1. AIPLA Webinar September 25, 2012
Biosimilars 2012
Denise Kettelberger, PhD, JD
Faegre Baker Daniels, LLP
AIPLA Webinar
September 25, 2012

2. Summary – US Biosimilars
Process is Front-Loaded
Litigation – fast paced
Confidential Disclosure
Prosecution bar on recipients
Patent List Exchange – list to litigate
Abbott’s Citizen’s Petition – “taking”
Strategies and Choices
Preparation for 2-Phase litigation

3. Front-Loaded: FDA “Extensive” Consultation with FDA
Disclose data to FDA before application
Advise on plan for further analysis and comparison
Assess if highly similar or not to Reference Product
Trade Secrets and Confidential Information?
FOIA to obtain information
Redact TS and confidential information from BLA action packet
What TS might be disclosed in “extensive” discussions?
FDA not advise both reference product and biosimilar?

4. Abbott Petition - Humira®
Retroactive use of Reference Product violates 5th Amendment
Taking property without just compensation
Trade Secrets are property
Information supporting BLA contains trade secrets
Retroactive legislation "takes” those trade secrets
Free-ride on RPS trade secrets
Legislation should only be applied to BLAs filed after enactment
(Do existing products get retroactive 12 years exclusivity?)

5. Legislated US Biosimilars Litigation
Negotiate patents for
immediate litigation
>15 days if not agree,
short list of patents for immediate litigation < 5d
<20 days
(k) app to RPS
< 60 days
(k) App Patent Statement and Patent List
< 60 days
RPS Patent Statement
< 180 days
Pre-launch (k) App Notice
< 60 days
RPS Patent List to (k)app
(k) App accepted
RPS seek Prelim Injunction
< 30 days
RPS must file litigation
Anticipated launch
Fail to do - RPS can DJ any patent 30
No Statement - RPS can DJ
RPS not sue <30 days – only reasonable royalty
RPS can’t sue on patent not listed
No 180 d Notice - RPS can DJ any listed patent

6. Step by Step – Confidential Review
(k) Application provided to RPS
Within 20 days of acceptance
Confidential Review by selected counsel
In house and/or outside counsel
cannot have participated in patent prosecution relevant or related
Cannot disclose to employees or outside consultant
Application contains comparisons and methods of manufacture
Penalty for disclosure = deemed irreparable harm – injunctive relief
Penalty for not timely providing copy = RPS can file DJ on any patent

7. Step by Step – Patent Lists
Reference Product Sponsor’s patent list
to (k) applicant within 60 days of receiving (k) application
List of all patents that could reasonably be asserted
Failure to list precludes use in litigation against (k) applicant
Also list patents willing to license to (k) applicant
Biosimilar (k) applicant’s patent list
to RPS within 60 days of receiving RPS Patent List
With analysis of RPS Patents and response to License Offer
In a claim by claim statement of non-infringement or invalidity
Failure to provide statement RPS can file DJ action
RPS response
To (k) applicant within 60 days with statement

8. Step by Step – Negotiation
15 days Good Faith Negotiation
List of patents to litigate immediately
Failure to decide – mandatory exchange of second lists
(k) applicant gives notice to RPS of number of patents listing
RPS provides own list (cannot be greater number than (k)’s list
If (k) lists zero patents, RPS can sue on only one patent
Within 30 days of agreed list – RPS must file suit against (k) applicant
If RPS does not timely file suit, remedy limited to reasonable royalty
First phase of litigation
Negotiation period provides opportunity for settlement or ADR
Timeline not halted more than 15 days
Antitrust considerations

9. Step by Step – Second Phase Litigaton
Triggered by (k) applicant’s Notice
Intent to launch approved biosimilar product
Provided to RPS at least 180 days prior to launch
After 180 days, RPS can seek a preliminary injunction
Patents identified initially but not listed in first or second lists
On failure of RPS to seek preliminary injunction
(k) applicant can seek DJ

10. Antitrust Review of Settlements
In re. K-Dur Antitrust Litigation
FTC – Reverse Payments constitute unfair methods of competition
“absent proof of other offsetting consideration, it is logical to conclude that the quid pro quo for payment was an agreement by the generic to defer entry beyond the date that represents an otherwise reasonable litigation compromise”
3rd Circuit not in agreement with Federal Circuit (and 6th, 11th)
(Merck Petition for Supreme Court Certiorari)

11. Choices ANDA or Biosimilar? BLA or Biosimilar?
Approval of “biological product” must be submitted under 351 PHSA
Except (until March 23, 2020)
if in a product class where application already approved FDCA
Unless another potential reference product licensed under PHSA BLA
BLA or Biosimilar?
Not “highly similar” = BLA
Choose different molecule (Teva Tbo-Filgastrim)
Weigh clinical costs vs. litigation costs, uncertainty
Potential 12 years exclusivity for BLA
Protein redefined – size determines eligibility for Biosimilar path

12. Protein Redefined Statute: Guidance: Flexibility?
Protein (other than a chemically synthesized polypeptide)
Guidance:
Protein means any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size.
Chemically synthesized polypeptide means any alpha amino acid polymer that is (a) made entirely by chemical synthesis and (b) is less than 100 amino acids in size.
Flexibility?

13. Recombinantly Produced
Size Matters!
Size determines eligibility for 512(k) pathway
Reference Product =12 years data exclusivity
< 40 AA AA
>100 AA
Chemically
Synthesized
5 yr
12 yr
Recombinantly Produced

14. Amino Acid Sequence Uncertainty Guidance:
Expectation encodes same AA sequence as RP
Minor modifications ( N/C- truncations)
Not change safety and efficacy
Single amino acid difference?
Only if unavoidable - Can have significant impact
Deliberate change in sequence?
Not allow in (k) pathway – in (a) BLA?
Potential to justify
Uncertainty

15. 271(e) Safe Harbor
Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc.
Under a proper construction of 35 U.S.C. § 271(e)(1), the fact that Amphastar’s testing is carried out to “satisfy the FDA’s requirements” means it falls within the scope of the safe harbor, even though the activity is carried out after approval.
Judge Rader’s dissent calls for en banc review
[271(e)] “won approval because it was limited in time, quantity, and type,” and that the majority opinion runs counter to legislative intent and significantly expands the scope of the provision.
Classen Immunotherapies v. Biogen IDEC 659 F.3d 1057 (Fed. Cir. 2011)
Safe harbor does not apply to information that may be routinely reported to the FDA long after marketing approval has been obtained.

16. Be Prepared RPS ALL potentially relevant patents Litigation prep
Identify team - counsel
Identify all relevant patents
Portfolio review, diligence
Reissue, re-exam, supplemental
Assignments, Exclusive licenses
Identify, in-license patents?
Litigation prep
Story, Experts, settlement
What patents to litigate, when
ALL potentially relevant patents
Product, process, sequence
Vector, host cell, expression system
3D-Structure, post-translational modification
Active site, binding site, fragments
Formulations, packaging
Process manufacture, use, administration
Diagnostics

17. Be Prepared (k) applicant Strategy Search and review
BLA documents (FOIA)
RPS relevant patents, licensed
Patent applications, literature
File own patents
License-in relevant patents
Post-grant challenge RFP patents
Non-infringement issues
Choice – Biosimilar, BLA, ANDA
Patents – how many, which?
Invalidity and non-infringement
Claim construction
Experts and litigation plan
271(e) safe harbor apply?

18. Questions? 18