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 .
Election/Restrictions
Claims 1, 3, 6-9, 11, 13, 16, 22, 43-44, 47-50, 52-54, 56-62 are pending.
Applicant’s election of Group IV, claims 49-50, 52-54, 56-57 in the reply filed on 07/03/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)) and made FINAL.
Claims 1, 3, 6-9, 11, 13, 16, 22, 43-44, 47-48, and 58-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/03/2025.
Claims 49-50, 52-54, 56-57 have been examined on their merits.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 inappropriately uses dashes to separate clauses. Claims should be constructed as single sentences. According to MPEP 608.01(m), “[e]ach claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.” While “[t]here may be plural indentations to further segregate subcombinations or related steps” dashes are used to indicate a range or pause and separate groups of words, not to separate a series of clauses. Instead, the subcombinations or related steps should be separated by an alphanumeric marker (e.g., “(a) obtaining . . . (b) supplying, etc.” 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 49-50, 52-54, 56-57 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.
Regarding claim 49, the phrase “preferably” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For compact prosecution, the choice is considered optional.
Regarding claim 53, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For compact prosecution, the choice is considered optional.
Regarding claim 54, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For compact prosecution, the choice is considered optional.
Claims 50, 52-54, 56-57 are rejected under 35 USC 112(b) for their dependence on claim 49.
Claim Rejections - 35 USC § 102
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 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 49-50, 52-53, 56-57 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated Benson et al. (WO2019178422A1, 2019, on IDS 05/27/2022).
In regards to claims 49, Benson discloses methods for treating subjects with cell proliferative disorders, such as cancers, with compositions comprising gene-edited T cells, which can be CD8+ T cells (also referred to as a cytotoxic T cell or CTLs) specifically, to elicit anti-tumor immune responses and cause regression of cancer (Abstract; claims 1, 157, 281-283; paragraphs [0067, 00162, 00441]).
Benson discloses that the T cell can be autologous (claims 164, 289), which means that they can be obtained from the subject.
Benson discloses that the cells are genetically edited to reduce function of the gene PTPN2 (claim 1; paragraph [00234]) and administered to subjects (claim 281; paragraph [0068]).
In regards to the step of administering a PTP1B (also referred to as PTPN1 in the art) inhibitor, it is noted that the instant specification explicitly states the inhibitor may be part of a CRISPR-based genome editing system (instant paragraph [0203]).
To this end, Benson discloses that effector cells comprising a gene-regulating system, such as CRSIPR, for reducing expression of PTPN1 (PTP1B) can be administered to a subject (claims 1, claim 281; paragraphs [0008, 00234]), which reads on this limitation.
In regards to claim 50, Benson discloses that the CD8+ T cells can be engineered to express a CAR (claims 150-151; paragraph [00134]).
In regards to claim 52, Benson discloses that PTPN2 is edited with a CRISPR/Cas9 system (paragraph [00234]).
In regards to claim 53, Benson discloses that the PTP1B inhibitor is a Cas9 that complexes with a gRNA directed to PTP1B (claims 52, 59; paragraphs [0030, 00101, 00234]).
In regards to claim 56, Benson discloses that the administration to a subject (which would comprise both PTPN2 edited cells and the PTP1B inhibitor) can be administered at one time (claims 1, 281-283; paragraph [00438]).
In regards to claim 57, Benson discloses that the CARs can be directed to HER2-specific tumor antigens (paragraph [00182]), an thus for HER2-positive cancers.
Therefore, Benson anticipates the invention as claimed.
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.
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Benson et al. (WO2019178422A1, 2019, on IDS 05/27/2022) in view of Krishan et al. (Nat Chem Biol, 2014).
Benson anticipates claim 49 as discussed above.
In regards to claim 54, Benson teaches that a subject may be administered immune checkpoint inhibitors, including small-molecule inhibitors, which result in enhanced therapeutic effect (paragraphs [00112, 00430-00431, 00445-00448]), but is silent on whether the small-molecule inhibitor is a PTP1b inhibitor specifically (it is noted PTP1b is a known checkpoint protein).
However, a person of ordinary skill in the art would have been motivated to administer a small drug inhibitor of PTP1b such as MSI-1436 (trodusquemine) because Krishnan teaches that PTP1b plays a critical role in HER2 signaling in breast cancer, but that inhibition with small molecule inhibitor MSI-1436 (trodusquemine) antagonizes HER2 signaling, inhibits tumorigenesis, and abrogates metastasis of breast cancer in subjects (Abstract, p1-2; MSI-1436 attenuated HER2-mediated tumorigenesis, p7-8; MSI-1436 specifically targeted PTP1B in breast cancer models, p8). Furthermore, because Krishnan teaches that MSI-1436 (trodusquemine) effectively attenuated HER2 signaling, resulting in extensive inhibition of tumor growth and abrogation of metastasis (Introduction, p2-3) and because, as above, Benson teaches that patients can be administered checkpoint inhibitors and that this enhances therapeutic effects, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Benson and Krishnan render obvious the invention as claimed.
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 49-50, 52-54, 56-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 9, 11, 13, 15-18, 37, 41, 46, 49-50, 52-53, and 56-58 of copending Application No. 17/058,551 in view of over Benson et al. (WO2019178422A1, 2019, on IDS 05/27/2022).
While the instant claims and claims 1-3, 6-7, 9, 11, 13, 15-18, 37, 41, 46, 49-50, 52-53, and 56-58 of copending Application No. 17/058,551, the instant claims are not patentable distinct because both inventions are drawn to inducing an immune response in a subject comprising administering a PTP1B inhibitor and T cells, derived from a subject, to a subject for treating cancer.
Copending Application No. 17/058,551 does not explicitly teach that the T cells are CD8+ T cells specifically or a step of editing the gene encoding PTPN2 in these cells.
However, a person of ordinary skill in the art would have been motivated to choose CD8+ T cells because Benson teaches that CD8+ T cells (also referred to as a cytotoxic T cell or CTL) can be used as immune effector cells for cancer immunotherapies (claims 1 and 281-283). A person of ordinary skill in the art would have been motivated to edit the gene encoding PTPN2 because Benson teaches that PTPN2-edited T cells are effective for treating cancers in subjects (claims 1 and 281-283; paragraphs [00219]).
Furthermore, because Benson teaches that gene-edited CD8+ T cells can be administered to tumorigenic subjects (paragraph [00485]), and teaches methods for editing the PTPN2 gene in T cells for treating cancer in subjects (Abstract; claims 1, 157, 281-283; paragraphs [0067, 00162, 00234, 00441]), it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 49-50, 52-54, 56-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45 and 48-54 of copending Application No. 17/014,737 in view of over Benson et al. (WO2019178422A1, 2019, on IDS 05/27/2022).
While the instant claims and claims 45 and 48-54 of copending Application No. 17/014,737 are not identical the instant claims are not patentable distinct because both inventions are drawn to methods for treating cancer in a subject comprising administering CD8+ T cells derived from the subject wherein these cells have been gene edited to remove or modify PTPN2.
Copending Application No. 17/058,551 does not explicitly teach a step of administering a PTP1B inhibitor to a subject.
However, a person of ordinary skill in the art would have been motivated to administer a PTP1B inhibitor because Krishnan teaches that PTP1b plays a critical role in HER2 signaling in breast cancer, but that inhibition with small molecule inhibitor MSI-1436 (trodusquemine) antagonizes HER2 signaling, inhibits tumorigenesis, and abrogates metastasis of breast cancer in subjects (Abstract, p1-2; MSI-1436 attenuated HER2-mediated tumorigenesis, p7-8; MSI-1436 specifically targeted PTP1B in breast cancer models, p8). Furthermore, because Krishnan teaches that MSI-1436 (trodusquemine) effectively attenuated HER2 signaling, resulting in extensive inhibition of tumor growth and abrogation of metastasis (Introduction, p2-3) it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631