This document discusses strategies for international prosecution and litigation of biotech patents in the EU. It provides an overview of the prosecution and litigation framework in the EU, including opposition proceedings before the European Patent Office and litigation in national courts. It also discusses the regulatory approval pathway for biosimilars in the EU and strategies for obtaining evidence and proving patent infringement in different EU countries.
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Crafting a Global Strategy: Best Practices for International Prosecution & Litigation to Maximize the Value of Your Biotech Patent Portfolio
1. 858807
Crafting a Global Strategy: Best Practices for
International Prosecution and Litigation to
Maximize the Value of Your Biotech Patent Portfolio
ACI's 14th Advanced Forum on Biotech Patents
Hyatt Regency Boston, 29 November 2012
Bert Oosting, Hogan Lovells International LLP
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The Prosecution and Litigation Framework in the EU
Prosecution 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 and
national 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 national
revocation action before validity court before end of opposition
– Suspension of national revocation proceedings pending opposition discretionary, but
unlikely if no EPO-hearing imminent
• EPO opposition decision not binding but (highly) persuasive
– NL strictly follows EPO practice (strict novelty test, problem/solution approach to
inventive step)
– UK follows "settled" EPO practice, unless "commodore is steering the fleet onto the
rocks", but expert testimony/cross-examination at Trial and common general
knowledge ("CGK") key
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The Prosecution and Litigation Framework in the EU
Prosecution 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 for
patentee) and using claims as guideline to determine invention behind the claims (reasonable certainty for
third parties)
– Article 2 Protocol on Interpretation: Due account must be taken of means equivalent to means specified in
claims
• Infringement determined under national law (Art. 64(3) EPC) and national
approaches 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
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The EPO and National Courts:
An example – Lilly v. HGS and the approach of the EPO and UK
Courts 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 make
industrial 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 have
common, 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 information
provided in the patent)
– Skilled man would regard the long listing of wide ranging possible uses in medical conditions as a numeration and generalisation of the
properties 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 TNF
ligand 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 ligand
super family were enough in itself to make it "plausible" that Neutrokine-α be usable for purpose of research work, which is industrial activity
in itself
• UK Court of Appeal:
– Assessment of sufficiency/enablement: patent sufficient/enabled
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The Regulatory Framework in the EU
Regulatory 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 of
additional, supplementary data to be provided must comply with criteria stated in Annex I Directive 2001/83 and related detailed general and product
specific (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 biological
medicinal 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 relevant
scientific 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
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• 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 and
efficacy
– Comparability demonstrated with Quality studies, supported, if necessary, by Pre-Clinical tests and Clinical (determined on a
case-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 authorised
outside 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, not
Interferon 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 authority
held invalid
The Regulatory Framework in the EU
Regulatory Approval Pathway for Biosimilars (2)
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The Regulatory Framework in the EU
Refused/Withdrawn Biosimilar Applications
REFUSED APPLICATIONS
• Omnitrope Lyophilized (Sandoz)
– Well-Established medicinal Use (WEU): bibliographic reference with Comparability
Studies
– 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 demonstrated
WITHDRAWN 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)
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The Regulatory Framework in the EU
Strategies 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 in
National Patent Law
• No Early Resolution Mechanism prior to MA/approval
– clearing the way? (UK/Germany)
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(1) No linkage... Except for "carve out" of patented indications and
dosage forms in generic/biosimilar SmPC and PIL
Applicant for MA of a generic/biosimilar can tailor its application to
"carve out" certain approved therapeutic indications and dosage
forms 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 patent
protection in EU Member States;
• this carve out of therapeutic indications and dosage forms is of exceptional
nature and limited duration. The marketing authorisation must be varied to cover
the carved out therapeutic indications and dosage forms once the related patent
protection has expired.
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The "Carve Out" and Patent Infringement
• Article 11 Directive 2001/83:
– For authorisations under Article 10, those parts of the summary of product
characteristics of the reference medicinal product referring to indications or
dosage forms which were still covered by patent law at the time when a
generic 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 all
circumstances, not just instructions for use, e.g. marketing, clinical
data, oral advertising to determine infringement question
• Reference to clinical data in Section 5 of the SmPC can still
contain information that suggests the patented use to the
doctor/patient:
– Can be direct infringement
– Or Inducement or Indirect/Contributory infringement
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The "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 pharmaceutical
composition for the treatment of chronic hepatitis C infection for the combination therapy
of ribavirin with (peg)interferon alfa, for a specific patient group and a specific duration of
treatment, namely:
a) naïve patients,
b) with a HCV-genotype 1 infection and with
c) a (high) viral load of more than 2 million copies per ml serum and
d) during a treatment of 40-50 weeks.
• The District Court held that the patent was not (directly) infringed as Teva had carved out
the specific patient group (naïve patients with a HCV-genotype 1 infection) from the
indications and dosage prescriptions (in Section 4.1) in the SmPC. Mentioning the
patient group in Section 5.1 of the SmPC (in the summary of clinical studies in the
pharmacodynamic properties section of the SmPC) could nevertheless constitute
inducement or contributory infringement if it can be established that the doctor
would prescribe generic ribavirin for the patented patient group (naïve HCV-genotype 1
patients) because of the mention of the patient group in the list of clinical studies in
Section 5.1 of the SmPC.
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Strategies for How, When and Where to pursue litigation in the EU
Obtaining Evidence and Proving Infringement (1)
Some background:
• Common Law (UK) has "discovery" or "disclosure" and protects
confidential and privileged information;
• Civil Law (Continental Europe) has none of these. Since there has not
been any discovery, there has not been much need to protect information
either. But there is room for confusion:
– Where Common Law and Civil Law interfere with each other, e.g. where Discovery
obligations refer to information in Civil Law countries, the question arises if that
information 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 is
useful 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 the
Netherlands for proceedings in other EU or non-EU jurisdictions
– Use of information obtained through disclosure in the UK in proceedings outside the UK
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Strategies for How, When and Where to pursue litigation in the EU
Obtaining Evidence and Proving Infringement (2)
• UK:
– no "discovery", but "limited disclosure" of internal documents (obligation of both parties to
disclose to the other party documents in their possession and/or control relating to issues
in the case)
– preparation of product or process description, in sufficient detail to address the issues in
the 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 specific
disclosure 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
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Strategies for How, When and Where to pursue litigation in the EU
Obtaining Evidence and Proving Infringement (3): An example of an evidentiary seizure
("Saisie") ordered by the Court in Düsseldorf (4b O 270/10)
Facts
Product claim: specific
ratio of two active
ingredients (A and B); B is
metabolite of pro-drug A
Problem: At time of sale,
the ratio protected by the
patent was not fulfilled
-known that during shelf
life parts of A turn into B
-Tests to prove protected
ratio reached during the
shelf life of 3 years take
too long
-Stability testing - part of
MA so the necessary
information had to be
included in MA
documents
Solution
File inspection according
to Sec. 140c Patent Act
- As it was known that
substance B is a
metabolite of substance
A, it was sufficiently
probable that the
protected ratio of the two
substances will be
reached through shelf life
-No ex-parte decision as
there was no danger that
respondent could
remove/alter evidence
- Court indicated file
inspection less invasive
than inspection of
production or even an
injunction so the
requirements were less
strict
• No bond was ordered
Decision
Respondents will provide
attorneys at law A and B
within two weeks after
service of this order with
the records on results of
stability tests prepared for
marketing authorization of
the products […]
according to sec. 22 para.
2 no. 14 AMG as well as
the files […] including
module 3… including
records on the content of
[…] substance B for
inspection and
preparation of
photocopies
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Strategies for How, When and Where to pursue litigation in the EU
Obtaining Evidence and Proving Infringement (4): The evidentiary
seizure (saisie) in the Netherlands
Saisie
• 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 proceedings
Access
• Only access to specific documents/evidence (no "fishing expedition") and only in case of legitimate
interest
• Access granted if there is evidence of sufficient specific facts and circumstances, substantiated by
reasonably available evidence to establish a reasonable suspicion of infringement
Benefits of
NL Saisie
• Saisie can be very effective
• Dutch Courts allow saisie in the Netherlands even if no patent in the Netherlands for use and
infringement abroad
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Strategies for How, When and Where to pursue litigation in the EU
Obtaining Evidence and Proving Infringement (5): Defences to
infringement: Research exemption and "Bolar"
Research exemption
• "acts done for experimental purposes
relating to the subject-matter of the
patented invention;"
• Non-uniform national laws
• Sometimes strict interpretation of national
research exemption
• Dutch research exemption: "acts done
solely for experimental purposes relating
to the subject matter of the patented
invention"
"Bolar"
• Directive 2001/83, article 10(6):
"Conducting the necessary studies and
trials with a view to the application of
paragraphs 1, 2, 3 and 4 [biosimilar
pathway] and the consequential practical
requirements shall not be regarded as
contrary to patent rights or to
supplementary protection certificates for
medicinal products."
• Limited Bolar
• Non-uniform implementation across the
EU
• Only for biosimilars under article 10(4)?
• Only patent rights for medicinal products?
• Territorial scope/use of clinical trials?
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What Relief can be obtained through judgments in
the 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 the
way"
– NL: Validity (no serious chance that patent will be revoked) and infringement
sufficiently established
• Preliminary Injunctions for "preparatory acts" and imminent
infringement
– 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 Teva
defendant not to allow and/or profit from patent infringement in Portugal
