The Patent Trial and Appeal Board (PTAB) has delivered a series of adverse rulings against Regeneron Pharmaceuticals' patent portfolio protecting EYLEA (aflibercept), potentially opening the door for increased biosimilar competition for the blockbuster ophthalmology drug that generated $5.89 billion in sales in 2023.
Multiple Patent Invalidations Challenge EYLEA Protection
On June 14, 2024, the PTAB issued a Final Written Decision in Samsung Bioepis's IPR2023-00442 determining that challenged claims of Regeneron's U.S. Patent No. 10,130,681 covering EYLEA are unpatentable. The patent is directed to methods for treating angiogenic eye disorders by sequentially administering multiple doses of a vascular epithelial growth factor (VEGF) antagonist to patients.
Samsung Bioepis's petition challenged claims 1, 3-11, 13-14, 16-24, and 26 of the patent as obvious, with the Board incorporating reasoning from previous inter partes review (IPR) decisions that found related patents unpatentable. The Board concluded that because the claims are anticipated by the Dixon prior art reference, they are also obvious over Dixon.
In a separate development on July 23, two PTAB panels granted adverse judgments for U.S. Patent Nos. 11,253,572 and 10,888,601 after Regeneron filed disclaimers with the USPTO for all claims of the former patent and certain claims of the latter. These IPRs were brought by multiple companies including Samsung Bioepis, Celltrion, and Biocon.
Regeneron Abandons Federal Circuit Appeals
Regeneron has voluntarily dismissed multiple appeals to the Federal Circuit, signaling a strategic retreat from defending certain patent positions. On July 8, the company dismissed appeals of six IPR final written decisions finding claims of U.S. Patent Nos. 9,669,069 and 9,254,338 unpatentable. These IPRs were initiated by Mylan, Celltrion, and Apotex.
On August 5, Regeneron moved to voluntarily dismiss its appeal of two additional IPR final written decisions that found other claims of the patent and a related patent, U.S. Patent No. 10,130,681, to be unpatentable. The motion for voluntary dismissal came on the same day Regeneron's opening brief was due in the matter.
Biosimilar Approval Meets Legal Challenges
Samsung Bioepis's EYLEA biosimilar Opuviz (aflibercept-yszy) received FDA approval as an interchangeable biosimilar on May 20, 2024. However, despite the patent invalidations, the commercial launch faces significant hurdles. On June 14, 2024, a court issued a preliminary injunction preventing the commercial launch of Opuviz in related litigation where the invalidated patent is also at issue.
Samsung Bioepis has appealed the preliminary injunction decision to the Court of Appeals for the Federal Circuit, with appeals filed on June 20, 2024, under case numbers 24-1965 and 24-1966, which remain ongoing.
Broader Patent Landscape Under Pressure
The PTAB decisions reflect a pattern of successful challenges to Regeneron's aflibercept-dosing patents. In the IPR final written decision, the Board found that each challenged claim of the patent was identical to challenged claims of related patents that were previously found unpatentable, except for certain exclusion criteria as an additional limitation. Because the Board determined the exclusion criteria limitations were not entitled to patentable weight, it found the patent claims unpatentable as anticipated by the same prior art Dixon reference.
The ongoing patent challenges involve multiple biosimilar developers and affect various patents listed in the Purple Book for EYLEA, suggesting continued pressure on Regeneron's intellectual property protection for the ophthalmology franchise.
