DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. The Applicant's submission filed on 02/25/2026 has been entered.
The claim listing filed on July 17, 2025 is acknowledged.
Claims 2, 3, and 8-11 are canceled.
Claims 1, 4-7, and 12-20 are pending and currently under investigation.
Claim 1 is an independent claim.
The Applicant has requested in the Remarks filed 02/25/2026 that the nonstatutory double patenting rejections (NSDP) over the claims of co-pending Application Nos. 18/478,247, 18/547,748, 18/719,814 set forth in the Office Action mailed on 08/25/2026 be held in abeyance until the claims are otherwise allowable. It is also noted that the Applicant failed to respond to the 9 other NSDP rejections.
Thus, in view of this response, the anticipation-type NSDP rejections to claims 1, 4-7, and 12-20 are maintained for the reasons of record.
The Applicant’s arguments, see pages 5-7 of the Remarks filed 02/25/2026, with respect to the rejection(s) of claim(s) 1, 4-7, and 13-18 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of a newly found prior art reference (MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424) for the reasons set for the in the rejection under 35 U.S.C. § 103 below.
Priority
The instant Application is a 371 of PCT/US2020/046439 filed 08/14/2020 which claims domestic benefit to provisional U.S. Application No. 62/888,055 filed on 08/16/2019.
Claim Objections
Claims 13, 19, and 20 are objected to because they do not end in a period. It is noted that each claim must begin with a capital letter and end with a period. See MPEP 608.01(m). Appropriate correction is required.
Claim Rejections - 35 USC § 112
Written Description
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 13 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to a method of suppressing alloreactive or autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of a Treg cell to suppress CD83-expressing alloreactive or autoreactive lymphocytes, wherein the Treg cell is genetically modified to express a CAR polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the costimulatory signaling region comprises the cytoplasmic domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40,PD-1, ICOS, lymphocyte function- associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and any combination thereof.
The Applicant has only disclosed CARs comprising up to two costimulatory domains (e.g. see Figure 1A; Tables 2 and 3; and [0212]).
When given the broadest reasonable interpretation in light of specification, the cytoplasmic domain of the instant invention are defined broadly to be any cytoplasmic domain that comprises one or more costimulatory molecules.
It is noted that the claims allow for the CAR to comprise more than two costimulatory domains.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The art (Weinkove et al. 2019 (Clin Transl Immunol, 8(e1049), 1-14) does not teach CARs with more than two costimulatory domains (e.g. see Figures 3A-E).
As noted above, the Applicant has only disclosed CARs comprising up to two costimulatory domains. Such a disclosure does not serve to provide sufficient written description of the claimed genera of cytoplasmic domains that encompass those that may comprises more than two costimulatory molecules. In view of the art which also does not teach CARs with more than two costimulatory domains, there is insufficient written description for the breadth of cytoplasmic domains as currently claimed.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of cytoplasmic domains as encompassed by the claims at the time the instant application was filed.
Amending claim 13 to recite “wherein the costimulatory signaling region comprises the cytoplasmic domain of one or two costimulatory molecules selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40,PD-1, ICOS, lymphocyte function- associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3” would obviate this part of the rejection.
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 1, 4-7, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424, an IDS reference filed 05/02/2022) in view of Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), Diehl et al. 2013 (WO2013006505, an IDS reference filed May 2, 2022), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022).
Claim 1 is drawn to a method of suppressing alloreactive or autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell to suppress CD83-expressing alloreactive or autoreactive lymphocytes, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, thereby suppressing CD83-expressing alloreactive donor cells in the subject; wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83;wherein the anti-CD83 scFv comprises a variable heavy (VH) domain having CDR1,CDR2 and CDR3 sequences and a variable light (VL) domain having CDR1, CDR2 and CDR3 sequences; wherein the CDR1 sequence of the VH domain comprises the amino acid sequence GFSITTGGYWWT (SEQ ID NO:1), CDR2 sequence of the VH domain comprises the amin oacid sequence GYIFSSGNTNYNPSIKS (SEQ ID NO:2), CDR3 sequence of the VH domain comprises the amino acid sequence CARAYGKLGFDY (SEQ ID NO:3), CDR1 sequence of the VL comprises the amino acid sequence TLSSQHSTYTIG (SEQ ID NO:4), CDR2 sequence of the VL domain comprises the amino acid sequence VNSDGSHSKGD (SEQ ID NO:5), and CDR3 sequence of the VL domain comprises the amino acid sequence GSSDSSGYV (SEQ ID NO:6), and wherein the subject is the recipient of transplant donor cells that are not HLA matched to the subject.
Dependent claim 4 limits the transplant donor cells to those that have less than 3, 4, 5, or 6 HLA-matched markers as the subject.
Dependent claim 5 limits the subject to that which has not received an immunosuppressant.
Dependent claim 6 limits the subject that which has an autoimmune disease.
Dependent claim 7 limits the alloreactive or autoreactive lymphocytes to T lymphocytes expressing CD83.
Dependent claim 14 limits the CAR polypeptide to that which is defined by the formula: SP-CD83-HG-TM-CSR-ISD or SP-CD83-HG-TM-ISD-CSR, wherein "SP" represents a signal peptide, wherein "CD83" represents a CD83-binding region, wherein "HG" represents an optional hinge domain, wherein "TM" represents a transmembrane domain, wherein "CSR" represents a co-stimulatory signaling region, wherein "ISD" represents an intracellular signaling domain, and wherein "-" represents a bivalent linker.
Dependent claim 15 limits the intracellular signaling domain to that which comprises a CD3 zeta (CD3𝞯) signaling domain.
Dependent claim 16 limits the donor cells to bone marrow cells comprising alloreactive T-cells, dendritic cells, or a combination thereof.
MacDonald et al. teach that adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host disease (GVHD) (e.g. see Abstract).
MacDonald et al. also teach a method of treating GVHD in a subject, the method comprising administering to the subject an effective amount of an antigen-specific regulatory T (Treg) cell, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a scFv-based antigen binding domain, a transmembrane domain, a CD3𝞯 intracellular signaling domain, and a co-stimulatory signaling region, and wherein the subject is the recipient of transplant donor cells (PBMCs) (e.g. see page 1422, right column, last paragraph; and Figure 1A). MacDonald et al. also teach that the antigen-specific CAR T regs are superior to polyclonal Tregs at preventing xenogeneic GVHD mediated by HLA-A2+ T cells (e.g. see paragraph spanning pages 1417 and 1418).
MacDonald et al. also teach that the specificity of human Tregs can be redirected toward a transplant-relevant antigen using a CAR (e.g. see page 1419, right column, third paragraph). Expression of an A2-CAR in Tregs enables antigen-specific activation and proliferation that is stronger than that stimulated by the endogenous TCR. Despite this relatively strong CAR-mediated activation and/or expansion, A2-CAR Tregs retained high expression of FOXP3 and other Treg markers and demethylation of the TSDR, had preserved suppression function in vitro, and did not have significant cytolytic activity. Adoptive transfer experiments revealed that A2-CAR Tregs that received in vivo CAR stimulation were markedly better than Tregs that only received stimulation through the endogenous TCR at preventing xenogeneic GVHD. Collectively, these data show that human Tregs redirected to recognize a specific alloantigen are more effective at preventing GVHD than Tregs not thus directed, supporting the rationale for CAR modification of Tregs as a means of generating therapeutic antigen-specific cells (e.g. see page 1419, right column, third paragraph).
MacDonald et al. also teach the feasibility of redirecting Tregs to a transplant-relevant antigen with a CAR and that CAR Tregs remain functionally and phenotypically stable in vitro and in vivo (e.g. see page 1421, right column, first paragraph). In the setting of transplantation, a bank of HLA-specific CARs could be used to overcome all of the limitations of current strategies to generate alloantigen-specific Tregs. These findings also set the stage for using CARs to redirect the antigen specificity of Tregs toward auto- and/or tissue-specific antigens for therapeutic use in autoimmunity (e.g. see page 1421, right column, first paragraph).
The teachings of MacDonald et al. differ from this instant invention by not teaching that (1) the method is specifically for CD83-expressing alloreactive or autoreactive lymphocytes, (2) the antigen-specific CAR T cells comprise an anti-CD83 antigen binding domain comprising SEQ ID NOs: 1-6, or (3) the transplant donor cells are not HLA matched to the subject.
Ju et al. teach that CD83 is important for immune function (e.g. see page 4621, left column, under discussion) and that activated T cells upregulate surface CD83 expression transiently (e.g. see page 4623, left column). Both human CD4+ and CD8+ T cells increase surface CD83 expression in vitro after nonspecific PHA stimulation, specific CD2/CD3/CD28 activation, or in response to allogeneic stimulation in a mixed leukocyte reaction (MLR). CD83 expression occurred relatively early (within hours) and decreased quickly (e.g. see page 4623, left and right columns). Ju et al. also teach that CD83 is expressed on in vivo activated human T cells in clinical allogeneic hematopoietic cell transplant (AlloHCT) patients (e.g. see page 4621, left column, second paragraph). Ju et al. also teach that their previous data showed that anti-hCD83 Abs depleted activated DC and were immunosuppressive, preventing T cell responses in MLR and GVHD in a xenogeneic model (e.g. see page 4623, right column). Ju et al. further teach that their work, showing that CD83 is neither present nor expressed to any great extent on unactivated human natural Treg, suggests that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (e.g. see page 4623, right column).
Diehl et al. teach that CD83 is a well-conserved type-1 membrane protein of the Ig superfamily found primarily on the surface of mature dendritic cells (DCs) (e.g. see [0269]). Diehl et al. also teach a method for treating or preventing an autoimmune disease in an individual comprising administering to the individual an effective amount of an anti-CD83 agonist antibody. (e.g. see claim 1). Diehl et al. specifically teach that an anti-human CD83 antibody, 60B10, which comprises the same CDRs as the CD83 antigen binding domain of the instantly claimed CAR (H-CDRs1-3 as SEQ ID NOs: 1-3 and L-CDRs1-3 as SEQ ID NOs: 4-6 as recited in instant claim 1; and sequence alignments below), can be applied in the method (e.g. see sequences on pages 101-104 and claims 18, 19, 23-27, and 29).
VH alignment (CDRs are bolded and underlined):
Query Match 100.0%; Score 648; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLKESGPGLVKPSQSLSLTCSVTGFSITTGGYWWTWIRQFPGQKLEWMGYIFSSGNTN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLKESGPGLVKPSQSLSLTCSVTGFSITTGGYWWTWIRQFPGQKLEWMGYIFSSGNTN 60
Qy 61 YNPSIKSRISITRDTSKNQFFLQLNSVTTEGDTARYYCARAYGKLGFDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YNPSIKSRISITRDTSKNQFFLQLNSVTTEGDTARYYCARAYGKLGFDYWGQGTLVTVSS 120
VL alignment (CDRs are bolded and underlined):
Query Match 100.0%; Score 587; Length 111;
Best Local Similarity 100.0%;
Matches 111; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QPVLTQSPSASASLGNSVKITCTLSSQHSTYTIGWYQQHPDKAPKYVMYVNSDGSHSKGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QPVLTQSPSASASLGNSVKITCTLSSQHSTYTIGWYQQHPDKAPKYVMYVNSDGSHSKGD 60
Qy 61 GIPDRFSGSSSGAHRYLSISNIQPEDEADYFCGSSDSSGYVFGSGTQLTVL 111
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GIPDRFSGSSSGAHRYLSISNIQPEDEADYFCGSSDSSGYVFGSGTQLTVL 111
Meyer and Negrin teach that human leukocyte antigens (HLA), also broadly referred to as Major histocompatibility complex (MHC) antigens, are protein molecules expressed on the surface of a cell that can confer an antigenic identity to that cell (e.g. see [0066]). HLA/MHC antigens are target molecules that can be recognized by T cells and natural killer (NK) cells as being derived from the same source of hematopoietic stem cells as the immune effector cells ("self”), or as being derived from another source of hematopoietic cells ("non-self). HLA is implicated in GVHD and can occur even if the donor and recipient are HLA-matched (e.g. see [0066] and [0069]). HLA matched refers to a donor-recipient pair for which all six of the six HLA-A, HLA-B, and HLA-DR alleles are matched between donor and recipient. HLA mismatched refers to a donor-recipient pair for which at least one HLA antigen is mismatched between the donor and recipient (e.g. see [0069]). A set of HLA alleles inherited from one parent forms a haplotype and identifying a patient's haplotypes can help predict the probability of finding matching donors (e.g. see [0070]).
Meyer and Negrin also teach a method of treating a human subject in need thereof, comprising administering to said human subject: a) a population of hematopoietic stem and progenitor cells (HSPCs); b) a population of cells comprising regulatory T cells (Tregs); and c) a population of conventional T cells (Tcons) (e.g. see [0004]). Cell populations can be obtained from one or more donors (e.g. see [0077]). Furthermore, a donor and a recipient can be allogenic, HLA matched, HLA mismatched, e.g. mismatched as 1, 2, 3, 4, 5, or 6 of the major HLA alleles, or haploidentical (e.g. see [0079]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified MacDonald et al. to incorporate the teachings of Ju et al., Diehl et al., and Meyer and Negrin to include that (1) the method is specifically for CD83-expressing alloreactive or autoreactive lymphocytes, (2) the antigen-specific CAR T cells comprise an anti-CD83 antigen binding domain comprising SEQ ID NOs: 1-6, that (3) the transplant donor cells are not HLA matched to the subject. This is because CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.).
Given that adoptive immunotherapy with Tregs be redirected toward a transplant-relevant antigen using a CAR is a promising treatment for allograft rejection and graft-versus-host disease (GVHD) (MacDonald et al.) and CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.); it would have been obvious to a skilled artisan to modify the method of treating GVHD in a subject with an antigen-specific scFv-based CAR T reg cell as taught by MacDonald et al. to specifically target CD83-expressing allo/autoreactive T cells with an anti-CD83 scFv-based CAR T reg with a reasonable expectation of success. In view of the art, skilled artisan would have reasonably expected that an anti-CD83 scFv-based CAR T reg would selectively suppress CD83-expressing allo/autoreactive T cells thereby allowing for Treg alloimmune regulation after transplantation.
Regarding the anti-CD83 scFv comprising instant SEQ ID NOs: 1-6, given that the antigen binding domain of the CAR T reg taught by MacDonald et al. comprises an scFv on an antigen-specific antibody, it would have been obvious to a skilled artisan to specifically use the anti-CD83 antibody taught by Diehl et al. as the template for constructing the anti-CD83 scFv of the anti with nti-CD83 scFv-based CAR T reg with a reasonable expectation of success. A skilled artisan would have readily recognized that this is common practice in the art of constructing an CAR scFv-based antigen binding domain with a desired target in mind.
Regarding the claim limitations “wherein the subject is the recipient of transplant donor cells that are not HLA matched to the subject” (claim 1) and “wherein the transplant donor cells have less than 3, 4, 5, or 6 HLA-matched markers as the subject” (claim 4); it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified MacDonald et al.’s method to include donor cells that are not HLA matched to the subject.
Given that HLA is implicated in GVHD (Meyer and Negrin) it would have been obvious to a skilled artisan to include HLA mismatched donor cells in MacDonald et al.’s methods in order to increase the pool of donors available to the recipient with a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 13 is rejected under 35 U.S.C. 103 as being unpatentable over MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424) in view of Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), Diehl et al. 2013 (WO2013006505, an IDS reference filed May 2, 2022), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022), as applied to claim 1, and further in view of Weinkove et al. 2019 (Clin Transl Immunol, 8(e1049), 1-14).
Dependent claim 13 limits the costimulatory signaling region to that which comprises the cytoplasmic domain of 4-1BB.
The combined teachings of MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin pertaining to claim 1 and the rationale for combining them is outlined in the 103 rejection above.
The combined reference teachings differ from the instant invention only by not teaching that the costimulatory signaling region of the CAR comprises the cytoplasmic domain of 4-1BB in place of CD28.
Weinkove et al. teach that CD28 and 4-1BB are the most frequently employed costimulatory domains in CARs (e.g. see page 9, right column, second paragraph). Weinkove et al. also teach that 4-1BB leads to prolonged T cell division when compared to CD28 and in clinical trials, second-generation CARs incorporating a 4-1BB costimulatory domain appear to favor longer CAR T cell persistence than those incorporating a CD28 domain (e.g. see page 5, right column, third paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin, as applied to claim 1, to incorporate the teachings of Weinkove et al. to include that the costimulatory signaling region of the CAR comprises the cytoplasmic domain of 4-1BB in place of CD28. This is because 41BB-based CARs may be more effective for the longer term CAR T cell persistence.
Given that CD28 and 4-1BB are the most frequently employed costimulatory domains in CARs and second-generation CARs incorporating a 4-1BB costimulatory domain appear to favor longer CAR T cell persistence than those incorporating a CD28 domain; it would have been obvious to a skilled artisan, with the desire to increase the persistence of the anti-CD83 CAR T reg taught by MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin, to experiment with substituting the CD28 costimulatory domain of the CAR for a 4-1BB costimulatory domain with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424) in view of Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), Diehl et al. 2013 (WO2013006505, an IDS reference filed May 2, 2022), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022), as applied to claim 1, and further in view of Fesnak et al. 2016 (Nat Rev Cancer 16, 566–581 (2016), a reference of record).
Dependent claim 17 limits the method to that which further comprises administering to the subject a checkpoint inhibitor.
Dependent claim 18 limits the checkpoint inhibitor to that which comprises an anti- PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
The combined teachings of MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin pertaining to claim 1 and the rationale for combining them is outlined in the 103 rejection above.
The combined reference teachings differ from the instant invention only by not teaching that the method further comprises administering a checkpoint inhibitor or that the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
Fesnak et al. that CAR T cells can be engineered to be resistant to immunosuppression (armored CARs) by genetically modifying them to no longer express various immune checkpoint molecules (for example, cytotoxic T lymphocyte-associated antigen 4 (CTLA4) or programmed cell death protein 1 (PD1)), with an immune checkpoint switch receptor, or by administering a monoclonal antibody that blocks immune checkpoint signaling (e.g. see page 574, Figure 5d).
The addition of programmed cell death protein 1 (PD1; also known as PDCD1) monoclonal antibody has been shown to enhance the function of CAR T cells in preclinical models, suggesting that, like endogenous immune cells, engineered T cells are subject to tumour immune suppression through immune checkpoints and would become more effective if disinhibited in this way (e.g. see page 576, left column, under Avoiding tumour suppression and escape).
Many groups are now attempting to generate CAR T cells resistant to PD1–PD1 ligand 1 (PDL1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)–CD80/CD86 signaling. Future T cell therapies are likely to incorporate multiple forms of immune checkpoint blockade to further enhance efficacy (e.g. see page 576, left column, under Avoiding tumour suppression and escape).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin, as applied to claim 1, to incorporate the teachings of Fesnak et al.to include the administration of a checkpoint inhibitor comprising an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
Immune checkpoint blockade can enhance the efficacy of T cell therapies, such as CAR T cells, and many groups are now attempting to generate CAR T cells resistant to PD1–PD1 ligand 1 (PDL1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)–CD80/CD86 signaling. For example, the addition of programmed cell death protein 1 (PD1; also known as PDCD1) monoclonal antibody has been shown to enhance the function of CAR T cells in preclinical models (e.g. see Fesnak et al. page 576, left column, under Avoiding tumour suppression and escape).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught by MacDonald et al. in view of Ju et al., Diehl et al., and Meyer and Negrin to further to include administering Fesnak et al.’s checkpoint inhibitors, such as anti-PD-1, PD-L1, and/or CTLA-4 antibodies with a reasonable expectation success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
As noted above, the Applicant requested that the NSDP rejections over the claims in co-pending Application Nos. 18/478,247, 18/547,748, 18/719,814 as set forth in the Office Action mailed 08/25/2026 be held in abeyance until the claims are otherwise allowable. It was also noted that the Applicant failed to respond to the 9 other NSDP rejections. Thus, the anticipation-type NSDP rejections to claims 1, 4-7, and 12-20 set forth in the Office Action mailed 08/25/2026 are maintained for the reasons of record.
It is noted that Application No. 16/969,056 (the ‘056 Application) matured to U.S. Patent No. 12,492,254.
Claims 1, 4-7, 12-16, 19, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of copending Application No. 18/547,748 (the ‘748 Application) in view of MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424), Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022).
The instant claims are drawn to a method of suppressing alloreactive or autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell to suppress but not kill CD83-expressing alloreactive or autoreactive lymphocytes, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, thereby suppressing alloreactive donor cells in the subject; wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83; wherein the anti-CD83 scFv comprises VH-CRDs1-3 and VL-CDRs1-3 comprising SEQ ID NOs: 1-6, respectively.
The claim in the ‘748 Application is drawn to a CAR polypeptide that identical to the instantly claimed CAR.
The claim in the ‘748 Application differs from the instant invention by not reciting that a Treg expresses the CAR or that the anti-CD83 CAR Treg is used in a method of suppressing alloreactive or autoreactive lymphocytes.
The teachings of MacDonald et al., Ju et al., and Meyer and Negrin are discussed in the 103 rejections above.
It would be obvious to one of ordinary skill in the art to modify the claim of the ‘748 Application to incorporate the teachings of MacDonald et al., Ju et al., and Meyer and Negrin to include that a Treg expresses the CAR and that the anti-CD83 CAR Treg is used in a method of suppressing alloreactive or autoreactive lymphocytes. This is because CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.).
Given that adoptive immunotherapy with Tregs be redirected toward a transplant-relevant antigen using a CAR is a promising treatment for allograft rejection and graft-versus-host disease (GVHD) (MacDonald et al.) and CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.); it would be obvious to a skilled artisan to apply the anti-CD83 CAR taught by the ‘748 Application and use it a Treg and to use the anti-CD83 CAR Treg in a method of suppressing alloreactive or autoreactive lymphocytes with a reasonable expectation of success. In view of the art, skilled artisan would reasonably expect that an anti-CD83 CAR T reg would selectively suppress CD83-expressing allo/autoreactive T cells thereby allowing for Treg alloimmune regulation after transplantation.
Regarding the claim limitations “wherein the subject is the recipient of transplant donor cells that are not HLA matched to the subject” (claim 1) and “wherein the transplant donor cells have less than 3, 4, 5, or 6 HLA-matched markers as the subject” (claim 4); it would be obvious to one of ordinary skill in the art to further include in the method of suppressing alloreactive or autoreactive lymphocytes that the donor cells that are not HLA matched to the subject.
Given that HLA is implicated in GVHD (Meyer and Negrin); it would be obvious to a skilled artisan to include HLA mismatched donor cells in the method in order to increase the pool of donors available to the recipient with a reasonable expectation of success.
Therefore, the claims in the ‘748 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4-7, 12-16, 19, and 20 are (provisionally) rejected on the ground of nonstatutory double patenting as being unpatentable over the following co-pending applications and Patent in view of MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424), Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022) for similar reasons as discussed in the provisional nonstatutory double patenting rejection over the ‘748 Application above.
The instant claims are drawn to a method of suppressing alloreactive or autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell to suppress but not kill CD83-expressing alloreactive or autoreactive lymphocytes, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, thereby suppressing alloreactive donor cells in the subject; wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83; wherein the anti-CD83 scFv comprises VH-CRDs1-3 and VL-CDRs1-3 comprising SEQ ID NOs: 1-6, respectively.
Claims 24-28 of copending Application No. 18/415,542 (claims are drawn to a population of immune cells, which are genetically modified to express a first chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain and a second CAR polypeptide comprising a CD19 antigen binding domain, wherein the population of immune cells selectively inhibit autoreactive B lymphocytes that express both CD83 and CD19, wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83, and wherein the anti-CD83 scFv comprises the instantly claimed CDRs).
Claims 5-7 of copending Application No. 17/759,271 (claims are drawn to a bi-specific genetically modified immune cell, comprising a first antigen binding moiety that is specific to CD83 and a second antigen binding moiety that is specific to interleukin 6 receptor (IL-6R), wherein the first antigen binding moiety specific to CD83 is a single chain variable fragment (scFv) that binds CD83, and wherein the anti-CD83 scFv comprises the same CDRs as the instant claims).
Claims 7-10 of copending Application No. 17/757,475 (claims drawn to a method for producing regulatory T (Treg) cells comprising transducing the activated Treg cells with a viral vector encoding a CAR polypeptide identical to the instantly claimed CD83 CAR).
Claims 1-10 of Patent No. 12,492,254 (App. No.16/969,056) (claims are drawn to a CD83 CAR comprising the instantly claimed CDRs for the anti-CD84 scFv and a Treg cell comprising a vector comprising an isolated nucleic acid sequence encoding the CAR).
Claim 19 of copending Application No. 18/719,814 (claim drawn to a method of treating or reducing the risk of developing an alloimmune condition or an autoimmune condition in a subject in need thereof, the method comprising (a) measuring CD83 in a population of immune cells from the subject, and (b) administering to the subject a CD83-targeted therapeutic; wherein the CD83-targeted therapeutic is an antibody that binds CD83, an antigen-binding antibody fragment that binds CD83, or an antibody-like construct that binds CD83, or an immune effector cell genetically modified to express a chimeric antigen receptor (CAR) polypeptide that selectively binds CD83).
Claims 3 and 4 of copending Application No. 18/856,207 (claim drawn to a dual-chimeric antigen receptor (CAR)-T cell, comprising an immune effector cell genetically modified to express a first CAR polypeptide that selectively binds CD83, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
Claims 9-11 of copending Application No. 18/565,831 (claim drawn to a method for treating ischemic stroke or acute coronary syndrome in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
Claims 1, 2, 5-12, 14, 15, and 17 of copending Application No. 17/635,111 (claim drawn to a method of treating acute myeloid leukemia (AML) in a subject, the method comprising administering to the subject an effective amount of an immune effector cell genetically modified to express a plurality of a single chimeric antigen receptor (CAR) polypeptide, wherein the CAR polypeptide comprises a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
The claims listed above differ from the instant invention by not reciting that a Treg expresses the CAR or that the anti-CD83 CAR Treg is used in a method of suppressing alloreactive or autoreactive lymphocytes.
The teachings of MacDonald et al., Ju et al., and Meyer and Negrin are discussed in the 103 rejections above.
It would be obvious to one of ordinary skill in the art to modify the claims in the above Applications and Patent to incorporate the teachings of MacDonald et al., Ju et al., and Meyer and Negrin to include that a Treg expresses the CAR and that the anti-CD83 CAR Treg is used in a method of suppressing alloreactive or autoreactive lymphocytes. This is because CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.).
Given that adoptive immunotherapy with Tregs be redirected toward a transplant-relevant antigen using a CAR is a promising treatment for allograft rejection and graft-versus-host disease (GVHD) (MacDonald et al.) and CD83 is well known to be upregulated on activated T lymphocytes and CD83 is neither present nor expressed to any great extent on unactivated human natural Treg suggesting that anti-CD83 immunotherapy could encourage Treg alloimmune regulation after transplantation (Ju et al.); it would be obvious to a skilled artisan to apply the anti-CD83 CAR taught by the above Applications and Patent and use it a Treg and to use the anti-CD83 CAR Treg in a method of suppressing alloreactive or autoreactive lymphocytes with a reasonable expectation of success. In view of the art, skilled artisan would reasonably expect that an anti-CD83 CAR T reg would selectively suppress CD83-expressing allo/autoreactive T cells thereby allowing for Treg alloimmune regulation after transplantation.
Regarding the claim limitations “wherein the subject is the recipient of transplant donor cells that are not HLA matched to the subject” (claim 1) and “wherein the transplant donor cells have less than 3, 4, 5, or 6 HLA-matched markers as the subject” (claim 4); it would be obvious to one of ordinary skill in the art to further include in the method of suppressing alloreactive or autoreactive lymphocytes that the donor cells that are not HLA matched to the subject.
Given that HLA is implicated in GVHD (Meyer and Negrin); it would be obvious to a skilled artisan to include HLA mismatched donor cells in the method in order to increase the pool of donors available to the recipient with a reasonable expectation of success.
Therefore, the claims in the above Applications and Patent would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection to the claims in the co-pending Applications.
Claims 17 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of copending Application No. 18/547,748 (the ‘748 Application) in view of MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424), Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022), as applied to claim 1, and further in view of Fesnak et al. 2016 (Nat Rev Cancer 16, 566–581 (2016), a reference of record).
The combined teachings of the ‘748 Application in view of MacDonald et al., Ju et al., and Meyer and Negrin pertaining to claim 1 and the rationale for combining them is outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention only by not teaching that the method further comprises administering a checkpoint inhibitor or that the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
The teachings of Fesnak et al. are outline in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to have modify the combined teachings of the ‘748 Application in view of MacDonald et al., Ju et al., and Meyer and Negrin, as applied to claim 1, to incorporate the teachings of Fesnak et al.to include the administration of a checkpoint inhibitor comprising an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
Immune checkpoint blockade can enhance the efficacy of T cell therapies, such as CAR T cells, and many groups are now attempting to generate CAR T cells resistant to PD1–PD1 ligand 1 (PDL1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)–CD80/CD86 signaling. For example, the addition of programmed cell death protein 1 (PD1; also known as PDCD1) monoclonal antibody has been shown to enhance the function of CAR T cells in preclinical models (e.g. see Fesnak et al. page 576, left column, under Avoiding tumour suppression and escape).
Therefore, it would be obvious to one of ordinary skill in the art to modify the method taught by the ‘748 Application in view of MacDonald et al., Ju et al., and Meyer and Negrin to further to include administering Fesnak et al.’s checkpoint inhibitors, such as anti-PD-1, PD-L1, and/or CTLA-4 antibodies with a reasonable expectation success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘748 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 17 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following co-pending applications and Patent in view of MacDonald et al. 2016 (J Clin Invest.126(4):1413-1424), Ju et al. 2016 (J Immunol. 197(12), 4613-4625 a reference of record), and Meyer and Negrin 2019 (WO2019157158, an IDS reference filed May 2, 2022), as applied to claim 1, and further in view of Fesnak et al. 2016 (Nat Rev Cancer 16, 566–581 (2016), a reference of record).
The instant claims are drawn to a method of suppressing alloreactive or autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell to suppress but not kill CD83-expressing alloreactive or autoreactive lymphocytes, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, thereby suppressing alloreactive donor cells in the subject; wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83; wherein the anti-CD83 scFv comprises VH-CRDs1-3 and VL-CDRs1-3 comprising SEQ ID NOs: 1-6, respectively.
Claims 24-28 of copending Application No. 18/415,542 (claims are drawn to a population of immune cells, which are genetically modified to express a first chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain and a second CAR polypeptide comprising a CD19 antigen binding domain, wherein the population of immune cells selectively inhibit autoreactive B lymphocytes that express both CD83 and CD19, wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83, and wherein the anti-CD83 scFv comprises the instantly claimed CDRs).
Claims 5-7 of copending Application No. 17/759,271 (claims are drawn to a bi-specific genetically modified immune cell, comprising a first antigen binding moiety that is specific to CD83 and a second antigen binding moiety that is specific to interleukin 6 receptor (IL-6R), wherein the first antigen binding moiety specific to CD83 is a single chain variable fragment (scFv) that binds CD83, and wherein the anti-CD83 scFv comprises the same CDRs as the instant claims).
Claims 7-10 of copending Application No. 17/757,475 (claims drawn to a method for producing regulatory T (Treg) cells comprising transducing the activated Treg cells with a viral vector encoding a CAR polypeptide identical to the instantly claimed CD83 CAR).
Claims 1-10 of Patent No. 12,492,254 (App. No.16/969,056) (claims are drawn to a CD83 CAR comprising the instantly claimed CDRs for the anti-CD84 scFv and a Treg cell comprising a vector comprising an isolated nucleic acid sequence encoding the CAR).
Claim 19 of copending Application No. 18/719,814 (claim drawn to a method of treating or reducing the risk of developing an alloimmune condition or an autoimmune condition in a subject in need thereof, the method comprising (a) measuring CD83 in a population of immune cells from the subject, and (b) administering to the subject a CD83-targeted therapeutic; wherein the CD83-targeted therapeutic is an antibody that binds CD83, an antigen-binding antibody fragment that binds CD83, or an antibody-like construct that binds CD83, or an immune effector cell genetically modified to express a chimeric antigen receptor (CAR) polypeptide that selectively binds CD83).
Claims 3 and 4 of copending Application No. 18/856,207 (claim drawn to a dual-chimeric antigen receptor (CAR)-T cell, comprising an immune effector cell genetically modified to express a first CAR polypeptide that selectively binds CD83, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
Claims 9-11 of copending Application No. 18/565,831 (claim drawn to a method for treating ischemic stroke or acute coronary syndrome in a subject, the method comprising administering to the subject an effective amount of a regulatory T (Treg) cell, wherein the Treg cell is genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
Claims 1, 2, 5-12, 14, 15, and 17 of copending Application No. 17/635,111 (claim drawn to a method of treating acute myeloid leukemia (AML) in a subject, the method comprising administering to the subject an effective amount of an immune effector cell genetically modified to express a plurality of a single chimeric antigen receptor (CAR) polypeptide, wherein the CAR polypeptide comprises a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the anti-CD83 CAR comprises the instantly claimed CDRs).
The combined teachings of the above Applications and Patent in view of MacDonald et al., Ju et al., and Meyer and Negrin pertaining to claim 1 and the rationale for combining them is outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention only by not teaching that the method further comprises administering a checkpoint inhibitor or that the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
The teachings of Fesnak et al. are outline in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to have modify the combined teachings of the above Applications and Patent in view of MacDonald et al., Ju et al., and Meyer and Negrin, as applied to claim 1, to incorporate the teachings of Fesnak et al.to include the administration of a checkpoint inhibitor comprising an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.
Immune checkpoint blockade can enhance the efficacy of T cell therapies, such as CAR T cells, and many groups are now attempting to generate CAR T cells resistant to PD1–PD1 ligand 1 (PDL1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)–CD80/CD86 signaling. For example, the addition of programmed cell death protein 1 (PD1; also known as PDCD1) monoclonal antibody has been shown to enhance the function of CAR T cells in preclinical models (e.g. see Fesnak et al. page 576, left column, under Avoiding tumour suppression and escape).
Therefore, it would be obvious to one of ordinary skill in the art to modify the method taught by the above Applications and Patent in view of MacDonald et al., Ju et al., and Meyer and Negrin to further to include administering Fesnak et al.’s checkpoint inhibitors, such as anti-PD-1, PD-L1, and/or CTLA-4 antibodies with a reasonable expectation success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the above Applications and Patent would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection to the claims in the co-pending Applications.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Grace H. Lunde whose telephone number is (703)756-1851. The examiner can normally be reached Monday - Thursday 6:00 a.m. - 3:00 p.m. (EST).
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/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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