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. Claims Status Claim(s) 1-2, 4-5, 7, 9-12, 14-15, 17, 19-21, 24-25, 28, 31 and 33 is/are currently pending and presented for examination on the merits. Specification The use of trade name(s) or mark(s) used in commerce (e.g., ThermoFisher , Gibco, BD Bioscience, StemCell Technologies, SepMate , BioLegend , eBioscience , FACSDiva , Spherotech , FlowJo , 10x Genomics, BioRad , Illumina, BD Rhapsody, Agilent, Qubit ), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Claim Rejections - 35 USC § 112(b) 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 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. Claim (s) 2, 7, 9 , 12, 17, and 19 is/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. Claim(s) 2, 7, 9, 12, 17, 19, recites the limitation " the other of ICOS and IL-1R1". There is insufficient antecedent basis for this limitation in the claim. For the purposes of compact prosecution, claim (s) is /are considered to read “…comprises (1) a first CAR comprising a n antigen binding domain that recognizes a first antigen , wherein the first antigen is either ICOS or IL-1R1 ; and (2) a second CAR comprising a n antigen binding domain that recognizes a second antigen ; wherein (a) the second antigen is IL-1R1 when the first antigen is ICOS; or (b) the second antigen is ICOS when the first antigen is IL-1R1 … ” . This rejection may be overcome by amending claim s 2, 9 , 12, and 19 to provide proper antecedent basis . Dependent claims 7 and 17 can overcome this rejection by amending claims 2 and 12, respectively, as recited above. Regarding claims 9 and 19, recite “the bi-functional switch molecule” which is recited in claim 2 (for claim 9) or claim 12 (for claim 19). However, the claim is indefinite because the binding requirements for the bi-functional switch molecule in claims 2(iv) or 12(iv) differ from the requirements in claims 9 or 19, respectively. Specifically, claims 2(iv) and 12(iv) recite “…the one or more agents comprise a logic-gated CAR T cell that co-expresses a first chimeric antigen receptor (CAR) that specifically binds one of ICOS and IL-1R1 , and a second chimeric antigen receptor (CAR) that specifically binds to the other of ICOS and IL-1R1 via a bi-functional switch molecule .. .”, whereas claims 9 and 19 recite “… the bi-functional switch molecule , wherein the bi-functional switch molecule comprises a first domain that specifically binds to the other of ICOS and IL-1R1 and a second domain that is specifically bound by the second CAR .” . The BRI of the above recitations is considered to conflict because claims 2 and 12 require two CARs wherein one is ICOS and the other is IL1R1 (in either order ; e.g., ICOS as first CAR or ICOS as second CAR) but claims 9 and 19 appear to require that the first CAR recognizes either ICOS or IL1R1 and that the second CAR may be any antigen that is not the same as the first CAR . Therefore, the conflicting requirements of claims 2 and 9 as well as 12 and 19 render the claim s 9 and 19 indefinite. For the purposes of compact prosecution, claim 9 is considered to recite the bi-functional molecule as recited in claim 2(iv) and claim 19 is considered to recite the bi-functional molecule as recited in claim 12(iv). This rejection may be overcome by amending claims 9 and 19 (1) as recited above, or (2) to otherwise clearly recite the limitations of the claimed invention. 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. Claim(s) 1 -2, 4 -5, 7, 9- 1 2, 14-15, 17 , 19-2 1, 24-25 , 28, 31 and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0298340 A1 (hereinafter “US 340 ”), in view of US 2020/0190191 A1 (hereinafter “US191”) and Tran et al. ( BLOOD, 21 May 2009, Vol. 113, No. 21 ; hereinafter “ Tran ”) FILLIN "Insert the prior art relied upon." \d "[ 2 ]" . Regarding instant claim(s) 1 -2, 4 -5 , 7 , 9- 1 2, 14-15, 17 , 19-2 1, 24-25, 28 , 31 , US 340 teaches method s for detecting and treating cancer comprising administering a composition comprising a logic-gated CAR T cell that binds two antigens [ e.g., title; abstract; ¶ 0003-0006, 0009, 0079-0089 , 0164, 0178 -0179, 0352 ] . US340 further teaches the cancer is a solid tumor [ e.g., ¶ 0082, 0089 ] and that the CAR is AND-gated (e.g., bifunctional switch requiring binding by both CARs to induce CAR T cell response) [ e.g., ¶ 0164, 0178, 0351 ] . US340 further teaches AND-gated CAR T cell activation results in target cell death [ e.g., ¶ 0126, 0132, 0158, 0159, 0164 ] . US340 further teaches the methods of the invention effectively treat (e.g., effective amount is administered to treat) disease s (e.g., solid tumor) with minimal side effects [ e.g., ¶ 0178, 0199 ] . Regarding instant claim(s) 33, US340 further teaches detection of target cells comprising contacting tumor cells from a subject with the detectably labeled CAR cells of the invention, wherein binding is indicative of presence of the target cells [ e.g., ¶ 0045-051, 0090-107, 0177, 0198, 0219, 0220 ; fig. 10 ; example 1 ] . US 340 does not expressly teach (1) an AND-gated CAR T cell bind ICOS and IL-1R 1, (2) a method treating cancer and/or depleting Tregs comprising administering a n ICOS and IL1R1 directed AND-gated CAR T cell wherein (a) administration of the CAR T cells reduces immunosuppressive conditions, (b) the antigen binding domain(s) of the CAR(s) are conjugated to a toxin, or (c) an anti-cancer antibody is administered as a second therapeutic agent that improve immune response against the tumor; or (3) a method of detecting tumor infiltrating Tregs in the TME comprising contacting a sample comprising tumor cells from the subject with a detectably labeled ICOS and IL1R1 directed AND-gated CAR T cell wherein detecting binding to a cell in sample indicate s the presence of tumor infiltrating Tregs. Regarding claims 1-2, 4, 7, 9-1 2, 14, 17 , 19 , 28, 31 , 33 , US191 teaches a multispecific (e.g., bispecific) antibody that binds ICOS and a second antigen for the treatment of solid tumors [ e.g., title; abstract; background ] . US191 further teaches ICOS expression is higher in intratumorally Tregs (e.g., tumor-infiltrating Tregs) compared with CD4+ and CD8+ effector cells in the TME, and that depletion (e.g., killing) of Tregs using antibodies directed to ICOS ha s demonstrated strong anti-tumor efficacy [ e.g., ¶ 0010 ] . Regarding claim s 5 , 15 , US191 teaches antibody binding domain(s) may be conjugated to other molecules (e.g., payloads) such as toxins [ e.g., ¶ 0058 ] . Regarding claim 10, US191 teaches ICOS+ Tregs are immunosuppressive (e.g., depleting these cells would naturally reduce immunosuppression) [ e.g., ¶ 0017 ] . Regarding claim s 20 -21, 24-25 , US191 teaches the administration of a second therapeutic agent wherein the second agent is an anti- tumor associated antigen (TAA) antibody or CAR T cell [ e.g., ¶ 0100, 0527-0563 ] . Tran teaches that IL 1R1 is expressed on activated Tregs, and not on non-Treg cells , and that such markers may be useful in the research and development of cell-based therapies [ e.g., title, abstract; pg. 5127, col. 2, ¶ 2; fig. 2 ] . Tran further teaches antibodies that bind IL1R1 [ e.g., pg.5126, “Methods”; fig. 2 ] . It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the generic antigen binding domains of the AND-gated CAR in the methods for detecting and/or treating solid tumors comprising the administration of AND-gated CAR T cell s as taught by US340, with the ICOS directed antigen binding domain as taught by US191 and the IL-1R1 direct antigen binding domain as taught by Tran , in the context of designing and developing a Treg directed CAR T cell for solid tumor treatment , Treg depletion and/or Treg detection. A PHOSITA would have been motivated to substitute the generic antigen binding domains of the AND-gated CAR in the methods for detecting and/or treating solid tumors comprising the administration of AND-gated CAR T cells as taught by US340, with the ICOS directed antigen binding domain as taught by US191 and the IL-1R1 direct antigen binding domain as taught by Tran , because US340 teaches the methods , the A ND-gated CAR T structure and that the CAR T can recognize a ny target antigen(s) desired [ e.g., ¶ 0179, 0352 ] , while US191 teaches that ICOS expression is higher in intratumoral Tregs and that depletion of Tregs using therapeutics directed to ICOS results in strong anti-tumor efficacy, and Tran further teaches that IL1R1 is a highly specific Treg marker not expressed on non-Tregs (and therefore a PHOSITA would be motivated to add this second antigen in addition to ICOS to decrease the potential for undesired cell targeting). There would have been a reasonable expectation of success for a PHOSITA to substitute the generic antigen binding domains of the AND-gated CAR in the methods for detecting and/or treating solid tumors comprising the administration of AND-gated CAR T cells as taught by US340, with the ICOS directed antigen binding domain as taught by US191 and the IL-1R1 direct antigen binding domain as taught by Tran because US340 teaches the methods and base CAR T cell, US191 and Tran collectively teach Treg-specific antigens, and US191 teaches the anti-cancer benefit of inhibiting and/or depleting intertumoral Tregs in solid tumors . This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141). Further, it would have been obvious to a PHOSITA to further modify the modified methods of treating solid tumors and/or depleting Tregs comprising administration of an ICOS and IL1R1 directed CAR T cell of US340, US191, and Tran (see above) to include the that (a) the administration of the CAR T cells reduces immunosuppressive conditions, (b) the antigen binding domain(s) of the CAR(s) are conjugated to a toxin, or (c) an anti-cancer antibody is administered as a second therapeutic agent that improve immune response against the tumor as taught by US191, because US340, US191, and Tran teach the methods and administered CAR T cell composition, and US191 further teaches additional modifications to the composition as well as the administration of a sec ond therapeutic agent for the treatment of solid tumors. There is an expectation of success for a PHOPSITA to substitute the modified methods of treating solid tumors and/or depleting Tregs comprising administration of an ICOS and IL1R1 directed CAR T cell as taught by US340, US191, and Tran to include the additional method and composition modifications as taught by US191, because US340, US191, and Tran teach the base methods and administered CAR T cell composition, and US191 further teaches additional modifications to the composition as well as the administration of a sec ond therapeutic agent for the treatment of solid tumors . This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141). Further, it would have been obvious to a PHOSITA to modify the modified methods of detecting tumor infiltrating Tregs comprising administration of an ICOS and IL1R1 directed CAR T cell of US340, US191, and Tran (see above) to include a method of detecting tumor infiltrating Tregs in the TME comprising contacting a sample comprising tumor cells from the subject with a detectably labeled ICOS and IL1R1 AND-gated CAR T cell and detecting binding to a cell in sample to indicate the presence of target cells (e.g., Tregs) as taught by US340, because US340 teaches the base method, US340, US191, and Tran teach the modified ICOS and IL1R1 directed AND-gated CAR T cell composition, and US340 further teaches details of the method(s) for detection of target cells comprising administration of the CAR T cells. There is an expectation of success for a PHOPSITA to substitute the modified methods of detecting tumor infiltrating Tregs comprising administration of an ICOS and IL1R1 directed CAR T cell of US340, US191, and Tran with the additional method details for the detection of target cells as taught by WO340 , because US340 teaches the base method, US340, US191, and Tran teach the modified ICOS and IL1R1 directed AND-gated CAR T cell composition, and US340 further teaches detailed method(s) for detection of target cells comprising administration of the CAR T cells . This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141). Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary. Conclusion No claims are currently allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT AMY M CHATTIN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0646 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT T-F 0600-1600 PST . 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, FILLIN "SPE Name?" \* MERGEFORMAT Julie Wu can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-5205 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMY M. CHATTIN/ Examiner, Art Unit 1643 /JULIE WU/ Supervisory Patent Examiner, Art Unit 1643