Hospira UK Ltd v Genentech Inc.
| Jurisdiction | England & Wales |
| Judge | The Hon. Mr Justice Birss,Mr Justice Birss |
| Judgment Date | 10 April 2014 |
| Neutral Citation | [2014] EWHC 1094 (Pat) |
| Docket Number | Case No: HC12C03487 |
| Court | Chancery Division (Patents Court) |
| Date | 10 April 2014 |
[2014] EWHC 1094 (Pat)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Royal Courts of Justice, Rolls Building
Fetter Lane, London, EC4A 1NL
Mr Justice Birss
Case No: HC12C03487
Richard Meade QC, Tom Mitcheson and Jeremy Heald (instructed by Taylor Wessing) for the Claimant
Michael Tappin QC and Mark Chacksfield (instructed by Marks & Clerk) for the Defendant
Hearing dates: 6th, 7th, 10th, 11th, 12th, 13th, 14th, 18th and 19th March 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 | 12 |
| The witnesses | 22 |
| The 115 patent | 32 |
| The skilled person and the common general knowledge | 32 |
| The 115 patent specification | 43 |
| Claim construction | 56 |
| Obviousness | 65 |
| Obviousness – the FDA label | 68 |
| Pharmacokinetics | 84 |
| The reaction of the clinician | 114 |
| Obviousness — conclusion | 118 |
| Sufficiency | 119 |
| Priority | 144 |
| The 455 patent | 163 |
| The skilled team | 163 |
| Common general knowledge | 164 |
| The 455 patent specification | 174 |
| Claim construction | 185 |
| Novelty | 194 |
| Andya | 195 |
| The disclosure of Andya compared to claim 1 | 202 |
| Obviousness | 218 |
| Waterside | 219 |
| Andya – obviousness | 243 |
| Obviousness over common general knowledge in general | 248 |
| Obviousness over common general knowledge based on Protein A | 249 |
| Declaration of non-infringement | 264 |
| Conclusion | 268 |
Introduction
1. Like all cancers, breast cancer is not a single disease. Much depends on the particular kind of cells which have become cancerous. The conventional therapeutic approaches were surgery, radiotherapy and chemotherapy or combinations of these various options. The agents used for chemotherapy were and are powerful drugs which are cytotoxic (i.e. cell killing). These drugs include Taxol (the trade name of paclitaxel), 5-flourouracil and many others. Generally these agents attack rapidly dividing cells. This will include cancer cells but will also include other rapidly dividing cells in the body. That is why hair loss can be a side effect of chemotherapy.
2. Some types of breast cancer can be treated with hormone therapy (such as Tamoxifen) but other types of breast cancer do not respond to hormone therapy. One class of breast cancers which was particularly difficult to treat was those in which the cells over-expressed a receptor known as HER2. The HER2 receptor (also known as the ErbB2 receptor) belongs to a class of receptors in the epidermal growth factor receptor (EGFR) family. 20% to 30% of breast cancers were classified as HER2 positive. They had a poor prognosis.
3. In general in pharmacology higher selectivity means that a drug can be given at an effective dose with fewer side effects. In other words the margin between safety and efficacy generally improves as selectivity increases. Thus an agent which could be targeted more closely to cancer cells in particular could be given at a higher dose in order to improve its efficacy, without compromising safety.
4. A major breakthrough in breast cancer therapy in recent years has been the availability of an agent known as Herceptin. Herceptin is the brand name of a monoclonal antibody called trastuzumab. This antibody targets the HER2 receptor. It was developed by Genentech and Roche.
5. Trastuzumab is different from conventional chemotherapeutic agents in a number of ways. Two important points stand out in the context of this case. First, it is highly targeted to a particular group of cancer cells, which in general terms means that the window between safety and efficacy is improved. Second, trastuzumab was at the time a new class of agent — a monoclonal antibody. Whereas conventional drug molecules are small, antibody molecules are large proteins. This difference has consequences relating to the manufacture and formulation of the drug and may also affect the manner in which the drug behaves in the body.
6. Before Herceptin was approved in the USA and then later in Europe, those working in oncology had heard about it. The positive results of a Phase II clinical trial were published in March 1996 and in May 1998 the results of the Slamon trial were published at ASCO. In September 1998 Herceptin was approved by the FDA in the United States and in Europe it was approved in August 2000. Herceptin has been and remains a huge success. Worldwide sales from 1999 to 2013 totalled 49 billion Swiss Francs (£33 billion at present exchange rates) which includes European sales from 2010 to 2013 of 8 billion Swiss Francs (£5 billion).
7. Hospira sells generic medicines, particularly in the cancer field. It wishes to sell a generic form of trastuzumab in the UK. Hospira does not challenge the basic underlying patent held by Genentech on trastuzumab (EP 0 590 058). The supplementary protection certificate for that patent (SPC/GB04/015) expires on 28 th July 2014. Hospira wishes to sell its generic trastuzumab product after that date. Genentech holds a number of patents of a later vintage which Hospira might infringe. Hospira contends that the patents are invalid and has brought this action to invalidate them. There is also a claim for a declaration of non-infringement in relation to one patent. When the case began there were three patents in suit but Genentech offered to surrender one of them a few months ago.
8. The two patents in suit are EP 1 210 115 entitled “Dosages for treatment with Anti-ErbB2 antibodies” and EP 1 308 455 entitled “A composition comprising anti-HER2 antibodies”.
9. The application for the 115 patent was filed on 25 th August 2000 claiming priority from two US applications, the first being filed on 27 th August 1999. It was granted on 5 th August 2009. The claims concern a dosing regimen for trastuzumab.
10. The application for the 455 patent was filed on 3 rd May 1999 claiming priority from a US filing on 6 th May 1998. It was granted on 22 nd March 2006. The claims concern a composition of trastuzumab with less than certain thresholds of certain impurities.
11. Both patents were opposed in the EPO. In both cases the Opposition Division has held the patent is invalid. Both are presently under appeal before the Technical Board of Appeal. The parties did not know when the appeals are likely to be heard. Even if either appeal succeeds it may not bring the EPO proceedings to an end because in that event the Board may remit the case to the Opposition Division.
The issues
12. The 115 patent relates to the use of a particular dosing schedule of trastuzumab to treat breast cancer. The dosing schedule involves administering trastuzumab every three weeks whereas the existing schedule was weekly.
13. Hospira contends that the claims of the 115 patent are not entitled to the earliest claimed priority date. Genentech maintains the claim to priority but accepts that if priority is lost the patent is invalid. Hospira also contends that even if entitled to priority, the patent is invalid. The invention is said to be obvious over the state of the art at the earliest priority date. The key item of prior art is the FDA label for Herceptin which was published when the product was approved by the FDA. Genentech accepts the FDA label is prior art but does not agree it makes the claimed dosing regimen obvious.
14. Hospira's primary case is that the invention is obvious but if the claims of the 115 patent do involve an inventive step then Hospira contends the patent is insufficient. Hospira argues essentially that if it was inventive to conduct a clinical trial over what was known from the prior art then the same logic will apply starting from the patent and the result must be insufficiency. Although it is true that the patent specification does contain more data than was in the state of the art, Hospira point out that the patent specification does not contain the result of a clinical trial of the claimed dosing regimen. Genentech does not agree with this either as a matter of reasoning or on the facts. It points out that the claimed dosing regimen is in fact safe and effective to treat the disease. Genentech also argues that, unlike the position over the prior art, a skilled person reading the patent in the light of their common general knowledge will have sufficient confidence to conduct a clinical trial.
15. Finally Hospira advanced a case based on added matter but by closing it became clear that the point does not need to be addressed.
16. The only relevant claim of the 115 patent is claim 1. In response to the way in which the arguments on priority developed, Genentech made an application to amend the claim to include a reference to “intravenously”. By the closing this was the only claim to be focussed upon.
17. The 455 patent is concerned with purifying trastuzumab and claim 1 relates to a composition of trastuzumab with less than about 25% of certain acidic variants of the antibody. Hospira argues that claims 1, 2 and 4 lack novelty over a previous Genentech PCT application PCT/US96/12251 (“Andya”) which was published as WO 97/04801 on 13 th February 1997 and entitled “Stable Isotonic Lyophilised Protein Formulation”. Andya describes stability tests on various trastuzumab formulations. Hospira contends Andya is an enabling disclosure of a composition of trastuzumab with 82% native protein and therefore no more than 18% acidic variants. Genentech does not agree. In addition to a point about exactly what is disclosed, the main debate over Andya concerns enablement. Hospira also contends that Andya makes...
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