1. Conference Series LLC Conferences Conference Series LLC is a pioneer and leading science event organizer, which publishes around 500 open access journals and conducts over 500 Medical, Clinical, Engineering, Life Sciences, Pharma scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. Conference Series LLC has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

2. Eurobiosimilars 2016, Valencia June 27-29, 2016 2 Supplementary Protection Certificates (SPCs) in Europe and their relevance for Biosimilars Dr. Lueder Behrens

3. 3 Overview The Problem – SPCs and Biosimilars Introduction to Supplementary Protection Certificates What do the Courts say? Recommendations

4. 4 Original vs. Biosimilar -ase Cell line A Cell line B Protein X Protein X*

5. 5 Original vs. Biosimilar Let us assume that…: The biosimilar has an identical amino acid sequence and seems to correspond to market-authorized reference product; The biosimilar has a different glycosylation pattern The biosimilar has different pharmacokinetic activity

6. 6 Original vs. Biosimilar In most cases, it can be assumed that a patent covering the original product would likely cover also the biosimilar product BUT: Would an SPC cover the biosimilar product?

7. 7 Importance of SPCs Patent expiry SPCPatent Sales Revenue 1991 1992 1993 1994 19951996 1997 1998 1999 SPC expiry SPC may extend market exclusivity after patent expiry Example: Sales of Prozac ® (fluoxetine) in the UK 1991-1999

8. 8 SPCs - Governing Laws and Courts In countries of the European Union (EU), SPC protection is governed by (EC) Regulation 469/2009 (“the SPC Regulation”); Applications for SPCs must be filed nationally; The highest tribunal hearing disputes involving SPCs is the Court of Justice of the European Union (CJEU)

9. 9 SPCs - Governing Laws and Courts SPC protection is also available under this Regulation in non-EU countries: Norway and Iceland (NO and IS); NO and IS are members of the European Economic Area (EEA); The European Free Trade Association (EFTA) Court is the equivalent of the Court of Justice of the European Union (CJEU) for matters referred by the national courts of the three EFTA countries (Iceland, Liechtenstein, Norway).

10. 10 SPCs - Governing Laws and Courts Switzerland, which is neither an EU nor EEA member, has its own SPC provisions in its national law; Swiss national law in this regard is, however, based on the EU SPC Regulation; Patents of Switzerland extend to Liechtenstein (which joined the EEA in 1 May 1995) and similarly Swiss marketing authorizations and SPCs take effect in Liechtenstein.

11. 11 Who can apply for an SPC? Only the holder of a patent that protects the (combination of) active ingredient(s) for which supplementary protection is sought The patentee need not be the proprietor of (or indeed have any connection with) the MA upon which the SPC will also be based

12. 12 How many SPCs can be granted for any one (combination of) active ingredient(s)? One SPC can be granted to any one patentee for a particular (combination of) active ingredient(s) Whether that patentee has multiple patents that protect the specified active ingredient(s) is irrelevant - patentee has to choose one of his patents to base the SPC upon

13. 13 Duration of SPC protection? If (and only if) the patent upon which an SPC is based reaches the end of its full term, the SPC comes into force immediately The SPC expires (the earlier date being applicable): 15 years from the first MA in the European Economic Area (EEA) for the specified (combination of) active ingredient(s); or 5 years from expiry of the patent upon which the SPC is based

14. 14 When is an SPC invalid? An SPC can be invalid if the basic patent: -lapses before the end of its full term; or -is revoked at least to the extent that the (combination of) active ingredients defined in relation to the SPC is no longer protected by that patent; -An SPC can also be invalid if it is granted contrary to the provisions of the SPC legislation.

15. 15 When is an SPC invalid? The basic patent on which an SPC was granted and the SPC as such can only be invalidated nationally, e.g. in nullity proceedings before the German Patent Court or the UK High Court, etc. Nullity proceedings can be initiated even after expiry of the basic patent Unified Patent Court (UPC) does not contain provisions on EU- SPCs

16. 16 Scope of protection provided by SPCs? SPC provides only very narrow, use-limited protection around the specified active ingredient(s) Scope of SPC protection is never broader than the protection conferred by a patent upon which the SPC is based Scope of SPC should not be greater than the marketing authorization

17. 17 Article 3 of (EC) No 469/2009* Conditions for obtaining a certificate a.The product is protected by a basic patent in force; b.a valid authorization to place the product on the market as a medicinal product has been granted in accordance with Directive 64/65 EEC or Directive 81/851 EEC, as appropriate; c.The product has not already been the subject of a certificate; d.The authorization referred to in b. is the first authorization to place the product on the market as a medicinal product *REGULATION (EC) No 469/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL concerning the supplementary protection certificate for medicinal products (Text with EEA relevance)

18. 18 Article 1 of (EC) No. 469/2009 Definitions ‘For the purposes of this Regulation, the following definitions shall apply: (a) “medicinal product” means any substance or combination of substances presented for treating or preventing disease in human beings or animals and any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans or in animals; (b) “product” means the active ingredient or combination of active ingredients of a medicinal product;...’

19. 19 Article 1 of (EC) No. 469/2009 Definitions ‘For the purposes of this Regulation, the following definitions shall apply: (c) “basic patent” means a patent which protects a product as such, a process to obtain a product or an application of a product, and which is designated by its holder for the purpose of the procedure for grant of a certificate; (d) “certificate” means the supplementary protection certificate.’

20. 20 What is the „Scope of „Product protected by a basic patent“ ? (Art. 3 a. of (EC) No. 469/2009 Consequences for originators and biosimilar companies? Recommendations „Product protected by a basic patent“

21. 21 “Product protected by a basic patent” Case law of the Court of Justice of the European Union (CJEU) “Simple” chemical and biological compounds Combinations of active ingredients Functionally defined compounds

22. 22 Scope of Protection - Example Patent claim: wherein R = F, Cl or COOH Marketing Authorization: Tablets with 5 mg of compound for treatment of hypertension SPC: for any use as a medicinal product authorized before expiry of the SPC

23. 23 „Product protected by a basic patent “ CJEU C-392/97 „Farmitalia“ An SPC can protect more than MA (in that case salts, esters, etc.) „[…] where a product in the form referred to in the MA is protected by a basic patent in force, the certificate is capable of covering that product, as a medicinal product, in any of the forms enjoying the protection of the basic patent” Scope must be determined by national courts!

24. 24 „Product protected by a basic patent in force“ It is getting closer to biologics … The CJEU‘s decision Eli Lilly (C-493/12)

25. 25 „Product protected by a basic patent in force“ Eli Lilly (C-493/12) HGS Inc. was proprietor of basic patent protecting an antibody against a specific protein X defined by functional binding characteristic („antibody specifically binding to protein X“) Eli Lilly was proprietor of MA for a specific antibody (tabalumab) directed against protein X Eli Lilly‘s antibody falls under the scope of patent of HGS

26. 26 „Product protected by a basic patent in force“ Eli Lilly (C-493/12) Eli Lilly was seeking for a declaration that any SPC, relying on HGS‘s patent and based on Eli Lilly‘s MA for a medicinal product containing talamumab should be invalid (no disclosure of the specific antibody in the patent)

27. 27 „Product protected by a basic patent in force“ Eli Lilly (C-493/12) Can an SPC be validly granted on the basis of a patent with functional claims? What is the scope of such SPC?

28. 28 „Product protected by a basic patent in force“ Eli Lilly (C-493/12) – the CJEU decided: In principle, an SPC can be validly granted on the basis of a patent with functional claims (taking into account the description), if the claims implicitly, but necessarily and specifically relate to the active ingredient subject to the MA The scope of such SPC has to be determined by national authorities

29. 29 „Product protected by a basic patent “ Eli Lilly (C-493/12) The following conclusions may eventually be drawn from said decision: i)Functional definitions applying to a genus are allowed for SPC applications directed to specific species ii)Claims and the specification can be used as a source of interpretation whether a specific product is eligible for an SPC in the sense of Art. 3(a) of the Regulation

30. 30 „Product protected by a basic patent “ Eli Lilly (C-493/12) iii)The extent of protection conferred by the SPC on the basis of a basic patent that defines the active ingredient in functional terms is vague and open for definition by national patent authorities Highly relevant for biologics!

31. 31 „Product protected by a basic patent in force“ Eli Lilly (C-493/12) What is the meaning of: „…claims relate, implicitly but necessarily and specifically, to the active ingredient in question“?

32. 32 „Product protected by a basic patent “ Open question after Eli Lilly Is it possible for a biosimilar company - before expiry of the SPC period - to produce, offer and market a biosimilar that is different from the reference product according to the MA, but that would have been covered by claim 1 of the basic patent? Does the Pharmaq v Intervet case (E-16-14) provide guidance? (EFTA Court case for non-EU states NO, IS and LI)

33. 33 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) Intervet and Pharmaq: Vaccines against viral pancreatic disease in salmon using different inactivated virus strains (SAV1 and SAV3, respectively) Intervet is proprietor of an SPC granted on the basis of Intervet‘s NO patent which broadly claims the F93-125 strain of virus together with all strains that share „similar genotypic and/or phenotypic characteristics and react serologically [with F93-125]“

34. 34 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) Intervet‘s vaccine (Norvax) held MA in 2011 for „Inactivated Salmon Pacreatic Disease Virus Strain F93-125“ (SAV1) Pharmaq‘s vaccine based on a different subtype of PD (SAV3) SAV3 is genetically distinct from SAV1

35. 35 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) Patent litigation in NO: Pharmaq‘s vaccine infringes Intervet‘s patent Pharmaq sought declaration before the Oslo DC that a Norwegian SPC held by Intervet is either invalid or does not cover the virus strain in the Pharmaq vaccine The SPC is based on MA for the specific strain used by Intervet, but the SPC was granted with a broader product definition that encompasses the Pharmaq strain

36. 36 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) The Oslo DC asked the EFTA Court: Does the scope of Intervet‘s SPC cover not only the specific strain in the medicinal product, but also other strains covered by the basic patent and the SPC product definition? Is an SPC is valid if it is granted with a product definition that is not limited to the authorized strain?

37. 37 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) Article 4 of the SPC Regulation entitled „Subject matter of protection“ reads: ‘Within the limits of the protection conferred by the basic patent, the protection conferred by a certificate shall extend only to the product covered by the authorisation to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorised before the expiry of the certificate.’

38. 38 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) The EFTA Court decided: Article 4 provides that an SPC „shall only extend to the product covered by the authorization“ SPC valid insofar as the product definition is the same as in the MA Protection should be „strictly confined“ to the authorized product

39. 39 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) However: An SPC can extend to cover a specific strain of virus (included in the basic patent but not mentioned in the MA), only if said strain: -Constitutes the „same active ingredient as the approved medicinal product“, and -has „therapeutic effects that fall within the same therapeutic indications for which a MA was granted“

40. 40 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) EFTA Court introduced a new requirement for the interpretation of Art. 4 of the Regulation: Does the active ingredient have the „therapeutic effects falling within the therapeutic indication“ for which the MA was issued? Remittal to Oslo DC to decide upon the Court‘s finding that the SPC granted to Intervet is expressly limited to the F93-125 strain.

41. 41 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) The Oslo District Court must decide whether the SPC is invalid on the basis that it extends beyond the scope of the MA (which is expressly limited to the F93-125 strain)

42. 42 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) The EFTA decision is not binding for the CJEU, but may provide some guidance for CJEU and national courts In the proceedings, the EU Commission submitted that „In the absence of therapeutic equivalence, a [MA] cannot by definition extend to a virus strain it does not mention. On the other hand, where an allegedly infringing strain is marketable under the [MA] covering the patented strain and is a therapeutic equivalent to the latter, the allegedly infringing strain is clearly covered by that [MA] for the purposes” in other words, a biosimilar seems to be covered by SPC if infringing basic patent and marketed under the original MA! The CJEU may in the future have to decide on referrals concerning the scope of protection of Art. 4, particularly for biosimilars and biobetter products

43. 43 „Product protected by a basic patent “ Pharmaq v. Intervet (E-16-14) Consequences for the Example case differently glycosylated Protein X: The CJEU and national courts may have to be decide, if the biosimilar has therapeutic effects falling within the therapeutic indication for which the MA was issued and an SPC was granted, if the MA is directed to a specific biological molecule

44. 44 Recommendations/Originators In patent applications relating to biological molecules include derivatives, fragments, etc., include potential biosimilars When combinations of active ingredients are to be used in medicinal products file separate patent applications, if the combinations are inventive File separate patent applications for separate second medical uses (i.e. different medical indications)

45. 45 Recommendations/Originators For biologics use also functional language to define the active ingredients Structurally define biological molecules (e.g. antibodies binding to new protein targets) when using functional claim language

46. 46 Recommendations/Biosimilars Surveillance of SPCs and clarification of scope of SPC, basic patent and MA are essential The CJEU emphasizes that – absent EU wide harmonization of the interpretation of the scope of patents and SPCs – the scope of the SPC must be interpreted by national courts Therefore, analyse the claims and the specification of the basic patent to determine whether an SPC would cover a biosimilar As a matter of precaution, ask your national patent lawyers for an interpretation of the scope of a patent/SPC (Due Diligence) In case of uncertainty, search for declaratory injunction that your biosimilar does not infringe an SPC

47. 47 THANK YOU!

48. LET US MEET AGAIN.. We welcome you to our future conferences of Conference Series LLC through 6 th International Conference and Exhibition on Biologics and Biosimilars October 19-21, 2016 Houston, TX, USA http://biosimilars-biologics.pharmaceuticalconferences.com/europe