US5977071A
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US
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Glucagon-like insulinotropic peptides, compositions and methods
Assignee: Eli Lilly and Co
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Filing: 1997-09-10
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Granted: 1999-11-02
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Expires: 2017-09-10
Abstract
Abstract The present invention provides novel complexes consisting of certain GLP-1 molecules associated with a divalent metal cation that is capable of co-precipitating with a GLP-1 molecule. Pharmaceutical compositions and methods of using such complexes for enhancing the expression of insulin in B-type islet cells is claimed, as is a method for treating maturity onset diabetes mellitus in mammals, particularly humans.
Inventors
- 👤 John A. Galloway
- 👤 James A. Hoffmann
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 23:48
CPC Classifications
C; C07; C07K; C07K17/00; C07K17/14; C07K14/00; C07K14/435; C07K14/575; C07K14/605; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/62; A61P; A61P3/00; A61P3/08; A61P3/10; A61P43/00; A61K38/00; Y; Y10; Y10S; Y10S977/00; Y10S977/70; Y10S977/773; Y10S977/902; Y10S977/904; Y10S977/915
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
143 words
A complex consisting of a divalent metal cation associated with and capable of co-precipitating with a compound of the formula: R.sub.1 -X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Y-Gly-Gln-Ala-Ala-Lys-Z-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-R.sub.2 wherein: R 1 is selected from the group consisting of L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, alpha-fluoromethyl-histidine, and alpha-methyl-histidine; X is selected from the group consisting of Ala, Gly, Val, Thr, Ile, and alpha-methyl-Ala; Y is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly; Z is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly; R 2 is selected from the group consisting of NH 2 , and Gly-OH; providing that the compound has an isoelectric point in the range from about 6.0 to about 9.0 and further providing that when R 1 is His, X is Ala, Y is Glu, and Z is Glu, R 2 must be NH 2 .
Claim 2
Dependent Claim
143 words
A complex consisting of a divalent metal cation associated with and capable of co-precipitating with a compound of the formula: R.sub.1 -X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Y-Gly-Gln-Ala-Ala-Lys-Z-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-R.sub.2 wherein: R 1 is selected from the group consisting of L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, alpha-fluoromethyl-histidine, and alpha-methyl-histidine; X is selected from the group consisting of Ala, Gly, Val, Thr, Ile, and alpha-methyl-Ala; Y is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly; Z is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly; R 2 is selected from the group consisting of NH 2 , and Gly-OH; providing that the compound has an isoelectric point in the range from about 6.0 to about 9.0 and further providing that when R 1 is His, X is Ala, Y is Glu, and Z is Glu, R 2 must be NH 2 .
Claim 3
Dependent Claim
12 words
A complex of claim 1 wherein said divalent metal cation is zinc.
Claim 4
Dependent Claim
18 words
A complex of claim 2 wherein R 1 is chosen from the group consisting of His and desamino-histidine.
Claim 5
Dependent Claim
18 words
A complex of claim 2 wherein X is chosen from the group consisting of Ala, Gly, and Val.
Claim 6
Dependent Claim
17 words
A complex of claim 2 wherein Y is chosen from the group consisting of Glu and Gln.
Claim 7
Dependent Claim
17 words
A complex of claim 2 wherein Z is chosen from the group consisting of Glu and Gln.
Claim 8
Dependent Claim
24 words
A complex of claim 2 wherein R 1 is His, X is Val, Y is Glu, Z is Glu, and R 2 is Gly-OH.
Claim 9
Dependent Claim
24 words
A complex of claim 2 wherein R 1 is His, X is Gly, Y is Gln, Z is Glu, and R 2 is Gly-OH.
Claim 10
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 1 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 11
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 2 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 12
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 3 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 13
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 4 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 14
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 5 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 15
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 6 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 16
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 7 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 17
Dependent Claim
23 words
A pharmaceutical composition which comprises a complex according to claim 8 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
Claim 18
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a mammal in need of such treatment an effective amount of a complex according to claim 1 to said mammal.
Claim 19
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 1 to said human.
Claim 20
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 2 to said human.
Claim 21
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 3 to said human.
Claim 22
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 4 to said human.
Claim 23
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 5 to said human.
Claim 24
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 6 to said human.
Claim 25
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 7 to said human.
Claim 26
Dependent Claim
32 words
A method of treating maturity onset diabetes mellitus which comprises administering to a human in need of such treatment an effective amount of a complex according to claim 8 to said human.
Claim 27
Dependent Claim
26 words
A method for enhancing the expression of insulin comprising providing to a mammalian pancreatic B-type islet cell an effective amount of a complex of claim 1.
Claim 28
Dependent Claim
25 words
The pharmaceutical composition of claim 9 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 29
Dependent Claim
25 words
The pharmaceutical composition of claim 10 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 30
Dependent Claim
25 words
The pharmaceutical composition of claim 11 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 31
Dependent Claim
25 words
The pharmaceutical composition of claim 12 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 32
Dependent Claim
25 words
The pharmaceutical composition of claim 13 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 33
Dependent Claim
25 words
The pharmaceutical composition of claim 14 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 34
Dependent Claim
25 words
The pharmaceutical composition of claim 15 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
Claim 35
Dependent Claim
25 words
The pharmaceutical composition of claim 16 wherein the complex is a substantially insoluble crystalline or amorphous suspension when prepared in a pharmaceutically acceptable aqueous diluent.
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