DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Non-final office action filed on 11/21/2025 is acknowledged.
3. Claim filed on 11/21/2025 is acknowledged.
4. New claims 30-32 have been added.
5. Claims 1-32 are pending in this application.
6. Applicant elected without traverse of compound 18 (SEQ ID NO: 200) with the structure Hy-H[Aib]EGSFTSELAT ILD[K([17-carboxy-heptadecanoyl]-isoGlu)QAAR DFIAWLIQHKITD-OH as species of GLP-1/GLP-2 dual agonist or pharmaceutically acceptable salt thereof; and inflammatory bowel disease as species of the condition to be treated in the reply filed on 7/16/2025.
Restriction requirement was deemed proper and made FINAL in the previous office action. The instant claims 1-32 are drawn to a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: R1-X*-U-R2, wherein: R1 is a hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide of formula I: H-X2-EG-X5-F-X7-X8-E-X10-X11-TIL-X15-X16-X17-A-X19-X20-X21-FI-X24-WL-X27-X28-X29-KIT-X33 (I) (SEQ ID NO: 3), wherein: X2 is Aib or G; X5 is T or S; X7 is T or S; X8 is S, E or D; X10 is L, M, V or Ψ; X11 is A, N or S; X15 is D or E; X16 is G, E, A or Ψ; X17 is Q, E, K, L or Ψ; X19 is A, V or S; X20 is R, K or Ψ; X21 is D, L or E; X24 is A, N or S; X27 is I, Q, K, H or Y; X28 is Q, E, A, H, Y, L, K, R or S; X29 is H, Y or Q; X33 is D or E; U is absent or a sequence of 1-15 residues, each, independently, selected from K, k, E, A, T, I, L and Ψ; the GLP-1/GLP-2 dual agonist contains one and only one Ψ, wherein Ψ is a residue of K, k, R, Orn, Dap or Dab in which the side chain is conjugated to a substituent having the formula Z1- or Z1-Z2-, wherein: Z1- is CH3-(CH2)10-22-(CO)- or HOOC-(CH2)10-22-(CO)-; and -Z2- is selected from -Zs1-, -Zs1-Zs2-, -Zs2-Zs1-, -Zs2-, -ZS3-, -ZS1-ZS3-, -ZS2-ZS3-, -ZS3-ZS1-, -ZS3-ZS2-, -ZS1-ZS2-ZS3-, -Zs1-Zs3-Zs2-, -Zs2-Zs1-Zs3-, -Zs2-Zs3-Zs1-, -Zs3-Zs1-Zs2-, -Zs3-Zs2-Zs1-, -Zs2-Zs3-Zs2-; wherein Zs1 is isoGlu, β-Ala, isoLys, or 4-aminobutanoyl; ZS2 is -(Peg3)m-, wherein m is 1, 2, or 3; and ZS3 is a peptide sequence of 1-6 amino acid residues independently selected from the group consisting of A, L, S, T, Y, Q, D, E, K, k, R, H, F and G; and wherein at least one of X5 and X7 is T; a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFI AWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200); and a method of treatment of ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, and mucositis or diarrhea induced by chemotherapy or radiation therapy in a subject in need thereof, the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200). A search was conducted on the elected species; and these appear to be free of prior art. A search was extended to the genus in claims 1, 31 and 32; and these too appear to be free of prior art. Claims 1-32 are examined on the merits in this office action.
Terminal Disclaimer
7. The terminal disclaimer filed on 11/21/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US patents 10905745 B2, 11130793 B2 and 11395847 B2 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Objections and Rejections
8. Objection to claims 1, 5-9, 11-20 and 26-28 is hereby withdrawn in view of Applicant’s amendments to the claim.
9. Rejection to claims 1-25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is hereby withdrawn in view of Applicant’s amendment to the claim.
10. Rejection to claim 23 under 35 U.S.C. 112(d) or 35 U.S.C. 112 (pre-AIA ), 4th paragraph is hereby withdrawn in view of Applicant’s amendment to the claim.
11. Rejections to instant claims on the ground of nonstatutory obviousness-type double patenting over claims of US patents 10905745 B2, 11130793 B2 and 11395847 B2 are hereby withdrawn in view of Applicant’s filing of terminal disclaimer on 11/21/2025.
12. Rejection to instant claims on the ground of nonstatutory obviousness-type double patenting over claims of co-pending Application No. 17/617675 is hereby withdrawn in view of Applicant’s abandonment of Application No. 17/617675.
Maintained/Revised Objections
13. (Revised due to Applicant’s amendment to the claim) Claim 2 remains objected to for the following minor informality: Applicant is suggested to amend claim 2 as “…(d) the fatty liver disease is parenteral nutrition associated gut atrophy, Parenteral Nutrition-Associated Liver Disease (PNALD), Non-Alcoholic Fatty Liver Disease (NAFLD), or Non-Alcoholic Steatohepatitis (NASH)…”.
Response to Applicant's Arguments
14. Applicant fails to address all the minor issues in claim 2. Therefore, the objection is deemed proper and is hereby maintained.
New Objections
15. Claim 23 is objected to for the following minor informality: Applicant is suggested to amend claim 23 as “…EKEKEΨ (SEQ ID NO: 16), and EkEkEΨ (SEQ ID NO: 17)”.
16. Claims 30 and 32 are objected to for the following minor informality: Claims 30 and 32 recite “inflammatory bowel disease, Crohn's disease, ulcerative colitis”. However, inflammatory bowel disease is the common name used to describe Crohn's disease and ulcerative colitis. Therefore, Applicant is suggested to amend this recitation in claims 30 and 32 as “inflammatory bowel disease” or “Crohn's disease, ulcerative colitis”.
Maintained/Revised Rejections
Scope of Enablement
17. The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
18. (Revised due to Applicant’s amendment to the claim) Claims 1-32 remain/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treatment of (a) malabsorption, peptic ulcers, drug-induced ulcers, short-bowel syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or graft versus host disease (GVHD) in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof with the recited GLP-1/GLP-2 dual agonist or pharmaceutically acceptable salt thereof, does not reasonably provide enablement for a method of treatment of ALL conditions recited in instant claims 1, 2 and 30-32 with the recited GLP-1/GLP-2 dual agonist or pharmaceutically acceptable salt thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with the instant claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (5) The breadth of the claims:
The instant claims 1-32 are drawn to a method of prophylaxis or treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject; a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSF TSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200); and a method of treatment of ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, and mucositis or diarrhea induced by chemotherapy or radiation therapy in a subject in need thereof, the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200). And instant claims 2 and 30 further limit the subject in need thereof recited in instant claim 1.
The condition recited in instant claims 1, 31 and 32 is very broad; and claims 2 and 30 further limit the subject to certain conditions recited in instant claim 1.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
With regards to a method of treatment of instant claimed conditions with a GLP-1/GLP-2 dual agonist, the art is unpredictable.
With regards to treating instant claimed conditions with a GLP-1/GLP-2 dual agonist, there is no prior art and any type of evidence and/or data disclosing any role of a GLP-1/GLP-2 dual agonist in treating cul-de-sac syndrome, tropical sprue, Zollinger-Ellison Syndrome, and ulcers related to all types of infections or other pathogens. Furthermore, Chis et al (Clujul Medical, 2018, 91, pages 117-119, cited and enclosed in the previous office action) teach targeting GLP-1 receptor via a GLP-1 receptor agonist induces acute pancreatitis, for example, Title; and Abstract.
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
With regards to instant claimed method, there is no working example disclosed in instant specification.
(8) The quantity of experimentation necessary:
Considering the state of the art regarding to a method of treatment of instant claimed conditions with a GLP-1/GLP-2 dual agonist, one of ordinary skill in the art would be burdened with undue experimentation to perform instant claimed method.
Response to Applicant's Arguments
19. Applicant fails to address every aspect of this rejection. Therefore, the rejection is deemed proper and is hereby maintained.
Obviousness Double Patenting
20. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
21. (Revised due to Applicant’s amendment to the claim) Claims 1-7, 11-13, 15, 16, 18-20 and 24-32 remain/are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 4-6 and 11-17 of co-pending Application No. 17/906871.
22. Instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32 are drawn to a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: R1-X*-U-R2, wherein: R1 is a hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide of formula I: H-X2-EG-X5-F-X7-X8-E-X10-X11-TIL-X15-X16-X17-A-X19-X20-X21-FI-X24-WL-X27-X28-X29-KIT-X33 (I) (SEQ ID NO: 3), wherein: X2 is Aib or G; X5 is T or S; X7 is T or S; X8 is S, E or D; X10 is L, M, V or Ψ; X11 is A, N or S; X15 is D or E; X16 is G, E, A or Ψ; X17 is Q, E, K, L or Ψ; X19 is A, V or S; X20 is R, K or Ψ; X21 is D, L or E; X24 is A, N or S; X27 is I, Q, K, H or Y; X28 is Q, E, A, H, Y, L, K, R or S; X29 is H, Y or Q; X33 is D or E; U is absent or a sequence of 1-15 residues, each, independently, selected from K, k, E, A, T, I, L and Ψ; the GLP-1/GLP-2 dual agonist contains one and only one Ψ, wherein Ψ is a residue of K, k, R, Orn, Dap or Dab in which the side chain is conjugated to a substituent having the formula Z1- or Z1-Z2-, wherein: Z1- is CH3-(CH2)10-22-(CO)- or HOOC-(CH2)10-22-(CO)-; and -Z2- is selected from -Zs1-, -Zs1-Zs2-, -Zs2-Zs1-, -Zs2-, -ZS3-, -ZS1-ZS3-, -ZS2-ZS3-, -ZS3-ZS1-, -ZS3-ZS2-, -ZS1-ZS2-ZS3-, -Zs1-Zs3-Zs2-, -Zs2-Zs1-Zs3-, -Zs2-Zs3-Zs1-, -Zs3-Zs1-Zs2-, -Zs3-Zs2-Zs1-, -Zs2-Zs3-Zs2-; wherein Zs1 is isoGlu, β-Ala, isoLys, or 4-aminobutanoyl; ZS2 is -(Peg3)m-, wherein m is 1, 2, or 3; and ZS3 is a peptide sequence of 1-6 amino acid residues independently selected from the group consisting of A, L, S, T, Y, Q, D, E, K, k, R, H, F and G; and wherein at least one of X5 and X7 is T; a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFI AWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200); and a method of treatment of ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, and mucositis or diarrhea induced by chemotherapy or radiation therapy in a subject in need thereof, the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200).
23. Claims 1, 4-6 and 11-17 of co-pending Application No. 17/906871 are drawn to a method for treating a patient who has undergone surgical resection of the bowel, the method comprising administering to the patient an agonist combination within about 7 days of said surgical resection, and wherein said agonist combination comprises is a dual glucagon-like peptide 1/glucagon-like peptide 2 (GLP-1/GLP-2) agonist of formula Hy-H[Aib]EGSFTSELATILD[K([17-carboxv-heptadecanoyl]-isoGlu)IQAARDFIAWLIQHK ITD-OH (Compound 18) (SEQ ID NO: 132).
In the instant case, in view of the combined teachings of claims 1, 4-6 and 11-17 of co-pending Application No. 17/906871, it would have been obvious to one of ordinary skilled in the art to develop a method of for treating short bowl syndrome in a patient who has undergone surgical resection of the bowel, the method comprising administering to the patient an agonist combination within about 7 days of said surgical resection, and wherein said agonist combination comprises is a dual GLP-1/GLP-2 agonist of formula Hy-H[Aib]EGSFTSELATILD[K([17-carboxv-heptadecanoyl]-isoGlu)IQ AARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 132).
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
24. (Revised due to Applicant’s amendment to the claim) For the same/similar reasoning/rational as the rejection set forth in Sections 21-23 above, instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32 remain/are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 2, 6-13, 15, 16, 18-22, 24-27 and 32-35 of co-pending Application No. 17/617670; claims 1-4 and 7-16 of co-pending Application No. 17/906888; claims 1-17 of co-pending Application No. 18/275195; and claims 1, 2, 7-9, 11-13, 15, 20, 22, 30-32 and 37-42 of co-pending Application No. 19/236746
These are all provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
25. (Revised due to Applicant’s amendment to the claim) Claims 1-7, 11-13, 15, 16, 18-20 and 24-32 remain/are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-21 of co-pending Application No. 18/037795 in view of Pedersen et al (WO 2016/066818 A1, filed with IDS).
26. Instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32 are drawn to a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: R1-X*-U-R2, wherein: R1 is a hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide of formula I: H-X2-EG-X5-F-X7-X8-E-X10-X11-TIL-X15-X16-X17-A-X19-X20-X21-FI-X24-WL-X27-X28-X29-KIT-X33 (I) (SEQ ID NO: 3), wherein: X2 is Aib or G; X5 is T or S; X7 is T or S; X8 is S, E or D; X10 is L, M, V or Ψ; X11 is A, N or S; X15 is D or E; X16 is G, E, A or Ψ; X17 is Q, E, K, L or Ψ; X19 is A, V or S; X20 is R, K or Ψ; X21 is D, L or E; X24 is A, N or S; X27 is I, Q, K, H or Y; X28 is Q, E, A, H, Y, L, K, R or S; X29 is H, Y or Q; X33 is D or E; U is absent or a sequence of 1-15 residues, each, independently, selected from K, k, E, A, T, I, L and Ψ; the GLP-1/GLP-2 dual agonist contains one and only one Ψ, wherein Ψ is a residue of K, k, R, Orn, Dap or Dab in which the side chain is conjugated to a substituent having the formula Z1- or Z1-Z2-, wherein: Z1- is CH3-(CH2)10-22-(CO)- or HOOC-(CH2)10-22-(CO)-; and -Z2- is selected from -Zs1-, -Zs1-Zs2-, -Zs2-Zs1-, -Zs2-, -ZS3-, -ZS1-ZS3-, -ZS2-ZS3-, -ZS3-ZS1-, -ZS3-ZS2-, -ZS1-ZS2-ZS3-, -Zs1-Zs3-Zs2-, -Zs2-Zs1-Zs3-, -Zs2-Zs3-Zs1-, -Zs3-Zs1-Zs2-, -Zs3-Zs2-Zs1-, -Zs2-Zs3-Zs2-; wherein Zs1 is isoGlu, β-Ala, isoLys, or 4-aminobutanoyl; ZS2 is -(Peg3)m-, wherein m is 1, 2, or 3; and ZS3 is a peptide sequence of 1-6 amino acid residues independently selected from the group consisting of A, L, S, T, Y, Q, D, E, K, k, R, H, F and G; and wherein at least one of X5 and X7 is T; a method of treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFI AWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200); and a method of treatment of ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, and mucositis or diarrhea induced by chemotherapy or radiation therapy in a subject in need thereof, the method comprising administering a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (Compound 18) (SEQ ID NO: 200).
27. Claims 1-21 of co-pending Application No. 18/037795 are drawn to a composition comprising: (a) one or more GLP-1/GLP-2 dual agonist comprising general formula A: H[Aib]EG-X5-F-X7-SELATILD-[Ψ]-QAARDFIAWLI-X28-HKITD (A), wherein X5 is T or S; X7 is T or S; X28 is Q, E, A, H, Y, L, K, R or S and at least one of X5 and X7 is T, wherein [Ψ] indicates an L or D lysine residue in which an albumin binding moiety is conjugated to the GLP-1/GLP-2 dual agonist, and wherein said albumin binding moiety is [K([17-carboxy-heptadecanoyl]-isoGlu)]; (b) one or more preservative, wherein the one or more preservative is or comprises benzoate, benzalkonium chloride and/or benzyl alcohol; and (c) phosphate buffer.
The dual agonist recited in claims 1-21 of co-pending Application No. 18/037795 meets the limitations of the GLP-1/GLP-2 dual agonist recited in instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32.
28. The difference between claims 1-21 of co-pending Application No. 18/037795 and instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32 is that it does not apply the dual agonist in the methods recited in instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32.
However, Pedersen et al, throughout the patent, teach a GLP-1/GLP-2 dual agonist of SEQ ID NO: 1, wherein the amino acid at position 29 is Thr, Ser, Lys or Arg; and the treatment or prophylactic treatment of human diseases, such as gastrointestinal inflammation, short bowel syndrome and Crohn's disease with such GLP-1/GLP-2 dual agonist, for example, Abstract; page 1, lines 5-12; and page 5, lines 10-24.
Therefore, in view of the teachings of Pedersen et al as a whole, it would have been obvious to one of ordinary skilled in the art to apply the dual agonist recited in claims 1-21 of co-pending Application No. 18/037795 and develop the methods recited in instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32.
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
29. (Revised due to Applicant’s amendment to the claim) For the same/similar reasoning/rational as the rejection set forth in Sections 25-28 above, instant claims 1-7, 11-13, 15, 16, 18-20 and 24-32 remain/are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/039857; and claims 1-20 of co-pending Application No. 18/039992; and in view of the teachings of Pedersen et al (WO 2016/066818 A1, filed with IDS) as set forth in Section 28 above.
These are all provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Response to Applicant's Arguments
30. Applicant argues that all these co-pending Applications are filed later than the effective filing date of instant application.
31. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about these provisional ODP rejections, the Examiner would like to point out that these provisional ODP rejections are not the only remained rejection in the current office action. Furthermore, a notice of allowance has been mailed on 11/18/2025 in Application No. 17/617670. Therefore, until a proper terminal disclaimer is filed and approved by the Office, these double patenting rejections are hereby maintained.
Examiner’s Notes
32. As stated in the previous office action, the methods recited in instant claims 1-32 are free of prior art. The closest prior art is Pedersen et al (WO 2016/066818 A1, filed with IDS). Pedersen et al teach a GLP-1/GLP-2 dual agonist of SEQ ID NO: 1, wherein the amino acid at position 29 is Thr, Ser, Lys or Arg; and the treatment or prophylactic treatment of human diseases, such as gastrointestinal inflammation, short bowel syndrome and Crohn's disease with such GLP-1/GLP-2 dual agonist, for example, Abstract; and page 5, lines 10-24. However, there is no teaching, motivation, or other type of suggestion to modify the GLP-1/GLP-2 dual agonist in Pedersen et al and arrive at the GLP-1/GLP-2 dual agonist used in the methods recited in instant claims 1-32. Therefore, the methods recited in instant claims 1-32 are both novel and unobvious over the prior arts of record.
Conclusion
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.
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658