DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of the antibody comprising HCDR 1 of SEQ ID NO: 65, HCDR 2 of SEQ ID NO: 66, HCDR 3 of SEQ ID NO: 67, LCDR 1 of SEQ ID NO: 62, LCDR 2 of LGS, and LCDR 3 of SEQ ID NO: 64 in the reply filed on 06/22/2026 is acknowledged. Upon further consideration, all claimed species of anti-TIGIT antibody have been rejoined.
Status of Claims
The amendment filed on 06/22/2026 amended claims 22-29 and 37. Claims 22-40 are pending. Claims 22-40 will be examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements filed on 06/17/2024, 01/02/2025, and 12/22/2025 have been considered. Signed copies are enclosed.
Claim Rejections - 35 USC § 112
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 22-24, 26-27, and 29-40 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The instant claims are drawn to an anti-TIGIT antibody defined by its CDRs, with claims 22 and 29 reciting lists of possible CDRs for HCDR1-3 and LCDR1-3, claim 23 and 26 narrowing claim 22 by defining the HCDRs or VH regions for five different heavy chains and claims 24 and 27 narrowing claim 22 by defining the LCDRs or VL regions for five different light chains, and claims 25 and 28 reciting specific antibodies with 3 specific HCDRs and 3 specific LCDRs, or defined VH and VL regions. Claims 30-40 further limit additional aspects of the antibody of claim 22 without further defining the CDRs of the antibody.
The specification teaches 10 anti-TIGIT antibodies, defined by six CDRs in Table 2 and by VH and VL region in Table 1. These 10 antibodies, some of which are defined in claims 25 and 28, meet the written description provision of 35 U.S.C. 112(a). However, the claims encompass many more antibodies than just these 10 anti-TIGIT antibodies. As written, any of the HCDR1 sequences listed in claim 22 (a) can be combined with any of the HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences in claim 22 (b)-(f), resulting in hundreds of antibody combinations. CDRs are known in the art to define the binding capabilities of an antibody, and there is no support in the art that these hundreds of antibodies would still bind to and inhibit activity of TIGIT. Similarly, claim 29 recites thousands of possibilities for antibodies. Claims 24 and 25 and claims 26 and 27 only define either the heavy or light chain variable region by grouped CDRs or VH or VL sequences; therefore, the other chain is still insufficiently defined to ensure the antibodies of claims 23-24 and 26-27 are able to antagonize TIGIT. Therefore, the specification does not provide sufficient support for claim 22 or 29 as written, or claims 23-24, and 26-27.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must 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." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
To fulfill the written description requirements set forth under 35 U.S.C. 112(a), the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession of the claimed invention. To adequately describe the genus of antibodies, Applicant must adequately describe which combination of variable regions and framework regions that give rise to an antibody with the claimed immunological function. The instant specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the antibody and its recited function (TIGIT binding), so that the skilled artisan could immediately envision, or recognize, at least a substantial number of members of the claimed genus of antibodies. The specification fails to disclose which amino acids might be added, replaced or deleted so that the resultant antibody retains the binding specificity of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant antibody retains the binding specificity of its parent. Beyond the 10 antibodies listed in Tables 1 and 2, the specification does not identify any limitations on which CDR combinations or residues must be maintained in order to preserve the antibody’s function. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of antibodies to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of antibodies.
As evidenced by the teachings below, the art is unpredictable. Skolnick et al. (Trends in Biotechnology (2000) 18:34-39) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily bind to a given antibody.
As stated above, the CDRs are vital for antigen binding, as evidenced by Kapingidza et al. (Vertebrate and invertebrate respiratory proteins, lipoproteins and other body fluid proteins, 2020, 465-497) (see page 468, lines 1-4, and pages 476-482). Sela-Culang et al. (Frontiers in immunology, 2016, 4:302.) expands on the importance of antibody sequence and function, explaining that amino acid residues outside of the CDRs can influence antigen binding (abstract, whole document). Additionally, Clark et al. (Journal of Structural Biology, 2014, 185(2), 223-227) show that mutational effects on interfaces are often unpredictable (see pg. 223, 2nd col. 1st full para), and that it is easy to damage an interface and decrease binding affinity. Therefore, a person of ordinary skill in the art at the time of filling would understand residues within the CDRs are integral to antigen binding or maintaining the structure of the region that binds to the antigen and substitutions in these regions would affect one or both these attributes. As there is no art-recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which variable CDRs, combinations of CDRs, or combinations of particular substitutions, would result in a structure that binds TIGIT.
Overall, based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the claimed invention at the time of filing. Consequently, in accordance with the MPEP, only the antibodies claimed in table 1 of the instant specification, not the full breadth of claims 22-24, 26-27, and 29, regarding any anti-TIGIT antibody or any antibody with any combination of possible CDRs, meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Claims 30-40 inherit this rejection, as they are dependent on claim 22 and do not rectify the issues laid out above.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
Allowable Subject Matter
Claims 25 and 28 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.
The following is a statement of reasons for the indication of allowable subject matter:
A sequence search returned no 100% sequence identity matches in the prior at to the HCDR1-3 and LCDR1-3 sequences of the invention of instant claim 25. At the time of filing, antibody functionality was known to depend on the entire structure, particularly a full complement of 6 CDRs. As evidenced by Herold et al. (Nature Sci Reports, 7: 12276, 25Sep2017), changes to the CDR sequence can in principal affect antigen binding in an unpredictable manner [e.g., pg. 14, para 2]. Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and one skilled in the art could not a priori make any predictions regarding such mutations in relation to antigen binding with any reasonable expectation of success.
Given that the anti-TIGIT antibody of the instant invention requires HCDRs1-3 and LCDRs1-3 in the combinations as defined in claim 25, that these HCDR1-3 and LCDR1-3 are not found in the prior art, and that the prior art teaches that changes to the CDRs are unpredictable, the anti-TIGIT antibodies comprising the HCDRs 1-3 and LCDRs 1-3 combinations recited in instant claim 25 are considered free from the prior art.
Therefore, claims 25 and 28, which require the anti-TIGIT antibody which binds to TIGIT that comprises a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3, and/or a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3, and wherein the CDRH1 comprises the amino acid sequence of GFNFDDYG (SEQ ID NO: 65), the CDRH2 comprises the amino acid sequence of ISWNSISI (SEQ ID NO: 66), the CDRH3 comprises the amino acid sequence of AKDGGDHYYYGMDV (SEQ ID NO: 67), the CDRL1 comprises the amino acid sequence of QSLLHSNGYKY (SEQ ID NO: 62), the CDRL2 comprises the amino acid sequence of LGS, and the CDRL3 comprises the amino acid sequence of MQALQTPLT (SEQ ID NO: 64), or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 19, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18 are considered free from the prior art. Similarly, the remaining antibodies of claim 25 and 28 did not return any 100% searches and are also free of the art.
For the reasons provided above, claims 25 and 28 are considered allowable but objected to as being dependent upon a rejected base claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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/AMELIA STEPHENS/ Examiner, Art Unit 1645
/ANNE M. GUSSOW/ Supervisory Patent Examiner, Art Unit 1683
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