Generics [UK] Ltd trading as Mylan v Yeda Research and Development Company Ltd and Another
Jurisdiction | England & Wales |
Judge | The Hon Mr Justice Arnold,Mr Justice Arnold |
Judgment Date | 11 July 2012 |
Neutral Citation | [2012] EWHC 1848 (Pat) |
Court | Chancery Division (Patents Court) |
Docket Number | Case No: HC11C00459 |
Date | 11 July 2012 |
[2012] EWHC 1848 (Pat)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Rolls Building
Fetter Lane, London, EC4A 1NL
The Hon Mr Justice Arnold
Case No: HC11C00459
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
Hearing dates: 14–18, 21–25, 29–31 May 2012
Approved Judgment
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.
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 |
Introduction
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.
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.
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.)
4. It is convenient to mention at this point that there has been parallel litigation in other countries, and in particular the USA.
Technical background
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.
Multiple sclerosis
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.
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.
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.
Experimental allergic encephalitis
9. The most widely used animal model for MS in 1994 was experimental allergic...
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