Immunex Corp. v. Sanofi-Aventis U.S. LLC

• Decision Date: 13 October 2020
• Docket Number: 2019-1749, 2019-1777
• Citation: 977 F.3d 1212
• Parties: IMMUNEX CORPORATION, Appellant v. SANOFI-AVENTIS U.S. LLC, Genzyme Corporation, Regeneron Pharmaceuticals, Inc., Cross-Appellants Andrei Iancu, Under Secretary of Commerce for Intellectual Property and Director of the United States Patent Trademark Office, Intervenor
• Court: U.S. Court of Appeals — Federal Circuit

977 F.3d 1212

IMMUNEX CORPORATION, Appellant

v. SANOFI-AVENTIS U.S. LLC, Genzyme Corporation, Regeneron Pharmaceuticals, Inc., Cross-AppellantsAndrei Iancu, Under Secretary of Commerce for Intellectual Property and Director of the United States Patent Trademark Office, Intervenor

2019-1749, 2019-1777

United States Court of Appeals, Federal Circuit.

Decided: October 13, 2020

Eldora Ellison, Sterne Kessler Goldstein & Fox, PLLC, Washington, DC, argued for appellant. Also represented by David Holman, David William Roadcap, Jon Wright.

Lauren Fornarotto, McKool Smith, P.C., New York, NY, argued for cross-appellants. Also represented by John Franklin Garvish, II, Matthew Cameron, Geoffrey Smith, Joel Lance Thollander, Austin, TX; Eric Sorensen Hansen, Mike McKool, Dallas, TX; Noah Samuel Frank, George W. Hicks, Jr., Nathan S. Mammen, Kirkland & Ellis LLP, Washington, DC.

Frances Lynch, Office of the Solicitor, United States Patent and Trademark Office, Alexandria, VA, argued for intervenor. Also represented by Sarah E. Craven, Thomas W. Krause, Farheena Yasmeen Rasheed.

Before Prost, Chief Judge, Reyna and Taranto, Circuit Judges.

Prost, Chief Judge.

This is a consolidated appeal from two Patent Trial and Appeal Board ("Board") decisions in inter partes reviews ("IPRs") of U.S. Patent No. 8,679,487 ("the '487 patent"), owned by Immunex Corp. ("Immunex"). Sanofi-Aventis U.S. LLC, Genzyme Corp., and Regeneron Pharmaceuticals, Inc. (collectively, "Sanofi") challenged the '487 patent, which covers isolated human antibodies that bind the human interleukin-4 receptor. The Board invalidated all challenged claims in one of the IPRs, No. IPR2017-01884. Immunex appeals, contesting the construction of the claim term "human antibodies." In the other IPR, No. IPR2017-01879, involving a subset of the same claims, the Board did not invalidate the patents for reasons of inventorship. Sanofi appeals, contesting the Board's inventorship determination. We consolidated the cases in the nature of an appeal and a cross-appeal. For the reasons below, we agree with the Board's claim construction in No. IPR2017-01884 (here, "the appeal"). Accordingly, we affirm that invalidity decision. Because this leaves valid no claims at issue in the second IPR, we dismiss Sanofi's inventorship appeal from No. IPR2017-01879 (here, the "cross-appeal").

BACKGROUND

I

The '487 patent is directed to antibodies that bind to the human interleukin-4 ("IL-4") receptor, the resulting inhibition of which is significant for treating various inflammatory disorders, such as arthritis, dermatitis, and asthma. See '487 patent col. 3 ll. 15–31; J.A. 3–4.

Claim 1 reads:

An isolated human antibody that competes with a reference antibody for binding to human IL-4 interleukin-4 (IL-4) receptor, wherein the light chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:10 and the heavy chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:12.

'487 patent (emphasis added). This appeal concerns what "human antibody" means in this patent.

First, the relevant science. Antibodies are proteins. Like all proteins, they are composed of numerous individual amino acids chained together in a particular sequence. Antibodies are roughly Y-shaped, made of four chains—two "heavy" and two "light." Each chain can be further divided into a "variable region" and a "constant region." And each variable region contains three relatively small "complementarity-determining regions" (CDRs) situated at the tips of the Y. The remainder of the variable regions are the "framework regions."

Particular antibody regions have particular biological implications. For instance, it is primarily the CDRs that give an antibody its ability to bind selectively to specific targets (i.e., antigens), despite making up just a sliver of its structure. See J.A. 1501, 7042–43. To that end, an antibody's exact amino acid sequence determines what the antibody binds to, which affects the antibody's therapeutic usefulness. The amino acid sequence of an antibody also determines whether the human immune system recognizes and rejects it as "non-human." Amino acid sequences that are human in origin—that is, sequences "consistent with the amino acid sequences of antibodies produced naturally by the human immune system," see Appellant's Br. 4—can avoid triggering immune responses.

Early efforts at therapeutic antibody development started with mice. For example, researchers could inject a mouse with an antigen, the mouse would generate antibodies to the antigen, and those antibodies would be harvested. In that case, the entire amino acid sequence was murine (i.e., from mice). These antibodies, disappointingly, tended to plague patients with "undesirable and harmful immune reactions." See Appellant's Br. 7–8. Too much of each antibody was "mouse" in origin, to the consternation of the human immune system.

Through various techniques, the proportion of an antibody that is recognized as "mouse" can be decreased. In "chimeric" antibodies, for instance, the constant regions tend to be human in origin, and the variable regions, including the CDRs, tend to be nonhuman—making the antibodies' amino acid sequences mostly human in origin. Appellant's Br. 8–9. In "humanized" antibodies, only the CDRs are nonhuman—the antibodies' amino acid sequences, including the portions responsible for immune reaction, are almost entirely human in origin.¹ Further, fully human antibodies can be made in which even the CDRs are human in origin.

Here, some of the disclosed embodiments are "partially human" and some are "completely human." E.g., '487 patent col. 19 ll. 38–44, col. 21 ll. 6–14. Among the former, the specification's embodiments specifically include humanized and chimeric antibodies. Id. at col. 18 ll. 36–37, col. 19 ll. 21–37.

The claim construction dispute is this: in the context of this patent, must a "human antibody" be entirely human? Or may it also be "partially human," including "humanized"?

II

Amid infringement litigation, Sanofi filed three IPR petitions challenging claims 1–17 of the '487 patent. Two were instituted.

In one final written decision, the Board concluded that claims 1–17 were unpatentable as obvious over two references, Hart and Schering-Plough. Sanofi-Aventis v. Immunex , No. IPR2017-01884, Paper 96, 2019 WL 643041 (P.T.A.B. Feb. 14, 2019) (" Final Written Decision ").

Hart describes a commercially available murine antibody that purportedly meets all the limitations of claim 1—except that it is fully murine, not human at all. Final Written Decision , 2019 WL 643041, at *7–8. But Schering-Plough teaches humanizing such murine antibodies by "grafting" their CDRs onto an otherwise fully human antibody. Id. Sanofi therefore argued that the claims were obvious in light of the humanized antibody that would result from this combination. Further, Sanofi argued in a second obviousness ground that the gap between "humanized" and "fully human" could be closed using the teachings of a third reference, Hoogenboom. J.A. 1095. The Board reached only the first ground, finding that the "humanized" antibody met its construction of "human antibody." Final Written Decision , 2019 WL 643041, at *9, *12. On appeal, Immunex insists only that the Board erred in this construction.

In the second final written decision, the Board concluded that Sanofi had not shown by a preponderance of the evidence that claims 1–14, 16, and 17 were anticipated by one of Immunex's own publications. Sanofi-Aventis v. Immunex , No. IPR2017-01879, Paper 88, 2019 WL 643024 (P.T.A.B. Feb. 14, 2019). Sanofi appealed, contending that the Board erred in determining that the disclosure was not § 102(e) prior art "by another." We consolidated Immunex's appeal and Sanofi's appeal in the nature of an appeal and a cross-appeal, respectively. See Order (July 10, 2019), ECF No. 21.

We have jurisdiction under 28 U.S.C. § 1295(a)(4)(A).

DISCUSSION

I

First, we consider the applicable claim construction standard in light of a post-briefing terminal disclaimer.

After appellate briefing was complete, Immunex filed with the Patent and Trademark Office ("PTO") a terminal disclaimer of its patent. The PTO promptly accepted it, and Immunex's patent therefore expired on May 26, 2020, just over two months before oral argument.

Immunex then filed a citation of supplemental authority under Federal Rule of Appellate Procedure 28(j), apprising us of (but not explaining the reason for) its terminal disclaimer and asking us to change the applicable claim construction standard. See Citation of Suppl. Authority (Apr. 10, 2020), ECF No. 66. Sanofi and the PTO insist that Immunex has waived the Phillips issue. We need not reach waiver, determining for the following reasons that the BRI standard applies.

Today, in all newly filed IPRs, the Board applies the Phillips district-court claim construction standard. 37 C.F.R § 42.100(b) (2020) ; Phillips v. AWH Corp. , 415 F.3d 1303 (Fed. Cir. 2005) (en banc).² But when Sanofi filed its IPRs, the Board applied this standard only to expired patents. To unexpired patents, it applied the broadest reasonable interpretation ("BRI") standard. 37 C.F.R. § 42.100(b) (2016) ; In re CSB–Sys. Int'l, Inc. , 832 F.3d 1335, 1341–42 (Fed. Cir. 2016). Immunex, with its letter, now urges us to apply Phillips , citing Wasica Finance GmbH v. Continental Automotive Systems, Inc. , 853 F.3d 1272, 1279 (Fed. Cir. 2017), and In re CSB–System International , 832 F.3d 1335. But unlike here, the patents in Wasica and CSB had expired before the Board's decision.

We have also applied the Phillips standard when a patent expired on appeal. See PTO Resp. Letter (Apr. 30, 2020), ECF No. 72 (citing Apple Inc. v. Andrea Elecs. Corp. , 949 F.3d 697, 707 (Fed. Cir. 2020) ). But we do not read Andrea Electronics to mean that whenever a patent expires on appeal, at any time and for any reason, Phillips applies. In Andrea Electronics , the patent's term expired as...