Horizon Medicines LLC v. Alkem Labs. Ltd.

• Citation: 503 F.Supp.3d 118
• Decision Date: 30 November 2020
• Docket Number: Civil Action No. 18-1014-RGA
• Parties: HORIZON MEDICINES LLC, Plaintiff, v. ALKEM LABORATORIES LTD., Defendant.
• Court: U.S. District Court — District of Delaware

503 F.Supp.3d 118

HORIZON MEDICINES LLC, Plaintiff,

v.ALKEM LABORATORIES LTD., Defendant.

Civil Action No. 18-1014-RGA

United States District Court, D. Delaware.

Filed November 30, 2020

Caryn C. Borg-Breen, Esq., Jessica Tyrus Mackay, Esq., Christopher W. Weber, Esq., GREEN GRIFFITH & BORG-BREEN LLP, Chicago, IL; Chad S.C. Stover, Esq., BARNES & THORNBURG LLP, Wilmington, DE, Attorneys for Plaintiff.

William A. Rakoczy, Esq., Amy D. Brody, Esq., Anuj K. Wadhwa, Esq., Kevin P. Burke, Esq., Melvin W. Gaddy, Esq., RAKOCZY MOLINO MAZZOCHI SIWIK LLP, Chicago, IL; Dominick T. Gattuso, Esq., HEYMAN ENERIO GATTUSO & HIRZEL LLP, Wilmington, DE, Attorneys for Defendant.

TRIAL OPINION

ANDREWS, U.S. DISTRICT JUDGE:

Horizon Medicines LLC brought this action against Alkem Laboratories Ltd. for infringement of six patents.¹ (D.I. 1). I held a bench trial from September 14 to 16, 2020.² By trial the parties had narrowed the case to U.S. Patent No. 8,067,033 ("the ’033 patent").³

Before the Court are the issues of validity and infringement of the asserted patent claims. Horizon asserts infringement of claims 1, 8, 11, and 14 of the ’033 patent. (D.I. 205). I have considered the parties’ post-trial briefing. (D.I. 216, 218, 226, 227, 231, 232).

For the following reasons, I find claims 1, 8, 11, and 14 of the ’033 patent invalid for obviousness and not infringed. I find claims 1, 8, 11, and 14 of the ’033 patent not invalid for indefiniteness.

I. BACKGROUND

Horizon owns New Drug Application No. 022519 for DUEXIS® (ibuprofen

and famotidine ) tablets, 800 mg / 26.6 mg. (D.I. 189 Ex. 1 ¶¶ 3-4). The Indications and Usage section of the prescribing information for DUEXIS® (Revised July 2019), as currently approved by the FDA (the "DUEXIS® Label"), states in part that DUEXIS® "is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications." (Id. ¶ 8). The asserted patent is listed in the Orange Book for DUEXIS®. (Id. ¶ 19). Alkem submitted Abbreviated New Drug Application (ANDA) No. 211890 on March 31, 2018 seeking FDA approval to engage in the commercial manufacture, use, and sale of ibuprofen and famotidine tablets, 800 mg / 26.6 mg ("ANDA Product"). (Id. ¶¶ 10, 11). The active pharmaceutical ingredients in Alkem's ANDA Product are Ibuprofen, USP and Famotidine, USP. (Id. ¶ 13). On May 29, 2018, Alkem sent a "Notification of Certification of Invalidity, Unenforceability and/or Non-Infringement for U.S. Patent Nos. 8,067,033 B2, 8,067,451 B2, 8,309,127 B2, 8,318,202 B2, 8,449,910 B2 and 8,501,228 B2 Pursuant to § 505(j)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act" to Horizon Pharma, Inc. and Horizon Pharma USA, Inc. Alkem indicated that it was seeking FDA approval of its ANDA so that it could engage in the commercial manufacture, use and sale of its ANDA Product before the expiration of, as relevant here, the ’033 patent. (Id. ¶ 12). Horizon then filed this action alleging infringement by Alkem's ANDA submission. (D.I. 1).

The asserted patent is directed to stable pharmaceutical compositions of famotidine

and ibuprofen in a single dosage form, comprising a famotidine core having a reduced or minimal surface area surrounded by a layer of ibuprofen. ( ’033 pat. at Abstract). Independent claim 1 and dependent claims 8, 11, and 14 of the ’033 patent read as follows:

1. A pharmaceutical composition comprising a first portion that comprises 800 mg ibuprofen

and a second portion that comprises 26.6 mg famotidine, wherein the surface area of direct physical contact between ibuprofen and famotidine does not exceed 130 mm², wherein no more than about 1% sulfamide is present when the composition is stored at 40° C. and 75% relative humidity for a period of one month, wherein the composition is formulated so that release of both the ibuprofen and the famotidine occurs rapidly at about the same time, wherein none of the composition, the famotidine, and the ibuprofen is enterically coated or formulated for sustained or delayed release, and wherein the composition is for use according to a TID (three times per day) administration schedule for reducing the risk of developing ibuprofen-induced ulcers in a human patient requiring ibuprofen for an ibuprofen-responsive condition.

8. The composition of claim 1 wherein the second portion comprises a layer of famotidine and the first portion comprises a layer of ibuprofen and the two layers are separated by a barrier layer.

11. The composition of claim 1 wherein the composition is formulated so that at least about 80% of the famotidine and at least about 80% of the ibuprofen are released from the composition into solution within 30 minutes at a pH of about 6.8 to about 7.4.

14. The composition of claim 1 wherein at least 98% of the ibuprofen and the famotidine are each present when the composition is stored under room temperature storage conditions of 25° C. and 60% relative humidity for a period of nine months.

I have construed the term "a first portion" to mean "an ibuprofen compartment that is not core" and the term "a second portion" to mean "a famotidine

compartment that is not shell." (D.I. 89 at 1). I have construed the term "surface area of direct physical contact between ibuprofen and famotidine does not exceed 130 mm²" to mean "the surface area over which no barrier layer that prevents physical contact is interposed between ibuprofen and famotidine does not exceed 130 mm²." (Id. at 2). I have construed the term "barrier layer" to mean "layer interposed between components or adjacent compartments of the unit dosage form to prevent contact between the components or adjacent compartments." (Id. ). I also adopted the parties’ agreed-upon construction of "direct physical contact" as "the absence of a barrier layer between components or adjacent compartments of a unit dosage form." (Id. ).

Horizon concedes that Alkem's ANDA Product does not literally infringe the ’033 patent. (D.I. 216 at 6). Horizon argues infringement under the doctrine of equivalents. Alkem contends that it does not infringe any of the asserted claims, while conceding that its product meets the claim limitation "wherein the composition is for use according to a TID administration schedule for reducing the risk of developing ibuprofen-induced ulcers in a human patient requiring ibuprofen for an ibuprofen-responsive condition" of claim 1 of the ’033 patent. (D.I. 205). Alkem argues that all the asserted claims are invalid as obvious in view of the prior art. Alkem also contends that the "no more than about 1% sulfamide" limitation in all asserted claims is invalid as indefinite.

II. OBVIOUSNESS

Under the Court's construction (D.I. 89), independent claim 1 of the ’033 patent contains multiple limitations directed to an 800 mg ibuprofen compartment that is not a core, a 26.6 mg famotidine

compartment that is not shell, as well as certain stability, release, and dosing limitations. The asserted dependent claims contain additional limitations, such as the ibuprofen compartment and the famotidine compartment are in a bilayer, separated by a barrier layer (claim 8), release limitations wherein at least about 80% of the famotidine and at least about 80% of the ibuprofen are released from the composition into solution within 30 minutes at a pH of about 6.8 to about 7.4 (claim 11), and stability limitations wherein at least 98% of the ibuprofen and the famotidine are each present when the composition is stored under room temperature storage conditions of 25° C. and 60% relative humidity for a period of nine months (claim 14).

Alkem argues that all the asserted claims are invalid as obvious over the prior art. (D.I. 218 at 22-30). Specifically, Alkem argues that a person of ordinary skill in the art ("POSA") would have been motivated to combine the prior art teachings of either (1) Taha and/or US 2007/0043096 A1 (the ’096 publication), USP, and US 2005/0020671 A1 (the ’671 publication) or (2) Taha and/or the ’096 publication, USP, and US 2005/0281876 A1 (the ’876 publication) to administer the combination of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen

and the H2 receptor antagonist (H2RA) famotidine in effective dosages (800 mg TID; 80 mg total daily dose, respectively) to reduce the risk of developing ibuprofen-induced ulcers. (Id. at 8, 22-30). With the exception of the ’096 publication, the references on which Alkem relies undisputedly qualify as prior art under 35 U.S.C. § 102(b). (Id. at 8-9). Alkem contends that the ’096 publication qualifies as prior art under 35 U.S.C. § 102(a) because the invention thereof was "known or used by others in this country" before the invention of the ’033 patent. (Id. at 9). Horizon contends that the ’096 publication cannot be used as prior art to the ’033 patent because the subject matter of the ’096 publication is not the work of "another" as required by 35 U.S.C. § 102(a). (D.I. 227 at 2).

A. Legal Standard

A patent claim is invalid as obvious "if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." 35 U.S.C. § 103 ; see also KSR Int'l Co. v. Teleflex Inc. , 550 U.S. 398, 406-07, 127 S.Ct. 1727, 167 L.Ed.2d 705 (2007). The determination of obviousness is a question of law with underlying factual findings. See Kinetic Concepts, Inc. v. Smith & Nephew, Inc. , 688 F.3d 1342, 1360 (Fed. Cir. 2012). "The underlying factual inquiries include (1) the scope and content of the prior art; (2) the differences between the prior art and the claims at issue; (3) the level of ordinary skill in the art; and (4) any relevant secondary considerations ...."...