Glaxosmithkline UK Ltd v Wyeth Holdings Llc
| Jurisdiction | England & Wales |
| Judge | Mr Justice Henry Carr |
| Judgment Date | 12 May 2016 |
| Neutral Citation | [2016] EWHC 1045 (Ch) |
| Docket Number | Case No: HP-2015000002 |
| Court | Chancery Division |
| Date | 12 May 2016 |
[2016] EWHC 1045 (CH)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Royal Courts of Justice
7 Rolls Buildings
Fetter Lane
London
EC4A 1NL
The Hon Mr Justice Henry Carr
Case No: HP-2015000002
Thomas Mitcheson QC and Stuart Baran (instructed by Rouse Legal) for the Claimant
Michael Tappin QC and William Duncan (instructed by Marks & Clerk Solicitors LLP) for the Defendant
Hearing dates: 9–11, 14–15.17–18 March 2016
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.
| Introduction | 1 |
| The issues | 4 |
| Technical Background | 5 |
| Meningitis | 6 |
| Neisseria meningitidis | 8 |
| Capsular Polysaccharide | 10 |
| Assays | 14 |
| The witnesses | 15 |
| The Microbiologists | 15 |
| The experts on PCR and sequencing | 23 |
| Witnesses of fact | 24 |
| The Skilled Addressee | 25 |
| The common general knowledge | 28 |
| Legal Principles | 28 |
| The serum bactericidal assay | 31 |
| OMVs and PorAs | 36 |
| Attitudes of the skilled addressee to new vaccine candidates | 40 |
| Reverse vaccinology | 44 |
| The Patent | 48 |
| The examples | 54 |
| Example 1 | 55 |
| Example 2 (and Example 6) | 58 |
| Example 3 | 59 |
| Example 5 | 60 |
| Example 8 | 61 |
| Example 9 | 65 |
| Example 10 | 66 |
| The claims alleged to be independently valid | 67 |
| Claim construction | 69 |
| Claim 1 | 70 |
| Claim 3 | 72 |
| Claims 18–20 | 81 |
| Infringement | 90 |
| Plausibility – AgrEvo obviousness/insufficiency | 93 |
| Legal principles | 94 |
| General observations on plausibility | 95 |
| The AgrEvo obviousness allegation | 101 |
| Sequence homology and breadth of claim | 102 |
| Non-lipidated 2086 proteins | 105 |
| At least one PorA protein | 109 |
| Adjuvants | 112 |
| Added Matter | 115 |
| Legal principles | 115 |
| Application to the facts | 120 |
| Priority | 128 |
| Legal principles | 128 |
| The first priority date | 129 |
| The combination of 2086 and PorA(s) | 129 |
| Sequence clusters | 133 |
| Mucosal delivery | 137 |
| Lack of plausibility | 140 |
| The second priority date | 142 |
| Novelty | 154 |
| Legal principles | 154 |
| Novelty over 885 (pre-PD1) | 156 |
| Individualised disclosure | 157 |
| Novelty over the Cuban Vaccine (pre-PD1) | 170 |
| Did the Cuban Vaccine contain fHbp before the priority date? | 174 |
| If fHbp had been present in the Cuban Vaccine, would analysis in 2001 have identified it? | 185 |
| Could the skilled person have identified the presence of fHbp in the Cuban Vaccine before the priority date? | 199 |
| Would the skilled person have been able to reproduce the Cuban Vaccine without undue burden? | 205 |
| In relation to claims 18–20, if fHbp was present, did it make any material contribution to the immune reaction produced by the Cuban Vaccine? | 209 |
| Conclusion in respect of the Cuban Vaccine | 211 |
| Novelty over Andersen (pre-PD1) | 212 |
| Novelty over 869 (between PD1 and PD2) | 222 |
| Novelty/obviousness over Bernfield and Farley posters/abstracts (between PD2 and filing date | 232 |
| Inventive step | 240 |
| Legal principles | 240 |
| Disclosure of 922 | 241 |
| Alleged squeezes | 258 |
| Conclusion | 259 |
Introduction
This is a claim by GlaxoSmithKline UK Limited ("GSK") for revocation and a declaration of non-infringement in respect of European Patent (UK) 2,343,308 ("the Patent"). Wyeth Holdings LLC ("Wyeth"), a subsidiary of Pfizer Inc., is the registered proprietor of the Patent. GSK markets a Neisseria meningitidis B ("Men B") vaccine product in the United Kingdom under the trade mark Bexsero. Wyeth counterclaims for infringement of the Patent by Bexsero.
The Patent claims, amongst other things, a composition comprising a protein which is now known as factor H binding protein ("fHbp"), which is referred to in the Patent as "2086 protein". The claimed composition additionally comprises at least one PorA protein. There are five recombinant Men B antigens in Bexsero, one of which is fHbp. Bexsero also comprises an outer membrane vesicle ("OMV") fraction containing, amongst other proteins, PorA protein.
Wyeth has also developed a Men B vaccine known as Trumenba, which has not yet received approval in Europe. In light of the public health requirement for effective vaccines against Men B, Wyeth does not seek injunctive relief if it succeeds in its counterclaim.
The issues
There are numerous issues, arising, in particular, from GSK's grounds of invalidity, which may be summarised as follows:
i) Entitlement to the first claimed priority date of 11 October 2001 ("PD1"). In particular, GSK alleges that there is insufficient basis in US 328101 ("the first priority document") for the claimed invention of 2086 and PorA.
ii) Entitlement to the second claimed priority date of 30 August 2002 ("PD2"). In particular, GSK relies on the absence of sequence listings from US 406934 ("the second priority document").
iii) Anticipation by:
a) WO 01/ 52885 A1, Outer membrane vesicle comprising N. meningitidis serogroup B outer membrane proteins ("885");
b) VA-MENGOC-BC, a vaccine developed at the Finlay Institute in Havana, Cuba and administered to patients before PD1 ("the Cuban Vaccine");
c) Andersen SR, Liang B, Guthrie T, Wong SYC, Hous S, Hyland L (2000), Immune responses to meningococcal outer membrane vesicles after intranasal immunisation (the abstract of a poster presented at the Twelfth International Pathogenic Neisseria Conference 12–17 November 2000 in Galveston, Texas) ("Andersen");
d) If PD1 is lost, WO 03/009869 A1, Vaccines comprising aluminium adjuvants and histidine ("869"); and
e) If PD2 is lost, two posters by Wyeth, presented at the Twelfth International Pathogenic Neisseria Conference ("IPNC") in Oslo, Norway in September 2002, which GSK contends amount to a single disclosure ("the Bernfield and Farley posters and abstracts").
iv) Obviousness over:
(a) WO 01/64922 A2, Heterologous Expression of Neisserial Proteins ("922");
(b) If PD2 is lost, the Bernfield and Farley posters and abstracts.
v) AgrEvo obviousness – GSK alleges that the Patent claims a mere arbitrary choice from a host of possible solutions which cannot involve an inventive step.
vi) Insufficiency (squeeze) – GSK alleges that any technical contribution which is new and not obvious is not rendered plausible or sufficient by the Patent. It claims that there is a squeeze between the construction of the claims (and what they contribute) and the prior art.
vii) Insufficiency (general) — GSK alleges that the specification does not enable (and/or does not render plausible) the claims, for a variety of reasons which I consider in detail below.
viii) Added Matter – GSK alleges that Wyeth made a series of selections from lists on amending the application as filed, which add subject matter. GSK also relies upon an alleged squeeze between the added matter attack and the disclosure of the prior art.
ix) Infringement – the issue relates to claim 3 of the Patent and its correct construction, which is amongst the claims alleged by Wyeth to be independently valid. This issue has relevance in the event that this is the only valid claim of the Patent.
Technical Background
The parties agreed a Technical Primer which was of considerable assistance. This was supplemented by expert evidence. I set out below a summary of certain technical aspects which may be helpful in understanding the issues in this case.
Meningitis
Meningitis is a severe and life-threatening disease, often sudden in its onset, where the membranes surrounding the brain and spinal cord become inflamed. For survivors, it can result in long term effects including brain damage, seizures, deafness and paralysis, and may entail the amputation of limbs and digits. One of the major causes of bacterial meningitis is the meningococcus Neisseria meningitidis. About two thirds of cases occur in the first five years of life (with peak prevalence in the first year); a second peak is observed in adolescents.
Prior to antibiotic treatment becoming available, approximately 70% to 90% of those who contracted bacterial meningitis died from the disease. The overall figure has fallen over the last 50 years; however, despite the advancement of modern antibiotic treatments, the overall mortality rate for meningococcal disease has remained high: between 5% and 15% of those who contract the disease. In the early 2000s, Neisseria meningitidis was still one of the leading causes of childhood deaths from infection in many industrialised countries and has been responsible for a number of devastating epidemics around the world. Despite the availability of effective antibiotics, meningococcal disease to this day remains a substantial health problem in most countries.
Neisseria meningitidis
Neisseria meningitidis is a Gram-negative bacterium from a genus of bacteria that commonly colonises human mucosal surfaces. The cell envelope of N. meningitidis comprises a number of layers as depicted in Figure 1 of the Technical Primer, reproduced below:
Figure 1: Schematic diagram of the cell envelope of N. meningitidis (from Gillespile and Hawkey (2006), Principles and practice of clinical Bacteriology (Second Edition), John Wiley & Sons Ltd)
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