Paper No. __
`Filed: February 12, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`________________
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`COALITION FOR AFFORDABLE DRUGS VI LLC
`Petitioner,
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`v.
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`CELGENE CORPORATION
`Patent Owner
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`________________
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`Case IPR2015-01102
`Patent 6,315,720
`________________
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`PATENT OWNER RESPONSE
`PURSUANT TO 35 U.S.C. § 313 AND 37 C.F.R. § 42.107
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`Filed: February 12, 2016
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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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`________________
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`COALITION FOR AFFORDABLE DRUGS VI LLC
`Petitioner,
`
`v.
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`CELGENE CORPORATION
`Patent Owner
`
`________________
`
`Case IPR2015-01102
`Patent 6,315,720
`________________
`
`PATENT OWNER 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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`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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`The history of thalidomide and the ’501 patent .................................... 3
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`B.
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`C.
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`By the filing date of the ’720 patent, the methods
`claimed in the ’501 patent had successfully
`prevented the predicted second thalidomide tragedy ............................ 4
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`Celgene conceived of Enhanced S.T.E.P.S.®
`based on confidential, nonpublic information ....................................... 5
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`III. CFAD HAS FAILED TO CARRY ITS BURDEN OF PROVING,
`BY A PREPONDERANCE OF THE EVIDENCE, THAT
`THE CLAIMED METHODS WOULD HAVE BEEN OBVIOUS ............... 9
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`A.
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`B.
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`C.
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`CFAD’s use of the wrong
`POSA dooms its obviousness analysis ................................................ 11
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`CFAD has failed to prove that there was a known need or
`problem to be solved at the time of the ’720 patent’s invention ......... 16
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`The asserted references do not disclose, teach, or
`suggest every element of the claimed inventions ................................ 20
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`1.
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`2.
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`Claim Construction ................................................................... 20
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`Scope and Content of the Prior Art ........................................... 24
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`(a)
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`Powell ............................................................................. 24
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`(b) Dishman .......................................................................... 26
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`(c) Cunningham .................................................................... 28
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`(d) Mundt .............................................................................. 31
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`(e) Mann, Vanchieri, Shinn, Linnarsson,
`Grönroos, Soyka, Hamera, Kosten, and Menill ............. 32
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`3.
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`Differences between the
`claimed inventions and the prior art ......................................... 33
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`(a)
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`Independent Claims 1 and 28 ......................................... 34
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`i.
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`ii.
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`Dishman would not have
`disclosed, taught, or suggested the
`claimed prescription approval code ..................... 34
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`The ’720 patent could not have
`disclosed, taught, or suggested the
`claimed prescription approval code ..................... 36
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`iii. Cunningham would not have
`disclosed, taught, or suggested the
`claimed prescription approval code ..................... 37
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`(b) Dependent Claims 2-27 and 29-32 ................................. 40
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`i.
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`ii.
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`Claims 5 and 6 ...................................................... 40
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`Claim 10 ............................................................... 47
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`iii. Claim 17 ............................................................... 48
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`D.
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`CFAD has failed to prove that a POSA would have been
`motivated to combine the asserted references ..................................... 51
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`1.
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`2.
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`3.
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`A POSA would not have been motivated to
`combine Cunningham, Dishman, and Powell ........................... 51
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`A POSA would not have been motivated to
`combine Mundt with Dishman or Powell ................................. 58
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`Applying Cunningham’s approval code
`was beyond the level of ordinary skill in the art ....................... 59
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`IV. CONCLUSION .............................................................................................. 60
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`Patent Owner Response
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`I.
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`INTRODUCTION
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`IPR2015-01102
`Patent 6,315,720
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`United States Patent No. 6,315,720 (the “’720 patent”) describes and claims
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`improved methods for delivering potentially dangerous drugs, such as teratogenic
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`drugs (in particular, thalidomide), to a patient while avoiding the occurrence of
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`side effects (such as thalidomide-related birth defects). Ex. 1001 at Claims. The
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`inventions were conceived as part of Celgene Corporation’s (“Celgene”) efforts to
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`improve its existing System for Thalidomide Education and Prescription Safety, or
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`S.T.E.P.S.®, which had been used to control patient access to Celgene’s Thalomid®
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`(thalidomide) drug product since it was approved by the U.S. Food and Drug
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`Administration (“FDA”) in July 1998. The original 1998 S.T.E.P.S.® program is
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`an embodiment of U.S. Patent No. 6,045,501 (the “’501 patent,” at issue in
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`IPR2015-01092). Celgene’s improved program—Enhanced S.T.E.P.S.®—is an
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`embodiment of the improved methods claimed in the ’720 patent.
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`Coalition for Affordable Drugs VI (“CFAD”) filed a petition for inter partes
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`review (“Petition” or “Pet.”) seeking cancelation of claims 1-32 of the ’720 patent.
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`The Board instituted trial on the only ground raised in the Petition—CFAD’s
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`assertion that claims 1-32 would have been obvious over Powell, Dishman,
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`Cunningham, Mundt, Mann, Vanchieri, Shinn, Linnarsson, Grönroos, Soyka,
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`Hamera, Kosten, and Menill. Paper 21 at 25. CFAD’s Petition lacks merit for
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`several reasons.
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`Patent Owner Response
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`IPR2015-01102
`Patent 6,315,720
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`First, CFAD conducted its obviousness analysis through the eyes of the
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`wrong person of ordinary skill in the art (“POSA”). Because obviousness must be
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`judged from the POSA’s viewpoint, and because CFAD’s POSA is improper,
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`CFAD’s arguments are deficient and fail as a matter of law.
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`Second, CFAD has failed to identify any known need or problem in the art at
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`the time that the ’720 patent was filed in October 2000. Without such an
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`identification, there is no reason to arrive at the claimed inventions and the claims
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`cannot have been obvious.
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`Third, CFAD has failed to prove that the asserted references would have
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`rendered the claimed inventions obvious because the references fail to disclose,
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`teach, or suggest each and every element of the claimed inventions.
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`Fourth, CFAD has failed to prove that a POSA would have been motivated
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`to combine the asserted references. As already noted, there was no problem to be
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`solved at the time of the ’720 patent’s invention and, therefore, no motivation to
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`combine the asserted references for that reason alone. Further, even if there had
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`been a problem to be solved, CFAD’s expert admitted that he chose to combine at
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`least Cunningham with the other asserted references because the ’720 patent claims
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`recite a “prescription approval code.” In other words, Dr. Fudin admitted that he
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`used the ’720 patent as a roadmap to arrive at the claimed methods. This
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`hindsight-driven analysis is impermissible and requires denial of the Petition.
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`In sum, CFAD has failed to prove, by a preponderance of the evidence, that
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`claims 1-32 of the ’720 patent would have been obvious over the asserted
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`references. Celgene respectfully requests that the Board reject the Petition and
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`confirm the patentability of claims 1-32.
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`II. BACKGROUND
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`A. The history of thalidomide and the ’501 patent
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`By 1998, thalidomide was a well-known teratogen. Ex. 2066; Ex. 2059 ¶19;
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`Ex. 2060 ¶18. Thalidomide had been marketed in Europe by Chemie Grünenthal
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`in the late 1950s and early 1960s as a sedative and a treatment for pregnant women
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`with morning sickness. Ex. 1001 at 1:39-45; Ex. 2002 at 1; Ex. 2059 ¶19; Ex.
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`2060 ¶18. Shortly after entering the European market, medical personnel realized
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`that thalidomide caused severe malformations in children of mothers who took the
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`drug during pregnancy, resulting in more than 10,000 birth defects. Id. CFAD’s
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`expert, Jeffrey Fudin, Pharm.D., described the thalidomide tragedy as an “absolute
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`disaster.” Ex. 2061 at 43:19-44:13. Fortunately, the FDA refused to approve
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`thalidomide in the early 1960s, preventing such a disaster in the United States. Ex.
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`2059 ¶19; Ex. 2060 ¶18; Ex. 2067.
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`Thalidomide remained unlawful in the United States until Celgene
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`introduced Thalomid® in 1998. Ex. 1031 at 0002-3; Ex. 2061 at 48:20-23. At that
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`time, FDA agreed to end its 40-year ban on thalidomide only on the explicit
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`condition that Thalomid® would be distributed under Celgene’s S.T.E.P.S.®
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`program. Ex. 2059 ¶20; Ex. 2060 ¶19. Indeed, the FDA’s approval letter states
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`that the “S.T.E.P.S.® restricted distribution program is an integral part of the
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`approved NDA for this product and is an essential component of the terms of this
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`NDA’s approval by FDA for marketing this product in the United States.” Ex.
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`1031 at 0003. Celgene claimed S.T.E.P.S.® in the ’501 patent. See, e.g., Ex. 2061
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`at 377:19-378:1.
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`B.
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`By the filing date of the ’720 patent, the methods
`claimed in the ’501 patent had successfully
`prevented the predicted second thalidomide tragedy
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`The ’720 patent was filed in October 2000. By that time, S.T.E.P.S.® had
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`proven 100% successful in preventing birth defects of the type associated with
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`thalidomide. Ex. 2059 ¶21; Ex. 2060 ¶20. In fact, not a single fetal exposure to
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`thalidomide had been reported to occur under the ’501 patent’s methods as of the
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`’720 patent’s October 2000 critical date.1
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`Instead, as Dr. Fudin admitted, as of October 2000, a POSA would have
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`known that S.T.E.P.S.® had avoided the second thalidomide tragedy that many had
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`1 During Dr. Fudin’s redirect deposition testimony, CFAD’s counsel introduced
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`new evidence published in 2010 that reported four worldwide fetal exposures to
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`thalidomide, but no birth defects. Ex. 1070 at 5. That article is not prior art.
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`predicted and thought inevitable before the FDA approved Thalomid® in 1998. Ex.
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`2061 at 380:6-14; see also id. at 380:15-18, 380:23-381:2, 381:18-21, 382:7-12,
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`455:11-15 (Dr. Fudin agreeing that nothing in the references he reviewed suggests
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`that S.T.E.P.S.® was not successful). Thus, as Dr. Fudin also admitted, no prior art
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`taught that there was a problem with S.T.E.P.S.® that needed to be addressed. Ex.
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`2061 at 380:19-22. Accordingly, as Dr. Fudin further admitted, there was no need
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`for the ’720 patent’s invention for any drug, and certainly not for thalidomide. Id.
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`at 2061 at 383:7-25. Celgene’s experts agree. Ex. 2059 ¶21-22; Ex. 2060 ¶20-21.2
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`C. Celgene conceived of Enhanced S.T.E.P.S.®
`based on confidential, nonpublic information
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`CFAD misunderstands and misrepresents the circumstances surrounding the
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`invention of the ’720 patent’s claimed methods. Specifically, CFAD argued that
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`“[t]he invention of the ’720 Patent was allegedly conceived in the context of the
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`FDA approval of thalidomide.” Pet. 4. This is false. Thalomid® was approved in
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`July 1998, more than two years before the ’720 patent was filed. Ex. 1031; Ex.
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`2059 ¶20; Ex. 2060 ¶19; Ex. 2061 at 376:16-377:17. The original S.T.E.P.S.®,
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`2 As discussed below, Dr. Fudin erroneously opined that Zeldis—which is not a
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`reference upon which the Board instituted trial in this proceeding—would have
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`motivated a POSA to come up with the ’720 patent’s inventions for drugs other
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`than thalidomide.
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`IPR2015-01 102
`Patent 6,315,720
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`which is claimed in the ’501 patent (Ex. 2061 at 377: 19-37821; Ex. 2059 ‘][24; Ex.
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`2060 ‘][19), was launched with Tha1omid® in July 1998. Ex. 1031 at 0002-3; Ex.
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`2061 at 70:20-71: 1. Enhanced S.T.E.P.S.®, which was not launched until
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`September of 2001, is claimed in the ’720 patent. Ex. 2008; Ex. 2009; Ex. 2061 at
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`377219-3782]; Ex. 2059 ‘][22; Ex. 2060 ‘][21. CFAD’s description of the ’720
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`patent’s conception is therefore incorrect.
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`Dr. Fudin could not think of any reason why, other than the ’720 patent
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`itself, a change was needed from S.T.E.P.S.® to Enhanced S.T.E.P.S.® Ex. 2061 at
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`71:21-72:5. That is because there was no problem to be solved. Dr. Fudin’s lack
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`of support for any motivation to arrive at the claimed methods, especially those
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`directed to teratogens and, in particular, thalidomide, is consistent with the prior
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`art. Indeed, S.T.E.P.S.® was 100% successful in preventing the predicted second
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`thalidomide tragedy. Thus, nothing in the prior art would have motivated a POSA
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`to arrive at the ’720 patent’s inventions. Ex. 2059 ‘][2l—22; Ex. 2060 ‘][20—2l.
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`Instead, the inventors of the ’720 patent—both Celgene employees—
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`conceived of the claimed improved methods using their confidential, nonpublic
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`knowledge regarding Celgene’s experience with S.T.E.P.S.
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` —
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` While S.T.E.P.S.® was 100% successful in
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`Patent Owner Response
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`IPR20l5-01 102
`Patent 6,315,720
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`preventing fetal exposure to thalidomide, the inventors saw room for significant
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`improvement based on their confidential knowledge. As the ’720 patent and its
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`file history make clear, improvements were made (in the form of the claimed
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`prescription approval code) to make the system and potential interventions more
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`proactive and prospective, and to simplify the S.T.E.P.S.® program’s demands on
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`the pharmacy. Specifically, as explained below, unlike Enhanced S.T.E.P.S.®,
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`which is claimed in the ’720 patent, the prior art discloses that the pharmacist in
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`original S.T.E.P.S.® was responsible for executing several critical components of
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`the program. See infra at § III.C.3.b.i. For example, the pharmacist was
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`responsible for verifying informed consent, registering the patient, and verifying
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`the patient’s registration and ability to receive thalidomide. Ex. 2062 at 1722; Ex.
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`1011 at 325; Ex. 2063; Ex. 2064; Ex. 2065.
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`Based on Celgene’s review of S.T.E.P.S.®
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`‘, improvements were made “to minimize and simplify the demands on the
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`pharmacy, thereby improving compliance with the system of distribution, and
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`reducing the risk that the drug will dispensed to a contraindicated individual.” Ex.
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`1001 at 28.12; Ex. 2059 <][22-23, 26; Ex. 2060 <][21—23m
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`The ’720 patent’s inventors effectuated these improvements through the use of the
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`claimed prescription approval code. Ex. 2059 ‘][27—28; Ex. 2060 ‘][24.
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`Patent Owner Response
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`IPR20l5-01 102
`Patent 6,315,720
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`As explained in greater detail below, the claimed prescription approval code
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`has a particular meaning within the ’720 patent. See infra at § III.C.l. During
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`prosecution, the applicants amended their claims to require a determination, based
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`upon risk—group assignment and information collected from the patient, regarding
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`whether the risk of the side effect occurring is acceptable. Ex. 1002 at 0085-88.
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`The applicants further amended the claims to require, upon determination that the
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`risk is acceptable, generation of a prescription approval code that must be retrieved
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`by the pharmacy before filling a prescription. Id.
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`Thus, as the ’720 patent explains, the pharmacy “need only retrieve the
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`approval code” to comply with the claimed methods. Ex. 1001 at 13:55-57; see
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`also Ex. 1002 at 0085 (“[W]hen the patient presents a prescription to the
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`pharmacy, all the registered pharmacy need do is consult the computer readable
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`storage medium, and the pharmacy is permitted to dispense the drug upon
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`successfully retrieving a prescription approval code therefrom.”). In other words,
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`the duties of verifying the informed consent and registering the patient were shifted
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`from the pharmacist (in S.T.E.P.S.®) to the prescriber (in Enhanced S.T.E.P.S.®).
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`Ex. 1001 at 13:55-65; Ex. 2059 ‘][23, 26-27; Ex. 2060 ‘][22-24.
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`Patent Owner Response
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` The change from S.T.E.P.S.® to Enhanced S.T.E.P.S.® made the risk
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`assessment more proactive and prospective.
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`The change also shifted duties
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`from the pharmacist to the prescriber, which led “to better compliance, and hence
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`decreased risk that the adverse side effects will occur.” Ex. 1001 at 10:35-40; see
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`also id. at 13:55-64; Ex. 2059 ¶22-23, 26; Ex. 2060 ¶22-23. Without Celgene’s
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`confidential, nonpublic knowledge of the inner workings of S.T.E.P.S.®—through
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`its own ongoing review and consultation with its vendors—the inventors would
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`have had no reason to conceive of Enhanced S.T.E.P.S.® and the ’720 patent.
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`III. CFAD HAS FAILED TO CARRY ITS BURDEN OF PROVING,
`BY A PREPONDERANCE OF THE EVIDENCE, THAT THE
`CLAIMED METHODS WOULD HAVE BEEN OBVIOUS
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`Obviousness is a legal question based on underlying facts, including: (1) the
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`level of ordinary skill in the art; (2) the scope and content of the prior art; and
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`(3) the differences between the claimed invention and the prior art. See Medichem,
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`S.A. v. Rolabo, S.L., 437 F.3d 1157, 1164 (Fed. Cir. 2006).
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`“In KSR, the Supreme Court noted that an invention may have been obvious
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`‘[w]hen there [was] . . . a design need or market pressure to solve a problem and
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`there [were] . . . a finite number of identified, predictable solutions.’” Eisai Co. v.
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`Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008) (quoting KSR, Int’l
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`Co. v. Teleflex, Inc, 550 U.S. 398, 402 (2007)). As such, “KSR assumes a starting
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`reference point or points in the art, prior to the time of the invention, from which a
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`skilled artisan might identify a problem and pursue potential solutions.” Id. Thus,
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`once the POSA has been determined, “the starting point for the obviousness
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`inquiry is the skilled artisan’s identification of a problem.” Janssen Pharms., Inc.
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`v. Watson Labs., Inc., No. 08-5103, 2012 WL 3990221, at *25 (D.N.J. Sept. 11,
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`2012). Without knowledge of a problem, a POSA would have no reason to arrive
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`at the claimed inventions, and they would not have been obvious. See Novartis
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`Pharms. Corp. v. Watson Labs., Inc., 611 Fed. Appx. 988, 995 (Fed. Cir. 2015).
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`If there is a known need or problem, then the Board must conduct “a
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`searching comparison of the claimed inventions—including all its limitations—
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`with the teachings of the prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir.
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`1995). The Federal Circuit has held that even if all of the claimed elements are
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`found in prior-art references, the obviousness analysis still requires evidence of a
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`motivation to combine the references to arrive at the claimed inventions. See
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`Medichem, 437 F.3d at 1164; see also KSR, 550 U.S. at 418 (“[T]here must be
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`some articulated reasoning with some rational underpinning to support the legal
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`conclusion of obviousness.”).
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`As explained below, the Petition must fail because CFAD has:
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`(1) conducted its analysis through the eyes of an inappropriate POSA; (2) failed to
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`prove that there was a known need or problem in the art at the time of the ’720
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`patent’s inventions; (3) failed to prove that the asserted references disclosed,
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`taught, or suggested every element of the claimed inventions; and (4) even if all
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`elements are disclosed, failed to prove that a POSA would have been motivated to
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`combine the asserted references.
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`A. CFAD’s use of the wrong POSA dooms its obviousness analysis
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`Obviousness must be judged from the viewpoint of a POSA at the time the
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`invention was made. Graham v. John Deere Co. of Kan. City, 383 U.S. 1, 3
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`(1966). CFAD has failed to define the correct POSA through whose eyes the
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`inventions in this case must be viewed. CFAD’s obviousness analysis is therefore
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`fatally flawed, and it has failed to carry its burden for this reason alone.
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`Non-exhaustive “[f]actors that may be considered in determining level of
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`ordinary skill in the art include: (1) the educational level of the inventor; (2) type
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`of problems encountered in the art; (3) prior art solutions to those problems;
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`(4) rapidity with which innovations are made; (5) sophistication of the technology;
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`and (6) educational level of active workers in the field.” Daiichi Sankyo Co. v.
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`Apotex, Inc., 501 F.3d 1254, 1256 (Fed. Cir. 2007).
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`The Petition did not offer any analysis of these or any similar factors.
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`Instead, CFAD relies solely on its purported expert’s unsupported, conclusory
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`assertion that the appropriate POSA is a pharmacist. Pet. 17. Specifically, Dr.
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`Fudin argued that POSA “would typically have either a Pharm. D. or a BS in
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`pharmacy with approximately 5-10 years of experience and a license to practice as
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`a registered pharmacist in any one or more of the United States.” Ex. 1027 ¶ 16.
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`Dr. Fudin testified that he arrived at his definition of a POSA by “Googl[ing] it,”
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`or going “back to a previous deposition and look[ing] at what [he] put down as a
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`POSA.” See Ex. 2061 at 161:17-163:12. For these reasons, and as explained
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`below, Dr. Fudin’s definition of a POSA is not supported by the Daiichi factors.
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`Celgene’s proposed POSA would have had at least a bachelor’s degree and
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`at least 2 years of experience in risk management relating to pharmaceutical drug
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`products, or a B.S. or M.S. in pharmaceutical drug product risk management or a
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`related field.3 Ex. 2059 ¶39. At the time, “risk management” would have included
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`3 Celgene offers the expert opinions of Lourdes Frau, M.D., whose opinions
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`respond to CFAD’s obviousness arguments through the eyes of Celgene’s POSA.
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`See generally Ex. 2059. In case the Board were to adopt CFAD’s POSA and/or to
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`fields such as safety surveillance, pharmacovigilance, or pharmacoepidemiology.
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`Id. Celgene’s proposal is supported by the Daiichi factors.
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`The inventors’ backgrounds and the problems they encountered in the art
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`support Celgene’s POSA. Neither of the inventors of the ’720 patent are
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`pharmacists. Ex. 2059 ¶46. Rather, they were Celgene employees who spent years
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`focusing on developing methods to control the distribution of a dangerous drug—
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`thalidomide—while avoiding side effects. See Ex. 1001 at 1:19-2:12. The Board
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`agreed that “the types of problems encountered by one of ordinary skill in the art
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`included creating a restricted drug distribution program to prevent adverse side
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`effects, such as teratogenic risks.” Paper 21 at 9.
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`This is the focus of the ’720 patent—avoiding adverse events associated
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`with drug products. Ex. 1001 at 1:8-16; Ex. 2059 ¶40-42. Dr. Fudin agreed. Ex.
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`2061 at 14:20-15:11, 16:3-7. Dr. Fudin also agreed that the ’720 patent has a
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`narrower focus than the broad realm of pharmaceutical prescriptions on which
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`pharmacists are focused. See id. at 16:20-25, 28:8-11. Despite this, Dr. Fudin
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`credit Dr. Fudin’s testimony, out of an abundance of caution, Celgene also offers
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`the expert opinions of Joseph DiPiro, Pharm. D. Dr. DiPiro offers no opinion on
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`the appropriate level of ordinary skill in the art, but responds directly to Dr.
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`Fudin’s opinions through the eyes of CFAD’s POSA. See generally Ex. 2060.
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`began his analysis of a POSA by referring to the relevant art as “pharmaceutical
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`prescriptions.” Ex. 1027 at ¶ 16. By ignoring the actual subject matter and focus
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`of the ’720 patent, and instead choosing to start with the exceedingly broad field of
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`“pharmaceutical prescriptions,” Dr. Fudin’s analysis was biased and unrelated to
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`the ’720 patent.
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`The education level of the active workers in the field also supports
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`Celgene’s POSA. As Dr. Frau explains, a POSA would have education or
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`experience focused on safety surveillance, pharmacovigilance, or
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`pharmacoepidemiology. Ex. 2059 ¶39, 47. For example, at the time of the ’720
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`patent, the active workers in the field would have had experience designing or
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`implementing risk management programs, or studying the impact and effectiveness
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`of such programs. Id. ¶39, 44-45, 47. These individuals would likely have been
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`employees of pharmaceutical companies that manufactured potentially dangerous
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`drugs—like the inventors of the ’720 patent—or would have had jobs in
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`government or academia that required them to focus on pharmaceutical risk
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`management. Id. ¶39. Dr. Fudin testified that his POSA would not need any such
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`experience. See 2061 at 171:15-21, 174:13-18. In fact, Dr. Fudin admitted that
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`CFAD’s POSA would not have been capable of designing or implementing the
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`claimed systems of the ’720 patent. See id. at 193:12-194:10, 201:1-10; 246:17-
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`247:2, 328:19-329:9. Dr. DiPiro agrees. Ex. 2060 ¶17.
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`Dr. Fudin testified that he disagreed with Celgene’s proposed POSA because
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`“none of those people actually have to work directly with patients or dispense
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`drugs, nor do they have experience dispensing drugs or working with real
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`patients.” Ex. 2061 at 183:25-184:16. But, as Dr. Fudin admitted, the ’720 patent
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`claims methods to distribute a drug subject to adverse events from start to finish,
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`i.e., from the manufacturer to the patient. Id. at 199:8-14.
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`Nevertheless, Dr. Fudin insisted that his POSA “doesn’t need to design [the
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`claimed] systems.” Id. at 199:8-200:9; see also id. at 201:1-10 (“Q. And they
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`[your pharmacist POSA] don’t need to know how to design the full system claimed
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`in the ’720 patent? A. No.”). Instead, Dr. Fudin testified that his pharmacist
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`POSA “needs to know how to use [the claimed] systems in real time. And they use
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`those systems.” Id. at 200:1-3; see also id. at 200:10-25 (“Pharmacists do not need
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`to know how to develop such programs. What they need to know is how to take
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`these programs and ensure patient safety.”). Dr. Fudin’s assertion is contrary to
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`law. The Federal Circuit has made clear that the POSA must be able to develop,
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`not simply use, the claimed inventions. See Daiichi, 501 F.3d at 1257 (noting that
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`the “level of ordinary skill . . . is that of a person engaged in developing” the
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`claimed inventions) (emphasis added).
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`In light of the foregoing, the Board should adopt Celgene’s proposed
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`definition of a POSA and reject Dr. Fudin’s misguided proposal. Further, because
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`CFAD’s obviousness analysis depends on Dr. Fudin’s erroneous POSA, its
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`analysis is improper and must be rejected. See Daiichi, 501 F.3d at 1256.
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`B. CFAD has failed to prove that there was a known need or
`problem to be solved at the time of the ’720 patent’s invention
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`The Federal Circuit has noted that without knowledge of a problem, a POSA
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`would have no reason to arrive at the claimed inventions and the inventions would
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`not have been obvious. See Novartis, 611 Fed. Appx. at 995. “Thus, the starting
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`point for the obviousness inquiry is the skilled artisan’s identification of a
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`problem.” Janssen, 2012 WL 3990221, at *25.
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`CFAD argued that a POSA would have been motivated to arrive at the
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`claimed methods because a POSA was allegedly “motivated to combine the
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`method for avoiding pregnancy with a computerized tracking system that only
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`permits filling prescriptions for the drug when certain conditions (e.g., non-
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`pregnancy) are met.” Pet. 14. But such methods were already known.
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`Indeed, in co-pending IPR2015-01096, CFAD admitted that “[a]n example
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`of this combination . . . is the System for Thalidomide Education and Prescribing
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`Safety (S.T.E.P.S.) [described in Zeldis].” See IPR2015-01096, Paper 1 at 14
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`(citing Zeldis, which is Ex. 1011 in this IPR). Zeldis discusses Celgene’s original
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`S.T.E.P.S.® program. S.T.E.P.S.® is an embodiment of Celgene’s ’501 patent. See,
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`e.g., Ex. 2061 at 377:19-378:1. Further, the reference that CFAD relied on for its
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`alleged motivation (see Pet. 14 (citing Ex. 1012)) came before S.T.E.P.S.® was
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`implemented in July 1998. CFAD has not identified any reason to modify or
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`improve upon S.T.E.P.S.®, which has proven to be effective from its launch in July
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`1998 up through (and after) the filing of the ’720 patent in October 2000. Ex. 2059
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`¶78; Ex. 2060 ¶25-28. Dr. Fudin agreed, and testified that S.T.E.P.S.® was 100%
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`successful in preventing the predicted second thalidomide tragedy at the time of
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`the ’720 patent’s invention. Ex. 2061 at 239:23-240:11, 380:6-381:2. Further,
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`CFAD’s cited references tout the success of S.T.E.P.S.® See, e.g., Ex. 2061 at
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`381:18-21, 455:11-15 (Dr. Fudin admitting that there is nothing in Zeldis to
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`suggest any problem with S.T.E.P.S.®). Thus, there would have been no
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`motivation to arrive at the ’720 patent’s claimed methods, especially claim 22,
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`which is specifically directed to thalidomide. Ex. 2059 ¶78, 82; Ex. 2060 ¶28.
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`Nevertheless, Dr. Fudin opined that Zeldis would have motivated a POSA to
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`come up with the ’720 patent’s inventions for drugs other than thalidomide. See,
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`e.g., Ex. 2061 at 381:3-15, 566:18-567:16, 591:15-592:9. Dr. Fudin’s opinion was
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`based on two disclosures from Zeldis. Both disclosures fail to supply a known
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`need or problem at the time of the ’720 patent’s invention. Ex. 2059 ¶82; Ex. 2060
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`¶29-32.
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`First, Dr. Fudin opined that, based on Zeldis’s discussion of isotretinoin and
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`clozapine, “somebody . . . may have taken initiative to try and improve
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`[S.T.E.P.S.®] to be all-inclusive.” Ex. 2061 at 381:3-15. But Dr. Fudin opined that
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`the existing distribution methods for isotretinoin and clozapine were already
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`successful. Id. at 209:14-24 (Dr. Fudin opining that the Accutane PPP was a
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`“tremendous success”), 235:15-236:9 (Dr. Fudin opining that it was “common
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`knowledge” that the clozapine distribution systems should be copied for
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`thalidomide). In fact, Dr. Fudin specifically testified that Zeldis confirmed the
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`success of those distribution methods. Id. at 565:10-566:17. Thus, Dr. Fudin’s
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`opinions are directly contradictory, and Zeldis fails to supply a POSA with any
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`reason to try to “improve” S.T.E.P.S.® to include isotretinoin and clozapine. Ex.
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`2059 ¶82; Ex. 2060 ¶29-30.
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`Second, Dr. Fudin opined (Ex. 2061 at 565:10-567:16) that Zeldis would
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`have motivated a POSA to “embellish” S.T.E.P.S.® based on the following:
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`Future cases are certain to arise in which a drug offers compelling
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`clinical benefits, but unrestricted distribution proposes profound risks
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`to patients or society. It is hoped that the S.T.E.P.S.™ program will
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`provide a model for resolving this recurring dilemma.
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`Ex. 1011 at 329. Dr. Fudin admitted, however, that a POSA would only
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`“embellish [S.T.E.P.S.] if it needs to be embellished.” Ex. 2061 at 566:18-567:16
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`(emphasis added). Celgene’s experts agree. Ex. 2059 ¶78; Ex. 2060 ¶29. Dr.
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`Fudin and CFAD have not provided any reason why S.T.E.P.S.® would have
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`needed to be embellished as of the ’720 patent’s critical date. Instead, Dr. Fudin
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`could only speculate about “future drugs” that “might” require modifying
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`S.T.E.P.S.® In other words, Dr. Fudin admitted that, at the time of the ’720
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`patent’s invention, there was no reason to modify S.T.E.P.S.®, and a POSA would
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`not have known what changes, if any, needed to be made to the original
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`S.T.E.P.S.® prog
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