Neutral Citation Number: [2009] EWCA Civ 1362
Case No: A3/2008/2966
IN THE HIGH COURT OF JUSTICE
COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION (PATENTS COURT)
The Hon Mr Justice Floyd
HC07C00963
Royal Courts of Justice
Strand, London, WC2A 2LL

Date: 18/12/2009
Before :

THE MASTER OF THE ROLLS
LORD JUSTICE JACOB
and
LORD JUSTICE RICHARDS

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Between :

	Dr Reddy’s Laboratories (UK) Limited	Claimant/
Appellant	
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	Eli Lilly and Company Limited	Defendant/Respondent	
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 (Transcript of the Handed Down Judgment of
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Henry Carr QC, Andrew Lykiardopoulos and James Whyte (instructed by Powell Gilbert LLP) 
for the Claimant/Appellant
Simon Thorley QC, Andrew Waugh QC and Miles Copeland (instructed by
 Howrey LLP) for the Defendant/Respondent

Hearing dates: 10/11 November 2009
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Judgment
Lord Justice Jacob (giving the first judgment at the invitation of the Master of the Rolls):
1.	This is an appeal by Dr Reddy’s (“DRL”) from Floyd J’s judgment of 13th October 2008, [2008] EWHC 2345, whereby he dismissed DRL’s application for revocation of Eli Lilly’s EP (UK) No. 0454436.
2.	Mr Henry Carr QC and Mr Andrew Lykiardopoulos argued the case for DRL.  Eli Lilly’s case was presented by Mr Simon Thorley QC, Mr Andrew Waugh QC and Mr Miles Copeland.
The Common General Knowledge at the priority date (25th April 1990)
3.	The Judge sets this out uncontroversially at [19-35].  There is no point in my attempting to do better so I borrow with gratitude:
Schizophrenia is a debilitating psychiatric disorder.  Its symptoms include delusions and hallucination, withdrawal, lack of motivation and disorganisation of mental function and deficits in memory, attention and executive function. It is treated with antipsychotic agents.
Chlorpromazine was the first effective antipsychotic agent. Its antipsychotic effect was discovered in 1953.  Later experiments by Carlsson & Lindqvist measured metabolism of dopamine in mouse brain tissue and showed that chlorpromazine led to a significant increase in turnover of dopamine in the brain. This led to the theory that chlorpromazine blocked the actions of dopamine as a brain neuro-transmitter.  The theory is known as the dopamine hypothesis of schizophrenia. 
Chlorpromazine has the chemical structure set out below:

                 Chlorpromazine
Chlorpromazine is a phenothiazine, so called because it has two phenyl rings (on the left and right) in the structure around a thiazene central ring. 
Whilst, by 1990, the dopamine hypothesis was the main scientific theory underlying the mechanism of action of chlorpromazine and other antipsychotics, it was also known that a number of neurotransmitters interacted with dopamine and so contributed to a variety of its CNS functions.  
A more or less contemporaneous SCRIP publication entitled ‘Current Trends in Antipsychotic Research’ (1990) (“the SCRIP report”) describes the other neurotransmitters that were implicated at the time.  The introduction to Chapter 2 states that: 
“The pathological changes responsible for the symptoms of schizophrenia are essentially unknown.  Nevertheless, hypotheses on the roles of particular neurotransmitters abound and it could be stated that the number of such theories grows proportionally to the number of neurotransmitters discovered.”  
The chapter concludes by quoting a 1987 paper: 
“Schizophrenia is most likely a multi-neurotransmitter-system disease, caused by a factor or factors that could be acting on any of these systems.”
The discovery of chlorpromazine’s antipsychotic properties led companies to synthesise other phenothiazine derivatives with similar properties and to the development of other agents on new chemical backbones: thioxanthenes and butyrophenones.  All these drugs were essentially designed to be like chlorpromazine in their pharmacological activity profile.  By 1990 the drugs of this type that were available were phenothiazines (such as a thioridazine) thioxanthenes (such as flupenthixol) and butyrophenones (such as haloperidol).  

Perphenazine (a phenothiazine)

Flupenthixol (a thioxanthene)

Haloperidol (a butyrophenone)
These various compounds are (at least now) grouped together as the typical, classical, or first generation antipsychotics (FGAs).  Whilst they undoubtedly demonstrated valuable therapeutic efficacy, the FGAs shared a number of unpleasant side effects, most notably motor side effects referred to collectively as Extra Pyramidal Symptoms (EPS).   EPS included Parkinsonism, akathisia (a type of motor restlessness), acute dystonia (which can take the form of arching of the back, standing in strange positions or staring with the eyes turned up), tardive dyskinesia (which consists of involuntary movements of the face, head, limbs and even body) and tardive dystonias (which are disabling, chronic distortions of posture and are often untreatable). 
The term “tardive” means that the side effect manifests itself only some time after exposure to the drug and, once established, tardive effects can continue even after discontinuation of treatment.  
Classical antipsychotics also caused an elevation of the hormone prolactin in both men and women.  
A breakthrough in antipsychotic drug therapy came with clozapine:

Clozapine
The advantage of clozapine was that it proved to be just as effective against the positive symptoms of schizophrenia as the earlier drugs, but did not produce their range of EPS or prolactin elevation. Hence clozapine was designated the first of the “atypical” antipsychotic drugs.  
Clozapine was discovered in 1959. Unfortunately, following its clinical introduction in the early 1970s, clozapine was implicated in the death of a number of patients who developed a fatal suppression of white blood cells (agranulocytosis) after taking the drug.  It was accordingly withdrawn.  The drug was eventually re-licensed in the UK (in 1989) but only under the strict condition that patients were required to undergo weekly blood tests.  This enforced regime made clozapine an expensive (and inconvenient) drug to prescribe.
The need in 1990 was thus for a safe and effective antipsychotic which shared clozapine’s lack of EPS but which did not share its agranulocytotoxicity. 
In 1990 it was not known what precisely gave clozapine its property of avoiding EPS.  As the SCRIP report stated in 1991: 
‘In addition to the antidopaminergic effects, clozapine has a multiplicity of receptor interactions including muscarinic, α-adrenergic, serotonergic, and histaminergic receptors.  It is at present unclear whether any specific combination of these contributes to its unique properties.’ (Page 39, first paragraph). 
In addition there was no explanation for the agranulocytosis observed with clozapine in clinical use.  
In subsequent research, when a new chemical entity was synthesised with a view to discovering a new antipsychotic agent, it was tested for its neuroleptic activity.  The term “neuroleptic” describes the pharmacological activity of compounds characterised by their ability to induce a particular profile of behaviour by blocking dopaminergic receptors. Mechanisms employed to assess neuroleptic activity included different ligand binding assays (dopaminergic, serotonergic, histaminergic, muscarinic) to establish a range of receptor affinities, and behavioural studies in animals e.g. a conditioned avoidance response, or “CAR” test” and a catalepsy test or “CAT” test. The idea of the latter tests was to see whether a given dose of the test substance could block the conditioned response (e.g. avoiding a shock which the rat was conditioned to know followed a buzzer) without producing catalepsy (i.e. a total blockade).  I shall have to return to the CAR and CAT tests in connection with one of the citations. 
The view expressed in the SCRIP report as of 1990 (page 62) was that:
“the chances for a major breakthrough in the field of drug treatment of schizophrenia to occur in the near future are rather slim. Progress is impeded by our profound ignorance of the real cause(s) and pathogenesis of schizophrenia”. 
4.	This last passage is important: the state of the art was not one where reliable predictions could be made.   Some drugs helped sometimes but even then no one was sure why, and there were severe problems with side effects even if they worked.
The Patent
5.	The priority date is 25th April 1990. Claim 3 (upon which all the argument concentrated) is for a single chemical entity which has the chemical name olanzapine.   This is now a widely used anti-psychotic agent for the treatment of schizophrenia.   Its chemical formula is as follows:

6.	The Patent begins by reciting some of the history of antipsychotic drugs and their unwanted side-effects, especially EPS.  It then mentions clozapine, its freedom from EPS but its tendency to cause agranulocytosis.
7.	It then acknowledges British Patent 1,533,235, the Provisional Specification for which is relied upon by DRL both for novelty and obviousness attacks.  It says this:
A further group of antipsychotic compounds is that described in British Patent 1 533 235.  These include thieno-benzodiazepines having the following structural nucleus.
[formula set out]
The lead compound from this group, flumezapine, (7-fluoro-2-methyl-10-(4-methyl-1-piperazinyl)-4H-thieno-[2,3-b][1,5]-benzododiazepine), was developed to the stage of being clinically administered to psychiatric patients suffering from schizophrenia.  A total of 17 patients received treatment with flumezapine before the clinical trial was terminated after consultation with the U.S. Food and Drug Administration, because of an unacceptably high incidence of raised enzyme levels in the treated patients.  The enzyme, creatinine phosphokinase (CPK), and the liver enzymes, serum glutamate oxalacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), estimated from blood samples taken from patients, were in substantial excess of normal values, indicating the possibility of toxicity.  In respect of its tendency to raise liver enzyme levels, flumezapine is similar to chlorpromazine, an antipsychotic which has long been in use but whose safety has been called into question.
8.	The Patent then goes on to tell the reader about olanzapine:
We have now discovered a compound which possesses surprising and unexpected properties by comparison with flumezapine and other related compounds.
9.	After setting out the structure of olanzapine the Patent descends into some detail about its advantages.  These are clearly based on real evaluations both in animals and in early clinical tests.   This is what it says:
“In the first completed open (as opposed to blind) study of the compound of the invention in schizophrenic patients, six out of eight patients who completed at least 2 weeks of treatment showed between 66% and 87% improvement at 4 weeks, as assessed on BRPS scale, at daily dosages between 5 and 30 mg.  Preliminary results from a further three ongoing clinical trials now appear to confirm this high level of efficacy and at doses lower than or at the low end of the dosage level used in the first study, for example, at 2.5 and 5 mg per day.
Moreover, there is a low incidence of only mild and transient elevation of liver enzymes in patients treated with therapeutic doses, and plasma levels of creatinine phosphokinase (CPK) are lower than with flumezapine, indicating a lower adverse effect on muscular tissue.  Furthermore, the compound of the invention causes lower elevation of prolactin levels than other currently used neuroleptic drugs and this suggests fewer disturbances of the menstrual cycle, and less gynecomastia and galactorrhea.  No alteration of white blood cell count has been observed in clinical studies.
In dog toxicity studies with a closely analogous compound, 2-ethyl-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b]-[1,5]benzodiazepine, at a dosage of 8 mg/kg, it was observed that four out of eight dogs showed a significant rise in cholesterol levels, whereas the compound of the invention did not show any rise in cholesterol levels.
Overall, therefore, in clinical situations, the compound of the invention shows marked superiority, and a better side effects profile than prior known antipsychotic agents, and has a highly advantageous activity level.”
10.	There is further detailed information obviously based on real experimental work:
As mentioned above, the compound of the invention has useful central nervous system activity.  This activity has been demonstrated in models using well-established procedures.  For example, the compound has been assessed in a number of standard behavioural tests predictive of antipsychotic activity.  It antagonised apomorphine-induced climbing behaviour and hypothermia in mice (Moore, N.A. et al. Psychopharmacology 94 (2), 263-266 (1988), and 96, 539 (1988)) at doses of less than 10 mg/kg.  The compound also inhibited a conditioned avoidance response in rats (ED50 4.7 mg/kg), but unlike standard compounds, it induced catalepsy only at much higher doses (ED50 39.4 mg/kg).  This separation between the doses required to block a conditioned avoidance response and to induce catalepsy indicates that the compound is less likely to induce extrapyramidal side effects in the clinic.
The compound of the invention was also active at doses of less than 10 mg/kg in a test based on the apomorphine-induced climbing test referred to above, which measured the ability of the compound to prevent the disruption of climbing response produced by 24 hour pre-treatment with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a dopamine receptor inactivating agent (Meller et al. Central D1 dopamine receptors, Plenum Press, 1988).  This test shows that the compound possessed activity at both the D-1 and D-2 receptors.
In addition, the compound of the invention has been found to have a favourable profile of activity in a number of invitro binding assays, designed to measure the degree of binding to neutral receptors.
In keeping with the observations made in the behavioural tests, the compound is active at both the dopamine D-1 and D-2 receptors as indicated by an IC50 of less than 1 μ M in the 3H-SCH23390 (Billard, W. et al. Life Sciences 35 1885 (1984)) and the 3H-spiperone (Seeman, P. et al. Nature 261 717 (1976)) binding assays respectively.
The compound has an IC50 of less than 1 μ M in the 3H-QNB binding assay described by Yamamura, HI and Snyder, SH in Proc.Nat.Acad.Sci. USA 71 1725 (1974) indicating that it has antimuscarinic-anticholiner-gic activity.  In addition, the compound shows its greatest activity at the 5-HT-2 receptor in that it displaces H-spiperone from binding sites in the rat frontal cortex (Peroutka, SJ and Snyder, SH Mol. Pharmacol. 16 687 (1979)) at low nanomolar concentrations.  The compound is also active at the 5-HT-IC receptor.
This profile of activity in vitro receptor binding assays, like that observed in the behavioural tests, would indicate that the compound is effective in the treatment of psychotic conditions but is less likely to induce extra pyramidal side-effects.
11.	So far as my experience goes, this information is much greater than that generally provided in a patent for a new pharmaceutical compound.  The general run of such patents contains a disclosure of some promising pharmaceutical activity by way of small scale in vivo  tests and no more.  This Patent has gone a lot further – even early clinical tests are reported.
12.	My own experience accords with that of the EPO and the British Patent Office.   Thus in T0609/02 the Board of Appeal said:
9 …. It is a well-known fact that proving the suitability of a given compound as an active ingredient in a pharmaceutical composition might require years and very high developmental costs which will only be borne by the industry if it has some form of protective rights. Nonetheless, variously formulated claims to pharmaceutical products have been granted under the EPC, all through the years. The patent system takes account of the intrinsic difficulties for a compound to be officially certified as a drug by not requiring an absolute proof that the compound is approved as a drug before it may be claimed as such. The boards of appeal have accepted that for a sufficient disclosure of a therapeutic application, it is not always necessary that results of applying the claimed composition in clinical trials, or at least to animals are reported. Yet, this does not mean that a simple verbal statement in a patent specification that compound X may be used to treat disease Y is enough to ensure sufficiency of disclosure in relation to a claim to a pharmaceutical. It is required that the patent provides some information in the form of, for example, experimental tests, to the avail that the claimed compound has a direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent per se. Showing a pharmaceutical effect in vitro may be sufficient if for the skilled person this observed effect directly and unambiguously reflects such a therapeutic application.
13.	Likewise the Hearing Officer at the British Office in Aeomica (BL O/286/05, 25th October 2005 said:
[40]  … not every compound falling within the scope of a claim would be tested in a human pharmaceutical context, and it is rare to have human or even animal data.  However in any application I would expect some evidence that the compound displays the properties claimed and all of the compounds claimed would be expected to display the same properties and have the same effect in a pharmaceutical context.   In other words I would expect a specification to identify at least one compound that had been shown to work.
The attacks on validity
14.	There are three principal attacks pursued on appeal (there were a number of others below):
(1)	Lack of novelty over a prior Lilly disclosure, British Provisional Specification 1,533,235 (“235”) published on the same day in November 1978 as the corresponding Complete Specification of the granted patent of the same number;
(2)	Obviousness over 235;
(3)	Obviousness over a review article published by a Lilly scientist, Dr Chakrabarti, in 1980.   Originally there were two forms of attack but the appeal is now limited to one based on a case of “SAR optimisation”.
A fourth attack, insufficiency, is also raised, but only on a contingent basis – as an answer to Lilly’s respondent’s notice point.
The Judgment below
15.	Floyd J rejected the three attacks I have identified.   Lilly had sought to defend the patent on a further ground, namely that it was a valid “selection patent” (as to the meaning of this term of art, see below). In case he was wrong on the main attacks, Floyd J went on to consider this point in an appendix to his judgment, rejecting Lilly’s selection argument.  If necessary Lilly raises the point by its respondent’s notice.   
16.	As a consequence of this two-part approach we initially heard only the appeal.  Having done so we considered it would be helpful to hear the respondent’s notice point also – we were right to do so for it helped us understand better the main appeal points.
What 235 discloses
17.	235 begins with a bare assertion:
This invention relates to a novel class of thienobenzodiazepines having useful central nervous system activity and/or which are useful as intermediates for preparing the novel compounds of the invention.
18.	The class is then set out by a so-called Markush formula:

19.	235 then sets out the possibilities for each of R1, R2, Q and T.   They are vast.  Formula I includes at least 1019 compounds.    
20.	Next 235 identifies a narrower class.   It says:
Preferred compounds falling within the scope of compounds defined in any of formulae (I) – (VII) above are those having one or more of the following characteristics:
Why this class is “preferred” is never explained.   And the class is far from narrow in any event, comprising as it does 86,000 compounds.  
21.	It also names about 100 compounds, but gives no indication that any of them have ever been made, still less tested.  There are 15 examples of the preparation of 15 specific compounds.   Nothing tells you about the specific properties of any individual compound.
22.	Finally 235 says a bit more about the utility of the compounds:
As stated previously, the compounds of formula (I) and acid addition salts thereof, have useful nervous system activity.   Specifically, they are potent centrally acting compounds with neuroleptic, sedative or relaxant effects.   These properties, coupled with their high therapeutic index, render them useful in the treatment of mild anxiety states and certain kinds of psychoses.
The statement is a mere assertion, unsupported by any experimental evidence. A skilled reader is quite unable to decide whether the assertion is true, or soundly based or plausible.  
Lack of Novelty over 235
23.	Olanzapine is one of the 1019 compounds of formula (I) and one of the 86,000 compounds of the “preferred” class.  It is not mentioned specifically.   
24.	DRL contends that nonetheless this specific compound lacks novelty – that in the language of EPC Art. 54 it formed “part of the state of the art” having been “made available to the public by means of a written .. description.”   The contention amounts to this:  that every chemical class disclosure discloses each and every member of the class.   It would, it seems, even apply if the formula had simply been written down without any suggested utility.
25.	I reject the contention for two reasons: firstly as a matter of a priori reasoning and secondly because it is inconsistent with settled EPO Board of Appeal case law.
26.	First then, the a priori considerations apart from case-law.   An old question and answer runs as a follows:  “Where does a wise man hide a leaf?  In a forest.”    It is, at least faintly, ridiculous to say that a particular leaf has been made available to you by telling you that it is in Sherwood Forest.   Once identified, you can of course see it.   But if not identified you know only the generality:  that Sherwood Forest has millions of leaves.
27.	The contention has no logical stopping place.  If there is disclosure of olanzapine here, why would one not regard an even more general disclosure as a disclosure of it.  Suppose the prior art had merely been of “3-ringed organic compounds?”      Such a description would encompass much much bigger numbers than the 1019 of formula I.  Yet the logic of the argument would be the same – that there is a disclosure of each and every member of the class.
28.	I would add that I would regard the listing out of a great number of compounds as opposed to the use of a Markush formula in the same way.   To say a particular book is identified by saying “the books in the Bodleian” is no different from saying it is identified by providing access to the catalogue of the Bodleian.
29.	Similarly it makes no sense to say that a generalised prior description discloses a specific matter falling within in.   The Judge’s example illustrates the point.  A prior disclosure of “fixing means” is not a disclosure of a particular fixing means e.g. welding or riveting even though you could list out a whole number of ways of fixing things together which would include these means.
30.	Thus logic dictates rejection of the argument that a disclosure of a large class is a disclosure of each and every member of it.  So also does EPO case-law. Mr Carr accepted that was so, so I can take the matter quite shortly, going to just one case, Hoescht Enantiomers T 0296/87 which effectively sums up earlier cases.  It said:
6.1 Here the Board is guided by the conclusions it reached in its "Spiro compounds" decision T 181/82 (OJ EPO 1984, 401) concerning the novelty of chemical entities within a group of substances of known formula. With regard to products of the reaction of specific spiro compounds with a (C1-C4)-alkyl bromide defined as a group, the Board drew a sharp distinction between the purely intellectual content of an item of information and the material disclosed in the sense of a specific teaching with regard to technical action. Only a technical teaching of this kind can be prejudicial to novelty. If any such teaching is to apply in the case of a chemical substance, an individualised description is needed.
So what one must look for by way of an anticipation is an “individualised description” of the later claimed compound or class of compounds.   This case is miles from that.   It is noteworthy that the Board’s application of that principle in that case to enantiomers was specifically followed by this Court in Generics v. Lundbeck  [2008] EWCA Civ 311; [2008] RPC 19 per Lord Hoffmann at [9].   
31.	It is not necessary here to go into what is sufficient to amount to an “individualised description.” Obviously the question may partly be one of degree, but other considerations may come in too, for instance the specificity of any indicated purpose for making the compounds.  A mere woolly indication of the possible use of the prior class may require less specificity than a precise one.   
32.	This view of the law accords with the decision of the House of Lords in Synthon’s Patent [2006] RPC 10.   Lord Hoffmann said:
[22]	If I may summarise the effect of these two well-known statements, the matter relied upon as prior art must disclose subject-matter which, if performed, would necessarily result in an infringement of the patent. That may be because the prior art discloses the same invention. In that case there will be no question that performance of the earlier invention would infringe and usually it will be apparent to someone who is aware of both the prior art and the patent that it will do so.
Where you have a patent for a particular chemical compound and a prior art general disclosure, performance of the general disclosure (which means no more than using anything within it) does not necessarily result in infringement of the patent.   In this case, for instance, you can “perform” 235 in any of 1019 ways – only one of them would result in infringement of the later patent.
33.	Accordingly I would reject the anticipation attack.  In so doing I am glad to find that the approach I adopt is not only the same as that in the EPO but also the same as that in Germany.    It was well-articulated in the case involving the German equivalent of the patent in suit, STADApharm No.1-2W 47/07 (29th May 2008).  The Bundespatentgericht had held the patent invalid.  But even so the Oberlandsgericht in Dusseldorf (an infringement only court) decided to enforce the patent, holding in effect that the Bundespatentgericht’s decision was so obviously wrong that it would surely be reversed on appeal (which it duly was).   In the context of novelty over 235 it said:
what is relevant is whether by the indications given by a prior art document on the chemical compound, the skilled person is able without difficulties to carry out the invention relating to this compound, i.e. whether he can actually obtain the relevant substance. For merely practical reasons the availability cannot be confirmed by stating that the person skilled in the art was able to work through the countless alternatives falling under this formula, and in doing so would eventually arrive at the compound in question. It is disclosed to him in a cited reference only when the prior document contains a concrete indication of the claimed compound, such as a description thereof as a preferred embodiment, and if the skilled person is able to produce the compound on the basis of this indication and his general technical knowledge.
On the appeal the Bundesgerichthof did not even find the allegations of invalidity over 235 as worthy of mention – perhaps they had been dropped by then.  
Obviousness over 235
34.	It was here that Mr Carr concentrated most of his argument.  There are some necessary preliminaries before I get to it.
35.	The “individualised description” approach was not part of the UK approach to anticipation under the pre-EPC law.   On the contrary the general rule was that “disclosure of the class prima facie deprives its members of novelty” and  “prima facie a general disclosure of a class is a disclosure of all members of the class, however obscure and whatever the consequences.” (Blanco White QC, Patents for Inventions 4th Edn. (1974)  p.120 fn.60,  fn. 62. and p.121.
36.	This is of great significance to understanding the previous law of “selection patents.”   To avoid a finding of anticipation a patent for a compound or sub-class had to disclose something special about the compound or sub-class, which led to the rules about so-called “selection patents”.   Those rules were famously formulated by Maugham J in I.G. Farbenindustrie’s Patents (1930) 47 RPC 289 at p.322-3:
Three general propositions may, however, I think, be asserted as true:- First, a selection patent to be valid must be based on some substantial advantage to be secured by the use of the selected members (the phrase will be understood to include the case of a substantial disadvantage to be thereby avoided).  Secondly, the whole of the selected members must possess the advantage in question.  Thirdly, the selection must be in respect of a quality of a special character which can fairly be said to be peculiar to the selected group.
They were actually formulated under the common law, which did not draw a distinction between lack of novelty and obviousness, both of which fell under the general umbrella “lack of subject-matter.”  The rules were carried over by the judges into the newly codified law in 1932 and remained, almost as a special sub-branch of patentability, as part of English law until the “new law of patents” (a recital to the Patents Act 1977) came in.
37.	The rule was last considered as part of the pre-1977 law by the House of Lords in Du Pont’s Patent [1982] FSR 303.  We had much debate before us analysing what Lords Wilberforce and Simon had to say about the position and the differences between them.  Interesting though it was, in the end I did not find it helpful.   It is most unlikely that the courts of any of the other 33 members of the European Patent Union would pay the slightest attention to English pre-1977 jurisprudence even of the highest court (why should they?).   The EPO does not use the IG rules. They form no part of the EPO Guidelines for Examination and no Board of Appeal decision was cited which applied them.  So I think the best thing to do is to regard them as part of legal history, not as part of the living law.
38.	In so saying I am conscious that this court referred to the IG rules in Hallen v Brabantia [1989] RPC 307, a case which was indeed under the 1977 Act.  But I do not regarding it as deciding that the rules were part of the post-1977 law – that was never argued.  The case involved no more than an attempt by the patentee to justify its patent by reference to the IG rules and an answer by the defendant that the patent did not comply with them because there was no disclosure of the alleged special advantage.
39.	I would only add this about the IG rules.  If one thinks about them, it is difficult to see how, realistically, they could be complied with unless the patentee carried out an enormous range of experiments.  How can you show your class (or compound) has a “substantial advantage” over the prior class without experimenting with at least quite a lot of the class – enough to make a sound prediction at the very least?  Or how can you show that the quality which makes your selected class is peculiar to that class?   If you put in your thumb and pull out a plum, how are you to say that there are no other plums in the pudding?
40.	So I think the better approach is to see what the EPO Boards do when a patented product or class of products falls within a greater class.    They deploy the objection of obviousness where the patentee has in truth made no real technical advance.  
41.	Before examining how they do that there is an initial point to make.   Obviousness, as always, is to be judged at the priority date of the patent.  So one of the considerations that can come into play is a difference in date between the earlier publication of the class and the priority date.   Whether it matters in an individual case will of course depend on the facts.
42.	Here, for instance, 235 was published in 1978 and the date of the patent is 1990 – a gap.  The Judge discounted the time difference as having any significance because he considered that the field was foreclosed by Lilly’s earlier 235 patent.  There was some evidence that people consider the patent position of rivals before deciding what to research and tend to steer clear.  But that cannot be a complete answer:  if there is a valuable drug to be found within a territory prima facie foreclosed by another, there is likely to be a real incentive to go for it.  After all you will be later in time (the earlier patent will expire earlier, perhaps even before your drug is anywhere near ready to market).  Moreover there will be cases where the earlier patent is invalid or very probably so – it is difficult to see, for instance, how the 235 patent could have been valid under the old law given that it had claims of substantial width and simply no material upon which a “sound prediction” (to use Graham J’s words in Olin Mathieson v Biorex [1970] RPC 157 at p. 193) as to pharmacological activity could be made.   For those reasons I am not sure I myself would have made a total discount of the time difference, but that does not mean that on appeal I should form a different view.  The Judge’s view was one he could legitimately take.
43.	Another matter which comes into play on the question of obviousness (as opposed to anticipation) is the very nature of the information in the prior publication.    Is it likely to be read by the skilled person as conveying serious technical teaching which he/she will take seriously and expect to be true?  Or is it no more than an unsubstantiated speculation?   If the latter, then the skilled person is far less likely to do anything with it and specifically identifying a compound and showing its utility is much more likely to be regarded as inventive.
44.	What then does the EPO do?   The answer is essentially this:   that it regards what can fairly be regarded as a mere arbitrary selection from a class as obvious.   If there is no more than an arbitrary selection then there is simply no technical contribution provided by the patentee.
45.	I go to the two most important of the cases relied upon by Mr Carr.   First is the well-known case of  AgrEvo T 0939/92.  I set out some of the important passages (bold passages are in the original):
2.4.2   ….it has for long been a generally accepted legal principle that the extent of the patent monopoly should correspond to and be justified by the technical contribution to the art [citations omitted]. Now, whereas in both the above decisions this general legal principle was applied in relation to the extent of the patent protection that was justified by reference to the requirements of Articles 83 and 84 EPC, the same legal principle also governs the decision that is required to be made under Article 56 EPC, for everything falling within a valid claim has to be inventive. If this is not the case, the claim must be amended so as to exclude obvious subject-matter in order to justify the monopoly.
2.5.3   …. a mere arbitrary choice from this host of possible solutions of such a "technical problem" cannot involve an inventive step [citation omitted].  In other words, the Board holds that, in view of the underlying general legal principle set out in point 2.4.2 above, the selection of such compounds, in order to be patentable, must not be arbitrary but must be justified by a hitherto unknown technical effect which is caused by those structural features which distinguish the claimed compounds from the numerous other compounds.
46.	Because AgrEvo was concerned with a sub-class claim the Board went on say something about such claims:
2.5.4 It follows directly from these considerations that a technical effect which justifies the selection of the claimed compounds must be one which can be fairly assumed to be produced by substantially all the selected compounds.
2.6	Therefore, the Board holds that, contrary to the Appellant's submission, the assessment of the technical contribution to the art must take account of the actual technical reason for providing the very compounds now being claimed, as distinct from the host of other theoretically possible modified chemical compounds. 
In view of this state of the art the technical problem which the present patent application asserts to solve is the provision of further (alternative) chemical compounds with herbicidal activity. However, in the light of the Board's finding in point 2.4.3 above, this technical problem could only be taken into account if it could be accepted as having been solved, i.e. if, in deciding the issue under Article 56 EPC, it would be credible that substantially all claimed compounds possessed this activity (see also point 2.5.4 above).
47.	The Board went on to hold on the facts that the claimed herbicidal activity of the class sought to be claimed was not shown to be credible,  the onus lying on the patentee to justify that its claimed selection had the properties claimed for it.   Such a point does not of course arise here where the claim is to a single compound which undoubtedly does have the properties claimed for it.
48.	Wyeth, T133/01, an appeal from the examining division, was the case Mr Carr relied upon most strongly.  There was a claim (claim 4) for a particular compound “which may be an individual enantiomer or a mixture of enantiomers or a pharmaceutically acceptable salt thereof.”    A prior disclosure, identified as the closest piece of prior art, disclosed a class which included the subject-matter of claim 4.   The prior art disclosure said the class were dopamine D2 receptor agonists.   The patent said the same thing about its claimed substances.   The patentee tried to justify his patent by saying his claimed compounds had better selectivity.  He did not rely on anything said or disclosed in his patent, but attempted to rely on an experiment comparing the claimed product with a single, arbitrarily chosen, compound of the earlier class.
49.	The Board upheld the objection of obviousness.  It rejected the comparison saying:
[4.4] … Thus, the Appellant's comparative test report is unfair in not truly reflecting the subject-matter disclosed in the closest prior document (1). While showing in general a dopamine D2 receptor agonist activity of the compounds according to the invention, the test report does not properly demonstrate that the purported improvement in selectivity of the claimed compounds has been successfully achieved vis-à-vis that state of the art. As a consequence, this test report is irrelevant and must be disregarded in the assessment of inventive step.
According to the jurisprudence of the Boards of Appeal, alleged but unsupported advantages cannot be taken into consideration in respect of the determination of the problem underlying the claimed invention [citations omitted]. Since in the present case the alleged improvement, i.e. a better selectivity of the dopamine D2 receptor agonist activity, lack the required adequate support, the technical problem as defined in point 4.3 above needs reformulation.
And it reached its conclusion of obviousness saying this:
In the absence of evidence to the contrary, the Board concludes that faced with the problem indicated above, namely to provide merely further compounds having a dopamine D2 receptor agonist activity, a skilled person would not require any inventive skill in picking out at random from structural variants outlined in document (1) the substitution of the basic 2,3-dihydro-1,4-dioxinoindol structure with an OH- and a benzylamino-methyl group thereby arriving without inventive ingenuity at the compound of claim 1, which is the solution proposed by the present application.
50.	Mr Carr submitted that in substance the EPO jurisprudence had re-created the IG rules albeit in the context of obviousness.  I do not accept that.  The EPO jurisprudence is founded firmly around a fundamental question:  has the patentee made a novel non-obvious technical advance and provided sufficient justification for it to be credible?  That is the basis of all the reasoning – see e.g. [2.4.2] of  AgrEvo.   A “selection” (by which I mean the later claimed compound or sub-class) which makes a real technical advance in the art is patentable.
51.	More specifically Mr Carr contended that a sub-class or individual member of a prior art published class was taken to be obvious if it was a random selection from the earlier class.  I have no difficulty with that.  Such a “selection” provides no technical contribution.   Mankind can learn nothing new from it.  Nor indeed does Lilly dispute that proposition.  It said in its skeleton argument:  “Lilly does not dispute that in relation to obviousness a selection from the prior art cannot be merely arbitrary.”
52.	Of course one has to consider here what is meant by an “arbitrary selection.”   The answer is to be found in the guiding principle – is there a real technical advance?
53.	So the real question is whether by identifying olanzapine and disclosing what it does about its properties, Lilly were making an arbitrary selection.   I am quite unable to see how that could be so.    I say that for two reasons:   
54.	Firstly it is quite clear that the problems identified by the Patent have nothing to do with selecting from a wider class in ‘235.  The problems identified in the patent were to find something like clozapine (with its freedom from EP side effects) but without clozapine’s unfortunate agranulocytosis side effect, and to find something better than flumezepine (with its EP side effects).   Flumezepine is described as a “lead” compound, itself implying (as Professor Roberts accepted) that there were other, less satisfactory compounds which had been investigated.   The Patent also discloses superior (because no rise in cholesterol levels in dogs) properties for olanzapine compared with the closely analogous compound ethyl olanzapine.
55.	None of that indicates a mere “arbitrary selection” telling the reader in effect no more than he would get from reading 235. 
56.	Secondly it is also quite clear that the disclosure of 235 would have been read in 1990 with at least a pinch (perhaps a sackful) of salt.  All the skilled reader would get from 235 is the rather vague promise of “neuroleptic, sedative or relaxant effects for all 1019 compounds” with the equally vague promise of “high therapeutic index” (which is plainly a term which can cover relative freedom from EPS but may cover other things such as relative freedom from toxicity generally) coupled with no evidence to support these promises.   The skilled reader’s common general knowledge would tell him about the general unpredictability in this field – an unpredictability caused by a lack of understanding of the causes of psychoses and the detailed manner of action of known drugs. 
57.	A particular aspect of unpredictability was, oddly, relied upon by Mr Carr.   Professor James agreed that although the Patent shows that olanzapine is better vis-à-vis cholesterol levels than ethyl olanzapine, you could not generalise from that as regards other compounds of the “preferred” class of 86,000.   I do not see how that helps Mr Carr.  Once it is accepted that the whole field is unpredictable, then the woolly teaching of 235, if not totally useless, is no guide to any particular compound. You cannot say a particular compound out of a vast class is obvious if you have no real idea as how any individualised member of that class might behave.   
58.	The Judge dealt with obviousness over 235 at [150-159].   I cannot see anything wrong in his assessment – indeed Mr Carr did not really direct his attack to the Judge’s approach.  His attack was based on the “arbitrary selection” theory, which in my judgment is simply misplaced on the facts.
59.	It is sufficient here, therefore to record one particularly powerful reason the Judge gave for finding non-obviousness over 235:
[156]	Secondly I consider that the skilled team would have been predisposed, on the basis of the common general knowledge, towards including an electron withdrawing group on the phenyl ring, rather than leaving it unsubstituted. The team would have no reliable basis for concluding that unsubstituted compounds would work at all. To include such compounds in the research is, in my judgment, not an obvious step to take. 
60.	That was unchallenged before us.  To my mind it alone is enough to defeat the appeal on obviousness over 235.
Obviousness over Chakrabarti 1980
61.	Originally this attack was two-fold.   Shortly before the hearing one of these was abandoned and we are left with the other, described by the Judge as “obvious by SAR optimisation.”  SAR is an acronym for “structure-activity relationships.”
62.	The Judge summarised the disclosure of Chakrabarti 1980:
[48]	Dr Chakrabarti was leader of the team at Lilly with the responsibility for developing novel anti-psychotic drugs.
[49]	In 1980, with co-authors from Lilly, Dr Chakrabarti published a paper in the Journal of Medicinal Chemistry entitled “4-piperazinyl-10-H-thieno[2,3-b][1,5]benzodiazepines as Potential Neuroleptics”.  This was Part 3, and not the final part, of a series of papers.  The article was impressive in that it reported the synthesis of some 59 compounds.  The article notes, early on, the fact that clozapine differs from other dibenzoepines in having a reduced incidence of EPS. The authors produce a figure and chart like this:

[50]	The authors drew attention to the fact that the atypical clozapine differed chemically from typical neuroleptics in having a chlorine substitution in position 8 in ring A, as opposed to position 2 in ring C. This effect had also been reported in the case of another classical neuroleptic, octoclothepin.  The authors discuss the reasons for this change in activity in the following way:
“There is no definitive explanation as to how the transposition of this halogen substitution can result in a profound change in activity. Molecular topography of clozapine and HF-2046, as determined by X-ray crystallography, does not reveal any significant difference. Electron transfer reactions have been often implicated in reversible attachment of biologically active molecules at a receptor site. Such a shift in nuclear substitution, as above, can contribute to the electronic imbalance between the two benzene rings of the asymmetrical tricyclic system.”
[51]	The authors surmise that, if an electron withdrawing group such as chlorine, can shift the electronic balance of the molecule to advantage, the same effect might be achievable by replacing ring C (the right hand ring as shown above) with a suitable heterocyclic ring i.e. a ring in which carbon is replaced by another atom, such as nitrogen or sulphur.  Such a ring would be electron-rich, and thus create or contribute to the electron imbalance in a different way.  In particular, the authors propose replacing benzene ring C with a thieno- ring, a five-membered ring with a sulphur hetero-atom:
 
[52]	In order to test this theory, a series of individual compounds is recorded as having been synthesised.  The compounds selected use a range of values of R1, R2 and R.  Compound 6 is ethyl olanzapine: in other words a compound identical to olanzapine but with a ethyl rather than a methyl substituent on the thieno- ring. Olanzapine is not included in the list.
[53]	The compounds recorded as synthesised were tested for neuroleptic activity by their ability to induce hypothermia in mice and by their comparative scores in conditioned avoidance response and catalepsy tests in rats.  The objective (in the case of the CAR and CAT tests) is (as mentioned earlier) to find a drug which blocks the conditioned avoidance response at doses that are lower than those required to induce catalepsy. 
[54]	The results were compared with those obtained with known anti-psychotics, clozapine, haloperidol, thioridazine and cis-flupenthixol.
[55]	From the results, the authors are able to draw certain conclusions about the relationship between structure and activity: 
(i) as to the substituent R on the piperazine ring, the authors say that higher alkyl substitution (i.e. anything bigger than methyl) leads to a reduction in activity.  However, compounds where R is a hydroxyalkyl group such as hydroxyethyl “retain good activity”;
(ii) the substitution of ring A with a halogen atom at position 7 on the retained benzene ring enhanced activity;
(iii) a short alkyl substitution (methyl, ethyl, iso-propyl) at position 2 on the thiophene ring seems to increase the activity, but compounds with a bulky (tertiary butyl) or long (n-hexane) group showed only minimal activity. 
[56]	The authors conclude the article in the following way:
“Unlike the standard neuroleptics tested, clozapine blocks the conditioned avoidance response in rats at doses which are very much lower than those required to produce catalepsy.  It is thought that this profile of activity is associated with the relative lack of extrapyramidal side effects produced by this compound in the clinic. A number of compounds in the present series, e.g. 9, 12, 17,29, and 34, have been found to be more potent than clozapine and show a similar, if less marked, separation of activity in these two tests. This profile of activity needs further development of this class of compounds.”
63.	Professor Roberts suggested that this information would lead a skilled team to synthesise a further 11 compounds for testing, one of which would be olanzapine.   The reasoning ran as follows:
i)	The skilled team would note that 5 of the tested compounds (9,12, 17, 29 and 34) show potent neuroleptic activity and yet maintain favourable separation of activity on certain assays which indicates that EPS are less likely.
ii)	It would note that within this group of 5 compounds, there were 2 substituents at the 4 position on the piperazinyl ring and 3 on each of the remaining rings.   
iii)	It would consider all the possible ways these substituents could be varied (2x3x3).  One would do this because one could not know from the existing data quite what substituent (or substituents) in what position(s) was giving the desirable activity – which combination was it?   You investigate the structure activity relationship caused by the substituents to try to find the best.  There are 18 compounds.
iv)	7 of these have already been made and tested by Chakrabarti.
v)	The logical thing to do would be to make the other 11 and test them.  And you would do that at an early stage of investigation to find the most promising, rather than just go ahead with more investigation with one of the Chakrabarti compounds.  
vi)	One of the 11 is olanzapine.  So it is obvious.
64.	The Judge rejected this argument.   He concluded:
[171]	Viewed without hindsight, the research program advocated by Professor Roberts would have been just that: an exploration of further compounds without any real prospect that any of them would have solved the problem with which the art was concerned.  The problem was not to find another compound like clozapine: but finding one which did not have the same impact on white blood cells. 
65.	The Judge gave a number of reasons for so concluding.   He accepted that those seeking to explore the SAR of a class of compounds would approach it systematically as described by Prof. Roberts and that Chakrabarti 1980 did not indicate that a halogen substituent on the phenyl ring was essential.
66.	But he did not accept that the skilled team would proceed as suggested by Prof Roberts because it would conclude, from the very large number of compounds tested, that there had already been a systematic investigation.  He said:
[168]	Given the scope and extent of the testing revealed by the paper, and the attractive levels of differentiation in the tests, I prefer the view of Professor Nichols that the skilled person would select one or more of the highlighted compounds to take forward into further testing, rather than embarking on a more systematic review by synthesising further compounds.  The skilled person would have no basis for believing that any better compound would be uncovered by such a systematic research program. 
67.	The Judge thought that was supported by the actual history of Lilly’s work.  It did not show the Roberts approach being followed
68.	Mr Carr attacked all that (as he had to) as wrong in principle.   He submitted that although the Judge had accepted Prof. Nichols’ evidence he was perverse to do so.
69.	The argument was this:  that the question was not “would you believe that you would get something better” but “why would you not carry out the standard step that everybody did?”   And Prof. Nichols’ answer to that,  that time was of the essence so one would not bother with SAR but press on with the actual Chakrabarti compounds, was not satisfactory because, being an academic, he had never worked in industry.
70.	I am not convinced by this.   No academic of Prof. Nichols’ standing could realistically be unaware of how his colleagues in industry went about things.  Moreover the Judge expressly said of Prof. Nichols’ evidence that “I have taken this lack of hands-on experience into account, to the extent it matters.”   I do not find the Judge’s acceptance of Prof. Nichols’ views as remotely describable as perverse.
71.	Nor do I think it unreasonable for the Judge to conclude that Chakrabarti’s statement, “this profile of activity needs further development of this class of compounds” would be taken as indication to press on with the class concerned, not to conduct a SAR exercise based on it.
72.	Finally in relation to this point, I should mention the Judge’s reliance on the actual history at Lilly.  Mr Carr said Chakrabarti was only published in 1980 (received January 1980).  There was very little time before Lilly abandoned flumezepine and went to olanzapine in 1982.   You could not do the SAR until you had the information in Chakrabarti.   So the history did not help.
73.	I am not impressed by this point either.   When Lilly had actually done the experiments reported in Chakrabarti was never properly explored in evidence (or perhaps even on disclosure).  Evidently lots must have been done much earlier (there are no less than 59 in the Table) and Dr Pullar from Lilly gave evidence as to the history which showed that many of the compounds had been made much earlier. That Lilly were only in a position to do a Roberts-type SAR in 1980 and did it as soon as they were was never put to him.   If it had been it seems unlikely he would have agreed.
74.	In the result this obviousness attack fails.
Insufficiency
75.	This was raised only as an answer to Lilly’s argument on the respondent’s notice.   It was to the effect that if it was necessary to show a unique unobvious advantage over the prior disclosed class in 235, that had not been done which in turn made the disclosure insufficient:  you must not only pull out a plum but you must disclose that what you have pulled out is a plum or your disclosure is insufficient.   Because it is unnecessary to consider Lilly’s respondent’s notice point I do not think it necessary to consider this point further.  As at present advised, however I cannot see what it really added to the argument – if Lilly had complied with the old selection rules so that olanzapine was novel and non-obvious by them, then that would be that.  Insufficiency would not come into it.  If not, they would have lost anyway.
76.	In the end Mr Carr accepted that this was so.  His key point throughout was that Lilly had not disclosed an advantage over the rest of the class, and that if that was so the patent had to be invalid one way or another – it did not really matter which of the boxes of lack of novelty, obviousness or insufficiency applied.   Since the main point fails because in truth there was a technical advance and one described in the patent, it is not necessary to say any more.
The Respondent’s Notice Point.
77.	The Judge concluded that if it been necessary to show compliance with the IG rules, the Patent failed to do so.  He did so in an Annex to his judgment because he did not think it necessary to come to a conclusion on the point.   I am of the same view and accordingly see no need to burden this judgment with the point further.
78.	I only have one further observation about the point.  It shows, to my mind, that the rules were too strict.  They would mean that a technical advance of the sort made by Lilly would be unpatentable.  That in turn would mean that it would not be worthwhile doing the sort of thing that Lilly did by developing the disclosure of their Patent further and bringing olanzapine to market.   Unpatentability would have meant this medicine would not have been available.
Foreign Decisions
79.	We were provided with two thick bundles of decisions about the corresponding patent in a host of jurisdictions (the US, Canada, the Czech Republic, Finland, Romania, Slovakia, Slovenia, Spain, China and Hungary).  In some countries there was more than one decision.   
80.	I did not find this all that helpful.  Mr Carr invited us particularly to follow the Canadian decisions (where the patent was held invalid) and in particular the decision of Hughes J of June 5th 2007.  He essentially followed the IG approach in saying that the Patent had to disclose an advantage over the prior art.   It does not seem he was shown the EPO case law (why should he have been?).   It does not seem that he was invited to consider patentability on the basis of whether the Patent disclosed real advantages over what was actually known.  So I decline Mr Carr’s suggestion.
81.	I do not find it necessary to refer to any of the other decisions, save for that of the German Supreme Court (the Bundesgerichthof) of 16th December 2008, which I have mentioned briefly already.  The Court held the Patent valid.  All the arguments before us were available to be considered, although only some were considered explicitly.  The Bundespatentsgericht had held the patent anticipated over Chakrabarti 1980 (a point not run here).  The BGH rejected both anticipation and obviousness over 235, pithily but essentially for the same reasons as Floyd J did and we do.  They had an expert who said that there was no reason to pick olanzapine out of the vast prior class and that was enough both for novelty and non-obviousness.  And they rejected in some more detail obviousness over Chakrabarti 1980.
82.	We of course are not bound by a decision of another national court.  And indeed it is quite possible for national courts applying the same law to come to different conclusions because the evidence is different.   So I say no more than that I am glad we reach the same decision as the BGH.  It is an example of the fact that, by and large, different courts in Europe do reach the same conclusions – even though, perhaps understandably, the rarer cases where they differ get more publicity.
Master of the Rolls:
83.	After a ten day trial, Floyd J concluded that European Patent (UK) No 0 454 436 (“the Patent”), registered in the name of Eli Lilly and Co Ltd (“Lilly”), was valid despite a number of attacks made by Dr Reddy’s Laboratories (UK) Ltd (“DRL”), mostly on the grounds of anticipation (or lack of novelty) or obviousness (or lack of inventive step). In this appeal, DRL rely on some, but not all, of those attacks.  
84.	The Patent is fully described for present purposes by Jacob LJ in paragraphs 5 to 10 of his judgment; it has a priority date in 1990, and the sole relevant claim for present purposes is for a single chemical compound, olanzapine. There are two items of prior art now relied on by DRL. The first is a paper (“Chakrabarti 1980”) published by Dr Chakrabarti and others which reported on the synthesis of 59 compounds, not including olanzapine; it is described by Floyd J in the passage quoted by Jacob LJ in paragraph 62. The second item is a British Provisional Specification 1,533,235 (“235”) published by Lilly in November 1978, corresponding to a patent of the same number (“the 235 patent”). 235 is more fully described by Jacob LJ at paragraphs 17 to 22. It extends to around 1019 compounds, of which some 86,000 are preferred, and it asserts, without putting forward any evidence whatever in support, that they “have useful nervous system activity … with neuroleptic, sedative or relaxant effects”, and that “these properties … render them useful in the treatment of mild anxiety states and certain kinds of psychosis”. Olanzapine is one of the 86,000-odd preferred compounds, but no specific reference is made to it in 235.
Obviousness over Chakrabarti 1980
85.	The appeal against Floyd J’s conclusion that the Patent was not obvious over Chakrabarti 1980 can only succeed if DRL can undermine his rejection of the evidence of their expert witness, Professor Roberts. That evidence was that the person ordinarily skilled in the relevant art would have been led by Chakrabarti 1980 to synthesise and test eleven compounds, one of which would have been olanzapine. In rejecting that evidence, the Judge relied on the evidence to the contrary of Lilly’s expert, Professor Nichols. 
86.	It is, of course, possible for a first instance finding on obviousness, which is supported by expert evidence, to be overturned on appeal. But, before taking that course, it would have to be shown that the judge had misunderstood the evidence or argument, that he had failed to have regard to relevant evidence, that he had disregarded relevant evidence, or that his finding was one that no reasonable judge could have made.  
87.	In the present case, for the reasons given by Jacob LJ in paragraphs 61 to 74, DRL cannot establish that Floyd J erred in any of these ways in reaching the conclusion that he did. On the contrary: his conclusion on obviousness over Chakrabarti 1980 was one which he was plainly entitled to reach. 
Obviousness and novelty over 235: the approach to be adopted
88.	The more significant attack on the validity of the Patent is that based on 235, over which DRL contend that the Patent is either anticipated or obvious. When considering the proper approach to arguments on novelty and obviousness, it is salutary to have in mind their statutory basis. As Lord Walker of Gestingthorpe said in Synthon BV v SmithKline Beecham plc [2005] UKHL 59, [2006] RPC 10, paragraph 57, “[t]he law of patents is wholly statutory”, although it is right to add that he then expanded on this by pointing out that “the courts have shown an inclination to enrich the bare simplicity of the statutory text with their own explanatory commentary”, which, he said “has over the years done much to clarify the abstract generalities of the statutes and to secure uniformity in their application”.
89.	The statute which currently governs the law of patents in this jurisdiction is, of course, the Patents Act 1977. Part I of that Act is headed “New domestic law”, reflecting the long title of the statute, which identifies one of its two main purposes as being “to establish a new law of patents”. The long title identifies the other main purpose as being “to give effect to certain international conventions on patents”, which include the European Patent Convention (“the EPC”), as provided for in Part II of the Act (titled “Provisions about international conventions”). 
90.	Part I comprises the bulk of the 1977 Act, and it includes sections 1 to 6, which are concerned with “Patentability”. Section 1(1) provides that, in order to be patentable, an alleged invention must, inter alia, “(a) [be] new” and “(b) [involve] an inventive step”. Section 1(1)(a) is expanded in section 2, subsection (1) of which provides that an invention is new “if it does not form part of the state of the art”. Section 2(2) expands on what that expression means; in summary, the state of the art includes “all matter which has at any time before the priority date of that invention been made available to the public” irrespective of the location or means. Subsections (3) and (4) contain some special rules as to the dates when matter contained in patents or patent applications is treated as becoming available for these purposes. Section 3 expands on section 1(1)(b), and explains that an invention involves an inventive step “if it is not obvious to a person skilled in the art” having regard to all matter falling within section 2(2). 
91.	Part III of the 1977 Act is headed “Miscellaneous and general”. It includes section 130, subsection (7) of which contains a declaration that certain sections, including sections 1(1) to (4), 2, and 3 “are so framed as to have, as nearly as is practicable, the same effects in the United Kingdom as the corresponding provisions of the [EPC and two other Conventions] have in the territories to which those Conventions apply.” Article 54 and article 56 of the EPC are couched in very similar terms to sections 2 and 3, respectively, of the 1977 Act.
92.	Especially in relation to those concepts covered by the sections of the 1977 Act identified in section 130(7), it is plainly desirable that there is, so far as possible, a consistency of approach when it comes to matters of principle between the domestic courts of the signatory states to the EPC, both among themselves and with the European Patent Office (“the EPO”). This proposition is supported by a number of recent decisions of, and dicta in, the House of Lords and this court. A recent example is Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] UKHL 49, in which Lord Hoffmann said this in paragraph 3:
There is still no European Patent Court. A European patent takes effect as a bundle of national patents over which the national courts have jurisdiction. It is therefore inevitable that they will occasionally give inconsistent decisions about the same patent. Sometimes this is because the evidence is different. In most continental jurisdictions, including [the EPO], cross-examination is limited or unknown. Sometimes one is dealing with questions of degree over which judges may legitimately differ. Obviousness is often in this category. But when the question is one of principle, it is desirable that so far as possible there should be uniformity in the way the national courts and the EPO interpret [the EPC].”

93.	An issue of principle between the parties on this appeal concerns the proper approach to be adopted when considering the validity of a patent, often known (at least in this jurisdiction) as a selection patent, which claims a relatively specific application for one chemical compound, when that compound is included in a large class of compounds which an earlier patent revealed could have applications, which include the specific application claimed in the patent. 
94.	DRL contends that the validity of a selection patent is to be assessed, in the light of the earlier patent, in accordance with the reasoning and approach applied by Maugham J in In the Matter of IG Farbenindustrie AG’s Patents (1930) 47 RPC 289, as expanded in the speeches of Lords Wilberforce and Simon of Glaisdale in EI Dupont de Nemours & Co (Witsiepe’s) Application [1982] FSR 303. In particular, DRL rely on the three stage test propounded by Maugham J in these terms in IG Farbenindustrie (1930) 47 RPC 289, 322-3:
“First, a selection patent to be valid must be based on some substantial advantage to be secured by the use of the selected members ….. . Secondly, the whole of the selected members must possess the advantage in question. Thirdly, the selection must be in respect of a quality of a special character which can fairly be said to be peculiar to the selected group.”
 
95.	Lilly, on the other hand, say that the English courts should follow the lead of the Technical Board of Appeal of the EPO (“the Board”) and apply the approach it has adopted in a number of decisions relating to novelty and obviousness in relation to selection patents (although the expression is one used in English law, and appears to have no European equivalent). 
96.	As to anticipation, the Board’s jurisprudence can be traced back to T 12/81 BAYER/diastereoisomers, where, in paragraph 14.2, it said that “[s]ubstances obtained … by selecting a specific pair of starting substances from an immense range of possibilities offered are in normal practice regarded … as not having been anticipated by prior description but as being a new selection.” In a subsequent decision, T 181/82 CIBA GEIGY/ Spiro Compounds, the Board identified in paragraph 8 the importance of drawing “a strict distinction … between [the] purely intellectual content of the definitions and their information in the sense of a specific teaching with regard to technical action”, a point it emphasised and applied in T 0296/87 HOECHST/Enantiomers, at paragraph 6.1. 
97.	In T 0133/92 Bleaching Activators/AKZO, the Board said at paragraph 4.2.2 that its case law established that “if the claimed subject-matter concerned a particular compound, whereas the prior art disclosed a family of compounds defined by a general structural formula covering this particular compound but not describing it explicitly, the claimed subject-matter had to be considered novel.” This approach has been consistently adopted: see T 1046/97 ZENECA/enantiomer at paragraph 2.1.1.4 for a more recent example. 
98.	As to obviousness, the Board’s approach is well illustrated by its reasoning in T 0939/92 Triazoles/AGREVO, where, at paragraphs 2.4.2 and 2.4.3, it started its analysis by referring to general principles. In the former paragraph, the Board identified the “generally accepted legal principle that the extent of a patent monopoly should correspond to and be justified by the technical contribution to the art”, a principle which was said by the Board to lead to the requirement that “everything falling within a valid claim has to be inventive”. At paragraph 2.4.3 it mentioned its “consistent” approach as being “to decide the issue of obviousness on the basis of an objective assessment of the technical results achieved by the claimed subject matter”.
99.	Bearing in mind these principles, the Board said at paragraph 2.5.3 of T 0939/92  that “the selection of such compounds, in order to be patentable, must not be arbitrary but must be justified by a hitherto unknown technical effect which is caused by those structural features which distinguish the claimed compounds from the numerous other compounds.” The difficulty for the applicant in that case, as one can see from paragraph 2.7, was that it was seeking to patent a group of compounds (a difficulty which does not, of course, arise here, as the Patent extends simply to olanzapine), and the Board held that, in such a case, it had to be shown that the “technical effect which justifies the selection of the claimed compounds must be one which can be fairly assumed to be produced by substantially all of the selected compounds” – paragraph 2.5.4. 
100.	The notion that a selection of a group of compound from a broader group can involve “an inventive step” if those selected compounds “achieve a particular technical result that would not be achieved by the other members of the broader group”, but not if the selection was based on “an arbitrary choice” was repeated in a number of subsequent decisions, the quoted words coming from paragraph 2.10 of T 0964/92 Benzodioxane derivatives/EISAI.  In its subsequent decision T 0133/01 Dopamine agonists/WYETH, the Board also made it clear, at paragraph 4.4 that “alleged but unsupported advantages cannot be taken into consideration in respect of the determination of the problem underlying the claimed invention”. In that case the application failed because “[i]n the absence of evidence to the contrary, … faced with the problem [sought to be solved], a skilled person would not require any inventive skill in picking out at random from structural variants outlined in [an earlier patent] [a particular set of variants, or compounds] thereby arriving without inventive ingenuity at the … solution proposed in the present application” – paragraph 4.6. 
101.	In connection with the point that a claim to a particular compound out of a group of previously known compounds must not be based on an arbitrary selection, it is right to refer to a passage in paragraph 5 of the Board’s reasoning in T 181/82. The Board there said that “if a meaningful statement is to be made in order to render an inventive step plausible, compounds having a maximum structural resemblance must be compared with one another” – a view consistent with the general guidance given in section 9.8 of the Case Law of the Boards of Appeal (Fifth edition, 2006).
102.	In my opinion, in so far as there is a difference between them, the approach of the Board since the 1977 Act came into force, rather than the approach of the English courts proceeding under the earlier law, is to be preferred, unless the former approach can be shown to be one-off, impractical, illogical, inconsistent with principle, not open as a matter of domestic law, or (perhaps) not applied in domestic courts of other signatory states of the EPC. Of course, where the approach is not well-established, for instance, because it was taken only in one Board decision, or does not represent the consistent approach of the Board, different considerations may well apply. So, too, at least where that approach has not been approved by the Enlarged Board of Appeal, it would often be different if the domestic court considered that the Board’s approach was impractical illogical or inconsistent with principle. Obviously, there would be no question of following the Board’s approach, if an English court were precluded from such a course as a matter of domestic law. It may also be easier to justify a refusal to follow the Board’s approach if courts in, say, Germany or the Netherlands, had also declined to do so.
103.	In the present instance, it seems to me that there is no good reason for not following the Board’s approach. Although IG Farbenindustrie (1930) 47 RPC 289 is a decision which has often been cited and relied on in this jurisdiction, and Witsiepe [1982] FSR 303 is a decision of the House of Lords, they were both concerned with patent validity under a different regime, namely the common law or the Patents Act 1949, i.e. purely domestic law relating to domestic patents. The 1977 Act, as already mentioned, was expressly enacted to create a “new” regime for patents, and it was avowedly intended to be interpreted in accordance with the EPC. (It is only right to add that this does not mean that it is now appropriate to ignore cases decided under earlier legislation when considering issues under the 1977 Act: the wisdom and experience of previous judges in the field of patent law is of great value when it comes to considering problems thrown up today in the same field. The fact that the 1977 Act has introduced a “new” law of patents which is, to a substantial degree, intended to align our law with certain international Conventions does not mean that our courts should need to reinvent the wheel.)
104.	Further, as I have tried to show, and as Jacob LJ’s analysis in paragraphs 44 to 50 demonstrates, the Board’s approach in cases such as these is consistent and clear, and it is based on its general approach to patent validity on novelty and obviousness. There is nothing in the 1977 Act (any more than there was in the 1949 Act, it is fair to say) which recognises, or even implies, a special approach to, or even the existence of, selection patents as a special category of patent, which require a different approach when determining validity from other patents. Indeed, although it involves a slightly different analysis, it seems to me that the point at issue is not dissimilar from the enantiomer/racemate issue, in relation to which this court and the House of Lords adopted the approach which had been taken by the Board – see Generics v Lundbeck [2009] UKHL 12; [2008]EWCA Civ 311, [2008] RPC 19, at paragraph 9 (where Lord Hoffmann specifically referred to and followed the Board’s reasoning in T 0296/87). Quite apart from this, as Jacob LJ points out in paragraph 39, there may be some difficulty in applying Maugham J’s three stage approach where the prior class of compounds is very large. 
105.	It cannot be suggested that this conclusion involves illegitimately departing from the only case in this court on the 1977 Act where IG Farbenindustrie (1930) 47 RPC 289 was relied on. In Hallen v Brabantia [1989] RPC 307, it was assumed that Maugham J’s three stage approach applied, but there was no argument to the opposite effect, and it is plain that the court’s conclusion would have been no different if the Board’s approach had been adopted. Indeed, as Jacob LJ points out at paragraph 32, the Board’s approach in cases such as these marches well with what Lord Hoffmann said in Synthon [2006] RPC 10, at paragraph 22, as expanded in the following two paragraphs. As to other domestic courts, the evidence strongly suggests that at least the German courts adopt the same approach as the Board - see STADApharm No. 1-2W 47/07 (29th May 2008), more fully discussed by Jacob LJ in paragraph 33. And there is nothing to suggest a different approach in the courts of any other signatory state to the EPC. (Indeed, the Lundbeck litigation in the Netherlands suggests that the same approach would be, indeed maybe is, adopted there).
106.	Having decided that the proper approach to be followed in this case is that adopted by the EPO, it is unnecessary to analyse precisely the nature of the approach taken in IG Farbenindustrie (1930) 47 RPC 289 and Witsiepe [1982] FSR 303, and decide whether it is the same, and, if not, how it is different. 
Obviousness and novelty over 235: the application of the correct approach
107.	Having rightly decided to follow the EPO’s approach to deciding whether the Patent was invalid on the ground of anticipation or obviousness over 235, Floyd J decided that what the Patent disclosed was both novel and inventive. I turn to consider whether he was right.  
108.	So far as novelty is concerned, it appears to me that the learning from the EPO, in the Board decisions to which I have referred, disposes of the contention made on behalf of DRL that the Patent fails on the ground of anticipation. That seems clear from the reasoning in the decisions of the Board discussed in paragraphs [14] and [15] above. Quite apart from that, it would, at least to my mind, be astonishing as a matter of common sense if the patent failed on the ground of lack of novelty over 235. Even if one limits oneself to the preferred class, there are 86,000 compounds included in the scope of 235, and it has no guidance whatsoever as to why those compounds are preferred over the other 1019-odd compounds covered by 235, or as to why or how any of those 86,000, or 1019-odd, compounds might produce the very wide class of claimed effects. In those circumstances, it would be little short of absurd to describe olanzapine as obvious over 235, a disclosure some twelve years earlier, particularly bearing in mind the common general knowledge, quoted from Floyd J’s judgment by Jacob LJ in paragraph 3, and what the Patent teaches, described by Jacob LJ in paragraphs 7 to 10.
109.	As for inventiveness, there is the jurisprudence of the Board, as discussed in paragraphs [16] to [19] above. This seems to me to establish that the correct question to ask is whether the selection of olanzapine, out of the class of 86,000 compounds in 235, was “arbitrary”, or whether the teaching of the Patent established that the selected compound achieved “a particular technical result”, and, in answering that question, one must bear in mind that it arises in the context of the broader proposition that “the extent of a patent monopoly should correspond to and be justified by the technical contribution to the art”.
110.	Whether one looks at the broader proposition or the narrower question, it appears to me that the answer is, unsurprisingly, the same. There can be no doubt but that the teaching of the Patent in relation to a single compound, as described by Jacob LJ in paragraphs 7 to 10, is unusual in its extent, as he points out in paragraphs 11 to 13, and it was at least open to the Judge to conclude that it represented a significant technical contribution to the art over and above the “teaching” (which is a generous description of what appears to be no more than mere speculation about a wide collection of different possible applications of an enormous number of compounds) of the 235 patent.
111.	As to the narrower question, I do not consider that it can be said that the selection of olanzapine was arbitrary. There is no doubt that the Patent credibly reveals that that single selected compound has technical applications or features which represent a contribution to the art, wholly absent from 235’s generalised and unsupported claims for 86,000 compounds which include the selected compound, although it is not referred to specifically. The Patent’s disclosure is not merely enormously more specific, in terms of both identifying the right compound and its technical application, than 235, but, unlike 235, but it also reports experimental evidence to support the claim. It is true that there is only limited evidence to show that no other compound claimed by the 235 patent has the same therapeutic benefits as olanzapine, but I do not consider that that can invalidate the Patent. As I have said, it is hard to see why Floyd J was not entitled to conclude, on the evidence, that the Patent was inventive over 235; indeed, I note that it is a view which he reached with some confidence, as he considered DRL’s case for attacking the Patent was stronger in relation to Chakrabarti 1980 than in relation to 235.
112.	It is true that the Board has indicated that, at least in some cases such as T 0181/82, a selection patent must show that the selected compound has (or compounds have) an advantage which the other compounds do not have. However, in paragraph 6 of that decision, the Board indicated that this requirement can be satisfied by comparing the claimed compound with the closest prior art, i.e. structurally the most similar compound in the group from which the claimed compound has been selected: if that similar compound does not have the technical effect which the Patent teaches or claims for the claimed compound, then the requirement is satisfied. The teaching of the Patent, as explained in paragraphs 7 to 10 above, discloses that a number of the compounds covered by 235 were tested and did not have the same beneficial therapeutic effect as olanzapine.  Thus, there are the thieno-benzodiezapines, in particular flumezapine, and, particularly importantly there is the “closely related compound, [ethyl-olanzapine]”. This latter compound differs from olanzapine in only one small respect: it has an ethyl group in one location where olanzapine has a methyl group. 
113.	RDL argue that this cannot assist Lilly as, in his evidence, Professor James, one of Lilly’s witnesses, agreed that it was not possible to extrapolate from the lack of success with ethyl olanzapine to the other 86,000 compounds preferred by 235, let alone to the other 1019 compounds covered by 235. I am very doubtful whether this argument should be given any weight in a case such as this, where the prior art amounts to no more than a generalised suggestion that a preferred class of 86,000 compounds may have beneficial psychological effects with no supporting experiments or other evidence whatsoever. 
114.	However, even assuming in favour of DRL that what the Board said in paragraph 6 of T 0181/82 applies in this case, it seems to me that the teaching of the Patent, referring as it does to ethyl olanzapine, which is very close to the claimed compound, as well as other compounds included in the prior art, satisfies any inventiveness requirement to which the Board’s jurisprudence can be argued to give rise. By referring to the results of experiments with ethyl olanzapine, the Patent complies with what the Board identified as sufficient evidence in paragraph 6 of its decision in T 0181/82. In many cases where a compound is found to have a therapeutic effect not shared by a very similar compound, it must be impossible to predict which, if any, other similar compounds will  have the effect in question, as the way in which the effect is chemically achieved will be unknown. To accept DRL’s argument would therefore in many cases undermine the clear and practical approach approved by the Board in T 0181/82. In any event, if, as Professor James’s evidence suggests, the success of a particular compound is wholly unpredictable, then there is no reason to think that any of the other 86,000, or even 1019, compounds referred to in 235 have any better chance of success than ethyl olanzapine, a view supported by the failure of the other compounds referred to in the Patent. Quite apart from this, at least in some cases, the Board appears to allow further evidence to support the validity; accordingly, although not referred to in the Patent, it may be appropriate to add that this conclusion is supported by the research reported in Chakrabarti 1980.
115.	The submissions of DRL as to why 235 should render the Patent invalid had as something of an undertone, even a refrain, that it was unfair and inappropriate that Lilly should be able, in effect, to re-monopolise olanzapine in 1990 given that they had already done so in 1978 with the grant of the 235 patent. Particularly given Floyd J’s finding in paragraph 186 of his judgment that the effect of the 235 patent was to prevent others from carrying out research into the multitudinous compounds which it covered, it is hard not to have sympathy for that view. However, it cannot alter the principles to be applied when deciding whether the patent’s teaching is novel and non-obvious over 235. The analysis and outcome must be the same if the 235 patent were claimed and owned by someone wholly unconnected to Lilly, or indeed if the teaching of 235 was in an article published in an academic journal in 1978. 
116.	It may be that, if there had been a challenge to the validity of the 235 patent on appropriate grounds (maybe under section 72(1)(c) of the 1977 Act), it would have been revoked. However, even if such a challenge had been made and had succeeded, it could not, I think, be suggested that, in those circumstances, there would be some principle of fairness, akin perhaps to estoppel, which would justify the court revoking the Patent, even though the attacks on it based on lack of novelty and lack of inventive step failed.
Conclusion
117.	For these reasons, which substantially mirror those more fully given by Jacob LJ (whose draft judgment I have found very valuable when finalising my views on counsels’ well-presented arguments), I would dismiss this appeal. 
118.	I should add that I draw comfort in reaching this conclusion from the fact that in Germany both the Oberlandsgericht, determining infringement in the decision I have mentioned in paragraph [23], and the Bundesgerichthof, determining validity on appeal from the Bundespatentgericht, reached the same conclusion, namely that the Patent was valid.
Lord Justice Richards:
119.	I agree with both judgments.