effective, and reduce the frequency of

administration.

XXV.

A.

Is the ‘802 Patent Invalid due to Lack of Utility or Sound Prediction of Utility?

Teva’s Submissions

[850] Teva submits that Pharmascience has not met its burden to establish inutility on a balance

of probabilities as it has not adduced any evidence to show that the invention was not useful. Nor

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has Pharmascience adduced evidence to establish that the utility of the invention was not soundly

predicted and supported by the information disclosed in the ‘802 Patent and the art incorporated

by reference.

[851] Teva submits that the actual utility of the invention has not been put into dispute.

Moreover, the subject matter of the claims has utility. Teva notes that glatiramer acetate 40 mg

has been approved for use as a subcutaneous injection administered three times per week for

treating RRMS. Teva submits that this approval would not have been granted without evidence

of efficacy. It is also clear from the evidence that doctors in Canada prescribe Copaxone 40 mg

in accordance with the asserted claims (i.e., to treat RRMS). Teva questions why Pharmascience

would want to replicate the invention if it were not useful.

[852] Teva argues that Pharmascience’s attack on the utility of the ‘802 Patent appears to be

more about the lack of disclosure of the utility. Teva submits that the disclosure requirement is to

ensure that the invention can be put into practice. The utility requirement is satisfied without any

disclosure provided the test set out in AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36 at

para 53 [AstraZeneca] is met. Teva submits that it is; the subject matter is capable of a practical

purpose, which is to alleviate symptoms of RRMS.

[853] Teva submits that all that is required for sound prediction is a “prima facie reasonable

inference of utility” (Eli Lilly Canada Inc v Novopharm Limited, 2010 FCA 197 at para 85).

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[854] Teva notes that the ‘802 Patent includes a detailed description of the Phase III clinical

study, including its protocol, mid- and end-points, and efficacy and safety results of 40 mg three

times per week, all of which provide the prediction for the basis of at least a scintilla of utility.

The patent also incorporates 18 references to support the invention. Teva submits that this

disclosure, coupled with the 18 references, is more than enough to meet the test.

[855] Teva further submits that the soundness of a line of reasoning can be assessed by

determining how the POSITA would interpret and accept the logic presented in the patent’s

specification (Bell Helicopter Textron Canada Limitée v Eurocopter, société par actions

simplifiée, 2013 FCA 219 at para 154 [Eurocopter]). Teva notes that Pharmascience did not

question the experts about whether they would accept the logic in the ‘802 Patent.

[856] Teva adds that Pharmascience’s expert, Dr. Green, did not provide any opinion on

whether this disclosure fails to meet the requirements for utility.

[857] Teva submits that it had a sound line of reasoning, including extensive internal research

into glatiramer acetate, including: pre-clinical studies showing efficacy in reduced frequency

dosing; proposing, planning and designing a detailed Phase III clinical study on the efficacy of

40 mg three times per week; and, commencing the clinical trial on RRMS patients.

[858] Teva submits that Dr. Kreitman described a process that was clearly not routine.

Dr. Kreitman explained that Teva’s decision to develop the 40 mg three times per week product

was based on the prior studies of glatiramer acetate, the studies to show the safety of 40 mg and

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the work done to understand the mechanism of action of Copaxone. Dr. Kreitman noted Teva’s

pre-clinical evidence and that it had conducted animal studies before August 2009.

[859] Teva argues that, despite filing no evidence, Pharmascience simply asserts that the

requirements of a demonstration or sound prediction of utility as of the filing date of the ‘802

Patent are not met and points to a confusing exchange with Dr. Prat on cross-examination.

[860] Teva submits that Pharmascience cannot rely on Dr. Prat’s responses to meet its burden

to demonstrate lack of utility or lack of sound prediction. Dr. Prat’s opinion was on the validity

of the ‘802 Patent. Dr. Prat clearly stated that he was not familiar with the legal tests for utility or

the notion of reasonable inferences as sought by Pharmascience. Dr. Prat provided his responses

based on the common general knowledge as of August 2009, which is not the relevant date for

the utility analysis. Dr. Prat stated that he was not aware of what may have been done by Teva

between August 2009 and August 2010.

[861] Teva also disputes Pharmascience’s suggestion that the outcome of a phase III clinical

trial cannot be predicted until all the data is compiled and, therefore, Teva could not soundly

predict utility. Teva notes that Pharmascience took the contrary view with respect to the validity

of the ‘437 Patent.

[862] Teva submits that the Supreme Court of Canada has rejected the notion that patents can

be invalidated because a phase III clinical trial had not been completed, noting that the

requirements for sound prediction of utility are not at the same level as the requirements for

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regulatory approval and that the doctrine of sound prediction recognizes that further work will be

done (Apotex Inc v Wellcome Foundation Ltd, 2002 SCC 77 at para 77 [Wellcome]).

B.

Pharmascience’s Submissions

[863] Pharmascience argues that if the ‘802 Patent is not obvious due to the state of the prior

art, then Teva cannot resort to the prior art that it discounts or rejects to support the utility or

sound prediction of utility of the ‘802 Patent. More particularly, Pharmascience argues that if

Teva is correct regarding the state of the prior art (i.e., as not teaching 40 mg every other day),

then Teva has no prior art to rely on before the filing date to soundly predict the utility of a three

times per week dosing regimen of 40 mg of glatiramer acetate.

[864] Pharmascience argues that there was no demonstration of use, i.e., no supporting data

regarding 40 mg three times per week. Pharmascience adds that Teva has not done or disclosed

any testing to support a sound prediction as of August 2010 that 40 mg of glatiramer acetate

three times per week would be effective to treat RRMS.

[865] Pharmascience notes that no data from the GALA trial was available until months later

and there was no factual basis available to Teva to make any prediction regarding the claimed

uses. Pharmascience notes that the first patient was enrolled in the GALA trial in late June 2010.

Pharmascience submits that Teva could not possibly have demonstrated utility by August 19,

2010 and, as a result, could not have soundly predicted the utility of 40 mg glatiramer acetate

three times per week for the treatment of RRMS in a human patient.

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[866] Pharmascience points to Dr. Prat’s responses on cross-examination, including his

statement that “I don’t see why the skilled person would infer that 40 mg three times a week

would work or would be better than 20 mg every day”.

[867] Pharmascience describes the example in the ‘802 Patent as “prophetic” as it refers to a

future study (GALA), which would not, once completed, provide any data regarding the

comparative efficacy of 40 mg three times per week to other dosage regimens because the

comparator is to placebo.

[868] Pharmascience also submits that Teva has a “fatal disclosure problem”. Pharmascience

submits that Teva cannot rely on Dr. Kreitman’s evidence describing Teva’s internal in vitro

and/or animal testing related to Copaxone and the TV-5010 glatiramoid product that may have

led Teva to believe that the products could be administered less frequently than once per day

because this was not disclosed in the ‘802 Patent. Pharmascience adds that there is no reason to

believe that the TV-5010 testing could have supported any prediction about glatiramer acetate.

[869] Pharmascience also suggests that Dr. Kreitman’s evidence is inconsistent with a

presentation made to Teva’s CEO in June 2009, which indicated that there was no supporting

data available for the three times per week 40 mg dosing regimen.

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C.

Principles from the Jurisprudence

[870] The Supreme Court of Canada clarified the test for utility in AstraZeneca and the

distinction between the Patent Act requirements in section 2 (regarding usefulness) and

subsection 27(3) (regarding disclosure) at paras 42-43:

[42] Section 27(3) of the Act provides that in the specification, a

“patentee must describe the invention ‘with sufficiently complete

and accurate details as will enable a workman, skilled in the art to

which the invention relates, to construct or use that invention when

the period of the monopoly has expired’” (Whirlpool, at para. 42,

quoting Consolboard, at p. 517).

[43] There is a difference between the requirement in s. 2 that an

invention be “useful” and the requirement to disclose an

invention’s “operation or use” as per s. 27(3). As explained by

Dickson J. (as he then was) in Consolboard, the former isa

“condition precedent to an invention” and the latter a “disclosure

requirement, independent of the first”:

. . . the Federal Court of Appeal erred also in

holding that s. 36(1) [now s. 27(3) and (4) ] requires

distinct indication of the real utility of the invention

in question. There is a helpful discussion in

Halsbury’s Laws of England (3rd ed.), vol. 29, at p.

59, on the meaning of “not useful” in patent law. It

means “that the invention will not work, either in

the sense that it will not operate at all or, more

broadly, that it will not do what the specification

promises that it will do”. There is no suggestion

here that the invention will not give the result

promised. . . .

. . . the Federal Court of Appeal has confused the

requirement of s. 2 of the Patent Act defining an

invention as new and “useful”, with the requirement

of s. 36(1) [now s. 27(3) ] of the Patent Act that the

specification disclose the “use” to which the

inventor conceived the invention could be put. The

first is a condition precedent to an invention, and

the second is a disclosure requirement, independent

of the first. [Emphasis added]

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(Consolboard, at pp. 525 and 527)

While the above passage uses the word “promise”, it does not refer

to, nor does it embody, the Promise Doctrine.

[871] In AstraZeneca at paras 54-58, the Court set out the test for utility and reiterated that

utility must be either demonstrated or soundly predicted:

[54] To determine whether a patent discloses an invention with

sufficient utility under s. 2 , courts should undertake the following

an analysis. First, courts must identify the subject-matter of the

invention as claimed in the patent. Second, courts must ask

whether that subject-matter is useful — is it capable of a practical

purpose (i.e. an actual result)?

[55] The Act does not prescribe the degree or quantum of

usefulness required, or that every potential use be realized — a

scintilla of utility will do. A single use related to the nature of the

subject-matter is sufficient, and the utility must be established by

either demonstration or sound prediction as of the filing date (AZT,

at para. 56).

[56] The utility requirement serves a clear purpose. To avoid

granting patents prematurely, and thereby limiting potentially

useful research and development by others, the case law has

imposed a requirement that an invention’s usefulness be

demonstrated or soundly predicted at the time of application, rather

than at some later point. This ensures patents are not granted where

the use of the invention is speculative. What matters is that an

invention “be useful, in the sense that it carries out some useful

known objective” and is not merely a “laboratory curiosity whose

only possible claim to utility is as a starting material for further

research” (Re Application of Abitibi Co. (1982), 62 C.P.R. (2d)

81 (Patent Appeal Board and Commissioner of Patents), at p. 91).

[57] The application of the utility requirement in s. 2, therefore,

is to be interpreted in line with its purpose — to prevent the

patenting of fanciful, speculative or inoperable inventions.

[58] Even though utility of the subject-matter is a requirement

of patent validity, a patentee is not required to disclose the utility

of the invention to fulfill the requirements of s. 2. As was stated by

Dickson J. in Consolboard:

. . . I do not read the concluding words of s. 36(1)

[now s. 27(4)] as obligating the inventor in his

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disclosure or claims to describe in what respect the

invention is new or in what way it is useful. He

must say what it is he claims to have invented. [p.

526]