METHODS AND COMPOSITIONS FOR TREATING GLUCOCORTICOID EXCESS

§102 §103 §DP

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 . Status Claims 19-38 are new, pending, and under examination. Claims 1-18 were canceled by Applicant. Priority This application is a continuation of U.S. Application No. 19/209,346, filed May 15, 2025, which is a continuation of U.S. Application No. 18/629,056, filed April 8, 2024, which is a divisional of U.S. Application No. 18/321,266 (abandoned), filed May 22, 2023, which is a bypass continuation of International Application No. PCT/US2023/067057, filed May 16, 2023, which claims the benefit of, and priority to, U.S. Provisional Application No. 63/364,759, filed May 16, 2022. Election/Restrictions The claims as originally presented were directed to a composition. As a result of the original presentation and examination of those claims, the composition invention was constructively elected. See MPEP § 821.03. Applicant has amended the claims such that the presently pending claims are directed to a method invention that is independent or distinct from the originally claimed composition invention. Although the newly presented method claims could be subject to election by original presentation under 37 CFR 1.145 (see MPEP §§ 818.02 and 821.03), the Examiner has elected, in this instance, to enter and examine the amended method claims. Examination of the method claims should not be construed as a determination that the method invention is not independent or distinct from the composition invention previously claimed. Information Disclosure Statement No Information Disclosure Statement was filed with Applicant’s recent reply. Response to Arguments Applicant’s arguments, see p. 1, filed 8/28/2026, with respect to the rejection of the claims 1-15 as being anticipated by Yoshimura (US 8,377,923 B2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Astellas, ClinicalTrials, and Sparrow Pharm. cited below. Claim Rejections - 35 USC § 102 New rejection, necessitated by amendment The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 19, 23, 24, 26, 27, 30-32 and 36-38 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Astellas (NCT02372578, Sponsor: Astellas, Study Number: 3662-CL-0049, September 2018, 5 pages (cited in 1/12/2026 IDS). Claimed invention A method for treating diabetes in a human patient, comprising administering a single daily dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is: PNG media_image1.png 80 217 media_image1.png Greyscale (SPI62), wherein: the single daily dose is about 0.6 mg, 2 mg, 6 mg, or 12 mg, and the compound does not show tachyphylaxis for HSD-1 inhibition in human adipose tissue. Prior art Astellas teaches administration of single daily 10 mg dose of ASP3662 (SPI-62, clofutriben) to human diabetic patients for painful diabetic peripheral neuropathy. See pp. 1 and 2. The disclosed amount of 10 mg ASP3662 at the least falls within the scope of the claimed “about 6 mg” and “about 12 mg” dosage when considered under its broadest reasonable interpretation (BRI). The specification provides that “about” accounts for variability and that the numerical parameters in the specification and claims are approximations that can vary depending on the desired properties sought to be obtained by a particular embodiment: Numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, used to describe and claim certain embodiments of the present disclosure are to be understood as being modified in some instances by the term “about.” In some embodiments, the term “about” is used to indicate that a value includes a measure of variability for the device or method being employed to determine the value. The numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. The numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the present disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the present disclosure may contain certain errors necessarily resulting from the variability found in their respective testing measurements. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. Specification 0107. Given that the term “about” encompasses such a broad definition, the disclosure of 10 mg falls within the claimed “about 6 mg” and “about 12 mg”. Regarding the limitation “wherein the compound does not show tachyphylaxis for HSD-1 inhibition in human adipose tissue”, this limitation constitutes an inherent pharmacodynamic property of ASP3662 when administered under the claimed conditions. The fact that this property was not recognized in the patients disclosed by Astellas does not preclude anticipation. See MPEP § 2112. Claim 23 limits claim 19, wherein the single daily dose is administered to the patient for at least 6 weeks or at least 8 weeks. Claim 24 limits claim 19, wherein the single daily dose is administered to the patient for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, or at least 6 months. See p. 1. Astellas discloses repeated treatment for 6 weeks. Thus, teaching once daily dose for at least 1 month. This also meets the limitation of Claim 36 and Claim 37. Claim 26 limits claim 19, wherein the single daily dose is administered to the patient orally, intravenously, intramuscularly, subcutaneously, by inhalation, intranasally, ocularly, or topically. Claim 27 limits claim 26, wherein the single daily dose is administered to the patient orally. Astellas teaches “patients took ASP3662 tablets (10 mg) once daily” clearly inferring oral administration. See p. 2. This also meets the limitation of Claim 38. Claim 30 and Claim 31 limit claim 19, wherein the single daily dose is about 6 mg and about 12 mg, respectively. Given the BRI as described above regarding the term “about”, the disclosure of 10 mg falls within the claimed “about 6 mg” and “about 12 mg”. Independent Claim 32 is similarly drawn to method for treating diabetes comprising administering a therapeutically effective amount of a ASP3362 wherein a total amount is about 0.6 mg, 2 mg, 6 mg, or 12 mg. Astellas disclosure of the single dose of 10 mg in a day meets the claimed total amount of “about 6 mg” and “about 12 mg”. Claim Rejections - 35 USC § 103 New rejection, necessitated by amendment 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 non-obviousness. 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 21, 22, 34, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Astellas (NCT02372578, Sponsor: Astellas, Study Number: 3662-CL-0049, September 2018, 5 pages (cited in 1/12/2026 IDS) in view of ClinicalTrials (ClinicalTrials.gov ID: NCT02372578; Sponsor Astellas Pharma Global Development, Inc. Posted 2019-03-26.) Claimed invention Claim 21 limits claim 19 and Claim 34 limits 32, wherein the diabetes is type 2 diabetes. Claim 22 limits claim 19 and Claim 35 limits claim 32, wherein the patient has a body mass index between 30.0 and 45.0. Prior art Astellas discusses the results of the NCT02372578 clinical trial. Astellas teaches administration of single daily 10 mg dose of ASP3662 (SPI-62, clofutriben) to human diabetic patients (having a BMI of < or equal to 40 – see p. 7) for painful diabetic peripheral neuropathy. See pp. 1 and 2. Astellas does not expressly teach the specific body mass index range between 30.0 and 45.0 or the patients have Type 2 diabetes. However, the patients in the NCT02372578 clinical trial discussed in Astellas were required to have an established diagnosis of Type I or Type II diabetes to be included. See 7th page of ClinicalTrials. A person of ordinary skill in the art (POSA) would have found it obvious to administer the 10 mg ASP3662 to Type II diabetes, since Type II diabetes was one of the two expressly identified diabetic populations eligible for treatment with ASP3662 in the disclosed clinical trial. The trial further required patients to have a BMI of 40 or less, thereby encompassing Type II diabetic patients having a BMI between 30 and 40, which falls within the claimed range of 30-45. Selecting and treating the expressly identified Type II diabetic population within the overlapping BMI range would have involved no change in the disclosed ASP3662 treatment regimen and would have amounted to a finite number of expressly identified patient populations with reasonable expectation that ASP3662 would be administered according to the disclosed regimen. Claims 20, 25, 28, 29 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Astellas (NCT02372578, Sponsor: Astellas, Study Number: 3662-CL-0049, September 2018, 5 pages (cited in 1/12/2026 IDS) in view of Sparrow Pharm. (WO2020106337A1 – cited in 1/12/2026 IDS). Prior art Astellas discusses the results of the NCT02372578 clinical trial. Astellas teaches administration of single daily 10 mg dose of ASP3662 (SPI-62, clofutriben) to human diabetic patients (having a BMI of < or equal to 40 – see p. 7) for painful diabetic peripheral neuropathy. See pp. 1 and 2. Astellas does not expressly teach the specific body mass index range between 30.0 and 45.0 or the patients have Type 2 diabetes. Sparrow Pharm. teaches HSD1 regulates intracellular glucocorticoid (GC) levels and that HSD1 “in vivo generally converts inactive cortisone to active cortisol.” See 0002. It further teaches that administration of an HSD1-selective inhibitor may ameliorate metabolic effects including hyperglycemia and insulin resistance. See 0003. Sparrow Pharm. additionally teaches determining HSD1 activity by measuring cortisol/cortisone-related biomarkers, including the ratio of mass-labeled cortisol and cortisone in blood or plasma and conversion of cortisone to cortisol in a fat biopsy. See 0102-0104. Sparrow Pharm. teaches, in some embodiments, the course of treatment is chosen from 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 6 months, and 1 year. See 0089. Sparrow Pharm. further teaches the HSD1 inhibitor is at least 0.7 mg. In some embodiments, the first dose of the HSD1 inhibitor is 0.7 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 1 mg. In some embodiments, the first dose of the HSD1 inhibitor is 1 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 2 mg. In some embodiments, the first dose of the HSD1 inhibitor is 2 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 2.5 mg. In some embodiments, the first dose of the HSD1 inhibitor is 2.5 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 3 mg. In some embodiments, the first dose of the HSD1 inhibitor is 3 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 4 mg. In some embodiments, the first dose of the HSD1 inhibitor is 4 mg. In some embodiments, the first dose of the HSD1 inhibitor is at least 5 mg. In some embodiments, the first dose of the HSD1 inhibitor is 5 mg. In some embodiments, the first dose of the HSD1 inhibitor is 6 mg. See 0073-0075. It specifically teaches 0.7 mg Compound A (i.e., SPI-62) dosing. See 0006, Fig. 2. Claim 20 limits claim 19 and Claim 33 limits claim 32, wherein the patient has previously been diagnosed with an elevated level of cortisol. A person of ordinary skill in the art (POSA) would have found it obvious to determine whether a diabetic patient had an elevated cortisol level and to administer SPI-62 to a patient identified as having such elevated cortisol, in order to inhibit HSD1-mediated cortisol generation and thereby address the associated metabolic abnormalities, e.g., hyperglycemia and insulin resistance. Claim 25 limits claim 19, wherein the single daily dose is administered to the patient for at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 15 months, at least 18 months, at least 24 months, at least 36 months, or at least 48 months. Sparrow Pharm. teaches, in some embodiments, the course of treatment is chosen from 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 6 months, and 1 year. See 0089. A person of ordinary skill in the art (POSA) would have found it obvious to administer SPI-62 at the claimed time periods, in order to provide treatment as needed for a subject with diabetes, i.e., a known chronic condition. Claim 28 and Claim 29 limit claim 19, wherein the single daily dose is about 0.6 mg or about 2 mg, respectively. A POSA would have found it obvious to administer the claimed dose amounts of SPI-62 because Sparrow Pharm. teaches 2 mg daily dosing and 0.7 mg daily dosing, which reasonably corresponds to about 0.6 mg, particularly in view of the approximate nature taught doses to obtain the disclosed HSD1 inhibition while administering SPI-62 according to the treatment regimen. Double Patenting New rejection, necessitated by amendment 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. A. Claims 19-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,734,155 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts, wherein tachyphylaxis is not displayed. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), oral route. The reference claims are drawn to a method of administering the same SPI-62 compound at amounts of 1-40 mg daily to treat symptoms of glucocorticoid excess , including metabolic symptoms such as diabetes, and further encompass patients previously diagnosed with elevated cortisol and treatment wherein SPI- 62 does not show tachyphylaxis for HSD1 inhibition in human adipose tissue. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. B. Claims 19-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,734,156 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts, wherein tachyphylaxis is not displayed. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), oral route. The reference claims are drawn to a method of administering the same SPI-62 compound at amounts of 1-40 mg daily to treat symptoms of glucocorticoid excess, including metabolic symptoms such as diabetes, and further encompass patients previously diagnosed with elevated cortisol and treatment wherein SPI- 62 does not show tachyphylaxis for HSD1 inhibition in human adipose tissue. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. C. Claims 19-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,329,745 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. D. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 70-89 of copending Application No. 19/209,346 (US 2025/0319072A1) in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. E. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-6, and 9-32 of copending Application No. 19/446,144 (US 2026/0137659A1) in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. F. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of copending Application No. 19/446,148 (US 2026/0137660A1) in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. G. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-28 of copending Application No. 19/724,433 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. H. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-28 of copending Application No. 19/724,433 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The reference claims further teach the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. I. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 19/724,443 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. J. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 19/724,435 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. K. Claims 19-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-29 of copending Application No. 19/724,440 in view of Astellas, ClinicalTrials, and Sparrow Pharm. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set is drawn to a method of treating diabetes in a human patient by administering the same compound, SPI-62 at overlapping or expressly mentioned dosage amounts. The reference claims recite the absence of tachyphylaxis. The cited conflicting claims further recite the same or overlapping patient populations, treatment durations (6 weeks-48 months), and oral route. Astellas further teaches administering SPI-62 to human patients having diabetes and expressly states that the patients took ASP3662 (SPI-62) tablets (10 mg) once daily.” Astellas discloses treatment extending 6 weeks. ClinicalTrials further teaches that patients eligible for the ASP3662 clinical trial could have Type I or II diabetes, required a BMI40 or less, and received ASP3662 once daily during the treatment period. Thus, the reference expressly identifies Type II diabetes patients and a BMI population overlapping the presently claimed BMI range of 30-44. Sparrow Pharm. further teaches administering SPI-62 at the presently claimed or closely corresponding dose amounts, including 0.7, 2, and 6 mg, including repeated daily administration for chronic periods of 1 months, 2 months, 3 months, and 6 months and 1 year, as well as oral administration. The Sparrow Pharm. reference further teaches that HSD1 converts inactive cortisone to active cortisol and teaches assessing cortisol/cortisone related biomarkers in connection with HSD1 activity. A POSA would have found it obvious to apply the SPI-62 treatment claimed in the reference claims to the expressly taught diabetic patient populations and treatment conditions of Astellas and ClinicalTrials and to employ the expressly taught SPI-62 doses, administration routes, and treatment durations of Sparrow Pharm., because all of the references concern administration of the same HSD1 inhibitor, SPI-62, for closely related therapeutic purposes and provide routine patients selection, dosing, route and duration parameters for its clinical use. The resulting method would encompass the currently claimed Type II diabetic patients, BMI, treatment duration, route of administration, and dose amounts. This is a provisional nonstatutory double patenting rejection. Conclusion No claims are allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. 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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. CHRIS E. SIMMONS Examiner Art Unit 1622 /CHRIS E SIMMONS/Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622