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/Action Summary
This action is in response to the papers filed on March 10, 2026.
Claims 4-6 were canceled in the amended claims. Claim 9 was newly added by amendment. Claims 1-3 and 7-9 are under examination. No other claims are currently pending in the present application.
Any objections and rejections not reiterated below are hereby withdrawn.
The 112(a) written description rejection of record is withdrawn in view of the amendments to the claims narrowing the claim scope from “treatment comprising surgical resection and immunotherapy and/or adjuvant chemotherapy…” to “treating the selected subject with pembrolizumab”.
The 112(b) indefiniteness rejection over the claim term “the tumor gene expression levels are above the reference gene expression levels” has been withdrawn in view of the persuasive argument in the response that the term “above” should be interpreted as having “its normal meaning – it simply requires that the levels determined are numerically above the reference levels.” (see claim interpretation section below)
The 112(b) indefiniteness rejection over the claim term “reference gene expression levels” has been withdrawn in view of the persuasive argument in the response that “this term is well known in the art, and the specification provides examples of how to determine what the appropriate reference gene expression levels would be (see paragraphs [0032]-[0037] of US 20230323468 A1); specific numbers can be determined using no more effort than is routine in the art”. (See claim interpretation section below).
The 112(b) rejection over claim 8 inadvertently omitted reasoning that the claim was indefinite because of its dependence from claim 1. This rejection is moot given the 112(b) rejections to claim 1 are now withdrawn.
The rejection under 35 U.S.C. 101 has been withdrawn in view of the amendments to the independent claim 1 now requiring treating the selected subject expressing the recited panel of 12 chemokines at higher levels than reference gene expression levels with the particular therapy pembrolizumab.
The rejection under 35 U.S.C. 103 over Magliocco et al. in view of Pfannstiel et al. over claims requiring “administering adjuvant chemotherapy comprising a platinum-based chemotherapeutic” has been withdrawn because the amended claims no longer recite this claim limitation, but rather require treatment with pembrolizumab (a monoclonal anti-PD1 antibody).
Priority
The present application, filed on February 24, 2023, is a 371 of PCT/US2021/048028, filed on August 27, 2021, which claims the benefit of U.S. Provisional Application 63/071,320, filed on August 27, 2020. Therefore, the effective filing date of the present application is determined to be August 27, 2020.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
In view of the persuasive arguments in the response filed March 10, 2026, the claim term “tumor gene expression levels above the reference gene expression levels” has been broadly interpreted as “simply requir[ing] that the levels determined are numerically above the reference levels”
In view of the persuasive arguments in the response filed March 10, 2026 referring to paragraphs [0032]-[0037] of US 20230323468 A1 and asserting the term “reference gene expression levels” is “well known in the art, and the specification provides examples of how to determine what the appropriate reference gene expression levels would be (see paragraphs [0032]-[0037] of US 20230323468 A1); specific numbers can be determined using no more effort than is routine in the art”. Therefore, the claim term “reference gene expression levels” has been broadly interpreted as encompassing expression levels “compared individually to levels in a reference… in a subject who has a good prognosis, or a long predicted survival time…, a subject who has a poor prognosis, or a shorter predicted survival time… levels in a subject who has lymphoid like structures present in the tumor… who lacks tumor lymphoid structures,” (i.e. positive or negative controls for known prognosis or survival time), or “an endogenous control gene” (i.e. an internal control, “reference” gene measured in the “cells from the tumor”) (US 20230323468 A1, paragraph [0032]-[0037]).
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.
Claims 1-3 and 7-9 are/remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Magliocco et al., WO 2015/157623 A1, published October 15, 2015.
This is a new grounds of rejection necessitated by the claim amendments now requiring treatment with pembrolizumab and the addition of new claim 9.
Regarding claim 1, Magliocco et al. teach methods of treating a subject who has a tumor of the bladder comprising selecting a treatment comprising chemotherapy when the gene expression levels of chemokines CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11, and CXCL13 in cells obtained from the tumor are above reference gene expression levels (Magliocco et al., page 3, lines 7-16). Magliocco et al. further teach the gene expression signature (high 12 chemokine expression) is particularly relevant to invasive bladder cancer (Magliocco et al., page 1, lines 18-30; page 8, line 4-5) and more particularly, muscle-invasive bladder cancer (Magliocco et al., page 21, lines 26-27).
Magliocco et al. further teach methods including “selecting and… administering treatment including one or more of: dendritic cells or peptides with adjuvant, DNA-based vaccines, cytokines, cyclophosphamide, anti-interleukin-2R immunotoxins, and/or antibodies such as… anti-PD1 (e.g. pembrolizumab)” (Magliocco et al., page 11, lines 14-21) (i.e. Pembrolizumab is an anti-PD1 antibody).
Therefore, Magliocco et al. teach each of the method steps recited by claim 1.
Regarding claim 2, Magliocco et al. teach determining protein levels of the recited genes (Magliocco et al., page 3, line 18).
Regarding claim 3, Magliocco et al. teach determining mRNA levels of the recited genes (Magliocco et al., page 3, lines 19-20).
Regarding claim 7, Magliocco et al. teach the subject is a human (Magliocco et al., page 4, line 33).
Regarding claim 8, Magliocco et al. teach comparing expression levels comprises calculating an expression score based on the gene expression levels, e.g., based on the weighted average of the gene expression levels, and comparing the expression score to a reference expression score (Magliocco et al., page 4, lines 28-31).
Regarding claim 9, Magliocco et al. teach “cells can be obtained by known methods, e.g. during a biopsy… or during a surgical procedure to remove all or part of the tumor (e.g. transurethral resection of the bladder tumor…” (Magliocco et al., page 9, lines 25-29) (i.e. the subject has undergone surgical resection for the MIBC).
Response to arguments
The response asserts “while Magliocco et al. teaches bladder cancer, including invasive bladder cancer, it neither teaches nor suggests the specific combination of muscle-invasive bladder cancer and the treatment pembrolizumab. For at least this reason… the pending claims are novel…” (Remarks March 10, 2026)
This assertion has been thoroughly considered and is not persuasive. As described in the 102(a)(1) rejection above, Magliocco et al. do indeed teach the claim elements muscle-invasive bladder cancer at least at (Magliocco et al., page 21, lines 26-27) and selecting and administering treatment comprising pembrolizumab based upon the expression levels of the recited chemokine genes at least at (Magliocco et al., page 11, lines 14-21).
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, 3-5, and 7 are/remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of U.S. Patent No. 10,583,183 B2 (herein referred to as ‘183) in view of Pfannstiel et al. and as evidenced by Kwok et al., “Pembrolizumab (Keytruda)”, Human Vaccines & Immunotherapeutics, 12:11, 2777-2789 (published July 26, 2016).
This is a new grounds of rejection necessitated by the amendments to the present claims and the addition of new claim 9.
Regarding claim 1, the claims of ‘183 recite a method of treating a subject who has urothelial carcinoma comprising: obtaining cells from the tumor, determining mRNA expression levels of CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11, and CXCL13 in the tumor cells, comparing the tumor expression levels to reference expression levels, and administering a treatment comprising anti-PD1, anti-PDL1, or anti-CTLA-4 antibodies (i.e. an immunotherapy) to a subject who has expression levels above the reference expression levels (‘183, claim 1). Claim 4 of ‘183 further requires that the treatment comprises an anti-PD1 antibody.
It is noted that the claimed treatment “pembrolizumab is… a[n] anti-PD1 antibody” (Kwok et al., page 1, abstract).
Furthermore, the present specification notes that “pembrolizumab (anti-PD-1)… [is] FDA approved for the treatment of patients with urothelial carcinoma that has spread beyond the bladder… having revolutionized the treatment paradigm for muscle invasive and metastatic bladder cancers” (US 20230323468 A1, PGPub of present application, paragraph 0003) (i.e. that pembrolizumab is a well-recognized treatment for muscle-invasive bladder cancer widely known in the art (i.e. “FDA Approved”) prior to the filing of the claimed invention).
The claims of ‘183 do not specify that the urothelial carcinoma is muscle invasive bladder cancer.
However, Pfannstiel et al. teach that approximately two-thirds of invasive urothelial bladder cancers are muscle-invasive bladder cancer, and that MIBC that is responsive to chemotherapy/immunotherapy tend to have increased prevalence of tumor-infiltrating lymphocytes and tertiary lymphoid structures as well as high expression of several of the recited chemokines.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art to have modified the method claimed by ‘183 comprising treating a subject with urothelial carcinoma (i.e. a genus of cancers) to treat subjects with muscle invasive bladder cancer (i.e. a species within the genus urothelial carcinoma) because of the teaching of Pfannstiel that MIBC comprises ~66% of invasive UC cases.
Regarding claim 3, the claims of ‘183 recite determining mRNA levels of the genes recited by present claim 1 (‘183, claim 1).
Regarding claim 7, the claims of ‘183 recite the subject is a human (‘183, claim 2).
Response to arguments
The response requests that the double patenting rejection be held in abeyance until allowable subject matter is reached. This request has been noted, however MPEP 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance, includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Bacus et al., US 20180080087 A1.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ZACHARY MARK TURPIN whose telephone number is (703)756-5917. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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