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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.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 8/21/2025 has been entered.
Claims 1, 3, and 5-6, of record 8/21/2025, are pending and subject to prosecution. No amendments to the claims were made with the submission of 8/21/2025.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1, 3, and 5-6 under 35 U.S.C. 103 over Levitsky (WO 2018102612 A1) in view of Sahin et al. (US 20160272711 A1):
The applicant asserts unexpected results in the form of superior induction of cytokine (IFN-γ, TNFα, and IL-2) secretion (Applicant Remarks, page 3-4). The applicant asserts that the enhanced cytokine production is due to B cell-T cell interaction, which could not have been predicted from the prior art (Applicant Remarks, page 4).
As stated in the previous Office Action, this argument is not found persuasive. The applicant has not provided evidence that the total concentration of antibody is similar between the transduced B cell and supernatant only treatment groups, as supernatant containing the BiTE antibody (BiTE-B), but not untransduced B cells (UB), is able to induce substantial cytokine secretion. The untransduced B cells are presumably activated by interaction with T cells and would therefore express MCHII, CD80, and CD86, per the applicant (Applicant Remarks, page 4), like the transduced cells; however, the untransduced cells induce virtually no cytokine production, which suggests that any induction is due solely to the antibody, contrary to the applicant’s argument.
Further, to overcome a finding of obviousness, any showing of unexpected results must be commensurate in scope with the claimed invention. See MPEP 716.02(d). The experimental results cited by the applicant involve B cells transduced to express a HER2-specific BiTE, with no mention of the immune cell antigen targeted by the BiTE, whereas the scope of the claims is considerably broader, with no limit placed on the tumor and immune cell antigens targeted by the BiTE in independent claim 1.
The rejection is maintained.
Maintained Rejections
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.
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, 3, and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Levitsky (WO 2018102612 A1) in view of Sahin et al. (US 20160272711 A1).
Regarding claims 1, 3 and 5-6: Levitsky teaches B cells engineered to secrete an exogenous protein for adoptive cell therapy (See Abstract). The protein can be a bispecific antibody (See ¶0167-0168). The protein can target a surface antigen on a tumor or cancer cell (See ¶0016-0017). The cells can be contained in a pharmaceutical composition with a pharmaceutically acceptable carrier (See ¶0097). The composition can be administered in a therapeutically effective amount and can be used in the treatment of diseases such as cancer (See ¶0112 and 0329). Levitsky teaches that the cultured B cells can be stimulated, activated, and/or propagated in connection with genetic engineering (See ¶0303). The conditions can be designed to induce activation, proliferation, and/or expansion (which reads on “activated in vitro to proliferate”) (See ¶0303). The cells are provided for adoptive therapy and express and/or secrete a therapeutic protein such as an antibody (which reads on “express the… antibody in vivo”) (See ¶0112). Levitsky teaches that an activation step could be readily carried out prior to adoptive transfer, wherein the cells would produce antibodies in a host (See ¶0303). Levitsky does not expressly teach a bispecific antibody that binds to a tumor cell antigen as well as an immune cell antigen.
Sahin et al. teach bispecific antibodies that target CD3 (which reads on “an immune cell antigen”) and a tumor-associated claudin molecule (which reads on “a tumor antigen on a tumor cell”) (See Abstract). Sahin et al. teach bispecific constructs having the sequence VH(CD3)—VL(CD3)—VH(claudin)—VL(claudin) (See fig. 1). The antibody chains can be interconnected by peptide linkers (See ¶0014).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the B cells of Levitsky to express the antibody taught by Sahin et al. One would be motivated to make this modification because Sahin et al. teach that binding agents targeting claudin and CD3 can induce T cell-mediated lysis and effectively treat tumors (See ¶0009). There would be a reasonable expectation of success in making this modification because Levitsky teaches that exogenous proteins such as bispecific antibodies can be expressed from B cells (See ¶0168).
Conclusion
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633