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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 29th, 2026 has been entered.
All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed May 29th, 2026, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
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.
Claim 112, and 114 – 126 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form) in view of Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Regarding claims 112, and 114– 126, Copland’955 teach a compound according to Formula (II)
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. See page 4 lines 1 – 2 . More specifically, Copland’955 teach the embodiment,
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, that is SSI-4, as a SCD1 inhibitor in methods for treating cancer where the cancer is selected from the group consisting of a breast cancer. See page 4 lines 16 – 17 and page 5 lines 15 – 18. See claim 112 limitation for a method of treating breast cancer comprising administering
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.
Additionally, Copland’955 teach an embedment for the method of treating cancer comprising administering to the subject a therapeutically effective amount of an SCD1 inhibitor, which includes SSI-4, in combination with a proteasome inhibitor. See page 5 lines 27 – 31. Moreover, Copland’955 teach embodiments wherein the SCD1 inhibitors, which includes SSI-4, can be combined with nivolumab, pembrolizumab, or an immunomodulatory agent in a method of treatment. See page 30 lines 1 – 3, 10 – 11, and 20 – 21. See claims 112, 116, 117, and 121 – 122 limitation for a method comprising administering an antibody programmed cell death protein-1 (anti-PD-1 antibody). See claims 118, and 122 limitation for a method where the two checkpoint inhibitor are independently selected from pembrolizumab or nivolumab is selected.
Furthermore, Copland’955 teach in some embodiments, that the SCD1 inhibitor which includes SSI-4, is administered concurrently or sequentially with a proteasome inhibitor. See page 6 lines 2 – 4. See claim 123 limitation for concurrent administration. See claim 124 limitation for concurrent administration. Moreover, Copland’955 teach that compounds of the disclosure, which include SSI-4, can be administered orally or as intravenously. See page 17 lines 19 – 22. See claim 125 limitation for oral administration. See claim 126 limitation for intravenous administration.
Additionally, Copland’955 teach that although the dosage will vary depending on the symptoms, age and body weight of the subject, the nature and severity of the disorder to be treated or prevented, the route of administration and the form of the drug, in general, a daily dosage of from 0.01 to 2000 mg of the compound is recommended for an adult human subject, and this may be administered in a single dose or in divided doses. See page 18 lines 3 – 8. Furthermore, Copland’955 teach that the compound s of the disclosure can be administered with an additional anti-cancer agent. See page 28 lines 17 – 18.
However, while Copland’955 teach the co-administration with an immunomodulatory agent; Copland’955 fails to specifically teach a combination comprising at least two or three immune checkpoint inhibitors. See claim 112 limitation for at least two check point inhibitors. See claim 114 limitation for at least two check point inhibitors. See claims 119 and 120 limitation for at least three check point inhibitors. Additionally, Copeland’955 fails to teach a method for treating breast cancer with the inclusion of an anti-CTLA-4 antibody and/or an anti-TIM-3 antibody. See claim 112 limitation for a method where the checkpoint inhibitors are independently selected from anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody. See claim 116 limitation for a method where anti- CTLA-4 antibody and anti- PD-1 antibody are administered. See claim 121 limitation for a method of where an anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody are administered. Moreover, Copland’955 fails to specifically teach a combination comprising three immune checkpoint inhibitors selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. See claim 122.
Nevertheless, Stagg et. al. teach that breast cancer is a heterogeneous disease composed of different subtypes. See page 169 column 1 paragraph 1. Additionally, Stagg et. al. teach that clinically, the classification of breast cancer depends on the expression of three biomarkers: estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) with breast cancers that are negative for ER, PR and HER2 considered triple-negative breast cancer (TNBC). See page 169 column 1 paragraph 1. Moreover, Stagg et. al. teach that TNBC represents 15–20% of newly diagnosed cases of breast cancer. See page 169 column 1 paragraph 1. Furthermore, Stagg et. al. teach that because TNBC lacks a therapeutic target, patients do not benefit from endocrine therapy or HER2-targeted therapy. See page 169 column 2 paragraph 2. Thus, Stagg et. al. teach that TNBC remains an important challenge in today’s clinical practice. See page 169 column 2 paragraph 2.
Additionally, Stagg et. al. teach that the identification of a TNBC subtype characterized by elevated expression of immune genes suggests that some patients may benefit from immune-based therapies. See page 170 column 2 paragraph 2. Stagg et. al. teach that in breast cancer, two large series, both in newly diagnosed or early stage breast cancer, support a correlation between immune gene signature and better clinical outcomes. See page 170 column 2 paragraph 2 and page 171 column 1 paragraph 1. Furthermore, Stagg et. al. teach that while CD8+ T-cell infiltrates are generally associated with better prognosis, CD4+ T cells, which include T-regulatory cells, and tumor-associated macrophages (TAMs) have been associated with worse outcomes. See page 171 column 1 paragraph 1. Thus, Stagg et. al. teach that CD8+ T cells can control human breast cancer, but the presence of immune suppressive cells, that is, CD4+ T-regulatory cells and macrophages, abrogates this action. See page 171 column 1 paragraph 2.
Specifically, Stagg et. al teach that anti-CTLA-4 mAb therapy, like with ipilimumab, enhances the anti-tumor function of CD8+ T cells, increases the ratio of CD8+ T cells to Foxp3+ T regulatory cells, and inhibits the suppressive function of T regulatory cells. See page 174 column 2 paragraph 2. Moreover, Stagg et. al. teach that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. See page 175 column 2 paragraph 1. Furthermore, Stagg et. al. teach that more recently, TIM-3 has been identified as another important inhibitory receptor expressed by exhausted CD8+ T cells. See page 175 column 2 paragraph 2. Additionally, Stagg et. al. teach that the combination of anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. See page 175 column 2 paragraph 2.
Thus, the prior art of Stagg et. al. not only suggest the use of immune-based therapies as a potential therapeutic strategy for a method of treating TNBC; but Stagg et. al. also suggest the use of a combinational approach with at least two check point immune checkpoint inhibitors. Furthermore, Stagg et. al. specifically teach the use of anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody in treating TNBC. Consequently, given that the skill level of one of ordinary skill in the pharmaceutical oncological art is relatively high, being that of a masters or doctoral degree, it would have been within the purview of such artisan to modify the teachings of Copeland’955 for a method for treating breast cancer comprising the SCD1 inhibitor SSI-4 in combination with the anti-PD-1 antibody of pembrolizumab and/or nivolumab in view of Stagg et. al. that is to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4.
One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages. Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination.
Claim 127 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form) and Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181), as applied to claims 112 – 126, and 128 128 above, and further in view of Mason et. al. ((2012), SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids, PLoS, 7, 1 – 8; cited on the IDS dated February 12th, 2024).
The teachings of Copland’955 and Stagg et. al. as they relate to claim 112 are given previously in this office action and are fully incorporated here.
However, while Copland’955 does teach a daily dosage of from 0.01 to 2000 mg of the compound is recommended for an adult human subject, that can be administered in a single dose or divided doses; Copland’955 does not expressly teach the dosage amount in mg/kg. See claim 127 limitation for a method of treating breast cancer where the compound is administered in an amount from about 200 mg/kg to about 250 mg/kg.
Nevertheless, Mason et. al. teach the oral administration of 160 mg/kg twice daily of #28c, a commercially available SCD1 inhibitor, in nu/nu mice having passage five HCT116 colon tumors, when tumors reached 200 mm3. See page 8 column 1 paragraph 2 and column 2 paragraph 2. Moreover, Mason et. al. teach an example SCD1 inhibitor #28c that showed moderate growth delay of HCT116 tumors in Figure 4c provided here
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. See page 5 column 1 paragraph 5.
While Mason et. al. fails to teach the administration of the specific SCD1 inhibitor SSI-4, Mason et. al. does teach the administration of a known in the art SCD1 inhibitor for the treatment of cancer. Consequently, given that Copland’955 teach the use of SSI-4 as a SCD1 inhibitor in the treatment of breast cancer and Mason et. al. teach the use of an SSI-4 inhibitor in the treatment of colon cancer it would have been obvious to one of ordinary skill in the art to substitute one SCD1 inhibitor for an alternative SCD1 inhibitor. One of ordinary skill in the art would have been motivated to make this modification because, as taught by Copland’955 and Mason et. al. both the SSI-4 and #28c are SCD1 inhibitors useful in the treatment of cancer, breast cancer, and colon cancer.
Furthermore, given that the prior art of Mason et. al. teach the oral administration of 160 mg/kg of the alternative #28c SCD1 inhibitor it would have been obvious to one of ordinary skill in the art the use a similar amount. Moreover, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (MPEP 2144.05(I)). Therefore, since the prior art of Mason et. al. teach the dosage of 160 mg/kg of an SCD1 inhibitor and given how close the value of 160 mg/kg is to “about 200 mg/kg,” the prior art teaching of 160 mg/kg renders obvious the limitation of claim 127.
Therefore it would have been obvious before the effective filling date of the instant application to modify the method of Copland’955 for the administration of the SCD1 inhibitor SSI-4 in view of Stagg et. al., that is to include at least two immune checkpoint inhibitors or three immune checkpoint inhibitors, and in further view of Mason et. al. to use a dosage amount of about 200 mg/kg. One of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the SCD1 inhibitor #28c showed moderate growth delay of HCT116 tumors cells.
Response to Arguments
Applicant's arguments filed May 29th, 2026, with regards to the prior art rejections of the claims 112, and 114 – 127 have been fully considered but have been modified in light of the claim amendments.
Applicant argues that the claim 112 has been amended to recite a method of treating breast cancer in a subject. Furthermore, the applicant argues that the amended was in response to the Office Action dated February 19th, 2026 ascertain of unexpected results. See Applicant’s remarks page 5 paragraph 4.
To address newly amended claim 112 new limitation for method for treating breast cancer, the above prior art rejection was modified to replace the reference of Ngiow et. al. ((2011), Anti-TIM3 Antibody Promotes T Cell IFN-g–Mediated Antitumor Immunity and Suppresses Established Tumors, Cancer Res, 71, 3540 – 3551; cited in the office action dated September 10th, 2025) with Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Moreover, the examiner contends that, upon further review of the data, that the unexpected results are still not commensurate to the scope of claim 112. Particularly, claim 112 recites the limitation for a method for treating breast cancer in a subject comprising administering SSI-4 in combination with at least two check point inhibitors. See claim 112. Furthermore, with regards to claims 119 – 121, the applicant must provide evidence to establish that the difference in results between the combination of SSI-4 with three check point inhibitors, as compared to the prior art teachings above, are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). See MPEP 716.02(b)(I). Moreover, evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980). See MPEP 716.02(b) (III). Furthermore, where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). See MPEP 716.02(c)(I).
In particular Figure 25, of the specification demonstrates some difference in the protein expression levels of PD-1, between the combination and PD-1 alone; however, the difference, as noted by the overlapping error bars is not markedly different. Moreover, in Figure 25 when comparing the combination of SSI-4 and PD-1 with SSI-4 alone the difference is even smaller and not statistically significant. Thus, the difference seems to apply an additive effect versus a synergistic effect. Furthermore, Figure 26 seems to imply that the combination of PD-1 with SSI-4 influence the CD4+ and CD8+ expression; however, the difference, as noted by the overlapping error bars is not markedly different. Moreover, in Figure 26 when comparing the combination of SSI-4 and PD-1 with SSI-4 alone the difference is even smaller and not once again not statistically significant. And thus, the difference in the CD4+ and CD8+ expression in seems to apply an additive effect versus a synergistic effect.
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 112, and 114 – 127 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10 of U.S. Patent No. US 11596629 B2 to Copland, III et. al. (Copland’629) in view of Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Copland’629 recite a method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula:
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or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a checkpoint inhibitor selected from an antibody of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and an antibody of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3). See reference claims 1, and 7 – 8. See examined claims 112, 115, and 121. Furthermore, Copland’629 recite a method where the checkpoint inhibitor is selected from ipilimumab and TSR-022. See reference claim 2. See examined claims 118 and 122. Moreover, Copland’629 recite a method where the compound, or a pharmaceutically acceptable salt thereof, is administered in an amount from about 200 mg/kg to about 250 mg/kg. See reference claim 3. See examined claim 127. Copeland’629 recite a method where cancer is selected from a group consisting of breast cancer. See reference claim 4. See examined claims 112, and 114 – 127. Additionally, Copeland’629 recite a method where the compound, or a pharmaceutically acceptable salt thereof, and the checkpoint inhibitor are administered concurrently or sequentially. See reference claims 5 and 6. See examined claims 123 and 124. Moreover, Copeland’629 recite a method where the checkpoint inhibitor is ipilimumab or TSR-022. See reference claims 9 – 10. See examined claims 118, and 112.
However, Copland’629 fails to recite a method further comprising an anti-PD-L1 antibody. See examined claim 112, 116, 117, and 121. Moreover, Copland’629 fails to specifically teach a combination comprising at least three immune checkpoint inhibitors. See claims 119 and 120 limitation for at least three check point inhibitors. Additionally, Copeland’629 fails to teach a method where the compound is administered orally or intravenously. See examined claims 125 – 126.
Nevertheless, the teachings of Stagg et. al., as they related to the prior art rejections of examined claims 112, and 114 – 126, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the invention of Copland’629 to administer SSI-4 in a method for treating breast cancer in view of Stagg et. al., that is to administer SSI-4 either orally or intravenously in further in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages. Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination.
Claims 112, and 114 – 127 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, and 6 – 9 of U.S. Patent No. US 10301273 B2 to Copland, III et. al. (herein after Copland’273), International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form), Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181), and Mason et. al. ((2012), SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids, PLoS, 7, 1 – 8; cited on the IDS dated February 12th, 2024).
Copland’273 recite a method for treating a cancer in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to Formula (II)
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. See reference claims 1 – 2, and 6 – 7. More specifically, Copland’273 recite a method where the compound according to Formula (II) is
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. See reference claims 8 – 9. See examined claim 112. Moreover, Copland’273 recite a method where the cancer is selected from the group consisting of a breast cancer. See reference claims 1 – 2. See examined claim 128.
However, Copland’273 fails to recite a method of treating breast cancer comprising a combination comprising at least two or three immune checkpoint inhibitors. See claim 112 limitation for at least two check point inhibitors. See claim 114 limitation for at least two check point inhibitors. See claims 119 and 120 limitation for at least three check point inhibitors. Additionally, Copland’273 fails to recite a method for treating breast cancer with the inclusion of an anti-PD-1 antibody, anti-CTLA-4 antibody and/or an anti-TIM-3 antibody. See claim 112 limitation for a method where the checkpoint inhibitors are independently selected from anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody. See claim 116 limitation for a method where anti- CTLA-4 antibody and anti- PD-1 antibody are administered. See claim 121 limitation for a method of where an anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody are administered. Moreover, Copland’273 fails to specifically recite a combination comprising three immune checkpoint inhibitors selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. See claim 122. Furthermore, Copland’273 does not recite a method where the compound is administered in an amount from about 200 mg/kg to about 250 mg/kg. See claim 127. Moreover, Copeland’273 fails to recite a method where the compound is administered either orally, intravenously, sequentially, and/or concurrently. See examined claims 123 – 126.
Nevertheless, the teachings of Copelamd’955, Mason et. al., and Stagg et. al., as they related to the prior art rejections of examined claims 112, and 114 – 127, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the invention of Copland’273 to administer SSI-4 in a method for treating breast cancer in view Copeland’955 that is to administer the compound either orally, intravenously, sequentially, and/or concurrently, in view of Stagg et. al., that is to administer SSI-4 in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4 further in view of Mason et. al. at an amount of about 200 mg/kg. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages.
Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination. Furthermore, one of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the SCD1 inhibitor #28c showed moderate growth delay of HCT116 tumors cells.
Claims 112, and 114 – 126 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7 of U.S. Patent No. US 11325892 B2 to Copland, III et. al. (herein after Copland’892) in view of International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form) and Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Copland’892 recite a compound according to Formula (II)
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. See reference claims 1 – 2. More specifically, Copeland’892 recite the compound of (reference) claim 1 where the compound is
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. See reference claim 6. See examined claims 112.
However, Copland’273 fails to recite a method of treating breast cancer comprising a combination comprising at least two or three immune checkpoint inhibitors. See claim 112 limitation for at least two check point inhibitors. See claim 114 limitation for at least two check point inhibitors. See claims 119 and 120 limitation for at least three check point inhibitors. Additionally, Copland’273 fails to recite a method for treating breast cancer with the inclusion of an anti-PD-1 antibody, anti-CTLA-4 antibody and/or an anti-TIM-3 antibody. See claim 112 limitation for a method where the checkpoint inhibitors are independently selected from anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody. See claim 116 limitation for a method where anti- CTLA-4 antibody and anti- PD-1 antibody are administered. See claim 121 limitation for a method of where an anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody are administered. Moreover, Copland’273 fails to specifically recite a combination comprising three immune checkpoint inhibitors selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. See claim 122. Moreover, Copeland’273 fails to recite a method where the compound is administered either orally, intravenously, sequentially, and/or concurrently. See examined claims 123 – 126.
Nevertheless, the teachings of Copelamd’955, and Stagg et. al., as they related to the prior art rejections of examined claims 112, and 114 – 126, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the invention of Copland’273 to administer SSI-4 in a method for treating breast cancer in view Copeland’955 that is to administer the compound either orally, intravenously, sequentially, and/or concurrently, in view of Stagg et. al., that is to administer SSI-4 in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages.
Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination.
Claim 127 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7 of U.S. Patent No. US 11325892 B2 to Copland, III et. al. (herein after Copland’892) in view of International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form), Mason et. al. ((2012), SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids, PLoS, 7, 1 – 8; cited on the IDS dated February 12th, 2024) and Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Copland’892 recite a compound according to Formula (II)
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130
336
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. See reference claims 1 – 2. More specifically, Copeland’892 recite the compound of (reference) claim 1 where the compound is
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200
400
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. See reference claim 6.
However, Copland’273 does not recite a method where the compound is administered in an amount from about 200 mg/kg to about 250 mg/kg. See claim 127.
Nevertheless, the teachings of Copelamd’955, Stagg et. al.. and Mason et. al., as they related to the prior art rejections of examined claims 127, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the invention of Copland’273 to administer SSI-4 in a method for treating breast cancer in view Copeland’955 that is to administer the compound either orally, intravenously, sequentially, and/or concurrently, in view of Stagg et. al., that is to administer SSI-4 in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4 further in view of Mason et. al. at an amount of about 200 mg/kg. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages.
Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination. Furthermore, one of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the SCD1 inhibitor #28c showed moderate growth delay of HCT116 tumors cells.
Claims 112, and 114 – 126 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 4 – 5, 7 – 16, and 18 – 21 of copending Application No. 18/631941 to Copland et. al. (herein after Copland’941) in view of International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form) and Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Copland’941 recite a method for treating cancer in a mammal, wherein said method comprises administering, to said mammal, a stearoyl CoA desaturase I (SCD 1) polypeptide inhibitor and a tyrosine kinase inhibitor, wherein the number of cancer cells within said mammal is reduced. See reference claim 1. See examined claim 112. Moreover, Copland’941 recite a method where the SCD1 polypeptide inhibitor is a compound having Formula (II) or Formula (Ila):
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130
678
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. See reference claim 31. More specifically, Copland’941 recite a method where the SCD1 polypeptide inhibitor is SSI-4, 2-{ [ 4-(2-Chlorophenoxy )piperidine-1-carbonyl] amino }-N-methylpyridine-4-carboxamide. See reference claim 5. See examined claim 112.
However, Copland’941 fails to recite a method of treating breast cancer comprising a combination comprising at least two or three immune checkpoint inhibitors. See claim 112 limitation for at least two check point inhibitors. See claim 114 limitation for at least two check point inhibitors. See claims 119 and 120 limitation for at least three check point inhibitors. Additionally, Copland’941 fails to recite a method for treating breast cancer with the inclusion of an anti-PD-1 antibody, anti-CTLA-4 antibody and/or an anti-TIM-3 antibody. See claim 112 limitation for a method where the checkpoint inhibitors are independently selected from anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody. See claim 116 limitation for a method where anti- CTLA-4 antibody and anti- PD-1 antibody are administered. See claim 121 limitation for a method of where an anti- CTLA-4 antibody, an anti-TIM-3 antibody, and anti- PD-1 antibody are administered. Moreover, Copland’941 fails to specifically recite a combination comprising three immune checkpoint inhibitors selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. See claim 122. Moreover, Copland’941 fails to recite a method where the compound is administered either orally, intravenously, sequentially, and/or concurrently. See examined claims 123 – 126.
Nevertheless, the teachings of Copelamd’955, and Stagg et. al., as they related to the prior art rejections of examined claims 112, and 114 – 126, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the copending Copland’941 to administer SSI-4 in a method for treating breast cancer in view Copeland’955 that is to administer the compound either orally, intravenously, sequentially, and/or concurrently, in view of Stagg et. al., that is to administer SSI-4 in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages.
Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination.
This is a provisional nonstatutory double patenting rejection.
Claim 127 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 4 – 5, 7 – 16, and 18 – 21 of copending Application No. 18/631941 to Copland et. al. (herein after Copland’941) in view of International Publication Number WO 2016/022955 A1 to Copland III et. al. (herein after Copland’955; cited on the ISR form), Mason et. al. ((2012), SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids, PLoS, 7, 1 – 8; cited on the IDS dated February 12th, 2024) and Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Copland’941 recite a method for treating cancer in a mammal, wherein said method comprises administering, to said mammal, a stearoyl CoA desaturase I (SCD 1) polypeptide inhibitor and a tyrosine kinase inhibitor, wherein the number of cancer cells within said mammal is reduced. See reference claim 1. See examined claim 112. Moreover, Copland’941 recite a method where the SCD1 polypeptide inhibitor is a compound having Formula (II) or Formula (Ila):
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130
678
media_image5.png
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. See reference claim 31. More specifically, Copland’941 recite a method where the SCD1 polypeptide inhibitor is SSI-4, 2-{ [ 4-(2-Chlorophenoxy )piperidine-1-carbonyl] amino }-N-methylpyridine-4-carboxamide. See reference claim 5. See examined claim 112.
However, Copland’941 does not recite a method where the compound is administered in an amount from about 200 mg/kg to about 250 mg/kg. See claim 127.
Nevertheless, the teachings of Copelamd’955, Stagg et. al.. and Mason et. al., as they related to the prior art rejections of examined claims 127, are given previously in this office action and are fully incorporated here.
Therefore, it would been obvious before the effective filing date of the instant application to modify the copending Copland’941 to administer SSI-4 in a method for treating breast cancer in view Copeland’955 that is to administer the compound either orally, intravenously, sequentially, and/or concurrently, in view of Stagg et. al., that is to administer SSI-4 in combination with an anti-PD-1 inhibitor and to include at least two to three immune check point inhibitors in the combinations of anti-PD-1/anti-TIM-3, anti-PD-1/anti-CTLA-4, anti-CTLA-4/anti-TIM-3, or anti-PD-1/anti-TIM-3/anti-CTLA-4 further in view of Mason et. al. at an amount of about 200 mg/kg. One of ordinary skill in the art would be motivated to make this modification to dismiss T cell energy/exhaustion/ tolerance pathways through modulating CD4+ T-regulatory cells and macrophages.
Additionally, one of ordinary in the art would have a reasonable expectation of success because the prior art establishes that the combination of an anti-CTLA-4 and anti-PD-1 antibody demonstrated that blockade of CTLA-4 and PD-1 in mice allows CD8+ and CD4+ T cells to survive in the tumor microenvironment, proliferate, and carry out effector function. Moreover, the prior art taught that anti-PD-1 and anti-TIM-3 mAbs had the most potent anti-cancer effect against well-established experimental and carcinogen-induced tumors. Thus one of ordinary skill in the art would have had a reasonable expectation of success that the combination of at least two check point inhibitors or three checkpoint inhibitors would be at least work as good as the dual combination. Furthermore, one of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the SCD1 inhibitor #28c showed moderate growth delay of HCT116 tumors cells.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed May 29th, 2026, with regards to the provisional nonstatutory double patent (NSDP) and NSDP rejections of instant claims 112, and 114 – 127 have been fully considered and have been modified in view of Stagg et. al. ((2013), Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects, Ther Adv Med Oncol, 5, 169 – 181).
Applicants’ arguments are similar to the arguments presented against the prior art rejections above. See Applicants’ remarks pages 6 – 7.
Therefore, the examiner’s response to the arguments against the provisional NSDP and NSDP rejections of examined claims 112, and 114 – 127 have been addressed above in the response to the prior art rejections.
Conclusion
Claims 112, and 114 – 127 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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