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 .
Claims Status
The amendments and remarks filed 08/07/2026 are acknowledged
Claims 1-10, 12, 14-31 are pending.
Claims 11 and 13 are canceled.
Claims 1 and 12 are amended.
Claims 6, 8-9, 14-26, 28, and 30-31 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/15/2025. Upon further consideration, the election of species requirement for the third linker of species Group B is withdrawn.
Therefore, claims 1-5, 7, 10, 12, 27, and 29 are under examination.
Withdrawn
The rejections of claims 1-5, 7, 10-13, 27, and 29 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended claim 1 and canceled claims 11 and 13 to overcome the rejection.
The rejections of claims 1-5, 7, 10-13, 27, and 29 under 35 U.S.C. 102 are withdrawn in view of Applicant’s amendment to claim 1 requiring that the antibody Fc region of the first polypeptide is linked, via its N-terminus, to the C-terminus of the antibody heavy chain of the second polypeptide by a third linker.
Applicant’s arguments, see pages 8-9 of the remarks filed 08/07/2026, with respect to the rejections of claims 1-5, 7, 10-13, 27, and 29 under 35 U.S.C. 102, have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, a new grounds of rejection necessitated by amendment under 35 U.S.C. 103 is made over Bernett (US 20180127501) in view of Wang (instant PTO-892). See below.
New Grounds of Rejection Necessitated by Amendment
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7, 10, 12, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Bernett (US 20180127501; 02/09/2026 PTO-892) in view of Wang et al., 2017 (instant PTO-892).
Regarding claims 1-2, 10, 12, and 27, Bernett teaches bispecific antibodies that monovalently bind a human costimulatory receptor and monovalently bind a human checkpoint receptor, wherein the bispecific can have the format as depicted in Figure 2D [see 0007, 0011, and Figure 2D shown below].
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Bernett teaches the structure of the one armed mAb (depicted in Figure 2N which lacks the scFv of Figure 2D), comprising one monomer that comprises only an Fc domain (i.e. hinge region-CH2-CH3; first polypeptide consists of the Fc domain), and another monomer that is a heavy chain (i.e. VH1-CH1-hinge-CH2-CH3), and further has a variable light chain domain (VL) and a constant light (CL) domain that associate with the heavy chain to form a Fab (i.e. anti-antigen 2; second antigen binding domain) [0395]. Thus, the description of the structure of Figure 2N can be applied to Figure 2D, which depicts an scFv (i.e. VH and VL with a first linker; first antigen binding domain) attached by a linker (second linker) to the VH of the Fab [see Figure 2D]. As evidenced by Brezski et al., 2011 (02/09/2026 PTO-892), the one-arm scFv-mAb of Bernett depicted in Figure 2D comprises a hinge region on both CH2 domains and depicts the scFv attached to the VH of the Fab [see page 1158, Figure 1 of Brezski].
However, Bernett does not specifically teach that the antibody Fc region of the first polypeptide is linked, via its N-terminus, to the C-terminus of the antibody heavy chain of the second polypeptide by a third linker.
Wang teaches a tandem Fc structure, termed IgG-2Fc-half, comprising a (GGGGS)2 linker (i.e. third linker) between the C terminus of one Fc region and the N terminus of another Fc region [page 394; Figure 1C]. Wang teaches that the IgG-2Fc-half format can be readily produced in large quantity, has good stability, maintains the binding affinity to FcyRs, FcRn and Clq, and has a PK profile comparable to that of the parental IgG1 despite its significantly reduced molecular weight, and using a knob-in-hole strategy eliminated unwanted mismatches between different heavy chains, thus, improving efficiency [page 400, right column, third paragraph].
The (GGGGS)2 linker of Wang has 100% sequence identity to SEQ ID NO: 2 of instant claim 12.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the construct of Bernett to have the first polypeptide comprising an antibody Fc domain be linked via its N terminus to the C terminus of the antibody heavy chain in the second polypeptide by a third linker (i.e. linked to the second CH3 region). One would have been motivated to have made this modification because Wang teaches a tandem Fc structure, termed IgG-2Fc-half, comprising a (GGGGS)2 linker between the C terminus of one Fc region and the N terminus of another Fc region, and that the IgG-2Fc-half format can be readily produced in large quantity, has good stability, maintains the binding affinity to FcyRs, FcRn and Clq, and has a PK profile comparable to that of the parental IgG1 despite its significantly reduced molecular weight, and using a knob-in-hole strategy eliminated unwanted mismatches between different heavy chains, thus, improving efficiency. Further, this is a known structure for Fc domains in the art, and it is obvious to use known variations in the prior art for predictable outcomes. See MPEP 2143 (F).
Claim 3 is included in this rejection because Bernett teaches that any linker is a “domain linker” used to link any two domains herein together, and a glycine-serine linker is utilized, such as (GGGGS)n, wherein n can be 3 [0215].
Claim 4 is included in this rejection because Bernett teaches that the scFv linker can be SEQ ID NO: 26219, which is a (GGGGS)3 linker, that attaches the VH and VL [see 0019-0020, 0213; Figure 8B]
Claim 5 is included in this rejection because Bernett teaches that the preferred scFv format, starting from the N-terminus, is VH-linker-VL [0155].
Claim 7 is included in this rejection because Bernett teaches that the bispecific antibodies (i.e. the first antigen binding domain and the second antigen binding domain) bind to antigen pairs which each antigen is on a different protein [0007-0010].
Claim 29 is included in this rejection because Bernett teaches that the Fc domains of the one armed mAb comprise a specific set of amino acid substitutions which can be T366S/L368A/Y407V:T366W [0397] and all constant region positions are numbered according to the EU index as in Kabat [0726].
Conclusion
No claims are 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.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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