Apotex, Inc.v.Novartis AG

Patent Trial and Appeal Board

Sep 24, 2015

12189323 (P.T.A.B. Sep. 24, 2015)

Trials@uspto.gov Paper 12
571-272-7822 Entered: September 24, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

TORRENT PHARMACEUTICALS LIMITED
and
APOTEX, INC. AND MYLAN PHARMACEUTICALS INC.,
Petitioners,

v.

NOVARTIS AG AND MITSUBISHI PHARMA CORP.,
Patent Owners.
____________

Case IPR2014-00784
Case IPR2015-00518
Patent 8,324,283 B2
_______________

Before LORA M. GREEN, CHRISTOPHER M. KAISER, and
ROBERT A. POLLOCK, Administrative Patent Judges.

KAISER, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318(a) and 37 C.F.R. § 42.73

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INTRODUCTION
Torrent Pharmaceuticals Limited (“Torrent”) filed a Petition to
institute an inter partes review of claims 1–32 of U.S. Patent No. 8,324,283
B2 (“the ’283 patent,” Ex. 1001). Paper 2 (“Pet.”).1 On December 1, 2014,
the Board instituted trial to review patentability of the challenged claims.
Paper 11 (“Dec. on Inst.”). Apotex, Inc. and Mylan Pharmaceuticals Inc.
(“Apotex,” or, together with Torrent, “Petitioners”) filed a separate Petition
also seeking to institute an inter partes review of claims 1–32 of the ’283
patent. IPR2015-00518, Paper 1 (“IPR-518 Pet.”). This second Petition was
accompanied by a motion seeking joinder with the trial that had been
instituted in IPR2014-00784. IPR2015-00518, Paper 2 (“IPR-518 Joinder
Mot.”). On February 17, 2015, the Board instituted trial in IPR2015-00518
and joined the proceedings in IPR2014-00784 and IPR2015-00518.
IPR2015-00518, Paper 8 (“IPR-518 Dec.”).
Thereafter, Novartis AG and Mitsubishi Pharma Corp. (“Patent
Owners”) filed a Response (Paper 28 (“PO Resp.”)), and Petitioners filed a
Reply (Paper 55).2 Patent Owners also filed a motion to amend the
challenged claims by replacing them with proposed amended claims 33–64
(Paper 26 (“Mot. to Amend”)), Petitioners filed an opposition to this motion
(Paper 52 (“Mot. to Amend Opp.”)), and Patent Owners filed a reply (Paper

1 This decision refers to papers and exhibits filed in both the joined
proceedings (IPR2014-00784 and IPR2015-00518). Except where noted
otherwise, citations are to the papers and exhibits filed in IPR2014-00784.
2 Redacted versions of the Response and Reply were filed as Paper 30 and
Paper 54, respectively.
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62 (“Mot. to Amend Reply”)).3 Both Petitioners and Patent Owners
requested oral argument, and an oral hearing was held July 31, 2015. A
transcript of the oral argument is included in the record.4 Paper 111 (“Tr.”).5
Each side filed a motion to exclude certain evidence submitted by the other
side. Paper 73; Paper 78. The parties filed oppositions to these motions to
exclude, Paper 80; Paper 83, as well as replies to the oppositions, Paper 91,
Paper 94. In addition, there are multiple pending motions to seal various
pleadings and exhibits.
We have jurisdiction under 35 U.S.C. § 6(c), and we issue this Final
Written Decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. We
conclude Petitioners have established by a preponderance of the evidence
that claims 1–32 of the ’283 patent are unpatentable. We also conclude that
Patent Owners have failed to establish by a preponderance of the evidence
that proposed amended claims 33–64 are patentable. In addition, we deny in

3 Redacted versions of the Motion to Amend, the Opposition to the Motion
to Amend, and the Reply to the Opposition to the Motion to Amend were
filed as Paper 27, Paper 53, and Paper 63, respectively.
4 The parties are directed to file a redacted version of the transcript that will
be publicly available. The redacted version of the transcript shall be filed no
later than one week after the entry of the present decision.
5 Patent Owner filed objections to the demonstrative exhibits used by
Petitioners at the hearing. Paper 105. In reaching our decision on the
merits, we have considered arguments and evidence that are presented in the
demonstrative exhibits only where those arguments and evidence were
presented previously and are supported by the record. We expunge all the
demonstrative exhibits themselves from the record, because they constitute
neither evidence nor, to the extent that they differ from the written briefing,
argument allowable under our rules.
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part and dismiss in part each side’s motion to exclude evidence, we seal
certain pleadings and exhibits, and we unseal several exhibits that we
substantively rely on in reaching our decision.

The ’283 Patent
The ’283 patent relates to a solid pharmaceutical composition suitable
for oral administration, wherein the composition comprises a sphingosine-1
phosphate (S1P) receptor agonist and a sugar alcohol. Ex. 1001, 1:11–14,
1:33–35. “The sugar alcohol may act as a diluent, carrier, filler or bulking
agent, and may suitably be mannitol.” Id. at 9:53–54. The ’283 patent
indicates that solid compositions comprising a sugar alcohol are
“particularly well suited to the oral administration of S1P receptor agonists,”
“provide a convenient means of systemic administration of S1P receptor
agonists, do not suffer from the disadvantages of liquid formulations for
injection or oral use, and have good physicochemical and storage
properties.” Id. at 1:36–42. According to the ’283 patent, a “particularly
preferred S1P receptor agonist . . . is FTY720, i.e. 2-amino-[2-(4-
octylphenyl)ethyl]propane-1,3-diol.” Id. at 8:23–25. FTY720 is also known
as fingolimod. Ex. 2007 ¶ 13; Tr. 31:13–15. The ’283 patent further
describes that solid compositions comprising a sugar alcohol “may show a
high level of uniformity in the distribution of the S1P receptor agonist
through the composition, as well as high stability” and “may be
manufactured on high speed automated equipment.” Ex. 1001, 1:42–48.
S1P receptor agonists are immunomodulating compounds, and solid
pharmaceutical compositions comprising S1P receptors may be useful for
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treating and preventing organ/tissue transplant rejection, autoimmune
disease/inflammatory conditions, or viral myocarditis and viral diseases
caused by viral mycocarditis. Id. at 1:18–22, 12:19–37.
Claims 1 and 19 of the ’283 patent are independent claims and are
illustrative of the claimed subject matter. They are reproduced below.
1. A solid pharmaceutical composition suitable for oral
administration, comprising:
(a) a SIP receptor agonist which is selected from 2-amino-
2-[4-(3-benzyloxyphenoxy)-2-chlorophenyl]propyl-1,3-
propane-diol or 2-amino-2-[4-(3-benzyloxyphenylthio)-
2-chlorophenyl]propyl-1,3-propane-diol, 2-amino-2-[4-
(3-benzyloxyphenylthio)-2-chlorophenyl]-2-ethyl-1,3-
propane-diol, and its phosphates or a pharmaceutically
acceptable salt thereof; and
(b) a sugar alcohol.

19. A solid pharmaceutical composition suitable for oral
administration, comprising mannitol and 2-amino-2-[2-(4-
octylphenyl)ethyl]propane-1,3-diol or a pharmaceutically
acceptable salt thereof.

Id. at 17:2–11, 18:7–10.

Reviewed Ground of Unpatentability
The Board instituted trial to review the patentability of the challenged
claims on the following ground:
Claim(s)
Challenged Basis References
1–32 § 103 Chiba6 and Aulton7

6 Chiba et al., US 6,004,565, issued Dec. 21, 1999 (“Chiba,” Ex. 1006).
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ANALYSIS
Claim Construction
In an inter partes review, the Board interprets a claim term in an
unexpired patent according to its broadest reasonable construction in light of
the specification of the patent in which it appears. 37 C.F.R. § 42.100(b);
see In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1276–79 (Fed. Cir.
2015). Under that standard, absent any special definitions, we assign claim
terms their ordinary and customary meaning, as understood by a person of
ordinary skill in the art, in the context of the entire patent disclosure. In re
Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Only terms
which are in controversy need to be construed, and then only to the extent
necessary to resolve the controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g,
Inc., 200 F.3d 795, 803 (Fed. Cir. 1999). For this reason, we do not construe
several terms for which constructions were proposed in the Petition but
about which the parties do not disagree.

Solid Pharmaceutical Composition Suitable for Oral Administration
In our decision instituting trial, we construed “solid pharmaceutical
composition suitable for oral administration” as “solid composition capable
of delivering a pharmaceutical effect when administered orally.” Dec. on
Inst. 5. In the post-institution briefing, neither party challenged this
construction, and we have not identified any reason to change it.

7 PHARMACEUTICS: THE SCIENCE OF DOSAGE FORM DESIGN, 223–321
(Michael E. Aulton ed., 1988) (“Aulton,” Ex. 1021).
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Accordingly, we maintain our previous construction of “solid
pharmaceutical composition suitable for oral administration” as “solid
composition capable of delivering a pharmaceutical effect when
administered orally.”

Is Stable
Patent Owners propose constructions for three terms used in the
proposed amended claims. First, they argue that “is stable,” with respect to
a pharmaceutical composition, means “meets stability requirements of a test
required by FDA for approval.” Mot. to Amend Reply 26–27. Petitioners
disagree with this proposed construction but do not offer an alternative
construction, arguing instead merely that the ’283 patent itself would not
lead a person of ordinary skill in the art to any understanding of the meaning
of “is stable” at all. Mot. to Amend Opp. 19–21. We are not persuaded by
this argument. Claim terms are to be construed in the context of the entire
patent disclosure, but they are also to be construed from the perspective of
the understanding of a person of ordinary skill in the art. Here, there is
evidence that a person of ordinary skill in the art would understand the
requirement for stability “in the context of requirements for FDA approval.”
Ex. 2042 ¶¶ 73–75.8 We have not been directed to any contrary evidence.
Accordingly, we construe “is stable” to mean “meets stability requirements
of a test required by FDA for approval.”

8 A public version is available at Ex. 2263 ¶¶ 73–75.
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Has Substantially Uniform Distribution . . . Throughout the Composition
Patent Owners propose that a pharmaceutical composition that “has
substantially uniform distribution . . . throughout the composition” is one
that “meets content uniformity requirements for active ingredients in solid
oral unit dosage forms as defined by the [United States Pharmacopeia].”
Mot. to Amend 27–28. Petitioners argue that this is incorrect, pointing out
first that the content uniformity requirements in the United States
Pharmacopeia are designed to ensure a consistent dose of an active
ingredient from one oral dosage unit (e.g., a tablet or capsule) to the next,
and noting next that “uniform distribution . . . throughout the composition”
would instead be interpreted by a person of ordinary skill in the art to refer
to a uniform distribution of the active ingredient throughout a single oral
dose unit. Mot. to Amend Opp. 17–19. Petitioners are correct that the
United States Pharmacopeia is directed at ensuring a minimum of variation
from one oral dosage unit to the next. Ex. 2072, 3–5.9 But there is evidence
of record that “[a] person skilled in formulation in 2003 would have also
used [the United States Pharmacopeia] analysis to infer that the drug was
homogeneously distributed within each tablet,” Ex. 2280 ¶ 49,10 and this
evidence is unrebutted. Accordingly, we construe a pharmaceutical
composition that “has substantially uniform distribution . . . throughout the
composition” as one that “meets content uniformity requirements for active

9 Unless stated otherwise, our citations are the page numbers of the exhibit
itself rather than to the page numbers of the original document from which
the exhibit is extracted.
10 A public version is available at Ex. 2285 ¶ 49.
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ingredients in solid oral unit dosage forms as defined by the [United States
Pharmacopeia].”

Rough Particle Surface
Patent Owners argue that “rough particle surface” means “with higher
surface area than a sphere.” Mot. to Amend 28. Petitioners dispute this
construction but do not provide an alternative, arguing instead only that a
person of ordinary skill in the art would be unable to determine the meaning
of this term at all. Mot. to Amend Opp. 21–22. Patent Owners’ evidence
shows that “rough particle surface,” with respect to sugar alcohol particles,
includes sugar alcohol particles “having a higher surface area than a routine
sugar alcohol particle obtained from a spray-dry method.” Mot. to Amend
28 (citing Ex. 1001, 9:60–10:1; Ex. 2042 ¶¶ 76–81). But “rough particle
surface” should not be limited to this narrow embodiment. See Phillips v.
AWH Corp., 415 F.3d 1303, 1323 (Fed. Cir. 2005) (en banc) (“[A]lthough
the specification often describes very specific embodiments of the invention,
we have repeatedly warned against confining the claims to those
embodiments.”). That said, to construe “rough particle surface” to mean
merely “with higher surface area than a sphere,” as Patent Owners suggest,
would be to interpret the term as essentially unbounded. Any particle, even
a perfect sphere, could be said to have a surface area higher than that of an
unspecified sphere, which could be arbitrarily small. In order to avoid this
problem, we construe a particle with a “rough particle surface” to be a
particle “with higher surface area than a sphere of a diameter equal to the
average diameter of the particle in question.”
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Prior Art Disclosures
Chiba
Chiba teaches immunosuppressive compounds with fingolimod as the
preferred species. Ex. 1006, 4:64–5:5. Chiba also teaches that the
immunosuppressive compounds it teaches are useful for treating
“transplantation rejection of organs or tissues” and “autoimmune diseases
such as . . . multiple sclerosis,” among other diseases and conditions. Id. at
6:26–49. Chiba teaches oral administration of fingolimod, including
“admix[ing] with [a] carrier, excipient, diluent, and so on and formulat[ion]
into . . . capsules [or] tablets . . . for administering to patients.” Id. at 8:19–
26. In discussing the preparation of these capsules and tablets for oral
administration of fingolimod, Chiba teaches that
[o]ne skilled in the art is familiar with numerous methods and
tests for determining the effectiveness of a selected route of
administration. Furthermore, pharmaceutically or
physiologically acceptable carriers or excipients for use with
the . . . compounds noted herein are known in the art or can be
readily found by methods and tests known in the art.
Id. at 11:22–28.

Aulton
Aulton teaches the use of tablets and capsules to administer drugs
orally. Ex. 1021, 5. It also teaches that “[t]he successful formulation of a
stable and effective solid dosage form depends on the careful selection of
excipients which are added to facilitate administration, promote the
consistent release and bioavailability of the drug and protect it from
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degradation.” Id. at 30–31. Aulton recommends a short list of “[p]rimary
excipients . . . for initial screening for table[t] and capsule formulations,” id.
at 31, Table 13.16, although no sugar alcohol appears on the list. Despite
this, Aulton lists mannitol as a common diluent used in “[t]ableting by the
wet granulation process,” which Aulton describes as “the most widely used
method for pharmaceutical materials.” Id. at 39–41, Table 18.1; see also id.
at 38 (identifying mannitol among the “[m]aterials currently available as
direct compression diluents”). Aulton teaches that mannitol is “expensive,”
but still “commonly used.” Id. at 41. In addition to these teachings
regarding mannitol, Aulton teaches that magnesium stearate “is the most
popular lubricant used” in tableting. Id. at 42.

Obviousness of Challenged Claims over Chiba and Aulton
Petitioners argue that claims 1–32 would have been obvious over
Chiba and Aulton. Pet. 20–43. Petitioners rely on the Declaration of John
S. Kent, Ph.D., to support the Petition. Ex. 1004. Patent Owners dispute the
unpatentability of claims 1–32, supported by the Declarations of Supriya
Rane, M.S. (Ex. 2007); Madhusudhan Pudipeddi, Ph.D. (Ex. 2041); Stephen
Byrn, Ph.D. (Ex. 2042); Tomoyuki Oomura, M.S. (Ex. 2043); Fred D.
Lublin, M.D. (Ex. 2044); and David Blackburn, Ph.D. (Ex. 2045). In
addition, Petitioners’ Reply relies on the Reply Declaration of John S. Kent,
Ph.D. (Ex. 1031) and the Declaration of Joel W. Hay, Ph.D. (Ex. 1041).
After reviewing the complete record, we conclude Petitioners have
shown that Chiba and Aulton teach or suggest each limitation of claims 1–32
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of the ’283 patent, that a person of ordinary skill in the art11 would have had
a reason to combine the teachings of Chiba and Aulton, and that a person of
ordinary skill in the art would have had a reasonable expectation of success
in combining the teachings of Chiba and Aulton. Even when considering the
record evidence of objective indicia of nonobviousness, we conclude that
Petitioners have shown, by a preponderance of the evidence, that each of the
challenged claims would have been obvious over the combination of Chiba
and Aulton.

Claim 19
Independent claim 19 recites “[a] solid pharmaceutical composition
suitable for oral administration, comprising mannitol and [fingolimod] or a
pharmaceutically acceptable salt thereof.” Ex. 1001, 18:7–10.
There is no dispute that Chiba and Aulton together teach all the
limitations of claim 19. Chiba teaches the claimed “solid pharmaceutical
composition suitable for oral administration, comprising” fingolimod, and
Aulton teaches the claimed mannitol excipient. Ex. 1006, 3:25–43, 4:64–
5:5, 8:19–28, 11:20–34; Ex. 1021, 40–41; Ex. 1004 ¶¶ 93–94, 170. The
remaining questions regarding whether claim 19 would have been obvious
over the combination of Chiba and Aulton are whether a person of ordinary

11 The parties do not dispute the level of skill in the art. We also note that
“[a] specific finding on the level of skill in the art is not . . . required where
the prior art itself reflects an appropriate level and a need for testimony is
not shown.” Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d
158, 163–64 (Fed. Cir. 1985).
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skill in the art would have had a reason to combine the teachings of the
references and whether that person would have had a reasonable expectation
of success in doing so. In addition, Patent Owners argue that several
objective indicia show that claim 19 would not have been obvious.

1. Reason to Combine Chiba’s Fingolimod Teaching and
Aulton’s Mannitol Teaching
In arguing against the unpatentability of claim 19, Patent Owners
argue first that the inventors of the ’283 patent discovered the reason to
combine mannitol and fingolimod and that Petitioners have failed to prove
adequately that a person of ordinary skill in the art at the time of the
invention would have had any reason to combine them. PO Resp. 34–48.
As an initial matter, we agree with Patent Owners that Petitioners bear
the burden of persuasion with respect to a reason for the person of ordinary
skill in the art to combine the teachings of Chiba and Aulton. Petitioners
“bear the burden of proving a proposition of unpatentability by a
preponderance of the evidence,” 35 U.S.C. § 316(e), and, to the extent that
Petitioners seek to prove the unpatentability of claim 19 by establishing that
it would have been obvious over the combined teachings of Chiba and
Aulton, they must establish as part of their “proposition of unpatentability”
that a person of ordinary skill in the art would have had a reason to combine
those teachings.
We disagree, however, with Patent Owners’ argument that the
inventors’ mere discovery of a new reason to combine fingolimod and
mannitol renders nonobvious an invention that was known in the prior art.
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Where the prior art teaches the claimed invention, a claim is not rendered
patentable by virtue of being motivated in the inventors’ minds by a newly-
discovered advantage of the prior-art combination; allowing such a claim to
stand “would remove from the public that which is in the public domain.” In
re Wiseman, 596 F.2d 1019, 1022 (CCPA 1979); see also Cross Med.
Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed.
Cir. 2005) (“One of ordinary skill in the art need not see the identical
problem addressed in a prior art reference to be motivated to apply its
teachings.”). Here, Patent Owners argue that the newly discovered low-dose
instability of fingolimod when mixed with common excipients motivated the
inventors’ choice of the allegedly less common mannitol as an excipient.
PO Resp. 12–15 (citing Ex. 2043 ¶¶ 14–19, 22, 24–36). As explained
above, though, it does not matter that the prior art failed to recognize this
advantage of a fingolimod-mannitol combination. “[T]he motivation in the
prior art to combine the references does not have to be identical to that of the
[patentee] to establish obviousness.” In re Kemps, 97 F.3d 1427, 1430 (Fed.
Cir. 1996).
We are not persuaded otherwise by Leo Pharmaceutical Products,
Ltd. v. Rea, discussed by Patent Owners at pages 35–36 of the Response. In
that case, although the inventors argued that they discovered a stability
problem with a combination of ingredients known in the prior art, in fact
there was evidence that the prior art taught away from combining those
ingredients. Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1353–54 (Fed.
Cir. 2013). Patent Owners have not alleged, and the record does not support,
that the prior art here taught away from combining mannitol and fingolimod.
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Thus, the fact that the inventors of the ’283 patent may have
discovered a new advantage of a combination of prior-art ingredients is not
sufficient to render the claims of the ’283 patent patentable, as long as there
was some reason to combine the prior-art teachings that those ingredients
should be used. Patent Owners argue that Petitioners have failed to prove
such a reason to combine, PO Resp. 41–49, but the record establishes
otherwise. First, Chiba teaches that a person of ordinary skill in the art
would have been able to identify or easily determine excipients that would
have been compatible with fingolimod. Ex. 1006, 11:24–28
(“pharmaceutically or physiologically acceptable carriers or excipients for
use with the . . . compounds noted herein are known in the art or can be
readily found by methods and tests known in the art”). Second, Aulton
teaches that mannitol is not only a known diluent for direct compression
manufacturing, but also commonly used in wet granulation, which Aulton
teaches is “the most widely used method for pharmaceutical materials.”12
Ex. 1021, 39–41, Table 18.1. This combination of teachings already
strongly suggests that mannitol likely would have been a target of
investigation for a person of ordinary skill in the art interested in finding an
excipient compatible with fingolimod, but there is additional evidence of the
reason to combine fingolimod and mannitol.

12 There is additional evidence that wet granulation is “[o]ne of the most
common steps in the manufacture of capsules and tablets.” Ex. 1031 ¶ 43.
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One prior-art reference, Sakai,13 directly instructs that the two
ingredients should be combined. Ex. 1005, 10:31–48. Patent Owners argue
that Sakai’s teaching of the combination of fingolimod and mannitol is
irrelevant because Sakai is limited to liquid-phase pharmaceutical
compositions, as opposed to the claimed solid oral dosage forms. PO Resp.
41 (citing Ex. 2042 ¶ 3014 (“The excipients used in liquid formulations are
not relevant for solid formulations.”)). But Patent Owners’ own declarant
(as the author of Ex. 2042), Dr. Stephen Byrn, wrote an article stating
otherwise: “Most, but not all, drug degradations in the solid state take place
via chemical mechanisms that are identical to those that occur in solution.
Hence, a mechanistic understanding gained from solution studies can be
very helpful.” Ex. 1030, 5. Although Patent Owners note that Exhibit 1030
goes on to discuss specific exceptions to this rule, Tr. 42:13–16, we have not
been directed to any evidence of record that suggests that any of those
exceptions applies here. The fact is that, according to Patent Owners’ own
declarant, a suggestion to combine ingredients in the liquid phase would
have been relevant to the determination of a person of ordinary skill in the
art to combine the same ingredients in the solid phase.15

13 Sakai et al., US 6,277,888 B1, issued Aug. 21, 2001 (“Sakai,” Ex. 1005).
14 A public version is available at Ex. 2263 ¶ 30.
15 Our conclusion in our institution decision that Sakai’s teaching of a
combination of mannitol and fingolimod in the liquid phase was not
sufficient on its own to “teach that mannitol is a conventional excipient for
use in solid pharmaceutical compositions,” Dec. on Inst. 12, does not require
us to ignore the record evidence that Sakai’s teaching would have been
relevant to the decision of which excipient to use in formulating a solid oral
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In addition to the direct teaching in Sakai that mannitol and
fingolimod should be combined, several documents that would have been
known to a person of ordinary skill in the art teach that mannitol provides
advantages when used as a diluent in tableting. Remington’s Pharmaceutical
Sciences, described as “[a] textbook and reference work for pharmacists,
physicians and other practitioners of the pharmaceutical and medical
sciences,” lists mannitol as one of nine diluents used “to make tableting
possible.” Ex. 2050, 5, 86. It also states that mannitol is one of nine
“common diluents” that are useful as “[d]irect-compression vehicles or
carriers” because they “have good flow and compressible characteristics.”
Id. at 96. The Theory and Practice of Industrial Pharmacy, described as “a
comprehensive reference source on modern industrial pharmacy” that is
“useful to practitioners in the pharmaceutical and allied health sciences . . .
and others seeking information concerning the design, manufacture, and
control of pharmaceutical dosage forms,” lists mannitol as one of fourteen
diluents in a table of “[c]ommon [t]ablet [e]xcipients.” Ex. 2049, 3, 39. The
Handbook of Pharmaceutical Excipients describes mannitol as “widely
used . . . as a diluent . . . in tablet formulations, where it is of particular value
since it is not hygroscopic.” Ex. 1014, 5. In addition, “[g]ranulations
containing mannitol have the advantage of being dried easily,” and
“[m]annitol does not undergo Maillard reactions.” Id. at 5, 8. These known

dosage form of fingolimod. Furthermore, “the knowledge of [a person of
ordinary skill in the art] is part of the store of public knowledge that must be
consulted when considering whether a claimed invention would have been
obvious.” Randall Mfg. v. Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013).
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advantages of mannitol as a tableting excipient16 provide a strong reason to
combine Chiba’s teaching of a solid oral dosage form of fingolimod and
Aulton’s teaching of mannitol as an excipient for making solid oral dosage
forms. Dystar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick,
Co., 464 F.3d 1356, 1368 (Fed. Cir. 2006) (“[A]n implicit motivation to
combine exists . . . when . . . the combination of references results in a
product or process that is more desirable. . . . [T]here exists in these
situations a motivation to combine prior art references even absent any hint
of suggestion in the references themselves.”).
Given (1) the knowledge in the art that mannitol provided advantages
in formulating tablets generally, (2) Chiba’s teaching that a person of
ordinary skill in the art would have been able to identify or easily determine
excipients that would have been compatible with fingolimod, (3) Aulton’s
teaching that mannitol was a diluent commonly used in the most common
form of pharmaceutical manufacture, (4) Sakai’s teaching that mannitol and
fingolimod should be combined in the liquid phase, and (5) Dr. Byrn’s

16 Mannitol has other advantages, such as a sweet taste and a negative heat
of solution, that are more relevant to chewable tablets than to other solid oral
dosage forms. Ex. 1021, 41. Although the claims of the ’283 patent are not
limited to non-chewable tablets, there is evidence of record that suggests that
fingolimod would be unlikely to be administered in a chewable tablet,
making these advantages less relevant to the reason-to-combine analysis.
Ex. 2263 ¶ 53; Ex. 2043 ¶ 38. Still, the evidence of record does not support
Patent Owners’ contention that mannitol was used only in chewable tablets.
See Ex. 1031 ¶ 27 (citing Ex. 1032; Ex. 1033; Ex. 1034; Ex. 1042; Ex. 1043;
Ex. 1044; Ex. 1045; Ex. 1046; Ex. 1047) (listing non-chewable tablets and
capsules containing mannitol that were marketed before 2003).
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statement that liquid-phase compatibility was relevant to the prediction of
solid-phase compatibility, we conclude that Petitioners have shown a reason
to combine the teachings of Chiba and Aulton.17 It is irrelevant that
Petitioners have failed to establish that the inventors’ actual subjective
reason for combining mannitol and fingolimod was known in the prior art.

2. Reasonable Expectation of Success in Combining
Fingolimod and Mannitol
Patent Owners argue next that Petitioners have failed to establish that
Chiba and Aulton provided a reasonable expectation of success in
combining mannitol and fingolimod. PO Resp. 49–51. According to Patent
Owners, because Chiba does not discuss mannitol specifically, and because
Aulton does not discuss fingolimod specifically, the combination of Chiba
and Aulton would not “have provided a reasonable expectation that
fingolimod and mannitol would be stable.” Id. at 50. Thus, argue Patent
Owners, a person of ordinary skill in the art only would have been motivated
to “vary all parameters or try each of numerous possible choices until one
possibly arrived at a successful result, where the prior art gave either no
indication of which parameters were critical or no direction as to which of
many possible choices is likely to be successful,” which is not sufficient to

17 Because the reason to combine mannitol and fingolimod is provided by a
teaching or suggestion in the prior art, we need not reach Petitioners’
alternate reasons to combine, such as the theory that Patent Owners describe
as an “obvious to try” argument. See KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 418 (2007) (requirement of “teaching, suggestion, or motivation to
combine known elements . . . captured a helpful insight”).
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establish a reasonable likelihood of success. Id. (quoting Medichem, S.A. v.
Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (quoting In re O’Farrell,
853 F.2d 894, 903 (Fed. Cir. 1988)) (internal quotation marks omitted). We
are not persuaded by this argument.
First, Sakai’s direct teaching that mannitol and fingolimod should be
combined would have provided a reasonable expectation that the
combination would be suitable for the purpose that Sakai teaches,
pharmaceutical administration, including any stability necessary to that
purpose. Second, the general stability of drug combinations with mannitol
was known in the art. A 1969 article by Ward18 studied the compatibility of
mannitol with various active drug compounds and concluded that mannitol
was “inert[] . . . in various mechanisms associated with drug-excipient
compatibility.” Ex. 1020, 7. Given the direct teaching by Sakai that
mannitol and fingolimod should be combined, and given the knowledge in
the art that mannitol was unlikely to react with active drug compounds when
used as an excipient, Petitioners have established that a person of ordinary
skill in the art would have had a reasonable expectation of success in
combining fingolimod and mannitol.

18 Donald R. Ward, Lyle B. Lathrop, & Matthew J. Lynch, Dissolution and
Compatibility Considerations for the Use of Mannitol in Solid Dosage
Forms, 58 J. PHARMACEUTICAL SCI. 1464, 1464–67 (Dec. 1969) (“Ward,”
Ex. 1020).
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3. Objective Indicia of Nonobviousness
Finally, Patent Owners argue that objective indicia of nonobviousness
show that the claimed combination of mannitol and fingolimod would not
have been obvious to a person of ordinary skill in the art. PO Resp. 52–58.
These objective indicia include two separate forms of unexpected results, a
long-felt but unmet need, industry praise, and commercial success. Id.

(a) Unexpected Results
Patent Owners first argue that the claimed combination of fingolimod
and mannitol shows unexpected results. “It is the established rule that
‘objective evidence of non-obviousness must be commensurate in scope
with the claims which the evidence is offered to support.’” Allergan, Inc. v.
Apotex Inc., 754 F.3d 952, 965 (Fed. Cir. 2014) (quoting In re Tiffin, 448
F.2d 791, 792 (CCPA 1971)). This is as true for evidence of unexpected
results as it is for any other type of objective evidence of non-obviousness.
See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“the applicant’s
showing of unexpected results must be commensurate in scope with the
claimed range”); In re Clemens, 622 F.2d 1029, 1035 (CCPA 1980) (“In
order to establish unexpected results for a claimed invention, objective
evidence of non-obviousness must be commensurate in scope with the
claims which the evidence is offered to support.”). The evidence of
unexpected results made of record is not commensurate in scope with claim
19.
First, according to Patent Owners, the claimed combination was stable
at low doses of fingolimod, even though combinations of fingolimod and
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other excipients were unstable at those same low doses. PO Resp. 54; see
also id. at 11–15 (citing Ex. 2042 ¶¶ 39–40; Ex. 2043 ¶¶ 14–19, 22, 24–36)
(describing difference in results between low-dose fingolimod-mannitol
mixtures and mixtures of low doses of fingolimod with other excipients).
But, as Petitioners note, Reply 3–4 (citing Ex. 1031 ¶ 85; Ex. 2271, 50:21–
51:919), claim 19 is not limited to any particular dose or dose range of
fingolimod. Instead, claim 19 recites only a solid oral dosage form
containing mannitol and either fingolimod or a pharmaceutically acceptable
salt of fingolimod. Ex. 1001, 18:7–10. Thus, even if the stability of the
mannitol-fingolimod combination at low doses was unexpected, it is
insufficient to support a legally significant finding of unexpected results.
Second, Patent Owners argue that the stability achieved with mannitol
“is superior to other choices [of excipient] to a surprising extent,” given that
“mannitol preserves 4.5 to 11 times as much fingolimod as lactose,
microcrystalline cellulose, and starch.” PO Resp. 54 (citing Ex. 2007 ¶¶ 12–
13). This evidence of unexpected results suffers from the same flaw
discussed above. See Reply 17 (citing Ex. 1031 ¶ 85). Not only is this
evidence limited to low doses of fingolimod, it is limited to a single,
specified dose, 0.25 mg. Ex. 2007, 5 (stating that testing was performed
using 25 µL of a 10 mg/mL drug substance solution). As such, it is evidence
of unexpected results only across a tiny portion of the unlimited dose range

19 A public version is available at Ex. 2276, 50:21–51:9.
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of claim 19, which is insufficient to support a finding of unexpected
results.20

(b) Long-Felt but Unmet Need
Next, Patent Owners argue that the invention claimed in claim 19
satisfied the long-felt but previously unmet need “for a solid oral [multiple
sclerosis] treatment.” PO Resp. 55 (citing Ex. 2044 ¶¶ 25–27). The
supporting evidence is a declaration stating that “some patients are resistant,
afraid, or even unwilling to use needles,” which caused some patients to
“drop[] the [multiple sclerosis] treatment”; that “parenteral medications were
universally inconvenient,” making patients less likely to take their
medication; and that “there were a number of side effects commonly
associated with parenteral [multiple sclerosis] treatments” that “discouraged
patients from continuing with their prescribed course[s] of treatment.”
Ex. 2044 ¶¶ 25–27. Although no other evidence is cited in Patent Owners’

20 Moreover, Ex. 2007, the only evidence cited to support Patent Owners’
argument that mannitol “is superior to other choices [of excipient] to a
surprising extent,” PO Resp. 54, is a declaration filed by a witness who was
not made available for cross-examination. For this additional reason, we
accord it little weight. Ex. 1029, 20:23–21:22. To the extent that Ex. 2007
shows a difference between the stability of mannitol and the stability of
other excipients that is contradicted by Ex. 1025, which does not suffer from
the evidentiary flaws of Ex. 2007, we give greater weight to Ex. 1025 and its
evidence that mannitol and the other excipients tested have similar stability.
See Ex. 1025, 13:37–53.
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briefing,21 additional record evidence shows that patients asked about the
availability of an oral medication as early as 1993, id. ¶ 34, and that the
introduction of the first oral medication in 2010 caused a “‘major shift in the
treatment landscape,’” with “‘many patients . . . switching to oral therapy,’”
id. ¶ 37 (quoting Ex. 2012, 1).
Petitioners argue, Reply 18–19, that there is no evidence that the long-
felt need was for claim 19’s combination of fingolimod and mannitol;
instead, as Patent Owners acknowledge, PO Resp. 55, the need was merely
“for a solid oral [multiple sclerosis] treatment.” According to Petitioners,
any need for a solid oral dosage form of a multiple sclerosis treatment was
satisfied by treatments that were known in the prior art but did not receive
FDA approval until after Patent Owners’ Gilenya product did. Reply 18–19.
Therefore, argue Petitioners, there was no longer any long-felt need by the
time of the invention claimed in the ’283 patent. Id.
We find Petitioners’ argument persuasive. If objective indicia of
nonobviousness are “due to an element in the prior art, no nexus exists.”
Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369 (Fed. Cir. 2011)
(discussing commercial success). Here, the evidence of long-felt need
shows that there was a need merely for a solid oral multiple sclerosis
medication, not specifically for a medication of the form recited in claim 19.
But the general need for a solid oral multiple sclerosis medication was

21 Patent Owners are reminded that 37 C.F.R. § 42.23(a) requires a Response
to “comply with the content requirements for motions,” and 37 C.F.R.
§ 42.22(a)(2) requires motions to include “a detailed explanation of the
significance of the evidence.”
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satisfied in the prior art. In 1999, Chiba itself suggested treating multiple
sclerosis using a solid oral form of fingolimod. Ex. 1006, 6:26–49, 8:19–26.
In addition, teriflunomide, marketed in solid tablet form as Aubagio®, was
known in the prior art at least by April 1, 2002, when it was disclosed to be
useful for treating multiple sclerosis when administered in tablets or
capsules. Ex. 1037, at [22], 1:19–30, 2:60–3:2, 5:1–21; Ex. 2045 ¶ 63.22
Similarly, a capsule form of dimethyl fumarate for the treatment of multiple
sclerosis, marketed as Tecfidera™, Ex. 1070, 2, was disclosed in U.S. Patent
No. 6,509,376 B1, issued January 21, 2003. Ex. 1097, at [45], 2:64–67,
4:25–27, 4:31–33.
Because the prior art contained solid oral multiple sclerosis treatments
using active ingredients other than fingolimod, the fingolimod claimed in
claim 19 was not necessary to satisfy any long-felt need for a solid oral
multiple sclerosis treatment. Nor was the mannitol recited in claim 19: the
evidence of record shows that sugar alcohols were not necessary to make
even fingolimod suitable for oral administration. Ex. 2271, 250:10–
251:15.23 Accordingly, claim 19 did not solve any need for a solid oral
multiple sclerosis treatment that was not already solved in the prior art.

(c) Industry Praise
Patent Owners next argue that Gilenya, which is alleged to be a
commercial embodiment of claim 19, “has received copious acclaim,”

22 A public version of Ex. 2045 ¶ 63 is available at Ex. 2265 ¶ 63.
23 A public version is available at Ex. 2276, 250:10–251:15.
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reflecting “the market’s view that the creation of a solid oral [multiple
sclerosis] treatment was a substantial achievement.” PO Resp. 58 (citing
Ex. 2044 ¶¶ 40–44). The cited supporting evidence shows that the authors
of the Phase III clinical trial study of Gilenya described an “oral treatment
option for relapsing-remitting multiple sclerosis [as] highly desirable,” that
the National MS Society spoke to the FDA “in favor of Gilenya’s approval,”
that the FDA granted Gilenya priority-level review and approved Gilenya as
the first oral MS treatment, that the European Medicines Agency approved
Gilenya noting its “benefit of being taken by mouth,” that the Research and
Development Council of New Jersey awarded the Thomas Alva Edison
Patent Award in the Pharmaceutical Formulation category to Novartis for
the ’283 patent, and that multiple patients using Gilenya have praised it
“with particular emphasis on its oral formulation.” Ex. 2044 ¶¶ 40–44.
Industry praise must be linked to the patented invention. Power-One,
Inc. v. Artesyn Techs., Inc., 599 F.3d 1343, 1352 (Fed. Cir. 2010). Again, if
objective indicia of nonobviousness are “due to an element in the prior art,
no nexus exists.” Tokai Corp., 632 F.3d at 1369. Here, the evidence shows
that what was praised about Gilenya was not the specific formulation recited
in claim 19, but rather the general fact that Gilenya was a solid oral multiple
sclerosis medication. As discussed above, however, a solid oral multiple
sclerosis formulation was known in the prior art, so there is no nexus
between the claimed invention and the industry praise.

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(d) Commercial Success
Lastly, Patent Owners argue that the commercial success of Gilenya
shows that claim 19 would not have been obvious. Here, Petitioners bear the
burden of proving the unpatentability of claim 19 by a preponderance of the
evidence. 35 U.S.C. § 316(e). Part of the evidence weighed in determining
the unpatentability of claim 19 is any relevant evidence of commercial
success. “Commercial success is relevant because the law presumes an idea
would successfully have been brought to market sooner, in response to
market forces, had the idea been obvious to persons skilled in the art.”
Merck & Co., Inc. v. Teva Pharm. USA, Inc., 395 F.3d 1364, 1376 (Fed. Cir.
2005). But commercial success is relevant only when it is “due to
[something] disclosed in the patent . . . which was not readily available in
the prior art.” Richdel, Inc. v. Sunspool Corp., 714 F.2d 1573, 1580 (Fed.
Cir. 1983). That is, as discussed above with respect to other objective
indicia of nonobviousness, “[i]f commercial success is due to an element in
the prior art, no nexus exists” between the commercial success and the
claimed invention. Tokai Corp., 632 F.3d at 1369. Patent Owners bear a
burden of production with respect to evidence of commercial success; they
must show “significant sales in a relevant market, and that the successful
product is the invention disclosed and claimed in the patent.” Ecolochem,
Inc. v. S. Cal. Edison Co., 227 F.3d 1361, 1377 (Fed. Cir. 2000). If Patent
Owners make such a showing, Petitioners may rebut the evidence of
commercial success by showing that “the commercial success was instead
due to other factors extraneous to the patented invention,” id., such as “the
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FDA approval process, Patent Owners’ promotion and marketing, and the
FDA’s new warnings to the labels of . . . other MS drugs,” Reply 25.
Thus, our first question is whether the success of Gilenya was due to
something in the prior art or to some feature claimed in claim 19. As
discussed above, at the time that Gilenya was introduced, it was the first oral
multiple sclerosis medication to be approved by the FDA, and there was
significant pent-up demand for such a drug. Patients and other interested
parties praised Gilenya because it was the first treatment for multiple
sclerosis not to suffer from the drawbacks of injectable medications.
Accordingly, it is not surprising that Gilenya would have seen large sales
figures; much of the demand for Gilenya was simply the demand for an oral
multiple sclerosis medication generally. Patent Owners do not identify any
evidence to the contrary. In fact, Patent Owners themselves argue that
“Gilenya’s sales, prescriptions and profits have been extraordinary in
comparison . . . especially [to] injectable treatments,” that “third-party
observers such as securities analysts attribute that success to Gilenya’s solid
oral form,” that “Novartis’s marketing materials emphasize the oral dose
form,” and that Novartis’s “surveys show that doctors rate Gilenya’s oral
form as a major reason for prescribing it.” PO Resp. 57 (citing Ex. 2045
¶¶ 30–39). Patent Owners’ evidence, the declaration of Dr. Blackburn,
discusses the solid oral formulation feature of Gilenya as the only feature
recited in the ’283 patent that is responsible for Gilenya’s commercial
success. Ex. 2045 ¶¶ 29–43. As discussed above, however, solid oral
dosage forms of multiple sclerosis medications were known in the prior art,
so any commercial success attributable merely to Gilenya’s solid oral
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formulation is not relevant to the issue of commercial success showing the
nonobviousness of claim 19. Because all the record evidence of commercial
success shows that Gilenya’s sales were driven by the known solid oral
dosage form feature, we find insufficient evidence of commercial success
that is relevant to proving claim 19’s nonobviousness.
Moreover, setting aside the issue of whether commercial success of
Gilenya should be probative of nonobviousness, we are not convinced that
Patent Owners have carried their threshold burden to show “significant sales
in a relevant market.” Ecolochem, 227 F.3d at 1377. We have not been
directed to any evidence as to what the relevant market in which Gilenya
competes is. Patent Owners’ briefing does not mention the relevant market
at all, while Dr. Blackburn sometimes suggests that the market might be all
oral and injectable multiple sclerosis treatments, Ex. 2045 ¶¶ 20, 23–24, and
sometimes suggests that the market might be limited to second-line (or later)
multiple sclerosis therapies, id. ¶ 21. In either case, Dr. Blackburn excluded
from his analysis any data regarding sales of Tysabri, id. ¶ 20 n.24,24 a
multiple sclerosis drug that generates more than $1 billion in annual sales,
Ex. 1041 ¶ 38; Ex. 1057, 5–6; Ex. 1058, 37. Dr. Blackburn’s evidence of
Gilenya’s market share is biased towards more significant sales of Gilenya
by this exclusion and, thus, is unreliable as evidence that Gilenya’s sales are
significant in relation to the relevant market as a whole. As for Dr.
Blackburn’s testimony regarding Gilenya’s absolute sales (such as net sales,
gross profits, contribution profits, and number of prescriptions), this type of

24 A public version is available at Ex. 2265 ¶ 20 n.24.
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information does not show commercial success in the absence of additional
evidence “as to what sales would normally be expected in the market.” Ex
parte Jellá, 90 USPQ2d 1009, 1012 (BPAI 2008) (precedential) (citing Ex
parte Standish, 10 USPQ2d 1454, 1458 (BPAI 1988)). Because we have not
been directed to any record evidence of what level of sales should have been
expected to which the actual sales of Gilenya can be compared, and because
the evidence of Gilenya’s market share is flawed, Patent Owners have not
borne the burden of production necessary to trigger Petitioners’ burden to
explain Gilenya’s commercial success as due to factors extraneous to the
claimed invention. Accordingly, we find insufficient evidence of
commercial success that is relevant to the determination of the obviousness
of claim 19 over the combination of Chiba and Aulton.

4. Conclusion with Respect to Claim 19
Chiba and Aulton together teach every limitation of claim 19, and the
evidence of record shows that a person of ordinary skill in the art would
have had a reason to combine the teachings of the references and a
reasonable expectation of success in doing so. In addition, there is
insufficient evidence of objective indicia of nonobviousness that is relevant
to the determination of whether claim 19 would have been obvious over the
combination of Chiba and Aulton. Accordingly, we conclude that claim 19
would have been obvious over the combination of Chiba and Aulton.

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Other Claims
In addition to claim 19, Petitioners challenge the remainder of claims
1–32 as obvious over the combination of Chiba and Aulton.

1. Claims 1, 3, 4, and 32
Petitioners challenge claims 1, 3, 4, and 32, and Patent Owners offer
no separate argument as to these claims. Claim 1 differs from claim 19 in
that it broadens the choice of excipient to include “a sugar alcohol” rather
than claim 19’s “mannitol.” Ex. 1001, 17:2–11, 18:7–10. The mannitol
recited in claim 19 is a species of the genus “sugar alcohol” recited in claim
1. Id. at 9:53–59. Claim 1 also broadens the choice of S1P receptor agonists
beyond the “[fingolimod] or a pharmaceutically acceptable salt thereof”
recited in claim 19. Id. at 17:2–11, 18:7–10. The list of S1P receptor
agonists in claim 1 includes fingolimod, because fingolimod is recited as
“the S1P receptor agonist” in claim 32, which depends from claim 1. Id. at
18:40–43. Thus, while the scope of claim 19 is limited to mannitol and
fingolimod, claim 32’s scope includes all sugar alcohols and fingolimod, and
claim 1’s scope includes all sugar alcohols and a genus of S1P receptor
agonists that includes fingolimod. Accordingly, claim 1 and claim 32 are
each broader than claim 19, and claim 1 and claim 32 each include within
their scope the entire scope of claim 19. Under these circumstances, neither
claim 1 nor claim 32 can be nonobvious if claim 19 is obvious. See
Callaway Golf Co. v. Acushnet Co., 576 F.3d 1331, 1344 (Fed. Cir. 2009)
(holding that a broader claim cannot be nonobvious where a narrower claim
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is obvious). Because we have already concluded that claim 19 is obvious,
we conclude that claims 1 and 32 are obvious.
Similarly, claims 3 and 4 both are broader than claim 19 but contain
within their scope all of claim 19’s scope. Claim 3 depends from claim 1
but narrows the scope of “sugar alcohol” to those that are non-hygroscopic,
while claim 4 depends from claim 1 but narrows the scope of “sugar
alcohol” to mannitol. Ex. 1001, 17:14–18. The mannitol of claim 19 is a
non-hygroscopic sugar alcohol, id. at 9:55–56; Ex. 1014, 5, so it falls within
the scope of claim 3’s recited “non-hygroscopic sugar alcohol.” Of course,
the mannitol recited in claim 19 is the same as the mannitol recited in claim
4. Because claims 3 and 4 are both broader than claim 19 but contain within
their scope the entire scope of claim 19, and because claim 19 is obvious
over the combination of Chiba and Aulton, we conclude that claims 3 and 4
are obvious over the combination of Chiba and Aulton.

2. Claim 2
Petitioners challenge claim 2, and Patent Owners offer no separate
argument as to this claim. Claim 2 depends from claim 1, narrowing it by
requiring the claimed S1P receptor agonist to be present as a hydrochloride
salt. Ex. 1001, 17:12–13. Chiba teaches fingolimod hydrochloride as a
preferred embodiment. Ex. 1006, 4:63–68. Accordingly, claim 2 is obvious
over the combination of Chiba and Aulton.

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3. Claims 5, 6, 20, and 21
Petitioners challenge claims 5, 6, 20, and 21, and Patent Owners offer
no separate argument as to these claims. Claims 5 and 6 depend from claim
1 and narrow it by requiring the addition of a lubricant to the claimed solid
oral dosage form (claim 5) or by requiring the addition of a lubricant that
comprises magnesium stearate to the claimed solid oral dosage form (claim
6). Ex. 1001, 17:19–22. Claims 20 and 21 depend from and narrow claim
19 similarly. Id. at 18:11–14. Aulton teaches that lubricants are commonly
added to solid oral dosage forms of pharmaceutical compositions and that
magnesium stearate is a commonly used lubricant for this purpose.
Ex. 1021, 42. Accordingly, claims 5, 6, 20, and 21 are obvious over the
combination of Chiba and Aulton.

4. Claims 7–12 and 22–24
Petitioners challenge claims 7–12 and 22–24, and Patent Owners offer
no separate argument as to these claims. Claims 7–12 depend either directly
or indirectly from claim 1 and specify the percentage by weight of the
claimed solid pharmaceutical composition that is S1P receptor agonist
(claims 7 and 8), sugar alcohol (claims 9 and 10), or lubricant (claims 11 and
12). Ex. 1001, 17:23–34. Claims 22–24 depend from claim 19 and similarly
specify the percentage by weight of the claimed solid pharmaceutical
composition that is fingolimod (claim 22), mannitol (claim 23), or lubricant
(claim 24). Id. at 18:15–25. Petitioners provide evidence that the selection
of the relative amounts of the constituents of the claimed formulation is the
result of routine optimization. Ex. 1004 ¶¶ 188 (“the amount of active
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present in a formulation is well within the skill of the ordinary artisan to
manipulate and optimize for the appropriate use”), 194 (“ordinarily skilled
artisans in formulation development certainly had the desire to optimize
excipient amounts appropriate for the formulation, approached the
formulation exercise with that intention, and had the skill to do so”), 195
(same). We have not been directed to any evidence of record contradicting
this evidence, so we find that a person of ordinary skill in the art familiar
with Chiba and Aulton would have been able and motivated to optimize the
amount of fingolimod, the amount of mannitol, and the amount of lubricant
to obtain an appropriately effective formulation. Accordingly, claims 7–12
and 22–24 would have been obvious to a person of ordinary skill in the art
over the combined teachings of Chiba and Aulton.

5. Claims 13 and 14
Petitioners challenge claims 13 and 14, and Patent Owners offer no
separate argument as to these claims. Claim 13 depends from claim 1 and
requires that the S1P receptor agonist included in the claimed composition
be “micronized.” Ex. 1001, 17:35–36. Claim 14 depends from claim 13 and
further requires that the S1P receptor agonist be “pre-screened with a 400 to
500 µm mesh screen.” Id. at 17:37–39. Petitioners argue that these
limitations are process steps in product-by-process claims and, therefore,
that they “do[] not add . . . patentably distinguishing element[s] to the claim
1 composition from which [they] depend[].” Pet. 38; see Pet. 39. We agree.
Claims 13 and 14 claim particular products, and these limitations focus on
the method of making those products. “In determining [the patentability] of
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a product-by-process claim, the focus is on the product and not on the
process of making it,” because “an old product is not patentable even if it is
made by a new process.” Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d
1340, 1369–70 (Fed. Cir. 2009). Accordingly, the limitations that claims 13
and 14 add to claim 1, from which they depend, add nothing to the
patentability analysis, making claims 13 and 14 obvious over the combined
teachings of Chiba and Aulton for the same reasons that claim 1 was
obvious.

6. Claims 15, 16, 25, and 26
Petitioners challenge claims 15, 16, 25, and 26, and Patent Owners
offer no separate argument as to these claims. Claims 15 and 16 depend
from claim 1 and require that the claimed solid pharmaceutical composition
be a tablet (claim 15) or a capsule (claim 16). Ex. 1001, 17:40–43.
Similarly, claims 25 and 26 depend from claim 19 and require that the
claimed solid pharmaceutical composition be a tablet (claim 25) or a capsule
(claim 26). Id. at 18:26–29. Aulton teaches both tablets and capsules as
dosage forms used for delivering pharmaceutical compositions. Ex. 1021, 5.
Chiba also teaches that fingolimod can be administered as a tablet or
capsule. Ex. 1006, 8:19–26. Accordingly, claims 15, 16, 25, and 26 are
obvious over the combination of Chiba and Aulton.

7. Claims 17 and 18
Petitioners challenge claims 17 and 18, and Patent Owners offer no
separate argument as to these claims. Claims 17 and 18 depend from claim
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1 and require that the claimed solid pharmaceutical composition be
administered to a subject to treat “organ or tissue transplant rejection, graft
versus host disease, an autoimmune disease, an inflammatory condition,
viral myocarditis or a viral disease caused by viral myocarditis” (claim 17)
or to treat multiple sclerosis (claim 18). Ex. 1001, 17:44–18:6. Chiba
teaches both treating autoimmune diseases generally and treating multiple
sclerosis using fingolimod. Ex. 1006, 6:26–49. Accordingly, claims 17 and
18 are obvious over the combination of Chiba and Aulton.

8. Claims 27–31
Petitioners challenge claims 27–31. Patent Owners argue the
patentability of these claims separately. PO Resp. 59. Claims 27–31 depend
from claim 19 and specify various parameters of the mannitol particles used
to make the claimed solid pharmaceutical composition. Ex. 1001, 18:30–39.
Claims 27 and 28 require that the mannitol particles have “a mean particle
size of” between 100 and 300 µm (claim 27) or between 150 and 250 µm
(claim 28). Id. at 18:30–33. Claims 29 and 30 require that the mannitol
have “a bulk density of” between 0.4 and 0.6 g/mL (claim 29) or between
0.45 and 0.55 g/mL (claim 30). Id. at 18:34–37. Claim 31 requires that the
mannitol have “a single point surface area of 1m2/g to 7 m2/g.” Id. at 18:38–
39. Petitioners argue that, according to the specification of the ’283 patent, a
form of mannitol was known in the prior art and commercially available at
the time the application that issued as the ’283 patent was written. Pet. 41–
42 (citing Ex. 1001, 10:10–12). According to Petitioners, “[i]t would have
been a matter of routine optimization for an ordinarily skilled artisan to
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select this commercially available mannitol product,” particularly given that
these claimed ranges of mannitol particle properties are not critical. Id. at
41.
In response, Patent Owners argue that claims 27–31 “reflect the
inventors’ discovery that mannitol of certain sizes and shapes promotes
fingolimod’s content uniformity.” PO Resp. 59. According to Patent
Owners, “the inventors here discovered a reason unknown in the art to use
mannitol of particular sizes and shapes,” and, because “Petitioners point to
no other motivation to combine these elements” than Patent Owners’ own
motivation, “Petitioners’ arguments fail.” Id.
With respect to content uniformity, Patent Owners identify evidence
that shows that Novartis, in developing Gilenya, encountered problems with
maintaining an even distribution of fingolimod particles through a mixture
of mannitol particles. Ex. 2041 ¶ 31. The first attempt to solve this problem
involved “micronizing the fingolimod substance prior to formulation” in
order to “more uniformly distribute fingolimod in the mixture.” Id. ¶ 30.
When this proved insufficient, the inventors decided to try the commercially
available mannitol particle described in the specification of the ’283 patent,
Parteck M200. Id. ¶ 32. This mannitol improved content uniformity, which
the inventors found surprising, because the difference in size between the
large mannitol particles and the small fingolimod particles should have
reduced content uniformity. Id. ¶¶ 33–34. Later, the inventors theorized
that the “rougher structure” of Parteck M200 (compared to other available
mannitol particles) “might promote fingolimod adhesion to the Parteck
mannitol surface.” Id. ¶ 36.
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This evidence shows that Patent Owners discovered a reason to use
Parteck M200 mannitol in formulating a solid pharmaceutical composition
containing mannitol, but it does not show that this reason was unknown in
the prior art. There is some record evidence to suggest that “combining
larger excipient particles with smaller active ingredient particles was
contrary to the conventional thinking at the time that all particles within a
formulation should be controlled within a similar range,” Ex. 2042 ¶ 80, but
the record also contains evidence that this approach was known in the prior
art to improve content uniformity, particularly with low-dose drugs.
Ex. 1031 ¶¶ 73–83; Ex. 1052, 2–3; Ex. 1053, 2, 5. Accordingly, the
preponderance of the evidence contradicts Patent Owners’ argument that
claims 27–31 reflect a discovery that was unknown in the prior art.
Moreover, we have not been directed to any evidence of record that
the ranges of mannitol particle properties that are claimed in claims 27–31
are critical in achieving the desired content uniformity. All the evidence
shows is that, whatever particular (but unspecified) properties Parteck M200
has, mannitol with those properties is better than mannitol with the
unspecified properties possessed by some other commercially available
mannitol particles. Thus, we are persuaded by Petitioners’ argument that it
was within the skill of a person of ordinary skill in the art to optimize the
properties of the mannitol particles used in formulating a solid oral dosage
form of fingolimod. Accordingly, claims 27–31 are obvious over the
combination of Chiba and Aulton.

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Motion to Amend
Because we find each of claims 1–32 unpatentable, we next address
Patent Owners’ motion to amend, in which claims 33–64 are proposed.
Motions to amend are permitted by 35 U.S.C. § 316(d) and 37 C.F.R.
§ 42.121. In moving to amend their claims, as the moving the party, Patent
Owners have the burden to show entitlement to the relief requested. 37
C.F.R. § 42.20(c). “The burden is not on the petitioner to show [the]
unpatentability [of the proposed claims], but on the patent owner to show
patentable distinction over the prior art of record and also [the] prior art
known to the patent owner.” Idle Free Sys., Inc. v. Bergstrom, Inc., Case
IPR2012-00027, slip op. at 7 (PTAB June 11, 2013) (Paper 26)
(representative). The “prior art of record” includes “any material in the
prosecution history of the patent,” “any material art of record in the current
proceeding, including art asserted in grounds on which the Board did not
institute review,” and “any material art of record in any other proceeding
before the Office involving the patent.” MasterImage 3D, Inc. v. RealD
Inc., Case IPR2015-00040, slip op. at 2 (PTAB July 15, 2015) (Paper 42)
(representative). If Patent Owners
set forth a prima facie case of patentability of narrower
substitute claims over the prior art of record, the burden of
production shifts to Petitioner. In its opposition, Petitioner may
explain why Patent Owner did not make out a prima facie case
of patentability, or attempt to rebut that prima facie case, by
addressing Patent Owner’s evidence and arguments and/or by
identifying and applying additional prior art against proposed
substitute claims. Patent Owner has an opportunity to respond
in its reply. The ultimate burden of persuasion remains with
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Patent Owner, the movant, to demonstrate the patentability of
the amended claims.
Id. at 4 (citing Microsoft Corp. v. Proxyconn, Inc., 789 F.3d 1292, 1306
(Fed. Cir. 2015)). As discussed below, we determine that Patent Owners
have not carried the burden of demonstrating the patentability of any of the
proposed claims.

Claim 51
As a replacement for claim 19, Patent Owners propose claim 51. Mot.
to Amend 38–39. Claim 51 is identical to claim 19 but for the addition of
three new limitations: “wherein the composition is stable, wherein the
composition has substantially uniform distribution of the agonist throughout
the composition, and wherein the composition is made on automated
equipment.” Id. Patent Owners argue that the stability and content
uniformity limitations contribute to patentability because “Petitioners fail to
offer any motivation to combine Chiba (or any other fingolimod-related art)
with a sugar alcohol to achieve stability and content uniformity.” Id. at 15–
16. As discussed above, Patent Owners argue that the inventors of the ’283
patent were the first to discover fingolimod’s low-dose stability and content
uniformity issues, so the prior art does not address these requirements of
claim 51. With respect to the requirement that the composition be made on
automated equipment, Patent Owners argue that the problems with content
uniformity were “especially acute when employing automated equipment.”
Id. at 6.
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Petitioners argue that each of the new limitations of claim 51 is taught
by Aulton as “a standard goal in the development of a pharmaceutical
dosage form.” Mot. to Amend Opp. 10 (citing Ex. 2052). We agree.
Aulton teaches that
[t]he principal objective of dosage form design is to achieve a
predictable therapeutic response to a drug included in a
formulation which is capable of large scale manufacture with
reproducible product quality. To ensure product quality,
numerous features are required — chemical and physical
stability, with suitable preservation against microbial
contamination if appropriate, uniformity of dose of drug,
acceptability to users including both prescriber and patient, as
well as suitable packaging and labelling.
Ex. 2052, 15 (emphases added). Thus, according to Aulton, each of the new
limitations of claim 51 was known to be a standard “principal objective of
dosage form design.” Id. In addition to these teachings regarding stability,
uniformity, and large-scale manufacture, other evidence exists in the record
that the manufacture of tablets and capsules on automated equipment was
part of the ordinary skill in the art.25 Ex. 2049, 21–29, 93–103. As
discussed above, the original limitations of claim 19, from which claim 51
depends, are taught by Chiba and Aulton, a person of ordinary skill in the art
would have had a reason to combine the teachings of Chiba and Aulton, and
a person of ordinary skill in the art would have had a reasonable expectation
of success in combining the teachings of Chiba and Aulton.

25 Moreover, at least with respect to Patent Owners’ argument that the
inventors of the ’283 patent were the first to discover fingolimod’s low-dose
stability and content uniformity issues, claim 51 is not limited to low doses
(or to any range of doses at all).
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Patent Owners also argue that objective indicia of nonobviousness
support the patentability of claim 51. Mot. to Amend 23–26. The particular
objective indicia Patent Owners point to are precisely the same ones that
Patent Owners argued supported the patentability of the existing claims of
the ’283 patent, discussed above. Compare id. with PO Resp. 52–58. For
the reasons discussed above, the evidence of record does not support a
finding that any of the referenced objective indicia of nonobviousness—
unexpected results, long-felt but unmet need, industry praise, and
commercial success—were present in any legally significant way.
Accordingly, claim 51 would have been obvious over the combination of
Chiba and Aulton, so Patent Owners have not demonstrated the patentability
of claim 51.
Claims 33, 35, and 36
Claim 33 is identical to claim 51, except that claim 33 recites “a sugar
alcohol” instead of claim 51’s mannitol. Compare Mot. to Amend 30–31
with id. at 38–39. This makes claim 33 broader in scope than claim 51, with
the entire scope of claim 51 included within claim 33’s scope. Accordingly,
because claim 51 is obvious over the combination of Chiba and Aulton, so is
claim 33. See Callaway, 576 F.3d at 1344. Claims 35 and 36 are narrower
than claim 33, limiting the recited sugar alcohol to one “selected from the
group consisting of mannitol, maltitol, inositol, xylitol and lactitol” (claim
35) or to mannitol (claim 36). Claim 35 is broader than claim 51 and
contains within its scope the entire scope of claim 51, while claims 36 and
51 have identical scope. Accordingly, claims 35 and 36 are both obvious
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over the combination of Chiba and Aulton. Patent Owners have not
demonstrated the patentability of claims 33, 35, and 36.

Claims 39, 40, and 54
Claim 39 depends from claim 33 and limits the amount of fingolimod
in the claimed composition to between 0.1 and 10 weight percent. Mot. to
Amend 33. Claim 40 depends from claim 39 and further limits the amount
of fingolimod in the claimed composition to between 0.5 and 5 weight
percent. Id. at 34. Similarly, claim 54 depends from claim 51 and limits the
amount of fingolimod in the claimed composition to between 0.5 and 5
weight percent. Id. at 40. Patent Owners argue that these content limitations
impart patentability over the prior art because the inventors of the ’283
patent were the first to discover that fingolimod was difficult to formulate
and had stability and content uniformity problems at low doses, and these
limitations require low-dose fingolimod. Id. at 4–5. Petitioners argue that
these limitations do not limit the fingolimod to any particular dose range and
that the prior art teaches or suggests tablets with fingolimod concentrations
falling within the claimed range. Mot. to Amend Opp. 12–13; see e.g., id. at
12 n.1 (“Neither the specification nor this limitation recite a dose as the total
weight is not provided.”).
As discussed above, there is evidence of record that the selection of
the relative amounts of the constituents of the claimed formulation is the
result of routine optimization. Ex. 1004 ¶ 188 (“the amount of active
present in a formulation is well within the skill of the ordinary artisan to
manipulate and optimize for the appropriate use”). Patent Owners do not
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direct us to any evidence of record contradicting this evidence, so we find
that a person of ordinary skill in the art familiar with Chiba and Aulton
would have been able and motivated to optimize the amount of fingolimod
to obtain an appropriately effective formulation. Accordingly, claims 39,
40, and 54 would have been obvious over Chiba and Aulton, so Patent
Owners have not demonstrated the patentability of these claims.

Claim 64
Claim 64 depends from claim 33 and requires that “the sugar alcohol
ha[ve] a rough surface.” Mot. to Amend 43–44. Patent Owners argue that
this claim is patentable because the inventors were the first to discover that
fingolimod had content uniformity problems during manufacture that could
be solved using rough-surface mannitol particles. Id. at 6. Petitioners argue
that using rough-surface mannitol would have been obvious because, under
Patent Owners’ proposed construction of “rough particle surface,” “all of the
commercially available spray-dried or granular forms of mannitol meet the
limitation of a rough surface because their surface [area] is necessarily
greater than [that of] a perfect sphere.” Mot. to Amend Opp. 13–14. We
agree. As discussed above, and as suggested by Patent Owners, we construe
a particle with a “rough particle surface” to be a particle “with higher surface
area than a sphere of a diameter equal to the average diameter of the particle
in question.” Under this construction, both Parteck M200 mannitol (the
mannitol particle that Patent Owners argue solved the content uniformity
problem) and SD200 mannitol (the mannitol particle with which the content
uniformity problem occurred) have a rough surface. Ex. 2041 ¶¶ 35–36; see
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Ex. 2271, 142:23–143:426 (“a rough particle is anything that has a higher
surface area than a theoretically perfect sphere”). Because both types of
mannitol are “rough,” and because content uniformity was a problem with
one type of mannitol but not with the other, the “rough surface” limitation of
claim 64 is not relevant to solving the issue of content uniformity.
Accordingly, given the above claim construction, there is insufficient
evidence to support Patent Owners’ argument that rough-surface mannitol
adds anything to the patentability of claim 64. Thus, claim 64 is obvious
over Chiba and Aulton for the same reasons that claim 33, from which it
depends, is obvious. Patent Owners have not demonstrated the patentability
of claim 64.
Claims 47 and 48
Claims 47 and 48 depend from claim 64 and require the claimed
pharmaceutical composition to be made on automated equipment. Mot. to
Amend 36–37. Claim 47 requires the composition to be in the form of a
tablet, while claim 48 requires the composition to be in the form of a
capsule. Id. As discussed above, Aulton teaches the manufacture of drugs
on automated equipment. Ex. 2052, 15 (“The principal objective of dosage
form design is to achieve a predictable therapeutic response to a drug
included in a formulation which is capable of large scale manufacture with
reproducible product quality.” (emphases added)). In addition, other
evidence exists in the record that manufacture of tablets and capsules on
automated equipment was part of the ordinary skill in the art. Ex. 2049, 21–

26 A public version is available at Ex. 2276, 142:23–143:4.
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29, 93–103. Further, both Chiba and Aulton teach the use of tablets and
capsules. Ex. 1006, 8:19–28; Ex. 1021, 5. Accordingly, claims 47 and 48
would have been obvious over the combination of Chiba and Aulton. Patent
Owners have not demonstrated the patentability of these claims.

Claims 34, 37, 38, 41–46, 49, 50, 52, 53, and 55–63
The remaining claims proposed in Patent Owners’ motion to amend
(claims 34, 37, 38, 41–46, 49, 50, 52, 53, and 55–63) are not amended from
their original forms (claims 2, 5, 6, 9–14, 17, 18, 20, 21, and 23–31), except
to change their dependency from the existing claims to the proposed
amended claims. These claims are obvious over the combination of Chiba
and Aulton for the reasons discussed above with respect to claims 2, 5, 6, 9–
14, 17, 18, 20, 21, 23–31, 33, 35, 36, 39, 40, 47, 48, 51, 54, and 64. Patent
Owners have not demonstrated the patentability of these claims.

Petitioners’ Motion to Exclude
Petitioners move to exclude (1) portions of Ex. 2041 and Ex. 2043
under Federal Rule of Evidence (“FRE”) 602 and FRE 802; (2) all of Ex.
2047 under FRE 802; and (3) portions of Ex. 2042 and Ex. 2280 under FRE
602, FRE 702, and 37 C.F.R. § 42.65. Paper 78, 1. In addition, Petitioners
seek exclusion of portions of Paper 62, Ex. 2280, Ex. 2281, and Ex. 2283 on
the ground that they are beyond the scope of a proper reply in support of a
motion to amend. Id. at 16–17. Finally, Petitioners move to exclude Ex.
2045, Ex. 2281, and portions of Ex. 2044, Ex. 2275, Paper 26, and Paper 31
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because these documents try, but fail, to show the presence of objective
indicia of nonobviousness. Id. at 17–20.

Ex. 2041
Petitioners argue that paragraphs 4–6, 8, 11–13, 21, and 22 of Ex.
2041 should be excluded under FRE 602 and FRE 802 because Dr.
Pudipeddi, the declarant, lacks personal knowledge of the facts to which he
testifies, rendering his statements hearsay. Paper 78, 10–11. We do not rely
on any of the cited paragraphs of Ex. 2041, so we dismiss this portion of
Petitioners’ motion to exclude as moot.

Ex. 2043
Petitioners argue that paragraphs 6–21 of Ex. 2043 should be
excluded because Mr. Oomura, the declarant, lacks personal knowledge of
the facts to which he testifies, rendering his statements hearsay. Id. at 1, 4–
8. We do not rely on paragraphs 6–13, 20, or 21, so we dismiss Petitioners’
motion to exclude those paragraphs as moot. As to paragraphs 14–19, we
note that Mr. Oomura’s personal knowledge of the low-dose compatibility
problems with fingolimod discovered by Yoshitomi comes from his review
of Yoshitomi documents and his discussions with Yoshitomi personnel.
Ex. 2273, 13:3–7, 16:25–17:7, 20:14–17. This is ample basis for him to
testify with personal knowledge of the facts under FRE 602. As to the
hearsay objection, FRE 803(3) makes admissible statements that describe
the declarant’s state of mind, and the testimony in paragraphs 14–19 goes to
the subjective motivation of Mr. Oomura and his colleagues to solve what
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they perceived as a low-dose compatibility problem with fingolimod.
Accordingly, we deny Petitioners’ motion to exclude paragraphs 14–19 of
Ex. 2043.

Ex. 2047
Petitioners move to exclude the entirety of Ex. 2047 as hearsay.
Paper 78, 9–10. We do not rely on Ex. 2047, so we dismiss this portion of
Petitioners’ motion to exclude as moot.

Ex. 2042
Petitioners move to exclude paragraphs 2–4, 13, and 39–50 of Ex.
2042 because those paragraphs merely retell the story told by Mr. Oomura,
without any personal knowledge on the part of Dr. Byrn, the declarant.
Paper 78, 8–9, 11. Petitioners also argue that this same testimony, as well as
paragraphs 11–13 and 76 of Ex. 2042, should be excluded under FRE 702,
both because it relies on tests performed by others for which Dr. Byrn had
access to the results but not information about “how the data was generated,”
and because Dr. Byrn did not conduct any independent analysis into how the
testing was accomplished. Id. at 11–16. We are not convinced that either
problem warrants exclusion of this testimony. Expert witnesses are allowed
to describe the facts that their opinions rest on, so Dr. Byrn’s retelling of Mr.
Oomura’s story need not be excluded simply because Dr. Byrn lacks
personal knowledge of that story. To the extent Petitioners argue that it was
improper for Dr. Byrn to rely on testing performed by others and about
which he did not know every detail, Dr. Byrn disagrees, providing evidence
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that sufficient information about the testing was made available to render his
reliance on that testing reasonable under FRE 702. See Ex. 2280 ¶ 32.
Accordingly, we deny Petitioners’ motion to exclude paragraphs 39, 40, and
76 of Ex. 2042. Because we do not rely on paragraphs 2–4, 11–13, or 41–50
of Ex. 2042, we dismiss Petitioners’ motion to exclude those paragraphs as
moot.

Ex. 2280
Petitioners move to exclude paragraphs 3, 4, 19, and 29–32 of
Ex. 2280 because these paragraphs merely retell the story told by Mr.
Oomura, without any personal knowledge on the part of Dr. Byrn, the
declarant. Paper 78, 8–9. We do not rely on any of the cited paragraphs, so
we dismiss Petitioners’ motion to exclude this testimony as moot.

Argument and Evidence Beyond Proper Scope of Reply
Petitioners seek exclusion of pages 2–9 of Paper 62; paragraphs 2–37
of Ex. 2280; Ex. 2281; and paragraphs 3–20 of Ex. 2283 on the ground that
they are beyond the scope of a proper reply in support of a motion to amend.
Id. at 16–17. A motion to exclude is not the proper vehicle for challenging
the scope of a reply. Conopco, Inc. v. Proctor & Gamble Co., IPR2013-
00505, slip op. at 29 (PTAB Feb. 10, 2015) (Paper 69). Accordingly,
Petitioners’ motion to exclude pages 2–9 of Paper 62; paragraphs 2–37 of
Ex. 2280; Ex. 2281; and paragraphs 3–20 of Ex. 2283 is denied.

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Argument and Evidence of Objective Indicia of Nonobviousness
Finally, Petitioners move to exclude Ex. 2045; Ex. 2281; paragraphs
16–44 of Ex. 2044; unspecified portions of Ex. 2275; pages 55–58 of Paper
26; and pages 24–26 of Paper 31 because this testimony makes only an
unsuccessful case of the presence of objective indicia of nonobviousness.
Id. at 17–20. This is an attack on the sufficiency of the evidence, not on its
admissibility. Such an attack has no place in a motion to exclude. Microsoft
Corp. v. Surfcast, Inc., Case IPR2013-00292, slip op. at 52–53 (PTAB Oct.
14, 2014) (Paper 93). Accordingly, we deny Petitioners’ motion to exclude
Ex. 2045; Ex. 2281; paragraphs 16–44 of Ex. 2044; unspecified portions of
Ex. 2275; pages 55–58 of Paper 26; and pages 24–26 of Paper 31.

Patent Owners’ Motion to Exclude
Patent Owners move to exclude (1) portions of Ex. 1004 and Ex. 1031
under FRE 702; (2) portions of Ex. 1041 under FRE 702; and (3) 53 separate
exhibits under FRE 402 and FRE 403. Paper 73, 4–20.

Ex. 1004 and Ex. 1031
Patent Owners seek to exclude paragraphs 75–96, 102–106, 146–152,
162–165, 168–196, and 198 of Ex. 1004 and paragraphs 10, 11, 13, 14, 34–
48, 72, and 77 of Ex. 1031. Id. at 5 n.2. According to Patent Owners this
testimony fails to satisfy the requirements of FRE 702 because the declarant,
Dr. Kent, offers only an “obvious to try” theory of obviousness that cannot
succeed as a matter of law. Id. at 5–8. This attack on the sufficiency of the
evidence is improper in a motion to exclude. Microsoft Corp. v. Surfcast,
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Inc., Case IPR2013-00292, slip op. at 52–53 (PTAB Oct. 14, 2014) (Paper
93). In any case, as discussed above, we do not agree that Dr. Kent relied on
the theory of obviousness that Patent Owners describe as an “obvious to try”
theory, in which a person of ordinary skill in the art would have been
motivated, at most, to choose mannitol as just one of a large number of
excipients to test for compatibility with fingolimod. Instead, the evidence of
record shows that a person of ordinary skill in the art would have been
directed by Sakai to combine mannitol and fingolimod and that mannitol had
several well-known advantages that would have motivated a person of
ordinary skill in the art to choose it as a pharmaceutical excipient. This is
sufficient, as discussed above, to show the obviousness of the fingolimod-
mannitol combination.
Patent Owners also argue that this testimony should be excluded
because Dr. Kent failed to provide evidence sufficient to show how a
formulator would “develop a list of excipients to test with fingolimod ex
ante.” Paper 73, 12. Again, this is an improper attack on the sufficiency of
the evidence, so we deny the motion to exclude. In any case, the
obviousness of the mannitol-fingolimod combination does not depend on the
ex ante prediction of a perfect fit between the active ingredient and the
excipient, but rather requires only a reasonable expectation of success.
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). As
discussed above, the evidence of record here shows the requisite reasonable
expectation of success.
Finally, Patent Owners argue that this testimony should be excluded
because Dr. Kent’s analysis is unreliable under FRE 702 due to its reliance
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on Budde,27 a phase I safety study, as teaching that a low dose of fingolimod
should be used in the formulation of a dosage form. Paper 73, 13–14. But
the evidence of record shows that Budde describes a clinical effect of a low
dose of fingolimod and that a formulator would attempt to use the proper
effective dose when studying compatibility with excipients. Ex. 2098, 1073
(“Single oral doses of FTY720 ranging from 0.25 to 3.5 mg . . . caused a
reversible selective lymphopenia.”); Ex. 1010, 5 (“drug-excipient ratios
should be selected and studies based on what is likely to be a reasonable
drug-excipient ratio in the final tablet or capsule”); Ex. 1012, 51 (drug-
excipient ratio “should be consistent with the ratio most likely to be
encountered in the final tablet”). Accordingly, Dr. Kent’s reliance on
Budde’s teaching of a low effective dose is not a reason to exclude his
testimony.
We do not rely on paragraphs 75–92, 95, 96, 102–106, 146–152, 162–
165, 168, 169, 171–187, 189–193, 196, and 198 of Ex. 1004 or on
paragraphs 10, 11, 13, 14, 34–48, and 72 of Ex. 1031, so we dismiss Patent
Owners’ motion to exclude these paragraphs as moot. Because none of
Patent Owners’ arguments for excluding paragraphs 75–96, 102–106, 146–
152, 162–165, 168–196, and 198 of Ex. 1004 and paragraphs 10, 11, 13, 14,
34–48, 72, and 77 of Ex. 1031 is persuasive, we deny the motion to exclude

27 Klemens Budde, Robert L. Schmouder, Reinhard Brunkhorst, Bjorn
Nashan, Peter W. Lücker, Thomas Mayer, Somesh Choudhury, Andrej
Skerjanec, Gerolf Kraus, & Hans H. Neumayer, First Human Trial of
FTY720, a Novel Immunomodulator, in Stable Renal Transplant Patients, 13
J. AM. SOC’Y NEPHROLOGY 1073–83 (2002) (“Budde,” Ex. 2098).
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the paragraphs we do rely on, paragraphs 93, 94, 170, 188, 194, and 195 of
Ex. 1004 and paragraph 77 of Ex. 1031.
Patent Owners also seek to exclude paragraphs 182 and 183 of
Ex. 1004 and paragraphs 94–98, 100, and 102 of Ex. 1031 because the Dr.
Kent, the declarant in Ex. 1004 and Ex. 1031, is not qualified to opine on
objective indicia of nonobviousness and presents only conclusory opinions.
Paper 73, 14–17. We do not rely on any of the cited paragraphs in reaching
our decision on the merits, so we dismiss Patent Owners’ motion to exclude
these paragraphs as moot.

Ex. 1041
Patent Owners move to exclude paragraphs 28–31, 34–36, 40–42, 57–
64, 76–83, 88–89, 91–94, and 96–112 of Ex. 1041. We do not rely on any
of the cited paragraphs, so we dismiss Patent Owners’ motion to exclude
these paragraphs as moot.

Other Exhibits
Patent Owners seek to exclude Exhibits 1005, 1008–1021, 1023–
1025, 1030, 1032–1034, 1036, 1038, 1042–1047, 1050, 1056–1065, 1067–
1069, 1072, 1074–1079, 1091, and 1103 under FRE 402 and FRE 403 as
“incomplete and/or irrelevant.” Paper 73, 20. Alternatively, Patent Owners
argue that, pursuant to FRE 106, additional portions that “Novartis identifies
in its objections” should be considered along with the portions of the
documents that make up these 53 exhibits. Id. With respect to Patent
Owners’ argument that these documents should be excluded pursuant to
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FRE 402 and FRE 403, Patent Owners do not explain why each of these
exhibits (or, indeed, any individual one of these exhibits) is irrelevant and
therefore inadmissible under FRE 402 or why any of the exhibits has
“probative value [that] is substantially outweighed by” any of the concerns
expressed in FRE 403. To the extent that Patent Owners explained their
arguments in their objections rather than in their motion to exclude, we note
that our rules prohibit incorporation of arguments by reference from Patent
Owners’ objections into their motion to exclude. 37 C.F.R. § 42.6(a)(3)
(“Arguments must not be incorporated by reference from one document into
another document.”). Accordingly, we deny the motion to exclude Exhibits
1005, 1008–1021, 1023–1025, 1030, 1032–1034, 1036, 1038, 1042–1047,
1050, 1056–1065, 1067–1069, 1072, 1074–1079, 1091, and 1103 under FRE
402 and FRE 403. Patent Owners’ request to have additional portions of
these exhibits considered under FRE 106 is not properly the subject of a
motion to exclude evidence and is not developed fully in its motion briefing.
In any case, we have considered all the evidence of record, including that
submitted by Patent Owners, in reaching our decision on the merits.

Pending Motions to Seal
The parties have filed multiple unopposed motions to seal. Paper 42;
Paper 48; Paper 51; Paper 64; Paper 71; Paper 76; Paper 82; Paper 84; Paper
87; Paper 93; Paper 95; Paper 101; Paper 103; Paper 109. Collectively,
these motions seek to seal Exhibits 1031, 1041, 1107, 1110–1112, 2041,
2271–2274, 2280, 2281, and 2299, as well as Patent Owners’ Response,
Petitioners’ Reply, Petitioners’ Opposition to the Motion to Amend, Patent
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Owners’ Reply to Petitioners’ Opposition to the Motion to Amend,
Petitioners’ Motion to Exclude, Patent Owners’ Motion to Exclude, Patent
Owners’ Opposition to Petitioners’ Motion to Exclude, Patent Owners’
Reply to Petitioners’ Opposition to Patent Owners’ Motion to Exclude,
Petitioners’ Motion for Observations, Patent Owners’ Motion for
Observations, Petitioners’ Response to Patent Owners’ Motion for
Observations, Petitioners’ Demonstrative Exhibits, Patent Owners’
Demonstrative Exhibits, and Patent Owners’ Objections to Petitioners’
Demonstrative Exhibits.28
The Board’s standards for granting motions to seal are discussed in
Garmin International, Inc. v. Cuozzo Speed Technologies, LLC, Case
IPR2012-00001 (PTAB Mar. 14, 2013) (Paper 34). In summary, there is a
strong public policy for making all information filed in inter partes review
proceedings open to the public. Id. at 1–2. The standard for granting a
motion to seal is “good cause.” 37 C.F.R. § 42.54. The moving party bears
the burden of showing that the relief requested should be granted. 37 C.F.R.
§ 42.20(c). Meeting the burden includes showing that the information is
truly confidential, and that such confidentiality outweighs the strong public
interest in having an open record. In addition, a motion to seal must include
a certification that the moving party has in good faith conferred, or
attempted to confer, with the opposing party in an effort to come to an
agreement on the scope of the protection sought. Garmin, slip op. at 3.

28 In addition, we previously sealed Exhibits 2042, 2043, 2045, 2047, 2055,
2187, and 2266–2268, as well as Patent Owners’ Motion to Amend. Paper
41.
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Having reviewed the motions to seal these documents, the documents sought
to be sealed, and the redactions in those cases where a redacted, public
version of a document has been filed, we find that the parties have
demonstrated good cause to grant the motions. Accordingly, except as
discussed below, we will seal the documents listed above.
We have previously informed the parties that, “if our Final Written
Decision substantively relies on any information in a sealed exhibit, that
exhibit will be unsealed by an Order of the Board.” Paper 41, 8. The
present decision substantively relies on non-public material from the
following exhibits that are the subject of pending motions to seal or
previously have been sealed: Ex. 1031, Ex. 1041, Ex. 2041, Ex. 2042,
Ex. 2043, and Ex. 2045. Accordingly, these exhibits will be unsealed 45
days after entry of the present decision. Before that time, the parties may
move instead to expunge these exhibits and replace them with public
versions that redact any confidential material not referred to in this decision.

CONCLUSION
Petitioner has shown, by a preponderance of the evidence, that claims
1–32 of the ’283 patent would have been obvious over the combination of
Chiba and Aulton. Patent Owner has failed to show, by a preponderance of
the evidence that proposed amended claims 33–64 are patentable. The
parties’ motions to exclude are dismissed in part as moot (to the extent that
they seek exclusion of evidence we do not rely on) and denied in part (to the
extent that they seek exclusion of evidence we rely on).

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ORDER
Accordingly, it is
ORDERED that claims 1–32 of the ’283 patent are unpatentable;
FURTHER ORDERED that Patent Owners’ motion to amend is
denied;
FURTHER ORDERED that Petitioners’ motion to exclude paragraphs
4–6, 8, 11–13, 21, and 22 of Ex. 2041; paragraphs 2–4, 11–13, and 41–50 of
Ex. 2042; paragraphs 6–13, 20, and 21 of Ex. 2043; Ex. 2047; and
paragraphs 3, 4, 19, and 29–32 of Ex. 2280 is dismissed as moot;
FURTHER ORDERED that Petitioners’ motion to exclude paragraphs
14–19 of Ex. 2043; paragraphs 39, 40, and 76 of Ex. 2042; pages 2–9 of
Paper 62; paragraphs 2–37 of Ex. 2280; Ex. 2281; and paragraphs 3–20 of
Ex. 2283; Ex. 2045; Ex. 2281; paragraphs 16–44 of Ex. 2044; unspecified
portions of Ex. 2275; pages 55–58 of Paper 26; and pages 24–26 of Paper 31
is denied;
FURTHER ORDERED that Patent Owners’ motion to exclude
paragraphs 75–92, 95, 96, 102–106, 146–152, 162–165, 168, 169, 171–187,
189–193, 196, and 198 of Ex. 1004; paragraphs 10, 11, 13, 14, 34–48, 72,
94–98, 100, and 102 of Ex. 1031; and paragraphs 28–31, 34–36, 40–42, 57–
64, 76–83, 88–89, 91–94, and 96–112 of Ex. 1041 is dismissed as moot;
FURTHER ORDERED that Patent Owners’ motion to exclude
paragraphs 93, 94, 170, 188, 194, and 195 of Ex. 1004; paragraph 77 of Ex.
1031; and Exhibits 1005, 1008–1021, 1023–1025, 1030, 1032–1034, 1036,
1038, 1042–1047, 1050, 1056–1065, 1067–1069, 1072, 1074–1079, 1091,
and 1103 is denied;
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FURTHER ORDERED that the pending motions to seal are granted to
the extent that Exhibits 1107, 1110–1112, 2271–2274, 2280, 2281, and
2299, as well as Patent Owners’ Response, Petitioners’ Reply, Petitioners’
Opposition to the Motion to Amend, Patent Owners’ Reply to Petitioners’
Opposition to the Motion to Amend, Petitioners’ Motion to Exclude, Patent
Owners’ Motion to Exclude, Patent Owners’ Opposition to Petitioners’
Motion to Exclude, Patent Owners’ Reply to Petitioners’ Opposition to
Patent Owners’ Motion to Exclude, Petitioners’ Motion for Observations,
Patent Owners’ Motion for Observations, Petitioners’ Response to Patent
Owners’ Motion for Observations, Petitioners’ Demonstrative Exhibits,
Patent Owners’ Demonstrative Exhibits, and Patent Owners’ Objections to
Petitioners’ Demonstrative Exhibits are sealed;
FURTHER ORDERED that Exhibits 1031, 1041, 2041, 2042, 2043,
and 2045 shall be unsealed and shall become publicly available 45 days after
entry of this decision, provided that the parties may move within 45 days of
entry of this decision to expunge these exhibits and replace them with public
versions that redact any confidential information not referred to herein;
FURTHER ORDERED that the parties shall file no later than one
week after the entry of this decision a redacted version of Paper 111, to be
made publicly available as a record of the oral hearing;
FURTHER ORDERED that Papers 99, 100, 107, and 108 shall be
expunged from the record; and
FURTHER ORDERED that, because this is a final written decision,
parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.
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FOR PETITIONER TORRENT PHARMACEUTICALS LIMITED:

Michael K. Levy
Paul Richter
Huiya Wu
KENYON & KENYON LLP
mlevy@kenyon.com
prichter@kenyon.com
hwu@kenyon.com

FOR PETITIONER APOTEX, INC.:

Jonathan M. Lindsay
Deborah Yellin
CROWELL & MORING LLP
jlindsay@crowell.com
dyellin@crowell.com

FOR PETITIONER MYLAN PHARMACEUTICALS INC.:

Brandon M. White
PERKINS COIE LLP
bmwhite@perkinscoie.com

FOR PATENT OWNERS NOVARTIS AG AND
MITSUBISHI PHARMA CORP.:

Jane M. Love, Ph.D.
Robert W. Trenchard
WILMER CUTLER PICKERING HALE & DORR LLP
jane.love@wilmerhale.com
robert.trenchard@wilmerhale.com

kis