       NOTE: This disposition is nonprecedential.


  United States Court of Appeals
      for the Federal Circuit
                ______________________

                    APOTEX INC.,
                      Appellant

                           v.

                    WYETH LLC,
                       Appellee
                ______________________

                      2015-1871
                ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2014-
00115.
                 ______________________

               Decided: August 16, 2016
                ______________________

   JOHN J. MOLENDA, Steptoe & Johnson, LLP, New
York, NY, argued for appellant. Also represented by
ROBERT GREENFELD; KATHERINE H. JOHNSON, Chicago, IL.

    DAVID I. BERL, Williams & Connolly LLP, Washing-
ton, DC, argued for appellee. Also represented by STANLEY
E. FISHER, ADAM D. HARBER, THOMAS H.L. SELBY, SARA
KAISER CREIGHTON.
                 ______________________
2                                   APOTEX INC.   v. WYETH LLC



    Before LOURIE, WALLACH, and HUGHES, Circuit Judges.
LOURIE, Circuit Judge.
     Apotex Inc. appeals from the U.S. Patent and Trade-
mark Office Patent Trial and Appeal Board (“the Board”)
final written decision in an inter partes review concluding
that claims 1–23 of U.S. Patent 7,879,828 (“the ’828
patent”) are not unpatentable as obvious. See Apotex Inc.
v. Wyeth LLC, No. 2014-00115, 2015 WL 1848261, at *14
(P.T.A.B. Apr. 20, 2015). For the reasons that follow, we
affirm.
                       BACKGROUND
     Wyeth LLC owns the ’828 patent, directed to a compo-
sition comprising tigecycline, a suitable carbohydrate, and
an acid or buffer. ’828 patent col. 1 ll. 10–11. Tigecycline
is a known antibiotic in the tetracycline family, id. col. 1
ll. 22–23, with the following structure:




see, e.g., id. col. 2 (formula 1). “It may be used as a treat-
ment against drug-resistant bacteria,” and often “work[s]
where other antibiotics have failed.” Id. col. 1 ll. 23–25.
     In solid and solution form, tigecycline experiences two
significant forms of degradation. At basic pH, tigecycline
primarily undergoes oxidation. See id. col. 2 ll. 25–27; id.
col. 2 ll. 31–33 (“[Tigecycline] possesses a phenol moiety,
and it is well known in the art of organic chemistry that
phenols are particularly prone to oxidation.”). As the pH
decreases, however, oxidation slows down, and epimeriza-
APOTEX INC.   v. WYETH LLC                                    3



tion emerges as the “predominant degradation pathway.”
See id. col. 2 ll. 45–50. Tigecycline and its epimer differ in
one respect: “[i]n tigecycline, the N-dimethyl group at the
4 carbon is cis to the adjacent hydrogen,” whereas in the
epimer, the “N-dimethyl group” and the adjacent hydro-
gen are trans to one another. See id. col. 3 ll. 16–19.
Because of that structural difference, the epimer lacks the
antibacterial efficacy of tigecycline, and is thus “an unde-
sirable degradation product.” See id. col. 3 ll. 19–22.
     The invention of the ’828 patent lessens both of the
above-mentioned degradation pathways, and provides for
a stable tigecycline composition in solid and solution form.
Id. col. 1 ll. 7–10; id. col. 4 ll. 49–51. In particular, “[t]he
inventive compositions” comprise tigecycline, an acid or a
buffer, and a suitable carbohydrate. See, e.g., id. col. 1 ll.
10–13. According to the specification, the acid minimizes
oxidative degradation, and the carbohydrate stabilizes the
tigecycline against epimer formation at acidic pH. See id.
col. 4 ll. 56–59.
      The ’828 patent contains 23 composition claims. See
id. col. 14 l. 35–col. 16 l. 10. For purposes of this appeal,
independent claim 1 is representative:
    1. A composition comprising tigecycline, lactose,
       and an acid selected from hydrochloric acid
       and gentisic acid, wherein the molar ratio of
       tigecycline to lactose is between about 1:0.2
       and about 1:5 and the pH of the composition in
       a solution is between about 3.0 and about 7.0.
Id. col. 14 ll. 35–39. Claim 12 is identical to claim 1 but is
limited to hydrochloric acid. See id. col. 14 ll. 62–65. The
remaining dependent claims further require a lyophilized
composition (claim 2); a solid form composition (claims 3
and 18–22); narrower pH ranges (claims 4, 5, 10, 11, and
14–17); and narrower molar ratios of tigecycline to lactose
(claims 9 and 13). See, e.g., id. col. 14 l. 35–col. 16 l. 10.
4                                  APOTEX INC.   v. WYETH LLC



     In March 2013, Apotex filed a petition to institute in-
ter partes review of the ’828 patent. The Board instituted
review based on one ground: that claims 1–23 would have
been obvious over the combination of Chinese Patent
Publication No. 1390550A (“CN ’550”); V. Naggar et al.,
Effect of Solubilizers on the Stability of Tetracycline, 29
PHARMAZIE 126 (1974) (“Naggar”); and E. Pawelczyk et
al., Kinetics of Drug Decomposition: Part 74: Kinetics of
Degradation of Minocycline in Aqueous Solution, 34 POL.
J. PHARMACOL. PHARM. 409 (1982) (“Pawelczyk”).
    In its final written decision, the Board evaluated the
relevant prior art of record and made the following factual
findings. First, the Board found that CN ’550 * discloses a
minocycline-based powder injection, acknowledging that
minocycline is a tetracycline antibiotic. Apotex, 2015 WL
1848261, at *4. The powder injection comprises “minocy-
cline hydrochloride, . . . [a] lyophilized powder supporting
agent, and a suitable amount of a pH adjusting agent.” Id.
The powder supporting agent can be lactose, and the “pH
adjusting agent is an inorganic acid, such as hydrochloric
acid.” Id. The composition is stable against “degradation
by light, heat, oxygen, and water.” See id. at *8.
    Next, the Board found that Pawelczyk addresses the
stability of minocycline in solutions over a broad range of
pHs, specifically “teach[ing] that oxidation is the predom-
inant minocycline degradation process above pH 5.” Id. at
*5. Last, the Board found that Naggar addresses the rate


    *   In its decision to institute, the Board relied on an
incorrect translation of CN ’550. See Apotex, 2015 WL
1848261, at *3–4. Apotex submitted a corrected transla-
tion in response to Wyeth’s objections, and the Board
relied on that corrected translation in its final written
decision. See id. at *4. Discrepancies between the two
translations are not relevant to this appeal. See Appel-
lant’s Br. 11 n.4.
APOTEX INC.   v. WYETH LLC                                 5



of tetracycline epimerization, specifically teaching that “at
a pH of 2–6, tetracycline undergoes a reversible epimeri-
zation at the C4 dimethylamino group.” Id. Further, the
Board found that Naggar teaches that such epimerization
occurs “most rapidly at a pH of 3–4,” and that solubilizers,
such as polysorbate 20, urea, and thiourea, help stabilize
tetracycline against epimerization. Id.
     After making those factual findings, the Board con-
cluded that the combination of CN ’550, Naggar, and
Pawelczyk did not render the claims of the ’828 patent
unpatentable as obvious. It first reasoned that Apotex
failed to explain why a skilled artisan “would have substi-
tuted tigecycline for minocycline in the CN ’550 composi-
tion for any reason, much less in an attempt to make a
lyophilized tigecycline composition that was stable
against epimerization.” Id. at *7. It then reasoned that
Apotex failed to establish why a skilled artisan would
have been motivated to combine CN ’550, Pawelczyk, and
Naggar, and use lactose, as a means for stabilizing tigecy-
cline against epimerization. Id. at *9.
   Apotex timely appealed; we have jurisdiction under 28
U.S.C. § 1295(a)(4)(A).
                         DISCUSSION
    We review the Board’s legal determinations de novo,
In re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), and the
Board’s factual findings underlying those determinations
for substantial evidence, In re Gartside, 203 F.3d 1305,
1316 (Fed. Cir. 2000). 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), such as what a
reference teaches, In re Beattie, 974 F.2d 1309, 1311 (Fed.
Cir. 1992), and whether a skilled artisan would have had
a reason to combine references, see In re Hyon, 679 F.3d
1363, 1365–66 (Fed. Cir. 2012).
6                                 APOTEX INC.   v. WYETH LLC



    Apotex challenges the Board’s conclusion regarding
obviousness in two respects. First, it contends that the
Board imported an epimeric stability limitation into the
claims, and thereby wrongly relied on the failure of CN
’550 to teach the epimeric stability of its composition.
Second, Apotex argues that the Board failed to consider
any motivation to combine the prior art of record beyond
the problem the patentee was trying to solve, in contra-
vention of KSR International Co. v. Teleflex Inc., 550 U.S.
398 (2007), and cases from this court. We address and
reject each challenge in turn.
     Regarding the first challenge, an obviousness inquiry
must focus on the limitations in the claims, see Graham v.
John Deere Co. of Kan. City, 383 U.S. 1, 16 (1966) (noting
that under § 103, an obviousness inquiry involves an
assessment of “the differences between the prior art and
the claims at issue”); see also Senju Pharm. Co. v. Lupin
Ltd., 780 F.3d 1337, 1346 (Fed. Cir. 2015) (“[T]he district
court properly found that corneal permeability is not
relevant in the discussion of composition claims 12–16
because these claims do not contain the corneal permea-
bility limitation found in method claim 6.”), and here, the
challenged claims do not require epimeric stability.
    The Board noted that “the claims do not recite epimer-
ic stability,” and therefore stated that the purported
“obviousness of the claims [could] be demonstrated with-
out a showing of epimeric stability in the prior art,”
Apotex, 2015 WL 1848261, at *9 (emphasis added), but in
the Board’s view, Apotex failed to do so. In any event, it
is hard to see how, in view of that statement, the Board
imported an epimeric stability limitation into the claims.
To the extent the Board considered epimeric stability
during its obviousness analysis generally, it did so in the
context of assessing whether a skilled artisan would have
been motivated to combine references. That is not the
same as importing a limitation into the claims.
APOTEX INC.   v. WYETH LLC                                 7



     Turning to Apotex’s second argument, the Board cor-
rectly considered several purported motivations to com-
bine the prior art beyond epimeric stability. See KSR, 550
U.S. at 419–20; see Alcon Research, Ltd. v. Apotex Inc.,
687 F.3d 1362, 1367–68 (Fed. Cir. 2012). In its brief to us,
Apotex argues that the Board failed to consider specific
motivations to combine the prior art references. Apotex
first contends that that the structural similarity of tigecy-
cline and minocycline would have motivated a skilled
artisan to replace minocycline with tigecycline in the CN
’550 composition. Appellant’s Br. 20. To that end, Apotex
invokes Senju, arguing that a skilled artisan necessarily
would have been motivated to “make the simple substitu-
tion of generational drugs.” See Oral Arg. at 4:35–4:43.
    From the Board’s opinion, it is clear that it fully con-
sidered that potential motivation to combine and found it
wanting. In its first paragraph of analysis, the Board
acknowledged Apotex’s assertion that one of skill in the
art “would find reason to substitute tigecycline for mino-
cycline” in CN ’550 because it “was known to work where
other antibiotics have failed,” and because “minocycline
and tigecycline are tetracycline antibiotics” with “identi-
cal A and B rings.” Apotex, 2015 WL 1848261, at *5. In
addressing that assertion, the Board rejected Apotex’s
proffered expert testimony on this point as unpersuasive.
Id. at *7 (“Dr. Nelson does not explain . . . why the
knowledge that tigecycline is effective ‘where other anti-
biotics have failed’ would lead a person having ordinary
skill” to substitute tigecycline for minocycline in CN ’550).
And Apotex did not establish that minocycline was known
to “have failed.”
     Moreover, the Board found that no evidence suggested
that tigecycline would be as stable in the CN ’550 compo-
sition, as the notion of “identical A and B rings” alone was
insufficient to show that. See id. at *8; cf. Joint App.
1729–34 (Wyeth’s expert noting that the oxidation rates
for tigecycline and minocycline differ because of their
8                                    APOTEX INC.   v. WYETH LLC



differing structures); ’828 patent col. 3 ll. 32–34 (“[T]he
rate of degradation may vary depending upon the tetracy-
cline”; “the epimerization rate of tigecycline is particularly
fast.”); id. col. 4 ll. 4–6 (“[E]pimerization is a more serious
problem with tigecycline than with other tetracyclines[,]
such as minocycline.”). Thus, there can be no question
that the Board considered the structural similarities
between tigecycline and minocycline as a potential moti-
vating factor for a skilled artisan to substitute tigecycline
for minocycline in the CN ’550 composition. The Board
simply found that the record did not support that finding,
and we decline to disturb its decision on appeal. Moreo-
ver, there is not necessarily a motivation to substitute one
antibiotic for a structurally related one when the prior-art
antibiotic has a favorable stability profile, and there is
nothing in the record here to show that the substitution
would solve any other problem.
    We further find Apotex’s invocation of Senju unper-
suasive. As an initial matter, Senju does not stand for the
general proposition that a skilled artisan would always be
motivated to try later generation compounds in an old
composition. Rather, the conclusion of obviousness in
Senju turned on the very specific factual findings made by
the district court about the teachings of the prior art and
the similarities across the quinolone family of compounds.
See, e.g., Senju, 780 F.3d at 1343 (“The ’470 patent also
teaches that each of the disclosed quinolones have ‘similar
substituents,’ and that pharmaceutical formulations of
gatifloxacin follow ‘the routes well known’ with respect to
‘oral[] and parenteral[]’ administration.” (internal citation
omitted)). Factual findings of that nature in Senju,
favorable to a conclusion of obviousness, are noticeably
absent here.
    In addition to addressing the structural similarities of
tigecycline and minocycline, the Board addressed epimeric
stability, and found that a skilled artisan would not have
been motivated to combine Pawelczyk, Naggar, and CN
APOTEX INC.   v. WYETH LLC                                   9



’550, and use lactose, to stabilize tigecycline against
epimer formation. See Apotex, 2015 WL 1848261, at *7,
*9–13. In particular, the Board found that (1) none of the
references discloses tigecycline; (2) Naggar and Pawelczyk
do not disclose lactose, much less disclose it as a stabiliz-
ing means against epimer formation; (3) CN ’550 teaches
lactose as a “powder supporting agent,” but does not teach
that it makes a composition stable against epimerization;
and (4) Apotex failed to show why a skilled artisan would
have been motivated to use lactose in view of Naggar,
when Naggar teaches a different polysaccharide, poly-
sorbate 20, as the least effective solubilizer in a larger list
of solubilizers, such as urea. Id. at *9, *13. Moreover, the
Board rejected Apotex’s expert testimony as “not support-
ed by objective evidence or analysis,” instead relying on
Wyeth’s evidence as persuasive. Id. at *10–11. Apotex
does not now meaningfully challenge any of those factual
findings; we likewise decline to disturb them.
    Apotex lastly argues that the Board failed to consider
whether a skilled artisan (1) would have been motivated
to combine the art of record to optimize the pH ranges in
CN ’550, or (2) would have modified the pH ranges in CN
’550 to the ranges recited in the dependent claims of the
’828 patent “because those ranges were commonly used in
conventional injection solutions.” See Appellant’s Br. 20,
29. Apotex correctly asserts that the Board did not ex-
pressly address those motivations, but we find no reversi-
ble error in that omission in view of Apotex’s ultimate
failure to establish why a skilled artisan would have been
motivated to substitute tigecycline for minocycline, the
dispositive issue here.
    In sum, while tigecycline is closely related to minocy-
cline structurally and in terms of benefit, the Board did
not err in concluding that there was insufficient basis in
the record to show that it would have been obvious to a
skilled artisan to substitute tigecycline in the prior art
minocycline composition.
10                               APOTEX INC.   v. WYETH LLC



                      CONCLUSION
    We have considered all of Apotex’s remaining argu-
ments, but conclude that they are without merit. The
Board’s decision was supported by substantial evidence
and not erroneous as a matter of law. For the reasons set
forth above, we affirm the Board’s decision.
                      AFFIRMED
