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 .
Claim Status
Claims 24-35 are cancelled. Claims 1-23 and 36 as filed on 26 July 2023 are pending and under examination.
Claim Objections
Claims 1 and 23 are objected to because of the following informalities: Claims comprise internal periods. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola V. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995); MPEP 608.01(m). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-6 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 includes the limitation “negative regulators is listed in Table 1”. Claim 6 includes the limitation of “positive regulators is listed in Table 2.” Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Claim 4 recites the limitation "the negative BTN3A1 regulators" in line 1, claim 4 depends form claim 1. There is insufficient antecedent basis for this limitation in the claim as claim 1 only recites BTN3A regulators.
Claim 5 recites the limitation "the negative BTN3A1 regulators" in line 1, claim 4 depends form claim 1. There is insufficient antecedent basis for this limitation in the claim as claim 1 only recites BTN3A regulators.
Further there are two “BTN3A negative regulators” in claim 1. The first in line 2 is something to be administered in a method and subpart c refers to expression level in a cell sample.
Claims 3 and 6 were examined as requiring the regulators in claims 4 and 7.
Claims 4 was examined as referring to BTN3A negative regulator in subpart c of claim 1. Claim 4 is interpreted to mean the cell sample has decreased expression of one of the listed negative regulators.
Claim 5 was examined as referring to the negative BTN3A regulator from line 2. Claim 5 is interpreted to limit the BTN3A negative regulators to be administered to a subject.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 10-12, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chiang (US 20200172864 A1) (PTO-892), as evidenced by Zocchi et. al. Oncoimmunology. 6(3):1-13. (2017) (PTO-892).
Chiang teaches cancer cell killing using the administration of Vγ9δ2 T cells wherein the cancer cells are K562 which expresses higher levels of BTN3A1 ([0291] and claims 1-3, 9, 18, and 278-28)
Regarding claim 10-12, Chiang teaches the administration of a pharmaceutical composition comprising the Vγ9δ2 T cells and zoledronate, which is a chemotherapeutic as evidenced by Zocchi (abstract) and modulates BTN3A regulator as defined by instant claim 11.
Claims 1, 3-4, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang (CN 107998396 A) (PTO-892).
Claims 1 and 9 require the detection of decreased BTN3A2 expression, as an applicant identified negative regulator of BTN3A, and the administration of a BTN3A inhibitor wherein the inhibitor is one of those listed including antibodies.
Tang teaches decreased BTN3A2 and BTN3A3 expression in Figure 4 relative to control (231-NC is control). Tang teaches the administration of an anti-BTN3A antibodies that act as inhibitors (claim 2).
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Farokhzad (US 20200085758 A1) (PTO-892).
Regarding claims 1 and 5, the terms “BTN3A negative regulators” are interpreted to mean the genes applicant recites as negative regulators of BTN3A. These are listed in Table 1 of the instant specification starting on page 119 and recited in claim 4. Claim 4 requires the administration of a BTN3A negative regulator as part of an expression cassette or expression vector to a subject that has increased expression of either BTN3A or BTN3A positive regulators or the decreased expression of BTN3A negative regulators, or any combination thereof.
Farokhzad teaches in vitro evaluation for tumor targeting ability ([0452]). Farokhzad teaches the loss of one or more tumor suppressor genes ([0017]). Farokhzad teaches RUNX1 is a tumor suppressor (Table 5). Farokhzad teaches a nanoparticle that comprises an inhibitory functional nucleic acid and a stimulatory nucleic acid that encodes a protein or peptide (claim 1). Farokhzad teaches the stimulatory functional nucleic acid is an mRNA or DNA (claim 5). Farokhzad teaches the active agents of its invention in vectors ([0095]) and promoters ([0145] and [0156])).
Claims 1 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bedoya (WO 2016057705 A1) (PTO-892).
The method of claims 1 and 6-7 require the administration of T cell therapies to a subject that expresses one or more of the listed BTN3A positive regulators.
Bedoya teaches identifying non-responders based on gene markers (page 12 in lines 29-30 and page 13 in lines 1-2). Bedoya teaches non-responders as increased activity of IRF8 in T effector cells, which applicant identifies as a BTN3A positive regulator (page 13 in lines 10-13 and claim 21). Bedoya further teaches the upregulation of STIP1, which applicant identifies as a BTN3A positive regulator, in activated TEFF cells (page 16 in lines 27-31 and page 17 in lines 1-9 in particular line 5). Bedoya teaches markers for activated TEFF cells are found in non-responders (NR) (page 248 in lines 5-10). Bedoya teaches administering a combination therapy to non-responders that comprises CAR T therapy with a checkpoint inhibitor (page 7 in lines 6-8). Bedoya then teaches the administration of T therapy with increased BTN3A regulators STIP1 and IRF8 as required by claims 6-7.
Claims 1 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Regev (US 20200157633 A1) (PTO-892).
Regarding claims 1 and 8, Regev teaches the detection of a novel gene signature and modulating treatment based on that gene signature wherein the novel gene signature predicts overall survival in cancer and can be targeted therapeutically (abstract and Figure 1). Regev teaches immune checkpoint inhibitor resistance (ICR) gene signature where ATP5G2 is upregulated in a high ICR score (claims 1-5). Regev teaches ICR patients are administered a treatment that targets the genes upregulated by antibody or CAR T cell therapy (claims 20-21, 32-33)
Claims 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamashiro (WO2010047117 A1) (PTO-892).
Yamashiro teaches a method of administrating an anti-BTN3A antibody for use in identifying the activated or inactivated lymphocytes and inhibiting proliferation of a lymphocyte by use of the antibody (abstract).
Yamashiro teaches the method of detecting and measuring the expression level of BTN3A1 (page 2 in par 8). Yamashiro teaches the measurement of BTN3A1 or BTN3A2 which applicant has listed as a positive regulator of BTN3A1 in instant claim 14 (page 3 in pars 8-9).
Claims 13 and 15-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuball (US 20200368278 A1) (IDS).
Regarding claims 13, 15-16, and 20-21, Kuball teaches a method comprising a ligand binding assay where one or more cells that express BTN3A1 is contacted with anti-CD277 (which is BTN3A1) monoclonal antibodies and assay detects BTN3A1 and quantifies the amount of BTN3A1 on the surface of cells including cells that are Vγ9δ2 T cells ([0131], [0023], [0246]).
Regarding claims 17-19, Kuball teaches the isolation of T cells from a tumor ([0089], [0107]). Kuball further teaches the cancer is lymphoma ([0181]) or from organs with cancer including pancreas, kidney, and liver ([0157]).
Regarding claim 22, Kuball teaches incubation with the antibodies that mark Vγ9δ2 T cells ([0305]). Kuball teaches the characterization of the isolated cells including cytokine production ([0156]) and ([0061] and Figures 15 A-D and Figure 18A).
Regarding claim 23, Kuball specifically teaches stratifying patients with reduced levels of CD277 (which is BTN3A1).
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, 6-7, 9-10, 12, and 36 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 17758866 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-2 and 6-7,the reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of BTN3A2 and NLRC5 (claims 1 and 26).
Regarding claim 9, the reference application recites decreasing BTN3A2 activity by using an antibody (claim 10)
The modulation of the reference claims would be the administration of a compound that modulates at least one positive BNT3A positive regulator as required by claim 10.
Regarding claim 12, the reference application recites the target cell is a cancer cell making the administered substance a chemotherapeutic (claim 3).
Regarding claim 36, the reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of IRF1 (claim 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 13 and 15-23 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 17758866 in view of Kuball (US 20200368278 A1) (IDS).
The recitations of the reference application from the previous double patenting rejection are incorporated here in full.
The reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of BTN3A2 and NLRC5 (claims 1 and 26).
The reference application recites decreasing BTN3A2 activity by using an antibody (claim 10)
The modulation of the reference claims would be the administration of a compound that modulates at least one positive BNT3A positive regulator as required by claim 10.
The reference application does not recite the method of detecting and quantifying the amount of BTN3A1 expression.
This deficiency is filled by Kuball.
Regarding claims 13, 15-16, and 20-21, Kuball teaches a method comprising a ligand binding assay where one or more cells that express BTN3A1 is contacted with anti-CD277 (which is BTN3A1) monoclonal antibodies and assay detects BTN3A1 and quantifies the amount of BTN3A1 on the surface of cells including cells that are Vγ9δ2 T cells ([0131], [0023], [0246]).
Regarding claims 17-19, Kuball teaches the isolation of T cells from a tumor ([0089], [0107]). Kuball further teaches the cancer is lymphoma ([0181]) or from organs with cancer including pancreas, kidney, and liver ([0157]).
Regarding claim 22, Kuball teaches incubation with the antibodies that mark Vγ9δ2 T cells ([0305]). The claim does not require any action but incubating for a time under conditions that allowed for measuring further data on the cell but does not require any measurements to occur.
Regarding claim 23, Kuball specifically teaches stratifying patients with reduced levels of CD277 (which is BTN3A1).
It would have been obvious at the time the application was filed to combine the method of modulating BTN3A and the related regulators with the method of detection taught by Kuball to determine the success of the method of the reference claims. One of skill in the art would have been motivated to determine if the modulation had worked and Kuball provides one of skill in the art an assay for the measurement of BTN3A1 which Kuball teaches is related to cancer therapeutics. There would have been a reasonable expectation of success as Kuball provides a functional method of measuring targets of interest to the reference claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-4, 6-9, and 13-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 17758866 in view of Wherry (WO 2019084493 A1) (PTO-892).
The recitations of the reference application from the previous double patenting rejections are incorporated here in full.
The reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of BTN3A2 and NLRC5 (claims 1 and 26).
The reference application recites decreasing BTN3A2 activity by using an antibody (claim 10)
The modulation of the reference claims would be the administration of a compound that modulates at least one positive BNT3A positive regulator as required by claim 10.
The reference application recites the increase and decrease of the expression of IRF1, NLRC5, IFNAR1, and BTN3A2 (claims 1 and 7).
The reference application does not recite the up regulation of BTN3A positive regulators.
This deficiency is filled by Wherry.
Wherry teaches obtaining a sample comprising T cells from a subject and measuring expression panels of interest. Wherry teaches measuring expression of T cell lineage specific markers. Wherry teaches the up and down regulation of the markers being tested (page 2 in lines 24-30 and page 3 in lines 1-8). Wherry teaches T cell lineage markers including CD277, which is BTN3A1, in claim 7.
Wherry teaches T cell exhaustion and epigenetic and transcriptional markers are related to clinical prediction, diagnosis and therapeutic development. Wherry teaches transcriptional markers have a role in T cell exhaustion (page 2 in lines 9-19, page 55 in lines 14-17, page 64 in lines 3-8, page 91 in lines 15-19, page 106 in lines 10-11, Example 19, and Figure 50).
Wherry then teaches the selection of a method of treatment based on the analysis with an engineered T cell as required by claim 1 (claim 62).
Wherry teaches epigenetic targets including JMHD6 (required by claim 7), HDAC8 (required by claim 4), and BRD2 (required by claims 7 and 14) (page 75 in lines 13-31) and transcriptional targets including Ndufb9 (required by claim 8), Gadd45a (required by claim 4), and Ndufs7 (required by claim 8), (page 76 in lines 6-10 and lines and starting in line 20 of page 76 to page 90 in line 19).
Wherry teaches the epigenetic markers JMHD6 that instant claim 7 identifies as a BTN3A [positive regulator (page 75 in line 25). Wherry teaches this is one of many epigenetic targets that can be targeted within a cell with a drug or with genome engineering (page 75 in lines 13-15).
It would have been obvious at the time the application was filed to combine the method of the reference claim that includes the up and down regulation of IRF1, NLRC5, IFNAR1, and BTN3A2 with the method of Wherry that includes the modulations of T cell regulators for improves therapy in cancer. One of skill in the art would have been motivated to further characterize the tumor microenviroment as taught by Wherry. There would have been a reasonable expectation of success as Wherry and the reference application are both working with modulation of T cell regulators.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 5 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 17758866 in view of Farokhzad (US 20200085758 A1) (PTO-892).
The recitations of the reference application from the previous double patenting rejections are incorporated here in full.
The reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of BTN3A2 and NLRC5 (claims 1 and 26).
The reference application recites decreasing BTN3A2 activity by using an antibody (claim 10)
The modulation of the reference claims would be the administration of a compound that modulates at least one positive BNT3A positive regulator as required by claim 10.
The reference application recites the increase and decrease of the expression of IRF1, NLRC5, IFNAR1, and BTN3A2 (claims 1 and 7).
The reference application recites modulating the expression of genes of interest using siRNA and microRNA.
The reference application does not recite a vector comprising a promoter operably linked to a negative regular of BTN3A1.
This deficiency is filled by Farokhzad
Farokhzad teaches in vitro evaluation for tumor targeting ability ([0452]). Farokhzad teaches the loss of one or more tumor suppressor genes ([0017]). Farokhzad teaches RUNX1 is a tumor suppressor (Table 5). Farokhzad teaches a nanoparticle that comprises an inhibitory functional nucleic acid and a stimulatory nucleic acid that encodes a protein or peptide (claim 1). Farokhzad teaches the stimulatory functional nucleic acid is an mRNA or DNA (claim 5). Farokhzad teaches the active agents of its invention in vectors ([0095]) and promoters ([0145] and [0156])).
It would have been obvious at the time the application was filed to combine the modulation of genes of interest of the reference claims with the modulation of the tumor suppressor RUNX1 taught by Farokhzad. One of skill in the art would have been motivated to further modify the tumor microenvironment as taught by increasing the tumor suppressor RUNX1 taught by Farokhzad. There would have been a reasonable expectation of success as Farokhzad and the reference claims both teach multiple modulations for the treatment of cancer patients.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 11 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 17758866 in view of Chiang (US 20200172864 A1) (PTO-892).
The reference application recites administering Vγ9δ2 T cells to a subject that will have increased expression of BTN3A2 and NLRC5 (claims 1 and 26).
The reference application recites decreasing BTN3A2 activity by using an antibody (claim 10)
The modulation of the reference claims would be the administration of a compound that modulates at least one positive BNT3A positive regulator as required by claim 10.
The reference application recites the increase and decrease of the expression of IRF1, NLRC5, IFNAR1, and BTN3A2 (claims 1 and 7).
The reference application does not recite the administration in combination with zoledronate.
This deficiency is filled by Chiang.
Chiang teaches cancer cell killing using the administration of Vγ9δ2 T cells wherein the cancer cells are K562 which expresses higher levels of BTN3A1 ([0291] and claims 1-3, 9, 18, and 278-28)
Regarding claim 11-12, Chiang teaches the administration of a pharmaceutical composition comprising the Vγ9δ2 T cells and zoledronate, which is a chemotherapeutic as evidenced by Zocchi (abstract).
It would have been obvious to combine the Vγ9δ2 T cells for use in treating cancer of the reference claims with the zoledronate taught by Chiang for use in combination with Vγ9δ2 T cells in the treatment of cancer. The combination of Vγ9δ2 T cells with zoledronate is prima facie obvious due to both being used in the treatment of cancer. There would have been a reasonable expectation of success as Chiang explicitly teaches the combination of the instant claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643