Takeda UK Ltd v F. Hoffmann-La Roche AG
| Jurisdiction | England & Wales |
| Judge | Mr Justice Birss |
| Judgment Date | 17 July 2019 |
| Neutral Citation | [2019] EWHC 1911 (Pat) |
| Docket Number | Case No: HP-2018-000008 |
| Court | Chancery Division (Patents Court) |
| Date | 17 July 2019 |
[2019] EWHC 1911 (Pat)
IN THE HIGH COURT OF JUSTICE
BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES
INTELLECTUAL PROPERTY LIST (ChD)
PATENTS COURT
Royal Courts of Justice
The Rolls Building
7 Rolls Buildings
Fetter Lane
London EC4A 1NL
Mr Justice Birss
Case No: HP-2018-000008
Andrew Waugh QC, Joe Delaney and Georgina Messenger (instructed by Bird & Bird) for the Claimant
Richard Meade QC, William Duncan and Thomas Jones (instructed by Marks & Clerk) for the Defendant
Hearing dates: 12th – 14th, 17th – 21st, 23rd – 27th June 2019
Judgment Approved by the court for handing down (subject to editorial corrections)
If this Judgment has been emailed to you it is to be treated as ‘read-only’. You should send any suggested amendments as a separate Word document.
| Topic | Paragraphs |
| Introduction | 1 |
| The witnesses | 14 |
| The skilled person and the common general knowledge | 29 |
| The patent and claim construction | 51 |
| Infringement | 102 |
| Novelty | 117 |
| Obviousness | 196 |
| Insufficiency | 226 |
| Conclusion | 256 |
Introduction
This is a patent action concerning European Patent (UK) No EP 2 007 809 entitled “Glycosylated Antibodies”. The patentee is the defendant Roche. The claimant Takeda has a product called Entyvio which is approved for ulcerative colitis and Crohn's disease. The product is a formulation of a monoclonal antibody called vedolizumab. Roche claims that vedolizumab infringes the patent. Takeda denies infringement and claims the patent is invalid. The action started with Takeda bringing a claim for revocation.
The patent was filed on 10 th April 2007 claiming its earliest priority from a European filing EP 06007565 on 11 th April 2006. The patent was granted on 12 th September 2012. It was opposed by GSK and Novartis. In decision T1784/15 of 22 nd June 2017 the Technical Board of Appeal of the EPO upheld the validity of the patent with slightly amended claims. The B2 specification was published on 12 th September 2018. The claims in this case are the claims upheld by the EPO. By the time the matter came before the Technical Board of Appeal Novartis had settled with Roche. GSK attended the hearing as an observer but did not present oral submissions.
Claim 1 is in this form:
Monoclonal antibody of human IgG1 or IgG3 type being glycosylated with a sugar chain at Asn297,
said antibody being characterized in that the amount of fucose within said sugar chain, related to the sum of G0, G1, G2 without mannose 4 and mannose 5 as 100% and as analyzed by Liquid Chromatography/Mass Spectrometry (LCMS) peptide map analysis is at least 99%
and in addition the amount of NGNA within said sugar chain, related to the sum of G0, G1, G2 without mannose 4 and mannose 5 as 100% and as analyzed by Liquid
Chromatography/Mass Spectrometry (LCMS) peptide map analysis, is 1% or less,
and the amount of N-terminal alpha 1,3 galactose within said sugar chain related to the sum of G0, G1, G2 without mannose 4 and mannose 5 as 100% and as analyzed by Liquid Chromatography/Mass Spectrometry (LCMS) peptide map analysis is 1% or less.
The clauses in claim 1 have been separated out for clarity. Claim construction will be addressed below but right away one can see that the claimed antibody is characterised by three relative quantities of things within the sugar chain.
Claims 2 to 9 are:
2. Antibody according to claim 1, characterized in that the amount of NGNA is 0.5% or less.
3. Antibody according to claims 1 or 2, characterized in that the amount of N-terminal alpha 1,3 galactose is 0.5% or less.
4. Antibody according to claims 1 to 3, characterized in that the antibody is a chimeric, humanized or human antibody.
5. CHO cell line DSM ACC 2795.
6. Use of an antibody according to claims 1 to 4 for the manufacture of a medicament.
7. Pharmaceutical composition comprising an antibody according to claims 1 to 4.
8. Use of a CHO cell according to claim 5 for the recombinant production of a monoclonal antibody according to claims 1 to 4.
9. Method for the recombinant production of a monoclonal antibody according to claims 1 to 4 in a CHO cell according to claim 5.
An amendment to claim 1 was proposed but that was dropped shortly before trial.
The issue of infringement turns on claim construction and questions of fact about the properties of vedolizumab. If vedolizumab is within claim 1, no other infringement issue arises. If it infringes claim 1, vedolizumab would also infringe claims 2, 3, 4, 6 and 7. These are the only relevant claims. The other claims (5, 8 and 9) are all limited to a particular deposited cell line DSM ACC 2795 which Takeda does not use.
In terms of validity, Takeda advances a large number of attacks. Many of them interrelate to some extent in that they arise from what Takeda contends is the lack of any technical contribution to the art made by the disclosure in the patent. The grounds on which validity is challenged are:
i) Lack of novelty over:
a) International Patent Application WO 2005/040221 A1 published 6 th May 2005 (“Bihoreau”);
b) The article by Shinkawa et al entitled“ The Absence of Fucose but Not the Presence of Galactosidase or Bisecting N-Acetylglucosamine of Human lgGl Complex-type Oligosaccharides Shows the Critical Role of Enhancing Antibody-dependent Cellular Cytotoxicity” (2003) in the Journal of Biological Chemistry, Vol.278, No.5, Issue of January 31, pp 3466–3473, 2003;
c) The article by Ferrara et al entitled “ The Carbohydrate at FcrR ll/a Asn-162 An Element Required for High Affinity Binding to Non-Fucosylated igG Glycoforms” published in The Journal of Biological Chemistry Vol.281, No.8 pp.5032–5036
d) A prior use by the company Novartis of chimeric monoclonal antibody known as basiliximab (trade name Simulect). This was advanced in the EPO opposition and supported by declarations given the numbers D57, D58 and D59.
ii) Lack of inventive step:
a) On the basis of lack of technical contribution;
b) Bihoreau;
c) Simulect;
iii) Insufficiency:
a) Ambiguity in that the skilled person cannot identify what calculation is required by the claims;
b) Ambiguity in that the skilled person cannot know whether they are carrying out the right test to find out if they are within the claims;
c) A breadth of claim argument linked to lack of technical contribution;
d) A classic insufficiency argument linked to deposited cell line DSM ACC 2795.
When the case was opened Takeda also relied on a paper by Jun et al. published in Applied Microbiology & Biotechnology (2005), vol. 69, pp.162–169 but that was dropped during the trial.
Further insufficiency grounds were pleaded however the points made are addressed within the ones set out above. The point on the deposited cell line DSM ACC 2795 was, Takeda argued, that when reconstituted the deposited cells do not produce antibodies within the claims. That point is not a free standing basis for a finding of invalidity of any of the relevant claims but it is relevant as a squeeze.
In terms of the relevant claims, claim 4 is not said to be independently valid. Also claims 6 and 7 stand or fall together.
Terminology
The critical feature of claim 1 is the requirement for at least 99% fucose. In evidence there were at least five different ways of calculating that quantity. It is sometimes important to appreciate which method is being used when referring to a given number. One may not know of course. Although it will make things a bit cumbersome at times, when necessary the figures will be used with a label. The detailed explanations for the labels will come in context. The labels are:
i) “99%-Roche” – means 99% calculated using the method advanced by Roche as its primary case on construction of claim 1.
ii) “99%-Takeda” – that means 99% calculated using the method advanced by Takeda as its primary case on construction of claim 1.
iii) “99%-TRM” – means 99% calculated using the method advanced by Roche as a modified version of the Takeda method. It is Roche's fall back alternative case for the construction of claim 1.
iv) “99%-Shields” – means 99% calculated by the method used in a seminal common general knowledge paper called Shields.
A further method (“99%-Morris”) was advanced by the professor in his oral evidence.
The witnesses
Takeda called four fact witnesses: Caterina Farnleitner, Prof. Friedrich Altmann, Pamela Brauer and Anne Kowal.
Ms Farnleitner is the Business Development Manager at InVivo BioTech Services GmbH. InVivo was engaged by Takeda to source a publicly available sample of deposited “clone 5” for the purposes making a recombinant antibody in accordance with the patent. Ms Farnleitner explains where the clones were sourced, how the cells were stored upon receipt, how they were revitalised and that they were cultured and the expressed recombinant antibody was purified, as described in Part A of Takeda's Notice of experiments. Ms Farnleitner's evidence was not cross-examined.
Prof. Altmann is a Professor of Natural Resources and Life Sciences at BOKU university in Vienna. He was engaged by Takeda to perform an LCMS peptide map analysis on the “clone 5” samples sent to him by InVivo in May 2018. His evidence is to confirm that peptide map analysis was performed under his supervision as described in Part B of Takeda's Notice of experiments. Prof. Altmann was not cross-examined.
Ms Brauer is a Scientist at Millennium Pharmaceuticals. Millennium developed Entyvio and were acquired by Takeda. From around 2004 Ms Brauer was part of the team responsible for supporting the development of vedolizumab into a commercial product. Ms Brauer is the scientist who conducted the experiments to develop and screen for the CHO cell line that became the cell line that was ultimately used in the...
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