Teva Pharmaceutical Industries Ltd and another v Merrell Pharmaceuticals Inc. and Others
| Jurisdiction | England & Wales |
| Judge | MR JUSTICE WARREN,Mr Justice Warren |
| Judgment Date | 12 October 2007 |
| Neutral Citation | [2007] EWHC 2276 (Ch) |
| Court | Chancery Division |
| Docket Number | Case No: HC06C02304 & HC06C02305 |
| Date | 12 October 2007 |
[2007] EWHC 2276 (Ch)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Royal Courts of Justice
Strand, London, WC2A 2LL
Mr Justice Warren
Case No: HC06C02304 & HC06C02305
Antony Watson QC & Michael Tappin (instructed by Taylor Wessing) for the Claimants
Andrew Waugh QC & Thomas Hinchliffe (instructed by Bird & Bird) for the Defendants
Hearing dates: 24th,25th,26th, & 30th April 2007
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. This case concerns an anti-histaminic drug called terfenadine and its acid metabolite, terfenadine carboxylate, which also has the generic name fexofenadine. Terfenadine features in litigation which found its way to the House of Lords: see Merrell Dow v Norton [1996] RPC 76. As Lord Hoffmann described the position in paragraph 1 of his speech:
“Merrell Dow Pharmaceuticals Inc. is a U.S. company with a United Kingdom subsidiary. I shall call them both “Merrell Dow”. About 25 years ago Merrell Dow discovered an anti-histamine drug called terfenadine. It is used by people who suffer from hay fever and similar allergies and has the advantage that, unlike some other anti-histamines, it does not have the side-effect of making one drowsy. In 1972 Merrell Dow obtained a patent for terfenadine in the United Kingdom. After a period of extension under the Patents Act 1977, it finally expired in December 1992. Other pharmaceutical companies then started to make and market terfenadine.
In these proceedings Merrell Dow claims that their monopoly in terfenadine continues by virtue of a later patent which still has another 5 years to run. It was obtained in the following circumstances. After they had patented terfenadine, they did some research into the way it worked. They found that it passed through the stomach to be absorbed in the small intestine and was then 99.5% metabolised in the liver. This was why it had no side-effects. They analysed the chemical composition of the acid metabolite formed in the liver. Its chemical name is 4-[4(4-hydroxydiphenylmethyl-1-piperidinyl)-1- hydroxybutyl]-á, á-dimethylbenzene-acetic acid, but I shall call it the acid metabolite. No one had identified it before. So they patented the acid metabolite as claim 24 of a patent granted in 1980 for a number of related anti-histamine products. This is the patent in suit.”
2.
Terfenadine was sold as Triludan in the UK and as Seldane in the USA. It was launched on the market in the early 1980s – 1981 in Europe and 1985 in the US. It became the market leader so that, by 1992 when the patent was about to expire, over 100 million people had taken the drug, as is common ground.
3. Cetirizine [Zirtek], a competing product and another second-generation anti-histamine, was launched in Europe in 1988 but by 1992, had not been approved in the US for use as a new drug. Loratadine [Clarityn] another competing product and another second-generation anti-histamine, was launched in Europe in 1989 and again, by 1992, had not been approved in the US for use as a new drug.
4. The only known active metabolite of terfenadine is the metabolite identified by Lord Hoffmann. Like Lord Hoffmann, I shall refer to it as the acid metabolite.
5. In Merrell Dow v Norton, Merrell Dow sued companies selling terfenadine; they did so under the acid metabolite patent (GB 2 048 258 B) alleging that it was infringed because patients produced the acid metabolite in their livers. It was held that, so far as the claim to the acid metabolite included its manufacture by the action of terfenadine in the human body, the patent was invalid because the invention was not new: the production of the acid metabolite in the liver was an inevitable result of working the terfenadine patent.
6. I will come to the patents in suit in a moment. But in essence, the Defendants' alleged invention is using the acid metabolite to make a medicament for use as an anti-histamine, and to treat allergic rhinitis and urticaria. Teva says that it was clear in 1992 that the acid metabolite was sufficiently effective and safe to be used as an anti-histamine. The Defendants, however, say that by 1990, occasional cases of a particular type of cardiac arrhythmia known as “torsades de pointes (“TdP”) had been reported in patients who had, for a variety of reasons, impaired liver metabolism or who had taken excess doses of terfenadine. The Defendants say that it was inventive to administer the acid metabolite rather than terfenadine itself and thus avoid the cardiac side effects of terfenadine. They say that it was not obvious, either, to use the acid metabolite or obvious to try it.
7. It is in fact common ground that, as of 1992, terfenadine was known to be a very safe drug. Any issues surrounding the very rare cardiac side effects had been adequately addressed (as I shall explain later) by changes to the labelling following a meeting of the Food and Drug Administration Advisory Committee meeting once the issues had come to light. Mr Waugh, who appears with Mr Hinchliffe, for the Defendants, says that this has a major impact on the question of motivation and risk/benefit analysis which would inevitably accompany any decision to consider an alternative compound for development (whether the acid metabolite or any other compound).
8. It is also common ground that by 1992 it was well-known (i) that terfenadine was extensively metabolised on a first pass through the liver and that normally terfenadine was not present to any significant degree (greater than 10ng/ml) and (ii) that terfenadine would have been about 97% protein bound. There is dispute about what follows from that.
9. The defendant Aventis Inc (“Aventis”) is the patentee of one of the patents in suit. The defendant Sepracor Inc (“Sepracor”) is the patentee of the other two. I shall refer to them together as “the Patents”. The invention (if such it be) was made independently by Merrell Dow (the proprietor of the original terfenadine patent which was about to expire) and Sepracor. Merrell Dow held one patent (EP (UK) Nos. 0 639 976) which is now in the name of Aventis and has a priority date of May 1992. Sepracor has two patents (EP (UK) 0 701 443 and EP (UK) 0 815 860) which have priority dates of August 1992. I will refer to them as 976, 443 and 860 respectively.
10. The Claimants are part of the Teva group of companies. Teva is a generic pharmaceutical manufacturer and wishes to sell generic fexofenadine hydrochloride in the UK. In their opening skeleton argument, Mr Watson and Mr Tappin asserted that each of the Patents should be revoked, on similar grounds namely:
a.Obviousness over:
i.A 1990 paper by Monahan et al: Torsades de Pointes occurring in association with terfenadine use, Journal of the American Medical Association, December 5 1990, Vol 264. No 21 (“Monahan”).
ii.The 1992 (46th Edition) Physician's Desk Reference entry for terfenadine under its US trade marked name Seldane (“the 1992 PDR”).
iii.A 1991 abstract by Chen et al entitled “Block of Delayed Rectifier Potassium Current, Ik, by Terfenadine in Cat Ventricular Myocytes”, Journal of the American College of Cardiology, 1991; 17: 140A. (“Chen”).
iv.US patent 4,254,129 (“Carr”) issued 3 March 1981, which is the US equivalent of the patent considered by the House of Lords in Merrell Dow v Norton.
v.The common general knowledge.
b.Related objections to the validity of the claims in the so-called Swiss form, having regard to the decision of the Court of Appeal in Bristol-Myers Squibb v. Baker Norton [2001] RPC 1, namely:
i.lack of novelty over Carr, the 1992 PDR and the 976 application (published as WO 93/23047);
ii.the claims are to a method of medical treatment; and
iii.the claims are to a discovery.
11. As will be seen later, these attacks have been narrowed.
The Law
12. There is no dispute about the correct approach to construction, novelty and obviousness.
Construction
13. In Kirin Amgen v TKT [2005] RPC 169, the House of Lords made it clear that the determination of the extent of protection conferred by a patent is an examination in which there is only one compulsory question, namely that set by Article 69 of the EPC and its Protocol: what would a person skilled in the art have understood the patentee to have used the language of the claim to mean?: see Lord Hoffmann at paragraph. 69.
Novelty
14. There are two requirements for a claim to be anticipated by an earlier published document. First, the earlier document must disclose the invention claimed in the patent in suit. Secondly, the skilled reader must be able to perform the claimed invention if he attempts to do so by using the matter disclosed in the earlier document and/or his common general knowledge: see Synthon BV v SmithKline Beecham plc [2006] RPC 10. In Synthon, the well known judgment of the Court of Appeal in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd [1972] RPC 457 at 485 concerning the issue of disclosure was approved by the House of Lords. See further the citation from Lord Hoffmann's speech at paragraph 7–28 of Terrell on the Law of Patents (16 th ed)
15. A prior art document has to be construed as at the date it was published: see Jacob LJ in SKB v Apotex [2005] FSR 23 at para 89. This means that the document has to be read in the light of the common general knowledge as of its date, not as of the priority date of the patent in suit.
Obviousness
16. The structured (but not...
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