Cipla’s patent challenged at PTAB

Argentum Pharmaceuticals has filed an Inter Partes Review petition IPR2017-00807 against Cipla’s United States Patent No.8,168,620 B2 (US ‘620).

US ‘620 claims a pharmaceutical formulation comprising Azelastine and fluticasone propionate .

Argentum Pharmaceuticals requested to cancel the claims 1, 4-6, 24-26, 29, 42-44 of the ’620 patent, the following grounds were considered to challenge the claims:

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Claim 1 (independent) of US ‘620 relates to 

A pharmaceutical formulation comprising: Azelastine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable ester of Fluticasone, wherein said pharmaceutical formulation is in a dosage form suitable for nasal administration.

Claim 24 (independent) of US ‘620 relates to 

A pharmaceutical formulation comprising Azelastine hydrochloride; and, Fluticasone propionate, wherein said formulation is in the dosage form of a nasal spray, and wherein said formulation is used in the treatment of conditions for which administration of one or more anti-histamine and/or one or more steroid is indicated.

Claim 25 (independent) of US ‘620 relates to 

A nasal spray formulation comprising (i) Azelastine, or a pharmaceutically acceptable salt thereof, (ii) a pharmaceutically acceptable ester of fluticasone, and (iii) a pharmaceutically acceptable carrier or excipient therefor.

US ‘620 is listed in Orange Book for DYMISTA®, a nasal spray incorporating fluticasone propionate (a corticosteroid), and azelastine (an antihistamine) which is marketed by Meda Pharmaceuticals Inc.

Meda has the exclusive license to US ‘620 and is set to expire in February 2026 (including 987 days of PTA).

Prior art cited by the petitioner:

  • Cited U.S. Patent No. 5,164,194 as the prior art, which claims a method for the treatment of irritation or disorders of the nose and eye which comprises applying directly to nasal tissues or to the conjunctival sac of the eyes a medicament which contains a member selected from the group consisting of Azelastine and its physiologically acceptable salts.”
  • Cited Astelin ® (Azelastine HCl) Label, which describes nasal spray that contains a concentration of azelastine hydrochloride of 0.1% w/v and the preservative benzalkonium chloride. The nasal spray is indicated for “treatment of the symptoms of seasonal allergic rhinitis.”
  • Cited U.S. Patent No. 4,335,121 which claims fluticasone propionate, US ‘121 also describes that the fluticasone propionate formulation is suitable for topical administration using “sprays,(e.g. for the nose, throat, lung or skin).” US ‘121 further stated that “steroid is micronised (particle size as defined in BPC 1973 pg. 911 for Ultra-Fine powder).” The “BPC 1973” reference, in turn, defines an ultra-fine powder as a “powder of which the maximum diameter of 90 per cent of the particles is not greater than 5μm and of which the diameter of none of the particles is greater than 50 μm.”
  • Cited Flonase® Label which describes a nasal spray containing an aqueous suspension of “microfine” particles of fluticasone propionate at a concentration of 0.5% w/w.The suspension also contains microcrystalline cellulose and carboxymethylcellulose sodium, dextrose, 0.02% w/w benzalkonium chloride, polysorbate 80, and 0.25% w/w phenylethyl alcohol.
  • Cited European Patent Application No. 0780127 (“Cramer”)  which relates to “pharmaceutical compositions for nasal administration comprising: a) a safe and effective amount of a glucocorticoid selected form the group consisting of beclomethasone, flunisolide, triamcinolone, fluticasone, mometasone, budesonide, pharmaceutical acceptable salts thereof and mixtures thereof; b) a safe and effective amount of a leukotriene inhibiting antihistamine selected from the group consisting of cetirizine, loratadine, azelastine, pharmaceutical acceptable salts thereof, optically active racemates thereof and mixtures thereof; and c) an intranasal carrier.”
  • Cited PCT Publication No. WO 98/48839 (“Segal”) which describes a coformulated nasal spray containing both Azelastine and Fluticasone.

The petitioner argued that each of the two claimed components (azelastine and fluticasone) were known to be used as a nasal spray in the treatment of allergy-related conditions;

The petitioner also argued that the priority application GB 0213739.6 lacks written description and does not demonstrate possession of the genus “pharmaceutically acceptable ester of fluticasone.” GB 0213739.6 provides no additional examples, no qualitative guidance, no definition, no test, and no structure-function relationship for what it considered “pharmaceutically acceptable” esters of fluticasone.

Further, the petitioner has made his arguments and shown how the claimed invention will be obvious to a POSA describing and comparing each and every element of the challenged claims with the cited prior art. Within 3 months Cipla may file preliminary response to the said IPR petition.

Meda Pharms has sued Apotex Inc,Teva Pharms and Perrigo UK Finco Ltd under the infringement of US ‘620 for filing ANDA’s to market a generic version of Meda’s DYMISTA®drug product—before expiration of US ‘620.