`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`YEDA RESEARCH AND DEVELOPMENT CO.,
`LTD.,
`Appellant
`
`v.
`
`MYLAN PHARMACEUTICALS INC., AMNEAL
`PHARMACEUTICALS LLC,
`Appellees
`______________________
`
`2017-1594, 2017-1595, 2017-1596
`______________________
`
`Appeals from the United States Patent and
`Trademark Office, Patent Trial and Appeal Board in
`Nos.
`IPR2015-00643,
`IPR2015-00644,
`IPR2015-
`00830, IPR2015-01976, IPR2015-01980, IPR2015-
`01981.
`
`______________________
`
`Decided: October 12, 2018
`______________________
`
` WILLIAM M. JAY, Goodwin Procter LLP, Washing-
`ton, DC, argued for appellant. Also represented by
`WILLIAM G. JAMES, II; ELIZABETH HOLLAND, New
`York, NY; DARYL L. WIESEN, Boston, MA; JOHN C.
`O'QUINN, Kirkland & Ellis LLP, Washington, DC;
`LESLIE M. SCHMIDT, New York, NY.
`
`
`
`
`
`2
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
` DAVID LEE ANSTAETT, Perkins Coie, LLP, Madi-
`son, WI, argued for appellees. Appellee Mylan Phar-
`maceuticals Inc. also represented by SHANNON
`BLOODWORTH, ROBERT SWANSON, BRANDON MICHAEL
`WHITE, Washington, DC; DAN L. BAGATELL, Hanover,
`NH; CHRISTINA JORDAN MCCULLOUGH, Seattle, WA.
`
`ANTHONY JAMES FITZPATRICK, Duane Morris LLP,
`
`Boston, MA, for appellee Amneal Pharmaceuticals
`LLC.
` Also represented by VINCENT CAPUANO,
`CHRISTOPHER S. KROON; PATRICK GALLAGHER, Boca
`Raton, FL.
`
`______________________
`
`Before REYNA, BRYSON, and STOLL, Circuit Judg-
`es.
`
`REYNA, Circuit Judge.
`In this consolidated appeal, Appellant Yeda Re-
`search & Development Co., Ltd. challenges the Patent
`Trial and Appeal Board’s final written decisions
`finding the claims of U.S. Patent Nos. 8,232,250,
`8,399,413, and 8,969,302 unpatentable as obvious in
`three inter partes review proceedings. We affirm the
`Board’s decisions.1
`
`
`1
`In a companion case decided today, Teva
`Pharmaceuticals USA, Inc. v. Sandoz Inc., No. 17-
`1575 (Fed. Cir. Oct. 12, 2018), Teva Pharmaceuticals
`USA, Inc., Teva Pharmaceutical Industries, Ltd.,
`Teva Neuroscience, Inc., and Yeda Research and
`Development Co., Ltd., appeal the decision of the
`United States District Court for the District of Dela-
`ware invalidating all asserted claims of U.S. Patent
`Nos. 8,232,250, 8,399,413, 8,969,302, and 9,155,776.
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`3
`
`BACKGROUND
`I. Patents at Issue
`Yeda Research and Development Co., Ltd.
`(“Yeda”)
`is the assignee of U.S. Patents Nos.
`8,232,250, 8,399,413, and 8,969,302 (the ’250, ’413,
`and ’302 patents, respectively), all entitled “Low
`Frequency Glatiramer Acetate Therapy.” The pa-
`tents, collectively referred to as the “Copaxone pa-
`tents,” share a common specification and claim
`priority to the same two provisional applications. See
`J.A. 267, 279, 291. The earliest priority date of the
`Copaxone patents is August 20, 2009. Id.
`The Copaxone patents describe and claim
`COPAXONE® 40mg/mL, a treatment for relapsing-
`remitting multiple sclerosis (“RRMS”). RRMS is a
`form of multiple sclerosis, an autoimmune disorder
`that causes the body’s immune system to attack the
`central nervous system. RRMS is characterized by
`unpredictable relapses followed by periods of remis-
`sion with no new signs of disease activity.
`The active ingredient in COPAXONE® 40mg/mL
`is glatiramer acetate (“GA”), a synthetic mixture of
`polypeptides. GA is also known as “copolymer 1” or
`“Cop. 1.” COPAXONE® 40mg/mL is supplied as a
`single-dose prefilled syringe. Broadly, the treatment
`consists of the injection of 40mg of GA three times a
`week, abbreviated “40mg GA 3x/week.” Relevant to
`this appeal, side effects of GA injections include
`injection-site reactions (“ISRs”) and immediate post-
`injection reactions (“IPIRs”). ISRs are physical symp-
`toms at the injection site, such as swelling or itchi-
`ness. IPIRs are reactions immediately following an
`injection, such as flushes, sweating, or palpitations.
`Prior to COPAXONE® 40mg/mL, in 1996 the Food
`and Drug Administration
`(“FDA”)
`approved
`
`
`
`
`4
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`COPAXONE® 20mg/mL, a regimen consisting of the
`daily injection of 20mg GA. Daily GA injections were
`known to subject patients to discomfort, including
`side effects in the form of ISRs and IPIRs. J.A. 6956.
`For analyzing the obviousness of the Copaxone
`patents, a key limitation of the claims is the admin-
`istration of a 40mg GA dose in three subcutaneous
`injections over seven days. Claim 1 of the ’250 patent
`is representative:
`1. A method of alleviating a symptom of re-
`lapsing-remitting multiple sclerosis in a hu-
`man patient
`suffering
`from
`relapsing-
`remitting multiple sclerosis or a patient who
`has experienced a first clinical episode and is
`determined to be at high risk of developing
`clinically definite multiple sclerosis compris-
`ing administering to the human patient a
`therapeutically effective regimen of three sub-
`cutaneous injections of a 40 mg dose of glati-
`ramer acetate over a period of seven days with
`at least one day between every subcutaneous
`injection, the regimen being sufficient to alle-
`viate the symptom of the patient.
`’250 patent col. 16 ll. 35–45.
`Certain claims of the ’250 and ’413 patents fur-
`ther require improved tolerability and/or reduced
`frequency of injection reactions in the claimed regi-
`men as compared to 20mg daily. ’250 patent col. 17 l.
`24–col. 18 l. 6; ’413 patent col. 16 ll. 51–54.
`Apart from claim 1 of the ’302 patent, all inde-
`pendent claims require at least one day between
`doses. ’250 patent col. 16 ll. 35–45, col. 17 l. 25–col.
`18 l. 6, col. 18 ll. 19–26; ’413 patent col. 16 ll. 26–36,
`col. 18 ll. 1–13, col. 18 ll. 14–28; ’302 patent col. 17 ll.
`4–12. Claim 1 of the ’302 patent does not specify any
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`5
`
`particular interval between doses, but dependent
`claims 4 and 5 limit injections to certain combinations
`of days of the week, all with at least one day between
`injections, and independent claim 10 of the ’302
`patent requires that the injection be administered
`“three times per week with at least one day between
`every subcutaneous injection.” ’302 patent col. 16 ll.
`37–41, col. 16 ll. 47–58, col. 17 ll. 4–12.
`II. Prior Art References
`The first clinical trial for using GA to treat multi-
`ple sclerosis was in 1987 by Dr. Bornstein et al.
`(“Bornstein”),2 which was followed later by a Teva
`Phase III clinical trial in 1995. Both Bornstein and
`the Phase III trial tested 20mg GA daily. J.A. 7279–
`80, 7282–85, 6895–7235. The 20mg/day dose was
`selected without performing conventional optimal-
`dose-finding studies. J.A. 7239.
`The Bornstein study showed that GA adminis-
`tered subcutaneously for two years at a daily dose of
`20mg “produced clinically important and statistically
`significant beneficial effects.” J.A. 7284. Participants
`in both Bornstein and the Phase III trial reported
`ISRs and IPIRs as side effects. J.A. 7284, 6934. The
`Phase III trial noted “adverse experience” as the main
`reason contributing to patient dropout, and “[t]he
`most common adverse event associated with dropout
`was injection site reaction.” J.A. 6934. A Phase III
`trial reviewer made recommendations for future
`researchers to explore dose-response and dose-
`ranging studies, asking “Is 20 mg the optimum dose?
`Are daily injections necessary?” J.A. 6956.
`
`
`2 Murray B. Bornstein et al., A Pilot Trial of
`COP 1 in Exacerbating-Remitting Multiple Sclerosis,
`317 New Eng. J. Med. 408, 408–14 (1987).
`
`
`
`
`6
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`In 1996, following both Bornstein and the Phase
`III clinical trial, FDA approved Teva’s New Drug
`Application (“NDA”) for COPAXONE® 20mg, 20mg
`GA injected daily. In its 1996 Summary Basis of
`Approval (“SBOA”), the FDA recommended that Teva
`“evaluate the necessity of daily [GA] injections as
`opposed to more infrequent intermittent administra-
`tion of the drug” because the daily dosing regimen
`“seems like it would subject the patient to an exces-
`sive amount of discomfort if it is not necessary to
`maintain efficacy.” J.A. 7146.
`A 2002 study by Flechter et al.3 (“Flechter”) eval-
`uated the treatment of RRMS with 20mg of GA ad-
`ministered every other day. J.A. 7236–40. Flechter
`concluded that “alternate-day treatment with Copol-
`ymer 1 is safe, well tolerated, and probably as effec-
`tive as daily Copolymer 1 in reducing relapse rate and
`slowing neurologic deterioration.” J.A. 7240. Flecht-
`er also noted that patient dropout rates decreased
`when GA was administered every other day as op-
`posed to daily. J.A. 7240 (“It should be stressed that
`the dropout rate was lower in the alternate-day group
`than in the daily-injection regime (39.7% versus
`60.3%, p < 0.01).”).
`A prior art patent application, International Pa-
`tent Application No. WO 2007/081975, Method of
`Treating Multiple Sclerosis (“Pinchasi”), was pub-
`lished in 2007. J.A. 6857–88. Pinchasi discloses a
`40mg GA, every other day dosing regimen for the
`treatment of RRMS. Pinchasi cites to the data from
`
`3 Shlomo Flechter et al., Copolymer 1 (Glati-
`ramer Acetate) in Relapsing Forms of Multiple Sclero-
`sis: Open Multicenter Study of Alternate-Day
`Administration, 25 Clinical Neuropharmacology 11,
`11–15 (2002).
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`7
`
`Cohen, another GA study, to conclude that “[t]he
`increased efficacy observed with 40 mg/day GA in
`reducing MRI-measured disease activity and relapse
`rate indicates that it is well tolerated and can im-
`prove the treatment of RRMS patients. The im-
`provement in efficacy, however, is not accompanied by
`a corresponding increase of adverse reactions which
`would be expected upon a doubling of the adminis-
`tered dose.” J.A. 6876.
`III. State of the Art Reference
`There is an additional reference relevant to this
`appeal, a 2009 study by Omar Khan4 (“Khan 2009”).
`J.A. 9331–32. Khan 2009 was published three weeks
`after August 20, 2009, the priority date of the assert-
`ed patents, and thus does not qualify as statutory
`prior art, but the study began two years earlier. J.A.
`9331–32. The study abstract noted that “[t]here is
`considerable interest in studying a more patient
`friendly dosing regimen of GA that may be as effica-
`cious and better tolerated than daily GA.” J.A. 9331.
`Following the results of an earlier study, Khan 2008,
`showing that alternate day administration of GA
`appears to be as effective as daily administration,
`Khan 2009 compared 20mg GA administered twice a
`week to 20mg GA administered daily in a pilot, pro-
`spective, randomized, and rater-blinded two-year
`study. J.A. 9331; see infra note 8.
`
`
`4 O. Khan et al., Glatiramer Acetate 20mg Sub-
`cutaneous Twice-Weekly Versus Daily Injections:
`Results of a Pilot, Prospective, Randomised, and
`Rater-Blinded Clinical and MRI 2-Year Study in
`Relapsing-Remitting Multiple Sclerosis, 15 Multiple
`Sclerosis S249, S249–50 (2009).
`
`
`
`
`8
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`IV. Proceedings before the Board
`Mylan Pharmaceuticals, Inc. (“Mylan”) filed peti-
`tions for inter partes review (“IPR”) in IPR2015-
`00643, IPR2015-00644, and IPR2015-00830, challeng-
`ing all claims of the ’250, ’413, and ’302 patents,
`respectively, on grounds pursuant to 35 U.S.C. §§ 102
`and 103. The Patent Trial and Appeal Board (the
`“Board”) instituted review of all claims of the Copax-
`one patents on two grounds: obviousness over
`Pinchasi in view of FDA’s 1996 SBOA, and over
`Pinchasi in view of Flechter.5 J.A. 644 (instituting
`
`
`5
`In each of its Institution Decisions, the Board
`instituted on all claims but less than all grounds
`petitioned. See J.A. 644, 1720–21, 2710–11. The
`Supreme Court held in SAS Institute Inc. v. Iancu
`that if the Director institutes IPR proceedings, the
`Board’s review must proceed “‘[i]n accordance with’ or
`‘in conformance to’ the petition,” including “‘each
`claim challenged’ and ‘the grounds on which the
`challenge to each claim is based.’” 138 S. Ct. 1348,
`1355–56 (2018) (alteration in original). Post-SAS,
`this court has held that remand to the Board can be
`appropriate to consider non-instituted grounds as well
`as non-instituted claims. See BioDelivery Scis. Int’l,
`Inc. v. Aquestive Therapeutics, Inc., 898 F.3d 1205,
`1208 (Fed. Cir. 2018) (collecting cases).
`At oral argument, Mylan stated that it did not
`seek remand on the grounds of partial institution in
`light of the Supreme Court’s decision in SAS. Oral
`Arg. at 6:12–7:05 (May 1, 2018), available at
`http://oralarguments.cafc.uscourts.gov/default.aspx?fl
`=2017-1594.mp3. In the absence of a request for
`relief on the basis of SAS, we are not sua sponte
`obliged to act on the SAS error in this case. See PGS
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`9
`
`IPR on the ’250 patent), 1720–21 (’413 patent), 2710–
`11 (’302 patent). Subsequently, Amneal Pharmaceu-
`ticals LLC filed for each patent substantially identical
`petitions to those already filed by Mylan, and moved
`to join Mylan’s proceedings. The Board subsequently
`consolidated Amneal Pharmaceuticals’ petitions with
`those already filed by Mylan. J.A. 894–898, 1970–74,
`3489–95. Amneal Pharmaceuticals and Mylan are
`collectively referred to as “Petitioners.”
`The Board’s analysis of the independent claims
`was similar for all three patents. The Board first
`noted that Pinchasi discloses every limitation of the
`independent claims of the Copaxone patents, except
`for the dosing regimen of three doses per seven day
`period. The Board found that a person of ordinary
`skill in the art (“POSITA”) would have been motivat-
`ed to use a 40mg dose, crediting the testimony of
`Petitioners’ expert, Dr. Green, who noted that
`Pinchasi demonstrated increased efficacy of 40mg GA
`compared to 20mg with no significant difference in
`side effects, and citing Cohen,6 a study which con-
`
`
`Geophysical AS v. Iancu, 891 F.3d 1354, 1362–63
`(Fed. Cir. 2018).
`6 J.A. Cohen et al., Randomized, Double-Blind,
`Dose-Comparison Study of Glatiramer Acetate in
`Relapsing-Remitting MS, 68 Neurology 939, 939–44
`(2007).
`Cohen, published in 2007, was a “Randomized,
`double-blind, dose-comparison study of glatiramer
`acetate in relapsing-remitting MS.” J.A. 6889–94.
`Cohen compared daily subcutaneous injections of
`20mg and 40mg GA dosages, and concluded that the
`40mg dose may be “more effective” than the 20mg
`dose “in reducing MRI activity and clinical relapses.”
`J.A. 6889. Cohen also noted that the onset of action
`
`
`
`
`10
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`cluded that daily administration of 40mg GA was
`effective, safe, and well tolerated. In reaching this
`finding, the Board also found that FORTE,7 a phase
`III clinical trial comparing 40mg GA and 20mg GA,
`would not have taught away from using 40mg because
`it did not criticize, discredit, or discourage the 40mg
`GA dose.
`The Board next considered whether there was a
`motivation to modify Pinchasi’s 40mg every other day
`
`
`of the 40mg dose is more rapid compared to 20mg.
`J.A. 6894. ISRs were the most frequent adverse event
`for both doses, occurring at roughly equal rates. J.A.
`6892–93. IPIRs occurred more frequently in the 40mg
`group than the 20mg group. J.A. 6892–93. Cohen
`thus concluded that the overall safety and side effect
`profile of the 40mg GA dose was “similar” to the 20mg
`dose, but “was associated with a greater incidence of
`certain adverse effects.” J.A. 6894.
`7 Giancarlo Comi, Jeffrey A. Cohen, Massimo
`Filippi for the FORTE Study Group, Results from a
`Phase III, One-Year, Randomized, Double-Blind,
`Parallel-Group, Dose-Comparison Study with Glati-
`ramer Acetate in Relapsing-Remitting Multiple Scle-
`rosis, 14 Multiple Sclerosis S299, S299–S301 (2008);
`J.A. 11532–40.
`The FORTE study evaluated the safety, tolerabil-
`ity, and efficacy of 40mg GA compared to 20mg GA,
`and concluded that there are “[n]o significant differ-
`ences in efficacy measures between GA 20mg and GA
`40mg,” and that the 40mg dose has a “[g]ood safety
`and tolerability profile” with “no unexpected adverse
`effect with the high dose.” J.A 11532–40. FORTE
`also confirmed a finding from an earlier study, Cohen,
`that the 40mg dose provides an earlier onset of action.
`J.A. 11540.
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`11
`
`regimen. The Board noted that the difference be-
`tween the challenged claims (6 doses over 2 weeks)
`and Pinchasi (7 doses over 2 weeks) was only one less
`injection every two weeks. The Board then found
`motivation to eliminate one injection every other
`week to increase patient compliance, relying in part
`on Petitioners’ expert Dr. Green, who testified that
`decreasing the frequency of injections helps with
`patient adherence to a treatment regimen, and FDA’s
`1996 SBOA, which recommended that the necessity of
`daily injections, as opposed to less frequent admin-
`istration, be evaluated. The Board further relied on
`other prior art references, including Flechter, Khan
`2008,8 and Caon,9 which showed that alternate-day
`
`8 Omar Khan et al., Randomized, Prospective,
`Rater-Blinded, Four-Year, Pilot Study to Compare the
`Effect of Daily Versus Every-Other-Day Glatiramer
`Acetate 20 Mg Subcutaneous Injections in Relapsing-
`Remitting Multiple Sclerosis, 14 Multiple Sclerosis
`S296, S296 (2008).
`This 2008 study by Omar Khan and others (“Khan
`2008”) compared the effect of daily versus every other
`day administration of 20mg GA subcutaneous injec-
`tions for the treatment of RRMS. J.A. 7252. The
`study abstract noted that although the recommended
`dose for treating RRMS is daily 20mg GA injections,
`“the optimal dose remains unknown” and there is
`“considerable interest in alternate dosing regimens of
`GA” because daily injections “can be challenging for
`long-term patient compliance.” J.A. 7252. Thirty
`patients were randomly assigned to receive 20mg GA
`dosed daily or every other day. After two years, there
`were “no differences” between the two groups in
`relapse rate or disease progression. J.A. 7252. Addi-
`tionally, after the first two years elapsed, patients in
`each group were given the option to continue or
`
`
`
`
`12
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`dosing of 20mg was safe, well-tolerated, as effective as
`daily 20mg, reduced injection reactions, and that
`patients in the daily-injection group preferred less
`frequent dosing. The Board also found Khan 2009
`probative of the fact that POSITAs were motivated to
`investigate dosing regimens of GA with fewer injec-
`tions to improve patient compliance.
`Having found a motivation in the prior art to pur-
`sue a less frequent dosing regimen, the Board found
`that a POSITA would have a reasonable expectation
`of success in administering 40mg GA three times per
`week in light of testimony that GA was “a forgiving
`drug,” and that combining a 40mg dose with three-
`times-a-week administration produced a weekly dose
`virtually identical to the FDA-approved regimen of
`20mg GA daily. The Board then concluded that, in
`light of the evidence presented, a POSITA would have
`had a reason to modify Pinchasi’s dosing regimen of
`40mg GA every other day to 40mg GA 3x/week, thus
`
`
`switch groups, and were monitored for an additional
`two years. Every patient in the daily group opted to
`switch to every other day administration. After four
`years, there was no difference between the crossover
`group and the group that was always dosed every
`other day.
`9 Christina Caon et al., Randomized, Prospec-
`tive, Rater-Blinded, Four Year Pilot Study to Compare
`the Effect of Daily Versus Every Other Day Glatiramer
`Acetate 20 mg Subcutaneous Injections in RRMS, 72
`Neurology (Suppl. 3) A317 (2009).
`The Caon reference, published in 2009, reports
`the same data from the Khan 2008 study, but further
`noted that “[i]njection related lipoatrophy was signifi-
`cantly less” in the every other day group. J.A. 7253.
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`13
`
`limitation
`
`rendering the claimed 40mg 3x/week
`obvious.
`The Board also considered additional limitations
`for each patent, including limitations requiring im-
`proved tolerability, reduced frequency of adverse
`reactions, and specific injection schedules, and also
`found them obvious in light of the prior art. With
`regard to the objective indicia of nonobviousness, the
`Board concluded that the objective indicia were
`insufficient to overcome the primary findings of
`obviousness. And finally, for similar but less detailed
`reasons as for Pinchasi/SBOA, the Board concluded
`that the claims are unpatentable over the combina-
`tion of Pinchasi and Flechter.
`Yeda moved for rehearing. The Board issued re-
`vised final written decisions that reached the same
`results. Mylan Pharm. Inc. v. Yeda Research & Dev.
`Co., IPR2015-00643, No. 90, at 40 (P.T.A.B. Dec. 2,
`2016) (“’250 patent FWD”); Mylan Pharm. Inc. v. Yeda
`Research & Dev. Co., IPR2015-00644, No. 91, at 41
`(P.T.A.B. Dec. 2, 2016) (“’413 patent FWD”); Mylan
`Pharm. Inc. v. Yeda Research & Dev. Co., IPR2015-
`00830, No. 85, at 37 (P.T.A.B. Dec. 2, 2016) (“’302
`patent FWD”). Yeda appeals the Board’s reliance on
`Khan 2009 and its obviousness decisions. We have
`jurisdiction pursuant to 28 U.S.C. § 1295(a)(4)(A).
`DISCUSSION
`We review decisions of the Board under the
`standard of the Administrative Procedure Act (APA).
`Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316,
`1323 (Fed. Cir. 2017). We hold unlawful and set aside
`the actions of the Board if they are “not in accordance
`with law” or “unsupported by substantial evidence.” 5
`U.S.C. § 706.
`
`
`
`
`14
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`I. Khan 2009
`Yeda contends that its due process rights and the
`APA were violated because it did not have notice of,
`and an opportunity to respond to, Khan 2009. Yeda
`also argues that the Board violated 35 U.S.C. § 311(b)
`by relying on Khan 2009, which does not qualify as
`statutory prior art.
`Khan 2009 was first introduced as part of the re-
`ply declaration of Dr. Green, Petitioners’ expert. In
`its patent owner response, Yeda had argued that, as
`of the priority date, a POSITA would have believed
`that more frequent than daily administrations of GA
`would have been the best way to enhance efficacy.
`J.A. 758. In his reply declaration, Dr. Green respond-
`ed that “[n]umerous prior art references suggested
`further investigation of less frequent dosing regimens
`prior to 2009.” J.A. 9529 ¶ 29. After citing other
`prior art references, namely the SBOA, Flechter,
`Khan 2008, and Caon, Dr. Green discussed Khan
`2009, noting that “before the priority date, POSAs
`had completed a clinical trial investigating 20 mg
`administered twice weekly, for a total weekly dose of
`only 40 mg.” J.A. 9532 ¶ 32. Dr. Green concluded
`that “the Khan 2009 reference demonstrates that—
`counter to what Patent Owner claims—POSAs were
`motivated before the priority date to explore less
`frequent alternative dosing regimens.” J.A. 9532–33
`¶ 32.
`We first consider whether Yeda’s due process
`rights were violated. “[T]he introduction of new
`evidence in the course of the trial is to be expected in
`inter partes review trial proceedings and, as long as
`the opposing party is given notice of the evidence and
`an opportunity to respond to it, the introduction of
`such evidence is perfectly permissible under the
`APA.” Genzyme Therapeutic Prods. LP v. Biomarin
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`15
`
`Pharm. Inc., 825 F.3d 1360, 1366 (Fed. Cir. 2016).
`Here, Yeda received notice of Khan 2009 in Dr.
`Green’s reply declaration, attached to Petitioners’
`reply. Yeda deposed Dr. Green after receiving his
`reply declaration; he discussed Khan 2009 in that
`deposition and was questioned about it. J.A. 11164–
`65, 11176–79. Yeda also moved to exclude Khan 2009
`as irrelevant, which the Board denied. J.A. 1153–54;
`see also ’250 patent FWD, at 35–36. Yeda could have,
`but did not, address Khan 2009 at the oral hearing or
`seek leave to file a surreply to substantively respond
`to Khan 2009, as encouraged by our precedent. See
`Genzyme, 825 F.3d at 1368.
`Based on this record, Yeda received proper notice
`of and an opportunity to respond to Khan 2009—an
`opportunity Yeda took advantage of when it moved to
`exclude the study. But Yeda contends that it had no
`notice that the Board “might rely extensively” on
`Khan 2009 and make it “an essential part of its
`obviousness analysis.” Appellant’s Reply Br. 27.
`Thus, although Yeda frames its argument as being
`about due process, it really only challenges the
`Board’s use of Khan 2009.
`In its final written decisions, the Board acknowl-
`edged that Khan 2009 does not qualify as statutory
`prior art, but because the study began two years
`before the priority date of the Copaxone patents, the
`Board concluded that Khan 2009 is “probative of the
`fact that those skilled in the art were motivated to
`investigate dosing regimens of GA with fewer injec-
`tions to improve patient compliance.” ’250 patent
`FWD, at 15; see also ’413 patent FWD, at 17; ’302
`patent FWD, at 16. With one exception, discussed
`below, the Board’s use of Khan 2009 falls squarely
`within this stated purpose of providing evidence of the
`motivation of a POSITA to explore less frequent
`dosing regimens as of the priority date. See ’250
`
`
`
`
`16
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`patent FWD, at 15, 18, 36; ’413 patent FWD, at 16–17,
`19; ’302 patent FWD, at 16, 18.
`Yeda contends that the Board relied on Khan
`2009 to supplement gaps in the prior art in violation
`of 35 U.S.C. § 311(b). Section 311(b) provides that the
`Board may consider the patentability of challenged
`claims “only on the basis of prior art consisting of
`patents or printed publications.” We note that, before
`the Board, Yeda only sought to exclude Khan 2009 on
`the ground that it was irrelevant, and thus its argu-
`ment regarding § 311(b) is arguably waived. J.A.
`1153–54. However, § 311(b) is unrelated to the ques-
`tion of whether the Board’s reliance on Khan 2009
`was proper. While Khan 2009 indisputably does not
`qualify as prior art, § 311(b) only addresses prior art
`and is silent on the question of other evidence. The
`question before us, therefore, is whether the Board
`may consider non-prior art evidence, such as Khan
`2009, in considering the knowledge, motivations, and
`expectations of a POSITA regarding the prior art.
`Based on the statutory scheme, the PTO’s own
`regulations, and prior Board decisions, the Board can
`rely on evidence other than just prior art. The statute
`permits IPR petitioners to rely on evidence beyond
`the asserted prior art. Section 312(a)(3) of Title 35
`specifies that a petition should include both “copies of
`patents and printed publications that the petitioner
`relies upon,” and “affidavits or declarations of sup-
`porting evidence and opinions.” So do the regulations.
`See 37 C.F.R. § 42.104(b) (describing the content of
`the petition, including both “the patents or printed
`publications relied upon for each ground,” and “sup-
`porting evidence relied upon to support the chal-
`lenge”). The Board has recognized that non-prior art
`evidence of what was known “cannot be applied,
`independently, as teachings separately combinable”
`with other prior art, but “can be relied on for their
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`17
`
`proper supporting roles, e.g., indicating the level of
`ordinary skill in the art, what certain terms would
`mean to one with ordinary skill in the art, and how
`one with ordinary skill in the art would have under-
`stood a prior art disclosure.” Dominion Dealer Sols.,
`LLC v. AutoAlert, Inc., IPR2014-00684, 2014 WL
`5035359, at *5 (P.T.A.B. Oct. 6, 2014).
`In this regard, Dr. Green’s reliance on Khan 2009
`is permissible, as it supports and explains his position
`that a POSITA would have thought less frequent
`dosing worthy of investigation as of the priority date.
`We note that Dr. Green also relied on multiple prior
`art references—namely the SBOA, Flechter, Khan
`2008, and Caon—in support of this opinion. J.A. 9532
`¶ 32. With one exception, the Board’s use of Khan
`2009 is in line with Dr. Green’s narrow interpreta-
`tion, and does not constitute error. See ’250 patent
`FWD, at 15 (“Khan 2009 is probative of the fact that
`those skilled in the art were motivated to investigate
`dosing regimens of GA with fewer injections to im-
`prove patient compliance.”); id. (“Khan 2009 con-
`cludes: ‘This study provides further evidence that GA
`administered less frequently than daily may be as
`efficacious and better tolerated than GA administered
`daily.’” (emphasis added)); id. at 18 (mentioning Khan
`2009 as one of many studies of less frequent dosing,
`undermining the opinion of Yeda’s expert that a
`POSA would want to administer more than once
`daily)10; id. at 35 (“[Khan 2009] reflects that, before
`
`
`10 We recognize that, in this instance, the Board
`included Khan 2009 at the end of a string citation
`listing “[n]umerous prior art references studying less
`frequent dosing.” ’250 patent FWD, at 18 (emphasis
`added); ’413 patent FWD, at 18 (same); ’302 patent
`FWD, at 18 (same). Having considered the Board’s
`
`
`
`
`18
`
` YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`the ’250 patent invention, those skilled in the art
`were motivated to investigate dosing regimens with
`less frequent than daily injections”); ’413 patent FWD,
`at 16–17 (same as ’250 patent FWD, at 15); ’302
`patent FWD, at 16 (same).
`In one instance, the Board relied on Khan 2009
`for a different purpose, namely, in deciding whether a
`POSITA would have had a reasonable expectation of
`success of a thrice-weekly regimen. ’250 patent FWD,
`at 21 (“[A]s discussed above, nearly two years before
`the priority date of the ’250 patent, Khan 2009 com-
`menced its study on 20 mg GA administered twice-a-
`week, further evincing that an ordinary artisan would
`have had a reasonable expectation of success in
`pursuing a 40 mg, three-times-weekly GA dosing
`regimen.”). To the extent that this reliance was error,
`we conclude that it was harmless error. Khan 2009
`was the last piece of evidence in a lengthy analysis, in
`which the Board also relied on Flechter, Khan 2008,
`Caon, Pinchasi, and testimony from Dr. Green in
`finding a POSITA would have had a reasonable
`expectation of success in the claimed regimen. Even
`if the Board’s reliance on Khan 2009 was improper, it
`is harmless error because substantial evidence other-
`wise supports the Board’s conclusion.
`II. Obviousness under 35 U.S.C. § 103
`Under 35 U.S.C. § 103(a), a patent may not be ob-
`tained “if the differences between the subject matter
`
`
`decision as a whole, and in particular the portion
`discussing how Khan 2009 is not statutory prior art,
`’250 patent FWD, at 15–16, we conclude that the
`Board’s characterization of Khan 2009 as being prior
`art was a simple oversight, constituting harmless
`error.
`
`
`
`YEDA RESEARCH AND DEVELOPMENT v. MYLAN
`PHARMACEUTICALS INC.
`
`19
`
`sought to be patented and the prior art are such that
`the subject matter as a whole would have been obvi-
`ous at the time the invention was made to a person
`having ordinary skill in the art.” 35 U.S.C. § 103(a)
`(2006).11
`Obviousness is a question of law with underlying
`factual findings relating to the scope and content of
`the prior art; the differences between the claims and
`the prior art; the level of ordinary skill in
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
