NZ804103A - Long?acting conjugate of GLP?2 derivatives - Google Patents
Long?acting conjugate of GLP?2 derivativesInfo
- Publication number
- NZ804103A NZ804103A NZ804103A NZ80410318A NZ804103A NZ 804103 A NZ804103 A NZ 804103A NZ 804103 A NZ804103 A NZ 804103A NZ 80410318 A NZ80410318 A NZ 80410318A NZ 804103 A NZ804103 A NZ 804103A
- Authority
- NZ
- New Zealand
- Prior art keywords
- glp
- lysine
- derivative
- glycine
- imidazoacetyldeshistidine
- Prior art date
Links
- 238000000034 method Methods 0.000 claims abstract 5
- TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 claims 31
- 239000004472 Lysine Substances 0.000 claims 19
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 19
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 18
- 239000004471 Glycine Chemical group 0.000 claims 16
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 14
- 239000004475 Arginine Substances 0.000 claims 13
- 101800000221 Glucagon-like peptide 2 Proteins 0.000 claims 13
- 102100040918 Pro-glucagon Human genes 0.000 claims 13
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 13
- 235000018417 cysteine Nutrition 0.000 claims 11
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 11
- 108060003951 Immunoglobulin Proteins 0.000 claims 9
- 102000018358 immunoglobulin Human genes 0.000 claims 9
- 229920000642 polymer Polymers 0.000 claims 9
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims 8
- 125000001151 peptidyl group Chemical group 0.000 claims 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 7
- QFLNJOIJUNDRFH-ROLXFIACSA-N [(5s)-1,5-diamino-5-carboxypentyl]-diazonioazanide Chemical compound [N-]=[N+]=NC(N)CCC[C@H](N)C(O)=O QFLNJOIJUNDRFH-ROLXFIACSA-N 0.000 claims 5
- 150000001413 amino acids Chemical group 0.000 claims 5
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 4
- 208000028774 intestinal disease Diseases 0.000 claims 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- IMOBSLOLPCWZKQ-UHFFFAOYSA-N 2-(dimethylazaniumyl)-3-(1h-imidazol-5-yl)propanoate Chemical compound CN(C)C(C(O)=O)CC1=CN=CN1 IMOBSLOLPCWZKQ-UHFFFAOYSA-N 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 2
- 235000004279 alanine Nutrition 0.000 claims 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 2
- ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical compound OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 238000003259 recombinant expression Methods 0.000 claims 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims 2
- DKXIKPOYTWCGIE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-methylbutanoate Chemical compound CCC(C)C(=O)ON1C(=O)CCC1=O DKXIKPOYTWCGIE-UHFFFAOYSA-N 0.000 claims 1
- FHNMAOLQZHUPIJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-methylpropanoate Chemical compound CC(C)C(=O)ON1C(=O)CCC1=O FHNMAOLQZHUPIJ-UHFFFAOYSA-N 0.000 claims 1
- DYMYLBQTHCJHOQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) butanoate Chemical compound CCCC(=O)ON1C(=O)CCC1=O DYMYLBQTHCJHOQ-UHFFFAOYSA-N 0.000 claims 1
- ZJIFDEVVTPEXDL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) hydrogen carbonate Chemical compound OC(=O)ON1C(=O)CCC1=O ZJIFDEVVTPEXDL-UHFFFAOYSA-N 0.000 claims 1
- DRLIANXPAARUMI-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) pentanoate Chemical compound CCCCC(=O)ON1C(=O)CCC1=O DRLIANXPAARUMI-UHFFFAOYSA-N 0.000 claims 1
- AASBXERNXVFUEJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) propanoate Chemical compound CCC(=O)ON1C(=O)CCC1=O AASBXERNXVFUEJ-UHFFFAOYSA-N 0.000 claims 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 1
- 206010000087 Abdominal pain upper Diseases 0.000 claims 1
- 206010003694 Atrophy Diseases 0.000 claims 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical group CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims 1
- 229920002101 Chitin Polymers 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 229920002307 Dextran Polymers 0.000 claims 1
- 208000007882 Gastritis Diseases 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010028116 Mucosal inflammation Diseases 0.000 claims 1
- 201000010927 Mucositis Diseases 0.000 claims 1
- 206010033645 Pancreatitis Diseases 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 1
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical group CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims 1
- 206010049416 Short-bowel syndrome Diseases 0.000 claims 1
- 208000007107 Stomach Ulcer Diseases 0.000 claims 1
- 125000003172 aldehyde group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 230000037444 atrophy Effects 0.000 claims 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000000718 duodenal ulcer Diseases 0.000 claims 1
- 206010013864 duodenitis Diseases 0.000 claims 1
- 201000005917 gastric ulcer Diseases 0.000 claims 1
- 150000004676 glycans Chemical class 0.000 claims 1
- 229920002674 hyaluronan Polymers 0.000 claims 1
- 229960003160 hyaluronic acid Drugs 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 208000009326 ileitis Diseases 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 208000037817 intestinal injury Diseases 0.000 claims 1
- 210000000936 intestine Anatomy 0.000 claims 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims 1
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 229920001451 polypropylene glycol Polymers 0.000 claims 1
- 229920001282 polysaccharide Polymers 0.000 claims 1
- 239000005017 polysaccharide Substances 0.000 claims 1
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 1
- -1 succinimidyl carboxymethyl Chemical group 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 102000051325 Glucagon Human genes 0.000 abstract 2
- 108060003199 Glucagon Proteins 0.000 abstract 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 abstract 2
- 229960004666 glucagon Drugs 0.000 abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 2
Abstract
The present invention relates to a glucagon?like peptide?2 (GLP?2) derivative, a conjugate thereof, and a use thereof. Additionally, the present invention relates to a method for preparing a glucagon?like peptide?2 (GLP?2) derivative and a conjugate thereof.
Claims (23)
1.[Claim 1] A glucagon-like peptide-2 (GLP-2) conjugate, wherein a GLP-2 derivative and an immunoglobulin Fc region are each covalently linked via a non-peptidyl polymer at both termini of the non-peptidyl polymer, and wherein the non-peptidyl polymer is selected from the group consisting of polyethylene glycol, polypropylene glycol, ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, polysaccharide, dextran, polyvinyl ethyl ether, lipid polymer, chitin, hyaluronic acid, and a combination thereof.
2.[Claim 2] The GLP-2 conjugate according to claim 1, wherein the GLP-2 derivative comprises an amino acid sequence of the following General Formula 1: [General Formula 1] X1X2DGSFSDEMNTILDNLAARDFINWLIQTX30ITDX34 (SEQ ID NO: 9), wherein, in the above formula, X1 is histidine, imidazoacetyldeshistidine, desaminohistidine, ßhydroxyimidazopropionyldeshistidine, N-dimethylhistidine, or ßcarboxyimidazopropionyldeshistidine; X2 is alanine, glycine, or 2-aminoisobutyric acid (Aib); X30 is lysine or arginine; and X34 is absent, or lysine, arginine, glutamine, histidine, 6-azido-lysine, or cysteine; with the proviso that any sequence identical to an amino acid sequence of SEQ ID NO: 1 in General Formula 1 is excluded.
3.[Claim 3] The GLP-2 conjugate according to claim 2, wherein (1) X2 is glycine, (2) X30 is arginine, or (3) X2 is glycine and X30 is arginine. 44
4.[Claim 4] The GLP-2 conjugate according to claim 2 or 3, wherein (1) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is cysteine; (2) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is lysine; (3) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is arginine, and X34 is lysine; (4) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is 6-azidolysine; (5) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is arginine, and X34 is cysteine; (6) X1 is imidazoacetyldeshistidine, X2 is Aib, X30 is lysine, and X34 is cysteine; or (7) X1 is histidine, X2 is Aib, X30 is lysine, and X34 is cysteine.
5.[Claim 5] The GLP-2 conjugate according to any one of claims 1 to 4, wherein at least one residue of the GLP-2 derivative is cysteine, lysine, arginine, glutamine, histidine, or 6-azidolysine.
6.[Claim 6] The GLP-2 conjugate according to any one of claims 1 to 5, wherein the GLP-2 derivative is an amino acid sequence selected from the group consisting of SEQ ID NOS: 2 to 8.
7.[Claim 7] The GLP-2 conjugate according to any one of claims 1 to 6, wherein one end of the non-peptidyl polymer is conjugated to the immunoglobulin Fc region and the other end thereof is conjugated to the hydroxyl group, thiol group, amino group, or azide group of the GLP-2 derivative. 45
8.[Claim 8] The GLP-2 conjugate according to any one of claims 1 to 7, wherein the immunoglobulin Fc region is non-glycosylated.
9.[Claim 9] The GLP-2 conjugate according to any one of claims 1 to 8, wherein the immunoglobulin Fc region comprises a hinge region.
10.[Claim 10] The GLP-2 conjugate according to any one of claims 1 to 9, wherein the immunoglobulin Fc region is an IgG4 Fc region.
11.[Claim 11] A GLP-2 derivative comprising an amino acid sequence of the following General Formula 1: [General Formula 1] X1X2DGSFSDEMNTILDNLAARDFINWLIQTX30ITDX34 (SEQ ID NO: 9), wherein, in the above formula, X1 is histidine, imidazoacetyldeshistidine, desaminohistidine, ßhydroxyimidazopropionyldeshistidine, N-dimethylhistidine, or ßcarboxyimidazopropionyldeshistidine; X2 is alanine, glycine, or 2-aminoisobutyric acid (Aib); X30 is lysine or arginine; and X34 is absent, or lysine, arginine, glutamine, histidine, 6-azido-lysine, or cysteine; with the proviso that any sequence identical to an amino acid sequence of SEQ ID NO: 1 in General Formula 1 is excluded.
12.[Claim 12] The GLP-2 derivative according to claim 11, wherein (1) X2 is glycine, (2) X30 is 46 arginine, or (3) X2 is glycine and X30 is arginine.
13.[Claim 13] The GLP-2 derivative according to claim 11 or 12, wherein (1) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is cysteine; (2) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is lysine; (3) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is arginine, and X34 is lysine; (4) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is lysine, and X34 is 6-azidolysine; (5) X1 is imidazoacetyldeshistidine, X2 is glycine, X30 is arginine, and X34 is cysteine; (6) X1 is imidazoacetyldeshistidine, X2 is Aib, X30 is lysine, and X34 is cysteine; or (7) X1 is histidine, X2 is Aib, X30 is lysine, and X34 is cysteine.
14.[Claim 14] An isolated nucleic acid encoding the GLP-2 derivative according to any one of claims 11 to 13.
15.[Claim 15] A recombinant expression vector comprising the nucleic acid according to claim 14.
16.[Claim 16] A transformant comprising the recombinant expression vector according to claim 15.
17.[Claim 17] A method for preparing the GLP-2 derivative according to any one of claims 11 to 13, comprising: a) culturing a transformant comprising a nucleic acid encoding the GLP-2 derivative according to any one of claims 11 to 13 to express the GLP-2 derivative; and 47 b) isolating and purifying the expressed GLP-2 derivative.
18.[Claim 18] A method for preparing a GLP-2 conjugate, comprising: (a) preparing a complex by reacting a non-peptidyl polymer having two or more terminal reactive groups with one of the GLP-2 derivative according to any one of claims 11 to 13 and an immunoglobulin Fc region such that the complex has the GLP-2 derivative or the immunoglobulin Fc region attached to one terminal end of the non-peptidyl polymer, and a reactive group at the other terminal end; and (b) preparing a conjugate by reacting the complex prepared in Step (a) with one of the immunoglobulin Fc region and the GLP-2 derivative not attached to the complex such that the GLP-2 derivative and the immunoglobulin Fc region are linked via a non-peptidyl polymer.
19.[Claim 19] The method according to claim 18, wherein the non-peptidyl polymer comprises one or more reactive groups selected from the group consisting of an aldehyde group, a propionaldehyde group, a butyraldehyde group, a maleimide group, and a succinimide derivative.
20.[Claim 20] The method according to claim 19, wherein the succinimide derivative is succinimidyl carboxymethyl, succinimidyl valerate, succinimidyl methylbutanoate, succinimidyl methylpropionate, succinimidyl butanoate, succinimidyl propionate, Nhydroxysuccinimide, or succinimidyl carbonate.
21.[Claim 21] A pharmaceutical composition for preventing or treating one or more diseases selected from intestinal disease, intestinal injury, and gastrosia, comprising the GLP-2 conjugate according to any one of claims 1 to 10 or the GLP-2 derivative according to any 48 one of claims 11 to 13.
22.[Claim 22] The pharmaceutical composition according to claim 21, wherein the intestinal disease is short-bowel syndrome, hypersensitive intestinal disease, inflammatory intestinal disease, Crohn’s disease, colonitis, colitis, pancreatitis, ileitis, mucositis, or intestine atrophy.
23.[Claim 23] The pharmaceutical composition according to claim 21, wherein the gastrosia is stomach cramps, gastritis, gastric ulcer, duodenitis, or duodenal ulcer.
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ804103A true NZ804103A (en) | 2023-09-29 |
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