Generics [UK] Ltd trading as Mylan v Yeda Research and Development Company Ltd and Another

JurisdictionEngland & Wales
CourtChancery Division (Patents Court)
JudgeThe Hon Mr Justice Arnold,Mr Justice Arnold
Judgment Date11 July 2012
Neutral Citation[2012] EWHC 1848 (Pat)
Docket NumberCase No: HC11C00459

[2012] EWHC 1848 (Pat)

IN THE HIGH COURT OF JUSTICE

CHANCERY DIVISION

PATENTS COURT

Rolls Building

Fetter Lane, London, EC4A 1NL

Before:

The Hon Mr Justice Arnold

Case No: HC11C00459

Between:
Generics [UK] Limited trading as Mylan
Claimant
and
(1) Yeda Research and Development Co. Ltd
(2) Teva Pharmaceutical Industries Limited
Defendants

Michael Tappin QC, Piers Acland QC and Lindsay Lane (instructed by Simmons & Simmons LLP) for the Claimant

Andrew Waugh QC, Thomas Hinchliffe and Jeremy Heald (instructed by Bird & Bird LLP) for the Defendants

1

Hearing dates: 14–18, 21–25, 29–31 May 2012

2

Approved Judgment

3

I direct that pursuant to CPR PD 39A para 6.1 no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic.

The Hon Mr Justice Arnold Mr Justice Arnold
4

Contents

Topic

Paragraphs

Introduction

1–4

Technical background

5–80

Multiple sclerosis

6–8

Experimental allergic encephalitis

9

Treatment for MS

10

Copolymer-1

11–12

Teitelbaum 1971

13–17

Techniques for testing copolymer-1

18–25

Suppression of EAE

19

Mouse lethality test

20

RBL degranulation test

21–24

Guinea pig skin irritation test

25

Clinical trials of copolymer-1

26–41

Abramsky 1977

27

Bornstein 1982

28

Bornstein 1987

29–34

Bornstein 1991

35

Phase III trial

36–37

Comi 2001

38

Wolinsky 2007

39

Comi 2009

40–41

Synthetic polypeptides

42–51

Amino acid analysis

52

Average molecular weights of polymers

53–57

Size exclusion chromatography

58–61

SEC mobile phase

62–63

SEC calibration

64–70

Calibration using narrow standards

66

Calibration using narrow self-standards

67

Single broad standard calibration

68–69

Universal calibration

70

Experimental error

71–80

Accuracy

72

Precision

73–78

Repeatability

79

Reproducibility

80

The skilled team

81–84

The expert witnesses

85–124

The clinicians

87–92

Dr Coles

87–89

Prof Schellekens

90–92

The toxicologists

93–96

Prof Kimber

93–94

Prof Baird

95–96

The synthetic chemists

97–105

Prof Hunter

97–103

Prof Sampson

104–105

The analytical chemists (amino acid analysis)

106–110

Prof Kent

106–108

Prof Sampson

109–110

The analytical chemists (SEC)

111–114

Dr Hunt

111

Prof Grant

112–114

The statisticians

115–124

Dr Altmann

116–123

Prof Sasieni

124

Factual witnesses

125–129

Prof Arnon

126–127

Dr Pinchasi

128–129

Common general knowledge

130–164

MS

132

EAE

133

Treatment for MS

134

The Phase III trial

135–142

Immunogenicity of tyrosine

143–144

Synthetic polypeptides

145–146

Amino acid analysis

147–154

Average molecular weight

155–159

SEC

160–164

The Patent

165–186

Background to the invention

165–167

Summary of the invention

168

Brief description of the drawings

169–171

Detailed description of the invention

172–186

The claims

187–190

Construction

191–257

Copolymer-1

195–219

Fraction

220–222

Average molecular weight

223–248

Molecular weight distribution

249–256

Predetermined by small scale reaction

257

Priority

258–276

Obviousness over the prior art

277–334

The law

277–281

Obviousness of the product claims over Bornstein 1987

282–285

Obviousness of the product claims over Johnson 1994

286–304

Obviousness of the process claims over Teitelbaum 1971

305–333

The polymerisation step

310–317

The HBr deprotection step

318–333

Secondary evidence of non-obviousness

334

Obviousness for lack of technical contribution

335–412

The law

336–352

Burden of proof

339–342

Evidence which post-dates the patent

343–352

The disclosure of the specification

353–375

Example 2A

361–364

Example 2B

365–374

Overall

375

Contemporaneous extrinsic evidence

376–387

Mouse lethality assay

379–384

Guinea pig skin irritation test

385–387

Post-dated evidence

388–412

The Cochrane Review

389–396

Dr Altmann's analyses

397–401

Prof Sasieni's analyses

402–404

The evidence of Dr Altmann and Prof Sasieni

405–407

Dr Coles' evidence

408–409

Prof Schellekens' evidence

410–411

Conclusions

412

Insufficiency

413–440

The law

413

Classical insufficiency

414–435

Choice of mobile phase

417–419

Calibration method

420–429

Different results

430–435

Ambiguity

436

Excessive claim breadth

437–440

Added matter

441–457

The law

441–442

Claims 2, 3, 5 and 6

443–448

Claim 4

449–450

Claims 7–10

451–457

Declaration of non-infringement

458–465

Not copolymer-1

459–462

Not a fraction

463–464

Not predetermined by small scale reaction

465

Summary of conclusions

466

5

Introduction

6

1. In this action the Claimant (“Mylan”) seeks revocation of European Patent (UK) No. 0 762 888 (“the Patent”) and a declaration of non-infringement. The First Defendant (“Yeda”) and the Second Defendant (“Teva”) are respectively the proprietor of, and the exclusive licensee under, the Patent. The Patent relates to a material known as copolymer-1 which was first described in 1971. Teva sells a product which it claims is protected by the Patent under the trade mark Copaxone (non-proprietary name glatiramer acetate) for the treatment of relapsing-remitting multiple sclerosis (“MS”). The purpose of this action is to enable Mylan to clear the way for the launch of its own generic glatiramer acetate in the United Kingdom.

7

2. The action raises a large number of issues. These can be broadly summarised as follows;

i) whether the claims are entitled to the first claimed priority date of 24 May 1994 or whether they are only entitled to the application date of 23 May 1995;

ii) whether the Patent is invalid for obviousness over the prior art;

iii) whether the Patent is invalid for obviousness as making no technical contribution, but rather being an arbitrary selection from the known copolymer-1 material;

iv) whether the Patent is invalid for insufficiency because the claims are ambiguous;

v) whether the Patent is invalid for insufficiency on classical grounds;

vi) whether the Patent is invalid for insufficiency because it makes no technical contribution;

vii) whether the Patent is invalid for added matter; and

viii) whether the sale of Mylan's glatiramer acetate product would infringe any of the claims of the Patent.

8

3. Partly as a result of the nature of the invention claimed in the Patent and partly as a result of the very broad range of issues, the action has involved expert evidence from experts in an unusually wide range of disciplines. The result was a trial lasting 12 days (spread over 13 days, not including the court's pre-reading time). It follows that this judgment is necessarily rather long. (For comparison, the combined length of the parties' written closing submissions is 947 paragraphs and 266 pages.)

9

4. It is convenient to mention at this point that there has been parallel litigation in other countries, and in particular the USA.

10

Technical background

11

5. As indicated above, the action involves a number of different areas of science and technology. In this section I will introduce the technical background topic by topic.

12

Multiple sclerosis

13

6. MS is an autoimmune disease. Autoimmune diseases are ones in which the body's immune system malfunctions and is no longer able to make the distinction between the body's own and foreign antigens. The result is that the body's immune cells attack structures in the body itself. In MS there is an inflammatory response that leads to the removal of the sheath around nerves. As this sheath is comprised of the protein myelin, this process is referred to as “demyelination”. Without the insulation provided by the myelin sheath, the nerve cells are not able to function correctly and control motor functions or to receive and relay information from the sensory systems. As MS progresses, it causes multiple lesions or scleroses to form on the brain and spinal cord, hence the name. MS is a chronic and progressive disease. The neurological effects, progression and disabilities associated with the disease are diverse. They include cognitive, motor and sensory impairments.

14

7. The clinical hallmarks of MS typically start in young adulthood. MS is usually characterised by episodes of neurological symptoms (called “relapses”) which often recover (or “remit”). This is referred to as “relapsing-remitting” MS (previously referred to as “exacerbating-remitting” MS). Over time, however, there is less recovery after relapses, leaving patients with increasingly persistent deficits. At about the age of 40, the relapses become less frequent and the patient enters a phase of “secondary progression” in which he or she experiences slow accumulations of disability between relapses. A much rarer form of MS is “primary progressive” MS. This resembles the secondary progressive disease, but without the preceding relapses.

15

8. The causes of MS were not known in 1994, and are still not known even today. Amongst the possible candidates are viral infections, genetic susceptibility to immune disorders, trauma, inadequate blood supply to the brain, diet, climate and other environmental factors. There is evidence, however, that its causes are complex and multifactorial, with factors such as the environment and the genetic susceptibility of the individuals implicated.

16

Experimental allergic encephalitis

17

9. The most widely used animal model for MS in 1994 was experimental allergic...

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1 firm's commentaries
  • The Basic Of Patent Law - Revocation, Non-Infringement And Clearing The Way
    • United Kingdom
    • Mondaq UK
    • 13 April 2017
    ...were within it or not). (See Idenix v Gilead [2016] EWCA Civ 1089, Warner-Lambert v Generics [2016] EWCA Civ 1006, Generics v Yeda [2012] EWHC 1848 (Pat)), Kirin-Amgen v Hoechst Marion Roussel [2005] UKHL A challenge of insufficiency is considered by reference to the person skilled in the a......

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