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 response to the previous Office action, dated August 21, 2026, has been received. By way of this submission, Applicant has amended claims 34-36, 38-41, 46-50, 54-56, and 59.
Claims 34-42 and 45-59 are pending in the application. Claims 42, 51-53, 56, and 58 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed May 31, 2025.
Claims 34-41, 45-50, 54, 55, 57, and 59 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated May 21, 2026.
Response to Amendment
Applicant argues that the claims as amended specify the activity of the anti-booster antigen chimeric antigen receptor (aBA-CAR) as targeting the booster antigen, separately from the activity of the modified therapeutic immune cells' TCR or another CAR.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 112(b) is hereby withdrawn.
Applicant argues that Dropulic does not teach every aspect of the claims as amended; specifically, Dropulic does not teach that the booster antigen recognized by the aBA-CAR is not the same as the target antigen on the target cell.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 102(a)(1) and (a)(2) over Dropulic is hereby withdrawn.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 34-41 and 45-48 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Berger (US20170246279A1) as evidenced by Wang (Exp Hematol Oncol. 2012 Nov 29;1(1):36, cited previously). This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
Berger teaches a method for boosting, augmenting or enhancing the efficacy of adoptive cellular immunotherapy or treating a hyperproliferative disorder by administering to human subject an effective amount of a composition comprising a population of modified human T cells comprising a nucleic acid molecule that encodes an antigen binding protein (e.g., a chimeric antigen receptor (CAR)), and a population of modified human immune system cells comprising a nucleic acid molecule that encodes the antigen specifically recognized by the extracellular binding component of the antigen binding protein (para. 0013). Berger also teaches that the cells expressing the antigen recognized by the CAR will boost the effect of the adoptive immunotherapy (para. 0056).
Berger further teaches that the modified T cells may specifically bind to a tumor or cancer antigen and a second target antigen on the cancer cell (para. 0091).
Berger further teaches that the antigen is useful for activating the T cells (para. 0065).
Berger further teaches that the antigen may be CD19 (para. 0032), which is pertinent to claims 36-37.
Berger further teaches that the modified immune system cell may be a B cell (para. 0021), which is pertinent to claims 35 and 38-40.
While Berger does not teach that CD19 comprises a transmembrane domain and a extracellular domain, Wang teaches that CD19 comprises a transmembrane domain and an extracellular N-terminus (i.e., an extracellular binding domain which can be recognized by the CAR-bearing therapeutic immune cell). Berger therefore inherently teaches these aspects of claim 41.
Berger further teaches that the CAR comprises a CD3 zeta domain and a 4-1BB domain (para. 0109), which is pertinent to claims 45 and 46.
Berger further teaches that the T cell is obtained from peripheral blood mononuclear cells (PBMC) (para. 110), which is pertinent to claim 48.
Claim Rejections - 35 USC § 103
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.
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.
Claims 49-50, 54-55, 57, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Berger as applied to claims 34 and 48 above, and further in view of Dropulic (WO2016201394A1, cited in IDS). The following paragraph numbers refer to the corresponding US publication of Dropulic, US20190134091A1, which is identical to the WIPO document. This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
The teachings of Berger have been discussed supra. Berger also teaches that a host cell can be modified to express two or more heterologous or exogenous nucleic acid molecules encoding desired antigen-specific binding proteins, such as CARs or TCRs (para. 0050). However, Berger does not teach modifying the T cells with patient-specific and tumor-specific TCRs, or cancer cells expressing Epstein Barr virus antigens.
Dropulic teaches an immunotherapy composition comprising autologous antigen presentation cells expressing patient-derived tumor antigens, which are capable of promoting in vivo expansion or persistence of patient-specific anti-tumor T-cells (para. 0014).
Dropulic further teaches that antigen presenting cells may prime or boost the activity of transduced T cells capable of recognizing the antigen (para. 0278).
Dropulic further teaches a chimeric antigen receptor (CAR), comprising an antibody that can bind to the antigen in question (para. 0030). Dropulic also teaches modifying the transduced T cells with said CAR (para. 0011).
Dropulic further teaches that the CAR may bind to viral antigens (para. 0094).
Dropulic further teaches that the autologous anti-tumor CAR-containing T cells may also be transduced with one or more patient-specific and tumor-specific TCRs (para. 0051), which is pertinent to claims 49 and 50.
Dropulic further teaches that the target cells may be cancer cells expressing Epstein Barr virus antigens or human papillomavirus (HPV) antigens (para. 0090), which is pertinent to claims 54-55, and 57.
Dropulic further teaches that the costimulatory domain may comprise CD28, 4-1BB, or ICOS (para. 0040), which is pertinent to claim 59.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Berger and Dropulic to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Berger and Dropulic are concerned with methods of enhancing CAR-T cell therapy by administering a booster antigen. As stated above, Berger teaches methods of enhancing the efficacy of adoptive cellular immunotherapy by administering CAR-T cells and immune cells that express the antigen recognized by the CAR to boost the effect of the adoptive immunotherapy. Dropulic teaches other embodiments of a similar system, such as a car that binds to viral antigens, or a CAR-T cell that is further transduced with one or more patient-specific and tumor-specific TCRs. One of ordinary skill could apply the improvements and alternative embodiments described by Dropulic to the method of Berger to arrive at the claimed invention. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1644
