Novartis Pharm. Corp. v. Accord Healthcare, Inc.

21 F.4th 1362

NOVARTIS PHARMACEUTICALS CORPORATION, Plaintiff-Appellee

v.ACCORD HEALTHCARE, INC., Aurobindo Pharma Ltd., Aurobindo Pharma USA, Inc., Dr. Reddy's Laboratories, Inc., Dr. Reddy's Laboratories, Ltd., Emcure Pharmaceuticals Ltd., Heritage Pharmaceuticals Inc., Glenmark Pharmaceuticals Inc., USA, Glenmark Pharmaceuticals Limited, Hetero USA, Inc., Hetero Labs Limited Unit-V, Hetero Labs Limited, Mylan Pharmaceuticals, Inc., Prinston Pharmaceutical Inc., Strides Global Pharma Private Limited, Strides Pharma, Inc., Torrent Pharma Inc., Torrent Pharmaceuticals Ltd., Zydus Pharmaceuticals (USA) Inc., Cadila Healthcare Ltd., Apotex Inc., Apotex Corp., Sun Pharmaceutical Industries, Ltd., Sun Pharmaceutical Industries Inc., Sun Pharma Global FZE, Defendants

HEC Pharm Co., Ltd., HEC Pharm USA Inc., Defendants-Appellants

2021-1070

United States Court of Appeals, Federal Circuit.

Decided: January 3, 2022

Jane M. Love, Gibson, Dunn & Crutcher LLP, New York, NY, argued for plaintiff-appellee. Also represented by Paul E. Torchia, Robert Trenchard.

Paul Skiermont, Skiermont Derby LLP, Dallas, TX, argued for defendants-appellants. Also represented by Sarah Elizabeth Spires; Mieke K. Malmberg, Los Angeles, CA.

Before Moore, Chief Judge, Linn and O'Malley, Circuit Judges.

O'Malley, Circuit Judge.

HEC Pharm Co., Ltd. and HEC Pharm USA Inc. (collectively, "HEC") appeal from a district court bench trial in which the court found that a patent assigned to Novartis Pharmaceuticals Corp. ("Novartis"), U.S. Patent No. 9,187,405 ("the ’405 patent"), is not invalid and that HEC's Abbreviated New Drug Application ("ANDA") infringes. HEC argues that the district court erred in finding that the ’405 claims do not fail the written description requirement of 35 U.S.C. § 112(a). Because we do not discern any clear error in the district court's decision, we affirm.

I. BACKGROUND

Novartis markets a 0.5 mg daily dose of fingolimod hydrochloride under the brand name Gilenya. The medication is used to treat relapsing remitting multiple sclerosis ("RRMS"), a form of multiple sclerosis ("MS"). MS is a debilitating immune-mediated demyelinating disease in which the immune system attacks the myelin coating the nerves in the central nervous system. Most MS patients initially present as RRMS patients, but many eventually develop a secondary progressive form of MS, causing them to experience growing disability. There is currently no cure for MS. The disease is managed by reducing or preventing relapses and thereby slowing disability.

HEC filed an ANDA seeking approval to market a generic version of Gilenya. Novartis sued, alleging that HEC's ANDA infringes all claims of the ’405 patent.¹

A. The ’405 Patent

The ’405 patent claims methods to treat RRMS with fingolimod (also known as FTY720 and 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in the ’405 patent ) or a fingolimod salt, such as fingolimod hydrochloride (also known as Compound A in the ’405 patent ), at a daily dosage of 0.5 mg without an immediately preceding loading dose. ’405 patent col. 12 ll. 49–55.

A loading dose is a higher than daily dose "usually given ‘as the first dose.’ " J.A. 27 (¶ 63) (quoting J.A. 23125 (Tr. 547:12–18) and citing J.A. 23344 (Tr. 766:4–6)). Both parties’ experts agreed with this definition. J.A. 23125 (547:12–18) (HEC's expert, Dr. Hoffman, testifying that "a loading dose is a higher-than-therapeutic level dose, usually given ... as the first dose in order to get therapeutic levels up quickly ... and it's usually for more acute situations"); J.A. 23344 (Tr. 766:4–6) (Novartis's expert, Dr. Steinman, agreeing that "a loading dose is a higher-than-daily dose"). It is undisputed that loading doses were well-known in the medical field generally and in the prior art. And the experts in this case agree that loading doses are used for some medicaments used in connection with MS.

The ’405 patent has six claims. Claim 1 of the ’405 patent recites:

A method for reducing or preventing or alleviating relapses in Relapsing-Remitting multiple sclerosis in a subject in need thereof, comprising orally administering to said subject 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, in free form or in a pharmaceutically acceptable salt form, at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen.

Claims 3 and 5 are similar but are directed to a "method of treating" RRMS and a "method of slowing progression of" RRMS, respectively, rather than a "method for reducing or preventing or alleviating relapses in" RRMS. Id. col. 12 ll. 59–64, col. 13 ll. 1–6. Claims 2, 4, and 6 are dependent claims that limit the methods of claims 1, 3, and 5, respectively, to administration of 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride, i.e., fingolimod hydrochloride. Id. col. 12 ll. 56–58, col. 12 ll. 65–67, col. 13 ll. 7–9.

The ’405 patent was filed on April 21, 2014. It claims priority to a British patent application that was filed on June 27, 2006. The parties, for the most part, focus their discussion on the specification of the ’405 patent, despite HEC's argument that the inventors did not possess the invention as of the 2006 priority date. HEC's argument that the 2006 application does not contain adequate written description of the ’405 claims requires reference to the 2006 application itself. Thus, we find it necessary to look to the specification of the 2006 priority application, despite the parties’ failure to fully explain the contents of that application. Although the specifications are different from each other, they are, in all aspects relevant to this appeal, substantively similar.

The specifications of the ’405 patent and the 2006 priority application both describe the use of a class of S1P receptor modulators, including fingolimod, to treat or prevent "neo-angiogenesis associated with a demyelinating disease, e.g. multiple sclerosis." ’405 patent col. 1 ll. 5–8; J.A. 23751. The specifications each identify fingolimod hydrochloride (Compound A) as a particularly preferred compound within the class of S1P receptor modulators. ’405 patent col. 8 ll. 17–30; J.A. 23759–60.

Both specifications describe the results of an Experimental Autoimmune Encephalomyelitis ("EAE") experiment. ’405 patent col. 10 ll. 32–col. 11 ll. 2; J.A. 23762–63. In the EAE experiment, a disease that mimics RRMS was induced in Lewis rats.² The rats suffered acute disease within 11 days after immunization, with almost complete remission around day 16 and relapse around day 26. The specifications report that an S1P receptor modulator, e.g., Compound A (fingolimod hydrochloride) "significantly blocks disease-associated neo-angiogenesis when administered to the animals at a dose of from 0.1 to 20 mg/kg p.o."³ ’405 patent col. 10 ll. 61–64; J.A. 23763. They further report that disease relapse was completely inhibited in rats to which Compound A was "administered daily at a dose of 0.3 mg/kg" or "administered p.o. at 0.3 mg/kg every 2nd or 3rd day or once a week." ’405 patent col. 10 ll. 64–col. 11 ll. 3; J.A. 23763.

Both specifications then describe a prophetic human clinical trial ("Prophetic Trial").⁴ ’405 patent col. 11 ll. 3–38; J.A. 23763–64. The Prophetic Trial describes a trial in which RRMS patients would receive 0.5, 1.25, or 2.5 mg of an S1P receptor modulator, e.g., Compound A (fingolimod hydrochloride), per day for two to six months. ’405 patent col. 11 ll. 8–14; J.A. 23763. The specifications do not mention a loading dose associated with the Prophetic Trial. ’405 patent col. 11 ll. 8–14; J.A. 23763.

Both specifications then describe a wide range of potential dosages, which "will vary depending upon, for example, the compound used, the host, the mode of administration and the severity of the condition to be treated." ’405 patent col. 11 ll. 20–24; J.A. 23764. Those potential dosages include a "preferred daily dosage range [of] about from 0.1 to 100 mg" and "a dose of 0.5 to 30 mg [of Compound A] every other day or once a week." ’405 patent col. 11 ll. 24–38; J.A. 23764.

B. The District Court Proceedings

After a four-day bench trial, the district court found that HEC's ANDA product would infringe claims 1–6 of the ’405 patent. The court also found that HEC had not shown that the ’405 patent is invalid for (1) insufficient written description for the no-loading-dose limitation and for the claimed 0.5 mg daily dose or (2) anticipation. HEC appeals the district court's findings as to written description for the 0.5 mg daily dose and no-loading-dose limitations.

With respect to the written description for the claimed 0.5 mg daily dose, the district court found that a skilled artisan would understand that the inventors possessed a 0.5 mg daily dose based on one of the successful doses in the EAE experiment results, 0.3 mg/kg weekly. The court credited the testimony of two of Novartis's expert witnesses, Dr. Lawrence Steinman, M.D., and Dr. William Jusko, Ph.D., to make the leap from a 0.3 mg/kg weekly rat dosage to a 0.5 mg daily human dosage. The court noted that the 0.5 mg daily dose is also illustrated in the Prophetic Trial. The district court concluded that there was sufficient written description for the 0.5 mg daily dosage limitation.

With respect to the written description for the "absent an immediately preceding loading dose" limitation, the district court again found sufficient written description in the EAE model and the Prophetic Trial. Neither the Prophetic Trial nor the EAE model recite a loading dose. The district court found that the "Prophetic Trial describes giving a ‘daily dosage of 0.5 ... mg’ fingolimod to treat RRMS, started ‘initially.’ " J.A. 26 (quoting ’405 patent col. 11 ll. 8–13). The court found, crediting expert testimony, that, "[i]f a loading dose were directed, the Patent would say that a loading dose should be administered ‘initially.’ " J.A. 26 (citing J.A. 23334–35 (Tr. 756:16–757:8); J.A. 23441–42 (Tr. 863:22–864:18)). Similarly, the...