Paper No. __
`Filed: July 30, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
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`COALITION FOR AFFORDABLE DRUGS VI LLC
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`Petitioner,
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`v.
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`CELGENE CORPORATION
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`Patent Owner
`________________
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`Case IPR2015-01096
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`Patent 6,315,720
`________________
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`PATENT OWNER PRELIMINARY RESPONSE
`PURSUANT TO 35 U.S.C. § 313 and 37 C.F.R. § 42.107
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`04841.00006/7046102.1
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`PROTECTIVE ORDER MATERIAL
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`Filed: July 30, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
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`COALITION FOR AFFORDABLE DRUGS VI LLC
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`Petitioner,
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`v.
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`CELGENE CORPORATION
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`Patent Owner
`________________
`
`Case IPR2015-01096
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`Patent 6,315,720
`________________
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`
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`PATENT OWNER PRELIMINARY RESPONSE
`PURSUANT TO 35 U.S.C. § 313 and 37 C.F.R. § 42.107
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`TABLE OF CONTENTS
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`Page
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`I.
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`INTRODUCTION ........................................................................................... 1
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`II.
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`BACKGROUND ............................................................................................. 3
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`A.
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`B.
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`The Challenge of Protecting A Fetus From A Teratogenic
`Drug While Allowing A Patient Access to Its Efficacy........................ 5
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`Previous Attempts to Control
`Access to Other Drugs Were Unsuccessful ........................................ 11
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`C.
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`The ’720 Patent ................................................................................... 14
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`III. ARGUMENT ................................................................................................. 18
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`A.
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`The Petition Should Be Denied Because
`CFAD Has Failed To Show A Reasonable Likelihood
`That The Challenged Claims Are Unpatentable ................................. 19
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`1.
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`CFAD’s Expert Declaration Is
`Entitled to “little or no weight” ................................................. 19
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`(a) Dr. Fudin Is Not A POSA ............................................... 19
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`(b) Dr. Fudin’s Opinions Are
`Unsupported, Verbatim Recitations of
`CFAD’s Conclusory Arguments .................................... 21
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`2.
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`Ground 1: Claims 1-32 Are
`Not Anticipated by the July 1998 Thalomid PI ........................ 22
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`(a)
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`Legal Standards .............................................................. 22
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`(b) The July 1998 Thalomid PI
`Does Not Disclose Each Claim Limitation,
`Either Expressly Or Inherently ....................................... 23
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`i.
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`Claim 1 ................................................................. 24
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`1)
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`Element 1(b) – “defining a set of
`information to be obtained from said
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`2)
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`3)
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`4)
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`patient, which information is
`probative of the risk that said adverse
`side effect is likely to occur if said
`drug is taken by said patient” ..................... 24
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`Element 1(c) – “in response to said
`information set, assigning said patient
`to at least one of said risk groups and
`entering said risk group assignment in
`said medium” ............................................. 25
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`Element 1(d) – “based upon said
`information and said risk group
`assignment, determining whether the
`risk that said adverse side effect is
`likely to occur is acceptable.” .................... 27
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`Element 1(e) – “upon a determination
`that said risk is acceptable, generating
`a prescription approval code to be
`retrieved by said pharmacy before
`said prescription is filled.” ......................... 28
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`ii.
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`Dependent Claims 2-27 ........................................ 29
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`1)
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`2)
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`Claim 5 – “Wherein said risk group
`assignment and said informed consent
`is verified by said prescriber at the
`time that said patient is registered in
`said computer readable storage
`medium.” .................................................... 30
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`Claim 6 – “wherein said risk group
`assignment and said informed consent
`is transmitted to said computer
`readable storage medium by facsimile
`and interpreted by optical character
`recognition software.” ................................ 32
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`3)
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`Claim 9 – “Wherein said diagnostic
`testing is probative of the
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`4)
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`5)
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`6)
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`concentration of said drug in a tissue
`of said patient.” .......................................... 33
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`Claim 10 – “wherein said diagnostic
`testing comprises genetic testing” .............. 35
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`Claim 15(h) – “entering said second
`set of information in said medium
`before said patient is approved to
`receive said drug” ...................................... 36
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`Claim 17 – “Wherein said survey is
`conducted telephonically using an
`integrated voice response system.” ............ 37
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`iii.
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`Independent Claim 28 and
`Dependent Claims 29-32 ...................................... 37
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`3.
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`Ground 2: Claims 1-32 Would
`Not Have Been Obvious Over
`The July 1998 Thalomid PI, Cunningham,
`and the Knowledge of a POSA ................................................. 39
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`(a)
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`The Petition Fails To Address
`The Redundancy With The
`2015-01102 and 2015-01103 Petitions ........................... 39
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`(b) CFAD Fails to Consider the
`Claim Language as a Whole or to
`Perform a Proper Graham Analysis ............................... 41
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`(c) CFAD Has Not Provided A
`Motivation To Combine the
`July 1998 Thalomid PI and Cunningham ....................... 43
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`(d) The July 1998 Thalomid PI, Cunningham,
`And The Knowledge Of A POSA
`Fail To Disclose, Teach, Or Suggest
`Key Elements Of The Claimed Inventions ..................... 46
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`i.
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`Claim 1(e) and 28(e) – “approval code” .............. 46
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`ii.
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`Claim 5 – “Wherein said risk group
`assignment and said informed consent is
`verified by said prescriber at the time that
`said patient is registered in said computer
`readable storage medium.” ................................... 47
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`iii. Claim 17 – “Wherein said survey is
`conducted telephonically using an integrated
`voice response system.” ....................................... 49
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`4.
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`CFAD Fails To Address The Objective Evidence of
`Nonobviousness Regarding the ’720 Patent ............................. 50
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`(a)
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`Long-felt Need Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 50
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`(b) Commercial Success Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 52
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`(c)
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`Third-Party Praise And Awards Further Supports
`The Nonobviousness Of The Claimed Inventions ......... 53
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`(d) Licensing by Others Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 53
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`(e) Unexpected Results Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 54
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`B.
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`C.
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`The Petition Should Be Denied
`Under 35 U.S.C. §§ 314(a) and 316(b) ............................................... 55
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`The Petition Should Be Denied
`For Failing To Name All Real Parties-In-Interest .............................. 58
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`IV. CONCLUSION .............................................................................................. 60
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`I.
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`INTRODUCTION
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`IPR2015-01096
`Patent 6,315,720
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`Pursuant to 35 U.S.C. § 313 and 37 C.F.R. § 42.107(a), Patent Owner
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`Celgene Corporation (“Celgene”) submits this Preliminary Response to Coalition
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`For Affordable Drugs VI LLC’s (“CFAD”) Petition for Inter Partes Review (the
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`“Petition”) of U.S. Patent No. 6,315,720 (the “’720 patent”).
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`The ’720 patent describes and claims improved methods for delivering a
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`potentially dangerous drug to a patient (including teratogenic drugs such as
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`thalidomide) while avoiding the occurrence of adverse side effects (such as birth
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`defects of the type associated with thalidomide). The inventions were conceived as
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`part of Celgene’s efforts to significantly improve its existing program for
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`controlling patient access to thalidomide, which was known as the System for
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`Thalidomide Education and Prescribing Safety, or S.T.E.P.S.® The improved
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`program, which Celgene called Enhanced S.T.E.P.S.®, is an embodiment of the
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`’720 patent and has been used in connection with thalidomide and other potentially
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`teratogenic pharmaceutical products since 2001. During that time it has
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`successfully prevented 100% of drug-related birth defects. In fact, the inventions
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`of the ’720 patent were so successful and innovative that the FDA required other
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`drug manufacturers to copy Celgene’s patented methods if they wanted to keep
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`their products on the market, resulting in licenses to several of Celgene’s patents,
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`including the ’720 patent.
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`Notwithstanding Celgene’s significant innovation, CFAD has filed the
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`present Petition as part of a hedge fund investment strategy developed by the real
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`parties-in-interest (“RPI”). CFAD’s Petition, however, has several fatal defects.
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`First, CFAD relies heavily on an expert declaration that is entitled to little or
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`no weight because the declarant is not a person of ordinary skill in the art (POSA),
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`and because the declaration merely reiterates CFAD’s conclusory arguments.
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`Second, CFAD’s Ground 1 anticipation argument fails on the merits because
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`the cited art—the original July 1998 Thalomid® package insert (“July 1998
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`Thalomid PI,” CFAD’s Ex. 1006)—does not disclose each and every element of
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`the ’720 patent claims. Indeed, CFAD admits that many of the claim limitations of
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`the ’720 patent are not expressly disclosed in the July 1998 Thalomid PI. Instead,
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`CFAD argues that the missing limitations are inherently disclosed, but those
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`limitations are not “necessarily present,” and CFAD fails to explain how or why
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`they allegedly are. Moreover, the July 1998 Thalomid PI is, at best, cumulative to
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`other references that were extensively considered by the Examiner during
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`prosecution. Ground 1 does not warrant an IPR trial of the ’720 patent.
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`Third, CFAD’s Ground 2 obviousness argument fails on the merits because
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`none of the cited references disclose, teach, or suggest all elements of the
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`challenged claims. CFAD’s proposed modifications to, and combinations of, the
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`alleged prior art disclosures are driven entirely by hindsight and supported only by
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`conclusory assertions by CFAD’s declarant, who merely parrots the arguments in
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`the Petition. There is also no rational basis for combining CFAD’s references, as
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`they are directed to different endeavors. Ground 2 does not warrant an IPR trial of
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`the ’720 patent.
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`Fourth, CFAD’s Petition is an improper use of the IPR proceedings.
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`Specifically, CFAD and the RPI are abusing and misusing the IPR process in an
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`attempt to effectuate changes in the stock prices of the targeted innovator
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`pharmaceutical companies. The self-serving actions of the RPI create unwarranted
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`burdens for both patent owners and the Board. The Board should exercise its
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`discretion under 35 U.S.C. §§ 314(a) and 316(b) and deny the Petition.1
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`Fifth and finally, the Petition should also be denied because it fails to name
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`all RPI—a threshold requirement for an IPR. Specifically omitted from the RPI
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`identification are the investors in the Hayman funds responsible for filing the
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`Petition. Having failed to name all RPI, the Petition cannot be considered.
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`II. BACKGROUND
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`Celgene is a biopharmaceutical company that is committed to improving the
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`lives of patients through research and development of drug products that treat
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`1 With the Board’s permission, Celgene has separately moved to dismiss the
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`Petition pursuant to 37 C.F.R. § 42.12.
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`cancers and other devastating conditions. Three drug products developed by
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`Celgene are relevant to this IPR: Thalomid®, Revlimid®, and Pomalyst®.
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`Thalomid® is approved for the treatment of (1) erythema nodosum leprosum
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`(“ENL”)—an inflammatory condition associated with leprosy; and (2) newly
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`diagnosed multiple myeloma (“MM”) (in combination with dexamethasone). Ex.
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`2001 at 1. The active ingredient in Thalomid® is thalidomide, which is well known
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`for its teratogenicity (or ability to cause severe birth defects). Unfortunately, as
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`described in more detail below, the devastating effects of thalidomide were felt
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`worldwide during the thalidomide tragedy of the 1950s and 1960s, and continue
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`today for the surviving victims. See, e.g., Ex. 2002 at 1; Ex. 1001 at 1:40-45.
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`Revlimid® is approved for the treatment of (1) transfusion-dependent anemia
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`due to low- or intermediate-1-risk myelodysplastic syndromes associated with a
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`deletion 5q abnormality with or without additional cytogenetic abnormalities;
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`(2) MM (in combination with dexamethasone); and (3) mantle cell lymphoma in
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`certain patients whose disease has relapsed or progressed after two prior therapies.
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`Ex. 2003 at 1. Pomalyst® (in combination with dexamethasone) is approved for
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`the treatment of MM in patients who have received at least two prior therapies and
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`whose disease has progressed. Ex. 2004 at 1. The active ingredient in Revlimid®
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`is lenalidomide, and the active ingredient in Pomalyst® is pomalidomide. Ex. 2003
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`at 1; Ex. 2004 at 1. According to the FDA-approved package inserts, lenalidomide
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`and pomalidomide are “thalidomide analogue[s],” and if these drugs are “used
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`during pregnancy, [they] may cause birth defects or embryo-fetal death.” Ex. 2003
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`at 1, 3, 7, 22-23; Ex. 2004 at 1, 2, 4, 14, 24. As described herein, due in large
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`measure to the inventions claimed in the ’720 patent (and other of Celgene’s
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`patents), Celgene’s FDA-approved systems for preventing fetal exposure to the
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`active ingredients in Thalomid®, Revlimid®, and Pomalyst® have been 100%
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`successful in preventing drug-related birth defects.
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`A. The Challenge of Protecting A Fetus From A Teratogenic
`Drug While Allowing A Patient Access to Its Efficacy
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`Beginning in 1958, thalidomide was marketed in Europe as a sedative and a
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`treatment for pregnant women with morning sickness. See Ex. 1001 at 1:40-45;
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`Ex. 2002 at 1. Shortly after entering the European market, it was discovered that
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`thalidomide caused deformities in children born to mothers who had taken the drug
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`during pregnancy. Id. As a result, by 1962, thalidomide had been withdrawn from
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`all markets. Id. By then, the damage had been done. Thalidomide had been
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`linked to more than 10,000 birth defects in at least 46 countries. Id. The birth
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`defects were severe. Some children were born with missing or abnormal limbs,
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`feet, or hands, a condition known as phocomelia (from the Greek for “seal”
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`“limb”). Id. Many other deformities and complications were linked to
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`thalidomide, including abnormal or absent ears, and heart and kidney problems.
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`Id. As a result of this tragedy, drug regulatory authorities worldwide, including the
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`FDA, revised their regulations to ensure that new drugs were screened for safety in
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`addition to efficacy, and were specifically investigated for their potential to cause
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`harm to a developing fetus. Id.; Ex. 2005.
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`Years later, it became clear that despite its teratogenicity, thalidomide had
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`the power to benefit certain patient populations. Ex. 1001 at 1:46-62.
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`Accordingly, Celgene believed it would be beneficial if the drug were made
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`available to those patient populations. Due to its known teratogenicity, however,
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`Celgene realized that to market thalidomide, it needed to develop a system that
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`would allow patients in need of thalidomide to access it while ensuring that no
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`thalidomide-related birth defects would occur. Ex. 1001 at 1:59-64.
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`In other words, Celgene was faced with a great challenge—find a way to
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`effectively avoid the teratogenic side effects of thalidomide while still making the
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`drug available to patients in need. Indeed, Celgene recognized that it would need
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`to create a system that was so effective at preventing birth defects of the type
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`associated with teratogenic drugs that it would convince skeptical FDA regulators,
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`and understandably vocal and concerned thalidomide victims around the world,
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`that Thalomid® could be safely marketed. In other words, the new system would
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`need to convince the FDA to lift its nearly 40-year ban on thalidomide.
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`Celgene rose to meet this challenge, first developing the methods claimed in
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`U.S. Patent No. 6,045,501 (the “Elsayed ’501 patent”) (Ex. 1003) (described in
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`Celgene’s Preliminary Response to IPR2015-01092). Celgene then improved upon
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`its own work by inventing the methods claimed in the ’720 patent (described
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`below). In other words, Celgene’s inventions for controlling access to thalidomide
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`(and other teratogens) came in two phases. Celgene first developed S.T.E.P.S.®,
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`which is claimed in the Elsayed ’501 patent and was first implemented with the
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`July 1998 Thalomid PI. The initial implementation of S.T.E.P.S.® only
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`retrospectively identified patient behaviors that posed a risk of fetal exposure to
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`thalidomide. See Ex. 2006 at 328. While this patented system was 100%
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`successful in preventing birth defects of the type associated with thalidomide in
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`patients taking Thalomid®, Celgene (and the inventors of the ’720 patent) still saw
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`room for significant improvement.
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`Thus, the ’720 patent’s inventors developed changes that transformed
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`S.T.E.P.S.® from a retrospective program into a prospective program called
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`Enhanced S.T.E.P.S.® See id. Specifically, from October 1999 to September
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`2001, the inventors focused on implementing changes that were “designed to
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`identify patients exhibiting behaviours providing risk for fetal exposure and to
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`remedy those behaviours prior to dispensing thalidomide.” Id. (emphasis added).
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`As explained in the ’720 patent, the inventors
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`came up with the authorization process of Enhanced S.T.E.P.S.®, which
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`involves generating a prescription approval code to be retrieved by the
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` pharmacy. Ex. 1001 at 13:43-45.
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`Enhanced S.T.E.P.S.® was implemented for the first time with the September
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`2001 Thalomid® package insert (“September 2001 Thalomid PI”), which is not
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`prior art to the 720 patent. See Ex. 2008. Specifically, the September 2001
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`Thalomid PI included the significant improvements claimed in the ‘720 patent.
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`Those improvements are reflected in the September 2001 revisions to July 1998
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`Thalomid PI, which CFAD relies upon here. For example:
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`DRUG MUST ONLY BE DISPENSED IN NO MORE THAN A 1
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`MONTH SUPPLY AND ONLY ON PRESENTATION OF A NEW
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`PRESCRIPTION WRITTEN WITHIN THE PREVIOUS 7 DAYS.
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`SPECIFIC INFORMED CONSENT (copy attached as part of this
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`package insert) AND COMPLIANCE WITH THE MANDATORY
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`PATIENT REGISTRY AND SURVEY ARE REQUIRED FOR ALL
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`PATIENTS (MALE AND FEMALE) PRIOR TO DISPENSING BY
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`THE PHARMACIST.
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`BEFORE DISPENSING THALOMID® (thalidomide), YOU MUST
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`ACTIVATE THE AUTHORIZATION NUMBER ON EVERY
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`PRESCRIPTION BY CALLING THE CELGENE CUSTOMER
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`CARE CENTER AT 1-888-4-CELGENE (1-888-423-5436) AND
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`OBTAINING A CONFIRMATION NUMBER. YOU MUST ALSO
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`WRITE THE CONFIRMATION NUMBER ON THE
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`PRESCRIPTION. YOU SHOULD ACCEPT A PRESCRIPTION
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`ONLY IF IT HAS BEEN ISSUED WITHIN THE PREVIOUS 7
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`DAYS (TELEPHONE PRESCRIPTIONS ARE NOT PERMITTED);
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`DISPENSE NO MORE THAN A 4-WEEK (28- DAY) SUPPLY,
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`WITH NO AUTOMATIC REFILLS; DISPENSE BLISTER PACKS
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`INTACT (CAPSULES CANNOT BE REPACKAGED); DISPENSE
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`SUBSEQUENT PRESCRIPTIONS ONLY IF FEWER THAN 7
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`DAYS OF THERAPY REMAIN ON THE PREVIOUS
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`PRESCRIPTION; AND EDUCATE ALL STAFF PHARMACISTS
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`ABOUT THE DISPENSING PROCEDURE FOR THALOMID®
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`(thalidomide).
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`Ex. 2009 at 4; see Ex. 2008 at 20.
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`Today, Enhanced S.T.E.P.S.® is known as the Thalomid REMS, which is an
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`FDA-approved Risk Evaluation and Mitigation Strategy (“REMS”). Enhanced
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`S.T.E.P.S.® is claimed in Jepson format in the ’720 patent as an improvement over
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`S.T.E.P.S.®, which was originally claimed in the ’501 patent. Celgene’s continued
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`success in preventing birth defects due to Thalomid®, Revlimid®, and Pomalyst® is
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`in large measure due to the inventions of the ’720 patent and other Celgene patents
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`(including the ’501 patent). Had Celgene not developed the claimed methods for
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`preventing fetal exposure to teratogenic (or potentially teratogenic) drugs,
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`Thalomid®, Revlimid®, and Pomalyst® would not be available to patients today.
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`The FDA first approved Thalomid® for the treatment of ENL in July 1998
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`subject to 21 CFR § 314.520 (“Subpart H”), which allowed the FDA to approve
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`drugs that were shown to be effective, but that could only be used safely under
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`restricted conditions. Ex. 1025 at 0002. Specifically, the approval letter stated that
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`Thalomid® was being approved because Celgene presented adequate information
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`to demonstrate that the drug would be safe and effective for use when marketed
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`under S.T.E.P.S.®, which is an embodiment of the methods described in Celgene’s
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`patents. Id. The FDA subsequently approved Celgene’s labeling changes that
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`incorporated the improvements of Enhanced S.T.E.P.S.®, which is an embodiment
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`of the methods described in the ’720 patent. See Ex. 2009 at 4; Ex. 2008 at 20.
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`Then, when Thalomid® was approved for the treatment of newly diagnosed MM in
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`2006, the FDA maintained the same restrictions on distribution of the drug. Ex.
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`2010 at 1. Similarly, the FDA conditioned its approval of both Revlimid® and
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`Pomalyst® (for all indications), on Celgene’s use of the same restrictions applied to
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`Thalomid®. Ex. 2011 at 1; Ex. 2012 at 7-10.
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`B.
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`Previous Attempts to Control Access to
`Other Drugs Were Unsuccessful
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`Others attempted to control access to the drugs Accutane® (isotretinoin) and
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`Clozaril® (clozapine) before Celgene invented S.T.E.P.S.®, but as described below,
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`those attempts failed to meet their goals. Both failed to provide a workable
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`solution for dealing with a drug like thalidomide, where even a single drug-related
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`birth defect was unacceptable.
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`Accutane® contains isotretinoin, a form of vitamin A (a vitamin A analogue)
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`that has been used as a treatment for severe cystic acne since 1982. Ex. 1011 at
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`101. Isotretinoin can and has caused birth defects in children whose mothers are
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`taking the drug. Id. Because of the teratogenic effects of isotretinoin, and instead
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`of removing the drug from the market, the manufacturer of isotretinoin
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`implemented the Pregnancy Prevention Program (“PPP”).
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`The PPP, however, was not effective in preventing women who were taking
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`Accutane® from becoming pregnant or from exposing fetuses to isotretinoin. In
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`fact, the Mitchell reference that CFAD relies upon (Ex. 1011) discloses that there
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`were more than 400 pregnancies that occurred during isotretinoin treatment, at
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`least six of which resulted in live born infants with at least minor anomalies, and at
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`least one with major anomalies. Id. at 103-04. Mitchell further reports that in the
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`first several months of the PPP, there was incomplete compliance with several
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`parts of the program, such as failures to ensure negative pregnancy tests before
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`beginning treatment, failures to wait until menses begins before treatment, and
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`failures to use effective birth control before, during, and after treatment. Id. at 104.
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`Compliance remained incomplete even after the manufacturer changed the
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`medication package to highlight the most important parts of the PPP. Id.
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`Publications in prominent scientific journals also disparaged the PPP. For
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`instance, an article in the New England Journal of Medicine reported that “[s]ince
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`the [PPP] was implemented in 1989, a substantial number of fetuses have been
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`exposed to the drug. As many as 30 percent of the women with exposed fetuses
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`did not use any mode of contraception, even though they were cognizant of the
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`high fetal risk.” Ex. 2013 at 1130.
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`Clozaril® contains clozapine, and is used to treat schizophrenia. Ex. 1008 at
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`899. Its release into the market was permitted only with certain prescribing and
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`distribution restrictions implemented by the manufacturer. Id. These restrictions
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`were put in place because the use of clozapine is associated with a high frequency
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`of agranulocytosis, a potentially fatal blood disorder. Ex. 2014 at 52. Clozapine is
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`not a teratogenic drug—it does not cause birth defects—and the system employed
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`to monitor its use was not tailored to restrict or prevent birth defects. Instead, the
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`manufacturer developed a program called the Clozaril National Registry to
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`“enhance patient safety by facilitating early detection of potentially dangerous
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`white blood cell suppression.” Id. at 52-53. But like the PPP, the clozapine system
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`was also a failure. Specifically, during its first five years, 382 patients developed
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`agranulocytosis, and 12 of those patients died as a result. Id. at 55.
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`When Celgene invented S.T.E.P.S.® and the methods claimed in the ’501
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`patent, the programs in place for both the Accutane® and Clozaril® were
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`ineffective. The ’501 patent was a significant innovation over those systems and,
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`as noted above, the ’720 patent was a significant improvement over the ’501
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`patent. To date, Celgene’s FDA-approved systems for preventing fetal exposure to
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`the active ingredients in Thalomid®, Revlimid®, or Pomalyst®—all of which are
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`covered by the claims of the ’720 patent—have been 100% successful in
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`preventing birth defects of the type associated with thalidomide. Celgene’s
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`patented methods were so successful that, in 2006, it became clear that the PPP
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`(and later attempts at managing the distribution of isotretinoin) were ineffective by
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`comparison. Consequently, the FDA required the manufacturers of isotretinoin to
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`use Celgene’s patented methods if they wanted to keep their products on the
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`market. This resulted in licenses to several of Celgene’s patents, including the
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`’720 patent, in connection with the distribution of isotretinoin under a program
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`known as iPledge. See Ex. 2015 at 11; Ex. 2016 at 1; and Ex. 2017 at 6.
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`C. The ’720 Patent
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`As discussed above, the ’720 patent describes and claims improved methods
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`for delivering a potentially dangerous drug to a patient (including teratogenic drugs
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`such as thalidomide) while avoiding the occurrence of adverse side effects (such as
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`birth defects). See Ex. 1001 at Abstract; 1:8-16. The claims are set forth in Jepson
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`format, with a preamble comprising a general description of the known elements of
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`the claimed invention (which are claimed in the Elsayed ’501 patent, and embodied
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`in S.T.E.P.S.® and the July 1998 Thalomid PI), and the novel improved elements
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`(which are embodied in Enhanced S.T.E.P.S.® and the September 2001 Thalomid
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`PI) set forth after the “improvement comprising” clause. See 37 C.F.R. § 1.75(e)
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`(describing the preferred format for claims to improvements). For example,
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`independent Claim 1 of the ’720 patent recites:
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`In a method for delivering a drug to a patient in need of the drug,
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`while avoiding the occurrence of an adverse side effect known or
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`suspected of being caused by said drug, wherein said method is of the
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`type in which prescriptions for said drug are filled only after a
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`computer readable storage medium has been consulted to assure that
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`the prescriber is registered in said medium and qualified to prescribe
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`said drug, that the pharmacy is registered in said medium and
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`qualified to fill the prescription for said drug, and the patient is
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`registered in said medium and approved to receive said drug, the
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`improvement comprising:
`a. defining a plurality of patient risk groups based upon a predefined
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`set of risk parameters for said drug;
`b. defining a set of information to be obtained from said patient,
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`which information is probative of the risk that said adverse side
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`effect is likely to occur if said drug is taken by said patient;
`c. in response to said information set, assigning said patient to at least
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`one of said risk groups and entering said risk group assignment in
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`said medium;
`d. based upon said information and said risk group assignment,
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`determining whether the risk that said adverse side effect is likely
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`to occur is acceptable; and
`e. upon a determination that said risk is acceptable, generating a
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`prescription approval code to be retrieved by said pharmacy before
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`said prescription is filled.
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`Ex. 1001 at Claim 1. The only other independent claim, Claim 28, includes all of
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`the elements of Claim 1 and adds the following further limitation: “wherein said
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`adverse side effect is likely to arise in patients who take said drug in combination
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`with at least one other drug.” Id. at Claim 28. The dependent claims further limit
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`and define the controls to avoid adverse side effects. See id. at Claims 2-27, 29-32.
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`During prosecution, the Examiner extensively considered the most
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`significant prior art, namely the ’501 patent (also known as “Elsayed”), and
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`concluded that it did not disclose, teach, or suggest the ’720 patent’s inventions.
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`Specifically, the Examiner found that “Elsayed et al. teaches a method for
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`delivering a drug to a patient while preventing the exposure to a fetus or to other
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`individuals with contraindications to the drug that includes registering prescribers,
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`pharmacists, and patients in a computer readable storage medium for authorizing
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`and monitoring distribution of the drug,” but noted that Elsayed “does not teach a
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`step of generating of a prescription number or code, which can be retrieved by a
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`pharmacy before said prescription is filled.” Ex. 1002 at 0091 (emphasis added).
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`In other words, the Examiner concluded that the Elsayed ’501 patent disclosed
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`only what was in the preamble of the ’720 patent’s Jepson claims, but did not
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`disclose, teach, or suggest the claimed improvements, which were
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