Evidently Plausible: post-published evidence in Mylan v. Yeda

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Evidently Plausible: post-published evidence in Mylan v. Yeda [2012] EWHC 1848 (Pat) Joe Lenthall 29 November 2012

Transcript of Evidently Plausible: post-published evidence in Mylan v. Yeda

Evidently Plausible: post-published evidence in Mylan v. Yeda

[2012] EWHC 1848 (Pat)

Joe Lenthall29 November 2012

Overview

• Key Issues

• Background to Invention

• Assessment of obviousness as to making no technical contribution• Plausibility of technical benefit

• Post-published evidence

• Conclusion

Key Issues• Decision considered:• Priority;

• Obviousness over prior art;

• Obviousness as making no technical contribution;

• Insufficiency because the claims are ambiguous;

• Insufficiency on classical grounds;

• Insufficiency because the patent makes no technical contribution;

• Added subject-matter; and

• Infringement

Key Issues• Decision considered:• Priority;

• Obviousness over prior art;

• Obviousness as making no technical contribution;• Insufficiency because the claims are ambiguous;

• Insufficiency on classical grounds;

• Insufficiency because the patent makes no technical contribution;

• Added subject-matter; and

• Infringement

Background to the invention

• Relates to “co-polymer 1” (COP-1):• Synthetic polypeptide of alanine, glutamic acid, lysine and

tyrosine

• Molecular weight and sequence is not fixed (as in natural polypeptides)

• Useful in the treatment of Multiple Sclerosis (MS)

Claim 1 of Patent

• A copolymer-1 fraction wherein said fraction contains:• less than 5% of species of COP-1 having a molecular weight

over 40 kilodaltons; and

• wherein 75% of said fraction is within a molecular weight range from 2 kilodaltons to 20 kilodaltons.

• So most of COP-1 is within 2-20 kDa range

Obviousness• Court considered claim 1 to be inventive over:• Johnson 1994 – presentation of clinical trial using 7 kDa

COP-1; and

• Teitelbaum 1971 – original study into treating MS with COP-1 of molecular weight in the range of 14–23 kDa

• Skilled person would not consider molecular weights to be significant from these documents

• Court also considered what technical contribution the molecular weight ranges provided

Technical Contribution• What is the technical contribution; is the claim merely

an arbitrary selection?

• Does the patent disclose enough to make the technical contribution plausible?

• To what extent can post-dated evidence be used to prove or refute the technical contribution

Technical Contribution• T 939/92 Argrevo/Triazoles

- Arbitrary selection does not involve inventive step.

Technical Contribution• T 939/92 Argrevo/Triazoles

- Arbitrary selection does not involve inventive step.

• Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49

- The key question is whether the specification discloses enough to make it plausible that the selection has the technical significance claimed for it.

“Plausibility”

• Supreme Court in HGS v Eli Lilly [2012] RPC 6

- “[for plausibility] there must be some real reason for supposing that the statement is true. The important point, however, is that the standard is not any higher than that"

Burden of Proof• T 1797/09 Unilever/Dish-wash compositions

- a technical problem is considered to be credibly solved by a claimed invention if there exist no reasons to assume the contrary

Burden of Proof• T 1797/09 Unilever/Dish-wash compositions

- a technical problem is considered to be credibly solved by a claimed invention if there exist no reasons to assume the contrary

- Opponent's burden to prove the opposite or at least provide evidence casting doubt on the alleged solution of the problem

Burden of Proof• T 1797/09 Unilever/Dish-wash compositions

- a technical problem is considered to be credibly solved by a claimed invention if there exist no reasons to assume the contrary

- Opponent's burden to prove the opposite or at least provide evidence casting doubt on the alleged solution of the problem

- However, if the Opponent succeeds to cast reasonable doubt on the alleged effect, the burden to prove its allegations is shifted to the Patent Proprietor

Assessing Technical Contribution

Mylan said there is a two-stage enquiry:

1.Does the patent disclose enough information to make the invention plausible?

2.Even if the invention is plausible, it remains open to the other party to cast doubt on this by post-dated evidence

Ave. MW (kDa) % of species with MW > 40kDa

No. mice alive after 48 hours

7.3 <2.5 5/58.4 <2.5 5/522 >5.0 2/5

• Claim 1 is to a copolymer-1 fraction containing:• less than 5% of species of copolymer-1 having MW > 40

kDa; and • 75% of the fraction is within a MW range from 2 kDa to 20

kDa

• Example 2A

Disclosure of the patent

Ave. MW (kDa) % of species with MW > 40kDa

% Serotonin Release

6.25 <2.5 12.47.3 <2.5 21.013 >5.0 66.9

14.5 >5.0 67.8

• Claim 1 is to a copolymer-1 fraction containing:• less than 5% of species of copolymer-1 having MW > 40

kDa; and • 75% of the fraction is within a MW range from 2 kDa to 20

kDa

• Example 2B

Disclosure of the patent

Contemporaneous evidenceBatch Average MW RBL Safety in

vivo Skin Irritation

123-094 6250 12.4 0/5 NT123-090 7300 21 0/5 14±2.5 (14±1.2)123-095 8400 25.6 0/5 11.6±1.5 (12±1.2)04792 9245 31.3 0/5 13.8±1 (14±1.2)04892 9600 50.5 (?) 0/5 NT04992 9900 51.5 (?) 0/5 13.8±1.2 (14±1.2)123-096 10,950 39.8 0/5 NT04592 11,050 41.3 0/5 16±1.2 (16.4±0.8)04692 11,900 41.7 0/5 NT04492 12,150 47.6 0/5 18±1.8 (17.2±1)196/2 13,000 66.9 0/5 16.2±1 (17±1.55)196/1 14,500 67.8 0/5 15.6±0.8 (14.8±1)186/1 22,000 60.3 3/5 NT

Contemporaneous evidence

• Shown in patent • Shown in evidence

Post-published evidence• Mylan referred to clinical trials data published in a

Cochrane Review for:• (i) Bornstein 1987 (14-23 kDa cop-1); and

• (ii) Johnson 1995 (7 kDa cop-1)

• Focussed on adverse side effects at injection site

• No direct comparison

• Evidence was inconclusive

Relevant case-law cited• T 1329/04 Johns Hopkins University School of

Medicine/Growth differentiation factor-9

• Richardson-Vicks Inc. Patent, EWHC, [1995] RPC 568

• Generics (UK) Ltd v H Lundbeck A/S, EWHC, [2007] RPC 32

• HGS v Lilly, EWCA, [2010] RPC 12

• Cannot provide plausibility with post-published data

Refuting technical benefit• If invention is plausible at the filing date from the

specification, can later published documents be used to show that it does not have the technical benefit that it appeared to have?

• The fundamental principle is that whether a claimed invention is obvious or not should be judged as at the priority or application date

Use of post-dated evidence• Post-dated evidence may be relied on to confirm that the

disclosure in the patent either does or does not make it plausible that the invention solves the technical problem

• Post-dated evidence may not be relied upon either to:• establish a technical effect which is not made plausible by the

specification in order to rebut an allegation of obviousness; or

• contradict a technical effect which is made plausible by the specification in order to found an allegation of obviousness

Conclusions• Post-dated evidence may be relied on only to

confirm that the disclosure in the patent either does or does not make it plausible that the invention solves the technical problem

• Whether or not the patent makes the invention plausible must be judged at the filing date

• What if data in the patent is wrong?

ANY QUESTIONS?

Joseph Lenthall, Ph.D.Mewburn Ellis LLP

[email protected]

Offices in London, Bristol, Cambridge and Manchester