Linagliptin – USA

On Mar. 16, 2020, Federal Circuit reversed in-part & affirmed in-part district court’s decision in a case involving DPP-IV inhibitors such as linagliptin.

Boehringer (Plaintiff) sued Mylan & Aurobindo (Defendants) in district court over U.S. Patent Nos. 8,853,156, 9,173,859 and 8,673,927, which relate to the treatment of type 2 diabetes mellitus. District court issued judgment on the pleadings under Federal Rule of Civil Procedure 12(c) & held that claims 10-17, 24 and 25 of the ’156 patent are directed to ineligible subject matter under 35 U.S.C. § 101. The district court also held that claims 1, 14, 15, 20, and 21 of the ’859 patent and claims 7, 9, 15, 17, 19, 25, and 26 of the ’927 patent are invalid for obviousness-type double patenting in light of the claims of US 8,178,541, and invalid as obvious in view of US 2004/0097510. Boehringer appealed.

35 U.S.C. § 101 (ineligibility):

Independent claim 1 of US’156:

   1.   A method of treating and/or preventing metabolic diseases in a patient for whom metformin therapy is inappropriate due to at least one contraindication against metformin comprising orally administering to the patient a DPP-IV inhibitor wherein the contraindication is selected from the group consisting of: renal disease, renal impairment or renal dysfunction, unstable or acute congestive heart failure, acute or chronic metabolic acidosis, and hereditary galactose intolerance.

   10.  The method according to claim 1 wherein the metabolic disorder is type 2 diabetes mellitus and wherein the contraindication is renal disease, renal impairment or renal dysfunction, and wherein said DPP-4 inhibitor is used for said patient in the same dose as for a patient with normal renal function.

Defendants argued that the claims are directed to the natural law that “certain DPP-IV inhibitors (including linagliptin) are metabolized by the liver rather than the kidney.” Boehringer argued that the claims are directed to a “method of treating a specific disease ([type 2 diabetes mellitus]) for specific patients (with renal impairment) using a specific compound (linagliptin) at specific doses (same dose in patients with renal impairment as in patients with normal renal function) to achieve a specific outcome.” Federal Circuit citing “Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018)”, held that the claims are directed to a particular method of treatment under step one and are therefore patent eligible. The claims of the ’156 patent are directed to a method of treating type 2 diabetes mellitus using a DPP-IV inhibitor, such as linagliptin. That certain DPP-IV inhibitors (including linagliptin) are metabolized by the liver rather than the kidney, does not make the claim ‘directed to’ that natural ability. Thus, claims are directed to a method of treatment at step one, as patent eligible and therefore need not reach step two.

Obviousness-type double patenting (ODTP) & 35 U.S.C. § 103 (Obviousness):

The claims at issue of both patents (US’859 & US’927) relate to the treatment of type 2 diabetes mellitus with linagliptin in 2.5 or 5 mg doses. US 8,178,541 (earlier expiring patent) was cited for ODTP & US 2004/0097510 was cited for obviousness. Federal Circuit sided with district court which found that the claimed invention’s doses of linagliptin in 2.5 mg and 5 mg fall within the ’510 publications disclosed range of 1–100 mg, thus there is a presumption of obviousness. Court also said that the person of ordinary skill in the art would have obtained the claimed dosages through routine experimentation. Based on the evidences & testimony it can be concluded that dose-ranging studies are common & are required for FDA approval. Dr. Grass testified that dose ranging studies are “conducted starting with a low dose, and sequentially moving through increasing doses.” Based on these facts & evidences, Federal Circuit affirmed district court & found asserted claims of the ’859 and ’927 patents invalid for obviousness and obviousness-type double patenting.