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 were pending. Claims 126 – 127, 129 – 130, 134, and 140 have been amended, and 128, 131 – 133 and 139 have been canceled. Claims 126 – 127, 129 – 130, 134 – 138, and 140 – 145 are currently pending and are the subject of this Office Action.
OBJECTION/REJECTION WITHDRAWN
Claim Objections
Claim 132 is objected to because of informalities.
In view of the cancelation of claim 132 in the reply of 06/05/2026, this objection is withdrawn.
Claim Rejections - 35 USC § 112
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.
In view of the Declaration by Dr. Maria Themeli (Themeli Declaration) of 06/05/2026, point 19, p. 6, this rejection is withdrawn.
Claim Rejections - 35 USC § 103
Claims 131 – 133 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 of 03/10/2026) in view of BENSUSSAN (WO 2021/009263 A1, published 01/21/2021; an IDS reference submitted 03/10/2025) as applied to claims 126 – 130, 134 – 135, and 137 – 145 above and further in view of SADELAIN 2 (WO 2019/157454 A1, published 08/15/2019; see PTO-892: Notice of References Cited of 03/10/2026).
In view of the cancelation of claims 131 – 133 in the reply of 06/05/2026, this rejection is withdrawn.
Double Patenting
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.
In view of the cancelation of claims 131 – 133 in the reply of 06/05/2026, this rejection is withdrawn.
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.
In view of the cancelation of claims 131 – 133 in the reply of 06/05/2026, this rejection is withdrawn.
REJECTIONS MAINTAINED IN MODIFIED FORM
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 – 127, 129 – 130, 134 – 135, 137 – 138, and 140 – 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 of 03/10/2026) in view of BENSUSSAN (WO 2021/009263 A1, published 01/21/2021; an IDS reference submitted 03/10/2025).
Present independent claim 126 is directed to a cell comprising: (a) an antigen-recognizing receptor that binds to a first antigen; and (b) a chimeric co-stimulating receptor (CCR) that binds to CD38, wherein the cell exhibits substantial cytolytic activity against cells that are singly positive for the first antigen, wherein the antigen-recognizing receptor is a chimeric antigen receptor (CAR),wherein the intracellular domain of the CAR comprises an intracellular co-stimulatory domain of CD28, and wherein the intracellular domain of the CCR comprises an intracellular co-stimulatory domain of CD28.
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 an 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. See SADELAIN at claim 16.
SADELAIN teaches that the immunoresponsive cell exhibits a greater degree of cytolytic activity against cells that are positive for both the first antigen and the second antigen as compared to against cells that are singly positive for the first antigen. See SADELAIN at claim 19.
SADELAIN teaches that "second generation" "Second-generation" CARs include those that provide both co-stimulation (e.g., CD28 or CD137). See SADELAIN at p. 20, lines 6 – 7. Under the heading “Intracellular Signaling Domain of a CAR”, SADELAIN also teaches that at least one co-stimulatory signaling region can include a CD28 polypeptide (see SADELAIN at p. 35, lines 31 – 32). Under the heading “Chimeric Co-Stimulatory Receptor (CCR)”, SADELAIN teaches that the CCR comprises an extracellular antigen-binding domain that binds to a second antigen, a transmembrane domain, and a co-stimulatory signaling region that comprises at least one co-stimulatory molecule and that the co-stimulatory molecules include CD28. See SADELAIN, p. 43, lines 26 – 30. Thus, SADELAIN teaches a cell with a CAR and a CCR both having intracellular co-stimulatory domains of CD28.
BENSUSSAN 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. BENSUSSAN teaches a 3rd generation CAR (3G) containing CD28, 4-1BB and CD3z signaling domains and a CCR containing CD28 and 4- IBB signaling domains, but lacking the CD3ζ domain (CCR CD38). See BENSUSSAN at the front page, Figure 3A and p. 40, lines 7 – 8.
BENSUSSAN also teaches that cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule as defined below and that costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 4-IBB (i.e., CD137), CD27 and/or CD28. See BENSUSSAN at p. 8, lines 19 – 23.
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 a functional 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 – 127, 129, 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.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of SADELAIN and BENSUSSAN. The artisan would have been motivated to make and use the cell of claim 1 because SADELAIN teaches novel therapeutic strategies to design CARs targeting antigens that are highly expressed in acute myeloid leukemia (AML) cells and limited expression in normal tissues for treating AML, and for strategies capable of inducing potent cancer eradication with minimal toxicity and immunogenicity and BENSUSSAN teaches CD38 is also expressed in a variety of malignant hematological diseases and CAR-T cells targeting CD38 (see abstract). The artisan would have a reasonable expectation of success from the combined teachings of SADELAIN and BENSUSSAN.
Regarding claim 130, SADELAIN teaches an antigen recognizing receptor that binds to an antigen selected from the group consisting of EMR2, CD33, ILIORB, PLXNC1, PIEZOl, CD300LF, CPM, ITFG3, TTYH3, ITGA4, SLC9A1, MBOAT7, CD38, SLC6A6, ENG, SIRPB l, MRP1, ITGA5, SLC43A3, MYADM, ICAM1, SLC44A1, CCRl, SLC22A5, TFR2, KCNN4, LILRB4, LTB4R, CD70, GYP A, FCGRIA, CD123, CLEC12A, ITGB5, PTPRJ, SLC30A1, EMCIO, TNFRSFIB, CD82, ITGAX, CR1, DAGLB, SEMA4A, TLR2, P2RY13, LILRB2, EMB, CD96, LILRB3, LILRA6, LILRA2, WT1, PRAME and SLC19A1. See SADELAIN at claim 1.
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 and 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 SADELAIN at 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 claims 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 SADELAIN at 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 136 is rejected under 35 U.S.C. 103 as being unpatentable over SADELAIN in view of BENSUSSAN as applied to claims 126 – 127, 129 – 130, 134 – 135, 137 – 138, and 140 – 145 above and further in view of SADELAIN 3 (WO 2020/172177 A1, published 08/27/2020; see PTO-892 of 03/10/2026).
The teachings of SADELAIN and BENSUSSAN are discussed above and fully incorporated here. Although SADELAIN in view of BENSUSSAN renders the method of claims 126, 134, and 135, from which claim 136 depends either directly or indirectly, neither SADELAIN nor BENSUSSAN teaches the limitation of present claim 136.
Additionally, SADELAIN teaches the CD3z domain comprises 3 ITAMs which transmits an activation signal to the cell and variants thereof. See paragraph bridging pp. 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 SADELAIN 3 at 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.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of SADELAIN, BENSUSSAN, and SADELAIN 3. The artisan would have been motivated to make and use the cell of claim 136 because SADELAIN teaches novel therapeutic strategies to design CARs targeting antigens that are highly expressed in acute myeloid leukemia (AML) cells and limited expression in normal tissues for treating AML, and for strategies capable of inducing potent cancer eradication with minimal toxicity and immunogenicity; BENSUSSAN teaches CD38 is also expressed in a variety of malignant hematological diseases and CAR-T cells targeting CD38 (see abstract); and SADELAIN 3 teaches immunoresponsive cells have improved therapeutic efficacy (see SADELAIN 3 at p. 1, 3. INTRODUCTION). The artisan would have a reasonable expectation of success from the combined teachings of SADELAIN and BENSUSSAN.
Response to Arguments
Applicant’s arguments, including the Declaration by Dr. Maria Themeli (Themeli Declaration), are insufficient to overcome the rejections of claims 126 – 127, 129 – 130, 134 – 138, and 140 – 145 based upon 35 USC 103 for the following reasons.
Regarding point 8 of the Themeli Declaration, SADELAIN and BENSUSSAN teaches the CD28 co-stimulatory domain in a CAR and CCR and render the CAR and CD38-targeting CCR combination obvious as discussed above.
Regarding point 9 of the Themeli Declaration, SADELAIN teaches that the disclosed immunoresponsive cell with the CAR and CCR (SADELAIN at claim 155) induces signal transduction or changes in protein expression in the cell resulting in initiation of an immune response, which leads to an increase of IL-2 production. See SADELAIN at p. 17, last paragraph.
Regarding points 10 – 18 of the Themeli Declaration, the example of unexpected effects provided is not commensurate in scope with the present claims. The example of BCMA28ζ-CAR+CD38_BB-CCR is limited to a specific structure and not commensurate in scope with present claim 126 which broadly recites an antigen-recognizing receptor that binds to a first antigen.
On p. 9 – 10 of the reply of 06/05/2026, Applicant argues unexpected advantages, stating that “the application describes experiments in which different CAR-CCR combinations were tested. In Example 4, starting on page 123 of WO 2022/204129, for example, a CD19-targeting CAR comprising a CD28 co-stimulatory domain was combined with a CD38- targeting CCR comprising a CD28 and a 4-1BB co-stimulatory domain (‘CD19-28 ζ + CD38- 28BB’) was compared to the same combination without a CD28 co-stimulatory domain in either the CAR (‘CD19- ζ + CD38-28BB’) or the CCR (CD19-28 ζ + CD38-BB). It was surprisingly found that a combination wherein the CAR and the CCR both have a CD28 co-stimulatory domain that had a lower tumor burden (see Figs. 11A and C) and resulted in a longer survival (see Fig. 11D). Additionally, this combination demonstrated increased cytotoxic capacity against leukemia cell lines (Fig. 7D) when compared to only CAR” (p. 9, second paragraph of the reply).
However, Example 4, like the example provided in the Themeli Declaration, is limited to a very specific CAR targeting CD19 and is thus not commensurate in scope with present independent claim 126, which recites an antigen-recognizing receptor that binds to a first antigen and not the CAR targeting CD19 discussed in the example.
On p. 10, under “(2) Non-obviousness”, second paragraph, Applicant argues that “BENSUSSAN describes a T cell having a CD38-targeting CAR comprising a CD28 co- activation domain and a CD38- targeting CCR comprising a CD28 co-activation domain (Example 2, Fig. 3). However, importantly, BENSUSSAN does not show co-expression of said CCR with said CAR (or with any other CAR). Said CCR is only used as a control in the experiments (p. 50, 1.19-21, Fig. 3A). If the skilled person were to implement BENSUSSAN's teachings in SADELAIN's cell, he/she would implement a CD38-targeting CAR, not a CD38-targeting CCR, as the latter was only used as a control.”
Applicant’s argument is not persuasive because although BENSUSSAN’s CD38 CCR is used as a control, it functions as designed, which is to provide co-stimulation without fully activating cytotoxicity (see BENSUSSAN at p. 50, line 32 – p. 51, line 1). Thus, because SADELAIN, which teaches an immunoresponsive cell 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 (see SADELAIN at claim 16) and BENSUSSAN teaches CCR CD38, which provides costimulation, it would have been obvious to one having ordinary skill in the art to use BENSUSSAN’s CCR CD38 in place of the CCR of SADELAIN’s immunoresponsive cell. There would have been a reasonable expectation of success considering that SADELAIN teaches that the CCR (which binds a second antigen) may bind CD38 (see SADELAIN at claim 16).
On p. 10, last paragraph – p. 11, last paragraph, Applicant argues that “[c]oncerning the intracellular CD28 co-stimulatory domains in both the CAR and CD38- targeting CCR, the prior art not only fails to suggest the claimed configuration but also points away from it. At the priority date, it was well understood that different co-stimulatory domains (e.g., CD28 and 4-1BB) confer distinct functional properties and were therefore selected to achieve complementary signaling effects. The skilled person would thus have been motivated to combine different co-stimulatory domains rather than identical ones, to balance activation, persistence, and exhaustion. Even if the skilled person had considered using identical co- stimulatory domains, there would have been no reasonable expectation that such a configuration would yield improved cytotoxicity, given the unpredictability of T cell signaling (see In re Cyclobenzaprine, 676 F.3d 1063).”
Applicant’s argument has been fully considered but not persuasive because SADELAIN teaches the intracellular CD28 co-stimulatory domains in both the CAR and CCR as discussed above. Furthermore, BENSUSSAN teaches that “the cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule as defined below. In some embodiments, the costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 4-IBB (i.e., CD137), CD27 and/or CD28.” See BENSUSSAN at p. 8, lines 19 – 23. Thus, SADELAIN and BENSUSSAN teach CARs and/or CCRs having co-stimulatory domains of CD28.
On p. 12, fourth paragraph, Applicant argues that “the secondary references SADELAIN 2 and SADELAIN 3 provide no teaching or suggestion to render obvious the subject matter of dependent claims 131-133, and claim 136, respectively.”
Claims 131 – 133 have been canceled and thus their rejections over SADELAIN 2 are withdrawn. SADELAIN 3 provides teaching that renders the limitations of present claim 136 obvious as discussed above. Thus, the rejection of claim 136 over SADELAIN in view of BENSUSSAN and SADELAIN 3 is maintained.
MAINTAINED/MODIFIED REJECTIONS
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 – 127, 129 – 130, 134 – 138, and 140 – 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, and SADELAIN 3.
Patented 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 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, and SADELAIN 3 disclose this difference.
The teachings of SADELAIN, BENSUSSAN, 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 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 – 127, 129 – 130, 134 – 138, and 140 – 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, and SADELAIN 3.
Patented 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 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, and SADELAIN 3 disclose this difference.
The teachings of SADELAIN, BENSUSSAN, 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 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.
Response to Arguments
On p. 13 of the reply of 06/05/2026, Applicant argues that “the amended claims are unobvious over SADELAIN, in view of BENSUSSAN, SADELAIN 2, and SADELAIN 3. Therefore, Applicant submits that the amended claims are patentably distinct from the claims 1 - 24 of U.S. Patent No. 10,654,928 in view of SADELAIN, BENSUSSAN, SADELAIN 2, and SADELAIN 3, and from the claims 1 - 36 of U.S. Patent No. 10,730,941 in view of SADELAIN, BENSUSSAN, SADELAIN 2, and SADELAIN 3.”
However, the amended claims are rendered obvious over SADELAIN in view of BENSUSSAN and SADELAIN in view of BENSUSSAN and SADELAIN 3 as discussed above. Thus, the claims are rejected on the ground of nonstatutory double patenting rejections over the patented claims above in view of SADELAIN, BENSUSSAN, and SADELAIN 3.
Conclusion
Claims 126 – 127, 129 – 130, 134 – 138, and 140 – 145 are rejected.
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 Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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