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
Pursuant to a preliminary amendment, claims 1-28 and 31, filed September 16, 2022 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 1 and 4-22, directed to a method of preparing an enriched population of T cells having antigenic specificity for a target antigen; and Applicant’s election of Species as follows:
Species (A): one or more of the markers recited in claim 1a (claim 1a);
Species (A)(I): CD4+, CXCL13+, ITM2A+, KLRB1+, TIGIT+, LTB-, LYAR, RGCC-, and S100A10-
Species (B): the election of Species (B) is moot, directed to Group II;
Species (B)(I): the election of Species (B) is moot, directed to Group II;
Species (C): wherein the gene expression profile comprises CXCL13+ (claim 5); and
Species (D): wherein selecting the isolated T cells, which have a gene expression profile comprises carrying out one or more single cell dimensional reduction methods (claim 16), in the reply filed January 13, 2026 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) the Office Action does not cite any prior art, nor does it allege that any special technical feature in the claims is taught in the prior art with regard to at least Groups I-V and IX (Applicant Remarks, pg. 3, last partial paragraph through pg. 4, first full paragraph).
Regarding (a), as noted in the Requirement for Restriction/Election mailed 11-13-2025, Groups I-IX lack unity of invention. Thus, the requirement for restriction and election is proper. Considering arguendo, Groups I-V and IX alone, these groups share a technical feature of cells and antigenic specificity for a target antigen, which does not make a contribution over the prior art in view of Anderson, which teaches that an immune response, such as a B cell or T cell (CD4+ or CD8+) response an be antigen-specific including where target cells presenting an antigen peptide are recognized by the T cell receptor (paragraphs [0147]-[-148]).
Claims 2, 3 and 23-28 and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on January 13, 2026.
Claims 4, 6-15, and 17-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 5, 16 and 22 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 16, 2022, is a 35 U.S.C. 371 national stage filing of International Application PCT/US2021/023240, filed March 19, 2021, which claims the benefit of US Provisional Patent Application 62992701, filed March 20, 2020.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application 61/839,352, filed June 25, 2013, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; “(e) one or more ABI3+…, and PD-1+” such as recited in claim 1, lines 26-47. Therefore, the priority date for the presently claimed invention is March 19, 2021, the filing date of PCT/US2021/023240.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 1 of the instant application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on September 16, 2022; November 20, 2024; March 19, 2025; June 13, 2025 and July 16, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Rejections - 35 USC § 112(b)
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, 5, 16 and 22 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “the unselected cells” such as recited in claim 1, line 5. There is insufficient antecedent basis for the term “the unselected cells” in the claim.
Claims 5, 16 and 22 are indefinite insofar as they ultimately depend from instant claim 1.
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 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 1, 5, 16 and 22 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Sade-Feldman et al. (hereinafter “Sade-Feldman”) (US Patent Application Publication No. 20200147210, published May 14, 2020, PCT filed May 11, 2018).
Regarding claims 1 and 5, Sade-Feldman teaches that the subject matter disclosed herein is generally directed to CD8+ tumor infiltrating lymphocytes comprising gene signatures associated with response to immunotherapy treatment, wherein the subject matter is generally directed to methods and compositions for use of the gene signatures; as well as, gene signatures associated with response to checkpoint blockade therapy and immune cell subtypes characterized by said gene signatures; and methods of using said gene signatures and immune cell subtypes; and pharmaceutical compositions comprising populations of CD8+ TILs enriched for a specific subtype (interpreted as CD8+, claim 1) (Abstract). Sade-Feldman teaches that the efficiency of checkpoint therapy depends on CD8+ T-cell recognition of neoantigens presented on human leukocyte antigen (HLA) class I by tumor cells (interpreting target antigens as neoantigens associated with a cancer-specific mutation, claim 1) (paragraph [0005]). Sade-Feldman teaches that the present invention provides for a method of predicting cancer clinical outcome in a subject in need thereof comprising detecting in a sample obtained from the subject the ratio of immune cells enriched for expression of a gene signature according to any of claims 1 to 3 as compared to immune cells enriched for expression of a gene signature according to claims 4 or 5, wherein a ratio greater than one indicates sensitivity to an immunotherapy and an increased overall survival, and wherein a ratio less than one indicates resistance to an immunotherapy and a decreased overall survival (interpreted as enriching cells having antigenic specificity for a target antigen; and having a gene expression profile, claim 1) (paragraph [0015]). Sade-Feldman teaches that the method comprises detecting mutations associated with loss of antigen presentation in tumor cells obtained from the subject, which indicates resistance to an immunotherapy and a decreased overall survival (interpreted as a cancer-specific mutation, claim 1) (paragraph [0017]).
Sade-Feldman teaches that the biomarkers of the present invention were discovered by analysis of expression profiles of single immune cells within populations of cells from freshly isolated tumors, thus allowing the discovery of novel gene signatures and immune cell subtypes that were previously unrecognized, wherein treatment of solid tumors has been revolutionized by immune checkpoint blockade therapies; yet even in melanoma, for which high response rates are observed, the majority of patients do not respond; and to identify key immunological components associated with success or failure of immunotherapy, such that 16,291 immune cells were profiled from 48 tumor samples of melanoma patients treated with checkpoint inhibitors, using single-cell transcriptomics, wherein samples were obtained from melanoma patients receiving checkpoint blockade therapy both before they received treatment and after they received treatment with a checkpoint inhibitor, such that a non-responder signature and a responder signature are identified in the CD8+ TILs (interpreted as isolating T cells from a tumor sample of a patient; and selecting isolated T cell that have a gene expression profile; and having antigenic specificity, claim 1) (paragraph [0105], lines 1-20). Sade-Feldman teaches that the invention provides for a method of detecting a checkpoint blockade (CPB) therapy responder gene signature comprising, detecting in CD8+ T cells obtained from a biological sample the expression of a gene signature comprising one or more genes or polypeptides including LTB and RGCC (interpreted as CD8+, LTB and RGCC, claim 1) (paragraph [0009]). Sade-Feldman teaches a method of detecting a checkpoint blockade (CPB) therapy responder gene signature comprising, detecting in CD45+ cells obtained from a biological sample the expression of a gene signature comprising one or more genes or polypeptides including LTB (interpreted as including LTB, claim 1) (paragraph [0008]). Sade-Feldman teaches a method of detecting a checkpoint blockade (CPB) therapy non-responder gene signature comprising, detecting in CD45+ cells obtained from a biological sample the expression of a gene signature comprising one or more genes or polypeptides including CXCL13, CD4, TIGIT (interpreted as including CXCL13, CD4, TIGIT, claims 1 and 5) (paragraph [0011]). Sade-Feldman teaches that “immune cells” include CD4+/CD8+ thymocytes, B-cells, etc. (interpreted as CD4+ and CD8+, claim 1) (paragraph [0141]). Sade-Feldman teaches in Figure 25B, a heatmap showing scaled expression values (log2(TPM+1)) of discriminative gene sets for each cluster defined in (A) including S100A10, CXCL13 and LTB (interpreted as including S100A10, CXCL13 and LTB, claim 1) (paragraph [0063], lines 5-8; and Figure 25B). Sade-Feldman teaches maker genes identified for the 6 different clusters, suggesting that these markers indeed highlight distinct biological functions (Table 10), wherein Table 10 includes the markers: CXCL13, LTB, TIGIT, and LYAR (interpreted as including CXCL13, LTB, TIGIT, and LYAR, claims 1 and 5) (paragraph [0642], lines 53-55; and pgs. 130-131, Table 10). Sade-Feldman teaches that unsupervised clustering of cells was initially performed on 16,291 cells that passed quality control, based on the -4,000 most variable genes across all cells, where Table 2C includes genes CXCL13 and ITM2A (interpreted as including ITM2A and CXCL13, claims 1 and 5) (paragraph [0636], lines 2-4 and 13; and Table 2C). Sade-Feldman teaches that dg T-cells are enriched in CD4/CD8 double negative (DN) T cells (Fig. 17); and that V61 T-cells have a high expression of inhibitory receptors and V62 T-cells have a higher expression of KLRB1 and other genes (interpreted as CD4, CD8 and KLRB1, claim 1) (paragraph [0629]). Sade-Feldman teaches the markers ITM2A, CXCL13, CD4, LTB, and KLRB1 in Table 2D (interpreted as ITM2A, CXCL13, CD4, LTB, and KLRB1 elected species, claim 1) (pgs. 181, 183 and 184; Tables 2D and 2E). Sade-Feldman teaches in claim 4e, and Tables 9 & 10, AFAP1IL2 (interpreted as AFAPIl2, claim 1) (claim 4e, and pg. 213, Table 9; pg. 219, Table 10).
Regarding claim 16, Sade-Feldman teaches that about 4000 genes were selected and the results were robust to this threshold, wherein dimension reduction is performed such that the genes with the most variance are used to further cluster the cells (e.g., tSNE analysis) (interpreting tSNE as a single cell dimensional reduction method; and selecting, claims 1 and 16) (paragraph [0611]).
Regarding claim 22, Sade-Feldman teaches that aspects of the invention involve the adoptive transfer of immune system cells, such as T cells, specific for selected antigens, such as tumor associated antigens or tumor specific neoantigens (see, e.g., Maus et al., 2014, Adoptive Immunotherapy for Cancer or Viruses, Annual Review of Immunology, Vol. 32: 189-225; and Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood. 2014 Jul. 17; 124(3):453-62) (interpreted to include cancer-associated viral antigens, claim 22) (paragraph [0309]). Sade-Feldman teaches that an antigen (such as a tumor antigen) to be targeted in adoptive cell therapy (such as particularly CAR or TCR T-cell therapy) of a disease (such as particularly of tumor or cancer) can be selected from a group including Human papillomavirus (HPV) including HPV E6 and HPV E7 (interpreted as the cancer-associated viral antigen is an HPV antigen, claim 22) (paragraph [0310], lines 1-5 and 29-30). Sade-Feldman teaches that HPV E6 and/or HPV E7 can be targeted in cervical cancer or head and neck cancer (interpreted as the cancer-associated viral antigen is an HPV antigen, claim 22) (paragraph [0315], lines 6 and 24-25).
Sade-Feldman does not specifically exemplify one or more of ASB2, HMOX1, and PDLIM4 (claim 1, in part).
Sade-Feldman meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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.
Claims 1, 5, 16 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Sade-Feldman et al. (hereinafter “Sade-Feldman”) (US Patent Application Publication No. 20200147210, published May 14, 2020, PCT filed May 11, 2018) in view of Fotin-Mleczek et. al. (hereinafter “Fotin-Mleczek”) (US Patent No. 11078247, issued August 3, 2021; WO2017/191274, filed May 4, 2017).
The teachings of Sade-Feldman as applied to claims 1, 5, 16 and 22 are described supra.
Sade-Feldman does not specifically exemplify one or more of ASB2, HMOX1, and PDLIM4 (claim 1, in part).
Regarding claim 1 (in part), Fotin-Mleczek teaches RNA encoding a therapeutic protein including RNA suitable for use as a medicament; and the use of the RNA, compositions or kits as disclosed herein for increasing the expression of said encoded protein, in particular in gene therapy (Abstract). Fotin-Mleczek teaches that a "therapeutic protein" as defined herein is typically a peptide or a protein, which is beneficial for the treatment or prophylaxis of any inherited or acquired disease or which improves the condition of an individual, wherein therapeutic proteins play a key role in the design of new therapeutic agents that could modify and repair genetic deficiencies, destroy cancer cells or pathogen infected cells, treat or prevent immune system disorders, or treat or prevent metabolic or endocrine disorders, among other functions (interpreted for the treatment of cancer or infections including papillomavirus infections (col 15, lines 12-20; and col 767, line 5). Fotin-Mleczek teaches that the term "therapeutic protein" refers to any one of the peptides or proteins described herein, and more preferably to any one of the peptides or proteins specified in Table 1 herein, wherein the at least one coding sequence of the RNA according to the invention thus preferably encodes a peptide or protein provided in Table 1, or a fragment or variant thereof (col 16, lines 55-63). Fotin-Mleczek teaches in Table 1, ASB2, HMOX1 and PDLIM4 (col 20, line 5; col 30, line 30; and col 38, line 24).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of treating cancer and/or infections using therapeutic peptides and/or proteins as exemplified by Fotin-Mleczek, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of using gene signatures associated with response to checkpoint blockade therapy and immune cell subtypes characterized by the gene signatures including the analysis and profiling of biomarkers obtained from isolated tumors including CXCL13, ITM2A, TIGIT, LTB, LYAR, RGCC and S100A10 as disclosed by Sade-Feldman, to include the expression of RNA encoding a therapeutic peptides and/or proteins; and/or compositions comprising therapeutic peptides and/or proteins including ASB2, HMOX1 and/or PDLIM4 as exemplified by Fotin-Mleczek with a reasonable expectation of success in using gene signatures to differentiate patients that are checkpoint blockade therapy responders or non-responders, to determine associations with tumor growth, and/or to determine clinical outcome; as well as, using expanded immune cell populations expressing the therapeutic peptides and/or proteins for the treatment of various cancers and/or viral infections.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
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, 5, 16 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over: claims 1-3, 5, 7, 8, 10, 11, 14, 17 and 53 of copending US Patent Application No. 17/906524.
US17/906524 teaches - a method of preparing an enriched population of T cells having antigenic specificity for a target antigen, the method comprising: isolating T cells from a blood sample of a patient; selecting the isolated T cells which have a gene expression profile; and separating the selected T cells from the unselected cells, wherein the separated selected T cells provide an enriched population of T cells having antigenic specificity for the target antigen, wherein the target antigen is a neoantigen encoded by a cancer-specific mutation, a cancer antigen, or a cancer-associated viral antigen, and the gene expression profile comprises: (a) one or more of ACTG1+…and ZFAS1- (claim 1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US17/912315 and the copending claims of US17/906524 encompass a method comprising preparing an enriched population of T cels having antigenic specificity for a target antigen, comprising: isolating, selecting, and separating, wherein the gene expression profiles overlap.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 5, 16 and 22 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684