CTFR 19/353,711 CTFR 95281 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application is a CON of 18/339,305 filed on 06/22/2023. 18/339,305 is a CON of 17/306,782 filed on 05/03/2021 now Patent 11738086. 17/306,782 is a CON of 16/461,329 filed on 05/15/2019 now Patent 11020484. 16/461,329 is a 371 of PCT/US2017/062838 filed on 11/21/2017. PCT/US2017/062838 has PRO 62/517,065 filed on 06/08/2017. PCT/US2017/062838 has PRO 62/424,979 filed on 11/21/2016. 02-26 AIA Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Information Disclosure Statement The information disclosure statement filed 10/17/2025, 11/04/2025 and 11/12/2025 fails to comply with the provisions of 37 CFR 1.97(a) because it lacks the appropriate size fee set forth in 37 CFR 1.17(v). It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Claim Status Claims 1-21 are pending. Claims 1, 14 are amended. claim 21 is new. Claims 1-21 are being examined on the merits in this office action. Drawings - Withdrawn The objection to the drawings is withdrawn in view of the amended Drawings. Claim Rejections - Withdrawn The rejection of claims 14-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, is withdrawn in view of the claim amendments. The rejection of claims 1-11, 14-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 21-30 of U.S. Patent No. US11020484B2 is withdrawn in view of the approved Terminal Disclaimer. The rejection of claims 1-11, 14-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. US11738086B2 is withdrawn in view of the approved Terminal Disclaimer. Claim Rejections - 35 USC § 103 – Maintained 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1-21 remain rejected under 35 U.S.C. 103 as being unpatentable over by Kolterman et al . (US6902744B1 – hereinafter “Kolterman”) in view Stoffers et al . (US20080269130A1 – hereinafter “Stoffers”) . Kolterman teaches exendin (9-39) analogs and teaches formulations that comprises the exendin and a buffer such as acetate buffer and an iso-osmolality modifier preferably mannitol (Col. 3, line 1-40; Col. 88, line 53-61; Col. 5, line 20-30; Col. 7, line 55-58). Kolterman teaches that the formulation has a pH of between 4.0 to about 6.0 (Col. 5, line 56). Kolterman teaches the formulation comprising up to 50 mg/ml of exendin (Col. 7, line 55-58). The difference between the Kolterman and the instant claims is that the Kolterman does not specifically teach that the exendin 9-39 is used with the combination of the recited agents in a particular formulation. Stoffers teaches compositions and methods (Abstract), wherein the composition comprises the GLP-1R antagonist exendin (9-39) [0062, 0064, 0085, 0099-0103]. Stoffers teaches the composition comprises mannitol [0106], and buffers such as acetate buffer [0109]. Stoffers teaches that the composition is subcutaneously administered [0100, 0104, 0108]. Stoffers teaches the composition for treating hypoglycemia in subjects with hyperinsulinism [0014-0017]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kolterman and Stoffers and use exendin 9-39 in the composition of Kolterman as the peptide of both Kolterman and Stoffers are similar. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in preparing such a composition so as to treat hypoglycemia. Regarding claim 2, Kolterman teaches that exendin can also be formulated as pharmaceutically acceptable salt such as acetate (Col. 17, line 65-67, Col. 18, line 11-13). Regarding claim 3, Kolterman teaches exendin (9-39) analogs and teaches formulations that comprises the exendin and a buffer such as acetate buffer and an iso-osmolality modifier preferably mannitol (Col. 3, line 1-40; Col. 88, line 53-61; Col. 5, line 20-30; Col. 7, line 55-58). Kolterman teaches that the formulation has a pH of between 4.0 to about 6.0 (Col. 5, line 56). Regarding claim 4, Kolterman teaches the formulation comprises acetate buffer in the amount of 30 Mm[ (col. 7, line 55-58). Examiner notes that the concentration of the active agent is a result effective variable and the determination of the optimum or workable ranges of said variable may be characterized by routine experimentation (See MPEP 2144 II). It would be obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the concentration to arrive at the concentration of the instant claim 4. Regarding claims 5-6, Kolterman teaches the formulation comprising up to 50 mg/ml of exendin (Col. 7, line 55-58). In addition, the concentration of the active agent is a result effective variable and the determination of the optimum or workable ranges of said variable may be characterized by routine experimentation (See MPEP 2144 II). It would be obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dosages to arrive at the dosages of the instant claims. Regarding claim 7, Kolterman teaches the formulation comprises mannitol at approximately 1-10% w/v (which is 10-100 mg/ml) (Col. 5, line 57-59) specifically, 4.3% w/v (which is 43mg/ml) (Col. 33, line 55-56). Regarding claims 8-9, Kolterman teaches exendin (9-39) analogs and teaches formulations that comprises the exendin and a buffer such as acetate buffer and an iso-osmolality modifier preferably mannitol (Col. 3, line 1-40; Col. 88, line 53-61; Col. 5, line 20-30; Col. 7, line 55-58). Kolterman teaches the formulation comprises mannitol at approximately 1-10% w/v (which is 10-100 mg/ml) (Col. 5, line 57-59) specifically, 4.3% w/v (which is 43mg/ml) (Col. 33, line 55-56). Examiner notes that Kolterman discloses the instant concentrations of mannitol that is used to produce the osmolality of the formulation. Thus, the instant osmolality recited in claims 8-9 is achieved by Kolterman since they teach mannitol as the osmolality modifier and teaches the instant concentrations of mannitol rendering the claims obvious. Further, the concentration of the active agent is a result effective variable and the determination of the optimum or workable ranges of said variable may be characterized by routine experimentation (See MPEP 2144 II). It would be obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the concentrations of mannitol to arrive at the osmolality of the instant claims. Regarding claim 10, Kolterman teaches the composition for subcutaneous administration (Col.10, line 2-4; Col. 12, line 1; Col. 17, line 40-41). Further, Stoffers teaches that the composition is subcutaneously administered [0100, 0104, 0108]. Regarding claim 11-13, Stoffers teaches that the formulation does not aggregate [0114]. Further, Examiner notes that the cited references teach the instant composition which will thus display the same properties of lacking aggregation or precipitation. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. MPEP 2112.01 (I). It would have been obvious to combine the teachings of Kolterman and Stoffers to arrive to such a composition. Regarding claims 14 and 21, Stoffers teaches that the composition is subcutaneously administered [0100, 0104, 0108]. Stoffers teaches the composition for treating hypoglycemia in subjects with hyperinsulinism [0014-0017]. Stoffers teaches that the method was effective in reducing an incidence of hypoglycemia [0007-0009, 0011-0017]. It would have been obvious to combine the teachings of Kolterman and Stoffers to arrive to such a composition for treating hyperinsulinemic hypoglycemia. Regarding claims 15-17, Stoffers teaches subjects with post-prandial hypoglycemia after Nissen fundoplication or gastric-bypass surgery [0050-0054]. Examiner notes that Nissen fundoplication and gastric-bypass surgery are a type of upper gastrointestinal procedure and post-prandial hypoglycemia after gastric bypass also reads on post-bariatric hypoglycemia which develops after a meal after the surgery. Regarding claim 18, Kolterman teaches that the formulation is administered 1 or 2 times per day (Col. 8, line 26-27). Regarding claims 19-20, Stoffer teaches a dose of 200 or 250 or 300 pmol/kg/min [0117-0118]. Examiner notes that dose of 300 pmol/kg/min translates to 0.06 mg/kg/hr, and for an adult of the average weight of about 63 kg, in 24 hours (day), the dose will be about 63x24x0.06 = 92 mg, which reads on claims 19-20 . Response to Arguments 07-37 AIA Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive. Applicant Arguments Applicant argues that there is no reasonable expectation of success and that Young focusses on formulations of exendins and exendin agonists and mentions exendin (9-39) in passing and the peptides are different and would impact solubility and stability (Page 2-4 of Arguments). Applicant further argues superior properties such as reduced aggregation and improved pharmacokinetic profile (Page 4 of Arguments). Examiner’s Response The arguments presented above have been fully considered but are unpersuasive. Examiner notes that the instant peptide is known in the art and known to be in a composition. Specifically, Kolterman teaches exendin (9-39) analogs and teaches formulations that comprises the exendin and a buffer such as acetate buffer and an iso-osmolality modifier preferably mannitol (Col. 3, line 1-40; Col. 88, line 53-61; Col. 5, line 20-30; Col. 7, line 55-58). Kolterman teaches that the formulation has a pH of between 4.0 to about 6.0 (Col. 5, line 56). Kolterman teaches the formulation comprising up to 50 mg/ml of exendin (Col. 7, line 55-58). One of ordinary skill in the art would be motivated to specifically use acetate buffer and mannitol in other peptide drugs such as exendin 9-39 peptide. Further, Examiner notes that Stoffers teaches compositions and methods (Abstract), wherein the composition comprises the GLP-1R antagonist exendin (9-39) [0062, 0064, 0085, 0099-0103]. Stoffers teaches the composition comprises mannitol [0106], and buffers such as acetate buffer [0109]. The use of acetate buffer and mannitol is known in the art and thus would be obvious to use the excipients in a composition comprising the instant peptide. With regards to Applicant argument of unexpected results, Examiner is not persuaded. These results would be expected since the patent teaches the same peptide comprising the same tonicity modifier and buffer. Additionally, Kolterman teaches the acetate buffer in a pH from about 4-5, which applicant claims prevents aggregation. This argument is unpersuasive and the rejections are maintained. Double Patenting – Maintained and Updated 08-33 AIA 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. 08-36 AIA Claim s 1-5, 10, 14-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-4, 6-10, 14-15, 17-21, 24, 31 of U.S. Patent No. US10993992B2 in view of Young et al . (WO2000041546A2 – hereinafter “Young”) . The claims of the patent a method for treating hyperinsulinemic hypoglycemia in a subject, the method comprising subcutaneously administering to the subject in need thereof an isotonic solution comprising a therapeutically effective amount of exendin(9-39) and at least one of an antimicrobial preservative, a tonicity adjusting agent, or a buffer; wherein the therapeutically effective amount is 2-100 mg of exendin(9-39); and wherein the exendin(9-39) is administered at a concentration of 20-45 mg/ml (claim 1), wherein the tonicity adjusting agent comprises mannitol (claim 2). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The instant claims recite method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 (claim 14). The claims of the patent do not recite the buffer is acetate buffer and the pH. Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including acetate buffer in the formulation since both references teach formulation comprising exendin. Regarding claim 2, Young teaches that the exendin can be formulated as salt such as acetate (Page 52, line 1-5). It would have been obvious to formulate exendin as an acetate salt as taught by Young. Regarding claim 3-4 Young teaches that the buffer is acetate buffer at 30mM (Claim 41). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. Regarding claim 5, the claims of the patent recite exendin 9-39 at a concentration of 20-45 mg/ml (claim 1, 10, 21, 24, 31). Regarding claim 10, the claims of the patent recite that the formulation is administered subcutaneously (claim 1, 10, 21, 24-25). Regarding claim 14-17, the claims of the patent recite a method for treating hyperinsulinemic hypoglycemia in a subject, the method comprising subcutaneously administering to the subject in need thereof an isotonic solution comprising a therapeutically effective amount of exendin(9-39) and at least one of an antimicrobial preservative, a tonicity adjusting agent, or a buffer (claim 1, 10, 21, 24, 31), wherein the patient has previously had bariatric surgery claim 6-7), wherein the patient has previously had gastrointestinal surgery (claim 8-9). Regarding claim 18, the claims of the patent recite wherein the exendin(9-39) is administered twice per day (claim 4, 31). Regarding claim 19-20, the claims of the patent recite wherein the therapeutically effective amount is 2-100 mg of exendin(9-39) (claim 1, 10, 21, 31) . 08-36 AIA Claim s 1-3, 5, 7, 10, and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-2, 4-10,15-21 and 24 of U.S. Patent No. US10993991B2 in view of Young et al . (WO2000041546A2 – hereinafter “Young”) . The claims of the patent recite a method for treating hyperinsulinemic hypoglycemia in a subject, the method comprising subcutaneously administering to the subject in need thereof an isotonic solution comprising a therapeutically effective amount of exendin(9-39) and at least one of an antimicrobial preservative, a tonicity adjusting agent, or a buffer; wherein the therapeutically effective amount is 10-30 mg of exendin(9-39); and wherein the exendin(9-39) is administered at a concentration of 4-20 mg/ml (claim 1), wherein the tonicity adjusting agent comprises mannitol (claim 2). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The instant claims recite method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 (claim 14). The claims of the patent do not recite the solution wherein the buffer is acetate buffer, and the pH of the composition or solution. Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity and pH. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including acetate buffer in the formulation since both references teach formulation comprising exendin. Regarding claim 2, Young teaches that the exendin can be formulated as salt such as acetate (Page 52, line 1-5). It would have been obvious to formulate exendin as an acetate salt as taught by Young. Regarding claim 3 Young teaches that the buffer is acetate buffer at 30mM (Claim 41). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. Regarding claim 5, and 7 the claims of the patent recite wherein the exendin(9-39) is administered at a concentration of 4-20 mg/ml (claim c). Regarding claim 10, the claims of the patent recite that the formulation is administered subcutaneously (claim 1, 10, 21, 24). Regarding claim 14-17, the claims of the patent recite wherein the patient has previously had bariatric surgery (claim 6, 17), wherein the bariatric surgery is Roux-en-Y gastric bypass, vertical sleeve gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, or pyloroplasty (claim 7, 18), wherein the patient has previously had gastrointestinal surgery (claim 8, 19), wherein the gastrointestinal surgery is gastrectomy, Nissen Fundoplication, or esophagectomy (claim 9, 20). Regarding claim 18, the claims of the patent recite wherein the therapeutically effective amount of the exendin (9-39) is administered once per day or twice per day (claim 4-5, 15-16) . 08-36 AIA Claim s 1-3, 5, 7, 10, and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-2, 6-13, 14-15, 19-23 of U.S. Patent No. US10639354B2 in view of Young et al . (WO2000041546A2 – hereinafter “Young”) . The claims of the patent recite a method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39) (claim 1), wherein the composition is formulated with a pharmaceutically acceptable diluent or carrier and one or both of a preservative and pH adjustment agent (claim 9). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The instant claims recite method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 (claim 14). The claims of the patent do not recite that the composition comprises a buffer such as acetate buffer, that the tonicity agent is mannitol and the pH of the composition or solution. Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate and mannitol to obtain the desired isotonicity and pH. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including acetate buffer and mannitol in the formulation since both references teach formulation comprising exendin. Regarding claim 2, Young teaches that the exendin can be formulated as salt such as acetate (Page 52, line 1-5). It would have been obvious to formulate exendin as an acetate salt as taught by Young. Regarding claim 3 Young teaches that the buffer is acetate buffer at 30mM (Claim 41). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. Regarding claims 5, 7 the claims of the patent recite composition comprises exendin(9-39) at a concentration range selected from 4-20 mg/ml, 10-20 mg/ml, 8-16 mg/ml, and 13-16 mg/ml (claim 10, 19-20, 22). Regarding claim 10, the claims of the patent recite that the formulation is administered subcutaneously (claim 1, 10-13, 21, 23). Regarding claim 14-17, the claims of the patent recite wherein the patient has previously had bariatric surgery or gastrointestinal surgery (claim6), wherein the bariatric surgery is selected from the group consisting of Roux-en-Y Gastric Bypass surgery, Vertical Sleeve Gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, and pyloroplasty (claim 7), wherein the gastrointestinal surgery is selected from the group consisting of gastrectomy, Nissen Fundoplication, and esophagectomy (claim 8). Regarding claim 18, the claims of the patent recite wherein the therapeutically effective amount of the exendin (9-39) is administered twice per day (claim 1-2, 10-13, 21, 23) . 08-36 AIA Claim s 1-3, 10, and 14-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 3-4, 7, 10-12, 14, 16-17 of U.S. Patent No. US12220444B2 in view of Young et al . (WO2000041546A2 – hereinafter “Young”) . The claims of the patent recite a method for treating hyperinsulinemic hypoglycemia in a subject, the method comprising subcutaneously administering to the subject in need thereof a therapeutically effective amount of exendin (9-39), wherein the therapeutically effective amount is 2-100 mg (claim 1), wherein the exendin (9-39) is administered as a solution (claim 4), wherein the solution comprises at least one of an antimicrobial preservative, a tonicity adjusting agent, or a buffer (claim 7). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The instant claims recite method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 (claim 14). The claims of the patent do not recite the buffer is acetate buffer, that the tonicity agent is mannitol and the pH of the composition or solution. Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate and mannitol to obtain the desired isotonicity and pH. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including acetate buffer and mannitol in the formulation since both references teach formulation comprising exendin. Regarding claim 2, Young teaches that the exendin can be formulated as salt such as acetate (Page 52, line 1-5). It would have been obvious to formulate exendin as an acetate salt as taught by Young. Regarding claim 3 Young teaches that the buffer is acetate buffer at 30mM (Claim 41). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. Regarding claim 10, the claims of the patent recite that the formulation is administered subcutaneously (claim 1, 12, 14). Regarding claim 14-17, the claims of the patent recite wherein the subject has previously had bariatric surgery (claim 10, 16), wherein the subject has previously had gastrointestinal surgery (claim 11, 17). Regarding claim 18, the claims of the patent recite wherein the therapeutically effective amount of the exendin (9-39) is administered once per day or twice per day (claim 3). Regarding claim 19-20, the claims of the patent recite wherein the therapeutically effective amount is 2-100 mg (claim 1, 12, 14). Claims 1-3, 10, 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 32-36, and 39 of copending application 18/745,091 in view of Young et al . (WO2000041546A2 – hereinafter “Young”). The claims of the copending application recite a method for treating hyperinsulinemic hypoglycemia in a patient in need thereof, the method comprising subcutaneous administration of a composition comprising a therapeutically effective amount of exendin(9-39) (claim 1), wherein the exendin(9-39) is administered once per day (claim 32), wherein the composition comprises at least one of an antimicrobial preservative, a tonicity adjusting agent, or a buffer (claim 39). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The instant claims recite method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 (claim 14). The copending claims do not recite the buffer is acetate buffer, that the tonicity agent is mannitol and the pH. Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the copending application to include buffers such as sodium acetate and mannitol to obtain the desired isotonicity. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including acetate buffer in the formulation since both references teach formulation comprising exendin. Regarding claim 2, Young teaches that the exendin can be formulated as salt such as acetate (Page 52, line 1-5). It would have been obvious to formulate exendin as an acetate salt as taught by Young. Regarding claim 3 Young teaches that the buffer is acetate buffer at 30mM (Claim 41). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent to include buffers such as sodium acetate to obtain the desired isotonicity. Regarding claim 10, the claims of the copending application recite that the formulation is administered subcutaneously (claim 1). Regarding claim 14-17, the copending claims recite wherein the patient has previously had bariatric surgery (claim 33), wherein the bariatric surgery is Roux-en-Y gastric bypass, vertical sleeve gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, or pyloroplasty (claim 34), wherein the patient has previously had gastrointestinal surgery (claim 35), wherein the gastrointestinal surgery is gastrectomy, Nissen Fundoplication, or esophagectomy (claim 36). Regarding claim 18, the copending claims recite wherein the exendin(9-39) is administered once per day (claim 32) . 08-35 AIA Claim s 1-3, 10-11, 14-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 29-34, 38-47 of copending Application No. 18/339,305 . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer having a pH in from about 5.1 to about 6 (claim 29), wherein the pH is from about 5.5 to about 6 (claim 30, 42-43), wherein the physiologically acceptable buffer comprises one or more of sodium acetate (claims 32-33), wherein the tonicity modifier comprises mannitol (claim 34). The instant claims recite a liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer, wherein the tonicity modifier comprises mannitol, wherein the physiologically acceptable buffer comprises an acetate buffer, and wherein liquid pharmaceutical formulation has a pH of about 5.5 (claim 1). The claims of the copending application anticipate the instant claims. Regarding claim 2, the claims of the copending application recite wherein the pharmaceutically acceptable salt of exendin (9-39) is exendin (9-39) acetate or exendin (9-39) trifluoroacetate (claim 38). Regarding claim 3, the claims of the patent recite wherein the physiologically acceptable buffer comprises sodium acetate (claim 32-33). Regarding claim 10, the claims of the patent recite the composition formulated for subcutaneous administration (claim 41). Regarding claim 11, the claims of the patent recite the formulation does not exhibit detectable aggregation in the formulation (claim 29, 39). Regarding claim 14-17, the claims of the patent recite a method of treating or preventing hyperinsulinemic hypoglycemia in a subject, comprising administering to the subject the liquid pharmaceutical formulation (claim 40), wherein the subject previous had bariatric surgery and/or a related metabolic procedure (claim 44-45), wherein the subject previous had a surgical procedure involving gastrointestinal system (claim 46), wherein the surgical procedure comprises esophagectomy, Nissen Fundoplication, or gastrectomy (claim 47) . This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Response to Arguments 07-37 AIA Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive. Applicant Arguments Applicant argues that the Young focusses on formulations of exendins and exendin agonists and mentions exendin (9-39) in passing and the peptides are different and would impact solubility and stability. Applicant further argues superior properties such as reduced aggregation and improved pharmacokinetic profile. Examiner’s Response The arguments presented above have been fully considered but are unpersuasive. Examiner notes that the claims of the patent and copending application recite a method that is administering a composition that comprises exendin(9-39) and the tonicity modifier comprises mannitol. The claims further recite that the composition comprises a buffer but do not recite that the buffer comprises acetate buffer. However, acetate buffer is known in the art as a physiologically acceptable and routinely used buffer for peptide drugs. Specifically, Young teaches a pharmaceutical formulation comprising exendin, buffer, and an iso- osmolality modifier (claim 1), wherein said buffer is an acetate buffer (claim 2), specifically sodium acetate (Page 51, line 4-5). Young further teaches exendin 9-39 peptide (Page 6, line 17-19; page 7). Young teaches the pH of the composition is about 5.0 (page 14, line 1-4) or pH from about 4.0 to about 6.0 (Page 15, line 5-6). One of ordinary skill in the art would be motivated to specifically use acetate buffer in other peptide drugs such as exendin 9-39 peptide. Further, Examiner cites Stoffers et al . (US20080269130A1 – hereinafter “Stoffers”) to rebut Applicant arguments. Specifically, Stoffers teaches compositions and methods (Abstract), wherein the composition comprises the GLP-1R antagonist exendin (9-39) [0062, 0064, 0085, 0099-0103]. Stoffers teaches the composition comprises mannitol [0106], and buffers such as acetate buffer [0109]. The use of acetate buffer is known in the art and thus would be obvious to use it as a buffer in a composition comprising the instant peptide. With regards to Applicant argument of unexpected results, Examiner is not persuaded. These results would be expected since the patent teaches the same peptide comprising the same tonicity modifier and buffer. This argument is unpersuasive and the rejections are maintained. Conclusion No claims are allowed. 07-39 AIA THIS ACTION IS MADE FINAL. 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 Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /MERCY H SABILA/Examiner, Art Unit 1654 /LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654 Application/Control Number: 19/353,711 Page 2 Art Unit: 1654 Application/Control Number: 19/353,711 Page 3 Art Unit: 1654 Application/Control Number: 19/353,711 Page 4 Art Unit: 1654 Application/Control Number: 19/353,711 Page 5 Art Unit: 1654 Application/Control Number: 19/353,711 Page 6 Art Unit: 1654 Application/Control Number: 19/353,711 Page 7 Art Unit: 1654 Application/Control Number: 19/353,711 Page 8 Art Unit: 1654 Application/Control Number: 19/353,711 Page 9 Art Unit: 1654 Application/Control Number: 19/353,711 Page 10 Art Unit: 1654 Application/Control Number: 19/353,711 Page 11 Art Unit: 1654 Application/Control Number: 19/353,711 Page 12 Art Unit: 1654 Application/Control Number: 19/353,711 Page 13 Art Unit: 1654 Application/Control Number: 19/353,711 Page 14 Art Unit: 1654 Application/Control Number: 19/353,711 Page 15 Art Unit: 1654 Application/Control Number: 19/353,711 Page 16 Art Unit: 1654 Application/Control Number: 19/353,711 Page 17 Art Unit: 1654 Application/Control Number: 19/353,711 Page 18 Art Unit: 1654 Application/Control Number: 19/353,711 Page 19 Art Unit: 1654 Application/Control Number: 19/353,711 Page 20 Art Unit: 1654 Application/Control Number: 19/353,711 Page 21 Art Unit: 1654 Application/Control Number: 19/353,711 Page 22 Art Unit: 1654 Application/Control Number: 19/353,711 Page 23 Art Unit: 1654 Application/Control Number: 19/353,711 Page 24 Art Unit: 1654 Application/Control Number: 19/353,711 Page 25 Art Unit: 1654 Application/Control Number: 19/353,711 Page 26 Art Unit: 1654 Application/Control Number: 19/353,711 Page 27 Art Unit: 1654
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