Crafting a Global Strategy: Best Practices for International Prosecution & Litigation to Maximize the Value of Your Biotech Patent Portfolio
858807Crafting a Global Strategy: Best Practices forInternational Prosecution and Litigation toMaximize the Value of Your Biotech Patent PortfolioACIs 14th Advanced Forum on Biotech PatentsHyatt Regency Boston, 29 November 2012Bert Oosting, Hogan Lovells International LLP
www.hoganlovells.com2 858807The Prosecution and Litigation Framework in the EUProsecution and Oppositions before the European Patent Office(EPO) and Litigation before the National Courts (1)• EPO and "patchwork" of National Courts– No presumption of validity (except in Preliminary Injunction proceedings in Belgium):invalidity as defence to infringement action or separate revocation action– EP is "bundle" of national patents after grant: EP-wide revocation in opposition andnational revocation for national patent of EP "bundle" in national revocation action• EPO opposition and litigation before National Courts run concurrently– Germany: Bifurcated treatment of validity and infringement and no nationalrevocation action before validity court before end of opposition– Suspension of national revocation proceedings pending opposition discretionary, butunlikely if no EPO-hearing imminent• EPO opposition decision not binding but (highly) persuasive– NL strictly follows EPO practice (strict novelty test, problem/solution approach toinventive step)– UK follows "settled" EPO practice, unless "commodore is steering the fleet onto therocks", but expert testimony/cross-examination at Trial and common generalknowledge ("CGK") key
www.hoganlovells.com3 858807The Prosecution and Litigation Framework in the EUProsecution and Oppositions before the European Patent Office(EPO) and Litigation before the National Courts (2)• Claim construction– Art. 69 EPC: Scope determined by claims, description used to interpret (wording of) claims– Protocol on Interpretation: Position between strict literal meaning of wording used in claims (fair protection forpatentee) and using claims as guideline to determine invention behind the claims (reasonable certainty forthird parties)– Article 2 Protocol on Interpretation: Due account must be taken of means equivalent to means specified inclaims• Infringement determined under national law (Art. 64(3) EPC) and nationalapproaches differ• UK:– Purposive construction and sensible meaning of wording in claims– No Doctrine Of Equivalence: No protection outside the claims• Germany:– No prosecution file arguments– Literal and equivalent infringement• NL:– Literal and equivalent infringement (function-way-result and insubstantial differences)– Prosecution file arguments• Limited harmonisation: Unified Patent Court
www.hoganlovells.com4 858807The EPO and National Courts:An example – Lilly v. HGS and the approach of the EPO and UKCourts on industrial applicability and sufficiency• Industrial applicability (Article 57 EPC) and sufficiency/enablement (Article 83 EPC)– Article 57 EPC: "An invention shall be considered as susceptible of industrial application if it can be made or used in any kind of industry"• "Lilly v. HGS (UK/EPO)"– HGS patent discloses the nucleotide and amino acid sequence structure of a novel member (Neutrokine-α) of the TNF ligand super family– The patent discloses list of wide ranging, possible uses for Neutrokine-α and its antibodies – from treating cancer to treating worms– EPO Opposition Division: patent invalid for added matter and lack of inventive step (industrial application not considered)• UK High Court (first instance)– List of "extravagant", "contradictory" and sometimes "inaccurate" possible (industrial) uses "speculative"; not enough basis to makeindustrial application/applicability of Neutrokine-α plausible– Patent invalid for lack of industrial application (among other things)• EPO-TBA (appeal)– Accelerated proceedings: decision delivered prior to UK Court of Appeals hearing– It was common general knowledge that all members of TNF ligand super family are involved in various medical conditions and havecommon, underlying, shared property (the ability to co-stimulate T-cell proliferation), this property was disclosed in the patent, therefore Art.57 EPC satisfied (not relevant that the patent made numerous additional, sometimes inaccurate, contradictory statements on possible uses,since the skilled man would be capable of distinguishing these kinds of "boiler plate" statements from the positive technical informationprovided in the patent)– Skilled man would regard the long listing of wide ranging possible uses in medical conditions as a numeration and generalisation of theproperties of the TNF ligand super family• UK Court of Appeal:– UK Courts would follow "settled" EPO practice, unless it would be clear that "the commodore is steering the fleet onto the rocks"– Industrial applicability not made "plausible"/"reasonably credible" (only TNFα has been shown to be actually useful, not the whole TNFligand super family)– Patent invalid for lack of industrial application• UK Supreme Court– Reverses earlier decisions: patent not invalid for lack of industrial application– Standard to strict (exacting)– Lower courts were wrong to focus on "speculative" nature of some of the listed therapeutic uses; the known activities of the TNF ligandsuper family were enough in itself to make it "plausible" that Neutrokine-α be usable for purpose of research work, which is industrial activityin itself• UK Court of Appeal:– Assessment of sufficiency/enablement: patent sufficient/enabled
www.hoganlovells.com5 858807The Regulatory Framework in the EURegulatory Approval Pathway for Biosimilars (1)• Article 10.4 Directive 2001/83 (Community Code on medicinal products)– Article 10(1): Abridged approval pathway for "generic medicinal products"– Article 10(2): Definition "generic medicinal product"– Article 10(4): Approval Pathway for Biosimilars: Where biosimilar does not meet definition of "generic medicinal product", "owing to, in particular,differences relating to raw materials or differences in manufacturing processes" additional, supplementary data shall be provided. The type and quantity ofadditional, supplementary data to be provided must comply with criteria stated in Annex I Directive 2001/83 and related detailed general and productspecific (EMA/CHMP) Guidelines• Annex I Directive 2001/83– Annex I, Part II, Section 4 (Similar Biological Medicinal Products):• “If the information required in the case of generic medicinal product does not permit the demonstration of the similar nature of two biologicalmedicinal products, additional data, in particular the toxicological and clinical profile shall be provided. (...) The type and amount of additional data(i.e. toxicological and other non-clinical and appropriate clinical data) shall be determined on a case by case basis in accordance with relevantscientific guidelines. (...) The general principles to be applied are addressed in a guideline published by the Agency."• General Guidelines– "Overarching" Biosimilar Guideline (general principles)– General Guidelines covering Quality Issues (Quality comparability exercise)– General Guideline covering Non-Clinical and Clinical Issues (non-clinical tests and clinical trials)• Product-Specific Guidelines– Recombinant Human Insulin– Somatropin (Recombinant Human Growth Factor)– Recombinant Human GCSF– Recombinant Erythropoetin– Interferon Beta– Recombinant Interferon Alfa– Recombinant FSH– Low Molecular Weight Heparin– Monoclonal Antibodies• Guidelines are Work in Progress– from Concept Paper to Adopted Guideline and Revision of adopted Guidelines
www.hoganlovells.com6 858807• BIOSIMILARITY: Comparability exercise to demonstrate biosimilarity– "Overarching" Guideline sets out "general principles" to be applied to demonstrate biosimilarity– Comparability exercise to demonstrate that biosimilar has comparable profile to reference product in terms of quality, safety andefficacy– Comparability demonstrated with Quality studies, supported, if necessary, by Pre-Clinical tests and Clinical (determined on acase-by-case basis on the basis of General and Product Specific Guidelines)– Chosen reference product must be EU authorised reference product: Data from comparability exercise with products authorisedoutside EU may be used once revised EMA Biosimilars Guideline is adopted (2013)– Chosen reference product must be similar in molecular and biological terms (Interferon alfa-2a vs. Interferon alfa 2a, notInterferon alfa 2b).– Pharmaceutical form strength and route of administration must be the same (if not, additional comparability data required)– Each claimed indication must be justified/demonstrated separately• BIOSIMILARITY: Naming and Interchangeability/Substitutability– Naming• Same INN or special INN Nomenclature for biosimilars? (No WHO/EMA Guidance)– Biosimilarity does not equate to/does not imply Interchangeability/Substitutability• Genotropin®/Humatrope® vs. Somatropin biosimilars (reference pricing):– Provisions Judge District Court The Hague 15 June 2010: INN not sufficient– District Court The Hague 6 June 2011: INN and Pharmacopeia– Council of State: INN (Pharmacopeia) sufficient• Neupogen® vs. Filgrastim biosimilars (reimbursement)– District Court Oslo 31 March 2011: INN (pharmacopeia) not sufficient: substitutability decision by Norwegian authorityheld invalidThe Regulatory Framework in the EURegulatory Approval Pathway for Biosimilars (2)
www.hoganlovells.com7 858807The Regulatory Framework in the EURefused/Withdrawn Biosimilar ApplicationsREFUSED APPLICATIONS• Omnitrope Lyophilized (Sandoz)– Well-Established medicinal Use (WEU): bibliographic reference with ComparabilityStudies– Positive EMA/CHMP Opinion, but Refused by Commission– Omnitrope Powder (Sandoz) approved• Alpheon (Interferon Alfa-2a) from BioPartners GmbH– Comparability vs. reference product (Roferon-A) not demonstrated• Biferonex (Interferon-beta-1A) from BioPartners GmbH– Comparability vs. reference product (Avonex®) not demonstratedWITHDRAWN APPLICATIONS• Insulin Human Rapid Marvel (Marvel Life Sciences Ltd.)• Insulin Human Lory Marvel (Marvel Life Sciences Ltd.)• Insulin Human 30/70 Mix Marvel (Marvel Life Sciences Ltd.)• Epostim (epoetin alfa) (Reliance Genemedix)
www.hoganlovells.com8 858807The Regulatory Framework in the EUStrategies for How, When and Where to pursue litigation in the EU• No Linkage: difficulty in generic/biosimilar readiness planning• No equivalent of US Orange Book or data exchange• Monitoring of MA applications and EMA product class specific guidance/consultations• Obtaining evidence and proving infringement– particularly process patents• Limited "Bolar" and sometimes strict interpretation of local Research Exemption inNational Patent Law• No Early Resolution Mechanism prior to MA/approval– clearing the way? (UK/Germany)
www.hoganlovells.com9 858807(1) No linkage... Except for "carve out" of patented indications anddosage forms in generic/biosimilar SmPC and PILApplicant for MA of a generic/biosimilar can tailor its application to"carve out" certain approved therapeutic indications and dosageforms of the reference medicinal product(Article 11 Community Code on medicinal products and Article 3(3)(b) EMA Reg)• if such therapeutic indications and dosage forms remain subject to patentprotection in EU Member States;• this carve out of therapeutic indications and dosage forms is of exceptionalnature and limited duration. The marketing authorisation must be varied to coverthe carved out therapeutic indications and dosage forms once the related patentprotection has expired.
www.hoganlovells.com10 858807The "Carve Out" and Patent Infringement• Article 11 Directive 2001/83:– For authorisations under Article 10, those parts of the summary of productcharacteristics of the reference medicinal product referring to indications ordosage forms which were still covered by patent law at the time when ageneric medicine was marketed need not be included.• But: Regulatory Law does not "exempt" from patent infringement –Carve out alone does not answer that question. Look at allcircumstances, not just instructions for use, e.g. marketing, clinicaldata, oral advertising to determine infringement question• Reference to clinical data in Section 5 of the SmPC can stillcontain information that suggests the patented use to thedoctor/patient:– Can be direct infringement– Or Inducement or Indirect/Contributory infringement
www.hoganlovells.com11 858807The "Carve Out" and Patent Infringement:An example• District Court of The Hague 10 November 2010, Schering v Teva (ribavirin)• The patent at issue related to the use of ribavirin for the preparation of a pharmaceuticalcomposition for the treatment of chronic hepatitis C infection for the combination therapyof ribavirin with (peg)interferon alfa, for a specific patient group and a specific duration oftreatment, namely:a) naïve patients,b) with a HCV-genotype 1 infection and withc) a (high) viral load of more than 2 million copies per ml serum andd) during a treatment of 40-50 weeks.• The District Court held that the patent was not (directly) infringed as Teva had carved outthe specific patient group (naïve patients with a HCV-genotype 1 infection) from theindications and dosage prescriptions (in Section 4.1) in the SmPC. Mentioning thepatient group in Section 5.1 of the SmPC (in the summary of clinical studies in thepharmacodynamic properties section of the SmPC) could nevertheless constituteinducement or contributory infringement if it can be established that the doctorwould prescribe generic ribavirin for the patented patient group (naïve HCV-genotype 1patients) because of the mention of the patient group in the list of clinical studies inSection 5.1 of the SmPC.
www.hoganlovells.com12 858807Strategies for How, When and Where to pursue litigation in the EUObtaining Evidence and Proving Infringement (1)Some background:• Common Law (UK) has "discovery" or "disclosure" and protectsconfidential and privileged information;• Civil Law (Continental Europe) has none of these. Since there has notbeen any discovery, there has not been much need to protect informationeither. But there is room for confusion:– Where Common Law and Civil Law interfere with each other, e.g. where Discoveryobligations refer to information in Civil Law countries, the question arises if thatinformation is discoverable or protected by privilege. The answers are, at best,fuzzy. Generally speaking, attorney client privilege is protected.– EU does not recognize privilege of communications with non EU counsel• In a globalized patent enforcement system more and more information isuseful outside the jurisdiction where it is located, e.g.– Use of USC 28 Sec. 1782 proceedings for the benefit of non-US proceedings– Use of materials obtained in evidentiary seizures (Saisies) in Germany, Belgium and theNetherlands for proceedings in other EU or non-EU jurisdictions– Use of information obtained through disclosure in the UK in proceedings outside the UK
www.hoganlovells.com13 858807Strategies for How, When and Where to pursue litigation in the EUObtaining Evidence and Proving Infringement (2)• UK:– no "discovery", but "limited disclosure" of internal documents (obligation of both parties todisclose to the other party documents in their possession and/or control relating to issuesin the case)– preparation of product or process description, in sufficient detail to address the issues inthe case– Repeat of Experiments– inspection of factory processes possible– provision of samples or ingredients– Cross-Examination of Expert/Witnesses at Trial• Germany: no discovery, but "saisie" and inspection of allegedly infringing products(BGH GRUR 2002, 1046 – Faxkarte)• The Netherlands: no discovery but provisional hearing of witnesses (no real cross-examination), access to evidence filed in parallel procedures, action for specificdisclosure of documents (843 Dutch Civil Procedure) and saisie• Belgium/France: no discovery, but Saisie Descriptive/Saisie contrefaçon;• Italy: no discovery, but (limited) sequestro conservativo• Spain: no discovery, but (limited) Diligencia
www.hoganlovells.com14 858807Strategies for How, When and Where to pursue litigation in the EUObtaining Evidence and Proving Infringement (3): An example of an evidentiary seizure("Saisie") ordered by the Court in Düsseldorf (4b O 270/10)FactsProduct claim: specificratio of two activeingredients (A and B); B ismetabolite of pro-drug AProblem: At time of sale,the ratio protected by thepatent was not fulfilled-known that during shelflife parts of A turn into B-Tests to prove protectedratio reached during theshelf life of 3 years taketoo long-Stability testing - part ofMA so the necessaryinformation had to beincluded in MAdocumentsSolutionFile inspection accordingto Sec. 140c Patent Act- As it was known thatsubstance B is ametabolite of substanceA, it was sufficientlyprobable that theprotected ratio of the twosubstances will bereached through shelf life-No ex-parte decision asthere was no danger thatrespondent couldremove/alter evidence- Court indicated fileinspection less invasivethan inspection ofproduction or even aninjunction so therequirements were lessstrict• No bond was orderedDecisionRespondents will provideattorneys at law A and Bwithin two weeks afterservice of this order withthe records on results ofstability tests prepared formarketing authorization ofthe products […]according to sec. 22 para.2 no. 14 AMG as well asthe files […] includingmodule 3… includingrecords on the content of[…] substance B forinspection andpreparation ofphotocopies
www.hoganlovells.com15 858807Strategies for How, When and Where to pursue litigation in the EUObtaining Evidence and Proving Infringement (4): The evidentiaryseizure (saisie) in the NetherlandsSaisie• IP owner must make plausible the actual/threatened infringement of its rights• Bailiff conducts seizure, possibly with e.g. patent attorney or IT expert• Purpose of saisie is preservation of evidence there is no automatic access to seized evidence• must be inter partes proceedingsAccess• Only access to specific documents/evidence (no "fishing expedition") and only in case of legitimateinterest• Access granted if there is evidence of sufficient specific facts and circumstances, substantiated byreasonably available evidence to establish a reasonable suspicion of infringementBenefits ofNL Saisie• Saisie can be very effective• Dutch Courts allow saisie in the Netherlands even if no patent in the Netherlands for use andinfringement abroad
www.hoganlovells.com16 858807Strategies for How, When and Where to pursue litigation in the EUObtaining Evidence and Proving Infringement (5): Defences toinfringement: Research exemption and "Bolar"Research exemption• "acts done for experimental purposesrelating to the subject-matter of thepatented invention;"• Non-uniform national laws• Sometimes strict interpretation of nationalresearch exemption• Dutch research exemption: "acts donesolely for experimental purposes relatingto the subject matter of the patentedinvention""Bolar"• Directive 2001/83, article 10(6):"Conducting the necessary studies andtrials with a view to the application ofparagraphs 1, 2, 3 and 4 [biosimilarpathway] and the consequential practicalrequirements shall not be regarded ascontrary to patent rights or tosupplementary protection certificates formedicinal products."• Limited Bolar• Non-uniform implementation across theEU• Only for biosimilars under article 10(4)?• Only patent rights for medicinal products?• Territorial scope/use of clinical trials?
www.hoganlovells.com17 858807What Relief can be obtained through judgments inthe EU?• Ex Parte Injunctions– Germany and the Netherlands– "Protective letters"• Preliminary Injunctions– UK: Balance of convenience and Clearing the Way– Germany: Bifurcated treatment of validity and infringement and "clearing theway"– NL: Validity (no serious chance that patent will be revoked) and infringementsufficiently established• Preliminary Injunctions for "preparatory acts" and imminentinfringement– Inclusion in pricelists– No Early Resolution Mechanism• NL: Cross-border preliminary injunctions and orders– Boehringer Ingelheim v. Teva: cross-border order vis-à-vis Dutch Tevadefendant not to allow and/or profit from patent infringement in Portugal