DETAILED ACTION
Receipt of Arguments/Remarks filed on June 9 2026 is acknowledged. Claims 6-7, 10-11, 14-16 and 18 were/stand cancelled. Claims 1, 5, 21-23 were amended. Claim 24 was added. Claims 1-5, 8-9, 12-13, 17 and 19-24 are pending. Claims 2-3, 8-9, 12-13 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 25 2025. Claims 1, 4-5 and 19-24 are directed to the elected invention.
The examiner notes that while the remarks indicate this in response to the final Office Action dated May 26 2025 but is actually in fact in response to the non-final Office Action dated February 9 2026, the response does appear to address all previous objections/rejections and therefore this is interpreted as a typo.
The examiner further notes that Applicants previously elected STEAP4 which has been removed as an option in the instant claims. Therefore, the species election has been expanded to include RPA1.
.
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 .
Withdrawn Objections/Rejections
The amendments to the drawings filed June 9 2026 are sufficient to overcome the objection to the drawings. The drawings are accepted.
The amendments filed June 9 2026 are sufficient to overcome the objection to claim 1 and 23. The abbreviations were spelt out and the misspelled words were corrected.
The amendments filed June 9 2026 are sufficient to overcome the rejection claims 1, 4-6, 16 and 18-23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. The reference to tables has been removed from the claims and the antecedent basis issues have been corrected.
The amendments filed June 9 2026 are sufficient to overcome the rejection of claims 1, 4-6, 16 and 19-23 under 35 USC 112(a) or 35 USC 112(pre-AIA ), first paragraph written description. Claim 1 was amended to incorporate formula A which was indicated as possessing written description support for the recitation ULK inhibitor.
The amendments filed June 9 2026 are sufficient to overcome the rejection of claims 1, 4-6, 16 and 18-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The scope of disorders claimed are those associated with elevated ULK levels. Since the claims are directed to administering a therapeutically effective amount of a ULK inhibitor, administration to subjects with a disorder associated with elevated ULK levels is implicitly supported.
The amendments filed June 9 2026 are sufficient to overcome the rejection of claims 1, 4-6, 16 and 18-22 under 35 U.S.C. 103 over Tang et al. (Oncology Reports, cited on PTO Form 1449 filed 5/12/25-C100) as evidenced by Dite et al. (Journal of Biological Chemistry, 2018) in view of Guise et al. (WO2019125184) and the rejection of claim 23 under 35 U.S.C. 103 over Tang et al. as evidenced by Dite et al. in view of Guise et al. and in further view of Li et al. (Chin J Cancer, 2017). The claims do not expressly include STEAP4 biomarker gene in the claim. Neither Tang et al. or Guise et al. expressly teach one of the instantly claimed biomarker genes. Therefore, Applicants’ arguments in light of the amendments are persuasive. However, a new grounds of rejection necessitated by the amendments is made below.
The amendments filed June 9 2026 are sufficient to overcome the rejection of claims 1, 4-6, 16 and 18-22 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,266,549 in view of Tang et al. as evidenced by Dite et al. and Guise et al.; the rejection of claims 1, 4-6, 16 and 18-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,689,397 in view of Tang et al. as evidenced by Dite et al. and Guise et al. ; the rejection of claims 1, 4-6, 16 and 18-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,774,092 in view of Tang et al. as evidenced by Dite et al. and Guise et al.; the rejection of claim 23 on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,774,092 or 10, 266,549 or 10689397 in view of Tang et al. as evidenced by Dite et al. and Guise et al. and in further view of Li et al. (Chin J Cancer, 2017); the rejection of claims 1, 4-6, 16 and 18-23 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 7-9, 14- 15, 18-20, 23-24, 50-54 and 57-58 of copending Application No. 17799641(USPGPUB No. 20230130766) in view of Guise et al.; the rejection of claims 1, 4-6, 16 and 18-21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 10-11, 14, 22, 25, 33, 38, 40, 43-44, 50, 191, 192-193, 195-196, 199-200 and 205 of copending Application No. 17799639 (USPGPUB No. 20230135635) in view of Guise et al.; the rejection of claims 1, 4-6, 16 and 18-21 on the ground of nonstatutory double patenting as being unpatentable over claims 54-57, 59-60, 65-66 of copending Application No. 17799634 (USPGPUB No. 20230099804) in view of Guise et al.; and the rejection of claims 22-23 on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 17799634 OR 17799639 in view of Guise et al. as applied to claims 1, 4-6, 16 and 18-21 above and in further view of Li et al. The claims do not expressly include STEAP4 biomarker gene in the claim. Neither Tang et al. or Guise et al. or any of the Patent/copending applications expressly teach one of the instantly claimed biomarker genes. Therefore, Applicants’ arguments in light of the amendments are persuasive.
New Objections/Rejections Necessitated by the Amendments filed June 9 2026
Claim Objections
Claim 1 is objected to because of the following informalities: a comma is missing between ST3GAL1 and SASH1. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: the claim should be to change “the disorder mediated by ULK” to “the disorder associated with elevated ULK levels” in order to be consistent with the changes made to claim 1 . Appropriate correction is required.
Applicant is advised that should claim 4 be found allowable, claim 24 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 4-5, 19-22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Tang et al. (Oncology Reports, cited on PTO Form 1449 filed 5/12/25-C100) as evidenced by Dite et al. (Journal of Biological Chemistry, 2018) in view of Li et al. (Carcinogenesis, 2017).
Applicant Claims
The instant application claims a method of treating a disorder associated with elevated ULK levels in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a ULK inhibitor of formula A, wherein a tissue affected by the disorder in the subject has a distinct expression of at least one of biomarker genes such as RPA1.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Tang et al. is directed to SBI020695, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell growth by modulating both autophagy and apoptosis pathways. Autophagy is a process of phagocytosis of unnecessary or dysfunctional components, fusion with lysosomes and degradation of the contents of the lysosomes to maintain cellular homeostasis. Dysregulation of autophagy is often observed in lung cancer. Inhibition of autophagy sensitizes NSCLC (non-small cell lung cancer) cells to chemotherapy (page 3449, right column). Ulk1 is upregulated in NSCLC cell lines and negatively correlated with prognosis in patients with NSCLC. Knockdown of ULK1 inhibited cell growth and sensitized NSCLC cells to cisplatin. Inhibition of ULK1 by SBI0206965 reduced the proliferation of NSCLC cells and induces cell apoptosis by inhibiting autophagy (page 3450, left column; page 3451, right column and Fig. 1). Ulk1 is required for autophagy in severe hypoxia (page 3456, left column). Many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These rules suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin (page 3452, last paragraph).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Tang et al. teaches the use of a ULK inhibitor in treating non-small cell lung cancer, Tang et al. does not expressly teach the use of biomarkers. However, this deficiency is cured by Li et al.
Li et al. is directed to hypoxia pathway genetic variants predict survival of non-small-cell lung cancer patients receiving platinum-based chemotherapy. Biomarkers have been shown to be associated with the survival of non-small cell lung cancer (NSCLC) (page 419, last paragraph). Hypoxia is a hallmark of solid tumors and is associated with advanced disease stage and poor clinical outcome. It was found that SNPs in exonuclease 1 (EXO1) and human replication protein A 1 (RPA1) gene associated with survival in late stage NSCLC patients receiving platinum-based chemotherapy. RPA1 is important in DNA repair, replication and recombination. RPA1 is involved in cancer development and progression. Previous studies have shown tumor cells had higher expression of RPA1 protein and mRNA than normal cells (page 422, last two paragraphs). It was shown that chemotherapy-treated NSCLC patients with RPA1: rs2270412 AA+GA genotype had a significantly worse survival than those with the GG genotype. The GG genotype had lower expression of RPA1 consistent with prior studies that lower expression of RPA1 was associated with better survival and higher expression with worse survival in other cancers (page 423, first paragraph). These data suggest that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes (page 423, second to last paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Tang et al. and Li et al. and administer a therapeutically effective amount of SBI020695, a novel inhibitor of Ulk1, to a subject affected with non-small cell lung cancer. One skilled in the art would have been motivated to administer SBI020695 as it inhibits the autophagy associated with NSCLC. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. Nonetheless, this suggests the tissue affected by the disorder taught in Tang et al. would possess a distinct expression of the biomarker gene RPA1.
Regarding claims 4-5, 21 and 24, Tang et al. teaches NSCLC which is a lung cancer.
Regarding the claimed ULK1 inhibitor, as evidenced by Dite et al., SBI-0205965 has the following structure:
PNG
media_image1.png
134
300
media_image1.png
Greyscale
. This reads on instantly claimed Formula A, wherein R10 is NR1R2 wherein R1 is H and R2 is optionally substituted aryl; R4 is optionally substituted aryloxy; R5 is halo; and R6 is H.
Regarding claim 19, Tang et al. teaches administration of just SBI-0206965 (i.e. a monotherapy). Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20 and 22, Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest administration of a ULK inhibitor to a subject with an additional therapeutic agent (i.e. cisplatin) as well as the cancer being refractory to a prior treatment.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Tang et al. as evidenced by Dite et al. in view of Li et al. as applied to claims 1, 4-5, 19-22 and 24 above and in further view of Li et al. (Chin J Cancer, 2017, referred to in the action as Li 2017).
Applicant Claims
The instant application claims the cancer is refractory to a prior treatment. The instant application claims he cancer is refractory to carboplatin, a carboplatin analog, an MEK inhibitor, trametinib, cobimetinib, binimetinib, selumetinib, erlotinib, gefitinib, osimertinib, crizotinib, pemetrexed, docetaxel, or pembrolizumab.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Tang et al. and Li et al. are set forth above. Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest the cancer being refractory to a prior treatment.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Tang et al. suggest the cancer being refractory to a prior treatment, Tang et al. does not expressly teach one of the instantly claimed drugs. However, this deficiency is cured by Li 2017.
Li 2017 is directed to autophagy and multidrug resistance in cancer. It is taught that multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Autophagy universally arises during the treatment of sensitive and MDR cancer (abstract). Substantial evidence demonstrates that MDR develops after autophagy. The enhanced autophagy levels detected in patients with poor prognosis indicate that the presence of autophagy may catalyze development of MDR. Inhibition of autophagy can re-sensitize resistance cancer cells and enhance the effect of chemotherapeutic agents (page 4, left column). Table 1 teaches docetaxel and cisplatin.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Tang et al., Li et al. and Li 2017 and administer a ULK inhibitor to a subject whose cancer is refractory. One skilled in the art would administer the inhibitor in order to inhibit autophagy and re-sensitize resistant cancer cells as suggested by both Tang et al. and Li 2017. Since multidrug resistance occurs frequently after long-term chemotherapy and cisplatin and docetaxel are known chemotherapy drugs, one skilled in the art would have been motivated to administer the ULK inhibitor to a cancer who has become resistant to known chemotherapeutics. Since Tang et al. and Li 2017 both teach that inhibition of autophagy can sensitize cells to chemotherapeutics there is a reasonable expectation of success.
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, 4-5, 19-22 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,266,549 in view of Tang et al. as evidenced by Dite et al. and Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a method of treating a disorder associated with elevated ULK levels in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a ULK inhibitor of formula A, wherein a tissue affected by the disorder in the subject has a distinct expression of at least one of biomarker genes such as RPA1.
Patent ‘549 claims a compound which includes
PNG
media_image2.png
348
520
media_image2.png
Greyscale
which as evidenced by Dite et al. is SBI-0205965.
While Patent ‘549 claims a compound which falls within the scope of the instantly claimed ULK inhibitors, Patent ‘549 does not expressly claim a method. However, this deficiency is cured by Tang et al. and Li et al.
Tang et al. is directed to SBI020695, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell growth by modulating both autophagy and apoptosis pathways. Autophagy is a process of phagocytosis of unnecessary or dysfunctional components, fusion with lysosomes and degradation of the contents of the lysosomes to maintain cellular homeostasis. Dysregulation of autophagy is often observed in lung cancer. Inhibition of autophagy sensitizes NSCLC (non-small cell lung cancer) cells to chemotherapy (page 3449, right column). Ulk1 is upregulated in NSCLC cell lines and negatively correlated with prognosis in patients with NSCLC. Knockdown of ULK1 inhibited cell growth and sensitized NSCLC cells to cisplatin. Inhibition of ULK1 by SBI0206965 reduced the proliferation of NSCLC cells and induces cell apoptosis by inhibiting autophagy (page 3450, left column; page 3451, right column and Fig. 1). Ulk1 is required for autophagy in severe hypoxia (page 3456, left column). Many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These rules suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin (page 3452, last paragraph).
Li et al. is directed to hypoxia pathway genetic variants predict survival of non-small-cell lung cancer patients receiving platinum-based chemotherapy. Biomarkers have been shown to be associated with the survival of non-small cell lung cancer (NSCLC) (page 419, last paragraph). Hypoxia is a hallmark of solid tumors and is associated with advanced disease stage and poor clinical outcome. It was found that SNPs in exonuclease 1 (EXO1) and human replication protein A 1 (RPA1) gene associated with survival in late stage NSCLC patients receiving platinum-based chemotherapy. RPA1 is important in DNA repair, replication and recombination. RPA1 is involved in cancer development and progression. Previous studies have shown tumor cells had higher expression of RPA1 protein and mRNA than normal cells (page 422, last two paragraphs). It was shown that chemotherapy-treated NSCLC patients with RPA1: rs2270412 AA+GA genotype had a significantly worse survival than those with the GG genotype. The GG genotype had lower expression of RPA1 consistent with prior studies that lower expression of RPA1 was associated with better survival and higher expression with worse survival in other cancers (page 423, first paragraph). These data suggest that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes (page 423, second to last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘549, Tang et al. and Li et al. and administer a therapeutically effective amount of SBI020695, a novel inhibitor of Ulk1, to a subject affected with non-small cell lung cancer. One skilled in the art would have been motivated to administer SBI020695 as it inhibits the autophagy associated with NSCLC. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Tang et al. would possess distinct expression of RPA1.
Regarding claims 4-5, 21 and 24, Tang et al. teaches NSCLC which is a lung cancer.
Regarding the claimed ULK1 inhibitor, as evidenced by Dite et al., SBI-0205965 has the following structure:
PNG
media_image1.png
134
300
media_image1.png
Greyscale
. This reads on instantly claimed Formula A, wherein R10 is NR1R2 wherein R1 is H and R2 is optionally substituted aryl; R4 is optionally substituted aryloxy; R5 is halo; and R6 is H. Thus the claimed compound of Patent ‘549 falls within the scope of instantly claimed Formula A.
Regarding claim 19, Tang et al. teaches administration of just SBI-0206965 (i.e. a monotherapy). Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20 and 22, Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest administration of a ULK inhibitor to a subject with an additional therapeutic agent (i.e. cisplatin) as well as the cancer being refractory to a prior treatment.
Claims 1, 4-5, 19-22 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,689,397 in view of Tang et al. as evidenced by Dite et al. and Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘397 claims a compound of formula A which has the same base structure as instantly claimed.
PNG
media_image3.png
256
580
media_image3.png
Greyscale
(claim 1). Claimed is R10 is NR1N2; R1 is H and R2 can be
PNG
media_image4.png
308
268
media_image4.png
Greyscale
and R6 is H (claim 2; 5). R4 is optionally substituted heteroaryloxy (claim 9).
While Patent ‘397 claims compounds which falls within the scope of the instantly claimed ULK inhibitors, Patent ‘397 does not expressly claim a method. However, this deficiency is cured by Tang et al. and Li et al.
The teachings of Tang et al. and Li et al. are set forth above
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘397, Tang et al. and Li et al. and administer a therapeutically effective amount of SBI020695, a novel inhibitor of Ulk1, to a subject affected with non-small cell lung cancer. One skilled in the art would have been motivated to administer SBI020695 as it inhibits the autophagy associated with NSCLC. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Tang et al. would possess distinct expression of RPA1.
Regarding claims 4-5, 21 and 24, Tang et al. teaches NSCLC which is a lung cancer.
Regarding the claimed ULK1 inhibitor 8, as evidenced by Dite et al., SBI-0205965 has the following structure:
PNG
media_image1.png
134
300
media_image1.png
Greyscale
. This reads on instantly claimed Formula A and formula A of Patent ‘397, wherein R10 is NR1R2 wherein R1 is H and R2 is optionally substituted aryl; R4 is optionally substituted aryloxy; R5 is halo; and R6 is H. Thus the claimed compound of Patent ‘397 falls within the scope of instantly claimed Formula A.
Regarding claim 19, Tang et al. teaches administration of just SBI-0206965 (i.e. a monotherapy). Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20 and 22, Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest administration of a ULK inhibitor to a subject with an additional therapeutic agent (i.e. cisplatin) as well as the cancer being refractory to a prior treatment.
Claims 1, 4-5, 19-22 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,774,092 in view of Tang et al. as evidenced by Dite et al. and Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘092 claims a compound of formula A which has the same base structure as instantly claimed.
PNG
media_image3.png
256
580
media_image3.png
Greyscale
(claim 1). Claimed is R10 is NR1N2; R1 is H and R2 can be
PNG
media_image4.png
308
268
media_image4.png
Greyscale
and R6 is H (claim 2; 5). A specific compound claimed is:
PNG
media_image5.png
396
568
media_image5.png
Greyscale
which is SBI020695.
While Patent ‘092 claims compounds which falls within the scope of the instantly claimed ULK inhibitors, Patent ‘092 does not expressly claim a method. However, this deficiency is cured by Tang et al. and Li et al.
The teachings of Tang et al. and Li et al. are set forth above
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘092, Tang et al. and Li et al. and administer a therapeutically effective amount of SBI020695, a novel inhibitor of Ulk1, to a subject affected with non-small cell lung cancer. One skilled in the art would have been motivated to administer SBI020695 as it inhibits the autophagy associated with NSCLC. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Tang et al. would possess distinct expression of RPA1.
Regarding claims 4-5, 21 and 24, Tang et al. teaches NSCLC which is a lung cancer.
Regarding the claimed ULK1 inhibitor and claim 18, as evidenced by Dite et al., SBI-0205965 has the following structure:
PNG
media_image1.png
134
300
media_image1.png
Greyscale
. This reads on instantly claimed Formula A and formula A of Patent ‘397, wherein R10 is NR1R2 wherein R1 is H and R2 is optionally substituted aryl; R4 is optionally substituted aryloxy; R5 is halo; and R6 is H. Thus the claimed compound of Patent ‘397 falls within the scope of instantly claimed Formula A.
Regarding claim 19, Tang et al. teaches administration of just SBI-0206965 (i.e. a monotherapy). Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20 and 22, Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest administration of a ULK inhibitor to a subject with an additional therapeutic agent (i.e. cisplatin) as well as the cancer being refractory to a prior treatment.
Claim 23 is rejected on the ground of nonstatutory double patenting as being unpatentable over 1-20 of U.S. Patent No. 10,774,092 or 10, 266,549 or 10689397 in view of Tang et al. as evidenced by Dite et al. and Li et al. as applied to claims 1, 4-5, 1-22 and 24 above and in further view of Li et al. (Chin J Cancer, 2017, referred to in the Action as Li 2017). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims the cancer is refractory to a prior treatment. The instant application claims he cancer is refractory to carboplatin, a carboplatin analog, an MEK inhibitor, trametinib, cobimetinib, binimetinib, selumetinib, erlotinib, gefitinib, osimertinib, crizotinib, pemetrexed, docetaxel, or pembrolizumab.
The teachings of Patent ‘092, ‘549, ‘397, Tang et al. and Li et al. are set forth above.
Tang et al. teaches many NSCLC cells acquire resistance to the cytotoxicity induced by cisplatin (i.e. refractory to a prior treatment) which limits the therapeutic efficacy. Knockdown of Ulk1 significantly impaired the viability of NSCLC cells after cisplatin treatment and markedly increased cisplatin-induced apoptosis. These results suggest that knockdown of ULK1 can sensitize NSCLC cells to cisplatin. This suggest the cancer being refractory to a prior treatment.
The cancer being refractory to one of the instantly claimed drugs is not claimed. However, this deficiency is cured by Li 2017
Li 2017 is directed to autophagy and multidrug resistance in cancer. It is taught that multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Autophagy universally arises during the treatment of sensitive and MDR cancer (abstract). Substantial evidence demonstrates that MDR develops after autophagy. The enhanced autophagy levels detected in patients with poor prognosis indicate that the presence of autophagy may catalyze development of MDR. Inhibition of autophagy can re-sensitize resistance cancer cells and enhance the effect of chemotherapeutic agents (page 4, left column). Table 1 teaches docetaxel and cisplatin.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘549 OR ‘397 OR ‘092 and Tang et al., Li et al. and Li 2017 and administer a ULK inhibitor to a subject whose cancer is refractory. One skilled in the art would administer the inhibitor in order to inhibit autophagy and re-sensitize resistant cancer cells as suggested by both Tang et al. and Li 2017. Since multidrug resistance occurs frequently after long-term chemotherapy and cisplatin and docetaxel are all known drugs used for cancer treatment, one skilled in the art would have been motivated to administer the ULK inhibitor to a cancer who has become resistant to known chemotherapeutics. Since Tang et al. and Li 2017 both teach that inhibition of autophagy can sensitize cells to chemotherapeutics there is a reasonable expectation of success.
Claims 1, 4-5, and 19-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14-15, 18, 53-54 and 57-58 of copending Application No. 17799641(USPGPUB No. 20230130766) in view of Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Copending ‘641 claims a method for treating cancer in a subject in need thereof the method comprising administering to the subject a therapeutically effective amount of a ULK inhibiting having a structure of formula A. Formula A is the same as instantly claimed. The administration can be a monotherapy (claim 3). An additional therapeutic is claimed (claim 5). Additional therapeutic agents include carboplatin, MEK inhibitor, trametinib, etc. (claims 7-9). The cancer can be lung cancer including non-small cell lung cancer (claims 14-15).The cancer is refractory to a prior treatment.
The difference between copending ‘641 and the instant claims is that copending ‘641 does not claim a biomarker. However, this deficiency is cured by Li et al.
The teachings of Li et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘641 and Li et al. and administer a therapeutically effective amount of the ULK inhibitors of copending ‘641 to a patient with lung cancer. One skilled in the art would have been motivated to administer the inhibitors in this manner as this is expressly claimed by copending ‘639.
Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Copending ‘641 would possess distinct expression of RPA1.
Claims 1, 4-5, 18-21 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 10-11, 14, 22, 25, 33, 38, 40, 43-44, 50, 191, 192-193, 195-196, 199-200 and 205 of copending Application No. 17799639 (USPGPUB No. 20230135635) in view of Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘639 claims a compound of formula IA:
PNG
media_image6.png
394
354
media_image6.png
Greyscale
R1A can be H or halogen (corresponding to instantly claimed R6); R2A can be H, halo (corresponding to instantly claimed R5); XA can be NR3AR4A or OR4A wherein R3A can be H, substituted or unsubstituted alkyl, R4A can be aryl (reading on instantly claimed R4) (claim 1). Claimed is a method of treating a ULK1 mediated disease in a subject in need thereof comprising administering to the subject the compound of claim 1. The ULK1 mediated disease is characterized by abnormal autophagy. Lung cancer is claimed. Additional therapeutics are claimed. Carboplatin and MEK inhibitor is claimed.
While copending ‘639 claims compounds which falls within the scope of the instantly claimed ULK inhibitors and that the inhibitors can be used in a method of treating a ULK mediated disease, copending ‘639 does not expressly claim a biomarker. However, this deficiency is cured by Li et al.
The teachings of Li et al. are set forth above
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘639 and Li et al. and administer a therapeutically effective amount of the ULK inhibitors of copending ‘639 to a patient with lung cancer. One skilled in the art would have been motivated to administer the inhibitors in this manner as this is expressly claimed by copending ‘639. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Copending ‘641 would possess distinct expression of RPA1.
Regarding claims 4-5 and 21, copending ‘639 claims the same cancer.
Regarding claim 19, copending ‘639 claims administration of just the ULK inhibitor. Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20, copending ‘639 claims additional therapeutic agents.
Claims 1, 4-5, 19-21 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of US Patent No. 12594277 (copending Application No. 17799634 (USPGPUB No. 20230099804)) in view of Li et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims are set forth above.
Patent ‘277 claims a compound such as
PNG
media_image7.png
228
238
media_image7.png
Greyscale
. This compound falls within the instantly claimed scope when R6 is H, R5 is substituted alkyl or halo, R4 and R10 together form a cyclic structure.
Claimed is a method of treating a ULK mediated disease in a subject in need thereof, the method comprising administering to the subject the compound. The ULK mediated disease is characterized by abnormal autophagy. The disease is lung cancer. The compound is administered with an additional therapeutic agent. Additional therapeutic agents include carboplatin, MEK inhibitor, etc.
While Patent ‘277 claims compounds which falls within the scope of the instantly claimed ULK inhibitors and that the inhibitors can be used in a method of treating a ULK mediated disease, Patent ‘277 does not expressly claim a biomarker. However, this deficiency is cured by Li et al.
The teachings of Li et al. are set forth above
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘277 and Li et al. administer a therapeutically effective amount of the ULK inhibitors of Patent ‘277 to a patient with lung cancer. One skilled in the art would have been motivated to administer the inhibitors in this manner as this is expressly claimed by Patent ‘277. Regarding the claimed “tissue affected by the disorder in the subject has a distinct expression of at least one biomarker gene…RPA1”, this limitation merely requires that the tissue affected by the disorder is identified as having a distinct expression of the biomarker not that it is required for treatment. Li et al. teaches that tumor cells, specifically non-small cell lung cancer, have different expression levels of RPA and lower expression is associated with better survival and higher expression is associated with worse survival. Thus, one skilled in the art would be motivated to measure the level of this biomarker to help better shape treatment decisions in an individual. This suggest the tissue affected by the disorder taught in Patent ‘277 would possess distinct expression of RPA1.
Regarding claims 4-5, 21 and 24, Patent ‘277 claims the same cancer.
Regarding claim 19, Patent ‘277 claims administration of just the ULK inhibitor. Furthermore, as taught by Li et al. data suggests that in addition to clinicopathological variables, genetic information may need to be considered when deciding whether patients should receive chemotherapy alone or chemoradiation. For those patients with unfavorable genotypes for chemotherapy outcome, adding radiation to chemotherapy may improve patient outcomes. Therefore, depending on the expression level of RPA1, one skilled in the art would recognize that chemotherapy alone may be sufficient or the chemotherapy must be supplemented with additional therapy such as radiation.
Regarding claim 20, Patent ‘277 claims additional therapeutic agents.
Claims 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 17799639 in view of Li et al. as applied to claims 1, 4-5, 19-21 and 24 above and in further view of Li 2017. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
The teachings of copending ‘639 are set forth above.
The cancer being refractory to one of the instantly claimed drugs is not claimed. However, this deficiency is cured by Li 2017.
The teachings of Li 2017 are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘639, Li et al. and Li 2017 and administer a ULK inhibitor to a subject whose cancer is refractory. One skilled in the art would administer the inhibitor in order to inhibit autophagy and re-sensitize resistant cancer cells as suggested by Li 2017. Since multidrug resistance occurs frequently after long-term chemotherapy and carboplatin and an MEK inhibitor are known drugs used for cancer treatment as claimed by copending ‘639, one skilled in the art would have been motivated to administer the ULK inhibitor to a cancer who has become resistant to known chemotherapeutics. Since Li 2017 teach that inhibition of autophagy can sensitize cells to chemotherapeutics there is a reasonable expectation of success.
Claims 22-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over US Patent No. 12594277 (copending Application No. 17799634) in view of Li et al. as applied to claims 1, 4-5, 19-21 and 24 above and in further view of Li 2017. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
The teachings of Patent ‘277 are set forth above.
The cancer being refractory to one of the instantly claimed drugs is not claimed. However, this deficiency is cured by Li 2017.
The teachings of Li 2017 are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of patent ‘277, Li et al. and Li 2017 and administer a ULK inhibitor to a subject whose cancer is refractory. One skilled in the art would administer the inhibitor in order to inhibit autophagy and re-sensitize resistant cancer cells as suggested by Li 2017. Since multidrug resistance occurs frequently after long-term chemotherapy and carboplatin and an MEK inhibitor are known drugs used for cancer treatment as claimed Patent ‘277, one skilled in the art would have been motivated to administer the ULK inhibitor to a cancer who has become resistant to known chemotherapeutics. Since Li 2017 teach that inhibition of autophagy can sensitize cells to chemotherapeutics there is a reasonable expectation of success.
Conclusion
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 ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636
Prosecution Insights