Novartis AG v. Torrent Pharm. Ltd.

• Decision Date: 12 April 2017
• Docket Number: 2016-1352
• Parties: NOVARTIS AG, Mitsubishi Pharma Corp., Appellants v. TORRENT PHARMACEUTICALS LIMITED, Apotex Inc., Mylan Pharmaceuticals Inc., Appellees
• Court: U.S. Court of Appeals — Federal Circuit

853 F.3d 1316

NOVARTIS AG, Mitsubishi Pharma Corp., Appellants

v.TORRENT PHARMACEUTICALS LIMITED, Apotex Inc., Mylan Pharmaceuticals Inc., Appellees

2016-1352

United States Court of Appeals, Federal Circuit.

Decided: April 12, 2017

Robert 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.

Joseph M. O'Malley, Jr. , Paul Hastings LLP, New York, NY, for appellant Mitsubishi Pharma Corp. Also represented by Eric William Dittmann .

Teresa 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.

Before Taranto, Chen, and Stoll, Circuit Judges.

Chen, Circuit Judge.

This is 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 Mitsubishi 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 .

BACKGROUND

I.

The '283 patent relates to a solid pharmaceutical composition suitable for oral administration, comprising a sphingosine-1 phosphate

(S1P) 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, S1P 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 S1P receptor agonists." See id. at col. 1, lines 36–39. They also "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 physiocochemical and storage properties." Id. at col. 1, lines 39–43. In such a composition, the S1P 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.

The '283 patent states that there are multiple known S1P 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 S1P receptor agonist of formula I is FTY720, i.e., 2-amino-2-[2-(4-octylphenyl) ethyl]propane-1,3-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.

Claims 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 administration, comprising:

(a) a S1P receptor agonist which is selected from 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, 2-amino-2-[4-(3-benzyloxyphenoxy)-2-chlorophenyl]propyl-1,3-propane-diol, 2-amino-2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]propyl-1,3-propane-diol, or 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 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 S1P receptor agonists and any sugar alcohol, whereas claim 19 is directed towards the specific combination of fingolimod and mannitol

in a solid oral composition.

The dependent claims are directed towards various refinements of the composition, including for example, the addition of a lubricant:

20. A composition according to claim 19, further comprising a lubricant.

Id. at col. 18, lines 11–12. Other claims are directed towards adjusting the respective amount of ingredients:

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 the composition.

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.

While 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.

II.

On May 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 challenges:

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 (Aulton); and2. claims 1–4, 7, 8, 19, 22 and 32 are unpatentable as anticipated by U.S. Patent No. 6,277,888 (Sakai) ; and

3. claims 1–32 are unpatentable as obvious over Chiba and Sakai.

Chiba teaches the use of immunosuppressive compounds with fingolimod as the preferred species. J.A. 18442.¹ Chiba also teaches that these immunosuppressive compounds are useful for treating "autoimmune diseases

such as ... multiple sclerosis," among other diseases and conditions. J.A. 18443. Chiba goes on to disclose 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." J.A. 18444. In discussing the preparation of these capsules and tablets for oral administration of fingolimod, Chiba teaches that "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." J.A. 18446. In other words, Chiba teaches a solid oral composition of fingolimod combined with a generic excipient.

Aulton teaches the use of tablets and capsules to administer drugs orally. J.A. 19041. It specifically teaches that "[t]he successful formulation of a stable and effective solid dosage form depends on the careful selection of the excipients which are added to facilitate administration, promote the consistent release and bioavailability of the drug and protect it from degradation." J.A. 19066–167. Aulton recommends 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." J.A. 19074–77. Aulton describes mannitol as "expensive," but "commonly used" as an excipient in solid oral compositions. J.A. 19077.

Sakai describes a pharmaceutical composition containing fingolimod as an active ingredient. J.A. 18421. More particularly, Sakai discloses that the composition can be formulated into a liquid preparation, or can be a solid lyophilized (freeze-dried) product. J.A. 18421–22. Sakai further discloses that the addition of a saccharide, such as sugar alcohol, to the composition can result in a less irritating resulting liquid solution. J.A. 18421. Sakai discloses a list of eight exemplary saccharides, including mannitol

. J.A. 18422. The saccharide, such as mannitol, can be dissolved in the liquid for dissolution, or alternatively may be contained in the lyophilized product along with the active ingredient. J.A. 18422. Sakai teaches that this liquid pharmaceutical composition can be used for immunosuppression in connection with organ or bone marrow transplantation, autoimmune diseases, or allergic diseases. Id. In short, Sakai teaches the specific combination of fingolimod and mannitol for a liquid formulation.

III.

On December 1, 2014, the Board granted in part Torrent's petition and instituted trial to review patentability of the challenged claims in IPR2014-00784. Specifically, the Board instituted on the first ground, the combination of Chiba and Aulton, but declined to institute on grounds two or three. The Board found that Chiba...