Although Sandoz’ application for FDA approval to market a biosimilar version of ENBREL® (etanercept) has yet to be approved, Amgen has brought suit under the Patent Act and Biologics Price Competition and Innovation Act (BPCIA) to enforce five patents relating to that product and approved methods of use. Some of the BPCIA issues raised in Amgen’s complaint are similar to those raised by Janssen Biotech, Inc. in its dispute with Celltrion Healthcare Co., Ltd. over Remicade® (infliximab), which I have written about here. Sandoz’ previous attempts to invalidate two of the patents at issue and a potential IPR proceeding involving one of those same patents makes this case even more interesting to follow.

The ENBREL Patents At Issue

The patents at issue include two patents owned by Hoffmann-La Roche Inc. and exclusively licensed to Immunex Corporation (U.S. Patent Nos. 8,063,182 and 8,163,522), and three patents owned by Immunex (U.S. Patent Nos. 7,915,225, 8,119,605, and 8,722,631). Immunex is a wholly owned subsidiary of Amgen Inc., and granted exclusive (sub)licenses to the patents to Amgen Manufacturing Limited, another wholly owned subsidiary of Amgen Inc.

As summarized in the complaint, the active ingredient in ENBREL® is etanercept, a genetically engineered fusion protein comprised of “the extracellular region of the human p75 version of the TNF receptor” and “a portion of a human immunoglobulin heavy chain (i.e., a portion of a human antibody).” Etanercept “binds to and inhibits TNF from binding to a TNF receptor,” making it useful in the treatment of “inflammatory responses implicated in certain disorders such as rheumatoid arthritis, psoriasis, and psoriatic arthritis.” According to the complaint, the FDA has approved ENBREL® for the treatement of “rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.”

The ’182 patent is said to cover the etanercept fusion protein, while the ’522 patent is said to cover constructs and methods of making the fusion protein. The other patents are said to “claim methods of using etanercept to treat psoriasis and/or psoriatic arthritis.”

The Alleged Enbrel Biosimilar Patent Infringement

According to the complaint, Sandoz infringed the patents by filing its biosimilar application. The BPCIA created 35 USC § 271(e)(2)(C), which makes filing a biosimilar application an act of patent infringement under certain circumstances:

It shall be an act of infringement to submit—
(C)(i) with respect to a patent that is identified in the list of patents described in section 351(l)(3) of the Public Health Service Act (including as provided under section 351(l)(7) of such Act), an application seeking approval of a biological product ….

42 USC § 262 (l)(3) and 42 USC § 262 (l)(7) correspond to 351(l)(3) and 351(l)(7)of the Public Health Service Act.

Here, Immunex listed the five patents at issue on its “list of patents” provided under 42 USC § 262(l)(3), one of the “patent dance” provisions of the BPCIA. (Please see this article for a more detailed discussion of the complicated steps of this “patent dance”.)

The complaint also seeks declaratory judgments of infringement, based on the assertion that “[i]f the FDA approves Defendants’ aBLA, Defendants will also infringe one or more claims of each of the patents-in-suit, under 35 U.S.C. § 271(a), (b), or (g), should they engage in the commercial manufacture, use, offer for sale, sale, distribution in, or importation into the United States of Defendants’ etanercept product.”

The Enbrel Biosimilar Patent Dance Issues

The complaint alleges that Sandoz failed to comply with the “patent dance” provisions of the BPCIA, but does not seek any specific relief for those violations.

In particular, the complaint notes that after Immunex provided its list of patents under 42 USC § 262(l)(3)(A), Sandoz provided a letter with “its patent contentions” (see 42 USC § 262(l)(3)(B)) that also “agree[d]” with the Immunex patent list and (according to the complaint) “stat[ed] that it no longer wished to follow the strictures of the BPCIA.” According to the complaint:

Sandoz Inc. … insisted that Immunex file an action for patent infringement pursuant to 42 U.S.C. § 262(l)(6) within 30 days, i.e., by February 26, 2016.

(This complaint was filed on February 26, 2016.)

The complaint alleges that because Sandoz did not follow all the steps of the patent dance, 42 U.S.C. § 262(l)(9) applies and gives “Immunex—but not Defendants” the right to “bring a declaratory action on patents related to Defendants’ biosimilar product.”

Other Proceedings Involving The Enbrel Patents

Sandoz previously sought to invalidate the ‘182 and ‘522 patents in a declaratory judgment action brought the day it began its Phase III clinical trial. As I wrote in this article, both the district court and the Federal Circuit found that the “immediacy” factor of the “case or controversy” requirement for declaratory judgment jurisdiction under 28 USC § 2201 was lacking at the time. Indeed, Sandoz had not yet filed its biosimilar application.

In the complaint filed in that case, Sandoz argued that the patents should be held invalid and unenforceable because prosecution was “unreasonably and inexplicably delayed” by the applicant’s tactics.  (The ‘182  and ‘522 patents are pre-GATT patents that were not published before grant and that have 17-year terms measured from their grant dates.) It will be interesting to see if Sandoz raises those arguments again here.

The ‘522 patent is the subject of an IPR petition brought by the Kyle Bass and the Coalition For Affordable Drugs. Amgen filed a Patent Owner Preliminary Response in that matter on December 14, 2016, and the PTAB should decide whether to institute an IPR proceeding by March 14, 2016. If so, it will be interesting to see whether and to what extent an IPR brought by a party who is not involved in the infringement litigation impacts the district court proceeding.