Microsoft word - meibom001-526.doc
SELECTION INVENTIONS IN THE PHARMACEUTICAL FIELD
Selection Inventions In The Pharmaceutical Field –
A selection invention involves the selection of individual elements or a sub-set of ele-ments from a broader class which has been defined only in general terms. Selection in-ventions are typically made in the chemical field where a general formula or list mayencompass a large number of individual compounds. Other types of selection may befrom a numerical range.
Selection inventions have recently been in the spotlight in several European jurisdic-
tions and at first sight there seem to be significant differences in approach to the appar-ently complex issues which they pose. However, a closer scrutiny of the developmentof the law reveals deeper similarities than are first apparent but also highlights the dan-gers of adopting a ‘pick and mix’ approach to patentability.
The justification for granting a state monopoly in respect of a selection invention is
no different from that for any other type of patent. The long established patent bargainrequires the public disclosure of the invention in return for a period of protectionduring which time the patentee may exclusively exploit the invention. This provides anopportunity for the patentee to obtain a return on the investment put into the makingof the invention while ensuring that details which would otherwise remain secret be-come publicly available. This bargain is even reflected in the original name: ‘LettersPatent for an invention’ derived from the Latin literae patentes
meaning ‘open letter’.
The public policy objectives behind the bargain are essentially the stimulation of in-
novation and development. A careful balance which aims at providing sufficient re-ward to incentivise potential inventors and investors without stifling future progressby unduly restricting the field to others is required. In a leading UK case on selectioninventions, E.I. du Pont de Nemours (Witsiepe’s) Application
2, Lord Simon specificallycommented on this:
“Before I turn to consideration of the law relating to selection patents, I venture to remarkthat Du Pont’s patent appears to satisfy the general ends to which the patent law is directed– encouragement of invention and of the publicising of invention so as to promote techno-logical advance by granting a temporary monopoly, on the one hand, without, on the other,
1 The author would like to thank Claire Robinson of Powell Gilbert for her assistance.
2 E.I. Du Pont & Co. (Witsiepes) Application  F.S.R. 303.
stultifying endeavour at improvement by perpetual or prolonged monopoly or (in historicalorigin) giving unearned reward to favoured persons.”
Nevertheless, the dilemma posed by selection inventions concerns one of the mostfundamental requirements of patentability: that an invention must be new over thestate of the art. Almost by definition a selection implies a choice made from pre-existing alternatives and indeed the term ‘selection invention’ has come to be used forinventions which lie within parameters previously marked out but for which a newand unexpected advantage has been discovered. The difficulty is therefore in decidinghow those pre-existing parameters impact upon novelty.
The approach to this issue has varied as the approach to patentability has historically
across Europe. The real question is whether this has led to the establishment of differ-ent legal principles and whether there is now a conformity of approach following theadoption of the European Patent Convention.
In the UK, the first case to directly address the question of the validity of a “chemicalselection patent” was that of I.G. Farbenindustrie A.G.’s Patents
3. This case concerneda patent for the manufacture of azo dyes. Azo dyes were known but the particular se-lected dyes were alleged to show excellent colour fastness.
In his judgment Maugham J. contrasted “originating patents” concerning the discov-
ery of a new reaction or compound with “selection patents” based upon “the selectionof related compounds such as homologues and substitution derivatives of the originalcompounds which presumably have been described in general terms and claimed in theoriginating patent”.
Maugham J. was clear that a selection invention should not benefit from any excep-
tion to the rules governing patentability: “a selection patent does not differ in naturefrom any other patent and is open to attack on the usual grounds of want of subject-matter, want of utility, want of novelty and so forth.”
Accordingly, this first case was concerned with the question of whether it is possible
to show “subject matter” (i.e. inventiveness) in respect of such a selection. MaughamJ.’s answer to this was undoubtedly yes. Although reluctant to state definitively theconditions upon which a selection patent depends, Maugham J. did make three generalpropositions:(i)
“First, a selection patent to be valid must be based on some substantial advantageto be secured by the use of the selected members. (The phrase will be understoodto include the case of substantial disadvantage to be thereby avoided.)”
(ii) “Secondly, the whole of the selected members must possess the advantage in
3 I.G. Farbenindustrie A.G.’s Patents (1930) 47 R.P.C. 289.
SELECTION INVENTIONS IN THE PHARMACEUTICAL FIELD
(iii) “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.”
In relation to the first proposition Maugham J. noted that a »substantial advantage at-tributable to the use of the selected members” is inherent in a selection invention andshould be differentiated from the requirement of utility. He explained that the secondand third propositions also follow from the basis upon which the grant of a patent isjustified:
“… if the selection embraces selected members which do not possess the alleged advantages,the selection is defective and the patent would be misleading and would also fail for insuffi-ciency and non-utility.”
The selection would be similarly defective if it did not encompass a significant propor-tion of the compounds possessing the special character. Consequently, it is essentialthat the nature of the characteristics possessed by the selection for which a monopolyis claimed is clearly defined:
“… in a selection patent the inventive step lies in the selection for a useful and special prop-erty or characteristic adequately defined …”
The patents being litigated were ultimately held to be invalid as the promised advan-tages of the selection were either not borne out or were too vague. Further, amend-ments which would have “… greatly diminished the number of the selected com-pounds described …” were disallowed on the grounds that “… the Patent can only bedefended as a selection of compounds possessing special properties or advantages …”.
Selection inventions continued to be recognised after the introduction of the 1949
Patents Act. In Beecham Group v. Bristol Laboratories
4 Maugham J. was cited by LordDiplock who summarised the nature of a selection invention:
“… The inventive step in a selection patent lies in the discovery that one or more membersof a previously known class of products possess some special advantage for a particular pur-pose, which could not be predicted before the discovery was made (In Re I. G. Farbenin-dustrie A.G.’s Patents (1930) 47 R.P.C. 283 per Maugham J. at pp. 322/3). The quid pro quofor the monopoly granted to the inventor is the public disclosure by him in his specificationof the special advantages that the selected members of the class possess.”
In the House of Lords Du Pont
2 case referred to above Lord Wilberforce describedthis excerpt as a compendious statement of the present position, adding: “The generalprinciple is now securely part of the law and needs no fresh discussion …”. LordSimon concurred:
“That the concept of selection patents is now firmly established in our law appears not onlyfrom Lord Diplock’s speech (in which the other members of the Appellate Committee con-curred) but also from the numerous authorities reviewed in the judgments appealed from, towhich must now be added that selection patents are recognised by the European law devel-
4 Beecham Group Ltd v Bristol Laboratories International S.A.  RPC 521.
oped under the Treaty of Rome: see Bayer A.G. (Baatz & Al.’s) Application O.J./E.P.O. 206.”
Selection inventions were therefore undoubtedly accepted as being capable of formingadequate subject matter for a patent by the time the Patents Act 1977 was enacted.
However, the Du Pont
case was primarily concerned with anticipation rather then in-ventive step as it was alleged that Du Pont’s 1975 patent application was anticipated bya prior I.C.I. specification. This earlier specification disclosed a new class of chemicalproducts, copolyesters, obtained by heating a preferred glycol with other specified in-gredients. The resulting copolyesters were said to have enhanced adsorptive capacityfor water enabling them to be more readily dyed in the form of fibres for textile mate-rials. The specification also suggested that using any one of another eight glycolswould produce copolyesters in the same class with the same properties but none ofthese compounds was exemplified. The Du Pont application included claims to the co-polyester which would result from using a particular one of these eight glycols. How-ever, the invention was directed to a very different use: the copolyesters were said tobe especially effective in injection moulding and high speed extrusion applications be-cause of their rapid hardening rates.
Lord Wilberforce summarised the issue before the court:
“First, it may be true to say as a general rule that where an invention for a substance is spe-cifically disclosed, with a claim for particular advantages, or where a substance is alreadyknown, a discovery that the disclosed or known substance has some advantage or usefulquality not previously recognised does not give a right to a patent. The difficulty ariseswhen disclosure is made of a group or class of substances for which some advantage isclaimed, and later it is found that one or more of this group or class possesses special ad-vantages not belonging to the rest of the group or class, and not previously identified.”
Was Lord Wilberforce thereby suggesting that there may be some exception to thestrict rule of novelty? The situation referred to is particularly likely to arise in relationto chemical inventions as the attributes of newly discovered chemical combinations arealso likely to be found in homologues or other variants which can easily be described,and therefore claimed, using a generic formula. The crux of the matter is thereforewhether such a disclosure is to be regarded as an anticipation:
“Is, then, the mere fact that he has disclosed or published in general terms the possibility ofthese combinations, in such a way that they can be made, a disclosure or publication of un-recognised advantages which may be found to be possessed by one or some of them?”
Lord Wilberforce considered it necessary for anticipation that the prior disclosureclearly indicated that use of the selected material would result in a product having ad-vantages predicted by the class. It is interesting (and in contrast to the approach of theEPO) that Lord Wilberforce considered it irrelevant whether the prior class was de-scribed by a generic formula or by a list of compounds including the later selectedcompounds. He observed that the skilled person could readily transform a genericformula into a list. Similarly he did not consider the size of the prior disclosed class tobe relevant to the issue of anticipation although it may be relevant to obviousness.
SELECTION INVENTIONS IN THE PHARMACEUTICAL FIELD
Shortly after the Du Pont
case the Patents Act 1977 became law and for the first time
the principles of patent law across Europe were brought into conformity in accordancewith the European Patent Convention. The case of Hallen v Brabantia
5 in 1990 con-firmed that the concept of selection inventions had survived the introduction of thenew law. In one of the only cases outside the field of chemistry, it was held that a pat-ent for self-pulling corkscrews coated with PTFE was not a valid selection invention asthe specification had failed to disclose the advantages which were peculiar to such de-vices over corkscrew coated with PTFE generally6.
In Ranbaxy v Warner-Lambert
7 the court returned its focus to novelty even though
the issue of selection inventions had been raised in relation to a lack of inventive stepreference. Pumfrey J. confirmed that as a matter of English law it is possible to make aselection invention where there was a prior disclosure of a class of compounds “ratherthan a disclosure of the individual members of that class as distinct entities”. PumfreyJ. considered that if the later patent did not state the advantage possessed by the se-lected class, it is merely an arbitrary selection among things already disclosed, andtherefore lacking novelty.
This set the scene for the most recent UK case on selection inventions, Dr Reddy’s v
8 but before examining that case it is convenient to consider the EPO approachto selection inventions.
III. EPO APPROACH TO SELECTION INVENTIONS
The EPO’s approval to novelty has in some ways been stricter than that of the UKcourts. Unlike the approach in DuPont
the discovery of a new technical effect cannever add novelty to a class of compound that is otherwise old. However, as a balanceto this the EPO had developed rules by which novelty can be conferred on the selec-tion of compounds per se
as discussed below.
The EPO’s Examination Guidelines explain that selection inventions “deal with the
selection of individual elements, sub-sets, or ranges, which have not been explicitlymentioned, from within a larger known set or range.”
The Technical Board of Appeal’s decision in T12/819 is described in the fifth edition
of the Case Law of the Boards of Appeal of the European Patent Office
as “a decisionof fundamental importance with regard to novelty in the field of chemistry”. It haslong been established law that substances which are the inevitable product of a processdescribed in a prior document cannot be novel. This case established when a substance
5 Hallen Co. and Anr. v Brabantia (UK) Ltd.  R.P.C. 195.
6 Apparently the coating unexpectedly ease extraction as well as insertion.
7 Ranbaxy UK Ltd v Warner-Lambert Co  F.S.R. 14.
8 Dr Reddy’s Laboratories (UK) Ltd v Eli Lilly and Co Ltd  EWHC 2345 (Pat).
9 T 12/81 (BAYER/Diastereoisomers) OJ 8/1982, 296.
is to be regarded as being an inevitable product in circumstances where the earlier dis-closure is framed in terms of classes of starting compounds and/or classes of processes.
In T12/81 the prior art listed 20 starting compounds and gave a choice between 5
different processes for reducing ketones to their corresponding secondary alcoholswhich could take two diastereomeric forms. The patent application was for the prod-uct resulting from the use of a particular starting compound and a particular process asit had been discovered that the resulting compound comprised a very high ratio of thepreferred diastereomer.
The Board differentiated circumstances where a choice is left open to the skilled per-
son in implementing a prior art teaching, highlighting that the concept of substanceselection presupposes that a choice has been made from a group of substances:
“If on the other hand two classes of starting substances are required to prepare the endproducts and examples of individual entities in each class are given in two lists of somelength, then a substance resulting from the reaction of a specific pair from the two lists cannevertheless be regarded for patent purposes as a selection and hence as new.”
At first sight this may seem to be somewhat arbitrary but the Board’s reasoning is thatwhere two starting compounds must be selected the end product is the result of twovariables parameters:
“The new element – indispensable if a substance selection is to be recognised as new for pat-ent law purposes – is not attributable to the absence of a reference to the end product but tothe fact that the combination actually selected from the wide range of possibilities has notbeen disclosed to the public.”
However, where only one starting compound must be selected (and these are all spe-cifically disclosed) the variable process parameter does not introduce a new element.
The selection of a sub-range from a broader numerical range is another important
category of selection invention. In T198/8410 it was established that such inventionsare novel if the selected sub-range (a) is narrow compared to the known range (b) issufficiently far removed from specifically disclosed examples and from the end pointsof the known range; and (c) importantly is not an arbitrary selection. This means thatit must not simply be an embodiment of the prior art but another invention i.e. it mustbe a purposive selection resulting from new technical teaching. The Board clarified thatthe sub-range singled out must be new per se
, a newly discovered effect occurring onlyin the sub-range cannot confer novelty but can confirm that the selection is not arbi-trary. The Board reiterated that the purpose of Art.54(1) of the EPC is to prevent thestate of the art being patented again.
This is perhaps the key to understanding the EPO approach (at least to inventions
relating to claimed sub-ranges). The subject matter of the new invention is the selec-tion of a narrower class or range of compounds. This selection must be purposive andconfer an advantage over the other, non selected members of the prior disclosed class,otherwise it is not in fact a new invention at all.
SELECTION INVENTIONS IN THE PHARMACEUTICAL FIELD
IV. OLANZAPINE IN THE UK – THE DECISION OF THE HIGH COURT
The principles established by the EPO were considered in Dr Reddy’s v Eli Lilly
8, thelatest UK case on selection inventions. Eli Lily had claimed the anti-psychotic agent,olanzapine. The prior art included a patent application for a wide class of compoundsdefined by reference to a general formula. This formula had four variable substituentsand was estimated to cover up to 1019 compounds. Preferred values for the substituentsnarrowed the class to 86,000 compounds. Olanzapine was included within this pre-ferred class but was not amongst the approximately 100 compounds listed in thespecification by name and nor was it one of the 15 synthetic examples provided.
The validity of the patent was challenged on several grounds, including an allegation
that it did not fulfil the criteria for a valid selection invention. In assessing the case thejudge, Floyd J., first considered novelty, referring extensively to EPO case law in thefield of selection inventions. In particular, Floyd J. applied case T12/81 (discussedabove) finding that there are two ways in which a novel selection can be made. Firstly,the selection may be of an “unmentioned” compound from territory marked out bythe state of the art and secondly, a valid selection may be made in circumstances where,in order to arrive at the compound, a combination of starting materials has to be cho-sen from “two lists of some length”. He inferred that it is the need to make a choicewhich prevents the disclosure from “unalterably establishing” the claimed compound.
In case T7/8611 Floyd J. found support for applying the principles of T12/81 to
polysubstituted chemical compounds where the individual substituents have to be se-lected from two or more lists of some length. Floyd J. also highlighted T181/8212 inwhich the Board distinguished between a compound which is merely covered by adefinition and one which is expressly taught or, in other words, the “purely intellectualcontent” of the definition and “the information content” in the sense of “a specificteaching with regard to technical action”. The Board held that a specifically mentionedcompound is disclosed whereas a group of compounds in which the substituent ischaracterised by a range only teaches the skilled person about individuals specificallydesignated from the group.
Following this analysis Floyd J. found that “a general formula with multiple sub-
stituents chosen from lists of some length will not normally take away the novelty of asubsequent claim to an individual compound”. He was also persuaded that “a priordisclosure does not take away the novelty of a claim to a specific compound unless thecompound is disclosed in ‘individualised form’”.
“i) In relation to lack of novelty, it is doubtful in the light of the EPO jurisprudencewhether a newly discovered effect complying with Maugham J’s principles could overcomea finding that a compound was specifically disclosed in a prior document.
11 T 7/86 (Draco/Xanthines).
12 T 181/82 (Ciba/Spiro compounds) OJ EPO 1984, 401.
ii) Whether or not that is so, provided there is novelty on conventional grounds, obvious-ness is to be decided according to ordinary principles.
iii) The existence of an advantage possessed by the selected compound will be relevant tothe overall assessment of obviousness, but is not an essential pre-requisite.
iv) Compliance with Maugham J’s principles in IG Farbenindustrie’s Patent
is equally notan essential requirement for inventive step to be found.”
Applying his conclusions, Floyd J. found olanzapine to be novel using the EPO’s ap-proach. The earlier patent application did not make an “individualised disclosure” ofolanzapine as the skilled person would have to make a number of choices of substitu-ents from the general formula. Inventiveness was found because there was no clear di-rection in the earlier document to make the particular selection of olanzapine based onstructure-activity considerations.
In essence, this reasoning completely side-steps the requirement to investigate as
part of the analysis of validity whether the narrower class is merely an arbitrary selec-tion from the prior, wider disclosure. It is a peculiarity of this approach that the priorgeneric disclosure does not appear to have been considered at all in assessing whether anew invention has been made. Once the generic disclosure was dismissed for noveltypurposes, given the breadth of the disclosure it formed no part of the obviousnessanalysis that the class of compounds including olanzapine had previously been claimedas useful for the very same purpose (as anti-psychotic drugs) as that for which olanza-pine is used.
It is interesting that (in case he was found to be wrong on appeal) Floyd J. also ap-
plied the Maugham J. principles in IG Farbenindustrie
discussed above. He found thatthe patent did not meet the “classic” requirements for a selection invention over theprior generic disclosure. The patent claimed only two advantages over individual com-pounds specifically described in the prior art rather than any quality which was of spe-cial character over the prior disclosed class as a whole. Nor was there any assertionthat olanzapine was special and that the advantages were not shared by the class as awhole.
V. OLANZAPINE IN THE UK – THE DECISION OF THE COURT OF APPEAL
In December 2009, the Court of Appeal confirmed the decision of the High Court.
The Court of Appeal dealt briefly with novelty, rejecting the notion that every chemi-cal class disclosure (for example, a Markush formula) discloses each and every memberof the class. Instead, the Court held that anticipation requires an “individualised de-scription” of the later claimed compound or class of compounds and simply noted that“This case is miles from that
”. The appeal focused on the arguments made in relation toobviousness. Most notably the English common law rules developed in I.G. Farbenin-dustrie A.G.’s Patents
have been rejected as “part of legal history, not … living law
” infavour of the approach of the EPO. The Court observed that no technical contribution
SELECTION INVENTIONS IN THE PHARMACEUTICAL FIELD
is provided by an arbitrary selection and that the EPO Boards “deploy the objection ofobviousness where the patentee has in truth made no real technical advance
”. Follow-ing consideration of EPO jurisprudence, the Court held that the correct question toask is
“whether the selection … was ‘arbitrary’, or whether the teaching of the Patentestablished that the selected compound achieved ‘a particular technical result’ and, inanswering that question, one must bear in mind that it arises in the context of thebroader proposition that ‘the extent of a patent monopoly should correspond to and bejustified by the technical contribution to the art’”
. For now, it seems “English” selec-tion inventions have been relegated to legal history.
– THE DECISION OF THE GERMAN SUPREME COURT
Eli Lilly’s patent on olanzapine had an eventful progress through the German courtsystem. As is well known, the patent was revoked by the Federal Patents Court butwhile the appeal was pending before the German Supreme Court, the Dusseldorf Ap-pellate Court granted preliminary injunctions to Lilly, casting severe doubts on theFederal Patent Court’s decision. The German Supreme Court subsequently over-turned the decision of the Federal Patents Court and declared the patent valid.
The majority of the discussion as to the validity of the olanzapine patents centred
not on the prior patent disclosure discussed above but on a separate piece of prior artby Lilly scientists, Chakrabarti 1980, which also disclosed a generic formula that couldencompass olanzapine.
The German Supreme Court, following EPO jurisprudence, held that the prior dis-
closure did not disclose olanzapine in individualised form. The German SupremeCourt also noted that this was consistent with the approach of Floyd J. in the parallelUK proceedings.
The Supreme Court also found that olanzapine was not obvious over the disclosure
in Chakrabarti, based on similar reasoning to that of Floyd J. (there were not sufficientdirections in Chakrabarti to focus on olanzapine based on the disclosed structure ac-tivity relationship).
The prior patent that disclosed the generic class including olanzapine was dealt with
quite quickly by the Supreme Court. Following the same reasoning as above, it did notdeprive the later patent to olanzapine of novelty. The closest specifically exemplifiedcompound in the earlier patent was ethyl-olanzapine and it was held that it would notbe obvious to replace the earlier ethyl substituent with a methyl substituent to formthe later patented compound.
In summary, the German Supreme Court appears to have taken a very similar ap-
proach to that of Floyd J. – an approach which does not appear to give any considera-tion to the particular issues raised by selection patents.
Although patent law in the UK has been harmonised with the European Patent Con-vention, the EPO’s approach to the examination of patentability differs slightly to theway in which the UK courts approach validity. The UK courts have increasinglysought to bring UK law into conformity with the approach of the EPO but are alsobound by precedent. The result can some times be a “crashing of gears” as establishedUK principles give way to a more European approach.
An example of this does appear to be the case of selection inventions. As has been
seen, the law on selection inventions in the UK was well understood and consistentlyapplied in the UK for some 80 years but is now in disarray. In fact it is doubtfulwhether there is any remaining application for “classic” selection inventions in the UKexcept perhaps in the case of numerical sub-ranges.
The UK has moved towards the EPO approach to novelty of chemical compounds.
A prior disclosure of a generic class encompassing a specific compound does not an-ticipate a later individualised disclosure of that compound. There are good policy rea-sons for this approach but also dangers. Is it right for a patentee to obtain a 20 yearmonopoly for a generic class of compounds and then obtain a further 20 year monop-oly simply by picking one compound out of the general formula? It is submitted thatthis should only be allowed where the selection itself is a new invention, which shouldbe defined in distinction to the wider class of compounds from which the selection wasmade. Assessing whether such an invention had been made would in practice involvethe application of Maugham J.’s selection criteria discussed above.
Perhaps the selection criteria can be resurrected in the assessment of obviousness,
taking the prior generic disclosure as the relevant prior art for this purpose. Thereshould be a requirement that the “objective technical problem” associated with thewider class of compounds is identified in the later patent specification and it should beestablished that the selected compounds solve this problem in contradistinction to thecompounds which do not form part of the selection. In this way, the classic UK ap-proach to selection inventions and the EPO approach to novelty and obviousness maybe brought into harmony.
VIII Spanish-Portuguese Conference on Controlled Drug Delivery Alcalá de Henares, Madrid, Spain Poster List P01: CYCLODEXTRIN-BIOADHESIVE NANOPARTICLES FOR ORAL DELIVERY OF LIPOPHILIC DRUGS M. Agüeros, M.A. Campanero, J.M. Irache. P02: INFLUENCE OF THE RHEOLOGICAL PROPERTIES OF TOPICAL EMULSIONS ON THE "IN VITRO" SALILYLIC ACID DELIVERY PROFILE THROUGH HUMAN SKIN AND SYN
Processrätt Reviderad 2011-10-07 Övningsuppgifterna syftar till att ni ska få möjlighet att träna er i att identifiera de juridiska problem som finns i uppgifterna samt att lösa dessa. En stor del av den juridiska problemlösningen handlar om att kunna argumentera för varför en viss lösning ska väljas. För att träna er i den konsten, inför tentan, är det för er egen del bra