Court Opinion

ID: 4363936
Source: CourtListenerOpinion
Date Created: 2019-02-01 17:01:14.584019+00
Date Added: 2024-06-11T14:16:27.009929
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
               ______________________

      MYLAN PHARMACEUTICALS INC.,
   BRECKENRIDGE PHARMACEUTICAL, INC.,
     ALEMBIC PHARMACEUTICALS LTD.,
                Appellants

                          v.

  RESEARCH CORPORATION TECHNOLOGIES,
                   INC.,
                  Appellee
           ______________________

           2017-2088, 2017-2089, 2017-2091
               ______________________

   Appeals from the United States Patent and Trade-
mark Office, Patent Trial and Appeal Board in Nos.
IPR2016-00204,     IPR2016-01101,     IPR2016-01242,
IPR2016-01245.
               ______________________

              Decided: February 1, 2019
               ______________________

   STEVEN WILLIAM PARMELEE, Wilson, Sonsini, Goodrich
& Rosati, PC, Seattle, WA, argued for all appellants.
Appellant Mylan Pharmaceuticals Inc. also represented
by MICHAEL T. ROSATO, JAD ALLEN MILLS; ADEN M.
ALLEN, NICOLE W. STAFFORD, Austin, TX.

   MATTHEW L. FEDOWITZ, Buchanan Ingersoll & Rooney
PC, Alexandria, VA, for appellant Breckenridge Pharma-
2      MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                               TECHS., INC.

ceutical, Inc.

    TODD S. WERNER, Carlson, Caspers, Vandenburgh,
Lindquist & Schuman, PA, Minneapolis, MN, for appel-
lant Alembic Pharmaceuticals Ltd. Also represented by
SARAH STENSLAND, Patterson Thuente Pedersen, PA,
Minneapolis, MN.

    JACK B. BLUMENFELD, Morris, Nichols, Arsht & Tun-
nell LLP, Wilmington, DE, argued for appellee. Also
represented by ALEXA HANSEN, Covington & Burling LLP,
San Francisco, CA; JENNIFER L. ROBBINS, New York, NY;
BETH S. BRINKMANN, PRISCILLA GRACE DODSON, EVAN
SMITH KRYGOWSKI, GEORGE FRANK PAPPAS, Washington,
DC.
                ______________________

    Before LOURIE, BRYSON, and WALLACH, Circuit Judges.
LOURIE, Circuit Judge.
    Mylan Pharmaceuticals Inc. (“Mylan”), Breckenridge
Pharmaceutical, Inc. (“Breckenridge”), and Alembic
Pharmaceuticals, Ltd. (“Alembic”) (collectively, “Appel-
lants”) appeal from the final written decision of the U.S.
Patent and Trademark Office Patent Trial and Appeal
Board (“the Board”) in an inter partes review concluding
that claims 1–13 of U.S. Reissue Patent 38,551 (“the ’551
patent”) are not unpatentable. See Argentum Pharm.
LLC v. Research Corp. Techs., IPR 2016-00204, 2017 WL
1096590, at *1–2 (P.T.A.B. Mar. 22, 2017) (“Decision”).
For the reasons detailed below, we affirm.
                       BACKGROUND
    Epilepsy is a neurological disorder that affects about
one percent of the human population. It is characterized
by two or more unprovoked seizures occurring more than
24 hours apart. Epilepsy can be associated with condi-
tions affecting the structure of the brain, but, for the vast
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION       3
TECHS., INC.

majority of affected individuals, no specific cause can be
identified. While there is no known cure for epilepsy,
treatment can include both drug therapy and surgery, and
most patients are treated via long-term administration of
anticonvulsant drugs to prevent seizures. The nature and
severity of seizures varies considerably across the patient
population, and treatment is typically tailored for each
specific patient.
    Research Corporation Technologies, Inc. (“RCT”) owns
the ’551 patent, which discloses and claims enantiomeric
compounds and pharmaceutical compositions useful in the
treatment of epilepsy and other central nervous system
(“CNS”) disorders. Claim 1 recites:
    1. A compound in the R configuration having the
    formula:

    wherein
        Ar is phenyl which is unsubstituted or
        substituted with at least one halo group;
        Q is lower alkoxy, and
        Q1 is methyl.
’551 patent col. 38 ll. 8–23.
4       MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                                TECHS., INC.

    At issue here are claims 8–13. 1 Claim 8 depends from
claim 1 and recites “[t]he compound according to claim 1
which            is           (R)-N-benzyl-2-acetamido-3-
methoxypropionamide,” referred to in the patent as
“BAMP” and referred to herein as lacosamide:

     Claim 9 claims lacosamide in 90 percent or greater
purity, claim 10, therapeutic compositions comprising the
claimed compounds, and claims 11–13, use of the com-
pounds for treating central nervous system disorders. Id.
col. 38 ll. 39–51. Because arguments have not been made
concerning the separate claims, we will consider them
together, as did the Board.

    1   Before the Board, Appellants challenged claims 1–
13, but, since this appeal was taken, claims 1–7 have been
voluntarily cancelled in a separate, ex parte reexamina-
tion proceeding. See Citation of Supplemental Authority,
Mylan Pharm. Inc. v. Research Corp. Techs., No. 2017-
2088 (Fed. Cir. Apr. 23, 2018), ECF No. 73. Because there
is no case or controversy regarding the finally cancelled
claims, we rule only on the still-existing claims 8–13. See
Fresenius USA, Inc. v. Baxter Int’l, Inc., 721 F.3d 1330,
1347 (Fed. Cir. 2013) (litigation became moot because of
the cancellation of claims).
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION     5
TECHS., INC.

     On November 23, 2015, Argentum Pharmaceuticals
LLC (“Argentum”) petitioned for inter partes review
(“IPR”) of the ’551 patent. In its petition, Argentum
challenged claims 1–13 on eight grounds. The Board only
instituted on two grounds involving three references:
(1) obviousness of claims 1–9 over Kohn 1991 2 and Sil-
verman 3 and (2) obviousness of claims 10–13 over Kohn
1991, Silverman, and U.S. Patent 5,378,729 (“the ’729
patent”). 4 The instituted grounds appear in the petition
as ground 3A and ground 3B.
    In its argument, Argentum advanced a lead com-
pound analysis. It relied on Kohn 1991 for disclosure of
compound 3l, its proffered lead compound. Kohn 1991,
authored by the named inventor of the ’551 patent, Dr.
Harold Kohn, discloses a series of functionalized amino
acids (“FAAs”) with anticonvulsant activity. Dr. Kohn
observed that FAA racemates with N-benzylamide moie-
ties and acetylated amino groups provided potent protec-
tion against seizures in mice. For his research presented
in the 1991 paper, Dr. Kohn began with (R,S)-2-
acetamido-N-benzyl-2-methylacetamide as a lead com-
pound and replaced the α-methyl group, denoted in the
structure below as “X,” with functionalized nitrogen,
oxygen, and sulfur substituents:

   2    Harold Kohn et al., Preparation and Anticonvul-
sant Activity of a Series of Functionalized α-Heteroatom-
Substituted Amino Acids, 34 J. Medicinal Chemistry
2444 (1991); J.A. 2404–12.
     3  Richard B. Silverman, The Organic Chemistry of
Drug Design and Drug Action (1st ed. 1992); J.A. 2413–
61.
     4  The application that led to the ’551 patent was
filed before March 16, 2013, and the pre-Leahy–Smith
America Invents Act, Pub L. No. 112-29, 125 Stat. 284
(2011), version of § 103 applies.
6    MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

Dr. Kohn then evaluated the potency of the compounds in
mice, reporting for each the effective dosage for 50 percent
of the tested population (“ED50”).
    Based on the reported ED50 values, Dr. Kohn conclud-
ed that “in the most potent analogues (2d, 3l, and 3n), a
functionalized oxygen atom existed two atoms removed
from the α-carbon atom.” J.A. 2407. The most efficacious
compound (i.e., the compound with the lowest ED50) was
compound 3l. In compound 3l, NH(OCH3) is at the α-
carbon position. J.A. 2405. Its structure is as follows:

    To supply a motivation to modify compound 3l, Argen-
tum relied on Silverman, a book chapter on drug discov-
ery, design, and development.           Silverman describes
bioisosterism as a “lead modification approach . . . useful
to attenuate toxicity or to modify . . . activity. ” J.A. 2430.
He specifically defines bioisosteres as “substituents or
groups that have chemical or physical similarities, and
which produce broadly similar biological properties.” Id.
As relevant here, Silverman explains that “classical
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION         7
TECHS., INC.

isosteres” are groups with the same number of valence
electrons but potentially different atoms. Under the
subheading “[b]ivalent atoms and groups,” he lists the
following compounds as classical isosteres: –CH2–, –NH–,
–O–, –S–, and –Se–. Id.
    As a third reference, relevant only to the second insti-
tuted ground of review, Argentum cited the ’729 patent,
another patent issued to Dr. Kohn and assigned to RCT.
The ’729 patent is directed to a genus of FAAs with activi-
ty “useful in the treatment of epilepsy and other CNS
disorders.” ’729 patent, Abstract. Specifically, a method
of treating CNS disorders in animals with a racemate of
N-benzyl 2-acetamido-3-methoxypropionamide (“racemic
lacosamide”) is recited in claim 132 of the ’729 patent.
     Based on Argentum’s petition, the Board instituted
review on (1) obviousness of claims 1–9 over Kohn 1991
and Silverman and (2) obviousness of claims 10–13 over
Kohn 1991, Silverman, and the ’729 patent. As for the
first ground, the Board was “persuaded that [Argentum]
sufficiently articulate[d] reasoning, with adequate ration-
al underpinnings, as to why an ordinary artisan would
have chosen derivative 3l from Kohn 1991 as a lead
compound for the purposes of making compositions exhib-
iting anticonvulsant activity.” J.A. 367. The Board noted
that Kohn 1991 identified compound 3l as “the most
potent derivative,” and, based on the record at the time, it
was not persuaded that “potential synthetic or stability
issues” would have counseled against its selection as a
lead compound. J.A. 367–68. The Board was also per-
suaded that “an ordinary artisan reading Silverman
would have had reason to substitute the amino group
(–NH–) in the X moiety of NH(OCH3) in derivative 3l from
Kohn 1991 with a methylene group,” “in an effort to
attenuate toxicity, modify activity, or positively affect the
metabolism of a compound.” J.A. 368. That change would
lead to lacosamide.
8       MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                                TECHS., INC.

    As for the second ground, the Board concluded that
Argentum had adequately supported its contention that
an ordinary artisan would have had reason to expect “that
compounds falling within claim 132 of the ’729 patent—
such as racemic lacosamide and R-lacosamide—would be
useful for treating CNS disorders, and would have a
reasonable expectation of success in using them for this
purpose.” J.A. 372.
     Three days after the Board instituted Argentum’s pe-
tition, Mylan, Breckenridge, and Alembic each filed their
own petitions for review with concurrent motions for
joinder. Each party had been sued for infringement of the
’551 patent in 2013, more than a year before the petitions
were filed. 5 On October 24, 2016, the Board instituted on
each petition and joined each proceeding with the Argen-
tum IPR. In its decision permitting joinder, the Board
noted that Mylan, Breckenridge, and Alembic “agree[d] to
be limited to an ‘understudy’ role, and limited to evidence
and arguments presented in the Argentum Petition in
relation to instituted Grounds 3A–3B.” J.A. 1463.
     Five months later, the Board issued its final written
decision, concluding that each challenged claim had not
been shown to be unpatentable. Regarding ground one,
Petitioners identified two reasons for modifying the
methoxyamino moiety of compound 3l in Kohn 1991:
(1) that the methoxyamino moiety was not a common
moiety in compounds that result in commercial pharma-

    5   UCB, Inc. v. Mylan Pharm. Inc., No. 1:13-cv-
01214-LPS (D. Del. Jul. 10, 2013); UCB, Inc. v. Alembic
Pharm. Ltd., No. 1:13-cv-01207-LPS (D. Del. Jul. 10,
2013); UCB, Inc. v. Breckenridge Pharm., Inc., No. 1:13-
cv-01211-LPS (D. Del. Jul. 10, 2013). We resolved the
appeal of these cases in UCB, Inc. v. Accord Healthcare,
Inc., 890 F.3d 1313 (Fed. Cir. 2018), cert. denied, No. 18-
441, 2018 WL 4899559 (U.S. Nov. 19, 2018).
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION       9
TECHS., INC.

ceutical compounds and (2) that the methoxyamino moie-
ty may present synthetic and stability problems. Accord-
ing to Petitioners, a person of skill in the art would have
been motivated to substitute the –NH– group in 3l for a –
CH2– group because it is a more common and acceptable
moiety for pharmaceutically active compounds. Further,
because Kohn 1991 disclosed a ten-fold higher activity for
3l, which has an R group of –NH(OCH3), over a compound
with an R group of –NH2, a person of skill in the art
would have been motivated to substitute the –CH3 group
with –CH2OCH3.
    Contrary to its views in the institution decision, the
Board disagreed with Petitioners. It “assum[ed] arguen-
do, that an ordinary artisan would have selected com-
pound 3l of Kohn 1991 as a lead compound” but found
that converting the methoxyamino group would have been
viewed as undesirable because the compounds in Kohn
1991 without a methoxyamino or nitrogen-containing
moiety at the α-carbon had reduced activity. Decision,
2017 WL 1096590, at *8–9.
    The Board also credited evidence suggesting that an
ordinary artisan would have understood the methoxy-
amino moiety to confer significant activity to the com-
pound and that substitution of nitrogen for carbon would
have led to a significantly different conformation and
biological activity. Id. at *10–11. While the Board
“acknowledge[d] Silverman’s teaching . . . that bioisoster-
ism has been shown to be useful to attenuate toxicity in
lead compounds,” it found a lack of “specific evidence
suggesting an ordinary artisan would have understood
that modifying the methoxyamino group of Kohn 1991’s
compound 3l would have reduced that compound’s toxici-
ty.” Id. at *12.
    Although the Board did proceed to evaluate objective
indicia of nonobviousness, it nonetheless concluded that
even without objective evidence of nonobviousness Peti-
10   MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

tioners failed to meet their burden to establish by a
preponderance of the evidence that challenged claims 1–9
would have been obvious. Id. at *13.
    Proceeding to the second ground relating to the de-
pendent claims, the Board declined to consider Petition-
ers’ arguments because they incorporated by reference a
separate ground, Ground 1B, on which the Board did not
institute review. Specifically, in Ground 1B, Petitioners
advanced arguments based on a LeGall thesis, a reference
not at issue in the proceeding as instituted. The Board
found that the second ground was “based on a conclusory
assertion referencing a distinct ground of unpatentability
discussing a different combination of references.” J.A.
129. Moreover, because it concluded that independent
claim 1 would not have been obvious over Kohn 1991 and
Silverman, the Board reasoned that it could not conclude
that the more limited dependent claims 10–13, the only
claims at issue in the second ground, would have been
obvious.
    Of the four petitioners, Mylan, Breckenridge and
Alembic appealed. RCT challenges whether Appellants
have standing to challenge the Board’s decision. We have
jurisdiction for this appeal under 28 U.S.C.
§ 1295(a)(4)(A) and 35 U.S.C. § 141(c). We review the
Board’s legal determinations de novo, In re Elsner, 381
F.3d 1125, 1127 (Fed. Cir. 2004), and its fact findings for
substantial evidence, In re Gartside, 203 F.3d 1305, 1316
(Fed. Cir. 2000). A finding is supported by substantial
evidence if a reasonable mind might accept the evidence
as sufficient to support the finding. Consol. Edison Co. v.
NLRB, 305 U.S. 197, 229 (1938).
                       DISCUSSION
                       I. STANDING
    As a threshold matter, we first address whether Ap-
pellants have standing to make this appeal. RCT does not
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION         11
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assert that Appellants lack Article III standing. Appel-
lee’s Br. 20. However, RCT submits that each Appellant
lacks standing because it does not fall within the zone of
interests of 35 U.S.C. § 319. According to RCT, Appel-
lants fall outside that zone because RCT brought an
infringement action against each Appellant more than a
year before it filed its IPR petition, and each Appellant’s
petition was therefore time-barred.
    In its institution and joinder decision, the Board exer-
cised its discretion to join each Appellant as a party to
Argentum’s IPR as permitted by 35 U.S.C. § 315(c). J.A.
670 (“[T]he later Petitioners are joined as parties . . . .”).
RCT does not challenge the propriety of the Board’s
joinder decision. However, RCT argues that the “statuto-
ry scheme here . . . does not authorize Appellants to seek
federal court review of the Board’s [final written] deci-
sion.” Appellee’s Br. 18. Its argument is that the initial
Petitioner, Argentum, would have lacked Article III
standing to appeal the Board’s decision, because “its IPR
was limited to an agency matter.” Id. at 18–19. The
parties appear to agree that Argentum, who is not a party
to this appeal, lacks standing. See Appellants’ Br. 71;
Appellee’s Br. 20.
    For their part, Appellants maintain that they have an
express, statutory right to appeal under 35 U.S.C. § 319
because they were joined as petitioners to Argentum’s
IPR. Appellants’ Br. 70–71. We agree.
    We presume that a statutory cause of action extends
only to litigants that “fall within the zone of interests
protected by the law invoked.” Lexmark Int’l, Inc. v.
Static Control Components, Inc., 572 U.S. 118, 129 (2014)
(quoting Allen v. Wright, 468 U.S. 737, 751 (1984)). The
zone of interests limitation “always applies and is never
negated.” Id. To determine whether an appellant falls
within the zone of interests, we apply traditional princi-
ples of statutory interpretation, asking not “whether in
12    MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                              TECHS., INC.

our judgment Congress should have authorized [the
appeal], but whether Congress in fact did so.” Id. at 128.
    We begin our analysis on this point with the text of
the statute. Section 315(c) provides for joinder as follows:
     If the Director institutes an inter partes review,
     the Director, in his or her discretion, may join as a
     party to that inter partes review any person who
     properly files a petition under section 311 that the
     Director, after receiving a preliminary response
     under section 313 or the expiration of the time for
     filing such a response, determines warrants the
     institution of an inter partes review under section
     314.
(emphasis added). Section 315 thus contemplates the
joining of petitioners as “parties.” Section 319 then
provides that “[a] party dissatisfied with the final written
decision” of the Board “may appeal the decision pursuant
to sections 141 through 144. Any party to the inter partes
review shall have the right to be a party to the appeal.”
(emphasis added).
     “It is a ‘fundamental canon of statutory construction
that the words of a statute must be read in their context
and with a view to their place in the overall statutory
scheme.’” Nielson v. Shinseki, 607 F.3d 802, 807 (Fed.
Cir. 2010) (quoting Davis v. Michigan Dep’t of Treasury,
489 U.S. 803, 809 (1989)). Joined parties, as provided in
§ 315, may appeal pursuant to § 319. Accepting RCT’s
argument would require us to read the word “party”
differently between § 315 and § 319, an argument for
which RCT provides no support.
    RCT also argues that, because Appellants’ role before
the Board was limited by agreement and prohibited
presentation of evidence independent of Argentum, Appel-
lants’ participation should not be “transformed into a
right to federal court review.” Appellee’s Br. 19–20. But
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION     13
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§ 315 provides the Board with discretion in joinder, and
that discretion allows for the Board to place requirements
and limitations on joined parties. RCT points to no sup-
port for the proposition that a party subject to such re-
strictions in its IPR should be considered to have less
standing to appeal than a party under § 319. RCT argues
that allowing Appellants’ appeal “would constitute an
end-run around the statutory time-limit for instituting
IPR proceedings,” id. at 19, but cites no provision in the
text or legislative history supporting its reading.
    Accordingly, we conclude that Appellants fall within
the zone of interests of § 319 and are not barred from
appellate review. We therefore proceed to the merits.
                       II. MERITS
    On the merits, Appellants challenge the Board’s non-
obviousness conclusion. Regarding claims 1–9, Appel-
lants assert a lead compound analysis, proposing
compound 3l in Kohn 1991 as the lead. In its final writ-
ten decision, the Board did not resolve whether compound
3l was an appropriate lead compound. Instead, it accept-
ed compound 3l as the lead and concluded that Petitioners
did not meet their burden to establish a motivation to
modify that compound. Because we agree with the Board
that Appellants failed to meet their burden to establish a
motivation to modify, we likewise need not resolve wheth-
er compound 3l would have been a suitable lead com-
pound. Accordingly, for our analysis below, we assume, as
the Board did, that compound 3l was an appropriate lead
compound.
    Obviousness is a question of law based on underlying
factual findings. In re Baxter Int’l, Inc. 678 F.3d 1357,
1361 (Fed. Cir. 2012).
   Appellants first argue that an ordinary artisan would
have recognized the methoxyamino group in compound 3l
to be uncommon and to have potential synthetic and
14   MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

stability problems. According to Appellants, a person of
skill in the art would then have been motivated to modify
compound 3l by replacing the amine of its methoxyamino
group with a methylene link to yield a more stable, syn-
thetically accessible, pharmaceutically common and
acceptable moiety.
    In proposing this modification, Appellants rely on the
principles of bioisosterism as recited in Silverman.
Appellants submit that, of the “classical bioisosteres” in
Silverman, only methylene would result in a more phar-
maceutically common and acceptable compound and
resolve the potential stability and synthesis concerns
presented by the methoxyamino moiety. Appellants’ Br.
23. Appellants maintain that Silverman would have
motivated a person of skill in the art to replace the amine
in the methoxyamino group with a methylene link and
have a reasonable expectation of success having done so.
    Appellants submit that their proposed modification
was consistent with Kohn 1991, which detailed “‘stringent
steric and electronic requirements that exist for maximal
anticonvulsant activity in this class of compounds,’ includ-
ing the size of the group on the α-carbon.” Id. at 24 (quot-
ing Kohn 1991, J.A. 2407). According to Appellants, their
proposed replacement retained a small moiety at the α-
carbon, which would have satisfied steric requirements
and would have left the N-benzylamide moiety and acety-
lated amino group unchanged. Appellants also argue
that, consistent with Kohn 1991, their proposed modifica-
tion retained a functionalized oxygen atom two atoms
removed from the α-carbon atom, which Kohn 1991 dis-
closed as associated with excellent potency.
    Appellants further contend that their proposed modi-
fication to compound 3l would have been expected to have
excellent potency. Specifically, Appellants point to Kohn
1991’s teaching that a terminal methoxy group added to
compound 3a resulted in compound 3l, which was ten
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION      15
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times more potent than compound 3a. Before the Board,
Appellants’ expert, Dr. Wang, testified that a person of
skill in the art would have reasonably expected a similar
ten-fold increase in activity from adding a terminal meth-
oxy group to the methyl compound 2a, yielding a racemic
mixture of lacosamide with a predicted ED50 value of 7.6
mg/kg. According to Dr. Wang, this ED50 value would
have been comparable or better than commercially avail-
able reference compounds, including phenytoin, pheno-
barbital, and valproate.
    Notably, Appellants’ predicted potency for “racemic
lacosamide” was less impressive than that of compound
3l. Appellants address that fact by stating that a person
of skill in the art would have sacrificed some potency to
achieve the superior stability of racemic lacosamide over
compound 3l. Appellants maintain that a person of skill
in the art would have had reason to modify 3l to address
stability, synthetic simplicity, and pharmaceutical famili-
arity and acceptability, even if doing so would result in
lower potency.
    As a final point, Appellants argue that a person of
skill in the art would have had reason to isolate the R
enantiomer from its “racemic lacosamide” mixture be-
cause Kohn 1991 teaches that the “anticonvulsant activity
resided primarily with the R stereoisomer.” Appellants’
Br. 32 (quoting Kohn 1991, J.A. 2404).
    RCT counters that, while the record supports the idea
that N–O bonds generally can be labile, the record lacks
evidence that the N–O bond in compound 3l specifically is
labile and would have motivated modification. According
to RCT, such an argument would have been contrary to
the teaching of Kohn 1991, which remarked that its
disclosed compounds, including 3l, were stable. RCT also
suggests that the record is devoid of evidence that the
potential stability issues with the N–O bond would have
outweighed other considerations, including potency and
16   MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

neurotoxicity. Instead, RCT contends that the record
supports that a person of skill in the art would consider
all of a compound’s properties together, as the Board did
in its analysis.
    RCT also argues that Appellants did not provide any
evidence that “only methylene would result in a more
pharmaceutically common and acceptable compound and
resolve the potential stability and synthesis concerns
presented by the methoxyamino moiety.” Appellee’s Br.
23. RCT submits that the ED50 values for the methox-
ymethyl compound, racemic lacosamide, would not have
been known, and Dr. Wang’s prediction of an ED50 was
based only on impermissible hindsight. Similarly, Appel-
lants’ position before the Board was that a person of skill
in the art would replace the NH group with CH2, but RCT
suggests that the FAA literature consistently showed that
removing the amino in the α-carbon amino substituents
reduced potency.
     We agree with RCT that the Board’s findings are sup-
ported by substantial evidence. Even if a person of skill
in the art would have been motivated to modify compound
3l, the record evidence suggests that compounds without a
methoxyamino or nitrogen-containing group at the α-
carbon had reduced activity. For example, compound 3a
in Kohn 1991, with an amine group at the α-carbon,
reported an ED50 of 65.1 mg/kg, whereas compound 2a,
with a methyl group at that position, was less potent with
an ED50 of 76.5 mg/kg. J.A. 2405. Likewise, compounds
3a, 3b, and 3c, with ED50 values of 65.1 mg/kg, 44.5
mg/kg, and 42.4 mg/kg, each have a nitrogen-containing
moiety at the α-carbon. Id. These compounds were more
potent than their oxygen-containing analogs, compounds
3r, 3s, and 3t, with ED50 values of 80.1 mg/kg, 98.3 mg/kg,
and 62.0 mg/kg, respectively. Id.
   The evidence also suggests that replacing the meth-
oxyamino in compound 3l would have yielded a different
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION        17
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conformation. Such a conformational change may have
affected interaction with receptors and altered biological
activity. J.A. 11113–14. Kohn 1991 itself explains that
“stringent steric and electronic requirements exist for
maximal anticonvulsant activity,” J.A. 2404, which would
counsel against modifying compound 3l in a way that
would change its conformation significantly.
    Appellants fault the Board for crediting the testimony
of Dr. Roush, RCT’s expert, regarding the three-
dimensional structures of compound 3l and racemic
lacosamide. The Board, however, provided a sufficient
rationale for relying on Dr. Roush’s testimony that the
three-dimensional structures of compound 3l and racemic
lacosamide would be “very different.” Decision, 2017 WL
1096590, at *10. Specifically, the Board compared Dr.
Roush’s testimony to that of Dr. Heathcock, who agreed
that a molecule’s shape and potency may differ upon
substitution of carbon for nitrogen. Id. at *10–11. The
Board was well within its discretion to credit Dr. Roush’s
testimony. See Yorkey v. Diab, 601 F.3d 1279, 1284 (Fed.
Cir. 2010) (“[T]he Board was well within its discretion to
give more credibility to [one expert’s] testimony over
[another expert’s testimony] unless no reasonable trier of
fact could have done so.”).
    The Board also was entitled to reject bioisosterism as
a basis for a motivation to modify compound 3l. While
Silverman does disclose that that bioisosterism may be
useful to attenuate toxicity in a lead compound, the record
does not indicate why bioisosterism would have been used
to modify compound 3l in particular, which already had a
high potency and low toxicity, and why methylene was a
natural isostere of methoxyamino.
    In light of the reductions in potency and the signifi-
cant conformational changes that would have been ex-
pected, the Board’s finding that a person of skill in the art
would not have been motivated to modify the methoxy-
18   MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

amino group in compound 3l was supported by substan-
tial evidence.
     Because we agree with the Board that Appellants
failed to establish a motivation to modify compound 3l, we
need not reach Appellants’ arguments regarding objective
indicia. Likewise, because we find that Appellants did not
meet their burden to show that claims 1–9 would have
been obvious over Kohn 1991 and Silverman, we conclude
that the Board did not err in concluding that Appellants
failed to meet their obviousness burden regarding claims
10–13, which depend therefrom. Dependent claims, with
added limitations, are generally not obvious when their
parent claims are not. W.L. Gore & Assocs., Inc. v. Gar-
lock, Inc., 721 F.2d 1540, 1555 (Fed. Cir. 1983).
    Aside from these factual issues, Appellants challenge
aspects of the Board’s legal analysis, contending that the
Board improperly required them to prove that the pro-
posed modification would increase or maintain potency
and that the Board negated their proposed motivation
argument without making a finding that the prior art
taught away from the proposed modification. None of
these arguments has merit. Appellants’ arguments are
merely an attack on factual findings under the guise of a
challenge to the Board’s legal analysis. As discussed
above, the Board appropriately considered all the facts
before making a final obviousness determination.
   Having considered the record below, we conclude that
the Board’s obviousness conclusion was supported by
substantial evidence.
    Finally, at oral argument, Appellants requested in the
alternative that the court remand this case in light of
SAS Institute, Inc. v. Iancu, 138 S. Ct. 1348 (2018). Oral
Arg. at 27:05–27:17, http://oralarguments.cafc.uscourts.go
v/default.aspx?fl=2017-2088.mp3. We decline to do so.
MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION       19
TECHS., INC.

    We have held that a party’s request for SAS relief can
be waived. PGS Geophysical AS v. Iancu, 891 F.3d 1354,
1362–63 (Fed. Cir. 2018). In cases where a litigant lodges
a prompt request for SAS-based relief, however, this court
has found waiver inapplicable and remanded to the Board
to consider noninstituted grounds. See, e.g., Adidas AG v.
Nike, Inc., 894 F.3d 1256, 1258 (Fed. Cir. 2018); Polaris
Indus. Inc. v. Arctic Cat, Inc., 724 F. App’x 948, 950 (Fed.
Cir. 2018) (per curiam); South-Tek Sys., LLC v. Engi-
neered Corrosion Sols., LLC, No. 2017-2297, 2018 WL
4520013, at *5 (Fed. Cir. Sept. 20, 2018); Baker Hughes
Oilfield Operations, LLC v. Smith Int’l, Inc., No. 2018-
1754, 2018 WL 4087705, at *2 (Fed. Cir. May 30, 2018).
    Here, Appellants’ request—made over 6 months after
the SAS decision—was not prompt. To be sure, the
Supreme Court’s SAS decision issued after the briefing
was complete in this case. But Appellants had opportuni-
ties to raise the SAS issue with the court before oral
argument (i.e., in a citation of supplemental authority as
authorized by Fed. Cir. R. 28(j)) and chose not to do so.
Indeed, Appellants could have raised their SAS argument
even in their opening oral argument. Instead, they chose
to raise it in their rebuttal argument—when RCT had no
meaningful opportunity to respond. Given the circum-
stances in this case, we find that Appellants have waived
their request for remand. Cf. Becton Dickinson & Co. v.
C.R. Bard, Inc., 922 F.2d 792, 800 (Fed. Cir. 1990) (stat-
ing that the court’s “sound practice” of finding arguments
absent from opening briefs to be waived “may as a matter
of discretion not be adhered to where circumstances
indicate that it would result in basically unfair proce-
dure”).
                       CONCLUSION
    In sum, we affirm the Board’s conclusion that Appel-
lants have failed to show that claims 8–13 would have
been obvious at the time of the invention. We have con-
20   MYLAN PHARMACEUTICALS INC. v. RESEARCH CORPORATION
                                             TECHS., INC.

sidered RCT’s remaining arguments and find them un-
persuasive.
    For the foregoing reasons, we affirm the decision of
the Board.
                      AFFIRMED