Filed: April 22, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`————————————————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`————————————————
`
`MYLAN PHARMACEUTICALS INC. and
`AMNEAL PHARMACEUTICALS LLC
`
`Petitioners,
`
`v.
`
`YEDA RESEARCH & DEVELOPMENT CO. LTD.
`
`Patent Owner.
`
`————————————————
`
`Case No. IPR2015-00643 (8,232,250 B2)
`Case No. IPR2015-00644 (8,399,413 B2)
` Case No. IPR2015-00830 (8,969,302 B2)1,2
`————————————————
`
`PETITIONERS’ OPPOSITION TO PATENT OWNER’S
`MOTION TO EXCLUDE
`
`
`1 Case Nos. IPR2015-01976, IPR2015-01980 and IPR2015-01981 have been
`
`joined with these proceedings.
`
`2 A word-for-word identical Opposition is being filed in each proceeding.
`
`

`
`TABLE OF CONTENTS
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 1
`
`INTRODUCTION ......................................................................................... .. 1
`
`THE BOARD SHOULD CONSIDER KHAN 2009 (EX. 1068 AND
`THE BOARD SHOULD CONSIDER KHAN 2009 (EX. 1068 AND
`1089) ................................................................................................................ 3
`1089) .............................................................................................................. -3
`
`III.
`
`THE BOARD SHOULD CONSIDER TEVA’S SHARED
`
`III. THE BOARD SHOULD CONSIDER TEVA’S SHARED
`SOLUTIONS WEBSITE (EX. 1086) .............................................................. 6
`SOLUTIONS WEBSITE (EX. 1086) ............................................................ ..6
`
`IV.
`
`THE BOARD SHOULD CONSIDER THE LEBANO ARTICLE
`
`IV. THE BOARD SHOULD CONSIDER THE LEBANO ARTICLE
`(EX. 1098) ....................................................................................................... 7
`(EX. 1098) ..................................................................................................... ..7
`
`V.
`
`THE BOARD SHOULD CONSIDER THE WOLINSKY
`
`THE BOARD SHOULD CONSIDER THE WOLINSKY
`TRANSCRIPT (EX. 1140) .............................................................................. 8
`TRANSCRIPT (EX. 1140) ............................................................................ ..8
`
`A.
`
`A.
`
`B.
`
`B.
`
`C.
`
`C.
`
`D.
`D.
`
`PATENT OWNER FAILED TO PRESERVE ITS OBJECTIONS TO THE
`
`PATENT OWNER FAILED TO PRESERVE ITS OBJECTIONS TO THE
`WOLINSKY TRANSCRIPT (EX. 1140) ........................................................ 9
`WOLINSKY TRANSCRIPT (EX. 1 140) ...................................................... ..9
`
`PATENT OWNER NEGLECTED ITS DUTY OF CANDOR BY NOT
`
`PATENT OWNER NEGLECTED ITS DUTY OF CANDOR BY NOT
`INFORMING THE BOARD OF THE WOLINSKY TRANSCRIPT (EX.
`INFORMING THE BOARD OF THE WOLINSKY TRANSCRIPT (EX.
`1140) .................................................................................................... 10
`1140) .................................................................................................. .. 10
`
`PATENT OWNER IMPROPERLY MAINTAINED
`
`PATENT OWNER IMPROPERLY MAINTAINED
`CONFIDENTIALITY OF THE WOLINSKY TRANSCRIPT (EX. 1140) ........... 13
`CONFIDENTIALITY OF THE WOLINSKY TRANSCRIPT (EX. 1 140) ......... .. 13
`
`THE WOLINSKY TRANSCRIPT (EX. 1140) IS RESPONSIVE TO
`THE WOLINSKY TRANSCRIPT (EX. 1140) IS RESPONSIVE TO
`PATENT OWNER’S QUESTIONING OF DR. GREEN .................................. 14
`PATENT OwNER’S QUESTIONING OF DR. GREEN ................................ .. 14
`
`VI. CONCLUSION .............................................................................................. 15
`
`CONCLUSION ............................................................................................ .. 15
`
`VI.
`
`
`
`
`
`i
`
`
`
`

`
`TABLE OF AUTHORITIES
`
`CASES
`Plant Genetic Sys., N.V. v. DeKalb Genetics Corp.,
`315 F.3d 1335 (Fed. Cir. 2003) ...................................................................... 8
`
`Syntex LLC v. Apotex, Inc.,
`407 F. 3d 1371 (Fed. Cir. 2005) .................................................................. 5, 6
`
`RULES
`
`37 C.F.R. § 42.11 ..................................................................................................... 10
`
`37 C.F.R. § 42.51 ..................................................................................................... 10
`
`37 C.F.R. § 42.64 ..................................................................................................... 10
`
`
`
`
`
`ii
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`

`
`I.
`
`INTRODUCTION
`
`The three patents at issue relate to a 40 mg dose of glatiramer acetate
`
`(“GA”) administered as few as three times per week. Since 1997, Patent Owner
`
`marketed a 20 mg GA product that required daily injections. From day one, the
`
`daily injections of Copaxone 20 mg were a problem. They caused injection site
`
`reactions and patients simply did not like daily administration. The problem
`
`became particularly acute as competitor products entered the market with less
`
`frequent dosing schedules. For years before the claimed August 2009 priority date,
`
`skilled artisans investigated dosing protocols that sought to address the well-known
`
`problems of daily administration of Copaxone 20 mg. The body of prior art gave
`
`the skilled artisan ample motivation to look to less frequent dosing schedules and
`
`to specifically believe a 40 mg three-times-per week schedule would be safe and
`
`efficacious. Patent Owner now seeks to exclude evidence that reinforces
`
`Petitioners’ positions. The motion has no merit.
`
`In its Motion, Patent Owner seeks to exclude five relevant references:
`
`Exhibits 1068, 1086, 1089, 1098 and 1140. Khan 2009 (Ex. 1068 and 1089), a
`
`clinical abstract published in 2009, reflects work that began no later than two years
`
`earlier in 2007. This work supports Petitioners’ evidence that skilled artisans were
`
`motivated to investigate less-than-daily GA dosing regimens.
`
`Teva’s patient-directed website (Ex. 1086) instructs patients that they may
`
`1
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`

`
`
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`skip a dose of Copaxone if they forget to take a daily injection. This instruction is
`
`not new, and the website cites no post-priority date clinical data in support. As Dr.
`
`Green testified, and as other unchallenged documentary evidence shows, skilled
`
`artisans have told patients to skip a missed dose for years.
`
`LeBano (Ex. 1098) establishes that even as of 2012, conventional techniques
`
`could not routinely evaluate gray matter pathology. This is proper evidence that as
`
`of August 2009, skilled artisans could not easily evaluate gray matter atrophy.
`
`The Wolinsky Transcript (Ex. 1140) is an excerpt from the deposition
`
`testimony of Dr. Jerry Wolinsky, the principal investigator on Teva GA clinical
`
`trials (including one relied on in these proceedings by Patent Owner) and a
`
`physician who qualifies as one of the world’s most knowledgeable about GA. Dr.
`
`Wolinsky testified that he prescribed Copaxone 20 mg GA on an every-other-day
`
`basis long before the August 20, 2009 priority date to combat injection site
`
`reactions in patients. That Dr. Wolinsky prescribed GA less frequently than daily
`
`for the purpose of reducing injection site reactions is powerful evidence that skilled
`
`artisans were interested in (and were indeed using) GA on a less than daily basis.
`
`Dr. Wolinsky’s testimony also flatly contradicts Patent Owner’s remarkable
`
`argument that skilled artisans would have expected fewer GA injections to increase
`
`injection site reactions. Patent Owner not only failed to disclose Dr. Wolinsky’s
`
`testimony to the Board, but they constructed roadblocks to try to prevent
`
`2
`
`

`
`
`
`Petitioners from doing so. Patent Owner’s current effort to exclude this evidence
`
`by blaming Petitioners for failing to timely submit the evidence simply fails.
`
`None of Patent Owner’s bases to exclude evidence have merit. The Board
`
`should consider all the aforementioned evidence, and deny Patent Owner’s motion.
`
`II. THE BOARD SHOULD CONSIDER KHAN 2009
`AND 1089)
`
`(EX. 1068
`
`Patent Owner seeks to exclude an article published by Omar Khan, Ex. 1068
`
`and 1089 (“Khan 2009”).3 Dr. Khan is a frequent publisher on clinical aspects of
`
`GA. See, e.g., Ex. 1010. Khan 2009 is an abstract published by Dr. Khan along
`
`with seven other experienced MS researchers in the prominent journal Multiple
`
`Sclerosis. Patent Owner’s objection appears to be that Khan 2009 is a post-priority
`
`abstract. Indeed, Khan 2009 was published a few weeks after the claimed priority
`
`date. However, Khan 2009 is highly probative of the direction the prior art was
`
`pushing skilled artisans just before the priority date.
`
`Khan 2009 is an abstract published in 2009 that plainly and unambiguously
`
`reflects clinical work begun more than 2 years earlier. Khan 2009 describes a
`
`study to compare the clinical outcomes of patients taking Copaxone 20 mg daily
`
`versus Copaxone 20 mg administered just twice per week. Ex. 1068 at 1-2. The
`
`clinical study called for administering Copaxone 20 mg to patients for at least two
`
`
`3 Exhibit 1068 and 1089 are the same document.
`
`3
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`

`
`years. Ex. 1068 at 2. Khan 2009 reports actual clinical data after the two-year
`
`study. Ex. 1068 at 2. The multi-year study concluded:
`
`
`
`This study provides further evidence that GA administered less
`frequently than daily may be as efficacious and better tolerated than
`GA administered daily. This may have a significant impact on
`improving compliance and tolerability while maintaining the desired
`immunomodulating effect of GA. Furthermore, this may also have a
`favorable economic
`impact.
` Larger, multi-center studies are
`warranted to confirm our findings and address a critical need of the
`MS patient community.
`
`Ex. 1068 at 2 (emphasis added).
`
`Khan 2009 unambiguously reflects that at least two years prior to its
`
`publication—and well before the August 20, 2009 priority date of the patents at
`
`issue—experienced clinical researchers familiar with GA were motivated to
`
`investigate dosing of GA on a less-than-daily basis, specifically, just two times per
`
`week. There is no dispute that Omar Khan and the seven other researchers began
`
`the clinical trial and treated patients with Copaxone 20 mg twice per week prior to
`
`August 20, 2009.
`
`That clinical researchers were conducting clinical trials (and Institutional
`
`Review Boards were approving the trials) of less than daily administration of GA
`
`well before the priority date refutes Patent Owner’s argument that the pre-2009
`
`clinical art taught away from the less-than-daily administration of GA. See Ex.
`
`4
`
`

`
`
`
`1085 at ¶ 32. By contrast, Patent Owner cites not a single clinical trial where
`
`physicians investigated more-frequent-than-daily administration of GA. The art
`
`was entirely directed to less-frequent-than-daily administration of GA. Khan
`
`2009—evidence of skilled artisans’ motivation in 2006-2007—reinforces that
`
`point.
`
`That Khan 2009 is published after August 20, 2009 is of no moment. There
`
`is no absolute requirement that a reference have a publication date prior to the
`
`claimed priority date. The Federal Circuit’s decision in Syntex LLC v. Apotex, Inc.
`
`is particularly instructive. 407 F. 3d 1371, 1379 (Fed. Cir. 2005). In that case, the
`
`Federal Circuit held that the district court erred in finding that a certain compound,
`
`octoxynol 40, was not used in pharmaceuticals prior to its use in the patented
`
`invention. In Syntex, a reference published five days after the priority date
`
`established that octoxynol 40 was a well-known ingredient in pharmaceutical
`
`products. Although Syntex, the patent owner, contended that because the reference
`
`was published five days after the priority date it disclosed no prior uses of
`
`octoxynol 40, the Federal Circuit found “it incredulous that octoxynol 40 could
`
`progress from no use, to ‘well known . . . in pharmaceutical products’ in a matter
`
`of five days.” Id. The Federal Circuit therefore held that the reference “reflects
`
`that the use of octoxynol 40 in pharmaceutical compositions was known in the art
`
`at the relevant time, an important fact to consider in assessing the obviousness of
`
`5
`
`

`
`
`
`the claims in suit.” Id.
`
`Just as in Syntex, the Board may look at post-priority evidence reflecting the
`
`earlier state of the art. Petitioners do not rely on the post-priority published results
`
`in Khan 2009, i.e., the information not available prior to August 20, 2009. Instead,
`
`Petitioners rely on Khan 2009’s irrefutable teaching that skilled artisans were
`
`motivated to conduct clinical research on less-than-daily administration of GA and
`
`were in fact doing so. Accordingly, Khan 2009 (Ex. 1068, 1089) should not be
`
`excluded.
`
`III. THE BOARD SHOULD CONSIDER TEVA’S SHARED SOLUTIONS
`WEBSITE (EX. 1086)
`
`Exhibit 1086 is a page from Teva’s patient-directed website informing
`
`patients that if they miss a dose of GA, they should skip the dose: “If you miss a
`
`dose, take your COPAXONE® as soon as you remember. If it is nearer to the time
`
`of your next scheduled dose, skip the missed dose and resume your usual dosing
`
`schedule.” Ex. 1086 at 2. Patent Owner objects to the exhibit as being dated after
`
`the claimed priority date.
`
`Although the website is dated after the claimed priority date,4 it serves to
`
`corroborate Dr. Green’s testimony that GA was long known to be a forgiving drug.
`
`See, e.g., Ex. 1004 ¶ 33; Ex. 1085 ¶ 19. The Copaxone website also affirms the
`
`4
`There is no suggestion by Patent Owner that some intervening clinical study
`
`changed the known state of the art with respect to missed doses of Copaxone.
`
`6
`
`

`
`
`
`prior art teachings cited by Dr. Green in his opening declaration, including the
`
`prior art teaching that, for daily Copaxone, “[i]f you miss a dose, take it as soon as
`
`you remember. If you do not remember until the following day, skip the missed
`
`dose and continue with your regular dosing schedule.” Ex. 1004 ¶ 33, citing Ex.
`
`1058. Exhibit 1086, Teva’s own patient-directed website, is consistent with and
`
`corroborates the prior art teachings and Dr. Green’s testimony that GA is a
`
`forgiving drug that allows for doses to be missed or skipped. Exhibit 1086 should
`
`not be excluded.
`
`IV. THE BOARD SHOULD CONSIDER THE LEBANO ARTICLE
`(EX. 1098)
`
`In his reply declaration, Dr. Green disagreed with Dr. Fox on whether skilled
`
`artisans would have expected gray matter atrophy to be reduced with the
`
`administration of GA. Ex. 1085 ¶¶ 94-96. As Dr. Green opined, it is irrelevant
`
`that a certain reference found for the first time that GA reduced gray matter
`
`atrophy. Ex. 1085 ¶ 96 (discussing Ex. 2094). Skilled artisans in 2009 knew that
`
`GA likely reduced brain atrophy, and they expected that GA likely reduced gray
`
`matter atrophy in particular. Id. ¶ 94. Because the technology needed to
`
`efficiently study gray matter atrophy was newly emerging, it would have been
`
`“expensive and difficult” to study gray matter atrophy in a multicenter clinical trial
`
`before the priority date. Id. ¶ 96. Dr. Green cites LeBano (Ex. 1098), the disputed
`
`reference, for the proposition that “conventional MRI techniques almost entirely
`
`7
`
`

`
`
`
`overlook gray matter pathology . . . . [G]ray matter lesions are still difficult to
`
`measure and not discernable using traditional MRI . . . .” (emphasis added).
`
`Because gray matter lesions remained difficult to detect as of its 2012 publication
`
`date, the Lebano reference is relevant to whether this was the case prior to 2009.
`
`For Patent Owner’s argument to be correct, the state of the art must have regressed
`
`such that gray matter lesions could have been efficiently studied in 2009, but not in
`
`2012. That assertion belies logic. LeBano (Ex. 1098) teaches that conventional
`
`techniques overlooked gray matter pathology—a point not refuted by Patent
`
`Owner—even as late as 2012. That teaching is probative of the techniques
`
`available to skilled artisans to investigate gray matter pathology three years earlier
`
`in 2009. Cf. Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335,
`
`1344 (Fed. Cir. 2003) (allowing the use of post-priority art to show that certain
`
`techniques were not known earlier in time). LeBano (Ex. 1098) should not be
`
`excluded.5
`
`SHOULD CONSIDER THE WOLINSKY
`V. THE BOARD
`TRANSCRIPT (EX. 1140)
`
`Exhibit 1140 (“the Wolinsky Transcript”) is an excerpt from the deposition
`
`transcript of Dr. Jerry Wolinsky, a medical doctor and principal investigator on
`
`several Teva clinical trials, including the GLACIER study relied on by Patent
`
`5
`Patent Owner has not moved to exclude Dr. Green’s testimony on the same
`
`point. See Ex. 1085 at ¶ 96.
`
`8
`
`

`
`
`
`Owner in these proceedings. Ex. 1140 at 38:15-17. The deposition was taken in
`
`the district court litigation involving the same patents at issue before the Board.
`
`Dr. Wolinksy was represented by Patent Owner’s counsel. Dr. Wolinsky was
`
`chosen as the GLACIER principal investigator because of his “expertise and
`
`involvement with the development of copolymer and COPAXONE over quite a
`
`long time.” Ex. 1140 at 42:15-17. Indeed, Dr. Wolinsky believes few others in the
`
`world have comparable experience. Ex. 1140 at 42:18-44-4.
`
`There is no basis to exclude the Wolinsky Transcript (Ex. 1140) as outside
`
`the scope of Petitioners’ reply evidence or the cross examination questioning of
`
`Petitioner’s expert witness Dr. Green. The Wolinsky Transcript was properly
`
`introduced on redirect and need not be submitted as supplemental evidence.
`
`A.
`
`PATENT OWNER FAILED TO PRESERVE ITS OBJECTIONS
`TO THE WOLINSKY TRANSCRIPT (EX. 1140)
`
`When the Wolinsky Transcript was introduced on re-direct in Dr. Green’s
`
`deposition, the only objections made by Patent Owner were “I want to object to
`
`this document being offered. It’s not part of the record in this proceeding. So I
`
`just object to any testimony on the document.” Ex. 1142 at 396:6-10. Patent
`
`Owner later objected on the basis that “this is not the kind of evidence that you can
`
`bring an IPR on. It’s not proper evidence in this proceeding.” Ex. 1142 at 399:5-8.
`
`Patent Owner did not object to the Wolinsky Transcript as outside the scope
`
`of Petitioners’ reply, of the cross examination of Dr. Green, or for failure to seek
`
`9
`
`

`
`
`
`leave under 37 C.F.R. § 42.123, the grounds it now moves on.6 Motion (Paper 67)
`
`at 9. As Patent Owner failed to make the objections on which it now moves during
`
`Dr. Green’s deposition, these objections are waived. 37 C.F.R. § 42.64(a) (“An
`
`objection to the admissibility of deposition evidence must be made during the
`
`deposition.”).
`
`B.
`
`PATENT OWNER NEGLECTED ITS DUTY OF CANDOR BY
`NOT INFORMING THE BOARD OF THE WOLINSKY
`TRANSCRIPT (EX. 1140)
`
`Patent Owner has a duty of candor to submit information to the Board
`
`inconsistent with its position. 37 C.F.R. § 42.11 (“Parties and individuals involved
`
`in the proceeding have a duty of candor and good faith to the Office during the
`
`course of a proceeding.”); 37 C.F.R. § 42.51 (b)(1)(iii) (“Unless previously served,
`
`a party must serve relevant information that is inconsistent with a position
`
`advanced by the party during the proceeding concurrent with the filing of the
`
`documents or things that contains the inconsistency….”).
`
`Dr. Wolinsky’s testimony is inconsistent with positions taken by Patent
`
`Owner in its Response. See, e.g., Response (Paper 26) at 7 n.1, 9, 15-16, 22-26,
`
`29-31, 54 (arguing
`
`that
`
`the prior art
`
`taught away from
`
`less-than-daily
`
`
`6 While Patent Owner did object to some of the re-direct questioning of Dr.
`
`Green as outside of the scope of the cross examination, this objection was not
`
`made with respect to the exhibit Patent Owner now seeks to exclude.
`
`10
`
`

`
`
`
`administration of GA). In his deposition, Dr. Wolinsky testified:
`
`Q. Have you ever prescribed COPAXONE 20 mgs for use three
`times a week?
`A. Yes.
`Q. And when did you do that?
`A.
`I’ve been doing that for a number of years for patients who are
`doing extremely well on the drug but are having trouble with
`injection site problems.
`Q. And did you do that prior to 2005?
`A.
`Probably. Actually, I should correct myself. I’m sorry. You
`said three times a week. Alternate day would be correct.
`
`Ex. 1140 at 64:25-65:13. In addition, Dr. Wolinsky testified that he would not
`
`have prescribed Copaxone for every other day administration if he believed that
`
`reducing the frequency of GA injections would increase the frequency of injection
`
`site reactions:
`
`Q. And you said that at least as of 2005, you were occasionally
`prescribing COPAXONE 20 milligram every other day to some
`patients who were having particular problems with injection-
`site reactions. Correct?
`A.
`Correct.
`Q. And I take it from that at least at that time you expected that
`injecting glatiramer acetate
`less frequently would
`likely
`decrease the number of injection-site reactions that a patient
`experiences. Is that fair to say?
`
`11
`
`

`
`
`
`A.
`
`Q.
`
`The answer is that these invariably were patients with
`significant problems with usually
`lipoatrophy, getting
`increasingly injection weary and doing extremely well on the
`drug. So they all were a very select group of patients, perhaps
`what one might call super-responders and – but having
`difficulty handling the drug.
`Q. Because of injection site reactions?
`A.
`Because of the problems with the many years of injections and
`a perhaps tendency to lipoatrophy.
`So you—it was your hope, at least, and your expectation that by
`counseling them to inject every other day rather than daily they
`might experience fewer
`injection site reactions or
`less
`lipoatrophy?
`A. At least they would be able to continue on the drug by virtue of
`injecting themselves less, less often.
`Q. And you certainly wouldn’t have encouraged them to inject less
`frequently if you thought that doing so would increase the
`frequency of their injection-site reactions, correct?
`A. Of course not.
`
`Id. at 222:18-224:14. Dr. Wolinsky’s testimony directly refutes Patent Owner’s
`
`position that skilled artisans were fearful of less-than-daily administration of GA
`
`because less frequent injections would lead to more frequent injection site
`
`reactions. Quite to the contrary, skilled artisans were, in fact, conducting human
`
`clinical trials on and even prescribing less-than-daily administration of GA before
`
`the priority date in order to improve tolerability and patient compliance. Patent
`
`12
`
`

`
`
`
`Owner was obligated to bring Dr. Wolinsky’s testimony to the Board’s attention
`
`but failed to do so.
`
`C.
`
`MAINTAINED
`IMPROPERLY
`OWNER
`PATENT
`CONFIDENTIALITY OF THE WOLINSKY TRANSCRIPT
`(EX. 1140)
`
`The now-unredacted testimony in the Wolinsky Transcript (Ex. 1140)
`
`should never have been designated confidential. As Patent Owner eventually
`
`conceded, it contains nothing confidential or proprietary. Nonetheless, Patent
`
`Owner maintained the Wolinsky Transcript as confidential until well after
`
`Petitioners’ reply evidence was submitted thereby preventing its disclosure to the
`
`Board.
`
`During the deposition of Dr. Wolinsky, Patent Owner’s counsel over-
`
`designated the entire transcript as outside counsel eyes only under the Protective
`
`Order in the parallel district court proceedings. Petitioners promptly sought to
`
`have the portions of the transcript shown in Exhibit 1140 correctly designated as
`
`non-confidential. Ex. 1143. On March 7, Patent Owner finally responded, stating
`
`“we confirm that Plaintiffs have marked the deposition transcript[] of Dr. Jerry
`
`Wolinsky . . . as outside counsel eyes only under the protective order because [his]
`
`testimony pertained to confidential proprietary research and development activity
`
`conducted by Teva.” Ex. 1144. Any reading of the now-public portions of the
`
`Wolinsky Transcript makes clear that the testimony in Exhibit 1140 was plainly
`
`13
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`

`
`
`
`not confidential. After a series of meet and confers, on March 30, 2016, Patent
`
`Owner finally relented and agreed that Dr. Wolinsky’s testimony was not
`
`confidential. Ex. 1145. Had Patent Owner not used the District Court’s protective
`
`order as a shield to prevent highly relevant information from being brought to the
`
`Board’s attention, the Wolinsky Transcript would have been part of Petitioners’
`
`reply evidence.
`
`D. THE WOLINSKY TRANSCRIPT (EX. 1140) IS RESPONSIVE
`TO PATENT OWNER’S QUESTIONING OF DR. GREEN
`
`During cross examination, Patent Owner asked Dr. Green whether the
`
`efficacy of GA is dependent not just on dose, but also on frequency of
`
`administration. See, e.g., Ex. 1142 at 302:24-303:2 (“Q. And in 2009, what is your
`
`opinion about how frequently a person of skill in the art would have thought they
`
`could space doses of GA and still achieve efficacy?”); see also id. at 301:24-302:2;
`
`302:15-17. He was asked about the suggestions in the art to administer GA 20 mg
`
`three times per week. Ex. 1142 at 305:5-7; see also Ex. 1142 at 303:14-15;
`
`304:15-17; 305:24-306:5; 306:14-17. The Wolinsky Transcript bears directly on
`
`these questions.
`
`The Wolinsky Transcript establishes what Petitioners and Dr. Green have
`
`contended from the outset: patients and physicians, including Dr. Wolinsky, one of
`
`the most experienced physicians with GA therapy in the world, understood that
`
`injection site reactions were a concern with daily administration of GA and that
`
`14
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`

`
`
`
`skilled artisans were motivated to, and in fact did, remedy this problem by
`
`reducing the frequency of injections. See, e.g., Petition (Paper 2) at 38, Reply
`
`(Paper 58) at 3-7. And the Wolinsky Transcript refutes wholly the Patent Owner’s
`
`notion (see Response (Paper 26) at 7 n.1, 9, 15-16, 22-26, 29-31, 54) that skilled
`
`artisans were taught away from dosing GA less frequently, whether due to an
`
`uncertain GA mechanism of action or an unsubstantiated7 histamine theory, or any
`
`other theory Patent Owner may concoct.
`
`The Wolinsky Transcript and the limited redirect questioning on the
`
`transcript are plainly responsive to whether skilled artisans believed that less
`
`frequent administration of GA would be safe and efficacious.
`
`VI. CONCLUSION
`For the reasons set forth above, Petitioners oppose Patent Owner’s motion to
`
`exclude exhibits 1068, 1086, 1089, 1098 and 1140.
`
`
`7
`Patent Owner’s suggestion that injection site reactions are caused by
`
`histamine release is not believable. Patent Owner has offered no evidence that
`
`physicians used anti-histamines to prevent ISRs in patients or any evidence that
`
`Teva—the manufacturer of Copaxone—ever instructed patients to
`
`co-administer an antihistamine with GA therapy. See Ex. 1142 at 380:10-25.
`
`15
`
`

`
`Dated: April 22, 2016
`
`
`
`
`
`
`
`/Brandon M. White/
`Brandon M. White
`Reg. No. 52,354
`Perkins Coie LLP
`700 13th St., NW, Suite 600
`Washington, D.C. 20005
`Telephone: (202) 654-6206
`E-mail: bmwhite@perkinscoie.com
`
`Attorney for Mylan Pharmaceuticals Inc.
`
`16
`
`

`
`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that the foregoing Petitioners’ Opposition
`
`to Patent Owner’s Motion to Exclude was served electronically via email as
`
`follows:
`
`Patent Owners:
`
`Elizabeth Holland
`Goodwin Procter LLP
`eholland@goodwinprocter.com
`
`William James
`Goodwin Procter LLP
`wjames@goodwinprocter.com
`
`Eleanor Yost
`Goodwin Procter LLP
`eyost@goodwinprocter.com
`
`Petitioner Amneal Pharmaceuticals LLC:
`
`
`Nicholas Mitrokostas
`Goodwin Procter LLP
`nmitrokostas@goodwinprocter.com
`
`Daryl Wiesen
`Goodwin Procter LLP
`dwiesen@goodwinprocter.com
`
`John Bennett
`Goodwin Procter LLP
`jbennett@goodwinprocter.com
`
`Vincent L. Capuano
`Duane Morris LLC
`VCapuano@duanemorris.com
`
`Christopher S. Kroon
`Duane Morris LLC
`CSKroon@duanemorris.com
`
`
`Dated: April 22, 2016
`
`
`
`/Brandon M. White/
`Brandon M. White
`
`Attorney for Mylan Pharmaceuticals Inc.
`
`
`
`1