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 .
Applicant's response to the previous Office action, dated November 13, 2025, has been received. By way of this submission, Applicant has amended the specification and claims 1, 17, and 40, cancelled claims 32, 56-57, 59, 68, 70, 72, 76-79, 89, and 91-93, and introduced new claim 111.
Claims 1, 15, 17, 24, 31, 40, 48, and 111 are pending in the application and under examination before the Office.
The rejections of record can be found in the previous Office action, dated August 13, 2025.
Specification
The disclosure was previously objected to because it contained an embedded hyperlink and/or other form of browser-executable code at page 46.
Applicant's amendment to the specification has addressed this issue, and this objection is hereby withdrawn.
Claim Rejections - 35 USC § 112
Claims 1, 15, 17, 24, 31-32, 40, and 48 were previously 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.
Applicant's amendments to the claims have addressed this issue, and this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 15, 17, 24, 31, 40, 48, and 111 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims recite a natural phenomenon, a method for predicting a subject's responsiveness to an autologous T cell therapy. This judicial exception is not integrated into a practical application because the claimed data gathering steps do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Applicant argues that the claims as amended recite a step of administering a particular therapy (a tyrosine kinase inhibitor (TKI)) to a subject having a particular renal cancer tumor microenvironment type (RC TME type E) and therefore integrates the judicial exception into a practical application.
Applicant's arguments have been considered fully but are not found to be persuasive.
Step (c) of amended claim 1 requires the step of identifying RC TME type E for the subject when the RC TME signature is associated with the particular RC TME, and step (d) recites the limitation of administering a tyrosine kinase inhibitor (TKI) to the subject when RC TME type E is identified for the subject. Both of these steps assume an RC TME type E signature is found. This is not always the case. If a non-type E signature is found, then step (d) would not be performed, and no treatment would be administered. This does not integrate the judicial exception into a practical solution in all cases.
If it is Applicant's intention that patients who do not have an RC TME type E signature are outside of the scope of the claims, this must be clearly and explicitly enumerated.
This rejection is therefore maintained and extended to encompass new claim 111.
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.
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, 15, 24, and 111 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Benjamin (US20210174908A1, cited in IDS).
Applicant argues that Benjamin does not teach every aspect of the claims as amended; specifically, Benjamin does not teach associating the RC TME signature to a particular RC TME signature cluster of the plurality of RC TME signature clusters, wherein the particular RC TME signature cluster is associated with RC TME type E; and identifying RC TME type E for the subject when the RC TME signature is associated with the particular RC TME, nor does Benjamin teach the specific gene groups recited.
Applicant's arguments have been considered but are not found persuasive.
Claim 1 requires obtaining RNA expression data for the subject, or at least some genes in each group of at least some of a plurality of gene groups. The claim requires only some genes in some of the groups, not all of the genes in all of the groups. As long as some of the genes in some of the groups are taught by the prior art, the claim limitation is anticipated. There is nothing in the claims which describes how the groups are to be used in performing the claimed method; the only required step is that some of the genes in some of the groups are used.
Benjamin teaches measuring the expression of CTLA4, LAG3, PDCD1LG2, PDCD1, TIGIT, and HAVCR2, which are members of the checkpoint inhibition group, and CXCL10, CXCL11, and CXCL9, which are members of the T cell traffic group, and GZMB, CD8B, and IFNG, which are members of the effector cells group (para. 0015 and Tables 1 and 2).
Benjamin also teaches the use of a clustering model as a mathematical model, in conjunction with a training population (para. 0397), which is pertinent to claim 111. Benjamin further teaches that applying such a model to the data will generate one or more classifiers (i.e., a signature cluster) using one or more gene panels, which is then used to classify a TME, as an angiogenic TME (para. 0398).
Benjamin teaches identification of a suitable therapeutic based upon TME type (para. 0373-0378). Benjamin further teaches that one such therapeutic maybe a tyrosine kinase inhibitor (TKI) (para. 0033, 0606, and 0708-0709). Benjamin also teaches that TKIs are useful in treating tumors with an angiogenic phenotype (para. 0599 and 0606). According to Applicant's specification at page 29, RC TME type E is characterized by elevated angiogenesis. Benjamin therefore anticipates the claimed treatment step.
This rejection is therefore maintained and extended to encompass new claim 111.
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.
Claims 1, 15, 17, 24, 31, 40, 48, and 111 are rejected under 35 U.S.C. 103 as being unpatentable over Benjamin in view of Weinschenk (US20100158931A1), as evidenced by GEO Accession Viewer (downloaded from the Internet July 31, 2025 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL570).
Applicant argues that Weinschenk does not remedy the alleged deficiencies of Benjamin. This is not found persuasive, for reasons described supra.
Applicant further argues that one of ordinary skill would not have combined the disclosures of Benjamin and Weinschenk to arrive at the claimed method.
Applicant's arguments have been considered fully but are not found to be persuasive.
As stated previously, both Benjamin and Weinschenk are concerned with panels of biomarkers for the assessment of renal cancer. Benjamin teaches that RNA expression levels may be determined using an Affymetrix microarray (para. 0014). Weinschenk teaches the use of the Affymetrix U133 Plus 2.0 array to generate RNA expression data from patients (para. 0354). According to GEO Accession Viewer, the Affymetrix U133 Plus 2.0 array includes all of the genes recited in claim 30. Weinschenk therefore inherently measuring RNA expression data from each of the genes listed in claims 15, 17, and 48.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06(I).
One of ordinary skill in the art could apply the Affymetrix U133 Plus 2.0 array of Weinschenk, which includes all of the claimed genes, to the method of Benjamin, with no change in their respective functions, and the combination would have yielded nothing more than predictable results.
It is noted that the claimed list of genes is an open list, recited with the transitional phrase "comprising", therefore other genes beside what is recited in the claim may be tested as well. The claims are not limited to testing only the recited genes. As the Affymetrix U133 Plus 2.0 array includes all of the claimed genes, the use of the Affymetrix U133 Plus 2.0 array, in its normal and usual function, would necessarily include testing of the genes recited in the claims.
Additionally, all of the genes recited in amended claim 48 are present in the Affymetrix U133 Plus 2.0 array, according to GEO Accession Viewer. A person of ordinary skill, when performing the Affymetrix U133 Plus 2.0 array according to Weinschenk, would also obtain RNA expression data from the recited group of genes. Benjamin teaches that sets of genes (i.e., gene groups) can be used to generate a score that is useful to reveal the dominant biologies represented by each signature and the TME phenotypes defined by the matrix of those signatures (para. 0092). Benjamin also teaches comparing patient biomarker levels to a threshold with a particular TME phenotype (para. 0102 and 0175).
This rejection is therefore maintained and extended to encompass new claim 111.
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, 15, 17, 24, 31, 40, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 7-9, 13-14, and 18-19 of U.S. patent 12,462,941 (formerly copending Application No. 18/634,443) in view of Benjamin and Weinschenk.
Applicant argues that the above amendments overcome this rejection. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained and extended to encompass new claim 111.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 8:00 to 4:00.
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/PETER JOHANSEN/Examiner, Art Unit 1644