CHEMICALS AND LIFESCIENCE Winter 2006 QUARTERLY The Intellectual Property Group
Introduction This quarterly newsletter from the Intellectual Property (“IP”) Group at Walker Morris intends to keep the IP Group’s clients and friends updated on some key developments in the legal environment affecting chemicals, pharmaceuticals, biotechnology and medical devices businesses. It is prepared by the lawyers in our corporate, commercial, intellectual property and environmental teams who have in-depth experience in the chemicals and life science sector. Since the IP Group was formed back in 1992, it has remained distinct and focused and has grown substantially such that we now have eight solicitors dealing exclusively with IP matters. Exceptionally for UK law firms, a high percentage of these solicitors have science backgrounds with three of them having PhDs and post-doctorate research experience. Moreover, no less than four of the solicitors have earned the highly-regarded diplomas in IP Law from either London University or Bristol University. The IP Group also contains a well respected specialist trade marks management team, staffed by MITMA qualified attorneys. Dr Peter Harrison Associate
Contents:
Chemicals
The advent of a Bolar-style regulatory trials exemption in Europe and the UK
Salty Tales, Racemates and Selection Patents: Ranbaxy and Arrow -v- Warner Lambert
Enabling Disclosure: Synthon BV v SmithKline Beecham plc
PREOS v. PROTEOS: Trade Mark Oppositions: Phonetic, Visual & Conceptual Similarity
Chemicals Regulation: Within REACH?
Slowly, but surely, the long and arduous gestation period for the European Union's new chemicals regulatory regime is coming to a close. In some quarters the new registration evaluation and authorisation of chemicals (REACH) regulatory regime is being seen as one of the most important pieces of legislation ever to come out of the European Commission. Certainly, it will have a significant impact on the chemicals industry and it has been a rallying call for the environmental NGO's. Likely Timetable for Implementation On 13 December 2005 the Council of Ministers reached a formal common position under which a number of amendments were made to the draft legislation which had been given its first reading by the European Parliament on 17 November 2005. It is expected that the common position will be formally adopted by the Council in late April 2006 after which the Parliament will have three months in which to carry out a second reading for the legislation to be resubmitted to the Council which will have a further three months to indicate its approval. The legislative mechanism then allows for an undoubtedly frenetic further six weeks for "conciliation" between the Parliament and Council. Against this likely timetable, most commentators expect that REACH will be brought into force (by way of a European regulation) at the beginning of 2007. However, as it will probably take a further year for the mechanics of the legislation to be put into place. The operational requirements are not likely to be applied until early 2008. The Importance of REACH
The perception of the European Commission is that the existing chemicals regulatory legislation is complex and does not offer adequate protection for the consumer and the environment. Current regulatory protection is provided by over 40 pieces of legislation, chief amongst which is Directive 67/548/EEC. This present regulatory regime distinguishes between "existing" chemicals (put on the market before 1981) and "new" chemicals (put on the market after 1981). The "new" chemicals are subject to what has been considered to be a slow and bureaucratic system. This is driven in a top down manner such that risk assessment is carried out on those substances which are identified by the regulatory authority (the European Chemicals Bureau) as requiring clearance. Under the system about 2700 "hazardous" compounds are regulated. Of these, only a limited number have completed full assessments. Under the present system, the burden of proof for proving that a compound is safe was placed upon the European Chemicals Bureau (ECB). It has been said that the current regime both discourages industry from replacing hazardous compounds with new and safer compounds and inhibits innovation. Very little is known of the toxicological and environmental profile of the estimated over 110,000 "existing" (pre 1981) compounds which fall outside the current legislation. It is in relation to these mystery compounds that the new legislation is directed. It is likely however that only 30,000 or so of these compounds are likely to fall within the ambit of REACH; this is because REACH will not cover non- hazardous compounds produced in amounts of less than 1 tonne per annum. Why is REACH Different? The fundamental ethos of the REACH regime is radically different to that which has gone before. Rather than the "top down" approach, the responsibility for obtaining approval and identifying problem compounds will lie squarely with the “manufacturers”, which term will also include importers of compounds into the European Union. The burden of proof will be reversed relative to that which has gone before. Under the
new legislation it will be for the manufacturer to demonstrate that the product is safe to be used. To this end, manufacturers will be responsible for compiling information on toxicity and conditions of use and developing a dossier on the particular chemical. This information and dossier will be submitted to the new regulatory authority, the (European Chemicals Agency or ECA) which will be set up in Helsinki. This ECA will be empowered to register chemicals, evaluate the chemical dossiers, track chemical uses and authorise the use of "dangerous" chemicals. Separate national authorities will have the role of processing registrations, coordinating analyses for the ECA and enforcing compliance. ECA registration and approval will be provided in relation to a particular chemical. A "one submission, one registration" or OSOR rule has been proposed. The thinking behind this single application approach is to relieve the pressure on the industry in general and to reduce the amount of animal toxicology testing required. We understand that the exact workings of the OSOR rule is one of the areas that requires reconciliation between the Commission and Parliament. In particular the issue of applicant data ownership and applicant data sharing has yet to be finalised. Whatever happens, it is likely that manufacturers will be required to "pool" resources and toxicological data to spread the burden and expedite approval. It is likely, therefore that manufacturers will form consortia, to progress a joint application. Although the European Commission has expressed its general support for this approach, it has warned that normal competition law considerations will not be suspended. Consortium members must remain alert to the usual competition rules, in particular those that prevent the exchange of market sensitive information between competitors or other acts likely to leave them open to accusations of price fixing or other anti-competitive collusion. Many players in the chemical sector are considering pooling some of their more commercially sensitive information (particularly regarding tonnage produced) for application through a third party. Clearly, mechanisms will develop to address these concerns. Consortium members will of course also need to give consideration to the maintenance of trade secrets. Issues will remain with regard to the sharing of costs across the consortium (especially if the costs are split on a pro rata basis by tonnage of chemical produced) and with regard to how new members of the consortium will be accommodated in terms of data ownership and cost sharing. The REACH legislation envisages differing levels of vigilance according to the total annual tonnage of chemical produced. From an environmental impact perspective, this approach may be sensible, however there are likely to be cases where its application might seem completely arbitrary. In any event REACH will only cover products traded in volumes of one tonne or more per annum, although some identified hazardous compounds will be subject to closer scrutiny i.e. those already classified as such under Directive 67/548/EEC which could be released under reasonably foreseeable conditions of use. The level of regulatory scrutiny will so increase according to tonnages produced. At ten tonnes production per annum a whole new range of additional data will need to be submitted (including data on skin irritation, corrosion and sensitisation, eye irritation, mutagenicity in prokaryotic cells, and aqauatic toxicity) and the development by the manufacturer of a "Chemical Safety Report". At over 100 tonnes per annum yet further data is required (including in vivo skin and eye irritation data, in vitro mutagenicity data in mammalian cells, and reproductive toxicity data). At over 1000 tonnes per annum a further set of data will be required (including data on stability in organic solvents, dissociation constants and viscosity, long-term fish-based aquatic toxicity, long-term reproductive toxicity, long-term carcogenicity and long-term mutagenicity). Existing data may be "recycled" if it is generated under appropriate ECA-compliant conditions. Predictive toxicology and quantitative structure-activity relationship (QSAR) programmes may also be used if they are ECA validated. This should allow extrapolation of toxicity data across a chemical family. This again is an allowance to prevent undue animal experimentation.
The timescale for implementation of the registration requirements is also likely to follow a tonnage based timetable with large tonnage compounds requiring earlier registration. Certain classes of compounds will be excluded from the regulatory regime, these include minerals, mineral ores and mineral fuels, radioactive materials (which are protected by separate regulation), hydrates of previously ECB-approved products, medicinal products (which are covered by separate regulation), common food oils, sweeteners and additives and storage and end use by-products. It is anticipated that polymers will initially be exempt provided that the polymer does not contain more than 2% of monomer. It is also expected that there will be a five year registration exemption for products used in research and development. To take advantage of this exemption, researchers must notify the ECA of the product and the notification must include the identity of the manufacturer, the identity of the substance, the classification of the substance and the nature of the research and development in which the chemical is to be used. Likely Final Format of REACH
Although the majority of elements of the regulatory proposals are finalised, a number of points remain to be negotiated between the Parliament (which is generally perceived to be more radical) and the Council (which is generally perceived to be more conservative). The key remaining difference between these two constitutional bodies relates to the replacement of hazardous substances with alternatives or whether to adopt strict authorisation. The Parliament in its first reading was keen that manufacturers be forced to replace hazardous substances with safe ones. The Council however believed that "adequate control" would be sufficient for granting authorisation (regardless of the existence of safer alternatives). Moreover, the draft from the parliamentary first reading also contains certain opt-outs from the requirements to share data under the OSOR rule, but these have been reversed by the Council, which has also restricted the "duty of care" and "right to know principles". These would have obliged companies to safely handle chemicals and to provide certain information to the public regarding the safety of compounds. These important areas are likely to form the battle ground between the Parliament and Council. Whatever the outcome the arrival of the REACH regime will result in a fundamental change in the regulatory environment for the European (and world) chemicals Industry. The changes of such a magnitude that questions have arisen as to whether there are enough toxicologists worldwide capable of handling the mountain of administration and analysis which it is envisaged will be created by the new regime. It looks as if for the foreseeable future toxicology will be a very secure career option.
The advent of a Bolar-style regulatory trials exemption in Europe and the UK
Pharmaceuticals companies will naturally be concerned that any launch by them of a generic pharmaceutical active should not constitute an infringement of any valid intellectual property rights. However, there is a strong economic driver for the company to be as ready as is legally permissible for the coming "off patent" of the pharmaceutical active to be launched. A key question, therefore, is whether the performance, during the term of any relevant patent, of laboratory and clinical trials to prepare a dossier for regulatory submission will constitute patent infringement. As this article will explain as a result of European directive 2004/27/EC of 31 March 2004 (the “Directive”), which as implemented in the UK as from 30 October 2005, the legal position in Europe on experimental usage is in the process of substantial change. What is a "Bolar" exemption? Under United States law there has long been a narrow experimental use exemption from patent infringement provided that the experiments in question are conducted "solely for amusement, to satisfy idle curiosity, or for strictly philosophical enquiryments are "in keeping with the legitimate business of the alleged infringerxperimental exemption will not apply. In Roche Products Inc.–v- Bolar Pharmaceuticals Co the United States Court of Appeals for the Federal Circuit unsurprisingly held that the use of a patented compound to obtain data for a regulatory application in respect of a generic version of that compound was not an experimental use and so constituted an infringement of the patent. In response to this decision the US Congress introduced a statutory provision to allow testing of generics during the monopoly term of a patented compound. The US Drug Price Competition and Patent Restoration Act ("Hatch- Waxman Act") created an exemption for regulatory tests stating that it is not an infringement to: "make, use, offer to sell, or sell within the US or import into the US a patented invention solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products This has come to be called the "Bolar" exemption after the case brought by Roche. Although many other jurisdictions, including Australia, Canada, Israel, Japan and New Zealand have a similar statutory regulatory trials exemption, there has until now been no such statutory provision in Europe. The Pre-Directive Position in the United Kingdom The legal position of regulatory trials in the UK prior to the implementation of Directive 2004/27/EC was akin to the pre-Hatch-Waxman position in the US. Section 60(5)(b) of the UK Patents Act (1977) states that: "An act which, apart from this subsection, would constitute an infringement of a patent for an invention shall not do so if it is done for. experimental purposes relating to the subject-matter of the invention". To what extent did laboratory and clinical work done to generate data for regulatory purposes fall within this experimental exemption? The UK Court of Appeal in Monsanto Co v Stauffer Chemical Co.e) drew a distinction between experiments done by a person for the purpose of satisfying themselves that a product could be manufactured commercially and experiments done by a person with a view to obtaining clearance to manufacture the product commercially (i.e. with a view to obtaining regulatory clearance). It was held that the field tests carried out by Stauffer with a view to obtain regulatory clearances (and not merely to ascertain whether Stauffer would be able to manufacture the product in question) should be considered as having a "clear commercial purpose" and, as such, did not fall within the experimental exception provided in s.60(5)(b). The UK Court of Appeal in Monsanto did not construe "relating to the subject matter of the invention" so narrowly as to entirely exclude all research that was directed to commercial exploitation. However, in Smith Kline & French v. Evans MedicalMonsanto was considered by the UK High Court and it was held that the words "relating to the subject matter of the invention" had a limiting effect. For the experimental exemption to apply the act must be done for purposes relating to the subject matter of the invention in the sense of having "a real and direct connection with the subject matter". As a rule of thumb it would appear that the greater the degree of commercial purpose to the testing, the greater the likelihood of falling outside the exemption.
1 Madey –v- Duke University 307 F.1351 (Fed Cir 2002) 2 Madey supra at 1362 3 221 USPQ 937 (Fed Cir 1984) 4 35 USC 271(e) 5 [1984] FSR 574 6 [1989] FSR 513
The Pre-Directive Position in Germany and France The experimental use exemption found in the 1977 UK Patents Act, of course, arises out of the European Patent Convention and so can be found in a similar form in the patent legislation of all the Convention signatory states. The exemption has not, however, been interpreted consistently across the signatories; both Germany and France had demonstrated a more permissive approach than in the UK. In Germany the Bundesgerichtshof (Federal Appeal Court) in Klinische Versuche (Clinicalgave a wide interpretation of the experimental exemption such that any activities with "research purposes" relating to the subject of the patented invention would fall within the exemption. This would cover the range from scientific discovery to commercially orientated trials. Such activities would not constitute a patent infringement simply because the activity served a commercial as well as a scientific or technical purpose. However, where the "research" is no longer linked to the scientific or technological purpose or where the scale of testing is such as to no longer justify "research purposes" then the testing would fall outside the experimental exemption. It has to be said that this is not a particularly clear distinction. The decisions of the French courts have been similarly unclear. Although earlier jurisprudence had followed a similar line to that in UK case of Monsanto (i.e. the experimental exemption would not apply if the testing was for a predominantly commercial purpose) the Paris District Court in Wellcome v Parexel 7 held in 1998 that clinical trials of reformulated acyclovir were permitted even though the trials were carried out on a large scale and the reformulation related to a planned new dosage regimen for the drug. This judgment was upheld by the Paris Court of Appeals in 1999. In the further case of Wellcome –v- Parexel and Flamel and CréapharmTribunal de Grande Instance de Paris, bioequivalence studies performed for generic regulatory approval were found to constitute experimental use. The New Regulatory Trials Exemption The Directive (which has its effect through amendment of previous directives, in particular directive No. 2001/83/EC on the Community Code Relating to Medicinal Products for Human Use) introduces a "Bolar"- type provision. As with much of European legislation that arises out of political compromise, it is awkwardly drafted. It provides that: ".conducting the necessary studies and trials with a view to the application [for registration of a generic medicinal product].and the consequential practical requirements shall not be regarded as contrary to patent rights or to supplementary protection certificates for medicinal products". (Revised Article 10(6) of Directive 2001/83/EC) The important point to realise is that this exemption covers only regulatory submissions caught under Article 10 of directive No. 2001/83/EC. Ostensibly these are studies and trials (and consequential practical requirements) necessary for application for marketing authorisation in relation to generic medicinal products under the so-called "abridged" procedure. These are applications where the applicant seeks to "piggy-back" on a marketing authorisation which has already been granted in relation to a "reference product". This article discusses below whether de novo marketing authorisation applications (where no reference product is to be relied upon) are also covered. "Medicinal product" in the context of directive No. 2001/83/EC covers any substance or combination of substances for use in preventing or treating diseases in humans, or which may be used or administered to humans with a view to restoring, correcting or modifying physiological functions by way of a pharmacological, immunological or metabolic action or to make a medical diagnosis. It does not include veterinary products although these are covered by comparable provisions in a veterinary product directive (2001/82/EC). 7 [1989] RPC 423 8 PIBD 2001, 729, III-530
A generic medicinal product for this purpose means a medicinal product which: "has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with reference to the reference medicinal product has been demonstrated by appropriate bioavailability studies" For this purpose: "different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance unless they differ significantly in properties with regard to safety and/or efficacy". Articles 10(3) and 10(4) of the Directive also cover extra testing relating to pre-clinical and clinical trials:
a) where the bioequivalence with the reference product cannot be demonstrated through
b) where there are differences from the reference product relating to the active substance(s),
therapeutic indications, strength, pharmaceutical form or route of administration; and
c) of a biological medicinal product which does not fit the definition of generic medicinal
product because of differences from the reference biological reference product relating to
raw materials or differences in manufacturing.
Implementation of the Directive the UK European directives, of course, have their effect through being implemented in the national law of each member state; the individual states being given deadline in which to enact the changes. The implementation of the "Bolar" provision in 2004/27/EC into UK law was brought into force on the directive deadline of 30 October 2005 and was effected through amendment to the UK Patents Act (Section 60(5)). The new paragraph (i) of that subsection reads: "An act which apart from this subsection would constitute an infringement of a patent for an invention shall not do so if – (i) an act done in conducting a study, test or trial which is necessary for and is conducted with a view to the application of paragraphs 1 to 5 of article 13 of Directive 2001/82/EC or paragraphs 1 to 4 of article 10 of Directive 2001/83/EC, or (ii) any other act which is required for the purpose of the application of those paragraphs." The Effect of Revised Article 10(6) Directive 2001/83/EC in the United Kingdom
In those states such as Germany and France which already had a permissive regime with regard to the experimental use exemption, the new Bolar exemption will provide useful legal clarity. In the UK, the implementation of the directive will create a greater change from the existing position. But what exactly will be permissible? The actual effect of revised Article 10(6) of Directive 2001/83/EC is currently untested in the courts or elsewhere but one point does, immediately spring to mind. The article, and amended Patents Act Section 60(5), states that "necessary" studies will not be contrary to patent rights or supplementary protection certificates. It would likely be argued by a patentee that any testing that is not necessary for the regulatory
application could still be covered by the pre-amendment position under Monsanto. What constitutes "necessary" in this context would be a point for argument in court in the light of the UK Medicines & Healthcare Regulatory Authority guidance to researchers and the Good Clinical Practice guidelines (see also the GCP Directive 2005/28/EC). The view of the UK Patent Office is that activities associated with the development of any product supported by an "abridged" regulatory dossier (relying on data for reference products without consent) would qualify for exemption from patent infringement. In this regard they also believe that the exemption would cover the following activities:
(a) the carrying out of chemical and biological synthetic processes for the making, disposal or
keeping of the active substances(s) including the manufacture or the import of batches in quantities
sufficient to provide material for preparing investigative batches of the medicinal product and to
validate the processes to the satisfaction of the competent authorities;
(b) the development, testing and use of the associated analytical techniques for the above;
(c) the development of the final pharmaceutical composition and manufacturing processes for the
medicinal product to be marketed including the making, disposal or keeping or import of product
batches in quantities sufficient to conduct the necessary pre-clinical tests, clinical and
bioavailability trials and stability studies of the medicinal product and to validate the processes to
the satisfaction of the competent authorities;
(d) the development, testing and use of the associated analytical techniques for the above;
(e) the manufacture and supply to the competent authorities of samples of active substances, their
precursors, intermediates or impurities and of finished product samples; and
(f) compilation and submission of a marketing authorisation or variation application and application
It is the further view of the UK Patent Office that tests and trials can be carried out from the date of amendment to the UK Patents Act without infringing any relevant patents provided that those activities are for the purposes of submitting an application under Article 10 paragraphs 1 to 4 of Directive 2001/83/EC, regardless of whether the reference products were submitted for authorisation before or after the coming into effect of the new provision of the UK Patents Act and regardless of whether the reference product is protected by old or new periods of data and market exclusivity. Are all regulatory trials covered by the Bolar exemption? The position in relation to trials conducted for approval under the abridged procedure would appear to be clear. However, it is often the case that the originator company will have patent protection that extends beyond the reference product itself. Without a broader scope to the regulatory trials exemption, regulatory work on known compounds or new chemical entities that are not generics of the reference product per se could constitute an infringement of any such broader patent protection. So, are studies other than those conducted for the purposes of obtaining regulatory approval under the abridged procedure covered? The exemption in s60(5)(i) is closely tied to the regulatory activities set out in Article 10 paragraphs 1 to 4 of Directive 2001/83/EC. Article 10(3) of the Directive expressly states that: "in cases where the medicinal product does not fall within the definition of generic medicinal product…the results of the appropriate pre-clinical tests or clinical trials shall be provided". I could be argued that these tests would, almost by definition, be performed outside of the requirements of the abridged procedure. If that is the case, the regulatory trials exemption under the amended Patents Act
will extend beyond work done to meet requirements under the abridged procedure to cover other trials performed on compounds that are not generics per se. This is an important distinction, and one which perhaps will not be entirely resolved until we have a decision from an appropriate Court. Generic biological medicinal products (sometimes called "biosimilars"), being larger-scale molecules produced through biotechnological methods, are rarely identical to the reference biological product due to differences in starting raw materials and production methods. There is often also a lack of precise characterisation of the reference product. The Directive envisages this situation and sets out a series of regulatory testing requirements for biosimilars under Article 10(4). Since Article 10(6) also refers to Article 10(4) the regulatory trials exemption should also cover such testing. It is of interest that in Germany Directive 2004/27/EC has been implemented to permit all forms of regulatory trials work performed to meet regulatory requirements in the European Union and beyond. Section 11 of the German Patent Act, which deals with the limitation of the effect of patents states that: The effect of a patent does not apply to 2b.
[effective as 6 September 2005] studies and trials, and the resulting practical demands, which are necessary for the acquisition of a medico-legal permission for putting into circulation in the European Union or for the acquisition of a medico-legal licence in the member-states of the European Union or in non-European Union member states; Conclusion The "Bolar" type exemption now introduced by the Directive, will be a very useful tool for manufacturers of generic pharmaceuticals but care should still be taken. It should not to be interpreted as a general broadening of the experimental use exemption. Any testing in the UK using a patented invention which falls outside of the safe harbour of the "Bolar" provision (for example where it is not necessary for regulatory approval) will be subject to the "old" test for the experimental use exemption. The question of whether the Bolar exemption in the UK extends beyond trials performed to meet the requirements of the abridged procedure is unresolved. Salty Tales, Racemates and Selection Patents: Ranbaxy and Arrow -v- Warner Lambert
In October 2005 the Patents Court (Pumfrey J) handed down its judgment in a case relating to two of Warner Lambert's patents relating to the cholesterol synthesis inhibitor atorvastatin (the hemicalcium salt of which is sold under the brand Lipitor). Warner Lambert had a "master" patent to atorvastatin and a later patent to the calcium salt of an enantiomer of atorvastatin. Indian-based generics business Ranbaxy sought a declaration of non-infringement of the master patent in relation to an optically pure enantiomer of atorvastatin (as a calcium salt) and both Ranbaxy and Arrow sought invalidity of the second Warner patent on the basis of lack of novelty and inventive step over the PCT application for the master patent and the master patent, respectively. In relation to claim construction of the master patent, the court unsurprisingly followed the well-established UK approach of "purposive construction" summarised by the House of Lords decision in Kirin Amgen –v- Hoechst (2005 RPC 9). Pumfrey J reiterated that an over-meticulous analysis is one that is too willing to draw from a detailed analysis of the grammar, the punctuation and the particular words and phrases used in the claim thereby giving the claim a meaning that the skilled person would not give it. The judge stated that
"Carefulness is not to be equated with over-meticulousness". The court found that the skilled person would understand that the relevant claim in the master patent covered both the racemic mixture of the claimed compound and the optically isolated enantiomers thereof, confirming that the Ranbaxy enantiomer was within the claim. In relation to the calcium salt patent Ranbaxy raised two points of invalidity: lack of novelty over the original PCT application and lack of inventive step over the master patent. In coming to this finding the court considered whether the calcium salt patent was patentable as a "selection patent" over the master patent. The PCT application for the master patent had a specific reference to the atorvastatin molecule and stated that the salts could be produced using a list of seven cations. One of those cations was calcium. Pumfrey J held that the calcium salt patent lacked novelty over the PCT application. The master patent also disclosed atorvastatin as a racemate and described a number of salt ions (including calcium). Although the calcium salt patent was to an enantiomer, the court found that resolution of racemic mixtures was part of the common general knowledge and so the calcium salt of the enantiomer was obvious. The court considered the principle of selection patents and stated that there is no doubt that where there is a disclosure of a class of compounds it is possible to select from that a sub-class of compounds united by a common feature: a so-called "selection patent". It also reiterated the position that the inventive step in such a selection patent lies in the discovery that one or more members of a previously known class possess some special advantage for a particular purpose which could not have been predicted before the discovery was made. Pumfrey J went on to state that unless the later patent states what is the advantage possessed by the selected class, it is merely an arbitrary selection among things already disclosed and will lack novelty. The first test should be that of novelty. Once novelty is established one should look to the presence of an inventive step. Pumfrey J., stated that from his examination of the jurisprudence although the selected class may still be obvious in the light of the prior art the nature of the technical advantage will be one of the factors to be taken into account in assessing obviousness. In relation to the question of inventive step Warner-Lambert had adduced evidence that the calcium salt of atorvastatin had advantages in terms of formulation over the sodium salt. Pumfrey J decided on the facts that the technical problem was only appreciated by the patentee following testing of the sodium salt; testing which occurred at the same time as the testing of the calcium salt. Essentially the technical problem was uncovered in-house at the same time as the solution to it was found. During opposition proceedings concerning the calcium salt patent before the European Patent Office (EPO) Board of Appeal Warner-Lambert had successfully presented the "after-discovered" advantage of the calcium salt. In contrast to the EPO position, Pumfrey J believed that problems would be encountered in finding inventive step based on an advantage that was known to the patentee before the priority date but not disclosed in the specification or which is discovered after the priority date. He held that a skilled person presented with atorvastatin would look to try a number of salts of atorvastatin to give the required bioavailability. In doing so that skilled person would (as had Warner-Lambert) come to the realisation of the advantages of the calcium salt over the sodium salt. The calcium salt was therefore obvious. The case is being appealed.
Enabling Disclosure: Synthon BV v SmithKline Beecham plc
The December 2005 judgment of the House of Lords in Synthon BV v SmithKline Beecham Plc allowed Synthon's appeal for the revocation of SmithKline Beecham's paroxetine patent and cast light on the concept of "enabling disclosure". Lord Hoffman found that a clear distinction should be made between the 'disclosure' element and the 'enablement' requirement of a prior art "enabling disclosure". Further, in cases concerning complex technology, regard should be had to what the ordinary man skilled in the art might consider in attempting to follow the disclosed material, notwithstanding the fact that "the prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee". The case emerged from Synthon's application to have SmithKline's patent for crystalline paroxetine methanesulfonate ("PMS") revoked on the ground that it was invalid for lack of novelty over Synthon's prior unpublished patent application. As a co-pending application the Synthon document was available as prior art, but only as to novelty. The Court of Appeal overturned the trial judge's decision, which had held that Synthon's patent disclosed the existence of PMS in the form specified in SmithKline's patent and that the ordinary skilled man in the art would be able to reproduce that form of PMS. Aldous LJ distinguished Synthon and SmithKline's disclosures on technical grounds. He added that "the crucial question was not whether the skilled addressee would expect success, but whether the application made available PMS as claimed…Once it had been established that [the PMS example in the Synthon application] did not disclose a successful route to PMS as claimed in the patent, the skilled addressee might have adopted obvious modifications. But such an approach is not permissible when considering novelty…". Synthon then referred the matter to the House of Lords. Lord Hoffman criticised Aldous LJ's failure to distinguish between the two requirements for anticipation "prior disclosure" and "enablement". He pointed out that for the purposes of disclosure "the matter relied upon as prior art must disclose subject matter, which, if performed, would necessarily result in an infringement of the patent". The same cannot be said for enablement: "Enablement means that the ordinary skilled person would have been able to perform the invention which satisfies the requirement of disclosure". The assumption is that the person skilled in the art is willing to make trial and error experiments to get it to work. Therefore the skilled person has no further part to play once the meanings of the prior disclosure and the patent have been determined. The disclosure is of an invention which either infringes the patent, or not. In terms of enablement, however, "the question is no longer what the skilled person would think the disclosure meant but whether he would be able to work the invention which the court has held it to disclose". Lord Hoffman concluded that Sython's application disclosed the existence of PMS crystals despite the fact that it contained some technical errors relating to its form. He was of the view that enablement depended on whether in fact the ordinary skilled man would have been able to make crystalline PMS. Thus errors in Synthon's application could be disregarded for this purpose, since the ordinary skilled man could be assumed to try obvious modifications to make it work.
PREOS v. PROTEOS: Trade Mark Oppositions: Phonetic, Visual & Conceptual Similarity
In 2002 on behalf of a USA pharmaceutical company, the Trade Marks Unit of Walker Morris filed for the registration of PREOS as a European wide Community mark for pharmaceutical preparations for, inter alia, the prevention or treatment of osteoprosis. The application was opposed by a French pharmaceutical company which had earlier, in France, registered PROTEOS for pharmaceuticals. The opponent claimed there was a likelihood of confusion in respect of goods which were identical to those protected under its earlier French mark, the conflicting marks possessed very similar vowel-consonant structure and were identical in a very substantial portion i.e. the combination "PR/EOS" making the marks similar in pronunciation as well as visually and conceptually similar.
Applying the principles laid down in the ECJ's decision in Sabel BV v. Puma AG, Rudolf Dassler Sportthat marks need to be compared globally for visual, phonetic and conceptual similarity, on 7 February 2006, the Office for the Harmonisation in the Internal Market – the European Trade Marks & Designs Department, ("OHIM"), rejected the opposition. On the question of whether there was visual similarity OHIM held that "-os" was a suffix frequently used in the pharmaceutical field and the fact that the earlier portions of the marks (PRE v. PROTE) are quite different was enough to avoid an allegation of visual similarity.
Turning to phonetic similarity, OHIM held that although there were some similarities in that the beginning consonants of PROTEOSn, namely PR and the ending "EOS" are included in PREOS and PROTEOS and are pronounced identically, the additional syllable "TE" in PROTEOS is a strong sound which will be clearly perceived and will give the first syllables a totally different pronunciation. OHIM held that this would result in differences between the phonetic rhythm and intonation of the earlier mark and PREOS and the marks were phonetically dissimilar.
Since the public would perceive both marks as invented words without any meaning, OHIM held that a conceptual link could not be established between the marks. OHIM held that the marks were dissimilar and the opponent should pay the applicant's costs of the proceedings.
For further information please feel free to contact any member of our team below Patrick Cantrill Partner – Head of Intellectual Property [email protected] Tel: 0113 283 2591 Dr. Peter Harrison Associate – Intellectual Property [email protected] Tel: 0113 283 4412
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Computertomographie (CT) Herz Sehr geehrte Patientin, sehr geehrter Patient! Die Computertomographie liefert mit Hilfe von Röntgenstrahlen und hochleistungsfähiger Computertechnologie Schnittbilder des Körpers und erlaubt somit eine exakte Aussage über die Beschaffenheit sowie krankhafte Veränderungen von Organen und Gefäßen. Aufgrund modernster Technik ist es möglich, neben einer
Form 13-3f Academic Year 2013-14 Drug-Testing Consent − NCAA Division III Sign and return to your director of athletics. Due date: Before your institution's first competition. Required by: NCAA Constitution 3.2.4.6 and NCAA Bylaw 14.1.4. Purpose: Effective date: This consent from shall be in effect from the date this document is signed and shall remain in effec
CHEMICALS AND 
Chemicals Regulation: Within REACH? 
new legislation it will be for the manufacturer to demonstrate that the product is safe to be used. To this end, manufacturers will be responsible for compiling information on toxicity and conditions of use and developing a dossier on the particular chemical. This information and dossier will be submitted to the new regulatory authority, the (European Chemicals Agency or ECA) which will be set up in Helsinki. This ECA will be empowered to register chemicals, evaluate the chemical dossiers, track chemical uses and authorise the use of "dangerous" chemicals. Separate national authorities will have the role of processing registrations, coordinating analyses for the ECA and enforcing compliance. ECA registration and approval will be provided in relation to a particular chemical. A "one submission, one registration" or OSOR rule has been proposed. The thinking behind this single application approach is to relieve the pressure on the industry in general and to reduce the amount of animal toxicology testing required. We understand that the exact workings of the OSOR rule is one of the areas that requires reconciliation between the Commission and Parliament. In particular the issue of applicant data ownership and applicant data sharing has yet to be finalised. Whatever happens, it is likely that manufacturers will be required to "pool" resources and toxicological data to spread the burden and expedite approval. It is likely, therefore that manufacturers will form consortia, to progress a joint application. Although the European Commission has expressed its general support for this approach, it has warned that normal competition law considerations will not be suspended. Consortium members must remain alert to the usual competition rules, in particular those that prevent the exchange of market sensitive information between competitors or other acts likely to leave them open to accusations of price fixing or other anti-competitive collusion. Many players in the chemical sector are considering pooling some of their more commercially sensitive information (particularly regarding tonnage produced) for application through a third party. Clearly, mechanisms will develop to address these concerns. Consortium members will of course also need to give consideration to the maintenance of trade secrets. Issues will remain with regard to the sharing of costs across the consortium (especially if the costs are split on a pro rata basis by tonnage of chemical produced) and with regard to how new members of the consortium will be accommodated in terms of data ownership and cost sharing. The REACH legislation envisages differing levels of vigilance according to the total annual tonnage of chemical produced. From an environmental impact perspective, this approach may be sensible, however there are likely to be cases where its application might seem completely arbitrary. In any event REACH will only cover products traded in volumes of one tonne or more per annum, although some identified hazardous compounds will be subject to closer scrutiny i.e. those already classified as such under Directive 67/548/EEC which could be released under reasonably foreseeable conditions of use. The level of regulatory scrutiny will so increase according to tonnages produced. At ten tonnes production per annum a whole new range of additional data will need to be submitted (including data on skin irritation, corrosion and sensitisation, eye irritation, mutagenicity in prokaryotic cells, and aqauatic toxicity) and the development by the manufacturer of a "Chemical Safety Report". At over 100 tonnes per annum yet further data is required (including in vivo skin and eye irritation data, in vitro mutagenicity data in mammalian cells, and reproductive toxicity data). At over 1000 tonnes per annum a further set of data will be required (including data on stability in organic solvents, dissociation constants and viscosity, long-term fish-based aquatic toxicity, long-term reproductive toxicity, long-term carcogenicity and long-term mutagenicity). Existing data may be "recycled" if it is generated under appropriate ECA-compliant conditions. Predictive toxicology and quantitative structure-activity relationship (QSAR) programmes may also be used if they are ECA validated. This should allow extrapolation of toxicity data across a chemical family. This again is an allowance to prevent undue animal experimentation.
The timescale for implementation of the registration requirements is also likely to follow a tonnage based 
for strictly philosophical enquiryments are "in keeping with the legitimate business of the 
The Pre-Directive Position in Germany and France 
A generic medicinal product for this purpose means a medicinal product which: "has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with reference to the reference medicinal product has been demonstrated by appropriate bioavailability studies" For this purpose: "different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance unless they differ significantly in properties with regard to safety and/or efficacy". Articles 10(3) and 10(4) of the Directive also cover extra testing relating to pre-clinical and clinical trials:
a) where the bioequivalence with the reference product cannot be demonstrated through
b) where there are differences from the reference product relating to the active substance(s),
therapeutic indications, strength, pharmaceutical form or route of administration; and
c) of a biological medicinal product which does not fit the definition of generic medicinal
product because of differences from the reference biological reference product relating to
raw materials or differences in manufacturing.
application could still be covered by the pre-amendment position under Monsanto. What constitutes "necessary" in this context would be a point for argument in court in the light of the UK Medicines & Healthcare Regulatory Authority guidance to researchers and the Good Clinical Practice guidelines (see also the GCP Directive 2005/28/EC). The view of the UK Patent Office is that activities associated with the development of any product supported by an "abridged" regulatory dossier (relying on data for reference products without consent) would qualify for exemption from patent infringement. In this regard they also believe that the exemption would cover the following activities:
(a) the carrying out of chemical and biological synthetic processes for the making, disposal or
keeping of the active substances(s) including the manufacture or the import of batches in quantities
sufficient to provide material for preparing investigative batches of the medicinal product and to
validate the processes to the satisfaction of the competent authorities;
(b) the development, testing and use of the associated analytical techniques for the above;
(c) the development of the final pharmaceutical composition and manufacturing processes for the
medicinal product to be marketed including the making, disposal or keeping or import of product
batches in quantities sufficient to conduct the necessary pre-clinical tests, clinical and
bioavailability trials and stability studies of the medicinal product and to validate the processes to
the satisfaction of the competent authorities;
(d) the development, testing and use of the associated analytical techniques for the above;
(e) the manufacture and supply to the competent authorities of samples of active substances, their
precursors, intermediates or impurities and of finished product samples; and
(f) compilation and submission of a marketing authorisation or variation application and application
will extend beyond work done to meet requirements under the abridged procedure to cover other trials performed on compounds that are not generics per se. This is an important distinction, and one which perhaps will not be entirely resolved until we have a decision from an appropriate Court. Generic biological medicinal products (sometimes called "biosimilars"), being larger-scale molecules produced through biotechnological methods, are rarely identical to the reference biological product due to differences in starting raw materials and production methods. There is often also a lack of precise characterisation of the reference product. The Directive envisages this situation and sets out a series of regulatory testing requirements for biosimilars under Article 10(4). Since Article 10(6) also refers to Article 10(4) the regulatory trials exemption should also cover such testing. It is of interest that in Germany Directive 2004/27/EC has been implemented to permit all forms of regulatory trials work performed to meet regulatory requirements in the European Union and beyond. Section 11 of the German Patent Act, which deals with the limitation of the effect of patents states that: The effect of a patent does not apply to 2b.
[effective as 6 September 2005] studies and trials, and the resulting practical demands, which
are necessary for the acquisition of a medico-legal permission for putting into circulation in the
European Union or for the acquisition of a medico-legal licence in the member-states of the
European Union or in non-European Union member states;
"Carefulness is not to be equated with over-meticulousness". The court found that the skilled person would understand that the relevant claim in the master patent covered both the racemic mixture of the claimed compound and the optically isolated enantiomers thereof, confirming that the Ranbaxy enantiomer was within the claim. In relation to the calcium salt patent Ranbaxy raised two points of invalidity: lack of novelty over the original PCT application and lack of inventive step over the master patent. In coming to this finding the court considered whether the calcium salt patent was patentable as a "selection patent" over the master patent. The PCT application for the master patent had a specific reference to the atorvastatin molecule and stated that the salts could be produced using a list of seven cations. One of those cations was calcium. Pumfrey J held that the calcium salt patent lacked novelty over the PCT application. The master patent also disclosed atorvastatin as a racemate and described a number of salt ions (including calcium). Although the calcium salt patent was to an enantiomer, the court found that resolution of racemic mixtures was part of the common general knowledge and so the calcium salt of the enantiomer was obvious. The court considered the principle of selection patents and stated that there is no doubt that where there is a disclosure of a class of compounds it is possible to select from that a sub-class of compounds united by a common feature: a so-called "selection patent". It also reiterated the position that the inventive step in such a selection patent lies in the discovery that one or more members of a previously known class possess some special advantage for a particular purpose which could not have been predicted before the discovery was made. Pumfrey J went on to state that unless the later patent states what is the advantage possessed by the selected class, it is merely an arbitrary selection among things already disclosed and will lack novelty. The first test should be that of novelty. Once novelty is established one should look to the presence of an inventive step. Pumfrey J., stated that from his examination of the jurisprudence although the selected class may still be obvious in the light of the prior art the nature of the technical advantage will be one of the factors to be taken into account in assessing obviousness. In relation to the question of inventive step Warner-Lambert had adduced evidence that the calcium salt of atorvastatin had advantages in terms of formulation over the sodium salt. Pumfrey J decided on the facts that the technical problem was only appreciated by the patentee following testing of the sodium salt; testing which occurred at the same time as the testing of the calcium salt. Essentially the technical problem was uncovered in-house at the same time as the solution to it was found. During opposition proceedings concerning the calcium salt patent before the European Patent Office (EPO) Board of Appeal Warner-Lambert had successfully presented the "after-discovered" advantage of the calcium salt. In contrast to the EPO position, Pumfrey J believed that problems would be encountered in finding inventive step based on an advantage that was known to the patentee before the priority date but not disclosed in the specification or which is discovered after the priority date. He held that a skilled person presented with atorvastatin would look to try a number of salts of atorvastatin to give the required bioavailability. In doing so that skilled person would (as had Warner-Lambert) come to the realisation of the advantages of the calcium salt over the sodium salt. The calcium salt was therefore obvious. The case is being appealed.
Enabling Disclosure: Synthon BV v SmithKline 
PREOS v. PROTEOS: Trade Mark Oppositions: 
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