Hospira UK Ltd v Genentech Inc.
| Jurisdiction | England & Wales |
| Judge | Mr. Justice Birss,Mr Justice Birss |
| Judgment Date | 21 November 2014 |
| Neutral Citation | [2014] EWHC 3857 (Pat) |
| Docket Number | Case No: HP-2013-000004 |
| Court | Chancery Division (Patents Court) |
| Date | 21 November 2014 |
[2014] EWHC 3857 (Pat)
Mr Justice Birss
Case No: HP-2013-000004
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Royal Courts of Justice, Rolls Building
Fetter Lane, London, EC4A 1NL
Richard Meade QC, Tom MitchesonQC (instructed by Taylor Wessing) for the Claimant
Michael Tappin QC and Mark Chacksfield (instructed by Marks & Clerk Solicitors) for the Defendant
Hearing dates: 14th, 15th, 16th, 17th, 20th and 21st October 2014
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 | Paragraph |
| Introduction | 1 |
| The issues | 8 |
| The witnesses | 17 |
| The skilled person | 36 |
| The common general knowledge | 37 |
| The common general knowledge of the clinician | 38 |
| The common general knowledge of the formulator | 47 |
| Common general knowledge regarding trehalose | 66 |
| The patent specification | 82 |
| Claim construction | 88 |
| Extension of scope | 105 |
| Product by process claims | 125 |
| Claim 1 of 628 as a product by process claim | 148 |
| Clarity | 161 |
| Added matter | 168 |
| Protein concentration | 175 |
| Lyophilisation conditions | 191 |
| Benzyl alcohol and multi use | 193 |
| Consisting of | 197 |
| Obviousness | 198 |
| Common general knowledge alone | 202 |
| Carter | 203 |
| Draber | 244 |
| Insufficiency | 245 |
| Conclusion | 246 |
| Annexes |
Introduction
This is another patent case between Hospira and Genentech about patents relating to the landmark breast cancer drug known as Herceptin. The active ingredient in Herceptin is trastuzumab. Trastuzumab targets the HER2 receptor. Over expression of this receptor had been associated with poor prognosis in breast cancer. This is the second Herceptin case I have decided in 2014. The first one was [2014] EWHC 1094 (Pat). The two cases are entirely distinct. This case relates to a priority date (14 th March 1996) which is much earlier than any of the priority dates in issue in the earlier case.
The patents are EP (UK) 1 516 628 and EP (UK) 2 275 119. They are divisionals from the same parent, filed on 23 rd July 1996. Their title is "Stable Isotonic lyophilized protein formulation". Priority is claimed from two applications but it is common ground that the correct priority date is 14 th March 1996.
The patents are concerned with the lyophilised (i.e. freeze dried) formulation of antibodies. Two antibodies are referred to in the specification. One is trastuzumab. It is called huMAb4D5–8 in the specification. The other antibody in the patents is rhuMabE25. The patents explain rhuMabE25 may have a role to play in treating allergy.
At the priority date phase III clinical trials of Herceptin were in the process of being set up. The phase II trials had been completed and results published in an abstract presented at the 1995 conference of the American Society for Clinical Oncology ("ASCO"). The abstract is Baselga et al " Phase II study of recombinant anti-HER2 monoclonal antibody (rhuMAb HER2) in stage IV breast cancer" Proc. of ASCO, 1995, 14, p.103, abstract no. 113. It was not until 1998 that the phase III results were announced and the drug was approved by the FDA. European approval came later.
Trastuzumab itself is protected by a different patent, EP (UK) 0 590 058 and supplementary protection certificate SPC/GB04/015. That SPC expired on 29 th July 2014. Hospira wishes to sell generic trastuzumab now that the SPC has expired. Hospira needs a generic authorisation based on the existing marketing authorisation for Herceptin and argued that the regulatory framework applicable to such biosimilar products at least strongly encourages, if it does not actually require, the generic to use the same formulation as the originator's product. This action is to clear the way.
Trastuzumab and rhuMAb E25 are monoclonal antibodies. Monoclonal antibodies are large protein molecules. Although by 1996 the pharmaceutical industry had had a long history of formulating small molecule drugs, the formulation of therapeutic proteins in general and antibodies in particular was not so well established. This is an important factor in this case.
Formulation patents are one of the kinds of pharmaceutical patent sometimes called second-generation patents, because they do not relate to the drug itself. Such patents are sometimes criticised as an attempt by the pharmaceutical company to unduly prolong its monopoly, after the first generation patent for a drug itself has expired (so called evergreening). There were hints of that in Hospira's submissions. However there is no legal principle that formulation patents should be treated in any way differently from any other patent. The principles applicable are the same.
The issues
Genentech has applied to amend both patents and before this court does not seek to defend the validity of the relevant claims as granted. Thus for the purposes of this case I need only be concerned with the proposed amended claims. They are set out in annexes 1 and 2 for 628 and 119 respectively. Claims 1 to 7 of 628 are sought to be deleted and replaced by new claims 1 and 2. The remaining claims are to be renumbered. All granted claims of 119 are sought to be deleted and replaced by new claims 1 to 4. Genentech contends that each of the newly proposed claims (1 and 2 of 628 and 1 to 4 of 119) are independently valid.
It is convenient to use the 628 patent specification as the relevant specification both for the claims of 628 itself but also for 119. There are only irrelevant differences between the specification of the 119 patent and the 628 patent. The real difference is simply the claims. From now on unless the context otherwise requires I will refer to the specification of the 628 patent only.
The claims refer to three excipients in the formulation as well as trastuzumab. They are polysorbate 20, histidine and trehalose. A major issue in this case is about the status of these three excipients (if any) in the common general knowledge of the skilled person.
Hospira's primary case is that each of the newly proposed claims (1 and 2 of 628 and 1 to 4 of 119) is obvious over common general knowledge alone.
Hospira also relies on two items of prior art, Carter and Draber:
i) "Carter" refers to two papers which it is agreed should be read together since they cross-refer. They are a 1994 paper " Towards an immunotherapy for p185 HER2 overexpressing tumors" by Carter et al published in Antigen and Antibody Molecular Engineering in Breast Cancer Diagnosis and Treatment and a PNAS paper published in 1992 called " Humanization of an anti-p185 HER2 antibody for human cancer therapy" by Carter et al.
ii) "Draber" is a 1995 paper " Stability of monoclonal IgM antibodies freeze-dried in the presence of trehalose", Journal of Immunological Methods 181 (1995) 37–43.
Hospira also contends that new claims 1 to 4 of the 119 patent are insufficient. This point is advanced as a squeeze relative to Hospira's primary case that those claims are obvious.
Finally Hospira contends that none of the amendments proposed should be allowed. This is on four grounds: extension of scope, a point on product by process claims, clarity and added matter.
Genentech denies the claims are obvious, denies the claims of 119 are insufficient and contends that the amendments are allowable. Genentech also advances an alternative amendment to deal with the point on extension of scope. This is to replace the word "comprising" in each claim with the words "consisting of". This amendment was properly foreshadowed with an application before trial.
If I find that all the claims proposed for 119 are not allowable as amendments or are invalid, then that patent must be revoked. However since Hospira does not challenge the validity of granted claims 8 to 11 of 628, it follows that if the attacked claims (newly proposed claims 1 and 2) are not allowable amendments and/or invalid then the consequence is that the 628 patent must be amended to delete granted claims 1 to 7, leaving behind claims 8 to 11 as granted. They would need to be renumbered.
The witnesses
Hospira relied on the evidence of Prof Gavin Halbert and Prof Robert Leonard.
Since 1992 Prof Halbert has been Director of the Cancer Research UK Formulation Unit at the Strathclyde Institute of Pharmacy and Biomedical Sciences at the university. Amongst other things, this role requires overall pharmaceutical and scientific management and active participation in the formulation of new cytotoxic agents for clinical trials. He has maintained a teaching role at the university since 1984 covering, amongst other things, formulation and biopharmaceutics.
Genentech submitted that Prof Halbert had spent his entire career at the University of Strathclyde and had no experience in the pharmaceutical industry. Genentech also pointed out that Prof Halbert had not formulated any protein drugs by March 1996 and work he had mentioned in his report on an antibody ( 105AD7) was not formulation work because it had been formulated already before he was involved. Genentech pointed out that Prof Halbert had not produced a lyophilised formulation of a therapeutic protein for use in a clinical trial. It submitted he lacked the necessary experience to assist in this case. I reject Genentech's submission. Prof Halbert has a wealth of experience in formulation science, had relevant experience and understanding relating to lyophilisation, relating to proteins and working with industry. Overall he has ample experience to assist.
Genentech also criticised Prof Halbert's approach to the use of...
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