Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s election without traverse of Group I, claims 1, 2, 4-17, and 21, in the reply filed on 05/22/2026 is acknowledged. Applicant also elected the five anti-PD-L1 single domain antibodies (sdAbs) of SEQ ID NO(s): 116-119 and 130.
Claims 1, 2, 4-22, 24, and 25 are pending.
Claims 18-20, 22, 24, and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/22/2026.
Claims 1, 2, 4-17, and 21 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 2, 4-17, and 21 have an effective filing date of 04/06/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/25/2023 and 05/09/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Rejoinder
Claim 1 is allowable with respect to the five elected anti-PD-L1 single domain antibodies (sdAbs) of SEQ ID NO(s): 116-119 and 130. As such the instant examination has been extended to all anti-human PD-L1 sdAb species, SEQ ID NO(s): 1-36, 114-122, and 123-130.
Claim Rejections
35 U.S.C. 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 16, 17, and 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a single domain antibody or a polypeptide comprising the single domain antibody, wherein the single domain antibody has binding specificity to the human PD-L1 protein and comprises a complementarity determining region 1 (CDR1), a CDR2 and a CDR3 of anyone selected from the group consisting of SEQ ID NO: 1-36, 114-122 and 123-130.
SEQ ID NO(s): 2, 4, 5, 7, 9, 10, 12, and 24 comprise the CDR1 of SEQ ID NO: 40, according to p. 29-33 of the specification. According to the Sequence Listing, dated 10/25/2023, SEQ ID NO: 40 comprises the sequence Ala-Met-Ala-Xaa, where Xaa may be a variable amino acid.
SEQ ID NO: 30 comprises the CDR3 of SEQ ID NO: 97, according to p. 29-33 of the specification. According to the Sequence Listing, dated 10/25/2023, SEQ ID NO: 97 comprises the sequence Arg-Glu-Tyr-Xaa, where Xaa may be a variable amino acid.
SEQ ID NO(s): 36 comprises the CDR1 of SEQ ID NO: 110, according to p. 29-33 of the specification. According to the Sequence Listing, dated 10/25/2023, SEQ ID NO: 110 comprises the sequence Gly-Met-Glu-Xaa, where Xaa may be a variable amino acid.
Due to the variability within the CDRs of the anti-PD-L1 sdAbs of SEQ ID NO(s): 2, 4, 5, 7, 9, 10, 12, 24, 30, and 36, the claims encompass a large genus of anti-PD-L1 sdAbs having diverse CDR amino acid sequences. The issue with respect to 35 U.S.C. 112(a), written description, is that one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which CDR sequences give rise to sdAbs capable of binding PD-L1. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
While the art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example in a series of experiments involving a monoclonal antibody to Legionella pneumophilia serotype 1, McCarthy et al. (J. Immunol. Methods, 251(1-2): 137-149, 2001) demonstrated that a single VH CDR3 substitution of tyrosine to serine at position 95 resulted in the total loss of antigen recognition in an ELISA. Lin et al. (African Journal of Biotechnology, 10(79):18294-18302, 2011) teach that a single amino acid substitution in the VL CDR3 of an anti-avian infectious bronchitis virus (IBV) single-chain antibody (ZL.80) may abrogate binding. For example at Figure 3, Lin et al. demonstrate that replacing either the Cys105 or Asp106 residue in the VL CDR3 of ZL.80 with an alanine residue reduces binding to near negative control levels. Lin et al. also teach that some single amino acid substitutions in the VL CDR3 of ZL.80 may significantly improve binding. For example replacing the Val108 residue in the VL CDR3 of ZL.80 with a tyrosine residue results in a 12.9-fold increase in affinity compared to parental ZL.80. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues of SEQ ID NO(s): 40, 97, and 110 could be changed such that the resultant variant CDR residues form an antigen-binding site capable of binding PD-L1. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general, guidance is needed.
Furthermore the disclosure fails to describe a sufficiently representative number of species comprised with in the genus claimed and also fails to disclose relevant, identifying structural characteristics, in the form of CDR amino acid sequences, that correlate with the ability to bind PD-L1. As such it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Although screening techniques can be used to isolate CDR variant sdAbs that possess the ability to bind PD-L1, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed sdAbs are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Applicant is informed that the rejection of the claim under 35 U.S.C. 112(a) may be overcome by submitting a new Sequence Listing that removes the variable amino acid residue from SEQ ID NO(s): 40, 97, and 110. In other words, it is recommended that 1) the listing for SEQ ID NO: 40 is changed to recite Ala-Met-Ala, 2) the listing for SEQ ID NO: 97 is changed to recite Arg-Glu-Tyr, and 3) the listing for SEQ ID NO: 110 is changed to recite Gly-Met-Glu.
Allowable Subject Matter
Claims 4-15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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