Sanofi-Aventis U.S. LLC, Genzyme Corporation, and Regeneron Pharmaceuticals, Inc. recently scored a victory in their ongoing dispute over a patent that Immunex Corporation claims covers Dupixent^®, Sanofi and Regeneron’s anti-IL-4 antibody marketed for treatment of moderate-to-severe eczema. In February, the Patent Trial and Appeal Board (“the Board”) instituted two petitions for inter partes review (“IPR”) (IPR No. 2017-01879 and IPR2017-01884) of Patent No. 8,679,487 (“the ’487 patent”) assigned to Immunex Corp (“Patent Owner”).  Sanofi-Aventis U.S. LLC, Genzyme Corp., and Regeneron Pharmaceuticals, Inc. (“Petitioners”) assert in the first petition (IPR No. 2017-01879) that claims 1–14, 16, and 17 of the ’487 patent are invalid as anticipated by U.S. Patent Application Publication No. 2002/0002132 A1 (“the ’132 Publication”).  The second petition (IPR2017-01884) alleges claims 1-17 of the ’487 patent are invalid as obvious over three prior art references.[1]

The ’487 patent is directed to compositions and methods for treating certain conditions induced by interleukin-4 (IL-4) by administering an IL-4 antagonist.  The sole independent claim requires “[a]n isolated human antibody that competes with a reference antibody for binding to human IL-4 interleukin-4 (IL-4) receptor,” wherein the light and heavy chains comprise SEQ ID NO:10 and SEQ ID NO:12, respectively.  The Petitioners challenged the validity of the ’487 patent, in part, based on experimental evidence provided by their expert declarant showing prior art antibodies inherently competed with reference antibodies described in the ’487 patent.

The IPR petitions are part of a larger legal battle over the ’487 patent.  As previously discussed here, Regeneron, Genzyme, and Sanofi filed a declaratory judgment action in Massachusetts district court in March 2017, seeking a declaration that the ’487 patent is invalid or not infringed.  Immunex counter-sued in the Central District of California.  The Massachusetts case was voluntarily dismissed in May 2017, but the California litigation has continued.

Just after filing their declaratory judgment action, Petitioners also filed a previous IPR petition (IPR No. 2017-01129, filed March 23, 2017), previously reported here.  That earlier petition challenged claims 1–17 of the ’487 patent as being invalid as anticipated by U.S. 2008/0160035 A1 (“the Stevens Publication”).  The Board denied institution of the petition, concluding that the Stevens Publication was not prior art under pre-AIA 35 U.S.C. § 102.

In each of the two IPRs that were ultimately instituted, Immunex argued that the Board should exercise its discretion and deny institution of the follow-on petitions.  Immunex argued the follow-on petitions were directed to the same claims of the same patent and that each of the seven factors applied in General Plastic favor denial.  See Gen. Plastic Indus. Co. v. Kaisha, Patent Tr. & App. Bd. No. IPR2016-01357 (Patent Tr. & App. Bd. Sept. 6, 2017) (Paper 19); see also NVIDIA Corp. v. Samsung Elec. Co., Case IPR2016-00134 (PTAB May 4, 2016) (Paper 9).  Specifically, the framework for exercising discretion to institute follow-on petitions, as applied in General Plastics, includes considering:

1. whether the same petitioner previously filed a petition directed to the same claims of the same patent;
2. whether, at the time of filing of the first petition, the petitioner knew of the prior art asserted in the second petition or should have known of it;
3. whether, at the time of filing of the second petition, the petitioner already received the patent owner’s preliminary response to the first petition or received the Board’s decision on whether to institute review in the first petition;
4. the length of time that elapsed between the time the petitioner learned of the prior art asserted in the second petition and the filing of the second petition;
5. whether the petitioner provides adequate explanation for the time elapsed between the filings of multiple petitions directed to the same claims of the same patent;
6. the finite resources of the Board; and
7. the requirement under 35 U.S.C. § 316(a)(11) to issue a final determination not later than one year after the date on which the Director notices institution of review.

General Plastic, IPR2016-01357, slip op. at 9-10.

Immunex argued that the Petitioners previously challenged the same claims of the ’487 patent and that they were aware of the cited references asserted in the subsequent petitions before filing the first petition, i.e. IPR No. 2017-01129.  In addition, the Petitioners had already received the Patent Owner’s preliminary response to the first petition and responded to certain arguments at the time of filing the two subsequent petitions.  Immunex finally contended that the Petitioners failed to provide an adequate explanation for why they filed multiple petitions.

However, the Petitioners responded that the petitions could only be filed after experiments were conducted to show the claimed feature, “[a]n isolated human antibody that competes with a reference antibody for binding to human IL-4,” was inherently disclosed in the prior art.  In addition, the Petitioners asserted that the ’487 patent does not specify how to determine whether an antibody “competes with a reference antibody,” as required by the claims, and it was not until November 23, 2016, in a European Patent Office proceeding, that the Patent Owner endorsed two competition assays.  Subsequently, the Petitioners retained experts to complete the experiments needed for the petitions.

The Board found the Petitioners’ reasoning persuasive and decided to institute.  The Board reasoned that the Petitioners did not appear to strategically stage prior art and arguments in multiple petitions.  See General Plastic, IPR2016-01357, slip op. at 17 (“The absence of any restrictions on follow-on petitions would allow petitioners the opportunity to strategically stage their prior art and arguments in multiple petitions, using our decisions as a roadmap, until a ground is found that results in the grant of review.”).  In particular, the Board noted that during prosecution of the ’487 patent, the Examiner did not have the benefit of the Petitioners’ additional experimental evidence relating to competition.  The Board also noted that the competition assay was not an issue in the first petition.  As a result, the Board concluded that the same or substantially the same prior art or arguments were not previously presented to the Office, and the delayed filing to allow time for completion of the additional experiments was reasonable.

As the Board concluded, the present petitions fall under a relatively unique set of circumstances.  However, the reasoning by the Board may provide guidance to parties that similarly find the need to file follow-on petitions in the face of new evidence of invalidity.  This is particularly true in the realm of biologics where many claims require a specific activity of the molecule.  During examination in the Patent Office, many patent applications may escape prior art where the reference describes similar molecules but fails to disclose a specific activity.  This will often require petitioners to retain experts in the field to conduct experiments that are outside the reach of the Patent Office.

We will provide updates as these IPR decisions come to light.

[1] Hart et al., Diminished Responses to IL-13 by Human Monocytes Differentiated in vitro: Role of the IL13Rα1 chain and STAT6, 29 EUR. J. IMMUNOL. 2087–97 (1999); Galizzi et al, EP 0 604 693 A1; and Hoogenboom, et al. US 5,565,332.