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 .
Applicant’s amendment and argument of 8/20/25 are entered.
Claims 1, 6, 9-10, 15, 17, 20, and 22 are amended.
Claims 2-3, 7-8, 11-14, 18, 21 and 30 are canceled.
Claims 1, 4-6, 9-10, 15-17, 19-20, and 22-29 are pending and considered herein.
Claim Status, Canceled Claims
In light of the cancelation of Claims 2-3, 7-8, 11-14, 18, 21 and 30, all rejections/objection thereto are withdrawn.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 15 provides a pairing the members of monomer 1 and monomer 2, as a Markush. However, the artisan, reading the claims in light of the specification, would not understand it to be anything but these pairings, as it is so-taught in the specification as they are used in binding their respective entities, TOGETHER (e.g., p. 6, paragraph 3). In addition, Claim 15 lists the affinity of the pairings, but such does not change the structure. Therefore, despite a slight difference in wording, these claims have substantially the same scope.
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.
In light of the amendments, the rejections of Claims 1, 4-6, 9-10, 15-17, 19-20, and 22-29 of record 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, with regard to the aspect of D3, are withdrawn.
However:
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. With regard to the depending claims, Claim 5 teaches that D1, D2, D4 and D5, may be scFV, VHH , a receptor, or a ligand, indicating that the broad claims are directed to generically more. Claim 9 requires D3 to generically bind HER3, EGFR, CD3 or NKG2D ligands. Claim 10 provides that the molecule has an affinity to Markush of protein species, which indicates that the same rejected D1, D2, D4 and/or D5 may be directed to these species. Claim 15 provides a Markush of specie sets for each of D1, D2, D4 and D5, requiring specific sequences which appear to match the sequences of Claim 1, leading to D3, but there is no requirement that this limits the structure of the monomers forming D3, and may be any generic portion of these sequences. Claim 16 is to generic CDRs having any affinity to CEA, and a generic sequence identity to a Markush of SEQ ID NOs. Claim 17 is to a multi-specific antibody, which comprises the CDR of Claim 16, and comprising a Markush of SEQ ID NOs. Claim 19 is to a generic CD3 binding CDR, having a generic sequence identity to a Markush of SEQ ID NOs. Claim 20 requires the CDR to be in a generic multi-specific antibody that comprises a nucleic acid sequence chosen from a Markush. Claim 22 parallels claim 1 but is to a generic nucleic acid encoding the multi specific antibody like protein. Claim 23 is to a an expression vector, Claim 24 is to a host cell comprising the nucleic acid. Claim 25 is to an immunoconjugate comprising the protein of Claim 1 and a cytotoxic agent. Claim 26 is to the protein of Claim 1, with a carrier. Claim 28 is to treating a patent for cancer, autoimmune disease, or infectious disease, by administration of the protein of Claim 1. Claim 29 is to making the and purifying the protein of Claim 1.
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.), and in view of the depending claim 5, it would appear that the same encompasses Fabs and other molecules also. 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, as well as the CH1-CH3 and CL of antibody structure, (e.g., Claim 5).
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 3/9/25 has been considered but is not found persuasive.
Applicant argues that they have amended to provide sequence identifiers for the monomers, and therefore they are structurally defined molecules, not merely functional binding domains (p. 1, last half of page).
Such is partly persuasive. The Examiner has removed the rejection of the elements of D3, however, the rejection has always specifically mentioned D1, D2, D4 and D5, and these have gone unaddressed.
Applicant argues that Claim 15 provides for specific embodiments, pairing the sequences, and thus it is defined, satisfying the written description requirement (p. 2, top half).
Such is not persuasive. Again, D1, D2, D4 and D5 are undefined.
Applicant argues Claims 16-17 and 19-20 provide CDRs defined by SEQ ID NOs and thus meet the requirements (p. 2, mid page).
Such is not persuasive. The sequences only require a generic sequence identity to one of the sequence identifiers, and thus, such may be ZERO identity, 1% identity, etc. Thus, the rejection is again properly applied here.
Applicant argues that the specification teaches the pairing of monomers, and thus, the written description is met (p. 2, end of page).
Such is only partly persuasive. Applicant has not addressed D1, D2, D4 or D5, which has been repeatedly rejected on the record here.
Applicant argues that the working examples demonstrate each specifically claimed embodiment, pointing to the figures and examples (pp. 2-3, paragraphs bridging).
Such is not persuasive. The generic structures of D1, D2, D3, and D4 are not addressed by this argument.
Applicant argues that the claims do not rely on a functionally defined genus, but specific sequences and thus the rejection is improper.
Such is not persuasive. The Argument does not address D1, D2, D4 and D5, which are generically defined binding entities.
Request for Contact Prior to Final Action
Applicant requested contact prior to issuing a final rejection. However, as it appears Applicant does not understand the generic scope they have claimed, it is hoped that further prosecution will allow applicant to now find a proper amendment to allow the claims.
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.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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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