Granted Patent B2

US 12,551,535 · App. 18/587,927 · Granted Feb 17, 2026

Inventor: John J. Nestor (Sugar Land, TX)

Assignee: Mederis Diabetes, LLC

A61K38/26A61K47/549C07K14/605A61K38/00

Abstract

Claims (72)

1 . A peptide product comprising a surfactant X covalently attached to a peptide that binds a glucagon receptor and a glucagon like peptide 1 (GLP-1) receptor:

wherein the surfactant X is a 1-alkyl glycoside class surfactant; and

the peptide comprises at least amino acid residues aa 1 -aa 28 from Formula II:

Formula II

(SEQ. ID. NO. 1)

aa 1 -aa 2 -aa 3 -aa 4 -aa 5 -aa 6 -aa 7 -aa 8 -aa 9 -aa 10 -aa 11 -aa 12 -

aa 13 -aa 14 -aa 15 -aa 16 -aa 17 -aa 18 -aa 19 -aa 20 -aa 21 -aa 22 -

aa 23 -aa 24 -aa 25 -aa 26 -aa 27 -aa 28 -aa 29 -aa 30 -aa 31 -aa 32 -

aa 33 -aa 34 -aa 35 -aa 36 -aa 37 -Z

wherein:

Z is —OH, —N—R 4 -His, or —NH—R 3 ,

wherein:

R 3 is H, or a substituted or unsubstituted C 1 -C 12 alkyl; and

R 4 is a C 2 -C 10 acyl group;

aa 1 is His, N—R 4 -His, pGlu-His, or N—R 3 -His;

aa 2 is Ser, D-Ser, Ala, Gly, Pro, MePro, Aib, Ac4c, or Ac5c;

aa 3 is Gln or Cit;

aa 4 is Gly or D-Ala;

aa 5 is Thr or Ser;

aa 6 is Phe, Trp, 2FPhe, MePhe, 2FMePhe, or Nal2;

aa 7 is Thr or Ser;

aa 8 is Ser or Asp;

aa 9 is Asp or Glu;

aa 10 is Tyr, Leu, Met, Nal2, Bip, or Bip2EtMeO;

aa 11 is Ser, Asn, or Bip;

aa 12 is Lys, Glu, Ser, or Arg;

aa 13 is Tyr, Gln, or Cit;

aa 14 is Leu, Met, or Nle;

aa 15 is Asp or Glu;

aa 16 is Glu, or Lys;

aa 17 is Glu, or Lys;

aa 18 is Arg, hArg, Ala, Aib, Ac4c, or Ac5c;

aa 19 is Ala, Val, Aib, Ac4c, or Ac5c;

aa 20 is Lys, or Glu;

aa 21 is Asp, Glu, Leu, Aib, Ac4c, or Ac5c;

aa 22 is Phe, Trp, Nal2, Aib, Ac4c, or Ac5c;

aa 23 is Val, Ile, Aib, Ac4c, or Ac5c;

aa 24 is Gln, Ala, Glu, or Cit;

aa 25 is Trp or Nal2;

aa 26 is Leu;

aa 27 is Leu;

aa 28 is Gin;

aa 29 is absent, Thr, Gly, Aib, Ac4c, or Ac5c;

aa 30 is absent, Lys, Aib, Ac4c, Ac5c, or Arg;

aa 31 is absent, Arg, Aib, Ac4c, or Ac5c;

aa 32 is absent, Asn, Aib, Ac4c, or Ac5c;

aa 33 is absent, Arg, Aib, Ac4c, or Ac5c;

aa 34 is absent, Asn, Aib, Ac4c, or Ac5c;

aa 35 is absent, Asn, Aib, Ac4c, or Ac5c;

aa 36 is absent, Ile, Ala, Aib, Ac4c, or Ac5C; and

aa 37 is absent;

wherein aa 16 and aa 20 are cyclized to form a lactam linkage; and

provided that aa 17 is covalently attached to the surfactant X.

2 . The peptide product of claim 1 , wherein the 1-alkyl glycoside class surfactant comprises a substituted or unsubstituted C 6 -C 30 alkyl group.

3 . The peptide product of claim 1 , wherein the 1-alkyl glycoside class surfactant comprises a substituted or unsubstituted C 6 -C 20 alkyl group.

4 . The peptide product of claim 3 , wherein the 1-alkyl glycoside class surfactant comprises a substituted or unsubstituted C 12 -C 20 alkyl group.

5 . The peptide product of claim 4 , wherein the surfactant X comprises 1-eicosyl beta-D-glucuronic acid, 1-octadecyl beta-D-glucuronic acid, 1-hexadecyl beta-D-glucuronic acid, 1-tetradecyl beta-D-glucuronic acid, 1-dodecyl beta-D-glucuronic acid, 1-decyl beta-D-glucuronic acid, 1-octyl beta-D-glucuronic acid, 1-eicosyl beta-D-diglucuronic acid, 1-octadecyl beta-D-diglucuronic acid, 1-hexadecyl beta-D-diglucuronic acid, 1-tetradecyl beta-D-diglucuronic acid, 1-dodecyl beta-D-diglucuronic acid, 1-decyl beta-D-diglucuronic acid, 1-octyl beta-D-diglucuronic acid, functionalized 1-eicosyl beta-D-glucose, 1-octadecyl beta-D-glucose, 1-hexadecyl beta-D-glucose, 1-tetradecyl beta-D-glucose, 1-dodecyl beta-D-glucose, 1-decyl beta-D-glucose, 1-octyl beta-D-glucose, 1-eicosyl beta-D-maltoside, 1-octadecyl beta-D-maltoside, 1-hexadecyl beta-D-maltoside, 1-tetradecyl beta-D-maltoside, 1-dodecyl beta-D-maltoside, 1-decyl beta-D-maltoside, 1-octyl beta-D-maltoside, 1-eicosyl beta-D-melibioside, 1-octadecyl beta-D-melibioside, 1-hexadecyl beta-D-melibioside, 1-tetradecyl beta-D-melibioside, 1-dodecyl beta-D-melibioside, 1-decyl beta-D-melibioside, 1-octyl beta-D-melibioside, the corresponding 1-alkyl alpha glycoside, or the corresponding glycoside with a 6-carboxyl group or 6,6′-dicarboxyl groups.

6 . The peptide product of claim 1 , wherein aa 17 is a lysine residue attached to X.

7 . The peptide product of claim 1 , wherein aa 2 is a glycine residue.

8 . The peptide product of claim 1 , wherein aa 2 is an Aib residue.

9 . The peptide product of claim 1 , wherein the peptide comprises one or more Aib residues.

10 . The peptide product of claim 1 , wherein the surfactant X comprises a dodecyl, tetradecyl, hexadecyl or octadecyl alkyl chain.

11 . The peptide product of claim 1 , further comprising a covalently linked one or more PEG moieties.

12 . The peptide product of claim 11 , wherein the one or more PEG moieties is a PEG chain comprising C 10 -C 3000 .

13 . A pharmaceutical composition comprising a therapeutically effective amount of a peptide product of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

14 . A method for treatment of insulin resistance comprising administering the pharmaceutical composition of claim 13 to an individual in need thereof.

15 . A method for treatment of insulin resistance comprising administering the pharmaceutical composition of claim 13 to an individual in need therein, wherein the peptide product comprises amino acid residues aa 1 -aa 27 of SEQ. ID. NO. 1.

16 . The method of claim 15 , wherein the treatment causes weight loss.

17 . The method of claim 15 , wherein the treatment prevents or delays type 2 diabetes.

18 . The method of claim 15 , wherein the treatment delays progression of pre-diabetes to type 2 diabetes.

19 . The method of claim 15 , wherein the treatment induces satiety and glucose-dependent insulin secretion.

20 . The method of claim 15 , wherein the treatment treats gestational diabetes.

Assignments (3)

Continuity (4)

References Cited (174)