Writing Strong Antibody Claims: Avoiding or Addressing USPTO Rejections for Written Description and Enablement

Written Description and Enablement Generally

The legal standards for written description and enablement are well-established. To meet the written description requirement, the specification must convey with reasonable clarity that as of the filing date the inventor was in possession of the claimed invention. See, Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560 (Fed. Cir. 1991); Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (specification must “clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). The enablement requirement is met if the specification would allow a person of ordinary skill in the art to make and use the claimed invention without undue experimentation. See, Amgen, Inc. v. Sanofi, 598 U.S. 594, 611 (2023).
The Supreme Court observed in Amgen that “[d]espite recent advances, aspects of antibody science remain unpredictable … [and] scientists understand that changing even one amino acid in the sequence can alter an antibody’s structure and function” in unpredictable ways. Amgen, 598 U.S. at 612-13. In Ariad, the Federal Circuit found that the disclosure of three types of molecules supporting the claimed substance for interfering with a gene transcription factor was insufficient to meet the written description requirement. Ariad, 598 F.3d at 1355-58. In Amgen, the Supreme Court held that a claim to antibodies for treating high cholesterol was not adequately enabled even though the specification disclosed multiple embodiments including 26 different antibodies identified by their amino acid sequences. Amgen, 598 U.S. at 612.
Below are best practices for drafting antibody claims and specifications.

Antibody Sequence Claims

Consider these example claims:
           

1. An antibody comprising an amino acid sequence having at least a 90% sequence identity to SEQ ID NO:1.
2. The antibody of claim 1, wherein the amino acid sequence comprises the sequence of SEQ ID NO: 1.

Claims to novel sequences for each disclosed antibody, while narrow, can be fairly easy to obtain if the sequences are disclosed in a proper Sequence Listing and other procedural requirements are met. Amino acid claims are typically broader than the nucleic acid claims.
For percent-identity variations (e.g., 80% sequence identity of SEQ ID NO: 1), a patent applicant must show the sequences’ actual variation and that each performs the desired function. Coverage may be possible for sequences with physically and chemically similar amino acid substitutions (e.g., non-polar, polar, basic, or acidic); however, recent Supreme Court rulings have reduced the likelihood of success as discussed further below. But even novel antibody sequences may face obviousness rejections if complementarity-determining regions (CDRs) or their modifications are already known in the art.
For antibodies having variants that differ by one or more amino acids, written description and enablement rejections are common. One strategy to consider may be to pursue an antibody as a composition without variants in a first patent application and then pursue the antibody with variants in a divisional or continuation application via a product-by-process claim.