from the United States Patent and Trademark Office, Patent
Trial and Appeal Board in Nos. IPR2014-00784, IPR2015-00518.
TRENCHARD, Gibson, Dunn & Crutcher LLP, New York, NY,
argued for appellants. Appellant Novartis AG also represented
by Jane M. Love; Michael A. Valek, Dallas, TX; ALEXANDER N.
HARRIS, San Francisco, CA.
M. O'Malley, Jr., Paul Hastings LLP, New York, NY, for
appellant Mitsubishi Pharma Corp. Also represented by Eric
Stanek Rea, Crowell & Moring, LLP, Washington, DC, argued
for appellees. Appellee Apotex Inc. also represented by
Vincent John Galluzzo; Jonathan M. Lindsay, Irvine, CA.
Michael K. Levy, Andrews Kurth Kenyon LLP, New York, NY, for
appellee Torrent Pharmaceuticals Limited.
Shannon Bloodworth, Perkins Coie, LLP, Washington, DC, for
appellee Mylan Pharmaceuticals Inc. Also represented by
BRANDON MICHAEL WHITE; Dan L. Bagatell, Hanover, NH.
TARANTO, Chen, and Stoll, Circuit Judges.
an appeal from the Final Written Decision of the United
States Patent and Trademark Office, Patent Trial and Appeal
Board (Board) in two consolidated inter partes
review (IPR) proceedings of U.S. Patent No. 8, 324, 283 (the
'283 patent), owned by Novartis AG and Mistubishi Tanabe
Pharma Corp. (collectively, Novartis). The Board instituted
IPRs on all claims of the '283 patent based on petitions
filed by Torrent Pharmaceuticals Limited, Apotex, Inc. and
Mylan Pharmaceuticals Inc. (collectively, Petitioners). After
reviewing the claims, receiving extensive briefing, and
hearing oral argument, the Board found all original claims of
the '283 patent and Novartis' proposed substitute
claims unpatentable as obvious. See Torrent Pharm. Ltd.
v. Novartis AG, Nos. IPR2014-00784, IPR2015-00518, 2015
WL 5719630 (PTAB Sept. 24, 2015) (Final Written
Decision). Novartis raises a series of challenges to the
Board's analysis of the evidence and ultimate
determination of unpatentability. For the reasons stated
below, we affirm.
'283 patent relates to a solid pharmaceutical composition
suitable for oral administration, comprising a sphingosine-1
phosphate (SIP) receptor agonist and a sugar alcohol, which
the patent explains is useful for the treatment of certain
autoimmune diseases such as multiple sclerosis. '283
patent, col. 1, lines 11-14, 33-35; col. 12, lines 19-49.
According to the specification, SIP receptor agonists
generally exhibit properties that make formulations suitable
for oral administration of a solid composition difficult to
create. However, "solid compositions comprising a sugar
alcohol provide formulations which are particularly well
suited to the oral administration of SIP receptor
agonists." See id. at col. 1, lines 36-39. They
also "provide a convenient means of systemic
administration of SIP receptor agonists, do not suffer from
the disadvantages of liquid formulations for injection or
oral use, and have good physiocochemical and storage
properties." Id. at col. 1, lines 39-43. In
such a composition, the SIP receptor agonist is the active
ingredient and the sugar alcohol acts as an excipient-the
substance formulated alongside the active ingredient as a
diluent, carrier, filler and/or bulking agent for the
composition. See id. at col. 9, lines 53-54.
'283 patent states that there are multiple known SIP
receptor agonists appropriate for use in the claimed
invention, set forth in the specification as formulas I-XIII.
Id. at col. 1, line 51 to col. 8, line 4. The
'283 patent also states that a "particularly
preferred SIP receptor agonist of formula I is FTY720, i.e.,
2-amino-2-[2-(4-octylphenyl) ethyl]propane-l, 3-diol in free
form or in a pharmaceutically acceptable salt form . . .
." Id. at col. 8, lines 23-26. FTY720 is also
known as fingolimod. The '283 patent further discloses
that the specific sugar alcohol used in the claimed
composition "may suitably be mannitol, " because of
its non-hygroscopic properties (i.e., it is not likely to
absorb moisture, which is beneficial in manufacturing solid
oral pills). Id. at col. 9, lines 53-54.
1 and 19 of the '283 patent are the only independent
claims and are illustrative of the claimed subject matter:
1. A solid pharmaceutical composition suitable for oral
(a) a SIP receptor agonist which is selected from
2-amino-2-[2-(4-octylpheny l)ethyl]propane-1, 3-diol,
3-propane-diol, 2-amino-2-[4-(3-b enzyloxyphenylthio) - 2
-chlorophenyl]propyl-1, 3-propane-diol, or
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 col. 17, lines 2-11; col. 18, lines 7-10.
Thus, claim 1 is directed towards a solid oral composition
comprised of the combination of one of a handful of SIP
receptor agonists and any sugar alcohol, whereas claim 19 is
directed towards the specific combination of fingolimod and
mannitol in a solid oral composition.
dependent claims are directed towards various refinements of
the composition, including for example, the addition of a
20. A composition according to claim 19, further comprising a
Id. at col. 18, lines 11-12. Other claims are
directed towards adjusting the respective amount of
22. A composition according to claim 19, wherein the compound
2-amino-2-[2-(4-octylphenyl)ethyl]propane-1, 3-diol, or a
pharmaceutically acceptable salt thereof, is present in an
amount of 0.5 to 5% by weight, based on the total weight of
23. A composition according to claim 19, wherein mannitol is
present in an amount of 90 to 99.5% by weight, based on the
total weight of the composition.
Id. at col. 18, lines 15-22.
the application leading to the '283 patent was pending at
the Patent Office, Novartis applied to the U.S. Food and Drug
Administration (FDA) for approval to sell a
fingolimod-mannitol pill to treat multiple sclerosis under
the "Gilenya" brand name. The FDA approved Gilenya
for the treatment of multiple sclerosis in 2010.
27, 2014, Torrent filed a petition to institute an inter
partes review of claims 1-32 of the '283 patent.
Torrent's petition presented three separate patentability
1. claims 1-32 are unpatentable as obvious over the
combination of U.S. Patent No. 6, 004, 565 (Chiba) and
Pharmaceutics: The Science of Dosage Form Design
2. claims 1-4, 7, 8, 19, 22 and 32 are unpatentable as
anticipated by U.S. Patent No. 6, ...