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. Status of the Claims Claims 126 – 145 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims. Claim Objections Claim 132 is objected to because of the following informalities: The abbreviations “TRAC” and “TRBC” are used in claim 132 without defining the acronym. At the first use in the claims, these abbreviations should be written out in expanded form to improve clarity and readability of the claims. Appropriate correction is required. 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. Claims 126 – 145 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 126 recites “ wherein the cell exhibits substantial cytolytic activity against cells that are single positive for the antigen”. However, neither the claims nor the present specification defines “singly positive for the antigen”, and thus it is not clear what “singly positive for the antigen” means or singly positive for the antigen includes or excludes Claims 127 – 145 depend from claim 126, either directly or indirectly, and thus inherit the deficiencies of claim 126. 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 126 – 13 0, 134 – 135, and 137 – 145 are rejected under 35 U.S.C. 103 as being unpatentable over SADELAIN ( WO 2018/027197 A1 , published 02/08/2018 ; see PTO-892: Notice of References Cited) in view of B ensussan ( WO 2021/009263 A1 , published 01/21/2021; an IDS reference submitted 03/10/2025 ) . The present application is directed to a cell comprising:(a) an antigen-recognizing receptor that binds to an antigen; and (b) a chimeric co-stimulating receptor (CCR) that binds to CD38, wherein the cell exhibits substantial cytolytic activity against cells that are single positive for the antigen. According to the present specification, “ CCRs mimic co-stimulatory signals, but unlike, CARs, do not provide an activation signal. In certain embodiments, the CCR lacks a CD3ζ polypeptide” (¶ 0080 of the pre-grant publication). SADELAIN is directed to an immunoresponsive T cell that can be engineered to express a combination of CAR, TCR, and/or CCR that bind to different antigens to achieve activation and stimulation of the immunoresponsive T cell , which is an effective therapeutic agent against a myeloid disorder, for example, acute myeloid leukemia (AML). See SUMMARY OF THE INVENTION , p. 4 and abstract . SADELAIN teaches a n isolated immunoresponsive cell comprising: (a) an antigen recognizing receptor that binds to a first antigen, wherein binding of the antigen recognizing receptor to the first antigen is capable of activating the immunoresponsive cell, and (b) a chimeric co-stimulating receptor (CCR) that binds to a second antigen, wherein binding of the CCR to the second antigen is capable of stimulating the immunoresponsive cell wherein each of the first antigen and the second antigen is CD38 , and the first antigen and the second antigen are different. See claim 16. B ensussan is directed to the targeting of CD38 in the treatment of a variety of malignant hematological diseases, including acute myeloid leukemia . See p. 1, last paragraph. BEN S USSAN teaches a 3rd generation CAR (3G) contain ing CD28, 4-1BB and CD3z signaling domains and a CCR contain ing CD28 and 4- IBB signaling domains, but lack ing the CD3 ζ domain. See front page , Figure 3 and p. 40, lines 7 – 8. Thus, because SADELAIN teaches a cell with a CAR and a CCR that activates and stimulates T cells in a treatment for cancer , and BENSUSSAN teaches that CD38 is an effective target in the treatment of a variety of malignant hematological diseases such as cancer and also teaches a CD38 CCR, it would have been obvious to modify SADELAIN’ s cell with BENSUSSAN ’s CD38 CCR to arrive to the invention of present claims 126 – 130 and 137 . There would have been a reasonable expectation of success considering that a cell with a CAR that binds to a cancer antigen and a CCR that binds to CD38 is known in in the study of cancer as evidenced by the applied art. Regarding the limitation “wherein the cell exhibits substantial cytolytic activity against cells that are single positive for the antigen” of present claim 126, while neither SADELAIN nor BENSUSSAN states that the taught composition would result in the cell exhibiting substantial cytolytic activity against cells that are single positive for the antigen, the composition rendered obvious by SADELAIN and BENSUSSAN would inherently result in a cell exhibiting substantial cytolytic activity against cells that are single positive for the antigen. Regarding claim 134, SADELAIN teaches that a CAR is an antigen-binding domain that is fused to an intracellular signaling domain capable of activating or stimulating an immune cell, and also comprises a transmembrane domain. See p. 19, last ¶ . SADELAIN also teaches CARs include those that provide both co-stimulation (e.g., CD28 or CD137) and activation (CD3ζ). See p. 20, lines 5 – 8. Thus, SADELAIN renders the CAR of present claim 134 obvious. Regarding claim 135, the components of the CAR may either be native or modified, and thus a CAR having either native or modified CD3ζ is rendered obvious by SADELAIN or BENSUSSAN . Regarding claims 138 – 140, BENSUSSAN teaches a CCR that binds CD38 and which has the co-stimulatory domains CD28 and 4-1BB. See front page, Figure 3A. Regarding claim 141, SADELAIN teaches a method introducing into the cell a nucleic acid molecule that encodes a chimeric co-stimulating receptor (CCR) that binds to CD38. See claim 84. Because the CAR and CCR of SADELAIN have an antagonistic effect with the binding of the antigens, it would have been obvious that the modification of the cell would reduce and/or abolish the expression of CD38 in a cell. Regarding claim s 127 and 142, SADELAIN teaches that the cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a Natural Killer T (NKT) cell, a human embryonic stem cell, and a pluripotent stem cell from which lymphoid cells may be differentiated. See claim 13. Regarding claim 143, SADELAIN teaches that in an additional aspect, a method for treating or preventing a myeloid disorder, comprising administering an effective amount of at least one antibody that binds to CD38. See p. 12, lines 29 – 33. Thus it would have been obvious to administer the CAR-T cell with an anti-CD38 antibody. Regarding claim 144, SADELAIN teaches that the compositions are pharmaceutical compositions comprising genetically modified immunoresponsive cells or their progenitors and a pharmaceutically acceptable carrier. See p. 76, lines 16 – 18. Regarding claim 145, SADELAIN teaches the administration of the pharmaceutical composition. See p. 76, lines 16 – 18. Claim s 131 -133 are rejected under 35 U.S.C. 103 as being unpatentable over SADELAIN in view of B ensussan as applied to claims 126 – 130, 134 – 135, and 137 – 145 above and further in view of SADELAIN 2 ( W O 2019/157454 A1 , published 08/15/2019; see PTO-892). The teachings of SADELAIN and B ensussan are discussed above and fully incorporated here. SADELAIN 2 is directed to a recombinant T cell receptor ( TCR ) comprising an antigen binding chain that comprises an extracellular antigen-binding domain and a constant domain, wherein the recombinant TCR binds to an antigen in an HLA - independent manner, wherein the constant domain comprises a native or modified TRAC peptide and/or a native or modified TRBC peptide. SADELAIN 2 teaches that the extracellular antigen-binding domain comprises a ligand for a cell-surface receptor, a receptor for a cell surface ligand, an antigen binding portion of an antibody or a fragment thereof or an antigen binding portion of a TCR (see claims 18 – 24) and that the antigen binding chain, upon binding to an antigen, is capable of activating the CD3z polypeptide associated to the antigen binding chain see claim s 6 and 8. Thus, because SADELAIN teaches a cell with a TCR (discussed above) and a CCR that activates and stimulates T cells in a treatment for cancer; BENSUSSAN teaches that CD38 is an effective target in the treatment of a variety of malignant hematological diseases such as cancer and also teaches a CD38 CCR; and SADELAIN 2 teaches a recombinant TCR having the limitations of claim 131, it would have been obvious to modify SADELAIN/BENSUSSAN’ s cell with SADELAIN 2 ’s TCR to arrive to the invention of present claim 131. There would have been a reasonable expectation of success considering that a cell with a TCR that binds to a cancer antigen and a CCR that binds to CD38 is known in in the study of cancer as evidenced by the applied art. Claim 136 is rejected under 35 U.S.C. 103 as being unpatentable over SADELAIN in view of B ensussan and MIHARA as applied to claims 126 – 130, 132 – 135, and 137 – 145 above and further in view of SADELAIN 3 ( WO 2020 / 172177 A1 , published 08/27/2020; see PTO-892) . The teachings of SADELAIN and B ensussan are d iscussed above and fully incorporated here. Additionally , SADELAIN teaches the CD3z domain comprises 3 ITAMs which transmits an activation signal to the cell and variants thereof. See paragraph bridging p p. 33- 34 . SADELAIN 3 is directed to an immunoresponsive cell comprising a first CAR comprising a first extracellular antigen-binding domain that binds to a first antigen and b) a second CAR comprising a second extracellular antigen-binding domain that binds to a second antigen and a second intracellular signaling domain comprising a second co-stimulatory molecule or a portion thereof, wherein the second co-stimulatory molecule is different from the first co-stimulatory molecule. See claim 1. SADELAIN 3 teaches a CAR with a CD3ζ polypeptide having one or more ITAM variant comprising one or more loss-of-function mutations, wherein each of the one or more ITAM variant is independently selected from the group consisting of an ITAM1 variant, an ITAM2 variant, and an ITAM3 variant. See claims 1, 4-6, 13, and 14. Thus, because SADELAIN teaches a cell with a CAR and a CCR that activates and stimulates T cells in a treatment for cancer; BENSUSSAN teaches that CD38 is an effective target in the treatment of a variety of malignant hematological diseases such as cancer and also teaches a CD38 CCR; and SADELAIN 3 teaches a dual CAR cell that has a similar function as SADELAIN ’s CAR and teaches a CAR with a CD3ζ polypeptide having one or more ITAM variant comprising one or more loss-of-function mutation, it would have been obvious to modify SADELAIN/BENSUSSAN’ s cell with SADELAIN 3 ’s CAR CD3ζ to arrive to the invention of present claim 136. There would have been a reasonable expectation of success considering that a cell with a TCR that binds to a cancer antigen and a CCR that binds to CD38 is known in in the study of cancer as evidenced by the applied art. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claims 126 – 145 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 24 of U.S. Patent No. 10,654,928 in view of SADELAIN, BENSUSSAN, SADELAIN 2, and SADELAIN 3 . P atented claim 1 recites an immunoresponsive cell comprising: a) a chimeric antigen receptor (CAR) that binds to a first antigen with a dissociation constant ( Kd ) of about 5×10−8 M or more, wherein binding of the CAR to the first antigen is capable of delivering an activation signal to the immunoresponsive cell, and b) a chimeric co-stimulating receptor (CCR) that binds to a second antigen, wherein binding of the CCR to the second antigen is capable of delivering a costimulatory signal to the immunoresponsive cell but does not alone deliver an activation signal to the immunoresponsive cell; patented claim 2 recites that the cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a human embryonic stem cell, and a pluripotent stem cell from which lymphoid cells may be differentiated; and patented claim 8 recites that said first and second antigens are selected from the group consisting of . . . CD38 . . .; and patented claim 24 recites a pharmaceutical composition comprising an immunoresponsive cell and a pharmaceutically acceptable excipient. The main difference between the present claims and the patented claims is that present clai ms 131 – 133 recite a TCR like fusion molecule ; present claim 136 recites that the modified CD3ζ polypeptide comprises a native ITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations ; present claim 141 recite s a method of reducing and/or abolishing expression of CD38 in a cell ; present claim 143 recites a method of treating and/or preventing a disease associated with and/or expressing CD38 in a subject ; and present claim 1 45 recite s a method treating a tumor . However, SADELAIN , BENSUSSAN , SADELAIN 2 , and SADELAIN 3 disclose this difference. The teachings of SADELAIN , BENSUSSAN , SADELAIN 2 , and SADELAIN 3 and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above. Because the patented claims recite a recite an immunoresponsive cell comprising a CAR that binds to an antigen and a CCR that binds to CD38 and the cited references teach the limitations of claims 131 – 133 , 136, 141, 143, and 145 as discussed above , it would have been obvious to one having ordinary skill in the art to use the patented claims ’ cell in the compositions and methods of the present claims . Claims 126 – 145 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 36 of U.S. Patent No. 10,730,941 in view of SADELAIN, BENSUSSAN, SADELAIN 2, and SADELAIN 3 . P atented claim 1 recites a chimeric antigen receptor (CAR), comprising an extracellular antigen-binding domain that binds to human CD56, a transmembrane domain, and an intracellular domain ; Patented claim 17 recites an immunoresponsive cell comprising the CAR of claim 1 ; Patented claim 19 recites the immunoresponsive cell of claim 17 , wherein the immunoresponsive cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a human embryonic stem cell, a lymphoid progenitor cell, a T cell-precursor cell, and a pluripotent stem cell from which lymphoid cells may be differentiated; Patented claim 22 recites the immunoresponsive cell of claim 1 , further comprising an antigen recognizing receptor that binds to a second antigen that is different than human CD56; Patented claim 23 recites the immunoresponsive cell of claim 22 , wherein the second antigen is selected from the group consisting of . . . CD38, . . .; Patented claim 25 recites The immunoresponsive cell of claim 22 , wherein the antigen recognizing receptor is a truncated CAR, or a chimeric co-stimulatory receptor (CCR) . Patented claim 30 recites a pharmaceutical composition comprising an effective amount of the immunoresponsive cell of claim 17 and a pharmaceutically acceptable excipient. The main difference between the present claims and the patented claims is that present claims 131 – 133 recite a TCR like fusion molecule; present claim 136 recites that the modified CD3ζ polypeptide comprises a native ITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations; present claim 141 recites a method of reducing and/or abolishing expression of CD38 in a cell; present claim 143 recites a method of treating and/or preventing a disease associated with and/or expressing CD38 in a subject; and present claim 145 recites a method treating a tumor. However, SADELAIN , BENSUSSAN , SADELAIN 2 , and SADELAIN 3 disclose this difference. The teachings of SADELAIN , BENSUSSAN , SADELAIN 2 , and SADELAIN 3 and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above. Because the patented claims recite a recite an immunoresponsive cell comprising a CAR that binds to an antigen and a CCR that binds to CD38 and the cited references teach the limitations of claims 131 – 133, 136, 141, 143, and 145 as discussed above , it would have been obvious to one having ordinary skill in the art to use the patented claims ’ cell in the compositions and methods of the present claims . Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Estella Gustilo whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-1706 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 9:30 AM - 5:30 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, FILLIN "SPE Name?" \* MERGEFORMAT Gregory Emch can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-8149 . 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. /ESTELLA M. GUSTILO/ Examiner, Art Unit 1646 /PETER J REDDIG/ Primary Examiner, Art Unit 1646