Hospira UK Ltd v Genentech Inc.
| Jurisdiction | England & Wales |
| Judge | The Hon Mr Justice Arnold,Mr Justice Arnold |
| Judgment Date | 24 June 2015 |
| Neutral Citation | [2015] EWHC 1796 (Pat) |
| Court | Chancery Division (Patents Court) |
| Docket Number | Case No: HP-2014000034 |
| Date | 24 June 2015 |
[2015] EWHC 1796 (Pat)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Rolls Building
Fetter Lane, London, EC4A 1NLL
The Hon Mr Justice Arnold
Case No: HP-2014000034
Richard Meade QC, Thomas MitchesonQC and Jeremy Heald (instructed by Taylor Wessing LLP) for the Claimant
Michael Tappin QC and Mark Chacksfield (instructed by Marks & Clerk Solicitors LLP) for the Defendant
Hearing dates: 8–10, 12 June 2015
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 | 1–8 |
| The witnesses | 9–16 |
| The Patent | 17–26 |
| The claims | 27–28 |
| The skilled person | 29–31 |
| Common general knowledge | 32–50 |
| Antibody therapies in general | 35 |
| HER2 overexpression and HER2 as an antibody target | 36 |
| Combination therapy | 37 |
| Mouse xenograft models | 38–40 |
| Phase I, II and III trials | 41 |
| Clinical endpoints | 47 |
| Response rates | 49 |
| The success rate in drug development generally | 50 |
| Construction | 51–59 |
| Baselga 97 | 60–80 |
| HER2/c-erbB-2/neu in Breast Cancer | 62 |
| Role of Monoclonal antibodies | 63 |
| HER2 Overexpression as a Predictor of | 64 |
| Response to Taxanes | |
| Dose-Response Effects to Anthracyclines | 65 |
| HER2 Overexpression and Taxane Sensitivity | 66 |
| Tentative Results With Polyclonal Antibody | 67 |
| Paclitaxel and the Signal Transduction Pathway | 68–69 |
| Combined Therapy with Anti-HER2 Agents and Chemotherapy | 70–72 |
| A "Humanised" Antibody | 73 |
| Anti-HER MoAb Combined With Chemotherapy | 74 |
| Paclitaxel/Doxorubicin/rhuMoAb HER2 Regimen | 75 |
| Cisplatin/rhuMoAb HER2 Therapy | 76 |
| Phase III Study of rhuMoAB HER2 | 77–78 |
| Combined With Chemo | |
| Future Directions | 79 |
| Conclusions | 80 |
| Novelty | 81–104 |
| The law | 81–93 |
| Assessment | 94–98 |
| The decision of the Board of Appeal concerning the Patent | 99–104 |
| Obviousness | 105–134 |
| The law | 105–115 |
| Assessment | 116–134 |
| Would the trial be burdensome | 120 |
| Would the trial present a risk to patients? | 121 |
| What alternative options were there? | 122 |
| The scientific context | 123 |
| No lions in the path | 124 |
| Failure rates in Phase III trials | 125 |
| How would the skilled person view the results reported in Baselga 97? | 126–131 |
| Secondary evidence | 132–133 |
| Conclusion | 134 |
| Conclusion | 135 |
Introduction
In this action the Claimant ("Hospira") seeks revocation of the Defendant's ("Genentech's") European Patent (UK) No. 1 037 926 ("the Patent"). The Patent relates to the use of trastuzumab in combination with a taxane for the treatment of HER2-positive breast cancer. HER2 (also referred to as ErbB2, among other names) is a gene the overexpression of which is associated with a particularly aggressive form of breast cancer. Trastuzumab, which is marketed by Genentech under the trade mark Herceptin, is a humanised anti-HER2 monoclonal antibody. The taxanes (also referred to as "taxoids") are a class of chemotherapeutic agents which include paclitaxel (marketed by Bristol Myers-Squibb under the trade mark Taxol) and docetaxel (marketed by Sanofi-Aventis under the trade mark Taxotere).
There is no challenge to the claimed priority date of the Patent of 12 December 1997. The only grounds of invalidity relied on by Hospira are that the claims lack novelty, alternatively an inventive step, in the light of a single item of prior art, namely Baselga et al, "HER2 Overexpression and Paclitaxel Sensitivity in Breast Cancer: Therapeutic Implications", Oncology, 11, Supp. 2, 43–48 (March 1997) ("Baselga 97"). Baselga 97 describes, among other things, a Phase III trial of trastuzumab in combinations with paclitaxel and other agents, but does not disclose any results from that trial.
The Patent contains a summary of the results of the trial, which show that trastuzumab in combination with paclitaxel yields a substantial increase in time to disease progression and tumour response rates in HER2-positive metastatic breast cancer patients compared to paclitaxel alone. It also shows that the combination of trastuzumab and paclitaxel achieves those clinical benefits without a significant increase in severe adverse events, and in particular without the cardiac side effects that are observed when trastuzumab is combined with anthracyclines.
The results contained in the Patent were first publicly presented at the American Society for Clinical Oncology ("ASCO") meeting in Los Angeles in May 1998, where they generated considerable excitement. They led to the approval of Herceptin as a first line treatment for HER2-positive breast cancer in combination with paclitaxel by the United States Food and Drug Administration on 25 September 1998. This was followed by approval in Switzerland on 29 July 1999 and in the European Union on 28 August 2000. Herceptin is now the standard of care worldwide for the majority of patients with HER2-positive breast cancer, and is usually given in combination with a taxane. It has transformed the treatment of HER2-positive breast cancer and has been a hugely successful product.
Hospira has not challenged the validity of the basic patent for the amino acid sequence of Herceptin (European Patent No. 0 590 058) or its associated Supplementary Protection Certificate (SPC/GB04/015). The SPC expired on 29 July 2014. Now that Genentech's basic monopoly has expired, Hospira wishes to market biosimilar trastuzumab. Hospira has therefore brought a series of actions to clear the way by revoking a number of other patents owned by Genentech relating to trastuzumab.
The first action related to three patents for various inventions, one of which Genentech surrendered before trial. The other two were held to be invalid by Birss J following a trial in March 2014 ( [2014] EWHC 1094 (Pat)). Genentech appealed the decision in respect of one of those patents. The appeal was heard by the Court of Appeal in January 2015 and dismissed ( [2015] EWCA Civ 57).
The second action related to two patents for lyophilised formulations of trastuzumab, both of which were held to be invalid by Birss J following a trial in October 2014 ( [2014] EWHC 3857 (Pat)). Genentech has appealed that decision, and the appeal is currently pending.
The Examining Division of the European Patent Office refused to grant the Patent, holding that it would lack novelty over Baselga 97, but that decision was reversed by the Technical Board of Appeal. As a result, the Patent was not granted until 15 January 2014. The Patent has been opposed at the EPO, but the opposition proceedings are at an early stage.
The witnesses
Hospira's expert was Professor Hilary Calvert, who is Emeritus Professor of Cancer Therapeutics at the University College London ("UCL") Cancer Institute. He obtained a degree in Medical Sciences and Mathematics from the University of Cambridge in 1969 and completed his clinical studies at UCL in 1972. Having held a number of clinical posts, he was Research Fellow at the Royal Marsden Hospital from 1975 to 1977, where he conducted clinical research into the chemotherapeutic treatment of cancers. From 1977 to 1989 he was successively Lecturer, Senior Lecturer and Reader in Clinical Pharmacology at the Institute for Cancer Research and Honorary Senior Registrar and then Honorary Consultant at the Royal Marsden. In 1981 he obtained an MD for research into antifolates and their application in cancer chemotherapy. From 1989 to 2009 he was Professor of Medical Oncology and Clinical Director of the Northern Institute for Cancer Research at the University of Newcastle upon Tyne and Honorary Consultant at the Northern Centre for Cancer Care. From 2009 until 2014 he was the Director of Cancer Drug Discovery and Development at UCL. He was also a Visiting Professor in the Department of Mathematics and Statistics at the University of Newcastle upon Tyne from 2009 to 2012.
Although Prof Calvert has specialised in ovarian cancer, he has maintained a clinical and research interest in breast cancer throughout his career. He was personally responsible for the diagnosis and treatment of breast cancer patients in 1991–1992. He has also led clinical trials in breast cancer (including at least one trial involving trastuzumab). He has 15 publications in the area of breast cancer to his credit, out of some 230. He was made a Fellow of the Royal College of Physicians in 1988 and has received a number of awards, including the British Oncological Association Lifetime Achievement Award in 2009 and the European Society of Medical Oncology Lifetime Achievement Award in 2010. He has served on numerous advisory and editorial boards and committees.
Counsel for Genentech accepted that Prof Calvert was an eminent scientist who had done his best to assist the court in his evidence. He submitted, however, that Prof Calvert's expertise was not as relevant to this case as that of Genentech's expert for three reasons. First, because he was not a breast cancer specialist. Secondly, because his involvement with trastuzumab was limited. Thirdly, because his research interests were focussed on the early stages of drug discovery and development.
In my judgment Prof Calvert was appropriately qualified to give expert evidence in this case. In particular, so far as the first two points are concerned, I am satisfied that Prof Calvert did have sufficient expertise in breast cancer and trastuzumab to assist the court with regard to the knowledge and perceptions of the person skilled in the art. So far as the third point is concerned, I do not accept that Prof...
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