A New Patent Dance: The Biologics Price Competition and Innovation Act

Transcription

1 A New Patent Dance: The Biologics Price Competition and Innovation Act J. Eric Thies David M. Conca Jeffrey A. Wolfson Jeffrey L. Kopacz Michael K. Kirschner

2 J. Eric Thies Assistant Counsel, Intellectual Property Group at Merck Rahway, NJ Chair, IPO Pharmaceutical Issues Committee 2

3 David M. Conca Partner, Litigation Department at Paul, Hastings, Janofsky & Walker, LLP New York, NY Chair of IPO Pharmaceutical Issues Subcommittee on Healthcare Legislation Moderator 3

4 Jeffrey A. Wolfson Partner at Haynes and Boone, LLP Washington, DC Vice-Chair of IPO Pharmaceutical Issues Subcommittee on Healthcare Legislation Panelist 4

5 Jeffrey L. Kopacz Senior Patent Counsel at Alnylam Pharmaceuticals Cambridge, MA Panelist 5

6 Michael K. Kirschner Hillis Clark Martin & Peterson, P.S. Seattle, WA Panelist 6

7 Presentation Outline Part 1: Overview of New Legislation Part 2: Hypothetical Patent Information Exchange Part 3: Resulting Litigation Part 4: FDA Regulatory Implementation 7

8 Part 1: Overview Title: Biologics Price Competition and Innovation Act of 2009 Effective date: March 23, 2010 Amends Section 351 of the Public Health Service Act to provide for abbreviated pathway for biosimilars based on regulatory data previously submitted for reference product 42 U.S.C. 262 (2010) 8

9 Part 1: Overview Data exclusivity for reference products, including pediatric exclusivity extension Regulatory pathway for biosimilars, including interchangeability incentives New patent litigation procedures with obligations on each side to disclose information 9

10 Part 1: Overview A follow on biologic can still be approved under 21 U.S.C. 355(b)(2) (505(b)(2)) if: The follow on biologic is in the same product class as the original biologic The original biologic was approved under section 505(b)(1) Not later than March 23, 2010 The follow on biologic application is submitted before March 23, U.S.C. 262 Note: PL (e)(1)-(e)(2) 10

11 Part 1: Overview (cont.) Exception: a follow on biologic application may not be submitted under 21 U.S.C. 355 if: Another biologic is approved under 42 U.S.C. 262 that could be a reference product for the follow on biologic application if submitted under that section 42 U.S.C. 262 Note: PL (e)(4) 11

12 Part 1: Overview (cont.) Phase Out: an approved application for a biologic under 21 U.S.C. 355 will be deemed a license for the biologic under 42 U.S.C. 262 on March 23, U.S.C. 262; PL (e)(4) 12

13 Deemed a License under such section 351 An approved application under Section 505 (21 U.S.C. 355) shall be deemed to be a license for the biological product under such section 351 on March 23, Exclusivity under 351 is for 12 years after the date on which the reference product was first licensed under subsection (a) PL (e)(4); 42 U.S.C. 262(k)(7)(A) 13

14 Part 2: Hypothetical Exchange Reference product sponsor Real Pharmaceutical Sciences, Inc. (RPS) files a biologics license application (BLA) under 351 for its drug Humorex, a biologic used to treat ipthealgia, a disease that produces uncontrollable, deadly laughter. RPS has obtained patents on the drug and processes of making it. RPS receives FDA approval for Humorex. 14

15 Part 2: What does that get RPS? Humorex is then entitled to 12 years of regulatory exclusivity Biosimilar applications cannot be filed less than 4 years after the date Humorex is approved 42 U.S.C. 262(k)(7)(A)-(B), (m)(3)-(4) RPS approval No Biosimilars Data Exclusivity Expires 4 years 12 years Discussion: What does regulatory exclusivity really mean? Compare Hatch-Waxman? Four year date? 15

16 Part 2: Pediatric Exclusivity? Pediatric exclusivity nets reference product sponsor an extra 6 months of regulatory exclusivity: Initial follow on biosimilar applications and their approval delayed 6 months, but Only if appropriate pediatric studies done and submitted and accepted under 505A at least 9 months before expiration of relevant period 42 U.S.C. 262(k)(7)(A)-(B), (m)(3)-(4) 16

17 Result of Pediatric Exclusivity 4 years 6 months 6 months 12 years Discussion: File for pediatrics late to extend twelve year term late rather than early? 17

18 Part 2: RPS can t get data exclusivity on A supplement to the original Humorex BLA; or A subsequent application (by RPS or a related entity) for Change (not structural) resulting in new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or Structural modification that does not result in change in safety, purity, or potency 42 U.S.C. 262(k)(7)(C) Discussion: Compare prior data necessary to get NCE. Is there guidance on threshold data required to show safety, purity, potency? 18

19 Part 2: Four Years Into Data Exclusivity 4 years after Humorex s approval, Biosimilar Aspirations, Ltd. (BA) files with the FDA an application for Funni, a biosimilar that claims Humorex as the reference biologic. BA also is called the subsection (k) applicant or sub(k) applicant. RPS approval BA can apply Data Exclusivity Expires 4 years 12 years 19

20 Part 2: FDA Guidance for BA FDA may issue guidance for approval of biosimilars, but it doesn t have to do so Guidance documents may state that FDA will not currently license a biosimilar for a certain product or class because science and experience currently does not allow it. But issuance or non-issuance of guidance shall not preclude FDA from reviewing or acting on an application FDA can later reverse or modify its position 42 U.S.C. 262(k)(8) Discussion: How/whether FDA guidance will affect followon biologic development. 20

21 Part 2: FDA Guidance for BA Product Class-Specific Guidance If issued, it must include criteria to determine both highly similar and interchangeable Public comment period 42 U.S.C. 262(k)(8)(D) Discussion: How/whether class-specific guidance will affect follow-on biologic development. 21

22 Part 2: What does BA have to show? For the FDA to approve Funni, BA has to prove that it is Biosimilar Optionally, BA can try to show that it is interchangeable Also, BA must show that the facility where Funni is manufactured, processed, packed, or held meets standards to ensure safety, purity, and potency 42 U.S.C. 262(k)(2)(A)(i), (k)(2)(b) Discussion: Investing/developing manufacturing facilities very early in biosimilar product s life cycle 22

23 Part 2: What is biosimilarity? 1. Highly similar to reference product notwithstanding minor differences in clinically inactive components; and 2. No clinically meaningful differences with regard to safety, purity, and potency 42 U.S.C. 262(i)(2) (as amended) Discussion: What showing will BA have to make for highly similar? 23

24 Part 2: Biosimilarity Studies I. Biosimilarity must be shown by: a) Analytical studies demonstrating that Funni is highly similar to Humorex notwithstanding minor differences in clinically active components; b) Animal studies (including assessment of toxicity); c) Clinical studies that demonstrate safety, purity, and potency in one or more conditions of use for which Humorex is licensed and intended to be used and for which licensure is sought But FDA can waive one or more biosimilarity studies 42 U.S.C. 262(k)(2)(A)(i)(I)-(II), (k)(2)(a)(ii) Discussion: What will FDA waive? Compare to Hatch-Waxman (bioequivalence studies) and European biosimilar pathway. 24

25 Part 2: What Else is Required for BA Licensure? II. Demonstration of the same mechanism or mechanisms of action, to the extent mechanisms of action are known to RPS III. Used for the same indications IV. Same route of administration, dosage form, and dosage strength as reference product; and V. Manufactured under FDA standards Discussion: Doctrine of Equivalents? 25

26 Part 2: Interchangeability BA must demonstrate that Funni is biosimilar to Humorex and Expected to produce the same clinical results; and If administered more than once to an individual, the risk of altering or switching is not greater than risk of using the reference product without alteration or switch 42 U.S.C. 262(k)(4) Discussion: Clinical studies necessary for switching? What are the risks? 26

27 Part 2: Interchangeability A determination of interchangeability would mean that Funni could be substituted for Humorex without the intervention of the health care provider that prescribed Humorex 42 U.S.C. 262(i)(3) (as amended) Discussion: How will this affect TE codes? What will be the market impact of biosimilar vs. interchangeable designation? 27

28 Part 2: Incentives to Prove Interchangeability, but If FDA determines that Funni is interchangeable with Humorex, BA gets data exclusivity against any other potential interchangeable biologics To the earlier of: 1 year after first commercial marketing of first interchangeable product; 18 months after a final court decision on all patents in suit in an action under this section against the first approved interchangeable product, or dismissal of an action under this section against first interchangeable product; 42 U.S.C. 262(k)(6) Discussion: BA only gets exclusivity as against other interchangeables. 28

29 Part 2: Incentives to Prove Interchangeability, but 42 months after approval of first interchangeable product if applicant has been sued under this section and litigation is still ongoing within the 42 month period; or 18 months after approval of first interchangeable product if applicant has not been sued under this section 42 U.S.C. 262(k)(6) Discussion: Impact on settling these cases? 29

30 Part 2: What else is in BA s application? Publicly-available information regarding the previous determination that reference product Humorex is safe, pure, and potent BA may include any other information to support the application, including publicly-available information about Humorex or another biological product However, BA s Funni application will not be evaluated for biosimilarity against more than one reference product 42 USC 262(k)(2)(iii); (k)(5) Discussion: What would you include if you were BA? 30

31 Part 2: After BA sends its application to FDA Once BA sends its biosimilar application to FDA with Humorex as its reference product, the FDA will notify it that the application was accepted for review. BA then has an obligation to notify RPS. 42 USC 262(l)(2) 31

32 Part 2: What Obligations Does BA have to RPS? Within 20 days after notification by the FDA, BA must provide RPS s counsel (under confidentiality provisions) A copy of its application for Funni Information about its manufacturing process BA may also provide: Any other information RPS requests and BA thinks appropriate to provide 42 USC 262(l)(2) Discussion: What would appropriate information be? Should BA include such information? 32

33 Part 2: Confidentiality Provisions for the Exchange of Information BA does not need to negotiate a protective order because confidentiality provisions are in the statute BA may not deny access to its biosimilar application (and other information exchanged between BA and RPS) to: RPS Outside counsel: one or more attorneys (if they do not engage formally or informally in relevant or related patent prosecution) RPS In-house counsel: one attorney with the same patent prosecution bar 42 U.S.C. 262(l)(1)(A)-(B) Discussion: Will parties need to negotiate the meaning of relevant patent prosecution for inside counsel? 33

34 Part 2: Confidentiality Provisions (cont.) BA may also not deny access to: A representative of a patent owner, where patent is exclusively licensed to RPS and right to sue has been retained, so long as owner agrees to be bound by the confidentiality provisions No disclosure to any other person without BA s consent But cannot be unreasonably withheld RPS and BA can negotiate a different protective order 42 U.S.C. 262(l)(1)(A)-(C) Discussion: Who else? Experts? Internal RPS employees? 34

35 Part 2: Exchange of Patent Information and Lists (The Dance) First Step: BA Provides Application to RPS Then during this exchange, RPS and BA each identify patents they think are relevant. BA provides application to RPS RPS provides patent list BA responds with reasoning RPS responds with reasoning Patent List Negotiation Day 1 Day 61 Day 121 Day 181? 35

36 Part 2: Second Step RPS Provides Its List to BA Within 60 days of receipt of information from BA, RPS must provide: List of all patents for which RPS believes a claim of patent infringement could reasonably be asserted Which of those patents it is prepared to license to BA 42 U.S.C. 262(l)(3)(A) Discussion: pre-suit investigations? 36

37 Part 2: Second Step RPS s Initial List to BA RPS: Humorex is covered by 6 patents which we believe will be infringed by Funni: We are willing to license the 005 patent. Discussion: With short deadlines, what should BA do to prepare for this exchange? 37

38 Part 2: Third Step BA Responds to RPS s Initial List BA must respond within 60 days: Factual and legal basis for belief each patent is invalid, unenforceable, or will not be infringed; or Will not begin commercial marketing until patent expires; and Response to each patent RPS will license What does the response need to be? BA can include its own list of patents on which it believes a claim of infringement could reasonably be asserted 42 U.S.C. 262(l)(3)(B) Discussion: What if there are several patents? What about 20? 38

39 Part 2: Third Step BA s Response to RPS s Initial List We will not infringe 001. The 002, 003, 004 and 006 are invalid or unenforceable. We do not need to license 005 because we also think it is invalid or unenforceable. These patents are not infringed, invalid, and/or unenforceable because Note that BA must provide a response to an offer to license 42 U.S.C. 262 (3)(B)(iii) 39

40 Part 2: Fourth Step RPS Responds to BA RPS must respond within 60 days Detailed statement describing factual and legal basis for belief that the patent will be infringed Response to statement concerning validity and enforceability 42 U.S.C. 262(l)(3)(C) Discussion: Response to validity and enforceability. 40

41 Part 2: Fourth Step RPS s Response to BA You will infringe patents They are all valid and enforceable for the following reasons RPS must provide its reasons for infringement, validity, and enforceability, showing its position to BA 41

42 Part 2: Fifth Step Patent List Negotiations RPS and BA must engage in good faith negotiations regarding which patents will be subject of the immediate infringement action 42 U.S.C. 262(l)(4)(A) Discussion: When should those negotiations begin? What do BA and RPS need to do to show good faith? 42

43 Part 2: Sixth Step Final Patent Lists What if RPS and BA fail to reach agreement on which patents to litigate within 15 days? They must then exchange final patent lists that will determine which patents will be litigated immediately 42 U.S.C. 262(l)(4)(B) 43

44 Part 2: Sixth Step Final Patent Lists BA notifies RPS of the number of patents that should be the subject of the infringement action Within 5 days parties simultaneously exchange lists of patents that should be the subject of the infringement action RPS cannot list more patents than the number proposed by BA (except if BA does not list any patent, then RPS can list one) 42 U.S.C. 262(l)(5) 44

45 Part 2: What Will RPS and BA Do in This Exchange? BA: We believe that 3 patents should be the subject of immediate litigation. RPS: We choose patents 002, 003, and 004. BA: We choose 002, 003, and 006. They still haven t come to agreement Discussion: Strategies for dealing with this? 45

46 Part 3: Litigation If the parties agree on a list RPS must commence action with respect to each patent on the list within 30 days of the agreement If the parties do not agree on a list RPS must commence action with respect to each patent on either list within 30 days of the exchange of the lists of patents during negotiations 42 U.S.C. 262(l)(6) 46

47 Part 3: RPS Must Sue on Four Patents Because RPS and BA didn t agree, RPS must commence litigation on patents 002, 003, 004 and 006 within 30 days of the exchange of final patent lists BA must notify FDA of the litigation If RPS and BA had agreed, only 3 patents would be litigated immediately Discussion: Is it more advantageous to agree or disagree? Is it okay to preview lists to ensure agreement/disagreement? 47

48 Part 3: Bringing an Action for Infringement: Limitations Bringing action after the 30 days has expired or bringing action then dismissing it without prejudice Sole remedy in any subsequent infringement action of that patent will be reasonable royalty Failure to disclose relevant patent Action for patent infringement under this section can never be brought No provision prohibiting settlement 35 U.S.C. 271(e)(6) Discussion: Does this section mean 271(e) or 271? 48

49 Part 3: Notice of Commercial Marketing and Preliminary Injunction Notice of intent to market BA must provide at least 180 days notice of intention to market, regardless of existence of patents Preliminary injunction RPS can seek a preliminary injunction after receiving BA s notice 42 U.S.C. 262(l)(8) To prevent marketing until court decides infringement, validity, and enforceability Discussion: Will there be substantial PI practice? 49

50 Part 3: Preliminary Injunction (Cont.) Eligible patents Patents in the original list of either of the parties, or in a newly issued patents list, but that are not included in the final lists (after negotiations) Parties must reasonably cooperate to expedite further discovery as needed for preliminary injunction 42 U.S.C. 262(l)(8) 50

51 Part 4: FDA Implementation FDA is given substantial discretion under the statute Unclear how FDA will implement the statute If FDA issues guidance on a case-by-case basis, an approval pathway will be difficult to predict for other biosimilar applicants Unclear what studies FDA will require, which could affect decisions by biosimilar applicants of which products to develop Discussion: What do you guys think? 51

52 Part 4: Recent FDA Actions The agency is in the early stages of deciding on an approval pathway A working group comprised of officials from CDER, CBER, and the Office of the Chief Counsel has been established by FDA to implement the statute Leah Christi has been tapped as the Office of New Drugs Associate Director of Biosimilars What else? Washington Drug Letter, Vol. 42 No. 25, Biosimilar Developers Told to Wait as FDA Crafts Regulatory Guidance, June 21, 2010; The Pink Sheet Daily, FDA Creates Biosimilars Overseer in Drug Office; Internal Panel to Advice Application Reviewers, May 20,