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
Status of the Claims
1. Claims 1-41 are all the original claims filed on 2/20/2023. In the Preliminary Amendment of 2/7/2024, Claims 3, 5, 7-9, 22, 24-26, 37, 39, and 41 are amended. In the Response of 5/22/2026, Claims 1, 18, 20, and 35 are amended. Claims 2, 19, and 36 are cancelled.
Claims 1, 3-18, 20-35 and 37-41 are pending.
Applicants amendment of the claims raises new grounds for objection and rejection. The Office Action is final.
Priority
2. USAN 18/042,267, filed 02/20/2023, is a National Stage entry of PCT/US2021/046770, International Filing Date: 08/19/2021, PCT/US2021/ 046770 Claims Priority from Provisional Application 63/068,306, filed 08/20/2020.
Information Disclosure Statement
3. As of 7/6/2026, a total of two (2) IDS are filed: 2/7/2024; and 2/7/2024. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
4. The objections to the disclosure because of informalities is withdrawn. Both clean and marked-up copies are filed in the Response of 5/22/2026.
a) The amendments to the specification rectify the improper use of the term, Sepharose, ATCC, nanobody, DuoBody, KinExa, which is a trade name or a mark used in commerce.
b) The amendments to the specification at [0012], [0021], [0038], [0060], [0069] and [0086] rectify the failure to include the sequence identifier (SEQ ID NO) for the peptide sequences > 4 amino acids in length as pursuant to 37 CFR 1.821-1.825.
Claim Objections
5. The objections to Claims 1-41 because of informalities in moot for the canceled claims and withdrawn for the pending claims.
a) Claims 1-41 are amended to clarify that mutations are substitutions.
b) Claim 19 is canceled.
c) Claim 36 is canceled.
Rejections Maintained
Claim Rejections - 35 USC § 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.
Written Description
6. The rejection of Claims
Applicants allege amending the claims to clarify a mutation is a substation and introducing the substitutions F126C, C220A, E123C, and C214A mutations that correspond to working embodiments, v2232 and v2233, overcomes the rejection.
Response to Arguments
Claims 1 and 3-17 are not defined in step (d) of claim 1 whether 1st and 2nd polypeptides of the 2nd Fab in step (d) are engineered thru the claimed method to “a cysteine at position 220” and “the cysteine at position 214”. It is not clear if the residues are required to be inherent to the 2nd Fab for the multispecific antigen binding protein and are otherwise excluded from the method of production.
Also, the terms “an” and “the” in step (d) of claim 1 act as strict rules of art rather than grammar. Using “a” introduces a new, unspecific element that is one or more, while “the” implies a specific element that was already introduced.
Review of the limited disclosure of 6 bispecifics generated in Tables 1 and 2 does not identify which of them corresponds to V2232 andV2233. The limited disclosure does not identify the isotype used in the V2232 and V2233 clones. The POSA cannot even reproduce the V2232 or V2233 clones from the limited disclosure in the specification at the time of filing. The sequence listing provides only linker sequence information.
The rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
7. The rejection of Claim(s)
a) Applicants allege impermissible hindsight reconstruction regards Yan teaching functional pairing of 1stFab and 2nd Fab having CH1 and CL positions of the pair of cysteines selected from groups that include 126 and 124 and 126 and 121 but do not include 126 and 123.
Response to Arguments
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Yan specifically teaches that CH1 amino-acid 126 contacts CL-kappa amino-acids 121, 123 and 124:
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It would have been obvious to try combining the elements and the result-effectiveness of the combination would have been reasonably predictable absent a showing to the contrary. MPEP 2142 states in part: " Exemplary rationales that may support a conclusion of obviousness include:…(E) “Obvious to try”- choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;…” and “the rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at ___, 82 USPQ2d at 1397.”
b) Applicants allege the selection of the 126C/123C pairing was the result of extensive screening to identify residues with optimal rotamer configuration. As disclosed in the specification, an extensive screening of CH1/CL interface was performed to identify two residues with optimal rotamer configuration of their side-chains and distance between respective Ca-Ca of around 4.5A. The specification further confirms that F126C in HC and E123C in the LC can successfully replace the canonical disulfide bond. This demonstrates that the claimed 126C/123C pairing was the result of specific experimental work to identify a functional non-canonical disulfide bond placement. The engineered F126C and E123C do not appear to negatively impact the capability of the cell to express these multispecific molecules. These results demonstrate that the specific 126C/123C pairing combined with the C220A and C214A mutations provides functional benefits that were not predictable from the prior art.
Response to Arguments
Review of the limited disclosure of 6 bispecifics generated in Tables 1 and 2 does not identify which of them corresponds to V2232 andV2233. The limited disclosure does not identify the antibody isotype used in the V2232 and V2233 clones. The POSA cannot even reproduce the V2232 or V2233 clones from the limited disclosure in the specification at the time of filing. The sequence listing provides only linker sequence information. Close inspection of the multispecific constructs comprising v2232 and v2233 allegedly unpredictable results for the embodiments comprise elements are not ascertainable from the limited disclosure in the specification as filed.
The rejection is maintained.
New Grounds for Objection
Claim Objections
8. Claims 3 and 20 are objected to because of the following informalities:
-) Claims 3 and 20 fail to include a coordinating conjunction (“and” “or”) between elements (g) and (h) for claim 3, and elements (iv) and (v) for claim 20.
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
9. Claims 1, 3-17, 20-21, 23 and 41 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
a) Claims 1 and 3-17 are indefinite in step (d) of claim 1. It not clear whether 1st and 2nd polypeptides of the 2nd Fab in step (d) are engineered thru the claimed method to “a cysteine at position 220” and “the cysteine at position 214” or that the residues are required to be inherent to the 2nd Fab for the multispecific antigen binding protein.
Also, the terms “an” and “the” in step (d) of claim 1 act as strict rules of art rather than grammar. Using “a” introduces a new, unspecific element that is one or more, while “the” implies a specific element that was already introduced.
b) Claims 20-21 and 23 are indefinite for the amended recitation “claim 18, wherein and…” in Claim 20. The POSA cannot reasonably ascertain whether material subject matter for the invention is missing or excluded in Claim 20.
c) Claim 41 depends from newly canceled claim 36. Claim 41 is indefinite.
Conclusion
10. No claims are allowed.
11. 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.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie 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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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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