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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/27/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of species: SEQ ID NOs: 1-6 and 19-20, 4-1BB, SP-CD83-HG-TM-CSR-ISD, anti-PD-1 antibody, acute myeloid leukemia, a subject not having been treated with hematopoietic stem cell transplantation, in the reply filed 04/30/2025 is acknowledged.
Claims 14-15 are withdrawn from consideration pursuant to 37 CFR1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 04/30/2025.
Claims 1-2, 5-12 and 17 are now under consideration in the instant Office Action.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 5-12, and 17 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.
Instant claims 1-2, 5-12, and 17 have been amended to recite “an immune effector cell genetically modified to express a plurality of a single chimeric antigen receptor (CAR) polypeptide”. It is unclear what is intended by the recitation of a “plurality of a single chimeric antigen receptor” and the instant specification does not provide sufficient disclosure of such terminology. It is unclear if the plurality of CAR polypeptides are of the same structure (binding to CD83), or if these structures may vary.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 5-12 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Dranoff et al. (WO 2017/149515 A1, in IDS filed 05/02/2022), in view of Diehl et al. (WO 2013/006505 A1, in IDS filed 05/02/2022) and Fesnak et al. 2016 (in PTO-892 filed 06/03/2025).
Dranoff discusses the advantages of immunotherapy with cells expressing CARs, particularly their ability to invoke a rapid and sustained immune response (e.g. see page 1, lines 17-20). Dranoff discloses a cell, which may be a regulatory T cell (e.g. page 14, lines 8-10), that includes a first CAR and a second CAR (e.g. see page 2, lines 21-23). Dranoff teaches that the present disclosure relates generally to the use of immune effector cells (e.g., T cells, NK cells) engineered to express a Chimeric Antigen Receptor (CAR) that targets B cells and engineered to express a CAR that targets cells expressing a tumor antigen other than a B- Cell antigen, e.g., cells expressing a solid tumor antigen, myeloid tumor antigen, or cells expressing an antigen of a hematological tumor not of B-Cell origin, to treat a disease associated with expression of the tumor antigen (e.g. see page 1, lines 9-14). Dranoff also teaches that the CARs can target CD83 (e.g. see page 3, lines 1-3).
Dranoff teaches chimeric antigen receptors as “CARs”, which refer to recombinant polypeptides comprising at least an extracellular antigen binding domain, a transmembrane domain, and a cytoplasmic signaling domain (also referred to as an intracellular signaling domain) comprising a functional signaling domain derived from a costimulatory molecule, such as 4-1BB, CD27, ICOS, and/or CD28 (e.g. see page 21, lines 8-22). The CAR may further comprise a leader sequence (or signal peptide) at the N-terminus of the extracellular antigen binding domain, wherein the leader sequence is optionally cleaved from the antigen recognition domain (e.g., a scFv) during cellular processing and localization of the CAR to the cellular membrane (e.g. see page 22, lines 5-9 and SEQ ID NO: 2 on table 1 on page 49). Furthermore, Dranoff discloses CARs that are comprised, from N- to C-terminus, a signal peptide (or leader), an extracellular antigen binding domain, a hinge domain, a transmembrane domain, a costimulatory signaling region, and an intracellular signaling domain comprising a CD3 zeta signaling domain (e.g. see CAR CTL019 (SEQ ID NO: 281) in table 10 on page 148 for example).
In addition to mAb therapy, immunotherapy with cells expressing CARs is advantageous given the ability of CARs to invoke a rapid and sustained immune response (e.g. see Dranoff page 1, lines 17-20). Dranoff discloses the design of cells, such as regulatory T cells, that express CARs that may target CD83 (e.g. see Dranoff page 2, lines 21-23; page 14, lines 8-10; and page 3, lines 1-3). These CARs comprise at least an extracellular antigen binding domain, a transmembrane domain, and a cytoplasmic signaling domain (also referred to as an intracellular signaling domain). Dranoff also teaches that the CARs can be used in a treatment against myeloid malignancies, in particular acute myeloid leukemia (e.g. see Dranoff see page 14, lines 26-27). Dranoff teaches that the subject has not undergone a previous stem cell transplant (e.g. see Dranoff page 260, line 1).
However, Dranoff does not teach the CDR sequences for the CD83 antigen-binding domain. Diehl et al. remedies this deficiency.
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, and SEQ ID NOs: 19-20 as the heavy and light chain variable regions as recited in instant claims 4-7), can be applied in the method (e.g. see sequences on pages 101-104 and claims 18, 19, 23-27, and 29). Diehl et al. teach that the CDR sequences in some embodiments are used in an antigen-binding fragment, for example, a fragment selected from the group consisting of Fab, Fab'-SH, Fv, scFv, and (Fab')2 fragments (e.g. see [0010]).
However, Dranoff and Diehl et al. do not teach additional therapeutics further comprising checkpoint inhibitors. Fesnak et al. remedies this deficiency.
Fesnak et al. teaches 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). 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).
Therefore, it would have been obvious to an artisan of ordinary skill to modify the teachings of Dranoff and Diehl et al., to genetically modify the Treg cells to express Dranoff’s anti-CD83 CAR comprising an extracellular antigen binding domain as an scFv of Diehl et al.’s anti-CD83 antibody, 60B10, and apply them in the method to treat myeloid malignancies in lymphocytes, such as Diehl et al.’s DCs and 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. Given the known advantages of using Tregs in conjunction with immunosuppressive drugs, such as checkpoint inhibitors to treat a myeloid malignancy such as acute myeloid leukemia, it would have been obvious to a skilled artisan to experiment with using Fesnak et al.’s checkpoint inhibitors, including anti-PD-1, PD-L1, and/or CTLA-4 antibodies, in order to enhance the efficacy of Dranoff’s CAR polypeptide therapies.
Therefore, claims 1-2, 5-12, and 17 are rejected as obvious over Dranoff et al., Diehl et al., and Fesnak et al.
Response to Arguments
Applicant's arguments filed 01/07/2026 have been fully considered but they are not persuasive.
Applicant argues “Dranoff does not teach or suggest that a CAR-T cell expressing only an anti-CD83 CAR would be able to treat AML as claimed.” This is not found persuasive.
Looking to the rejection supra, Dranoff et al. teaches a cell, which may be a regulatory T cell (e.g. page 14, lines 8-10), that includes a first CAR and a second CAR (e.g. see page 2, lines 21-23). Dranoff teaches that the present disclosure relates generally to the use of immune effector cells (e.g., T cells, NK cells) engineered to express a Chimeric Antigen Receptor (CAR) that targets B cells and engineered to express a CAR that targets cells expressing a tumor antigen other than a B- Cell antigen, e.g., cells expressing a solid tumor antigen, myeloid tumor antigen, or cells expressing an antigen of a hematological tumor not of B-Cell origin, to treat a disease associated with expression of the tumor antigen (e.g. see page 1, lines 9-14). Dranoff also teaches that the CARs can target CD83 (e.g. see page 3, lines 1-3). In addition to mAb therapy, Dranoff et al. teaches how immunotherapy with cells expressing CARs is advantageous given the ability of CARs to invoke a rapid and sustained immune response (e.g. see Dranoff page 1, lines 17-20). Dranoff also teaches that the CARs can be used in a treatment against myeloid malignancies, in particular acute myeloid leukemia (e.g. see Dranoff see page 14, lines 26-27).
At the time of filing, Dranoff discloses the benefits of using an anti-CD83 CAR T-cell alone as a treatment against acute myeloid leukemia, and also teaches that combination therapies including immunotherapies would be additionally advantageous. The abstract of Dranoff et al. also teaches that “the invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein by administration of a cell comprising a chimeric antigen receptor that binds a B-Cell antigen and a chimeric antigen receptor which binds a tumor antigen.” As such, Dranoff et al. sufficiently teaches an invention capable of treating acute myeloid leukemia as claimed.
Applicant argues that the 103 rejection which states that “the combination of Dranoff, Diehl, and Fesnak do not teach that CD83 CAR-T cells can treat AML with a reasonable expectation of success” is improper due to the discovery of unexpected results, as well as “none of the cited references overcame the primary deficiency of Dranoff, i.e. providing a reasonable expectation of success in treating AML with an anti-CD83 CAR alone.” This is not found persuasive.
The evidence of unexpected results must be commensurate in scope with the claimed invention (see MPEP §716.02(d)).
There is no unexpected result since the prior art already taught that the use of an anti-CD83 CAR T-cell would be advantageous in treating acute myeloid leukemia, especially when used in addition to other immunotherapies, as shown in Dranoff et al. Please see MPEP 7106.0 (a), I, which states that “a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (Evidence showing greater than additive sweetness resulting from the claimed mixture of saccharin and L-aspartyl-L-phenylalanine was not sufficient to outweigh the evidence of obviousness because the teachings of the prior art lead to a general expectation of greater than additive sweetening effects when using mixtures of synthetic sweeteners.).“ The evidence provided by applicant of unexpected results falls into the additive sweetness combination example and does not show a greater than expected outcome and therefore, the instant invention is obvious over the combination of references. Additionally, the combination of references teaches every element of the instant invention so it is unclear how the same anti-CD83 CAR T-cell taught in the prior art would behave in a different manner than the one that is instantly claimed by Applicant.
Applicant argues that “one of ordinary skill in the art reading Dranoff would reasonably assume that an anti-CD83 CAR would have no therapeutic benefit if it did not also include a CAR binding a tumor antigen. Since none of the cited references overcome this deficiency, the combination of references fail to teach the claimed method with a reasonable expectation of success.” This is not found persuasive.
It is unclear what claim limitation Application is referring to in the inclusion of a “CAR binding a tumor antigen” in their argument. This limitation is not recited in the claims and as such, not required to be included in the prior art rejections. The rejections citing Dranoff et al., Diehl et al., and Fesnak et al. teach all the recited limitations of the instant claims as outlined above. Additionally, the abstract of Dranoff et al. discloses “a chimeric antigen receptor that binds a B-Cell antigen and a chimeric antigen receptor which binds a tumor antigen”. Given that the invention of Dranoff et al. discloses that their anti-CD83 CAR can bind to tumor antigens, it would be obvious to one of ordinary skill in the art that this function is tied to its structure and thus capable of achieving the recited effect of binding a tumor antigen and working as a therapeutic for B cell malignancies.
Therefore, the rejection is maintained.
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 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 9-16 of copending Application No. 18/478,247 (the ‘247 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a method of treating a myeloid malignancy in a subject , the method comprising administering to the subject an effective amount of an immune effector cell 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-CDRs1-3 and VL-CDRs1-3 comprising SEQ ID NOs: 1-6; wherein the anti-CD83 scFv comprises VH and VL domains comprising SEQ ID NOs: 19-20, respectively.
The claims in the ‘247 Application are drawn to a method of suppressing alloreactive donor cells in a subject receiving transplant donor cells, the method comprising administering to the subject an effective amount of a first immune effector cell genetically modified to express a first 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. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 10) and anti-CD83 scFv comprises the same CDRs (claim 11), VH and VL domains (claim 12), and amino acid sequence (claim 13) as the instant claims.
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘247 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘247 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 1-13 and 16) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘247 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4 and 16-19 of copending Application No. 18/547,748 (the ‘748 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
‘748’s claims are drawn to a method of providing an anti-cancer immunity in a subject with a CD83- expressing B and/or T cell acute lymphoblastic leukemia (ALL), the method comprising administering to the subject an effective amount of an immune effector cell genetically modified to express a first chimeric antigen receptor (CAR) polypeptide that selectively binds CD83, thereby providing an anti-tumor immunity in the mammal. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 4) and anti-CD83 scFv comprises the same CDRs (claim 4) as the instant claims.) Claims 16-19 of ‘748 also recite that the immune effector cell genetically modified to express the CAR polypeptide is a regulatory T cell, further administering a checkpoint inhibitor, and the checkpoint inhibitor is an anti-PD-1 antibody.
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘748 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘748 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 4 and 16-19) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘748 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 8-15, 17, and 19 of copending Application No. 18/041,542 (the ‘542 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
‘542’s claims are drawn to a method of inhibiting autoreactive lymphocytes in a subject, the method comprising administering to the subject an effective amount of an immune cells 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 inhibiting autoreactive lymphocytes in the subject. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 9) and anti-CD83 scFv comprises the same CDRs (claims 10-13) as the instant claims.) ‘542 also recites that the immune effector cell genetically modified to express the CAR polypeptide is a T cell.
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘542 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘542 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 1, 5-6, 8-15, 17 and 19) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘542 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 12-15, and 17-20 of copending Application No. 17/635,119 (the ‘119 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
‘119’s 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 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. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 1) and anti-CD83 scFv comprises the same CDRs (claims 1, 12, 20) as the instant claims.) ‘119 also recites that the immune effector cell genetically modified to express the CAR polypeptide is a regulatory T cell.
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘119 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘119 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 1, 5, 12-15, 17-20) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘119 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, 13-16, and 18-19 of copending Application No. 16/969,056 (the ‘056 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
‘056’s claims are drawn to a method of suppressing alloreactive donor cells in a subject receiving transplant donor cells, the method comprising administering to the subject an effective amount of an immune effector cell genetically modified to express the CAR polypeptide, thereby suppressing alloreactive donor cells in the subject, comprising 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. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 1) and anti-CD83 scFv comprises the same CDRs (claims 1 and 6) as the instant claims.) Claims 13, 16, and 18-19 of ‘056 also recite that the immune effector cell genetically modified to express the CAR polypeptide is a regulatory T cell, further administering a checkpoint inhibitor, and the checkpoint inhibitor is an anti-PD-1 antibody.
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘056 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘119 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 1, 6-9, 13-16, and 18-19) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘056 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8-14 of copending Application No. 18/565,831 (the ‘831 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
’831’s claims are drawn to a method for treating ischemic stroke or acute coronary syndrome, the method comprising administering to the subject an effective amount of a regulatory T cell wherein the Treg cell is genetically modified to express the CAR polypeptide, comprising 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. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 8) and anti-CD83 scFv comprises the same CDRs (claims 9-12) as the instant claims.)
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘831 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘831 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 1 and 8-14) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘831 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-13 of copending Application No. 17/757,475 (the ‘475 Application). Although the claims at issue are not identical, they are not patentably distinct from each other.
‘475’s claims are drawn to a method for producing regulatory T cells, the method comprising administering to the subject an effective amount of a regulatory T cell wherein the Treg cell is genetically modified to express the CAR polypeptide, comprising 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. Said CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83 (claim 6) and anti-CD83 scFv comprises the same CDRs (claims 7-10) as the instant claims.)
The co-pending claims are drawn to the methods of using the same CD83 CAR recited above.
Regarding the limitation “a method of treating a myeloid malignancy in a subject” (claim 1), the ‘475 Application is silent on these properties. However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). It is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the CD83 CAR Treg cell taught by the ‘475 Application would necessarily have the claimed properties recited in instant claims 1-13 and 16.
When a claim recites using an old composition or structure (e.g., CD83 CAR Treg cell) and the use is directed to a result or property of that composition or structure (properties recited in claims 4-13) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Therefore, the claims in the ‘475 Application would render the instant claims anticipated. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-12, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 19 of copending Application No. 18/719,814, in view of Diehl et al. (WO 2013/006505 A1, in IDS filed 05/02/2022) and Fesnak et al. 2016 (in PTO-892 filed 06/03/2025).
The instant claims are drawn to a method of treating a myeloid malignancy in a subject , the method comprising administering to the subject an effective amount of an immune effector cell 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-CDRs1-3 and VL-CDRs1-3 comprising SEQ ID NOs: 1-6; wherein the anti-CD83 scFv comprises VH and VL domains comprising SEQ ID NOs: 19-20, respectively.
The claim in the ‘814 Application is 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.
The claims in the ‘814 Application differ from the instant invention by not reciting a method of treating a myeloid malignancy, administering an effective amount of an immune effector cell genetically modified to express a chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain (comprising the instantly claimed CDRs), a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region.
The teachings of Diehl et al. and Fesnak et al. are discussed in the 103 rejection above.
It would thus be obvious to one of ordinary skill in the art to have modified the method of claims 1 and 19 of the ‘814 Application with the teachings of Diehl et al. to include the claimed sequences in an extracellular antigen binding domain in a scFv for the anti-CD83 antigen binding fragment, 60B10, and apply them in the method to treat myeloid malignancies in lymphocytes while including administering Fesnak et al.’s checkpoint inhibitors, such as anti-PD-1, PD-L1, and/or CTLA-4 antibodies with a reasonable expectation success. Given the known advantages of using Tregs in conjunction with immunosuppressive drugs, such as checkpoint inhibitors to treat a myeloid malignancy such as acute myeloid leukemia, it would have been obvious to a skilled artisan to experiment with using Fesnak et al.’s checkpoint inhibitors, including anti-PD-1, PD-L1, and/or CTLA-4 antibodies, in order to enhance the efficacy of ‘814’s CAR polypeptide therapies. The rationale for combining these references to result in the instantly claimed a method of treating a myeloid malignancy in a subject is discussed in the 103 rejection above.
Therefore, the claims in the ‘814 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 01/07/2026 have been fully considered but they are not persuasive.
Applicant argues that the rejection of claims 1-2, 5-12, and 17 be held in abeyance until it is the only rejection outstanding in accordance with MPEP § 714.02 and 37 C.F.R. § 1.111(b) as the claims may be further examined notwithstanding with the rejection. This is not found persuasive.
The amendments to the claims do not overcome the provisional double patenting rejections of claims 1-2, 5-12, and 17. Additionally, there are other remaining rejections over the instant claims. Thus, in view of this response, all of the double patenting rejections are maintained for the reasons of record.
Conclusion
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675