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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/30/2026 has been entered.
Claims 1, 16-17, 19-20, 22 are amended.
Claims 5, 9-10, and 15, are canceled.
Claims 1, 4, 6, 16-17, 19-20, 22-29 remain pending and are considered herein.
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 1, 4-6, 9-10, 15-17, 19-20, and 22-29 remain 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 aspects of D1, D2, D4 and D5. 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.
The rejections maintained are rewritten for clarity as to the aspects left.
The claims are generic for the structure of the binding domains D1, D2, D4 and D5, as in seen Claim 1, where (i) D1 may be a structure that generically binds to CD3, EGFR, or CD20 or may be a NKG2D receptor; (ii) D2 may be a structure that generically binds to HER3, CD3, or CD19; (iii) D4 may be a structure that generically binds to 4-1BB, and (iv) D5 may be a structure that generically binds to PD-L1. Claim 22 follows similar language but is to the nucleic acid encoding the same. The dependent claims to Claims 1 and 22 do not alter the generic bindings.
The specification provides antecedent basis for D1, D4, D2 and D5 linked to the N and C termini of the two monomers (e.g., p. 2, paragraph 3). D1-D5 are taught to bind any of EGFR, CD3, HER3, NGK2D, 4-1BB, PD-L1, or CD19 (e.g., p. 4, penultimate paragraph).
To be clear, the Examiner is pointing to the binding domains, and their structure, and stating that the generic structure for such is not provided by the specification and art.
The specification further delineates that D1, D2, D4 and D5 may be an scFv, VHH, receptor, or ligand (e.g., p. 3), and D3 may be formed of the first and second binding monomers, to form an Fab or a NKG2D receptor (e.g., Id.). Further, the laundry list of molecules that these bind, is also provided in the Summary of the Invention (e.g., pp. 4-5). Finally, there is a long list of examples which bind to each various molecules (Tables). However, it should be noted that no matter what the case, the description is centered around these as requiring the variable regions of antibodies (e.g., Table 9).
With regard to the Art, it is well known in the art of antibodies, that the constant regions are generally from a small number of known sequences, that highly variable structure is found in the antigen binding region, and most variability comes from the 3 CDRs, the intervening framework being less variable. Goel teaches an example where 3 antibodies were made that bind to the same 12-mer antigen, but have very distinct CDRs (Goel et al. 2004. Plasticity within the Antigen Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response. The Journal of Immunology 173(12):7358-7367. See figures 2 and 3 in particular.) This demonstrates that knowing some structures does not correlate to understanding the structure required for the genera of structures which are claimed. Further, Lloyd et al. 2009. Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens. Protein Engineering, Design & Selection 22(3):159-168, demonstrates that about 120 antibodies in their library can bind a given antigen (e.g., ABSTRACT). This demonstrates that there is a large number of structures which can bind any particular antigen. Moreover, Edwards et al. 2003. The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BlyS. Journal of Molecular Biology 334:103-118, demonstrates that a library that contained over 1000 antibodies, bound to a single protein, including 1098 distinct VH and VL sequence, and 568 CDR3 regions, providing very high diversity (e.g., ABSTRACT). This demonstrates again the highly diverse nature of the regions that bind, in the context of the distinct CDRs.
Thus, given the limited showing, and knowledge in the Art of highly diverse regions which can bind to the same antigen, as well as less diverse regions that bind highly diverse antigens, the Artisan would not understand the structure required of a generic VL and/or VH to be possessed, by the description of its intended binding antigen, and thus, further, for those embodiments with no requirement for an antigen to bind, there is even less of an understanding of possession.
Therefore, the Artisan would not understand Applicant to have been in possession of those antigen/ligand/receptor binding regions, except those regions shown in the specification.
Response to Argument – written description, binding region structure
Applicant’s argument of 6/30/26 has been considered but is not found persuasive.
Applicant argues that the claims now have SEQ ID NOs for the paired monomers, and thus, recite specific structural embodiments identified by amino acid sequence and corresponding binding domain placement/specificity (p. 2, paragraph 1).
Such is not persuasive. While D3 is necessarily defined by the given structure, D1, D2, D4 and D5 are outside the defined sequences on the N- and C- termini, and are defined only by a wish to bind a specific element.
Applicant argues Claims 16 and 19 are amended to remove the previously objected-to sequence identity formulation and recite a specific sequence defined CDR having affinity to CEA and Claim 19 is to a CDR sequence having affinity for CD3 (p. 2, paragraph 2).
Such is persuasive. Claims 16 and 19 are no longer rejected and are in allowable condition.
Applicant argues that Claims 17 and 19 are to specific sequences, and thus, are also not properly rejected (p. 2, paragraph 3).
Such is persuasive. Claims 17 and 20 are no longer rejected and are in allowable condition.
Applicant argues that Claim 22 has been amended to correspond to the sequence defined protein embodiments of Claim 1, and thus the rejections are similarly overcome (p. 2, paragraph 4).
Such is not persuasive. The rejection remains for the same reasons for D1, D2, D4, and D5.
Applicant argues Claims 4, 6, and 23-29 are similarly free of the rejections as the base claim has overcome the written description rejection (p. 2, paragraph 5).
Such is not persuasive. The base claims do not overcome the rejections for the reasons given.
Claims Free of the Art
Repeated for the record: It should be noted that the Examiner’s search of the prior art did not yield any information to teach or suggest to the Artisan the specific mini GNC antibodies as claimed, with the claimed regions. The closest prior art the Examiner found is the same art as found in the search report and written opinion of the PCT parent to the present 371 Application. The closest prior art is WO 2019/005640 A2, to Systimmune, which has 2 common inventors, and distinct inventors. The document though, contrary to what was stated in the written description, does not anticipate even the broad claims. To wit, while teaching these antibodies that have the structure seen in Figure 1 of the document, which allows the VH domain to be bound to the CH1-CH2-CH3, the VL domain is never suggested to be exchanged, or to replace, the VH domain linked to the CH1-CH2-CH3, and thus, even with the broad reading taken by the PCT analysis, the Examiner disagrees. To wit, in the written opinion, it is suggested that between page 12, paragraph 7, page 2, paragraph 3, page 13, paragraph 2, that the CH1 and CL domains are linked through SS bonds, and thus, CL is N terminal to the hinge (p. 4 of the written opinion). The Examiner disagrees with this analysis. To wit, the claim is to two monomers, each comprising the elements, from N-term to C-term. The Examiner interprets the invention of the cited Art here, WO 2019/005640 A2, to be dimeric protein, joined by SS bonds. Additionally, the Examiner has not found in the specification, any suggestion that a monomer would be considered a dimer bound by SS bonds. Thus, the Art applied in the PCT prosecution is deemed deficient for an anticipation rejection.
Similarly, Claims 16, 17, 19, and 22 are to sequences not found in the prior art, and are otherwise allowable.
Conclusion
Claims 1, 4, 6, and 22-29 are rejected.
Claims 16-17 and 19-20 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638
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