Apotex challenged Novartis Fingolimod patent at PTAB

Apotex inc has filed an IPR2017-00854 challenging the validity of Novartis US patent 9,187,405 B2, which claims method for treating Relapsing-Remitting multiple sclerosis using Fingolimod.

US ‘405 (US 14/257,342) was issued to Novartis on Nov 17, 2015 and is set to expire on Jun 25, 2027. US ‘405 listed in Orange Book for Fingolimod.

Fingolimod description:

Fingolimod is a sphingosine 1-phosphate receptor modulator.  Chemically, Fingolimod is 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol hydrochloride. Its structure is shown below:

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Fingolimod discovered by Mitsubishi Pharma Corporation; Taito and licensed to Novartis for the further development.

Fingolimod is approved by FDA in September 2010 which is marketed by Novartis under the brand name GILENYA (capsule; oral 0.5mg)

IPR2017-00854 brief summary

US ‘405 claims (claim 1)

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.

Also claims (claim 3) a method for treating 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.

Also claims (claim 5) a method for slowing progression of 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.

US ’405 claims priority as June 27, 2006 (GB 0612721.1), the application in US has been filed on June 25, 2007, which is the filing date of PCT/EP2007/005597. As per 35 U.S.C. § 102(b) the  effective filing date of US ‘405 is June 25, 2007 .

what Prior art says 

Kovarik WO 2006/058316 filed by Novartis which was published on June 1, 2006, WO ‘316 teaches daily oral dosage regimens of Fingolimod hydrochloride (FTY720) for the treatment of “autoimmune diseases, e.g. multiple sclerosis,” and for preventing organ rejection, it further teaches that the standard daily (maintenance) dosage of 0.5 mg FTY720 may be administered for the treatment of multiple sclerosis and that the lo ading dose regimen allows for a steady-state concentration of FTY720 to be achieved in less than one week.

Thomson, CORE EVIDENCE, 1(3): 157-167 (2006) (published on March 31, 2006)this paper teaches that  FTY720 reduces inflammatory disease activity, thereby reducing relapse rates, increasing the time to first relapse, and increasing intervals between relapses;

U.S. Patent No. 6,004,565 to Chiba-US ‘565 teaches  that FTY720, fingolimod hydrochloride, suppresses the immune response of mammals through accelerated lymphocyte homing and is useful for the treatment of MS. It further  teaches oral administration of FTY720 in a 0.01-10 mg daily oral dose.

Kappos, etal. JOURNAL OF NEUROLOGY 252(Suppl 2): 11/41, Abstract O141 (2005)This paper discloses the results of a Phase II randomized, double-blind, placebo-controlled study sponsored by Novartis Pharma AG Basel. The trial evaluated the efficacy of daily oral doses of FTY720 for the treatment of relapsing multiple sclerosis patients.

NEW ENGLAND JOURNAL OF MEDICINE, 362(5):387-401 (2010)- According to the petitioner the claims recite that 0.5 mg Fingolimod is administered “absent an immediately preceding loading dose regimen.” This negative claim limitation first appeared in the ’342 application in a preliminary amendment submitted August 18, 2014. The originally filed ’342 application, the resulting ’405 patent, and each of the priority documents on which the ’342 relies, are otherwise silent on whether or not to use a loading dose regimen. Although the negative limitation was also added to the claims in the related ’468 application, this occurred after its 2011 filing date. This paper teaches that, as compared to placebo, daily oral doses of 0.5 mg FTY720 significantly reduced rates of relapse, progression of clinical disability, and MRI evidence of inflammatory lesion activity and tissue destruction.

Apotex has made his arguments to show how the claimed invention is obvious over the cited prior art alone and in combination with each other.

Apart from this IPR; Apotex is also in litigation (ANDA) with Novartis which is pending.

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