Ipsofactoj.com: International Cases [2004] Part 8 Case 7 [CAEW]


COURT OF APPEAL, ENGLAND & WALES

Coram

Istituto Gentili SpA

- vs -

Teva Pharmaceutical

Industries Ltd

SIR ROBERT ANDREW MORRITT, V-C

LORD JUSTICE BUXTON

LORD JUSTICE LAWS

6 NOVEMBER 2003


Judgment

Vice-Chancellor

INTRODUCTION

  1. 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.

  2. 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 re-absorption". 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,

    1. Blum,

    2. 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

    3. a paper by Fleisch and others, published in 1981, entitled "Disphosphonates: History and Mechanisms of Action" ("Fleisch").

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. The P-C-P bisphosphonates with which this case is concerned have the following general chemical structure:

  10. 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.

  11. 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.

  12. Other aminohydroxy bisphosphonates 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.

  13. 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 resorption and this is the basis of their therapeutic activity. Inhibition of bone mineralisation was known to occur especially with etidronate, but there was a narrow therapeutic window between doses required to inhibit bone resorption and those that impaired bone mineralisation.

  14. It is not suggested that the state of the art altered materially between the publication of Blum in November 1981 and the priority date of 042 in April 1982. Accordingly it is appropriate to describe at this stage the extent of common general knowledge, as found by Jacob J, in April 1982. As set out in paragraph 28 of his judgment it included the following matters:

    (a)

    There was widespread interest in the clinical use of bisphosphonates to treat medical disorders of excess bone destruction.

    (b)

    The oral administration of etidronate was approved for use for the treatment of Paget’s disease in the UK and elsewhere.

    (c)

    The oral administration of etidronate, clodronate and pamidronate had been shown to be clinically effective in treating several medical disorders of excess bone destruction.

    (d)

    The 3 bisphosphonates which had been shown to be clinically effective in treating medical disorders of excess bone destruction had different efficacies and in particular, that etidronate had a relatively narrow therapeutic window.

    (e)

    The existing non-bisphosphonate treatments for medical disorders of excess bone destruction did not satisfy all clinical needs and there was room for a better therapy.

    (f)

    There were established tests which could be used for assessing the potential of a new therapeutic agent for use in the treatment of medical disorders of excess bone destruction.

    In paragraphs 29 and 30 Jacob J indicated that additional matters relied on by the appellants based on the evidence of their expert witness Professor Papapoulos were either unacceptable or substantially the same but with different emphases to those he had already accepted.

    BLUM

  15. As I have already indicated Blum is a European Patent Application which was published on 4th November 1981. It is described as a better way of making C4, C5, and C6 bisphosphonates. It states

    The amino alkanediphosphonic acid described [C4, C5 and C6] excels by a high complexing power towards multivalent metal ions, particularly towards alkaline-earth ions and heavy metals, like iron and copper. Therefore they can be used especially for water-softening processes. Therein, it is not necessary to work with stoichiometric quantities, but by using quantities lower than stoichiometric quantities the precipitation of calcite can be considerably delayed.

    Owing to their properties they are also suitable for the production of cosmetic and pharmaceutical preparations.

    [emphasis added]

    042

  16. As I have also indicated the title of the invention is "Pharmaceutical compositions containing pharmacologically active bisphosphonates". The priority date is 15th April 1982. It starts with the statement that

    The invention especially relates to pharmaceutical compositions suitable for the treatment of urolithiasis and capable of inhibiting bone reabsorption.

    The specification continues with an acknowledgement of pyrophosphate which, as Jacob J concluded, would be understood to refer to the work of Professor Fleisch and his group in Berne. The specification continues

    In view of the great interest connected with pyrophosphate, investigations have been carried out for the purpose of making substances with similar activity but resistant to hydrolysis. This object has been achieved partially with the synthesis of bisphosphonates, that is substances which contain the group P-C-P instead of the group P-O-P. The action of the bisphosphonates on calcium salts is similar to the action of pyrophosphate; indeed, even in low concentration they exhibit the following actions:

    [details are given - essentially blocking crystallisation in vitro – and continues]

    Several pharmacological and clinical studies in the scientific literature, however demonstrate that, in spite of certain analogies in activity, the several bisphosphonates used up to the present time in treatment of osteopathia exhibit some quite serious drawbacks with respect to the degree of toxicity in animals and the tolerability or the inducement of negative collateral side effects in men.

    It has now been found surprisingly that [the C4 (alendronate) and the C5 (anondronate)] are very suitable for the treatment of urolithiasis and as inhibitors of the bone reabsorption because they exhibit high activity which is not accompanied by the side effects hereinabove mentioned with respect to pyrophosphate.

  17. There follows a lengthy passage to which Jacob J referred in paragraphs 18 to 22 dealing with the composition of R1 and R2 as shown in the general formula. Jacob J pointed out some oddities in this passage which I do not need to repeat. But it is relevant to note, as he observed, that the specification did not acknowledge that

    an amino alkyl hydroxybisphosphonate had already been made and was common general knowledge - namely the C3, pamidronate. Actually neridronate had also been made and disclosed.

  18. In relation to certain pharmacological tests the specification states

    The purpose of this study is to investigate the effect of a series of novel biphosphonates on a culture of skull cells and on the bone reabsorption and the mineralization in vivo.

    After describing the methods used it continues

    It appears that the C5 amino is the most active in inhibiting the bone reabsorption. However, there is observed a toxicity at the higher dosage. The substances alendronate and neridronate are also active on the reabsorption with a result slightly superior to clodronate. A significant difference is with respect to the mineralization because neridronate induces strong inhibition of mineralization in the dose of 10 mg of P/kg while alendronate has no effect or only a slight effect or only an effect to a very small extent.

    These results show that the amino compounds with an odd number of carbon atoms are somewhat toxic but are much more active in inhibiting the bone reabsorption. The compounds with an even number of carbon atoms have an activity slightly superior to clodronate. Another significant fact is that alendronate does not induce or induces only to a very small extent the inhibition of mineralization at high dosage while neridronate exhibits high inhibition. Consequently, alendronate appears to be more suitable for use in diseases with an increased reabsorption of bone in humans.

    In fact, for a long time, a bisphosphonate capable of inhibiting the growth of the crystals without affecting the bone has been the subject of research. It is concluded, therefore, that the two substances alendronate and the C5 amino compound are destined to become medicaments capable of inhibiting the bone reabsorption.

  19. The relevant claims are as follows:

    1.

    A pharmaceutical composition which contains as the active ingredient at least one [of alendronate or anondronate] or a salt thereof with an alkali metal or an organic base or a basic amino acid, together with a pharmaceutically acceptable carrier or diluent.

    2.

    A pharmaceutical composition according claim 1 in a form for oral administration

    ....

    7.

     

    A pharmaceutical composition according to any one of the preceding claims which contains as an active ingredient [alendronate].

    WANT OF NOVELTY

  20. The first issue referred to in paragraph 7 above is whether claim 1 of 042 was wanting in novelty or, as it is sometimes put, was anticipated by Blum. The relevant statutory provisions are contained in ss.1(1)(a) and 2(1) and (2) Patents Act 1977. They provide that

    1.

    (1)

    A patent may be granted only for an invention in respect of which the following conditions are satisfied, that is to say-

    (a)

    the invention is new,

    2.

    (1)

    An invention shall be taken to be new if it does not form part of the state of the art.

    (2)

    The state of the art in the case of an invention shall be taken to comprise all matter (whether a product, a process, information about either, or anything else) which has at any time before the priority date of that invention been made available to the public (whether in the United Kingdom or elsewhere) by written or oral description, by use or in any other way.

  21. It is common ground before us, as it was before Jacob J, that the principles to be applied in accordance with the Act are as described by Sachs LJ in giving the judgment of the Court in The General Tire Co v The Firestone Tyre & Rubber Co Ltd [1972] RPC 457. Though long the passage is worth quoting in full. At page 485 he said

    In the present case we are not concerned with anticipation by earlier use of the patentee’s device but with anticipation by prior publication: that is to say, it is contended that the plaintiffs’ invention as claimed in their patent was at the priority date of their claim something which was known in the United Kingdom by reason of prior publications. To determine whether a patentee’s claim has been anticipated by an earlier publication it is necessary to compare the earlier publication with the patentee’s claim. The earlier publication must, for this purpose, be interpreted as at the date of its publication, having regard to the relevant surrounding circumstances which then existed, and without regard to subsequent events. The patentee’s claim must similarly be construed as its own date of publication having regard to the relevant surrounding circumstances then existing. If the earlier publication so construed, discloses the same device as the device which the patentee by his claim, so construed, asserts that he has invented, the patentee’s claim has been anticipated, but not otherwise. In such circumstances the patentee is not the true and first inventor of the device and his claimed invention is not new within the terms of section 32(1)(e).

    The earlier publication and the patentee’s claim must each be construed as they would be at the respective relevant dates by a reader skilled in the art to which they relate having regard to the state of knowledge in such art at the relevant date. The construction of these documents is a function of the court, being a matter of law, but since documents of this nature are almost certain to contain technical material the court must, by evidence, be put in the position of the kind to whom the document is addressed, that is to say, a person skilled in the relevant art at the relevant date. If the art is one having a highly developed technology, the notional skilled reader to whom the document is addressed may not be a single person but a team, whose combined skills would normally be employed in that art in interpreting and carrying into effect instructions such as those which are contained in the document to be construed. We have already described the composite entity deemed to constitute the notional skilled addressee.

    When the prior inventor’s publication and the patentee’s claim have respectively been construed by the court in the light of all properly admissible evidence as to technical matters, the meaning of words and expressions used in the art and so forth, the question whether the patentee’s claim is new for the purposes of section 32(1)(e) falls to be decided as a question of fact. If the prior inventor’s publication contains a clear description of, or clear instructions to do or make something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, the patentee’s claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated. The prior inventor, however, and the patentee may have approached the same device from different starting points and may for this reason, or it may be for other reasons, have so described their devices that it cannot be immediately discerned from a reading of the language which they have respectively used that they have discovered in truth the same device; but if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.

    If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated, although it may fail on the ground of obviousness. To anticipate the patentee’s claim the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented: Flour Oxidizing Co. Ltd v Carr & Co. Ltd.((1908) 25 R.P.C. 428 at 457, line 34, approved in B.T.H. Co Ltd. v Metropolitan Vickers Electrical Co. Ltd. (1928) 45 R.P.C. 1 at 24, line 1). A signpost, however clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.

  22. Having referred to this passage and the relevant excerpt from Blum Jacob J expressed his conclusion in the following terms:

    32.

    [The respondents] submit that this could not be clearer: Blum is specifically proposing the use of all three compounds for the production of pharmaceutical preparations. That must mean use as an active ingredient in such a preparation.

    33.

    I think that must be right. A skilled man, aware as he would be of the C3 compound (pamidronate) would naturally read this as a proposal to use the C4-C6 compounds as the active ingredient in a pharmaceutical. The point is straightforward and incapable of elaboration.

    Jacob J then dealt specifically with the counter-arguments advanced by the patentee, many of which have been repeated before us and concluded

    34.

    None of these arguments persuades me that claim 1 is not anticipated. It is true that claim 1 also requires a pharmaceutically acceptable carrier or diluent. The use of these with an active ingredient is a plain consequence of the teaching to use alendronate in the production of a pharmaceutical.

  23. The patentee submits that Jacob J was wrong. The argument is summarised in the written argument of counsel for the patentee as follows:

    (i)

    his conclusion is not supported by the wording of the passage – there is simply no express or implicit disclosure in Blum of the use of the compounds as the active agent in pharmaceutical compositions i.e. compositions which comprise an active agent together with diluents and carriers etc. In other words, there are no clear and unambiguous directions in Blum to do something that would infringe claim 1 (and a fortiori claims 2 and 7) of the 042 Patent;

    (ii)

    he ignored the reference to "cosmetic preparations" in the relevant passage, concentrating solely on the word "pharmaceutical";

    (iii)

    he considered what a skilled person may have thought on reading Blum, rather than what Blum actually disclosed to such a person.

  24. I can deal with the second and third points quite shortly. The suggestion that the judge ignored the reference to cosmetic preparations implies that he should have read the passage conjunctively so that Blum was referring to the production of preparations which were both cosmetic and pharmaceutical. So read the relevant property of the bisphosphonate was that of a complexing agent. In my view so to interpret Blum would be to ignore both the usual principles of interpretation and the state of the art. There is nothing in Blum itself to support such an interpretation and, as the judge concluded, the skilled man would not so understand it. In any event the state of the art and common general knowledge included the use of etidronate in the treatment of Paget’s disease. Such use was pharmaceutical but not cosmetic.

  25. Counsel for the respondents submitted that the distinction suggested by the third point is without a difference because what the skilled man thought on reading Blum is the same as what Blum teaches. I understood from the oral submissions of counsel for the patentee that the point is that made by Sachs LJ in the last two sentences of the quotation from the judgment of the court in General Tire set out in paragraph 21 above. Does Blum contain clear and unmistakeable directions to do what is set out in claim 1 of 042? But so formulated the point is the same as that summarised in paragraph (i).

  26. The argument on that point as developed orally was that in the passage relied on in Blum the reference to "Owing to their properties ...." is a reference to their complexing power which would bring to the mind of the skilled man the possibility of inhibiting mineralisation and therefore narrowing, possibly to the point of extinction, the therapeutic window referred to in paragraph 14(d) above. Accordingly, so it was submitted, the skilled man would not read it as a direction to make and use the preparation in the treatment of bone disorders. Similarly counsel for the patentee relied on the omission of any statement in Blum as to the use for which the pharmaceutical preparation was suitable and should be devoted nor how and for what purpose C4, C5 or C6 should be used in its preparation. Specifically the patentee relied on the fact that Blum does not direct the use of C4 as an active ingredient.

  27. In support of this submission we were referred to the evidence of Professor Russell, currently Norman Collison Professor of Musculoskeletal Sciences at Oxford Medical School, the expert witness for the respondents. It is clear that his evidence was preferred by the judge to that of Professor Papapoulos, Professor of Medicine and Director of Bone and Mineral Research at Leiden University, the expert witness for the patentee. Jacob J described the evidence of the latter as "rather rigid and a little extreme". In both his witness statement and under cross-examination Professor Russell referred to "the potential use" of the compounds referred to in Blum for some clinical application. This, it was argued, is not a sufficiently clear and unmistakeable direction.

  28. Ultimately the issue was one of fact for the judge. In my view he was right for the reasons he gave. In deference to the argument of counsel before us I would amplify them somewhat.

    • First, the direction in Blum was to use all three bisphosphonates, in particular C4, in the production of a pharmaceutical preparation.

    • Second, the evidence showed that those bisphosphonates had never been used in such a preparation in any way other than as the active ingredient. This is why the judge said in paragraph 33(b) of his judgment that the idea of some other use would not cross the mind of the skilled man. In addition he pointed out in paragraph 33(d) that use as a stabiliser would be unthinkable.

    • Third, the skilled man would know of the uses of etidronate and pamidronate in the treatment of bone disorders. Accordingly, if and in so far as it is necessary to show that Blum was indicating not only a pharmaceutical use as an active ingredient but also that it should be used in the treatment of bone disorders this would be clearly understood by the skilled man. Even if use in the treatment of bone disorders was not known, use in the treatment of ectopic calcification was. That was also a pharmaceutical use even if of historical interest only.

    • Fourth, the fact that Professor Russell referred to "the potential use of these compounds for clinical applications to treat medical disorders of excess bone destruction" does not detract from the fact that there was a clear and unmistakeable direction to use them as active ingredients in the production of a pharmaceutical preparation. The extent to which such preparations may, in the event, prove to be clinically valuable does not detract from the nature or clearness of that direction.

  29. In summary, therefore, I agree with the judge on his factual conclusion. In any event it is clear that there was ample evidence to support it. That conclusion is sufficient to justify the dismissal of the patentee’s appeal in respect of claim 1 of 042. But as we heard full argument on the question of obviousness by reference to Blum I should deal with that issue too in relation to claim 1 as well as claims 2 and 7.

    OBVIOUSNESS

  30. The relevant provisions of Patents Act 1977 are ss.1(1)(b) and 3. They provide that

    1.

    (1)

    A patent may be granted only for an invention in respect of which the following conditions are satisfied, that is to say-

    ....

    (b)

    it involves an inventive step,

    ....

    3.

     

    An invention shall be taken to involve an inventive step if it is not obvious to a person skilled in the art, having regard to any matter which forms part of the state of the art by virtue only of section 2(2) ....

  31. It is common ground that the principles to be applied in accordance with the Act are as described by Oliver LJ in giving the judgment of the court in Windsurfing International Inc v Tabur Marine (Great Britain) Ltd [1985] RPC 59. At page 73 he said

    There are, we think, four steps which require to be taken in answering the jury question. The first is to identify the inventive concept embodied in the patent in suit. Thereafter, the court has to assume the mantle of the normally skilled but unimaginative addressee in the art at the priority date and to impute to him what was, at that date, common general knowledge in the art in question. The third step is to identify what, if any, differences exist between the matter cited as being "known or used" and the alleged invention. Finally, the court has to ask itself whether, viewed without any knowledge of the alleged invention, those differences constitute steps which would have been obvious to the skilled man or whether they require any degree of invention.

  32. In David J. Instance v Denny Bros Printing Ltd [2002] RPC 14 Aldous LJ, with whom the other members of the court agreed, pointed out (paragraph 16) that though the structured approach of Windsurfing is useful it is not essential provided that the judge dons the mantle of the skilled man and asks himself the right question. He also pointed out that the approach of an appellate court to questions of obviousness should be that indicated by the House of Lords in Designers Guild Ltd v Russell Williams (Textiles) Ltd [2001] FSR 11, namely

    because the decision involves the application of a not altogether precise legal standard to a combination of features of varying importance .... an appellate court should not reverse the judge’s decision unless he has erred in principle.

  33. The reasoning and conclusion of Jacob J are set out in paragraphs 36 to 40 of his judgment. He said

    36.

    I begin with claim 1. Its inventive concept is the use of, amongst other things, alendronic acid or a salt thereof as the active ingredient in the pharmaceutical composition. What then is the difference between Blum and that inventive concept? If Blum is not an anticipation, the only difference is the idea of using these substances as an active ingredient.

    37.

    The skilled man would know that pamidronate (and for that matter etidronate and clodronate) were clinically proven to be effective. In short, the skilled man would know that C3 and C6 compounds worked clinically. Seeing Blum would immediately put him in mind of the use of the C4 and C5 also.

    38.

    Of course he would not know whether the C4 and C5 were better or worse than the C3 and C6. He would know that C3 had proved to be successful. He may know that the C6 was less successful, although still active (I am not actually satisfied that much was widely known about C6). On the basis of this Merck suggest that the skilled man would not bother with trying the C4 or C5, that he would assume there is a linear fall in efficacy between C3 and C6 and not bother to try the C4 and C5. That is plain bad science for the reasons explained by Professor Russell: you cannot just draw a straight-line graph between the two and be logical. Moreover, no one knew whether or not pamidronate was the best. It was merely the best that had been found so far.

    39.

    I conclude that the skilled man would certainly put the C4 and C5 compounds (and probably the C2) high up on a testing programme and that he would want to do those tests. Dr Newton’s evidence entirely corroborates that. Claim 1 is an obvious consequence of that.

    40.

    So also are claims 2 and 7 - it is impossible to see anything inventive about the idea of oral administration (claim 2) or that the particular compound should be alendronate (claim 7) or both together.

  34. The patentee contends that Jacob J was wrong. A helpful summary of counsel’s submission is contained in paragraph 88 of their written argument. They submit

    In conclusion, on the Judge’s finding that as of April 1982 there was no expectation that any of the three bisphosphonates disclosed by Blum (and in particular alendronic acid) would be better or worse than the then current and most promising bisphosphonate (pamidronate), it was indeed surprising and non obvious that alendronic acid (C4) has been found to be 10 times more active than pamidronate (C3) (see Papapoulos 1 para 24.2). This is to be contrasted to neridronate (C6) which is some 10 times less active than pamidronate (see Russell XX D1/p9713-22). Given that there was no reason to choose one or more of the Blum bisphosphonates to test for improved activity as opposed to any other of the prior disclosed bisphosphonates, it is submitted that selecting alendronic acid (C4) or the pentylidene compound (C5), and in particular alendronic acid, was not obvious.

  35. In support of this submission we were referred to a number of authorities to the effect that the next step must be considered to be at least worthwhile if it is to be obvious. Thus in Johns-Manville Corporation’s Patent [1967] RPC 479, 493 Diplock LJ described it as "well worth trying out", in Technograph Printed Circuits Ltd v Mills & Rockley (Electronics) Ltd [1972] RPC 346, Lord Reid described it as "worth trying" and in Norton Healthcare Ltd v Beecham Group plc (Court of Appeal 19th June 1997 unreported) Aldous LJ pointed to the need in cases where it was necessary to show that it was obvious to try the next step that there was "an expectation of a good result".

  36. Counsel for the patentee again relied on the evidence of Professor Russell as to the "potential use" of the compounds referred to in Blum for some clinical application. What he asked rhetorically is there in Blum pointing to C4, C5 and C6 for testing as opposed to all the other bisphosphonates? The fact that they were potential candidates is not, he submitted, enough.

  37. The answer to that rhetorical question lies in the evidence of Professor Russell. In his first report (para 5.8) he said:

    I have no doubt that the reference [in Blum] to pharmaceutical preparations would be taken by the notional skilled person as a reference to the potential use of these compounds for clinical applications to treat medical disorders of excess bone destruction.

    In his response to this report Professor Papapoulos contended in his report (para 14.15) that the statement in Blum was ambiguous and disclosed no useful information. Professor Russell disagreed. In his second report he commented on the evidence of Professor Papapoulos in these terms:

    I disagree. By 1982, bisphosphonates were known to be inhibitors of bone resorption by everyone interested in the field of medical disorders of excess bone destruction. If such a person had been presented with [C4] in 1982 I have no doubt that, for the reasons I explained in my first report, he would have expected it to have had a biological and potential therapeutic effect. Although its potency and toxicity profile would need to have been considered, this could readily have been done with further studies.

  38. Professor Russell was extensively cross-examined by leading counsel for the patentee, but did not qualify the evidence in his reports I have quoted in the previous paragraph. With regard to the last sentence of Blum quoted in paragraph 15 above he said:

    I think it lays the way open for that [suitability for therapeutic use] because this rests on the interpretation of what is meant by pharmaceutical .... I think this is a chemistry patent which refers to the potential biological and other commercial applications.

    [T1/118]

    Later in his cross-examination he said that anything closely related to pamidronate might be expected to have biological activity. [T1/125] He considered [ibid] that the bisphosphonates with which Blum was concerned, C4, C5 and C6, would be expected to have quite strong effect on bone resorption when tested.

  39. Counsel then suggested to Professor Russell that there would be no expectation that the bisphosphonates in the Blum patent [C4, C5, and C6] would be likely to have as good or better potency with less side-effects than pamidronate itself. He replied:

    I think if we go back to what we have already established was known in 1982, we had pamidronate [C3] with a quite extensive clinical experience. We already had the amino hexane [C6] coming on the scene. Both of these compounds are active. I think if you took a vote among 100 people as to whether the two compounds in between would, first of all, work and secondly, be quite potent, you would get the majority saying that they would be .... They would not be inactive; they would probably be active. They may be more or less active than the compounds either side in that series.

    The witness then agreed with the suggestion put to him by Jacob J that you would not know whether the side effects would be the same, better or worse. Later Professor Russell expressed the view [T1/131] that

    Given the compounds either end of the Blum series are active, I still make the point that things in the middle of the series would also likely [to be active].

  40. I consider that this evidence from a person the judge described as "a fair and in my view objective witness" showed quite clearly that C4 was "worth trying" as indicated in the dicta to which I have referred in paragraph 35 above. Accordingly there was evidence to justify the judge’s conclusions in paragraphs 37-39 of his judgment which I have quoted in paragraph 33 above. In my view the judge was entitled, having formed the views of the evidence of Professors Russell and Papapoulos to which I have already referred, to accept the evidence of the former in preference to that of the latter. Further he was fully entitled to prefer the oral evidence of Professor Russell to the opinion of Professor Fleisch expressed in an article published in 1983 on which he, that is Professor Fleisch, had not been cross-examined. I see no ground for interfering with the judge’s decision on what, in the end of the day, is a question of fact even if, as I understood to be conceded (Transcript Day 2 page 103 lines 13-18 and Day 3 page 36 line 20 to page 37 line 7), the judge’s reliance on Dr Newton in paragraph 39 was misplaced if and in so far as it related to Blum rather than Fleisch. Accordingly the patentee’s appeal from the order of Jacob J revoking 042 fails on this ground also.

    292

  41. As Jacob J recorded, things had moved on between the priority date of 042 in April 1982 and the priority date of 292 in July 1997. By the latter date common general knowledge included the following matters:

    1.

    Alendronate had come onto the market in 1995, approved in two oral dosage forms: 10mg daily for osteoporosis and 40mg daily for Paget’s disease.

    2.

    The Paget’s treatment was only for six months, whereas the osteoporosis treatment was effectively for life.

    3.

    There was a side effect problem – that alendronate could affect the gastrointestinal (GI) tract. The initial recommendations for administration were stringent: that it should be taken at least 30 minutes before the first food or drink of the day with a full glass of water and that the patient should not lie down for 30 minutes after administration.

    4.

    Compliance with the conditions had some problems – not only would some elderly patients find them inherently difficult but also the very strict rules of the regime would not always be obeyed.

    5.

    Marketing approval for the use of alendronate for osteoporosis was based on a number of clinical trials which would have been well known to bone disease clinicians. From these clinicians would have known that alendronate was a potent resorption inhibitor and had good anti-fracture efficacy.

    6.

    Post-marketing surveillance showed that in rare cases only there were severe upper GI adverse events. Most of these were due to non-compliance – as Merck’s Dr Yates testified. It was not known whether poor compliance was the sole cause of the problem.

    7.

    Although Paget’s disease is much rarer than osteoporosis, a substantial number of patients had taken alendronate in the 40mg daily dose for the 6-month period required for that disease. There was no evidence that associated GI problems were any greater with that dose as compared with the 10mg dose for osteoporosis.

    8.

    In early 1996, because of the compliance problem, Merck made the instructions for administration more explicit – contraindicating for patients unable to comply with the 30-minute rule and those with certain oesophageal abnormalities.

    9.

    This was expected (and did in the event) improve matters, but (as was also expected) there would continue to be a compliance problem.

    10.

    Bisphosphonates had low oral bioavailabilty – which was reduced further if taken with food (hence the regime).

    11.

    However once absorbed they had a long duration of action.

    12.

    The size of their effect mainly depended on the total amount administered over time, not on the frequency of administration. Daily treatment was not critical to their effect on bone.

  42. 292 was described in its title as a "Method for Inhibiting Bone Resorption". Claim 1 in its original form was

    Use of alendronic acid .... for the manufacture of a medicament for inhibiting bone resorption in a human wherein the said medicament is adapted for oral administration in a unit dosage form which comprises from about 8.75mg to 140mg of alendronic acid .... according to a continuous schedule having a periodicity from about once every 3 days to about once every 16 days.

    During the course of the hearing before Jacob J the claims and the specification were amended with the leave of the judge. Claim 1 became

    Use of alendronic acid .... for the manufacture of a medicament for inhibiting bone resorption for treating osteoporosis in a human in need thereof wherein said medicament is adapted for oral administration in a unit dosage form which comprises about 70mg of alendronic [acid] .... according to a continuous schedule having a dosing interval of once weekly.

  43. In both the original and amended versions of the specification paragraphs 0108, 0109 and 0110 stated:

    [0108]

    Tablets containing about 35mg of alendronate, on an alendronic acid active basis, are prepared using the following relative weights of ingredients

    [table referred to]

    [0109]

    The resulting tablets are useful for administration in accordance with the methods of the present invention for inhibiting bone resorption.

    [0110]

    Similarly, tablets comprising other relative weights of alendronate, on an alendronic acid basis are prepared: e.g. about 8.75, 17.5, 70 and 140 mg per tablet.

  44. In his judgment Jacob J dealt first with a question of interpretation of the claim. In paragraphs 69 and 70 he said:

    69.

    .... it is necessary to construe the claim. In particular is it in substance merely to a 70mg dosage form, for example an oral dose containing about 70mg of alendronate?

    70.

    I think the answer to this is clearly that the claim is wider. The patent does not teach that a particular dosage unit is new. It teaches that a particular dosing regime is new. How that regime is achieved is not material to the inventive concept of the claim. You can take 7 10mg pills or two 35mg pills or a liquid dose measured out from a bottle. Very likely the claim covers taking two of the known and available 40mg pills too - for on a purposive construction the claim cannot be limited to a mathematically precise 70mg dose. At one point I thought the claim might be to a method of preparation of a single dose of 70mg – single pills or separately prepared liquid doses (e.g. in sachets). But this cannot be so – the patent specifically contemplates 35mg tablets which are said to be useful for administration in accordance with the invention.

    APPLICATION TO AMEND THE SPECIFICATION

  45. On 6th October 2003, that is 15 days before the hearing of this appeal started, the patentee applied to amend the specification to delete paragraphs 0108 to 0110. This was opposed by the respondents on the grounds that the amendment was unnecessary or, if necessary, was precluded by s.76(3)(a) Patents Act 1977 or should be refused as a matter of discretion under s.75(1).

  46. Section 76(3)(a) precludes an amendment to the specification "if it .... results in the specification disclosing additional matter". Counsel for the respondents submitted that the proposed amendment disclosed additional matter. The additional matter relied on would be the further teaching of the importance of the quantity of the single dose. Instead of any number of pills aggregating a dose of about 70mg it would teach that a single pill comprising 70mg of alendronate was essential. This was disputed by counsel for the patentee. He contended that the proposed amendment would not add matter at all. By contrast it would restrict the ambit of claim 1.

  47. In my view it is necessary to approach this question on the assumption that the amendment, if made, will affect the interpretation of claim 1. But in that event it will be seen that the deletion of the three paragraphs in question adds to the teaching of the patent by pointing out the importance, as claimed, of a single pill or other administration comprising 70mg or thereabouts of alendronate. It is true that such an addition will have the effect of restricting the ambit of claim 1. The decision of Aldous J in Bonzel v Intervention (No.3) [1991] RPC 553, 574 shows that what is material is the addition of any subject matter relevant to the claimed invention and that such addition may be accomplished by either addition to or deletion from the specification.

  48. On that basis in my view the objection taken under s.76(3)(a) is well founded. If the question is, as counsel for the patentee submitted, whether the proposed amendment would widen or restrict the scope of the claim then it would not be precluded by the subsection. But that is not the question. The right question is whether the proposed amendment would result in the specification disclosing additional matter. The basis on which I am considering this issue, namely that the amendment will alter the scope of claim 1, indicates that the answer must be in the affirmative. It adds to the teaching of the patent the requirement for a single pill or other administration vehicle comprising 70mg of alendronate. The fact that it does so by deletion is neither here nor there.

  49. In addition I consider that the application should be refused as a matter of discretion under s.75 Patents Act 1977. The amendment now sought goes well beyond that allowed by Jacob J at the trial. It was made two weeks before the hearing of this appeal. No explanation has been forthcoming as to why it was not sought at the time of the application for the first amendment nor why the application is made now, nearly nine months after the judgment of Jacob J.

    IS THE INVENTION CLAIMED BY 292 A PARTICULAR DOSING REGIME OR THE PREPARATION OF A SINGLE DOSE OF 70mg?

  50. I have quoted the relevant passages in the judgment of Jacob J in paragraph 44 above. Counsel for the patentee contends that the judge was wrong to conclude that the claim was to a particular dosing regime. He points out that in October 1995 the patentee marketed alendronate under the trade name of Fosamax as a 10mg daily dose for the treatment of osteoporosis. Instructions for its use indicated that it had to be taken with a glass of water first thing in the morning not less than 30 minutes before any food or drink was consumed with the patient remaining in an upright position for 30 minutes thereafter. Problems with oesophagitis came to the patentee’s notice in March 1996. This led to the issue of further instructions emphasising the importance of observing the instructions for use.

  51. 292 as first amended describes the field of the invention in paragraph [0001] as relating to

    .... the use of a bisphosphonate for the manufacture of oral medicaments for inhibiting bone resorption by treating osteoporosis in a mammal while minimising the occurrence of or potential for adverse gastrointestinal effects. These medicaments comprise a pharmaceutically effective amount of a bisphosphonate as a unit dosage for use according to a continuous schedule having a dosing interval of once weekly dosing.

    Paragraphs 7 to 12 deal with the problems of such gastrointestinal effects. Paragraph 15 states

    In the present invention it is found that the adverse gastrointestinal effects that can be associated with daily or cyclic dosing regimens can be minimised by administering the bisphosphonate at a relatively high unit dosage according to a continuous schedule having a dosing interval of once weekly dosing. In other words it is found that the administration of a bisphosphonate at low relatively dosing frequency causes less adverse gastrointestinal effects...compared to the administration of a low relative dosage at a high relative dosing frequency.

    In paragraph 16 it is claimed that

    .... the methods of the present invention would also be more convenient than daily or cyclic dosing regimens. Patients would be subjected less frequently to the inconvenience of having to take the drug on an empty stomach and having to fast for at least 30 minutes after dosing.

  52. In paragraph [0047] it is stated that

    The present invention utilizes higher unit dosages of the bisphosphonate at each dosing point than as heretofore has been typically administered, yet because of the dosing schedule chosen the potential for adverse gastrointestinal effects are minimised.

    In paragraphs [0077] and [0078] it is stated that "a unit dosage comprises about 70mg of the alendronate compound". The example given following table 1 indicates how "Alendronate tablets or liquid formulations containing about 70mg of alendronate" are prepared and administered. Paragraphs [0108] to [0110] are set out in paragraph 43 above. Paragraph [0111] refers to a liquid formulation containing 70mg of alendronate in about 75ml of liquid. It concludes in paragraph [0113] that the resulting liquid formulation is useful for administration as a unit dosage in accordance with the methods of the present invention. I have already set out the terms of claim 1 in paragraph 42 above.

  53. Counsel for the patentee emphasises that the claim is for "oral administration in a unit dosage form which comprises about 70mg of alendronic [acid] ...." He contends that the addition of the word "unit" shows that a single administration of 70mg of alendronate is required. He relies on definitions of the word "unit" appearing in the 10th Edition of The Concise Oxford English Dictionary and volume XIX of the 2nd Edition of the Oxford English Dictionary. He submits that none of the meanings appearing in either dictionary envisages multi-dosing in more than one unit aggregating 70mg of alendronate.

  54. I am unable to accept this submission. Section 125(3) Patents Act 1977 enjoins us to apply the Protocol on the Interpretation of Article 69 of the European Patent Convention. That provides that

    Article 69 should not be interpreted in the sense that the extent of the protection conferred by a European patent is to be understood as that defined by the strict, literal meaning of the wording used in the claims, the description and drawings being employed only for the purpose of resolving an ambiguity found in the claims. Neither should it be interpreted in the sense that the claims serve only as a guideline and that the actual protection conferred may extend to what, from a consideration of the description and drawings by a person skilled in the art, the patentee has contemplated. On the contrary, it is to be interpreted as defining a position between these extremes which combines a fair protection for the patentee with a reasonable degree of certainty for third parties.

  55. Section125(1) Patents Act 1977 provides that the invention is to be taken to be that

    specified in a claim of the specification .... as interpreted by the description and any drawings contained in that specification, and the extent of the protection conferred by a patent shall be determined accordingly.

  56. Nowhere in the lengthy specification is there any suggestion that there is merit in taking a single pill comprising 70mg of alendronate, rather than 2 of 35 mg each or any other combination aggregating a dose of 70mg. It is hard to see how such a method of administration could be translated into taking the medicament in liquid form as envisaged by claim 5. Moreover if the claims were so interpreted, in the absence of the provisions of s.4(2) Patents Act 1977 they would scarcely provide the fair protection for the patentee the protocol envisages. Counsel for the patentee accepted that on his interpretation the administration of two pills one of 60mg and the other of 10mg of alendronate would not infringe the patent. Further the word "unit" in a medical or scientific context is apt to connote quantity, dimension or other magnitude. This is evident from such well known works as Black’s Medical Dictionary as well as the Oxford English Dictionary to which we were referred. Accordingly even though claim 1 refers to "a unit dosage form which comprises about 70mg of alendronate" the word unit does not require the administration of a single pill or other dosage form as opposed to an aggregate, however made up, of 70mg of alendronate.

  57. Were there any doubt about the matter, and I do not think there is, then the provisions of paragraphs [0108] to [0110] would resolve it in favour of the respondents. Indeed the very fact that no application to amend the specification so as to exclude these paragraphs until two weeks before the hearing of this appeal indicates that they were regarded as consistent with the other provisions of the specification.

  58. Accordingly I conclude that the judge was right on the interpretation of the patent for the reasons he gave. It follows from this interpretation, as was conceded, that claim 1 is not novel. There were in existence pills containing 10mg and other quantities. A 70mg pill could not be new in the sense required by s.2 Patents Act 1977.

    IS SUCH A CLAIM FOR A METHOD OF TREATMENT WITHIN SECTION 4(2) PATENTS ACT 1977?

  59. In paragraph 80 of his judgment Jacob J concluded with regret that on the basis of his interpretation of claim 1 and applying the decision of this court in Bristol-Myers Squibb v Baker Norton [2001] RPC 1 s.4(2) applied so as to deny patent protection to the claimed invention. As I have indicated the patentee recognises that we are bound by that decision and having upheld the judge on the question of interpretation are bound to reach the same result. As I have also indicated the patentee reserves the right to contend elsewhere that Bristol-Myers Squibb v Baker Norton was wrongly decided.

    SUMMARY

  60. For all these reasons I conclude that:

    1. 042 is invalid for anticipation and obviousness,

    2. 292 is invalid for anticipation and incapacity for industrial application.

    I would dismiss the appeal.

  61. Like Buxton LJ I am concerned that the role of this court has once again not been fully appreciated by the patentees. An immense amount of paper was produced which could not have been relevant to any issue of principle. We heard much argument which, on analysis, did not amount to more than a contention that the judge had wrongly decided the facts. I agree that the practice suggested by Buxton LJ should be adopted in all appeals of this nature. It appears to me that the issue might usefully be considered by the Civil Procedure Rule Committee with a view to amending Rule 52 or the practice direction supplementing that rule both in respect of patent appeals and also all other appeals in which the principle applied by the House of Lords in Designers Guild Ltd v Russell Williams (Textiles) Ltd [2001] FSR 11 and by this court in David J. Instance v Denny Bros Printing Ltd [2002] RPC 14 is material.

    Buxton LJ

  62. I agree that this appeal should be dismissed for the reasons given by the Vice-Chancellor. I add only a few words on a point of procedure.

  63. This appeal obliges the court to set out yet again its proper role when faced with appeals in patent cases that complain of findings by the trial judge on issues of fact, and on issues of judgment in particular relating to anticipation and obviousness. Although the law as to the court’s powers is clearly settled, the present appeal showed that the practice in this area still does not in every respect comply with that law. I therefore venture some observations about how such cases should be conducted in the future.

  64. The appellants correctly recognised the guidance given by this court in Instance v Denny [2002] RPC 14[15], supported by many other cases, including the authority of the House of Lords in Designers Guild v Russell Williams (Textiles) [2001] FSR 11, that this court should interfere with the view of the trial judge only if he can be shown to have erred "in principle". The latter phrase has never been defined, and probably cannot be and does not need to be. At the least, however, it can be said that an error of principle can only arise if the judge has departed from a rule or practice that applies also outside the boundaries of the facts of the instant case; that rule or practice can be coherently encapsulated in verbal form; and can be demonstrated to be binding on the judge. In particular, it is likely to be very difficult to establish that such matters of principle are involved in decisions made by the judge in assessing technical evidence and its bearing on the issues that he has to decide.

  65. The Grounds of Appeal frequently, though not invariably, preceded their complaints by asserting that the judge erred "in principle", but in no case was the relevant principle identified or justified in the manner outlined above, and some assertions were made that on no view could involve errors of principle. Thus, the judge was said to be "wrong" [Grounds of Appeal, §19] in not acting on the papers generated by the CEMO conference in relation to the issue of the activity of neridronate (despite the evidence of Professor Russell and Dr Newton having criticised the conclusions drawn from those papers); he was said to have "wrongly evaluated the evidence" [Grounds of Appeal, §30] in relation to the obviousness of the 292 patent; and he was said to have been "wrong to conclude" on the evidence that in the light of Fleisch no avenue of investigation other than alendronate readily suggested itself.

  66. In other cases, whilst there might have been a matter of principle involved, it was difficult to extract what that principle was. Thus, in §5 the Grounds complained that the judge "erred as a matter of principle .... in holding that a medicinal chemist would form part of a notional research team constituting the "skilled man"’. The objection appeared to be that medicinal chemists were not working in "the field" (scil., of bisphosphonates) at the priority date of the 042 patent because pharmaceutical companies were not working in that field. That submission has very wide implications, and if correct as a matter of principle would seem to protect any step from one field of application to another against an attack on grounds of obviousness. The complaint was in any event unfounded, for the reasons given by the judge in §26 of the judgment. Its nature would however have been much easier to understand if the "principle" said to have been infringed by the judge had been spelled out.

  67. Next, in some cases "principles" were stated or implied, but not then acted on. The appellants complained [Grounds, §3(iii)] that the judge had wrongly construed Blum, by giving no or no sufficient weight to the words "owing to their properties". It would no doubt be an error of principle simply to ignore a phrase in a document; but the judge certainly did attend to the properties described by Blum, and sets them out in §31 of his judgment In truth, as §10 of the Grounds showed, the complaint was not in the general terms asserted in §3(iii) of the Grounds, but rather that the judge failed to draw the conclusion, urged on him by the appellant, but as my Lord points out in §27 above contrary to the evidence before him, that the high complexing powers referred to in Blum’s description indicated that the preparation had no relevance to use as an active agent in bone resorption. That did not involve any issue of principle, but only a matter of judgment well within the peculiar sphere of the judge. Somewhat similarly, the error of principle in alleged in §3(ii) of the Grounds in identifying the common general knowledge in relation to the 042 patent turned out [Grounds of Appeal, §8] to consist simply of a failure to accept within the knowledge various matters asserted by the Appellants.

  68. Apart from issues relating to patent 292 that do not arise for decision I have succeeded in identifying only three complaints within the Grounds that could properly be said to raise issues of principle. Those are

    1. Failure to construe claim 1 of patent 292 according to its literal wording

    2. Failure to take into account the motivation of the skilled man [Grounds, §14]

    3. In assessing anticipation, considering ‘what the "skilled man" would think about [the] disclosed properties" [Grounds, §11].

  69. Not even all of these, so stated, proved on inspection to involve any, or at least any supportable, point of principle. Had the appellant been required to set out authority for point (ii), it would rapidly have become apparent that there is no such principle as stated. That is clear not least from the observations of this court in Pharmacia v Merck [2002] RPC 41 [123]-[124]. Rather, the complaint was, again, as to the judge’s assessment of the evidence: a complaint that, as my Lord has demonstrated in §§34-40 above, was not open to the appellants. Point (iii) proved, during argument, not to be an independent issue at all: see §25 above. Here again, had the provenance and authority for the principle been set out, the true nature of the complaint would have been immediately apparent.

  70. In the light of experience in this appeal, I would venture to suggest that in future, when it is sought to challenge the trial judge’s conclusions on anticipation or obviousness, the Grounds of Appeal should, in respect of each complaint, contain a succinct statement of the principle that the judge is said to have infringed. It should further be demonstrated, unless the matter is self-evident, what is the authority for that principle. I have already indicated in the context of this appeal a number of instances in which that requirement, if applied, would have produced a much clearer understanding of the issues.

  71. If such a discipline is adopted, it may well become apparent that many of the complaints are unsustainable. That would have the effect that the jurisprudence of this court and of the House of Lords in respect of such appeals would be honoured in practice as well as in theory. It should also produced a much more economic and focussed disposal of the appeal; for instance, in the present case, it would not have been thought necessary to copy for the court 21 files, containing in effect all of the material that had been before the trial judge.

  72. I would further venture to suggest that trial judges may wish to have this approach in mind when considering whether to grant permission to appeal. I appreciate that it may not be appropriate at that stage to produce full Grounds of Appeal, but counsel might be asked to demonstrate, before permission is granted, that issues of principle will indeed be engaged in the appeal.

    Laws LJ

  73. I agree with both judgments and have nothing to add.


Cases

Bristol-Myers Squibb v Baker Norton [2001] RPC 1; The General Tire Co v The Firestone Tyre & Rubber Co Ltd [1972] RPC 457; Windsurfing International Inc v Tabur Marine (Great Britain) Ltd [1985] RPC 59; David J. Instance v Denny Bros Printing Ltd [2002] RPC 14; Designers Guild Ltd v Russell Williams (Textiles) Ltd [2001] FSR 11; Johns-Manville Corporation’s Patent [1967] RPC 479; Technograph Printed Circuits Ltd v Mills & Rockley (Electronics) Ltd [1972] RPC 346; Norton Healthcare Ltd v Beecham Group plc (Court of Appeal 19th June 1997 unreported); Bonzel v Intervention (No.3) [1991] RPC 553; Instance v Denny [2002] RPC 14; Pharmacia v Merck [2002] RPC 41

Legislations

Patents Act 1977: s.1(1)(a), (b), s.2(1), (2), s.3, s.4(2), s.75(1), s.76(3)(a), s.125(3)

Protocol on the Interpretation of Article 69 of the European Patent Convention

Authors and other references

Concise Oxford English Dictionary, 10th Edn

Oxford English Dictionary, 2nd Edn vol XIX

Black’s Medical Dictionary

Representations

Mr. David Young QC and Mr. Thomas Hinchliffe (instructed by Messrs Lovells) for the 1st and 2nd Appellants

Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs Bird and Bird) for the 1st Respondents

Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs S J Berwin) for the 2nd Respondents

Mr. Simon Thorley QC and Mr. Michael Tappin (instructed by Messrs Taylor Wessing) for the 3rd Respondents


all rights reserved