On May 17, 2024, the Patent Trial and Appeal Board (PTAB) affirmed a rejection of a claim directed to a purification method using single-domain antigen-binding proteins that bind mammalian IgG as lacking adequate written description (Appeal 2023-000567). The claim at issue in U.S. Application No. 16/282,082 (the '082 Application) recites:
Claim 77. A method for the purification of a molecule comprising an epitope present in the Fc domain of a human IgG antibody, the method comprising the steps of:
a) bringing a sample comprising the molecule comprising the epitope present in the Fc domain of a human IgG antibody into contact with an immunoadsorbent material comprising a variable heavy-heavy (VHH) antigen-binding protein under conditions that allow for binding of the molecule to the immunoadsorbent material;
b) optionally, performing a washing step; and
c) eluting the bound molecule comprising the epitope present in the Fc domain of a human IgG antibody under conditions that decrease the affinity between the molecule and the VHH antigen-binding protein,
wherein the VHH antigen-binding protein has binding affinity for the Fe domain of the human IgG molecule but does not have binding activity for the Fe domain of a mouse, a bovine, a rat, a Syrian hamster, a guinea pig, a dog, a cat, a goat, or a sheep IgG molecule, and
wherein the VHH antigen-binding protein comprises four framework regions, FRI to FR4, and three complementarity determining regions, CDRI to CDR3, that are operably linked in the order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein the CDR3 region comprises the amino acid sequence Arg Phe Gly Ser Glu Trp Asp Tyr (SEQ ID NO: 108).
The Examiner rejected Claim 77 under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The Examiner stated that the species of binding proteins that can be used in the immunoadsorbent material, as claimed, was extremely broad while the Specification identified only a single VHH protein. Because of the unpredictability associated with VHH engineering and the impact of structure on binding ability and stability of the proteins, the Examiner reasoned, the disclosure of a single species of VHH was insufficient to meet the written description requirement.
Appellant argued that the Specification disclosed the amino acid sequences of 49 VHH binding antigen proteins which bind to mammalian IgG antibodies. The Appellant furthered that Claim 77 recited four functional requirements (features (a), (b), (c), and (d)) for the VHH antigen-binding proteins, with fifteen of the 49 disclosed VHH antigen-binding proteins possessing features (a), (b), and (c), and one of the 49 possessing features (a), (b), (c), and (d). The Appellant asserted, based on these fifteen identified VHH antigen-binding proteins, that one of ordinary skill in the art would have recognized that the inventors had possession of the claimed subject matter at the time of filing, thus satisfying the written description requirement.
The Board did not agree with the Appellant, but rather affirmed the Examiner's rejection, stating that the claims embraced a broad genus of proteins that could be used to create the immunoadsorbent material with only one protein meeting all the requirements of Claim 77. The Board furthered that disclosure of a single protein was not sufficient to satisfy the written description requirement without identification of structural features common to all members of the genus or a sufficient number of representative species encompassing the breadth of the genus.
This decision serves as a reminder for practitioners that a common structural feature or disclosing a sufficient representative species encompassing the breadth of the genus may overcome a written description rejection under § 112 when claiming a broad genus. Further, while there is not an established number of species that must be disclosed when claiming a genus, practitioners should avoid disclosing too little when dealing with genus claims in a field the Office may see as unpredictable.
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