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
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Claim 20-34 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/23/2026 .
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lima, Oncotarget, May 23, 2016, Vol. 7, No. 18, pp. 25885-25901; Coleman, British journal of cancer, Published online: 16 December 2020 (= December 16, 2021, Vol. 124, No. 5, pp. 857-859; Krushkal, Clinical Epigenetics (2020) 12:93, Thomas, J. Clin. Oncol., 36 (2018), Horita, Sci Rep. 2015 Oct 21;5:15437, pp. 1594-1602, and Schwendenwein, Molecular Therapy: Oncolytics Vol. 20 March 2022.
Base Claim 1: A method for treating a subject with small cell lung cancer (SCLC) or with a neuroendocrine cancer, the method comprising administering a combination of lurbinectedin and an ATR (taxia telangiectasia and Rad3-related protein ) inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression
Lima titled, "Dual Inhibition of ATR and ATM Potentiates the Activity of Trabectedin and Lurbinectedin by Perturbing the DNA Damage Response and Homologous Recombination Repair” teaches a method for treating a subject with cancer (a method for treating a cell (subject) with cancer such as a HeLa cell; abstract; page 25886, 2nd column, 1st paragraph), the method comprising administering a combination of lurbinectedin and an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject (administering a combination of lurbinectedin and an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a cell (subject); abstract; page 25886, 2nd column, 2nd paragraph; figures 3-4).
Lima does not teach a method for treating a subject with small cell lung cancer "SCLC"
Coleman titled, “The role of Schlafen 11 (SLFN11) as a predictive biomarker for targeting the DNA damage response” teaches a method for treating a subject with small cell lung cancer "SCLC" (a method for treating a patient (subject) with small cell lung cancer "SCLC"; page 857, 2nd column, 2nd paragraph), the method comprising administering a combination including an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression in a biological sample from the subject (administering a combination with an ATR inhibitor to a patient that has low or absent SLFN11 expression in a tumor (biological sample) from a patient; page 857, 1st column 4th paragraph to 2nd column, 1st paragraph).
That SLFN11 expression is inexorably linked to SCLC is also taught in Krushkal titled Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets, who at page 20, column B, depression of SLFN11 have emerged as significant predictors of SCLC response to DNA-damaging agents).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the method of treating a cell with cancer of LIMA to include a method for treating a subject with small cell lung cancer "SCLC", the method comprising administering a combination including an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression in a biological sample from the subject, as taught by Coleman, in order to gain the advantages of providing a promising predictor of sensitivity to cytotoxic chemotherapies (see Coleman page 857, 1st column, 2nd to 3rd paragraph).
Lima at page 25890 further discloses the ATR inhibitor comprises VE-821, LR-02, RP-3500, SC-0245, M-1774, M4344, ATG-018, IMP-9064, nLs-BG-129, BAY-1895344, berzosertib, ART-0380, ATRN-119, ATRN-212, BKT-300, AZ-20, ceralasertib, or combinations thereof (the ATR inhibitor includes VE-821; figures 3-4; page 25890, 1st to 2nd column) (for claims 2-3)
Claims 4-15: SLFN11 expression and assay. Coleman at page 857 discloses wherein the subject was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a biological sample from the subject (the patient was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a tumor (biological sample) from the patient; page 857, 2nd column, 2nd paragraph). It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the method of treating a cell with cancer wherein the subject was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a biological sample from the subject, as taught by Coleman, in order to gain the advantages of confirming if SLFN11 is a bona fide predictive biomarker and if the efficacy of such combination regimens are attributed to low or absent tumor SLFN11 (see Coleman page 857, 2nd column, 1st paragraph).
The combination of ATR inhibitors with established anticancer drugs has been suggested for treating SCLC. For example, Thomas, titled, “Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumor teaches in a phase 1 trial for patients with a variety of solid tumors”, teaches that three out of five patients with platinum-resistant SCLC derived durable clinical benefit with topotecan plus ATR inhibitor berzosertib. Likewise, the limitations of claims 16-19 (humans!, not having been treated with established SCLC drugs, recurrent SCLC which given that with over 50% of patients experiencing relapse within 1-2 years of initial treatment, and types of SCLC are well-within the purview of one of skill in the art (see Horita, Topotecan for Relapsed Small-cell Lung Cancer: Systematic Review and Meta-Analysis of 1347 Patients Schwendenwein titled Review, Molecular profiles of small cell lung cancer subtypes: therapeutic implications).
As such there is extensive overlap in the conflicting claims.
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-onlin`e/eterminal-disclaimer.
Claims 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim q of copending Application No. 18549857 (reference application) further in view of Lima, Oncotarget, May 23, 2016, Vol. 7, No. 18, pp. 25885-25901; Coleman, British journal of cancer, Published online: 16 December 2020 (= December 16, 2021, Vol. 124, No. 5, pp. 857-859; Krushkal, Clinical Epigenetics (2020) 12:93, Thomas, J. Clin. Oncol., 36 (2018), Horita, Sci Rep. 2015 Oct 21;5:15437, pp. 1594-1602, and Schwendenwein, Molecular Therapy: Oncolytics Vol. 20 March 2022. . Although the claims at issue are not identical, they are not patentably distinct from each other in the context of the teachings in the secondary reference, is reiterated below, though redundant) as explained below:
Claim 1 of 18549857:
A method for treating a subject with small cell lung cancer (SCLC) or with a neuroendocrine cancer, the method comprising administering one or more therapeutics to a subject that has had been evaluated for SLFN11 expression in a biological sample from the subject; wherein the one or more therapeutics comprise lurbinectedin.
The difference is that the combination possibility in the ‘one or more therapeutics’ and lurbinectedin does not explicitly include ATR inhibitor. That ATR inhibitors are included in the above claimed method is obvious from the recitation in claim 16 of 18549857, which explicitly excludes ATR inhibitor, thereby making it clear that claim 1 of 18549857 includes ATR inhibitor.
The inclusion of the following here, in the obviousness analysis is consistent with the Graham factual inquiries as per MPEP [R-01.2024] relating what is known to one of skill in the art
Lima titled, "Dual Inhibition of ATR and ATM Potentiates the Activity of Trabectedin and Lurbinectedin by Perturbing the DNA Damage Response and Homologous Recombination Repair” teaches a method for treating a subject with cancer (a method for treating a cell (subject) with cancer such as a HeLa cell; abstract; page 25886, 2nd column, 1st paragraph), the method comprising administering a combination of lurbinectedin and an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject (administering a combination of lurbinectedin and an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a cell (subject); abstract; page 25886, 2nd column, 2nd paragraph; figures 3-4).
Lima does not teach a method for treating a subject with small cell lung cancer "SCLC"
Coleman titled, “The role of Schlafen 11 (SLFN11) as a predictive biomarker for targeting the DNA damage response” teaches a method for treating a subject with small cell lung cancer "SCLC" (a method for treating a patient (subject) with small cell lung cancer "SCLC"; page 857, 2nd column, 2nd paragraph), the method comprising administering a combination including an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression in a biological sample from the subject (administering a combination with an ATR inhibitor to a patient that has low or absent SLFN11 expression in a tumor (biological sample) from a patient; page 857, 1st column 4th paragraph to 2nd column, 1st paragraph).
That SLFN11 expression is inexorably linked to SCLC is also taught in Krushkal titled Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets, who at page 20, column B, depression of SLFN11 have emerged as significant predictors of SCLC response to DNA-damaging agents).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the method of treating a cell with cancer of LIMA to include a method for treating a subject with small cell lung cancer "SCLC", the method comprising administering a combination including an ATR "taxia telangiectasia and Rad3-related protein" inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression in a biological sample from the subject, as taught by Coleman, in order to gain the advantages of providing a promising predictor of sensitivity to cytotoxic chemotherapies (see Coleman page 857, 1st column, 2nd to 3rd paragraph).
Lima at page 25890 further discloses the ATR inhibitor comprises VE-821, LR-02, RP-3500, SC-0245, M-1774, M4344, ATG-018, IMP-9064, nLs-BG-129, BAY-1895344, berzosertib, ART-0380, ATRN-119, ATRN-212, BKT-300, AZ-20, ceralasertib, or combinations thereof (the ATR inhibitor includes VE-821; figures 3-4; page 25890, 1st to 2nd column) (for claims 2-3)
Claims 4-15: SLFN11 expression and assay. Coleman at page 857 discloses wherein the subject was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a biological sample from the subject (the patient was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a tumor (biological sample) from the patient; page 857, 2nd column, 2nd paragraph). It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the method of treating a cell with cancer wherein the subject was evaluated for SLFN11 expression by evaluating SLFN11 in an immunohistochemistry assay performed on a biological sample from the subject, as taught by Coleman, in order to gain the advantages of confirming if SLFN11 is a bona fide predictive biomarker and if the efficacy of such combination regimens are attributed to low or absent tumor SLFN11 (see Coleman page 857, 2nd column, 1st paragraph).
The combination of ATR inhibitors with established anticancer drugs has been suggested for treating SCLC. For example, Thomas, titled, “Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumor teaches in a phase 1 trial for patients with a variety of solid tumors”, teaches that three out of five patients with platinum-resistant SCLC derived durable clinical benefit with topotecan plus ATR inhibitor berzosertib. Likewise, the limitations of claims 16-19 (humans!, not having been treated with established SCLC drugs, recurrent SCLC which given that with over 50% of patients experiencing relapse within 1-2 years of initial treatment, and types of SCLC are well-within the purview of one of skill in the art (see Horita, Topotecan for Relapsed Small-cell Lung Cancer: Systematic Review and Meta-Analysis of 1347 Patients Schwendenwein titled Review, Molecular profiles of small cell lung cancer subtypes: therapeutic implications).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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