The new year has brought a wave of activity for EYLEA^® (aflibercept) biosimilars. Following up on our previous report (EYLEA^® (aflibercept) and Soliris^® (eculizumab) IPR and BPCIA Litigation Updates, December 31, 2023), in this report we provide an update of recent Inter Partes review (“IPR”) Final Written Decisions (“FWDs”) and BPCIA litigations related to EYLEA^®.

EYLEA^® IPRs

U.S. Patent Nos. 10,130,681 and 10,888,601

On January 9, 2024, the PTAB issued FWDs in IPR2022-01225 finding claims 1, 3-11, 13, 14, 16-24, and 26 of Regeneron’s U.S. Patent Nos. 10,130,681 (“the ’681 patent), and in IPR2022-01226 finding claims 1-9, 34-39, 41-43, and 45 of Regeneron’s U.S. Patent No. 10,888,601 (“the ’601 patent”) unpatentable. Both patents are directed to methods of treatment.  The patents were challenged by Mylan Pharmaceuticals (“Mylan”), Biocon Biologics, Inc. (“Biocon”), Samsung Bioepis Co., Ltd. (“Samsung Bioepis”) and Celltrion, Inc. (“Celltrion”).

Celltrion’s aBLA for its proposed EYLEA^® biosimilar CT-P42 (aflibercept) was accepted by the FDA in June 2023, and Samsung Bioepis’s aBLA for its proposed biosimilar SB15 (aflibercept) was accepted by the FDA on an undisclosed date.  Both aBLAs are currently pending.

The January 2024 decisions mark the fourth and fifth FWDs for an EYLEA^® patent. In the previous FWDs, the PTAB found the challenged claims of two method of treatment patents (U.S. Patent Nos. 9,254,338 and 9,669,069) and a syringe patent (U.S. Patent No. 9,220,631) unpatentable. (Mylan v. Regeneron IPR2021-00880, IPR2021-00881 and Novartis v. Regeneron IPR2021-00816).

In the IPR2022-01225 FWD, the PTAB Board (“the Board”) found that challenged claims 1, 3-11, 13, 14, 16-24, and 26 of the ’681 patent are unpatentable as anticipated by the prior art (the Dixon reference) that disclosed “the same molecular structure” as claimed in the ‘681 patent, relying on the same reasoning as used in the FWD in IPR2021-00881 concerning Regeneron’s U.S. Patent No. 9,254,338.  In making that determination, the Board rejected Regeneron’s argument that the ‘681 patent’s “method for treating” claim limitation requires a “high level of efficacy” comparable to that achieved by Lucentis^® or Avastin^®, and instead only requires “a therapeutically effective amount” of the claimed VEGF receptor antagonist as disclosed in the ‘681 patent specification because, while the claims “encompass a clinical result, they do not require such a result.”  In addition, the Board construed the exclusion criteria limitations in the ‘681 dependent patent claims are “not entitled to patentable weight” under the printed matter doctrine because they “recite informational content that does not result in a manipulative difference in the steps of the claim” and are “not functionally related” to the claims.  Because the Board found that the Dixon reference anticipates the claims as construed, they did not reach the additional Grounds of the -01225 Petition.

The ’681 patent’s claims 1, 3-11, 13, 14, 16-24, and 26 (the same claims that are the subject of IPR2022-01225) have also been challenged by Samsung Bioepis in IPR2023-00422, whose Petition was filed on January 6, 2023. The IPR was instituted on July 19, 2023 and is currently pending.

In the IPR2022-01226 FWD, the Board found that challenged claims 1-9, 34-39, 41-43 and 45 of the ’601 patent are unpatentable as anticipated by the prior art (the Dixon reference) for substantially the same reasons as in the IPR2022-01225 FWD.  Specifically, as in the -01225 FWD, the Board rejected Regeneron’s argument that the claim term “effective” requires “a high level of efficacy” comparable to that achieved by Lucentis^® or Avastin^®, and instead only requires “a therapeutically effective amount” of the claimed VEGF receptor antagonist as disclosed in the ‘601 patent specification.  The Board also adopted the same reasoning as in the -01225 FWD to find that the exclusion criteria limitations in the ‘601 patent dependent claims are not entitled to patentable weight. Regarding other limitations recited in the ‘601 patent dependent claims, the Board found that those limitations are expressly or inherently disclosed in the Dixon reference, and therefore, the dependent claims are anticipated by Dixon.  As in the -01225 FWD, the Board determined that because the Dixon reference anticipates the ‘601 patent claims as construed, they did not reach the additional Grounds of the -01226 Petition.

In addition to the -01225 IPR, claims 11 and 19 of the ’601 patent are also the subject of BPCIA litigation 1:22-cv-00061 (N.D.W. Va.) that found those claims invalid (see EYLEA^® BPCIA Litigations below).

U.S. Patent No. 10,464,992

On January 22, 2024, Regeneron requested termination of IPR2023-00462 (Petitioner Celltrion, which was joined by Samsung Bioepis IPR2023-01312), challenging claims 1-18 of Regeneron’s U.S. Patent No. 10,464,992, directed to formulations, as a result of Regeneron’s statutory disclaimer of the challenged claims. Regeneron’s termination request is pending and is unopposed.

EYLEA^® BPCIA Litigations

As we previously reported in EYLEA^® (aflibercept) and Soliris^® (eculizumab) IPR and BPCIA Litigation Updates, December 31, 2023, claims 11 and 19 of the ’601 patent were found to be invalid in a BPCIA litigation brought by Regeneron against Mylan (1:22-cv-00061 (N.D.W. Va.). Regeneron filed an appeal to the Federal Circuit on January 29, 2024 (CAFC-24-1402) and Biocon and Mylan filed a cross-appeal (CAFC-24-1405).

On January 10, 2024, Regeneron filed an infringement litigation against Amgen’s proposed biosimilar ABP 938 (aflibercept) in the Central District of California (2:24-cv-00264 (C.D. Cal.)), the aBLA for which was accepted by the FDA in October 2023.  Regeneron’s Complaint listed 32 patents, including 9 patents with method of treatment claims, 7 patents with formulation/composition claims, 4 patents with composition of matter claims, 16 patents with manufacturing claims, one patent with device claims, and 2 patents with packaging claims.  All of the patents asserted in the Amgen litigation have previously been asserted in EYLEA^® litigations against other proposed biosimilars, including U.S. Patent No. 11,084,865, whose asserted claims were found valid and infringed in Regeneron v. Mylan (1:22-cv-00061 (N.D.W. Va.) (previously reported in EYLEA^® (aflibercept) and Soliris^® (eculizumab) IPR and BPCIA Litigation Updates, December 31, 2023). This is the sixth BPCIA litigation brought by Regeneron for EYLEA^®. Shortly after filing the Central District of California litigation, Regeneron filed a Motion to Transfer to the Western District of West Virginia where all of the other EYLEA^® BPCIA litigations are pending.  The Transfer motion is currently pending.

While Regeneron’s Complaint did not mention whether Amgen provided Regeneron with a 180-day notice of commercial marketing, similar to the other EYLEA^® biosimilar litigations, Regeneron requested a schedule for a preliminary injunction proceeding, and a scheduling conference is currently set for April 5, 2024.

EYLEA^®’s U.S. sales were reported to be about $6.26 billion in 2022.

We continue to monitor these cases and will provide updates as they become available. For more information about these and other biosimilar patent disputes, visit BiologicsHQ.

 

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The authors would like to thank April Breyer Menon for her contributions to this article.