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            3
PHARMACEUTICALS INC.


                     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             5
PHARMACEUTICALS INC.


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            7
PHARMACEUTICALS INC.


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            9
PHARMACEUTICALS INC.


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           11
PHARMACEUTICALS INC.


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          13
PHARMACEUTICALS INC.


rendering the claimed 40mg 3x/week limitation
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           15
PHARMACEUTICALS INC.


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           17
PHARMACEUTICALS INC.


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           19
PHARMACEUTICALS INC.


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 the perti-
nent art; and any secondary considerations of nonob-
viousness. ZUP, LLC v. Nash Mfg., Inc., 896 F.3d
1365, 1371 (Fed. Cir. 2018) (citing Graham v. John
Deere Co. of Kan. City, 383 U.S. 1, 17–18 (1966)). The
inherent teaching of a prior art reference is a question
of fact. Par Pharm., Inc. v. TWi Pharm., Inc., 773
F.3d 1186, 1194 (Fed. Cir. 2014).
    On appeal, Yeda disputes the Board’s conclusion
that the 40mg GA 3x/week dosing regimen disclosed
in the Copaxone patents would have been obvious to a
person of skill in the art. Yeda also appeals the
invalidation of the ’250 patent’s claims relating to
increased tolerability, the ’413 patent’s claims relat-
ing to decreased frequency of side effects, and the ’302
patent’s claims relating to specific-day dosing regi-



    11  Congress amended § 103 when it passed the
Leahy-Smith America Invents Act (AIA). Pub. L. No.
112–29, § 3(c), 125 Stat. 284, 287 (2011). Because the
applications that led to the patents at issue have
never contained a claim having an effective filing date
on or after March 16, 2013 (the effective date of the
statutory changes enacted in 2011), or a reference
under 35 U.S.C. §§ 120, 121, or 365(c) to any patent or
application that ever contained such a claim, the pre-
AIA § 103 applies. Id. § 3(n)(1), 125 Stat. at 293.
20          YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                               PHARMACEUTICALS INC.


mens. Yeda does not appeal on the objective indicia of
nonobviousness. We address each argument in turn.
       A. 40mg GA 3x/week Dosing Regimen
     Yeda contends that the Board erred as a matter of
law in finding the claimed 40mg GA 3x/week dosing
regimen obvious. Specifically, Yeda claims that, in
finding that a POSITA had a reasonable expectation
of success, the Board disregarded inherent uncertain-
ties associated with GA. Yeda also argues that the
Board engaged in hindsight bias, considered the
obviousness of individual claim elements separately
rather than the claimed invention as a whole, and
failed to account for the “minimum effective dose”
principle in considering what the prior art taught
POSITAs.
    We first consider Yeda’s argument that the Board
erred as a matter of law in finding a reasonable
expectation of success of the claimed regimen by
disregarding certain uncertainties associated with
GA, namely the fact that GA’s pharmacokinetic and
pharmacodynamic (“pk/pd”) profile, mechanism of
action, optimal dose, and active species are all un-
known. Yeda contends that this case is “indistin-
guishable” from In re Cyclobenzaprine Hydrochloride
Extended-Release Capsule Patent Litigation, 676 F.3d
1063 (Fed. Cir. 2012), and argues that a reasonable
expectation of success is categorically impossible in
the absence of a pk/pd profile. Appellant’s Opening
Br. 38–39.
    In Cyclobenzaprine, we held that bioequivalence
alone could not establish obviousness because “skilled
artisans could not predict whether any particular PK
profile, including a bioequivalent one, would produce
a therapeutically effective formulation.” 676 F.3d at
1070. The court applied traditional motivation and
reasonable-expectation-of-success analysis, reasoning
YEDA RESEARCH AND DEVELOPMENT    v. MYLAN           21
PHARMACEUTICALS INC.


that “[w]hile it may have been obvious to experiment
with the use of the same PK profile [from an immedi-
ate-release formulation] when contemplating an
extended-release formulation, there [wa]s nothing to
indicate that a skilled artisan would have had a
reasonable expectation that such an experiment
would succeed in being therapeutically effective.” Id.
In Cyclobenzaprine, there were no prior art clinical
studies to suggest what would be a therapeutically
effective formulation.
    We do not read Cyclobenzaprine as establishing a
rigid rule categorically precluding obviousness deter-
minations without pk/pd data. There, the court’s
error was relying on bioequivalence alone, without
any evidence in the prior art teaching or suggesting a
therapeutically effective formulation to one skilled in
the art, such as pk/pd data. Here, however, the Board
committed no such error; the record is replete with
prior art that would have taught or suggested a
therapeutically effective formulation to a POSITA.
The Board pointed to clinical studies that taught the
effectiveness of 20mg daily (Copaxone® 20mg), 20mg
every other day (Flechter, Khan 2008, Caon), and
40mg daily (Cohen, FORTE), and the Pinchasi appli-
cation, which suggested that 40mg every other day
would be therapeutically effective. See ’250 patent
FWD, at 12–14, 20; ’413 patent FWD, at 16–18, 21–22;
’302 patent FWD, at 15–16, 20, 29–30.
    Further, the evidence considered by the Board re-
veals that pk/pd data was largely irrelevant to the
invention. The Board credited testimony from Peti-
tioners’ expert Dr. Green, who testified that POSITAs
considered GA to be a “forgiving drug,” with a wide
range of likely efficacious doses. E.g., ’250 patent
FWD, at 16–17. Yeda itself argued to the Board that
the “plasma half-life of GA . . . is irrelevant to the
pharmaceutical effect of the drug,” and that “GA
22          YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                               PHARMACEUTICALS INC.


cannot be measured in the plasma and no PK/PD
correlation is even possible.” J.A. 772 (citation omit-
ted). In light of Yeda’s own representations to the
Board that “the standard small molecule textbook
pharmacokinetic principles . . . cannot be used to
predict the therapeutic effects of GA,” id., we decline
to find error in the Board’s obviousness decision
simply because it lacked pk/pd data.
    Yeda makes challenges to the Board’s factual
findings concerning reasonable expectation of success,
none of which we find persuasive. Although Yeda
contests the Board’s finding that GA is a “forgiving
drug,” leading POSITAs to have a reasonable expecta-
tion in administering 40mg GA 3x/week, this conclu-
sion is supported by substantial evidence, including
Dr. Green’s expert testimony. ’250 patent FWD, at
18–19. The Board’s finding that the uncertainty
around GA’s mechanism of action would motivate a
POSITA to stick to dosing regimens with existing
clinical support, such as 20mg and 40mg, is supported
by substantial evidence from Dr. Green. Id. at 18.
Because “the expectation of success need only be
reasonable, not absolute,” we find no error in these
findings. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1364 (Fed. Cir. 2007).
    Next, Yeda argues that the Board improperly con-
sidered the claimed dose amount and the claimed
frequency separately, “manipulat[ing] both parame-
ters at the same time,” without finding an affirmative
reason to combine them. Appellant’s Opening Br. 45,
48. We disagree. The Board’s analysis began with
Pinchasi, which it found disclosed every claim ele-
ment except the requirement to inject 40mg GA
3x/week, as opposed to every other day. ’250 patent
FWD, at 10. The only difference between the prior art
and the claimed invention was, therefore, the differ-
ence between thrice weekly and every other day
YEDA RESEARCH AND DEVELOPMENT     v. MYLAN           23
PHARMACEUTICALS INC.


administration. We do not read the Board’s decision
as manipulating both parameters simultaneously, but
rather, as considering the claimed regimen in the
context of the prior art regimens, both in terms of
dose size and frequency.
     Nor do we find, as Yeda urges, that the Board im-
properly engaged in hindsight by starting its analysis
with Pinchasi as the closest prior art reference.
Appellant’s Reply Br. 3–4. At the outset, we note that
this argument was raised by Yeda for the first time in
its reply brief, and thus is waived. And while we have
previously cautioned against relying on hindsight bias
in selecting a lead prior art reference after the fact,
we find no hindsight in the Board’s analysis. See, e.g.,
WBIP, LLC v. Kohler Co., 829 F.3d 1317, 1337 (Fed.
Cir. 2016) (“The real question is whether that skilled
artisan would have plucked one reference out of the
sea of prior art . . . .”); Ortho-McNeil Pharm., Inc. v.
Mylan Labs., Inc., 520 F.3d 1358, 1364 (Fed. Cir.
2008). Here, far from a “sea of prior art,” the refer-
ences before the Board presented a finite and known
pool of dose and frequency options easily traversed to
show obviousness. See KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 421 (2007) (“When there is a design
need or market pressure to solve a problem and there
are a finite number of identified, predictable solu-
tions, a person of ordinary skill has good reason to
pursue the known options within his or her technical
grasp.”). The dosages in the prior art that had clinical
support for being effective and safe consisted of only
two: 20mg and 40mg. The prior art disclosed both
daily and every other day administration, and the
Board found a motivation for both less frequent
injections and a thrice-weekly regimen specifically.
’250 patent FWD, at 13–16. Given the small field of
prior art references with clinical support, we find no
clear error in the Board’s finding that the “[p]otent
24           YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                                PHARMACEUTICALS INC.


and promising activity in the prior art” would have
encouraged a POSITA to traverse the experimental
options to produce this invention. See Daiichi Sankyo
Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1354 (Fed.
Cir. 2010); Ortho-McNeil, 520 F.3d at 1365.
    The Board thoroughly addressed Yeda’s argu-
ments to the contrary, namely, that a POSITA would
not use 40mg of GA on any dosing schedule, would not
have used a 3x/week dosing regimen, and that there
would not have been a reasonable expectation of
success of 40mg GA 3x/week being therapeutically
effective. See ’250 patent FWD, at 11. In so doing, the
Board found that a POSITA would have been moti-
vated to use 40mg, id. at 11–13, that a POSITA would
have been motivated to use a 3x/week dosing regimen,
id. at 13–16, and that a POSITA would have had a
reasonable expectation of success in using 40mg GA
3x/week to be therapeutically effective, id. at 16–22.
Given these findings, and given that the difference
between the claimed invention and the prior art is
only one dose per two week period, the Board did not
need to articulate a further motivation to combine the
40mg dose and the 3x/week schedule.
    Yeda makes other arguments attacking the
Board’s fact finding regarding motivation to combine.
For instance, Yeda points to Cohen, which reported a
slightly higher rate of adverse effects in 40mg com-
pared to 20mg doses, as evidence that a POSITA
would not have been motivated to inject 40mg doses.
However, the Board also considered the FORTE
study, which noted that the higher 40mg dose “main-
tained the favorable safety and tolerability profile” of
20mg GA. ’250 patent FWD, at 12–13. Yeda also
contests Dr. Green’s testimony relating to Rebif®,
another RRMS drug that uses a 3x/week dosing
regimen. Yeda argues that it was improper to rely on
Rebif as proof of efficacy, in that GA and Rebif have
YEDA RESEARCH AND DEVELOPMENT     v. MYLAN           25
PHARMACEUTICALS INC.


different mechanisms of action. However, Dr. Green
did not rely on Rebif to demonstrate GA’s efficacy, but
rather for the point that patients adhered well to
Rebif’s regimen of thrice-weekly injections, suggesting
that a 3x/week GA injection regimen would improve
patient compliance. Id. at 16; J.A. 6628–29 ¶ 53. We
have considered Yeda’s other arguments to this effect
and find them unpersuasive.
     Finally, Yeda argues that the Board erred in fail-
ing to consider the “minimum effective dose” princi-
ple. According to Petitioners’ expert, Dr. Peroutka,
the minimum effective dose is the lowest dose of a
drug that will achieve a desired effect, and in general,
is preferred unless higher doses lead to increased
efficacy with an acceptable amount of side effects.
Mylan Pharm. Inc. v. Yeda Research & Dev. Co.,
IPR2015-00643, Ex. 1003, ¶ 44 (P.T.A.B. Mar. 3,
2015) (“Peroutka Decl.”). Based on this principle,
Yeda argues that following the FORTE study—which
concluded that the GA 40 mg dose did not demon-
strate increased efficacy in reducing the relapse rate,
J.A. 11308—a POSITA “would have had no motiva-
tion to pursue a 40mg dose, on any schedule.” Appel-
lant’s Opening Br. 52. Yeda argues that the Board’s
failure to address minimum effective dose is legal
error.
    Although the Board did not address the minimum
effective dose principle by name in its decisions, these
omissions do not constitute reversible error. First, as
an initial matter, the Board is “not require[d] . . . to
address every argument raised by a party or explain
every possible reason supporting its conclusion.”
Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d
1309, 1322 (Fed. Cir. 2016), overruled on other
grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290,
1296 n.1 (Fed. Cir. 2017) (en banc). And while agen-
cies are required to address “important aspect[s] of
26           YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                                PHARMACEUTICALS INC.


the problem,” Motor Vehicle Mfrs. Ass’n of U.S., Inc. v.
State Farm Mut. Auto Ins. Co., 463 U.S. 29, 43 (1983),
here, minimum effective dose is mentioned only
briefly in Yeda’s patent owner responses, in a single
paragraph discussing Petitioners’ expert, Dr. Perout-
ka. See J.A. 752, 1828, 3365. As we have said nu-
merous times, failure to explicitly discuss every
fleeting reference or minor argument does not alone
establish that the Board did not consider it. See
Novartis, 853 F.3d at 1328 (citing cases).
    Second, the record on appeal indicates that the
Board considered the minimum effective dose princi-
ple. At oral argument, the Board discussed the effect
of less frequent dosing on dose size. Yeda’s counsel
argued that, under the minimum effective dose prin-
ciple, a POSITA would have “no reason to go to
40[mg].” J.A. 1352. In response, the Board queried
whether, if a POSITA would have been motivated to
move to less frequent dosing, “doesn’t it open up the
world of possibilities again that we can start with 20
and 40 and then start all over and figure out which is
the proper less frequent dosing?” J.A. 1352; see also
J.A. 1353–54. Further, Yeda’s reliance on the mini-
mum effective dose principle in its response was in
support of its position that FORTE taught away from
using 40mg. See Mylan Pharm. Inc. v. Yeda Research
& Dev. Co., IPR2015-00643, No. 26, at 17–19
(P.T.A.B. Nov. 20, 2015) (patent owner response)
(discussing minimum effective dose under the sub-
heading: “After the FORTE trial, a POSA would not
have used a 40 mg dose of GA to treat MS”). The
Board expressly addressed whether FORTE taught
away from a 40mg dose in the final written decisions.
See, e.g., ’250 patent FWD, at 13 (“Because nothing in
FORTE criticizes, discredits, or discourages the use of
40 mg of GA, we determine that FORTE does not
teach away from the use of 40 mg of GA.”).
YEDA RESEARCH AND DEVELOPMENT    v. MYLAN           27
PHARMACEUTICALS INC.


     In light of the foregoing, we conclude that sub-
stantial evidence supports the Board’s reliance on the
clinical data and its conclusion that a POSITA would
be motivated to combine Pinchasi’s 40mg every other
day dose with a less frequent dosing regimen, such as
3x/week, and would have had a reasonable expecta-
tion of success in therapeutic effectiveness and pa-
tient compliance. Accordingly, we affirm the Board’s
finding that the 40mg GA 3x/week regimen is obvious
in light of the prior art.
          B. Increased Tolerability Claims
     Claim 15 of the ’250 patent, from which claims
16–18 depend, requires that the claimed 40mg GA
3x/week regimen improve tolerability as compared to
the daily 20mg regimen. ’250 patent col. 17 l. 24–col.
18 l. 6. In the ’250 patent, “tolerability” “relates to
the level of discomfort associated with GA treatment,”
and “is associated with the frequency and severity of
post injection reactions and injection site reactions.”
Id. col. 7 ll. 33–37.
    Yeda argues that the Board did not sufficiently
address the tolerability limitations of claims 15–18 of
the ’250 patent. We disagree, and find that substan-
tial evidence supports the Board’s finding that a
POSITA, considering the prior art teachings as a
whole, had a reason to switch from 20mg GA daily to
a 40mg GA 3x/week regimen, and would have known
that doing so would increase the tolerability of the GA
regimen as compared to 20mg GA daily. ’250 patent
FWD, at 25. The Board pointed to Khan 2008 and
Caon, which reported that 20mg every other day had
increased tolerability over 20mg daily, including
significantly less lipoatrophy, as showing that every
other day dosing decreases injection-related side
effects. Id. at 24–25.
28          YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                               PHARMACEUTICALS INC.


    Yeda now claims that the Board disregarded other
prior art references that contradict Khan 2008 and
Caon, including Flechter and FORTE. Concerning
Flechter, the Board concluded that Flechter does not
show that every other day administration is less
tolerable than daily administration. Id. at 33–34.
This conclusion was based on the Board’s rejection of
testimony of Yeda’s expert, Dr. Ziemssen, who com-
pared Flechter with another study, Meiner, on the
grounds that cross-study comparisons are not reliable.
Having concluded elsewhere that Flechter makes no
statement as to tolerability, there would be no reason
for the Board to cite Flechter with respect to claims
15 to 18. And although FORTE was not cited in this
section, the Board earlier in the decision noted
FORTE’s conclusion that the 40mg dose “maintained
the favorable safety and tolerability profile of
COPAXONE® 20mg.” Id. at 13. Because the Board
found that an increased dose does not decrease toler-
ability and the evidence reveals that a POSITA would
believe that decreased injection frequency would
increase tolerability, we conclude that the Board’s
decision is supported by substantial evidence and
legally proper.
         C. Reduced Frequency of ISRs and
                  IPIRs Claims
    Claim 7 of the ’413 patent depends on claim 1,
and further requires that the claimed method reduce
the frequency of an IPIR or ISR relative to daily
administration of 20 mg GA. ’413 patent col. 16 ll.
51–54. The Board found all dependent claims of the
’413 patent unpatentable as obvious in light of
Pinchasi and the 1996 SBOA. ’413 patent FWD, at
23–24.
    In finding claim 7 obvious, the Board adopted the
reasoning in Dr. Green’s declaration discussing how
YEDA RESEARCH AND DEVELOPMENT     v. MYLAN           29
PHARMACEUTICALS INC.


decreasing the frequency of injections decreases the
frequency of reactions relative to 20mg daily. Id. at
23 (citing Mylan Pharm. Inc. v. Yeda Research & Dev.
Co., IPR2015-00644, Ex. 1004 ¶ 109 (Feb. 7, 2015) (“It
would have been and is common sense that reducing
the frequency of administration from 20 mg daily
would in turn decrease the frequency of injection site
reactions and immediate post injection reactions.”)).
The Board also considered, and rejected, Yeda’s
argument that 40mg doses are associated with more
injection site reactions, on the grounds that it was not
supported by the prior art. Id. at 24. Moreover, in
the paragraph discussing claim 7, the Board cited
portions of Petitioners’ reply—which in turn relied on
Khan 2008, Caon, Dr. Green’s testimony, and other
evidence—discussing how less frequent dosing would
increase tolerability by reducing ISRs. Id. (citing J.A.
2117–20).
    Yeda faults the Board for not considering all of its
arguments. “[W]e will uphold a decision of less than
ideal clarity if the agency’s path may reasonably be
discerned.” In re NuVasive, Inc., 842 F.3d 1376, 1383
(Fed. Cir. 2016) (quoting Bowman Transp., Inc. v.
Ark.-Best Freight Sys., Inc., 419 U.S. 281, 286 (1974)).
Having reviewed the Board’s decision, we conclude
that while the Board’s analysis regarding claim 7 is
concise, it is supported by substantial evidence.
     We are further convinced that the Board did not
err because the record is replete with Board findings
that increased tolerability claims would be obvious.
As in the ’250 patent, the ’413 patent defines tolera-
bility to be associated with the frequency of ISRs and
IPIRs. ’413 patent col. 7 ll. 28–32. And although
claim 7 of the ’413 patent does not itself reference
tolerability, the parties and the Board referred to
claim 7 as concerning tolerability. See, e.g., J.A. 138
(Board’s decision granting-in-part request for rehear-
30           YEDA RESEARCH AND DEVELOPMENT v. MYLAN
                                PHARMACEUTICALS INC.


ing) (“We note that none of the claims, other than
claim 7, recite any limitation regarding tolerability.”);
J.A. 1371 (statement of Yeda’s counsel at oral argu-
ment) (“One set of claims have to do with the in-
creased tolerability of the GA treatment, and what
I’m talking about now is ’250, claims 14 to 17, and
’413, claim 7.” (emphasis added)). In light of the
substantive overlap between the reduced frequency
and the increased tolerability claims, and given our
earlier holding that the Board did not err in finding
the increased tolerability claims obvious, we affirm
the Board’s finding regarding claim 7 of the ’413
patent. See supra Discussion, section II.B.
         D. Specific Dosing Regimen Claims
    Claims 4, 5, and 11 of the ’302 patent each specify
a particular three-day schedule in a seven-day period
on which GA injections are administered. For exam-
ple, claim 4 of the ’302 patent requires that the three
subcutaneous 40mg GA injections “are on three days
each week selected from the group consisting of day 1,
day 3 and day 5; day 1, day 3 and day 6; day 1, day 4
and day 6; day 2, day 4 and day 6; day 2, day 4 and
day 7; [day] 2, day 5 and day 7; and day 3, day 5 and
day 7.” ’302 patent col. 16 ll. 47–52.
    In response to Yeda’s argument that Pinchasi did
not disclose all elements of these claims, the Board
explained that the question is not whether Pinchasi
discloses administering 40mg of GA three times
weekly to meet the further limitations of claims 4, 5,
and 11, but rather, “we must look at what the prior
art teaches as a whole.” ’302 patent FWD, at 22. In
considering these specific dosing regimen claims, the
Board adopted the reasoning of Dr. Green in his
expert declaration, namely that “[c]hoosing specific
days each week, such as Monday, Wednesday, and
Friday, for example” is obvious, and that “choosing
YEDA RESEARCH AND DEVELOPMENT   v. MYLAN           31
PHARMACEUTICALS INC.


specific days for injections increases patient adher-
ence and compliance.” J.A. 6654 ¶ 107. The Board
also adopted reasoning from the petition, including
that “[t]he three specific days of the week are a mat-
ter of patient and physician choice from a limited
number of possibilities.” J.A. 2590.
    We see no error in the Board’s finding. “[A] court
can take account of the inferences and creative steps
that a person of ordinary skill in the art would em-
ploy.” KSR, 550 U.S. at 418. Having already found
the 40mg GA 3x/week limitation obvious, merely
identifying the specific days for the thrice-weekly
regimen is the natural application of the method, with
a finite number of identified and predictable solu-
tions, and requires not innovation but ordinary skill
and common sense. See id. at 421.
                    CONCLUSION
    In light of the foregoing, we conclude that the
Board did not err in finding all claims of the Copax-
one patents unpatentable as obvious.
                    AFFIRMED
                       COSTS
   No costs.
