DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Formal Matters
A. In the response filed 1/6/26, Applicants elected CD19, TRAC, RFX5 and HLA-E.
B. Claims 1-20 are pending and are the subject of this Office Action.
2. Claim Objections
Claim 1 is objected to since there should be a hyphen between “II” and “related”. Claims 2-20 are objected to since they depend from claim 1.
3. 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.
A. Claims 1, 10 and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al.
The claims are generally drawn to an engineered immune cell expressing an anti-CD7 antibody and having suppressed or silenced expression of endogenous CD7, a TCR/CD3 gene and an MHC-II-related gene.
Gomes-Silva teaches the expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells which eliminates CD7+ AML cell lines, but not myeloid and erythroid progenitor cells (Abstract). The CD7KO would spare normal T cells while retaining functionality (4th paragraph of Introduciton). Gomes-Silva also teaches that this CD7 CAR T cell protects mice against leukemia in a xenograft model (Abstract). Th CD7KO T cell would suppress/silence CD7 gene expression as recited in claim 1. Claims 16-19 are also taught since Gomes-Silva teaches the use of T cells to treat AML (e.g. Title).
Gomes-Silva does not teach silencing a TCR/CD3 and MHC-related gene. However, Rasaiyaah teaches that disrupting the TCR/CD3 complex allows for CD3-specific antileukemic T cell immunotherapy (e.g. Title; Abstract) since in order to be activated, T cells bind to both CD3 via the TCR/CD3 complex and the MHC-antigen peptide complex on the surface of antigen-presenting cells.
Neither Gomes-Silva nor Rasaivaah teach targeting the MHC-II-related gene RFX5. However, Villard teaches that a domain of RFX5 plays an essential role in the transcriptional activation of MHC-II genes (Abstract). Therefore, as with silencing CD7 expression, suppressing/silencing expression of the TCR/CD3 gene and critical MHC-II genes in a CAR-T cell can avoid attack on normal cells.
B. Claims 2 and 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. and further in view of Miller and Manus.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. None teach the specific domains recited in claims 2 and 6-8, nor the use of CD19 recited in claims 4 and 5. However, Miller and Manus do teach CAR T cells comprising a CD8a transmembrane domain, a CD3z intracellular domain and a CD28 or 4-1BB costimulatory domain (first full paragraph of page 684) as well as the importance of CAR T cells which target the cell-surface molecule CD19 for treatment of B-cell malignancies (Abstract). Therefore, it would have been obvious at the time to have produced a CAR T cell expressing an additional antibody to this molecule.
C. Claims 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. further in view of Hong et al.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. None teach silencing TRAC. However, Hong does teach CAR T cells with an edited TRAC gene in order to ablate TCRab function to reduce alloreactive T cells (first entry in Table 1), thereby enhancing non-alloreactive T cell function in T cell-directed treatment.
D. Claims 12-15 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. further in view of Cook et al. and further in view of van Hall.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. None teach an engineered immune cell further expressing an NK inhibitory molecule. However, Cook teaches that NK depletion prevents T cell exhaustion. Therefore, in order to increase the therapeutic effects of CAR T cells, it would have been obvious to have suppressed NK cells. Cook does not teach the use of an antibody (claim 13), including one which targets NKG2A (claim 20), nor the use of HLA-E as an inhibitory ligand (claim 14). However, van Hall does teach that blocking antibodies to NKG2A results in tumor control in multiple mouse models (Abstract). Given that NKG2A is an inhibitor receptor which engages HLA-E (lines 1-4 and last paragraph of left column of page 2), it would have been obvious to have targeted either NKG2A (e.g. antibody), or its ligand HLA-E.
4. Nonstatutory 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.
A. Claims 1-3, 6-8, 10 and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-14, 20 of copending Application No. 18/034,170 (reference application) in view of Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to engineered immune cells comprising the same CD7 antibody and CAR domains.
The copending claims do not recite the silencing of CD7, a TRC/CD3 and MHC-II-related genes, nor a pharmaceutical composition and the treatment of cancer. However, Gomes-Silva teaches the expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells which eliminates CD7+ AML cell lines, but not myeloid and erythroid progenitor cells (Abstract). The CD7KO would spare normal T cells while retaining functionality (4th paragraph of Introduction). Gomes-Silva also teaches that this CD7 CAR T cell protects mice against leukemia in a xenograft model (Abstract). Th CD7KO T cell would suppress/silence CD7 gene expression as recited in claim 1. Claims 16-19 are also taught since Gomes-Silva teaches the use of T cells to treat AML (e.g. Title).
Gomes-Silva does not teach silencing a TCR/CD3 and MHC-related gene. However, Rasaiyaah teaches that disrupting the TCR/CD3 complex allows for CD3-specific antileukemic T cell immunotherapy (e.g. Title; Abstract) since in order to be activated, T cells bind to both CD3 via the TCR/CD3 complex and the MHC-antigen peptide complex on the surface of antigen-presenting cells.
Neither Gomes-Silva nor Rasaivaah teach targeting the MHC-II-related gene RFX5. However, Villard teaches that a domain of RFX5 plays an essential role in the transcriptional activation of MHC-II genes (Abstract). Therefore, as with silencing CD7 expression, suppressing/silencing expression of the TCR/CD3 gene and critical MHC-II genes in a CAR-T cell can avoid attack on normal cells.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
B. Claims 4 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-14 and 20 of copending Application No. 18/034,170 (reference application) in view of Gomes-Silva et al. further in view of Rasaiyaah et al. further in view of Villard et al. and further in view of Miller and Manus.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. The copending claims do not recite, nor do Gomes-Silva, Rasaivaah, nor Villard teach the use of CD19. However, Miller and Manus do teach CAR T cells comprising a CD8a transmembrane domain, a CD3z intracellular domain and a CD28 or 4-1BB costimulatory domain (first full paragraph of page 684) as well as the importance of CAR T cells which target the cell-surface molecule CD19 for treatment of B-cell malignancies (Abstract). Therefore, it would have been obvious at the time to have produced a CAR T cell expressing an additional antibody to this molecule.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
C. Claims 9 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-14, 20 of copending Application No. 18/034,170 (reference application) in view of Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. and further in view of Hong et al.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. The copending claims do not recite, nor do Gomes-Silva, Rasaivaah, nor Villard teach silencing TRAC. However, Hong does teach CAR T cells with an edited TRAC gene in order to ablate TCRab function to reduce alloreactive T cells (first entry in Table 1), thereby enhance T cell function in T cell-directed treatment.
D. Claims 12-15 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-14, 20 of copending Application No. 18/034,170 (reference application) in view of Gomes-Silva et al. in view of Rasaiyaah et al. further in view of Villard et al. further in view of Cook et al. and further in view of van Hall.
The teachings of Gomes-Silva, Rasaivaah and Villard are discussed in paragraph A of this section. The copending claims do not recite, nor do Gomes-Silva, Rasaivaah, nor Villard teach an engineered immune cell further expressing an NK inhibitory molecule. However, Cook teaches that NK depletion prevents T cell exhaustion. Therefore, in order to increase the therapeutic effects of CAR T cells, it would have been obvious to have suppressed NK cells. Cook does not teach the use of an antibody (claim 13), including one which targets NKG2A (claim 20), nor the use of HLA-E as an inhibitory ligand (claim 14). However, van Hall does teach that blocking antibodies to NKG2A results in tumor control in multiple mouse models (Abstract). Given that NKG2A is an inhibitor receptor which engages HLA-E (lines 1-4 and last paragraph of left column of page 2), it would have been obvious to have targeted either NKG2A (e.g. antibody), or its ligand HLA-E.
E. Claims 1-3, 6-11 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of copending Application No. 18/861,000 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to engineered immune cells with knockout of CD7, TRAC and RFX5.
Copending claims 8-11 require the immune cell engineered to express a CD7 CAR having the same domains as the instant claims. Copending SEQ ID NO:11 and 12 comprise instant SEQ ID NO:1-3 and 4-6, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
F. Claims 4 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of copending Application No. 18/861,000 (reference application) in view of Miller and Manus.
The copending claims do not recite the use of CD19. However, Miller and Manus do teach CAR T cells comprising a CD8a transmembrane domain, a CD3z intracellular domain and a CD28 or 4-1BB costimulatory domain (first full paragraph of page 684) as well as the importance of CAR T cells which target the cell-surface molecule CD19 for treatment of B-cell malignancies (Abstract). Therefore, it would have been obvious at the time to have produced a CAR T cell expressing an additional antibody to this molecule.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
G. Claims 12-15 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of copending Application No. 18/861,000 (reference application) in view of Cook et al. and further in view of van Hall.
The copending claims do not teach an engineered immune cell further expressing an NK inhibitory molecule. However, Cook teaches that NK depletion prevents T cell exhaustion. Therefore, in order to increase the therapeutic effects of CAR T cells, it would have been obvious to have suppressed NK cells. Cook does not teach the use of an antibody (claim 13), including one which targets NKG2A (claim 20), nor the use of HLA-E as an inhibitory ligand (claim 14). However, van Hall does teach that blocking antibodies to NKG2A results in tumor control in multiple mouse models (Abstract). Given that NKG2A is an inhibitor receptor which engages HLA-E (lines 1-4 and last paragraph of left column of page 2), it would have been obvious to have targeted either NKG2A (e.g. antibody), or its ligand HLA-E.
H. Claims 17-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of copending Application No. 18/861,000 (reference application) in view of Gomes-Silva et al.
The copending claims do not teach a pharmaceutical composition comprising the immune cell, nor treatment of the claimed diseases. However, Gomes-Silva teaches the expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells which eliminates CD7+ AML cell lines, but not myeloid and erythroid progenitor cells (Abstract). The CD7KO would spare normal T cells while retaining functionality (4th paragraph of Introduction). Gomes-Silva also teaches that this CD7 CAR T cell protects mice against leukemia in a xenograft model (Abstract). The use of a pharmaceutical composition would be required to perform these studies.
5. Conclusion
No claim is allowable.
Advisory information
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647