DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The Amendment filed December 23, 2025 in response to the Non-final rejection of July 3, 2025 is acknowledged and has been entered.
Claims 1, 3-9, 12, 14, 19, and 41-43 are currently pending.
Claims 1, 3-9, and 12 were amended or previously presented. Claims 41-43 were newly added.
Claims 14 and 19 remain withdrawn and new claims 42-43 are withdrawn from further consideration by the examiner under 37 CFR 1.142(b) as being drawn to non-elected inventions or species.
Claims 1, 3-9, 12, and 41 are currently under consideration.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Objections Withdrawn
The objection to the specification (para 5, non-final mailed 07/03/25) for amino acid disclosures is withdrawn in view of applicant’s amendments.
Rejections Withdrawn
The rejection of claim 9, under 35 USC 112 (b) in the action mailed 07/03/25 is withdrawn because of applicant’s cancellation of the “for example” language.
The rejection of Claims 1-13 and 15-16 under 35 U.S.C. 102(a)(1) as being anticipated by TRIEBEL et al. is withdrawn in view of applicant’s arguments. Specifically, applicants argue (page 32) that antibody 34F4 of Triebel has more than five variant amino acids compared to SEQ ID NO:3. Further, amended claim 1 excludes binding molecules comprising VH CDRs 1-3 (SEQ ID Nos: 1-3 or 7-9) and VL CDRs 1-3 (SEQ ID Nos: 4-6 or 10-12).
The rejection of Claims 1-13 and 15-16 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11680104 B2 in view of TRIEBEL et al., (WO 2017037203) is withdrawn in view of applicant’s arguments and amendments to the claims.
Rejections Maintained (inclusive of applicant’s reincorporation of cancelled claims 15-18, 20)
Claims 1, 3-9, 12, and 41 are rejected under 35 U.S.C. 112(b) for the same reasons that now canceled claims 15-18 and 20 were rejected in the action mailed 07/03/25, para 10. Applicants do not specifically address the non-final action’s rationale for the indefiniteness. As set forth previously, the examiner stated: The examiner does not understand how the limitation “… which excludes an antibody, or antigen-binding fragment thereof…” would be applied to these claims. For instance, said limitation, as recited, could be interpreted to apply to the binding molecule as a whole, thereby claiming any other binding molecule besides an antibody or antigen-binding fragment thereof comprising the defined set of CDRs; examples might include a chimeric antigen receptor (CAR) or a fusion scaffolding protein or scaffold-like protein. Alternatively, said limitation could be interpreted to apply to the CDRs themselves, thereby claiming any other anti-LAG-3 antibody or antigen-binding fragment thereof comprising any set of undefined CDRs or variable regions.
In other words, applicants cannot both claim variable regions with CDRs comprising SEQ IDs 1-6 (or SEQ IDs 7-12) while simultaneously excluding an antibody that also contains these same CDRs. Thus, the rejection is maintained.
Claims 1, and 3-9 remain rejected and claims 12 and 41 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 for the reasons of record in the action mailed 07/03/25, beginning at para 12.
Applicants argue (Remarks, page 18) that amended claim 1 recites structural requirements of the claimed binding molecule by including the variable heavy and variable light sequences (SEQ IDs 1-6). Applicant add that the binding molecule is also defined structurally in that it binds specifically to a discontinuous epitope within the extracellular Ig superfamily domain D1 of a LAG-3 protein. Applicants further point to Example 1 of the specification that demonstrates the functional agonist activity of the IMP761 antibody and that Example 2 describes mapping of the epitope where synthesis of structural mimics used Chemically Linked Peptides on Scaffolds (CLIPS) technology. Applicants argue (page 19) that identification of the discontinuous epitope bound by anti-LAG-3 antibody IMP761 “allows related antibodies to be identified which have similar properties to this antibody” and reiterate the teachings of pages 15-16 of the specification.
Applicants further point out (pages 21-22) that the CDRs of the 13E2 and 34F4 antibodies (Table 1 and Table 2 of the specification) have minimal differences and that the skilled person can readily determine which amino acid residues are conserved in the CDRs of 13E2 and 34F4. Thus, applicants argue, the specification teaches minimal structural sequence(s) common to the CDRs of these agonistic antibodies.
These arguments have been considered but are not found persuasive. As set forth previously, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C). The claims remain broadly drawn to a genus of binding molecules with limited structure but also inclusive of a wide variety of variant structures. This includes up to 5 amino acid substitutions, deletions, or additions in any or all of the critical complementary determining regions while still maintaining the claimed agonistic functioning. Since the claimed genus of antibodies has six unique CDRs functioning together, the total number of unique full-antibody sequences that can bind to the degenerate epitope with up to 5 mutations each comprises a vast number (at least millions) of possible variations for each one of the six CDR regions. Tables 1 and 2 which compare similar CDRs does not adequately reflect the scope of the genus claimed. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Thus, applicant’s arguments have not been found persuasive and the rejection is maintained.
Claims 1, 3-9, 12, and 41 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 enablement requirement for the same reasons that now canceled claims 17-18 and 20 were rejected in the action mailed 07/03/25, para 13.
Applicants largely reiterate their arguments that addressed the lack of written description above including pointing out the same structural features of the binding molecule and methods of determining the discontinuous epitope (page 24-26). Applicants argue as there are only a few differences between the sequences, the skilled person can readily make changes to a relatively small number of specific amino acid residues in the CDRs and test whether the resulting antibody binds to the discontinuous epitope and is an effective agonistic anti-LAG-3 antibody. These arguments have been considered but are not found persuasive. As set forth previously, and now incorporated into the base claim, the genus of "binding molecules" in claim 1 do not identify specific structural constraints wherein the scope potentially encompasses “quintillion” unique species. In contrast, the specification discloses one anti-LAG-3 agonist antibody defined by specific CDR sequences (13E2/IMP761, see table 1 on page 15). In Amgen v. Sanofi, 598 U.S. 594 (2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies and disclosed two “trial and error” methods (“the roadmap” and “conservative substitution”) that Amgen insisted scientists could use to make other antibodies that perform these two functions. The case law applies to the instant claims which require a genus of "binding molecules", binding specifically to LAG-3 including the agonistic effects, downstream signaling effects and overall effect on T cell activation and differentiation described in the specification.
Applicants have further argued (pages 27-28) that evidence for the plasticity of CDRs, and thus support for the claimed CDR sequences with up to five amino acid substitutions, deletions, or additions per CDR sequence is enabled is found in the teachings of Townsend et al. (of record, IDS 10/2024). Applicants argue that this reference describes the generation of combinatorial libraries using a technique called "Augmented Binary Substitution" (ABS). Each library is based on a single starting antibody: rat anti-RAGE, rabbit anti-A33, and chicken anti-pTau. These libraries were built into human germ-line frameworks of high predicted stability and solubility, then interrogated via phage display and screened to identity lead clones with epitope specificity and affinity equivalent to the parental clone. However, the use of augmented binary substitution does not adequately compensate for the vast quantity of experimentation necessary to make or use the invention as broadly claimed. Extensive trial and error would still be required to validate the binding affinity for LAG-3 and assess their function and downstream effect on T cell activation. Thus, Applicant’s arguments have been considered but have not been found persuasive and the rejection is maintained.
Claims 1, 3-9, and 12 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 26-28 of copending Application No. 17/607,784 (reference application) for the reasons of record.
Claims 1, 3-9, and 12 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 11, 12 and 107-111 of copending Application No. 18/312,629 (reference application) for the reasons of record.
Applicants request the Office to hold the rejection in abeyance until allowable subject matter is identified. This argument has been considered but is not found persuasive as a rejection cannot be held in abeyance. The reply by the applicant must be reduced to a writing which distinctly and specifically points out the supposed errors in the examiner’s action or a submission of a terminal disclaimer.
New Objections
Claim 1 is objected to for reciting parenthetical expressions such as “superfamily domain D1 (SEQ ID NO:14)” or “extra-loop sequence (SEQ ID NO:18)” as it’s not immediately clear that the entities within the parenthesis encompass the claimed SEQ ID Nos or are merely exemplary. This objection can be obviated by reciting “comprising SEQ ID NO:14” and “comprising SEQ ID NO:18”.
New Rejection
Claim 41 contains the trademark/trade name Biacore. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe how a dissociation constant is determined, and, accordingly, the identification/description is indefinite.
Conclusion
21. No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
23. Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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