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
Applicant’s election without traverse of Group IV, claims 53-64, and further election of species “genome engineering” in the reply filed on 08/21/2026 is acknowledged. Based on the amendment, claims 57-64 constitute the elected invention. The requirement for election of species as to the alternatives recited in claim 58 is withdrawn.
Claims 1-52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/21/2026.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code; see pages 31, 125, 128, 129, 131, 131, 133, 134, 135, 135, 135. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 57-62 are objected to because of the following informalities: Claim 57, line 1 refers to “a patient”, but thereafter refers to “the subject”. A similar situation occurs in claim 62. Consistent terminology should be used throughout the claim. Claims 58-61 depend from claim 57 and are objected to for the same reason. 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.
Claim 59 is 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 59, the phrase "for example" (i.e., “e.g.”) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 62 is 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.
The term “high priority epigenetic pathway” in claim 62 is defined in the specification as follows (emphasis provided): “High priority epigenetic pathways are genes, loci, or proteins that fulfill one of the following criteria: a) are genes/proteins with a known or potential role in generating or changing epigenetic marks; or b) genes with known roles in T cell exhaustion based on transcriptional profiling studies that also have distinct epigenetic modifications in exhausted T cells.”
The problem with such definition is, what is “known” can change over time. Things that are unknown now may become “known” tomorrow. In addition, the term “potential” is vague and indefinite. Any gene or protein might have a “potential” role, and the very use of the word “potential” indicates that it is not yet “known”. This ever-changing boundary is not the sort of definite boundary required for ascertaining the scope and breadth of a patent claim.
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.
Claim(s) 63 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scott-Browne (Immunity 45:1327-1340 (2016), IDS ref).
Scott-Browne disclosed:
using an open chromatin region (OCR) assay comprising an OCR panel to identify an OCR footprint unique to the exhausted T cells as compared with control T cells
Scott-Browne used a technique called ATAC-seq (an open chromatin region assay) to identify “exhaustion-specific accessible regions” (an OCR footprint unique to exhausted T cells). See Summary. Scott-Browne identified these “exhaustion-specific accessible regions” by comparing accessible regions between different T cell subsets: naïve, effector, memory, and exhausted CD8+ T cells (page 1328, first full paragraph). The first three subsets can be considered “control T cells”. Scott-Browne noted (page 1328, last paragraph, left column): “…we restricted our analysis to 70,532 regions that met a minimum threshold of mean ATAC-seq signal in at least one cell type…”. This constitutes “a panel”.
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.
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 64 is rejected under 35 U.S.C. 103 as being unpatentable over Scott-Browne (Immunity 45:1327-1340 (2016), IDS ref) in view of Buenrostro (Curr. Protoc. Mol. Biol. 109:21.29.1-21.29.9 (2015), IDS ref).
The disclosure of Scott-Browne has been discussed. Scott-Browne disclosed that the method comprised preparing ATAC-seq libraries, PCR with 10-12 cycles with barcoded primers, and 2× 50 cycle paired-end sequencing (page 1338, section entitled “ATAC-Seq”). Scott-Browne did not disclose performing “qPCR”.
Buenrostro disclosed an ATAC-seq protocol for assaying chromatin accessibility (see title, e.g.). Buenrostro’s protocol comprised performing a qPCR (page 21.29.4 under “Perform qPCR”): “To reduce GC and size bias in PCR, the appropriate number of PCR cycles (N) is determined using a qPCR, allowing us to stop amplification prior to saturation.” See also page 21.29.6, first four lines: “The purpose of this qPCR step is to generate libraries that are minimally PCR amplified. Most PCR bias comes from later PCR cycles that occur during limited reagent concentrations. This determination of the optimal number of cycles to amplify the library reduces artifacts associated with saturation PCR of complex libraries.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to modify the method of Scott-Browne by including the qPCR step of Buenrostro in order to determine the optimal number of PCR cycles to use to avoid saturation and consequent introduction of PCR bias. It is noted that Scott-Browne’s protocol involved only 10-12 PCR cycles, which is consistent with a goal of avoiding the saturation point.
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 57, 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,906,511 in view of Barrero (International Journal of Molecular Sciences 18:1108 (23 May 2017)).
‘511 claim 1 disclosed the method of detecting exhausted T cells according to instant claim 57 but did not disclose reinvigorating the exhausted T cells.
Barrero taught that during chronic antigen exposure in cancer, T cells become exhausted and dysfunctional. Barrero taught that antibodies that block the interaction of CTLA-4 or PD-1 with their ligands were able to reinvigorate exhausted T cells and showed long-term favorable response in a percentage of cancer patients. See section 3, page 3.
It would have been obvious to modify the method of ‘511 claim 1 by reinvigorating the exhausted T cells in the context of cancer patients as Barrero taught this provided a long-term favorable response in a percentage of cancer patients.
Regarding claim 58, antibodies that block the interaction of CTLA-4 or PD-1 with their ligands can be considered “drugs”.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY BENZION can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
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