Paper No. __
`Filed: July 28, 2015
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`
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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
`Petitioner,
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`v.
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`CELGENE CORPORATION
`Patent Owner
`
`________________
`
`Case IPR2015-01103
`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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`
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`
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`04841.00006/7042666.1
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`PROTECTIVE ORDER MATERIAL
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`Filed: July 28, 2015
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`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`________________
`
`COALITION FOR AFFORDABLE DRUGS VI LLC
`Petitioner,
`
`v.
`
`CELGENE CORPORATION
`Patent Owner
`
`________________
`
`Case IPR2015-01103
`Patent 6,315,720
`________________
`
`
`
`PATENT OWNER PRELIMINARY RESPONSE
`PURSUANT TO 35 U.S.C. § 313 AND 37 C.F.R. § 42.107
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`04841.00006/7042666.1
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`PROTECTIVE ORDER MATERIAL
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`Patent Owner Preliminary Response
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`IPR2015-01103
`Patent 6,045,501
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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 ................................................................................... 13
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`III. ARGUMENT ................................................................................................. 19
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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 Claims Are Obvious .......................................... 20
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`1.
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`CFAD’s Expert Declaration Is
`Entitled To “little or no weight” ............................................... 20
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`(a) Dr. Fudin Is Not A POSA ............................................... 20
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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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`3.
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`The Petition Fails To Address The Redundancy
`With The 1096, 1102 And 1103 Petitions ................................ 22
`
`Ground 1: The Claimed Inventions
`Would Not Have Been Obvious Over
`Mitchell, Dishman, and Cunningham ....................................... 24
`
`(a) CFAD Fails To Address Both the
`Claims and the Prior Art “As a Whole” ......................... 25
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`(b) CFAD Has Not Provided A Motivation To
`Combine Mitchell With Dishman or Cunningham ........ 26
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`(c)
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`The Ground 1 References Fail To
`Disclose, Teach, or Suggest
`Key Elements of the Claimed Inventions ....................... 32
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`i.
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`Claim 1 Would Not Have Been Obvious
`Over Mitchell, Dishman, And Cunningham ........ 32
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`1)
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`2)
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`3)
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`Element 1(c) ............................................... 32
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`Element 1(d) ............................................... 35
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`Element 1(e) ............................................... 35
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`ii.
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`Dependent Claims 2–27 Would Not Have
`Been Obvious Over Mitchell In View Of
`Dishman And The Knowledge Of A POSA ........ 38
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`1)
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`2)
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`3)
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`4)
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`5)
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`6)
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`7)
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`Claim 5 ....................................................... 39
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`Claim 6 ....................................................... 40
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`Claim 9 ....................................................... 41
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`Claim 10 ..................................................... 42
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`Claims 13, 14, 23-25 .................................. 42
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`Claim 17 ..................................................... 44
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`Claims 18 and 19 ....................................... 44
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`iii.
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`Independent Claim 28 And Dependent
`Claims 29–32 Would Not Have Been
`Obvious Over Mitchell In View Of Dishman
`In Further View Of Cunningham And
`Knowledge Of A POSA ....................................... 46
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`1)
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`2)
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`Claim 28 ..................................................... 47
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`Claims 29-32 .............................................. 47
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`4.
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`CFAD Fails To Address The Objective Evidence of
`Nonobviousness Regarding the ’720 Patent ............................. 49
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`(a)
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`Long-felt Need Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 49
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`(b) Commercial Success Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 51
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`(c)
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`Third-Party Praise And Awards Further Supports
`The Nonobviousness Of The Claimed Inventions ......... 52
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`(d) Licensing by Others Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 52
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`(e) Unexpected Results Further Supports The
`Nonobviousness Of The Claimed Inventions ................. 53
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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) ............................................... 54
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`The Petition Should Be Denied For
`Failing To Name All Real Parties-In-Interest ..................................... 57
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`IV. CONCLUSION .............................................................................................. 60
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`I.
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`INTRODUCTION
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`IPR2015-01103
`Patent 6,045,501
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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 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 are driven entirely by hindsight and supported only by conclusory
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`assertions by CFAD’s declarant, who merely parrots the arguments in the Petition.
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`There is also no rational basis for combining CFAD’s references, as they are
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`directed to different endeavors. For example, one of CFAD’s cited references,
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`Cunningham, is not related in any way to restricted drug distribution, assessing
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`risks associated with pharmaceuticals, or preventing the occurrence of adverse
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`events, let alone to teratogenic side effects. Ground 1 does not warrant an IPR trial
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`of the ’720 patent.
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`Third, 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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`Fourth and finally, the Petition should also be denied because it fails to
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`name all RPI—a threshold requirement for an IPR. Specifically omitted from the
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`RPI 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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`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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`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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`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 in the
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`original July 1998 Thalomid® package insert (“July 1998 Thalomid PI,” Ex. 2032).
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`The initial implementation of S.T.E.P.S.® only retrospectively identified patient
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`behaviors that posed a risk of fetal exposure to thalidomide. See Ex. 2006 at 328.
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`While this patented system was 100% successful in preventing birth defects of the
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`type associated with thalidomide in patients taking Thalomid®, Celgene (and the
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`inventors of the ’720 patent) still saw 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 that they
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`called Enhanced S.T.E.P.S.® See id. Specifically, from October 1999 to
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`September 2001, the inventors focused on implementing changes that were
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`“designed to identify patients exhibiting behaviours providing risk for fetal
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`exposure and to remedy those behaviours prior to dispensing thalidomide.” Id.
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`(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.® that is
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`conducted by the registered pharmacy consulting the computer readable
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`medium to retrieve a prescription approval code. 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 revisions to the “Storage and Dispensing”
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`section of the July 1998 Thalomid PI, which CFAD relies upon in IPR2015-01096:
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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. 1031 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. 1010 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 preventing birth defects. In fact, the
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`Mitchell reference that CFAD relies upon (Ex. 1010), discloses that there were
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`over 400 pregnancies that occurred during isotretinoin treatment, at least six of
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`which resulted in live born infants with at least minor anomalies, and at least one
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`with major anomalies. Id. at 103-04. Mitchell further reports that in the first
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`several months of the PPP, there was incomplete compliance with several parts of
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`the program, such as failures to ensure negative pregnancy tests before beginning
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`treatment, failures to wait until menses begins before treatment, and failures to use
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`effective birth control before, during, and after treatment. Id. at 104. Compliance
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`remained incomplete even after the manufacturer changed the medication package
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`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] program was implemented in 1989, a substantial number of fetuses have
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`been exposed to the drug. As many as 30 percent of the women with exposed
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`fetuses did not use any mode of contraception, even though they were cognizant of
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`the high fetal risk.” Ex. 2013 at 1130.
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`Clozaril® contains clozapine, and is used to treat schizophrenia. Ex. 1007 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 4, 8-9; Ex. 2016 at 1; and Ex. 2017 at 1.
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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; 1:13-16. The claims are set forth in
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`Jepson format, with a preamble comprising a general description of the known
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`elements of the claimed invention (which are claimed in the Elsayed ’501 patent,
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`and embodied in S.T.E.P.S.® and the July 1998 Thalomid PI), and the novel,
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`improved elements (which are embodied in Enhanced S.T.E.P.S.® and the
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`September 2001 Thalomid PI) set forth after the “improvement comprising”
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`clause. See 37 C.F.R. § 1.75(e) (describing the preferred format for claims to
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`improvements). For example, 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;
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`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 the occurrence of adverse side effects. See id. at
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`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 Elsayed ’501 patent, and concluded that it did not
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`disclose, teach, or suggest the ’720 patent’s inventions. Specifically, the Examiner
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`found that “Elsayed et al. teaches a method for delivering a drug to a patient while
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`preventing the exposure to a fetus or to other individuals with contraindications to
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`the drug that includes registering prescribers, pharmacists, and patients in a
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`computer readable storage medium for authorizing and monitoring distribution of
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`the drug,” but noted that Elsayed “does not teach a step of generating of a
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`prescription number or code, which can be retrieved by a pharmacy before said
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`prescription is filled.” Ex. 1002 at 0091 (emphasis added). In other words, the
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`Examiner concluded that the Elsayed ’501 patent disclosed only what was in the
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`preamble of the ’720 patent’s Jepson claims, but did not disclose, teach, or suggest
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`the claimed improvements, which were not implemented or publicly disclosed until
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`the September 2001 Thalomid PI.
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`With respect to the “approval code” limitation, the Examiner originally
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`rejected the claims over U.S. Patent No. 6,202,923 to Boyer (Ex. 1005), stating
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`that “Boyer et al, teaches a method of an automated pharmacy system (see
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`abstract) that improves prescription processing,” and that it would have been
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`obvious to “use an automated pharmacy arrangement as taught by Boyer et al.
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`which includes a step for generating a prescription number or code associated with
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`said prescription by a computer workstation.” Ex. 1002 at 0092. The ’720 patent’s
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`inventors overcame this rejection.
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`Specifically, the inventors explained that the automated prescription code in
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`Boyer was a number that was merely associated with every prescription, whereas
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`the prescription approval code of the ’720 patent was based on a risk assessment of
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`information collected from the patient, and was generated only if and when the risk
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`was deemed acceptable. The inventors noted that the claims required “an
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`affirmative decision” to be made before the prescription was filled, and Boyer did
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`not require such an approval code, nor did it require an approval code to be
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`generated before the prescription may be filled. Id. at 0106-07. In response to this
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`argument, the Examiner allowed all the claims of the ’720 patent.2
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`Here, CFAD relies on three references in its Petition to argue that “Claims 1-
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`32 are unpatentable under 35. U.S.C. § 103”: Mitchell (Ex. 1010), Dishman (Ex.
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`1007) and Cunningham (Ex. 1008). Pet. at 11. Mitchell and Cunningham do not
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`contain any new material, information, or disclosures that were not previously
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`considered by the Examiner during prosecution of the ’720 patent, and Dishman
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`does not disclose anything that is relevant to the claimed inventions.
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`Mitchell is a 1995 article that “report[s] the results of an ongoing survey
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`designed to assess compliance with” Accutane’s PPP, which was implemented in
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`an attempt to minimize pregnancies among women exposed to the drug
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`2 The Examiner’s first Office Action also indicated that Claims 28-32 were
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`allowable if written in independent form because “none of the prior art, either
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`alone or in combination, teaches or suggests a method for delivering a drug to a
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`patient while preventing exposure to a contraindicated individual that includes
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`screening for possible interaction between the drug and a second drug that has been
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`administrated to the subject.” Ex. 1002 at 0059.
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`isotretinoin. Ex. 1010 at 101. Dr. Allen Mitchell, who designed
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