Valeant Pharmaceuticals Intl. v. Mylan Pharmaceuticals Inc. ( 2020 )

Case: 18-2097 Document: 89 Page: 1 Filed: 04/08/2020
United States Court of Appeals
for the Federal Circuit
______________________
VALEANT PHARMACEUTICALS
INTERNATIONAL, INC., SALIX
PHARMACEUTICALS, INC., PROGENICS
PHARMACEUTICALS, INC., WYETH LLC, FKA
WYETH,
Plaintiffs-Appellees
v.
MYLAN PHARMACEUTICALS INC., MYLAN INC.,
MYLAN LABORATORIES LIMITED,
Defendants-Appellants
ACTAVIS LLC,
Defendant
______________________
2018-2097
______________________
Appeal from the United States District Court for the
District of New Jersey in Nos. 2:15-cv-08180-SRC-CLW,
2:15-cv-08353-SRC-CLW, 2:16-cv-00035-SRC-CLW, 2:16-
cv-00889-SRC-CLW, 2:17-cv-06714-SRC-CLW, Judge
Stanley R. Chesler.
______________________
Decided: April 8, 2020
______________________
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2 VALEANT PHARMACEUTICALS INTL. v. MYLAN
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BRYAN DINER, Finnegan, Henderson, Farabow, Garrett
& Dunner, LLP, Washington, DC, argued for all plaintiffs-
appellees. Plaintiffs-appellees Valeant Pharmaceuticals
International, Inc., Salix Pharmaceuticals, Inc., Progenics
Pharmaceuticals, Inc. also represented by JUSTIN JAMES
HASFORD, CORA RENAE HOLT, ESTHER LIM; JESSICA C.
LEBEIS, Boston, MA; CHARLES E. LIPSEY, Reston, VA.
CHARLES H. CHEVALIER, Gibbons P.C., Newark, NJ, for
plaintiff-appellee Wyeth LLC. Also represented by
JONATHON BRUGH LOWER.
ROBERT FLORENCE, Parker Poe Adams & Bernstein
LLP, Atlanta, GA, argued for defendants-appellants. Also
represented by MICHEAL L. BINNS, KAREN L. CARROLL.
______________________
Before LOURIE, REYNA, and HUGHES, Circuit Judges.
LOURIE, Circuit Judge.
Mylan Pharmaceuticals Inc., Mylan Inc., and Mylan
Laboratories Ltd. (collectively, “Mylan”) appeal from the
U.S. District Court for the District of New Jersey’s grant of
summary judgment that claim 8 of U.S. Patent 8,552,025
(“the ’025 patent”) is not invalid. Valeant Pharm. Int’l, Inc.
v. Mylan Pharm., Inc., No. 2:15-cv-08180 (SRC), 2018 WL
2023537 (D.N.J. May 1, 2018) (“Decision”). For the reasons
detailed below, we reverse and remand.
BACKGROUND
Valeant owns the ’025 patent, which claims stable me-
thylnaltrexone pharmaceutical preparations. According to
the ’025 patent specification, methylnaltrexone, a quater-
nary amine opioid antagonist derivative, can be useful for
reducing the side effects of opioids but is unstable in aque-
ous solution. The inventors discovered, however, that
when the pH of a methylnaltrexone solution is adjusted,
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optimally to between 3.0 and 3.5, the percentage of total
degradants drops significantly. ’025 patent col. 2 l. 39.
The inventors’ preferred manufacturing process for
their formulation, as described in Example 2, includes sev-
eral ingredients acting in concert. Example 2 includes me-
thylnaltrexone, sodium edetate as a chelating agent,
sodium citrate and citric acid as buffering agents, and so-
dium chloride as an isotonicity agent. Each ingredient in
the formulation plays its own role. For example, the buffer
stabilizes the formulation’s pH, which can drop during an
autoclaving step, and adding isotonicity agents matches
the formulation to the osmotic potential of human extracel-
lular fluids. Chelating agents reduce methylnaltrexone
degradation on their own, and the addition of disodium
edetate in particular yields an additional, synergistic effect
in concert with pH manipulation. The specification thus
explains that “manipulating other parameters in concert
with pH resulted in stable formulations of methylnaltrex-
one anywhere in a range from a pH of 2.0 to 6.0.” ’025 pa-
tent col 8. ll. 62–66.
Relevant here are claim 1 and claim 8 of the ’025 pa-
tent. Claim 8 depends from claim 1, which recites:
A stable pharmaceutical preparation comprising a
solution of methylnaltrexone or a salt thereof,
wherein the preparation comprises a pH between
about 3.0 and about 4.0.
’025 patent col. 19 ll. 25–27. Claim 8 recites “[t]he phar-
maceutical preparation of claim 1, wherein the preparation
is stable to storage for 24 months at about room tempera-
ture.” Id. col. 19 ll. 44–46. Notably, claim 8 recites the
same preparation as claim 1, but with a newly stated re-
sult: 24-month stability. Given that there are no limita-
tions indicating any difference between the preparation of
claim 1 and claim 8, it is unclear what, if anything, ac-
counts for the added stability limitation. Apparently only
the nature of methylnaltrexone and the pH matter. And
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there are no limitations in the claim to bring about the
stated stability.
The ’025 patent is listed in the Orange Book for Re-
listor®, an injectable drug used to treat constipation as a
side effect of taking opioid medication. Mylan filed an Ab-
breviated New Drug Application (“ANDA”) seeking ap-
proval from the U.S. Food and Drug Administration to
market a generic version of Relistor®, and Valeant re-
sponded by bringing suit against Mylan in the District of
New Jersey, alleging that Mylan’s proposed product would
infringe the ’025 patent. As relevant here, Mylan ulti-
mately conceded that its ANDA product would infringe
claim 8 of the ’025 patent but maintained that claim 8 was
invalid as obvious over solutions of similar anti-opioids.
The parties stipulated to the construction of claim 8’s
stability limitation, and the district court did not hold a
claim construction hearing. Specifically, the court entered
the parties’ stipulation that the phrase “the preparation is
stable to storage for 24 months at about room temperature”
means “the methylnaltrexone degradation products in the
preparation do not exceed 2.0% of the total methylnaltrex-
one present in the preparation and the preparation is suit-
able for pharmaceutical use when stored for 24 months at
room temperature.” Stipulation and Order, Valeant
Pharm., Int’l v. Mylan Pharm. Inc., 2:15-cv-08180-SRC-
CLW (May 30, 2017), ECF No. 148; J.A. 651.
Before the district court, Valeant moved for summary
judgment that claim 8 would not have been obvious, and
the district court granted Valeant’s motion. The court re-
jected Mylan’s expert testimony and cited references as in-
sufficient, largely because the references did not teach
methylnaltrexone formulations but instead formulations of
similar but different compounds, naloxone and naltrexone.
Decision, 2018 WL 2023537, at *8. The court also rejected
Mylan’s theory that the claimed pH range would have been
obvious to try. Ultimately, the court held that there was
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nothing in the record suggesting that a pH of 3–4, “without
added stabilizers,” was associated with 24-month stability
for injectable pharmaceutical solutions. Id. at *10.
Mylan appealed, and we have jurisdiction under 28
U.S.C. § 1295(a)(1).
DISCUSSION
We review a grant of summary judgment under the law
of the regional circuit, which in this case is the Third Cir-
cuit. See Charles Mach. Works, Inc. v. Vermeer Mfg. Co.,
723 F.3d 1376, 1378 (Fed. Cir. 2013) (citing Grober v. Mako
Prods., Inc., 686 F.3d 1335, 1344 (Fed. Cir. 2012)). We ex-
ercise plenary review over the district court’s grant of sum-
mary judgment, Capps v. Mondelez Glob., LLC, 847 F.3d
144, 151 (3d Cir. 2017) (citing Seamans v. Temple Univ.,
744 F.3d 853, 859 (3d Cir. 2014)), reviewing it de novo,
Heraeus Med. GmbH v. Esschem, Inc., 927 F.3d 727, 733
(3d Cir. 2019) (citing Faush v. Tuesday Morning, Inc., 808
F.3d 208, 215 (3d Cir. 2015)).
Summary judgment is appropriate when the moving
party demonstrates that “there is no genuine dispute as to
any material fact and the movant is entitled to judgment
as a matter of law.” Fed. R. Civ. P. 56(a); Celotex Corp. v.
Catrett, 477 U.S. 317, 322–23 (1986). We construe the evi-
dence in the light most favorable to the nonmovant and
draw all reasonable inferences in that party’s favor. Capps,
847 F.3d at 151 (citing Prowel v. Wise Bus. Forms, Inc., 579
F.3d 285, 286 (3d Cir. 2009)). “Only disputes over facts
that might affect the outcome of the suit under the govern-
ing law will properly preclude the entry of summary judg-
ment.” Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248
(1986).
The sole issue in this appeal is obviousness. Obvious-
ness is a question of law, supported by underlying fact
questions. In re Baxter Int’l, Inc., 678 F.3d 1357, 1361 (Fed.
Cir. 2012). In our obviousness analysis, we consider the
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scope and content of the prior art, differences between the
prior art and the claims at issue, the level of ordinary skill
in the pertinent art, and any secondary considerations.
Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); see
also Apple Inc. v. Samsung Elecs. Co., 839 F.3d 1034, 1048
(Fed. Cir. 2016) (en banc) (“Objective indicia of nonobvious-
ness must be considered in every case where present.”).
Before the district court, Mylan argued that claim 8
would have been obvious in view of three references teach-
ing formulations of either naloxone or naltrexone and in
view of two treatises on pharmaceutical formulation. We
begin by reviewing those references.
The primary reference at issue here is U.S. Patent
5,866,154 (“Bahal”), entitled “Stabilized Naloxone Formu-
lations” and issued to inventors Surendra Mohan Bahal
and Lei-Shu Wu. Bahal teaches stable compositions of na-
loxone for injection with a pH of 3.0 to 3.5. Similar to the
methylnaltrexone formulation described in the ’025 patent,
the Bahal solutions comprise an opioid antagonist deriva-
tive—in this case, naloxone—an acidic or buffer compo-
nent, a tonicity-adjusting agent, and a stabilizing agent.
Mylan also relied on Oshlack, U.S. Patent Application
Publication 2003/0229111, which describes stable naltrex-
one hydrochloride compositions. Oshlack teaches dissolv-
ing a “stabilizer” in solution before adding naltrexone
hydrochloride. Stabilizers can be organic acids, and, in cer-
tain preferred embodiments, the stabilizer is butylated hy-
droxytoluene or ascorbic acid. Oshlack ¶ 0051. Thereafter,
the pH of the solution may be adjusted to about 3 to about
5, but preferably to about 4. Id. ¶ 0054.
The respective structures of methylnaltrexone, nalox-
one, and naltrexone are as follows:
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explains that many products are formulated at a slightly
acidic pH because of solubility or stability considerations
and that the majority of licensed products have a pH be-
tween 3 and 9. According to Gibson, more acidic pH can
cause phlebitis and pain, while more basic pH can cause
tissue necrosis.
Similarly, another pharmaceutical treatise, Reming-
ton, teaches that drugs with amide or ester linkages are
prone to hydrolysis. Remington explains that many hydro-
lytic reactions are catalyzed by hydronium and hydroxyl
ions, so pH is a relevant consideration in determining the
rate of decomposition. 1 REMINGTON: THE SCIENCE AND
PRACTICE OF PHARMACY 643 (Alfonso R. Gennaro et al. eds.,
19th ed. 1995); J.A. 3255. According to Remington, “[t]he
pH range of minimum decomposition (or maximum stabil-
ity) depends on the ion having the greatest effect on the
reaction,” but, “[i]n general, hydroxyl ions have the
stronger effect.” Thus, Remington concludes, the minimum
reactivity “is often found between pH 3 and 4.” Id.
Relying on these references, Mylan argued that a per-
son of skill in the art would have been motivated to prepare
and would have arrived at the preparation of claim 8 via
routine optimization of pH. Bahal, Oshlack, and Fawcett
each taught pH ranges that overlapped with the “about 3
to about 4” range in claim 8, but those references detailed
formulations of naloxone and naltrexone. In Mylan’s view,
however, the references still established a prima facie case
of obviousness because naloxone and naltrexone were
structurally and functionally similar to methylnaltrexone.
Mylan also argued that the pH range in the claim would
have been obvious to try.
The district court disagreed, rejecting Mylan’s argu-
ments about Bahal, Oshlack, and Fawcett because none of
the references taught methylnaltrexone formulations. In
the court’s view, overlapping ranges only establish a prima
facie case of obviousness when the only difference between
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the prior art is the “range or value of a particular variable.”
Decision, 2018 WL 2023537, at *4.
The district court then turned to what it deemed to be
Mylan’s main argument—that a pH range of 3 to 4 would
have been obvious to try. The court expressly rejected
Mylan’s view that the range was just one of a finite number
of options between pH 3 and 7 that a person of skill would
try, holding that “given any two unequal numbers, the
quantity of number ranges falling between the two is infi-
nite, not finite,” adding that this conclusion was one of
“basic math.” Decision, 2018 WL 2023537, at *5. Mylan
cited Gibson and testimony from two experts that adjusting
pH could improve stability, but the court rejected this evi-
dence because, in its view, the evidence did not support
that “adjusting pH would be the first variable formulators
would consider to improve stability.” Id.
Next, the court rejected Mylan’s assertion that long-
term stability of methylnaltrexone was a predictable result
of arriving at a pH range of 3 to 4. The court faulted the
expert report of Dr. Khan, Mylan’s expert, because he
stated that a person of skill would have expected “stable
formulations” of methylnaltrexone at an acidic pH. The
court held that there was a “large gap” between this testi-
mony and the specific claimed pH range of 3 to 4 with its
claimed stability profile of 24 months. Id. at *7.
In the remainder of its analysis, the district court de-
tailed how the prior art references and expert testimony of
record failed to establish that methylnaltrexone could be
stabilized based on pH alone. The court expressly rejected
Bahal and Oshlack for their reliance on stabilizers in addi-
tion to pH manipulation, holding that neither reference
taught a formulation “without added stabilizers.” Id. at
*7–9. The court recognized that the prior art suggested
that pH was “generally important in formulating pharma-
ceuticals” and could “have an effect on stability,” but, in its
view, the art did not contemplate an injectable solution
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“made stable over the long term by pH alone.” Id. at *10.
After stating that the art recognized that adjusting pH was
only “one dart among a number of others,” the court
granted Valeant’s motion for summary judgment that
claim 8 would not have been obvious. Id. at *10–11.
In this appeal, Mylan argues that the district court
erred in at least two respects: (1) by failing to hold that
Mylan established a prima facie case that claim 8 would
have been obvious because the pH range in the claim over-
laps with pH ranges in the prior art for similar compounds
and (2) by resolving disputed fact issues at summary judg-
ment. We address each argument in turn.
I
Mylan cites three prior art references involving differ-
ent compounds, but each discloses formulations with pH
ranges that overlap with the range recited in claim 8, pH
between about 3 and about 4. Specifically, Bahal teaches
a naloxone composition with a pH of 3 to 3.5, Oshlack
teaches a naltrexone composition with a pH of about 3 to
about 5 and about 4, and Fawcett discloses a naltrexone
formulation with a pH of 3.5 that fell to 3.2 over 90 days.
In Mylan’s view, these references establish a prima facie
case of obviousness because the pH ranges they teach over-
lap with those in claim 8. While no reference contemplates
methylnaltrexone specifically, Mylan submits that methyl-
naltrexone bears significant structural and functional sim-
ilarity to both naloxone and naltrexone such that a person
of skill in the art would seek to use prior disclosed pHs for
naloxone and naltrexone when formulating solutions of
methylnaltrexone.
Valeant responds that overlapping ranges for different
chemical compounds that fail to meet claim 8’s stability re-
quirement do not establish obviousness. According to Va-
leant, the structural and functional similarities of the
compounds are not relevant because claim 8 recites a solu-
tion of methylnaltrexone with a stability profile
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unrecognized and unattained in the prior art. Neverthe-
less, Valeant submits, methylnaltrexone, naloxone, and
naltrexone function differently because of their structural
differences, and nothing about the shared function of the
drugs is relevant to their stability in solution.
We agree with Mylan that the record supports a prima
facie case of obviousness here. In Peterson, this court rec-
ognized that “[a] prima facie case of obviousness typically
exists when the ranges of a claimed composition overlap
the ranges disclosed in the prior art.” In re Peterson, 315
F.3d 1325, 1329 (Fed. Cir. 2003) (citing In re Geisler, 116
F.3d 1465, 1469 (Fed. Cir. 1997)); In re Woodruff, 919 F.2d
1575, 1578 (CCPA 1990); In re Malagari, 499 F.2d 1297,
1303 (CCPA 1974)). At issue in Peterson was a claim to a
nickel-base single-crystal superalloy used in the manufac-
ture of turbine engines. The claimed composition included
a relatively small amount of rhenium—about 1 to 3 per-
cent. The prior art of record taught compositions with 0 to
7 percent rhenium, an overlapping range within which the
narrower, claimed range fell. We explained that “[s]elect-
ing a narrow range from within a somewhat broader range
disclosed in a prior art reference is no less obvious than
identifying a range that simply overlaps a disclosed range.”
Peterson, 315 F.3d at 1329–30. We thus held that the over-
lapping ranges were sufficient to establish a prima facie
case of obviousness, shifting the burden to the patentee to
show that the invention would not have been obvious.
Here, the pH range recited in claim 8 clearly overlaps
with the pH range in the record art, but none of the refer-
ences disclose the same drug as the one claimed. We are
thus presented with the question whether prior art ranges
for solutions of structurally and functionally similar com-
pounds that overlap with a claimed range can establish a
prima facie case of obviousness. We conclude that they can
and, in this case, do.
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We have held that, for chemical compound claims, a
prima facie case of obviousness “frequently turns on the
structural similarities and differences between the com-
pounds claimed and those in the prior art.” Daiichi Sankyo
Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1352 (Fed. Cir.
2010) (citing In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990)
(en banc)). Our case law reflects an understanding that
skilled artisans can expect structurally similar compounds
to have similar properties. See, e.g., Dillon, 919 F.2d at 692
(“[S]tructural similarity between claimed and prior art
subject matter, proved by combining references or other-
wise, where the prior art gives reason or motivation to
make the claimed compositions, creates a prima facie case
of obviousness . . . .”); In re Deuel, 51 F.3d 1552, 1558 (Fed.
Cir. 1995) (“Structural relationships may provide the req-
uisite motivation or suggestion to modify known com-
pounds to obtain new compounds.”). We have also
recognized that an obviousness analysis can rely on prior
art compounds with similar pharmacological utility in ad-
dition to structural similarity. See, e.g., In re Merck & Co.,
Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (holding that a
person of skill in the art would have expected amitriptyline
to resemble imipramine in the alleviation of depression in
humans because of the drugs’ close structural similarity
and similar use); Application of Payne, 606 F.2d 303, 314
(CCPA 1979) (“Because of the close structural similarity
between the claimed compounds at issue here and the com-
pounds [in the prior art], and because those prior art com-
pounds possess pesticidal activity, we conclude that the
required motivation is present here.” (citing In re Wood,
582 F.2d 638, 641 (CCPA 1978)); Application of Rosselet,
347 F.2d 847, 850 (CCPA 1965) (“[A]ppellants have failed
to present adequate evidence to overcome a prima facie
showing of obviousness by reason of the admitted ‘gross
structural similarities’ of the art compounds, coupled with
the fact those compounds are shown to have utility in the
same area of pharmacological activity.”).
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Our previous cases address claims to compounds and
their uses. But the principle established in these cases ap-
plies more broadly: a person of skill in the art can expect
that compounds with common properties are likely to share
other related properties as well. See Anacor Pharms., Inc.
v. Iancu, 889 F.3d 1372, 1384 (Fed. Cir. 2018) (“Where the
patent is directed to a new treatment using a known com-
pound, it is reasonable to assume that similar compounds
that share certain common properties are apt to share
other related properties as well.” (citing Merck, 800 F.2d at
1096)). When compounds share significant structural and
functional similarity, those compounds are likely to share
other properties, including optimal formulation for long-
term stability.
Here, the art teaches stable formulations of naloxone,
naltrexone, and methylnaltrexone. All three compounds
are well-known opioid antagonists that operate by binding
to the body’s opioid receptors without activating them.
Each is an oxymorphone derivative, and the group mem-
bers have remarkably similar structures, as indicated ear-
lier. The only structural difference between these three
molecules is the identity of the functional group attached
to the nitrogen atom. Naloxone is a neutral tertiary amine.
Naltrexone, also a neutral tertiary amine, has a cyclo-
propylmethyl group attached to the nitrogen. Methylnal-
trexone, a derivative of naltrexone, is a quaternary
ammonium salt and has both a cyclopropylmethyl group
and a methyl group attached to its nitrogen with a positive
charge. Because of the strong structural and functional
similarity between the molecules, a person of skill could ex-
pect similar stability of the molecules at similar pH ranges
in solution. The district court erred by rejecting this infer-
ence as a matter of law at the summary judgment stage.
Because these three molecules bear significant struc-
tural and functionality similarity, and because the prior
art of record teaches pH ranges that overlap with the pH
range recited in claim 8, Mylan has at least raised a prima
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facie case of obviousness sufficient to survive summary
judgment.
Our holding should not be misconstrued to mean that
molecules with similar structure and similar function can
always be expected to exhibit similar properties for formu-
lation. Indeed, when this case is tried to a factfinder, the
factfinder should consider whether Valeant has rebutted
Mylan’s prima facie case, by, for example, establishing that
the claimed pH range is critical or that the quaternary ni-
trogen results in unexpected beneficial properties. See,
e.g., Geisler, 116 F.3d at 1469; Woodruff, 919 F.2d at 1578.
Valeant may also attempt to rebut Mylan’s case by showing
that the prior art teaches away from the claimed invention
in any respect. Peterson, 315 F.3d at 1331 (citing Geisler,
116 F.3d at 1469). Whether methylnaltrexone’s structural
similarity in an overlapping range of pH in solution is suf-
ficient to yield a prima facie case of obviousness depends
on the facts of record. In re Jones, 958 F.2d 347, 350 (Fed.
Cir. 1992) (“Every case, particularly those raising the issue
of obviousness under section 103, must necessarily be de-
cided upon its own facts.”). Contrary to the district court’s
view in this case, however, such a theory of obviousness is
not defective as a matter of law, and summary judgment to
that effect was granted in error.
II
Next, we address Mylan’s argument that there were
factual disputes precluding summary judgment. Many of
Mylan’s arguments have been adequately addressed by our
analysis above. Mylan raises a significant concern, how-
ever, with the district court’s obvious-to-try analysis. In
evaluating Mylan’s obvious-to-try argument, the district
court held that there was not a finite number of options
between pH ranges falling between 3 and 7. The court held
that, as a matter of “basic math,” “given any two unequal
numbers, the quantity of number ranges falling between
the two is infinite, not finite.” Decision, 2018 WL 2023537,
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at *5. The court also rejected Mylan’s citations of expert
testimony and prior art references because none of the ref-
erences identified pH as the “first variable” that an experi-
enced formulator would consider and because Mylan’s
expert concluded that a person of skill would have expected
only “stable formulations,” not formulations stable for 24
months at room temperature. Id. at *6–7.
In Mylan’s view, the district court disregarded Mylan’s
obvious-to-try evidence because the pH ranges taught in
the prior art were not sufficiently narrow. Mylan submits
that the adequacy of a prior art range is a classic question
of fact and that the district court imposed a heightened pre-
dictability requirement.
Valeant does not appear to defend the district court’s
“basic math” reasoning and, respectfully, we disagree with
the court’s view of basic math. Instead, Valeant responds
that a pH range of 3 to 4 would not have been obvious to
try because the asserted prior art did not disclose a formu-
lation exhibiting 24-month stability and because Mylan’s
experts did not explain why such stability would have been
expected.
We agree with Mylan that the district court’s obvious-
to-try analysis is inconsistent with precedent. “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.” KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). If one of
these predictable solutions leads to the anticipated success,
the combination was obvious to try. Id.
The bounded range of pH 3 to 4 presents a finite num-
ber of narrower pH ranges for a skilled artisan to try. As
a matter of math, there may be an infinite potential num-
ber of ranges within the range 3 to 4, but only if the reali-
ties of pH values (and the limitations of commercially
available pH meters) are ignored. But on this record, there
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is no indication that pH is measured to any significant fig-
ure beyond two digits. And in our view of basic math and
based on the record, there is only one significant figure af-
ter the decimal point, in which case the range of pH varia-
bles is ten, or, if one considers two significant figures after
the decimal point, one hundred, not an infinity.
The district court rejected record evidence because no
reference listed pH as the “first variable” that an artisan
would manipulate. But there is no requirement that for a
variable to be obvious to try, it must be the first variable a
person of skill would alter. And as to the stability limita-
tion, a factfinder could draw the inference from this record
that trying a pH of 3–4 would lead to a methylnaltrexone
formulation stable at room temperature. Absolute predict-
ability that the proposed pH range would yield the exact
stability parameters in the claim is not required. Moreo-
ver, it is important to note that pH is in fact the only vari-
able in claim 8, not one of many variables that can be
experimented with. And, lacking anything in the claim
that is a stabilizer, it can be presumed, if the claim is valid,
that the stability for up to 24 months must be due to the
nature of the compound in the solution and the claimed pH
level. Thus, the district court’s grant of summary judg-
ment on Mylan’s obvious-to-try theory was in error.
CONCLUSION
We have considered the parties’ remaining arguments
but find them unpersuasive. In light of the foregoing, we
reverse the district court’s grant of summary judgment
that claim 8 would not have been obvious and remand this
case for further proceedings consistent with this opinion.
REVERSED AND REMANDED