Teva Pharmaceutical Industries Ltd and Others v Istituto Gentili SpA and Another
| Jurisdiction | England & Wales |
| Judge | the Vice-Chancellor,Vice-Chancellor |
| Judgment Date | 06 November 2003 |
| Neutral Citation | [2003] EWCA Civ 1545 |
| Docket Number | Case No: A3/2003/0274 |
| Court | Court of Appeal (Civil Division) |
| Date | 06 November 2003 |
[2003] EWCA Civ 1545
IN THE SUPREME COURT OF JUDICATURE
COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE CHANCERY DIVISION
MR. JUSTICE JACOB
The Vice-chancellor
Lord Justice Buxton and
Lord Justice Laws
Case No: A3/2003/0274
Mr. David Young QC and Mr. Thomas Hinchliffe (instructed by Messrs Lovells) for the 1 st and 2 nd Appellants
Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs Bird and Bird) for the 1 st Respondents
Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs S J Berwin) for the 2 nd Respondents
Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs Taylor Wessing) for the 3 rd Respondents
Introduction
Bone consists of calcium phosphate within an organic matrix made primarily of the protein collagen. It is renewed by a process of remodelling whereby old bone is resorbed (that is removed) by cells called osteoclasts and replaced by new bone by means of cells called osteoblasts. Normally the two processes balance each other but an imbalance can lead to the conditions known as osteoporosis, Paget's disease and osteomalacia. A similar disorder of ectopic calcification called urolithiasis relates to the formation of gall and kidney stones.
The first appellant, Istituto Gentili SpA, is the patentee in relation to UK Patent No:2 118 042, for which the priority date is 15th April 1982, entitled "Pharmaceutical compositions containing pharmacologically active bisphosphonates". The specification states that such a composition is "suitable for the treatment of urolithiasis and capable of inhibiting the bone reabsorption". The validity of one or more claims in this patent were challenged by the respondents on grounds of want of novelty and obviousness. In respect of want of novelty they claimed that claim 1 had been anticipated by the publication in November 1981 of European Patent Application No:0 039 033A ("Blum"). In relation to obviousness they relied on common general knowledge and, amongst other prior publications, (i) Blum, (ii) a paper entitled "Synthesis and acid-base and complexing properties of [certain bisphosphonates]" by Kabachnik and others published in February 1978 and the paper by Yu.E.Vel'tischev and others specified in note 3 thereto ("Kabachnik") and (iii) a paper by Fleisch and others, published in 1981, entitled "Disphosphonates: History and Mechanisms of Action" ("Fleisch").
The second appellant, Merck & Co Inc., is the patentee in relation to European Patent (UK) 0 998 292, for which the priority date is July 1997, in respect of an invention claimed as "use of alendronic acid…for the manufacture of a medicament inhibiting bone resorption for treating osteoporosis…adapted for oral administration in a unit dosage form which comprises about 70mg of alendronic….acid…" The respondents contended that this patent is invalidated by s.4(2) Patents Act 1977 on the grounds that the invention is for "a method of treatment of the human..body..by therapy". They also alleged that it lacked novelty and was obvious by reference to publications of 'Lunar News' in April and July 1996.
The various proceedings relating to both patents were heard together by Jacob J in November 2002. By his order made on 23rd January 2003 he revoked both patents and gave the patentees permission to appeal. In relation to the first patent ("042") he held that claim 1 was anticipated by Blum and that claims 1, 2 and 7 were obvious by reference to each of Blum, Kabachnik and Fleisch. In relation to the second patent ("292") he interpreted claim 1 as referring to a particular dosing regime not the preparation of a single dose of 70mg of alendronate. On the basis of that construction and applying the decision of the Court of Appeal in Bristol-Myers Squibb v Baker Norton [2001] RPC 1 he concluded that s.4(2) rendered the patent invalid. In addition he found that 292 lacked novelty and was obvious on all the grounds alleged.
The respective patentees appealed against each of these conclusions. In addition Merck sought permission to amend 292 so as to delete three paragraphs of the specification referred to by Jacob J on the issue of construction relevant to s.4(2). In relation to 042 Counsel for the patentee accepted that if the order revoking that patent was to be set aside then he had to satisfy us that Jacob J was wrong on both want of novelty and obviousness by reference to each of Blum, Kabachnik and Fleisch. Having heard argument from both sides on want of novelty and obviousness by reference to Blum we indicated that we were satisfied that the judge was right so that further argument on obviousness by reference to Kabachnik or Fleisch was not necessary for the conclusion of the appeal. Accordingly I express no view on whether Jacob J was right in respect of the latter issues.
In relation to 292 it was apparent from the written arguments that if Jacob J was right on the interpretation of the claim and the application of s.4(2) then the issues of want of novelty and obviousness did not arise either. Accordingly we heard argument from both sides on whether or not permission to amend the specification should be granted, whether or not the judge was right on the issue of construction and whether or not on the basis of that construction he correctly applied s.4(2). We concluded that permission to amend should be refused and that Jacob J was right on both the issue of construction and the application of s.4(2). On this basis want of novelty was conceded. I should record, in case the matter goes further, that counsel for the appellants reserved for future argument the question whether Bristol-Myers Squibb v Baker Norton [2001] RPC 1 had been correctly decided. The issue of obviousness by reference to either issue of Lunar News was neither argued nor conceded and I express no view on it.
Accordingly in this judgment I give my reasons for concluding that:
(1) 042 lacked novelty by reference to Blum,
(2) 042 was obvious by reference to Blum,
(3) permission to amend 292 should be refused,
(4) on its true interpretation the invention claimed by 292 is a particular dosing regime not the preparation of a single dose of 70mg of alendronate, and
(5) such a claim is for a method of treatment within s.4(2) Patents Act 1977.
Although the two patents relate to the same general area of medicine and science the issues are quite distinct, not least because the priority date for 042 is 15 years and 3 months earlier than that of 292 during which much happened. Accordingly the starting point is the state of the relevant art and common general knowledge in early 1982.
The state of the art and common general knowledge in early 1982
I start with an explanation of what bisphosphonates are. I have taken it from paragraphs 4 to 8 of the judgment of Jacob J supplemented by the document setting out the parties' contentions on common general knowledge put before him at the trial. Bisphosphonates are synthetic compounds. They have not been found to occur naturally. They are characterised by two carbon-phosphorus bonds. There are no known enzymes that can cleave such bonds with the consequence that bisphosphonates are absorbed, stored and excreted from the body unaltered. Their physiochemical effect is similar to that of pyrophosphate in that they bind strongly to the surface of solid-phase calcium phosphate and by doing so inhibit the formation, delay the aggregation and slow down the dissolution of calcium phosphate crystals.
The P-C-P bisphosphonates with which this case is concerned have the following general chemical structure:
The two R groups can be varied. By 1982 three bisphosphonates had been studied clinically. Their structures and shortened chemical names were as follows:
The R2 and R1 groups for etidronate are hydroxyl and methyl; for clodronate, two chlorines; and for pamidronate a hydroxyl, and an amino attached to a C2 alkyl. It is often described in this case as the "C3" compound —counting all the carbons.
Alendronate, with which this case is concerned, is similar to pamidronate, save that the alkyl chain is one C longer. It is the C4 compound. So its structure is:
As Jacob J explained in paragraph 7 of his judgment
"Its full chemical name is 4-aminobutylidene-1-hydroxy-1,1-bisphosphonic acid. The full name is based on the central alkyl chain which is 4 carbons long (hence butyl). The carbon numbered 1 has a hydroxy (hence "1-hydroxy") and the two phosphonic groups (hence 1,1 bisphosphonic). Carbon 4 has the amine group (hence "4-amino"). Actually the term alendronate (like the others) is used not only for the acid but also for its salts."
Other aminohydroxybisphosphonates featuring in the case are the C5 and the C6. The former has no short name so I will refer to it as "Anondronate", the latter is called neridronate. In a number of places different terminology is used. To simplify matters I have, like Jacob J, used the above-names wherever possible, including in quotations from the patents.
The first reported clinical uses of bisphosphonates to treat bone disorders were in the late 1960s/early 1970s with publications in the Lancet and elsewhere on clinical trials involving the use of etidronate to treat heterotopic ossification and Paget's disease. The first reported clinical use of pamidronate to treat Paget's disease was in the late 1970s and of clodronate was in 1979/80. The main pharmacological effect of bisphosphonates is to inhibit bone...
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