Claims
- 1. A complex consisting of a divalent metal cation associated with and capable of co-precipitating with a compound of the formula:
- 2. A complex of claim 1 wherein said divalent metal cation is zinc.
- 3. A complex of claim 2 wherein R1 is chosen from the group consisting of His and desamino-histidine.
- 4. A complex of claim 2 wherein X is chosen from the group consisting of Ala, Gly, and Val.
- 5. A complex of claim 2 wherein Y is chosen from the group consisting of Glu and Gln.
- 6. A complex of claim 2 wherein Z is chosen from the group consisting of Glu and Gln.
- 7. A complex of claim 2 wherein R1 is His, X is Val, Y is Glu, Z is Glu, and R2 is Gly-OH.
- 8. A complex of claim 2 wherein R1 is His, X is Gly, Y is Gln, Z is Glu, and R2 is Gly-OH.
- 9. A pharmaceutical composition which comprises a complex according to claim 1 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 10. A pharmaceutical composition which comprises a complex according to claim 2 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 11. A pharmaceutical composition which comprises a complex according to claim 3 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 12. A pharmaceutical composition which comprises a complex according to claim 4 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 13. A pharmaceutical composition which comprises a complex according to claim 5 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 14. A pharmaceutical composition which comprises a complex according to claim 6 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 15. A pharmaceutical composition which comprises a complex according to claim 7 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 16. A pharmaceutical composition which comprises a complex according to claim 8 in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
- 17. 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.
- 18. 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 mammal.
- 19. 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 mammal.
- 20. 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 mammal.
- 21. 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 mammal.
- 22. 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 mammal.
- 23. 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 mammal.
- 24. 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 mammal.
- 25. 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 mammal.
- 26. 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.
- 27. A process of preparing a GLP-1 complex, which comprises steps of;
a) mixing a GLP-1 molecule of the formula: R1-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-R2 wherein:
R1 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 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; R2 is selected from the group consisting of NH2, and Gly-OH; providing that the compound has an isoelectric point in the range from about 6.0 to about 9.0; with a divalent metal cation to form a mixture and; b) incubating for a time and a temperature sufficient to form a complex.
- 28. The process of claim 27, wherein X is selected from the group consisting of Val, Thr, Ile, and alpha-methyl-Ala.
- 29. The process of claim 27, wherein R1 is L-histidine, X is Val, Y is Glu, Z is Glu, and R2 is Gly-OH.
- 30. The process of claim 27, wherein RI is L-histidine, X is Gly or alpha-methyl-Ala, Y is Glu, Z is Glu, and R2 is —NH2.
- 31. The process of claim 27, wherein the divalent metal cation is zinc.
- 32. The process of claim 28, wherein the divalent metal cation is zinc.
- 33. The process of claim 29, wherein the divalent metal cation is zinc.
- 34. The process of claim 30, wherein the divalent metal cation is zinc.
- 35. The process of claim 27, further comprising the step of adding a buffer to the mixture.
- 36. The process of claim 35 wherein the buffer has a pH in the range of about 6 to about 9.
- 37. The process of claim 31, wherein the zinc is provided at a molar ratio of up to about 50 molecules of zinc for each molecule of GLP-1.
- 38. The process of claim 37, wherein the molar ratio is about 1 molecule of zinc for each molecule of GLP-1.
- 39. The process of claim 37, wherein the molar ratio is about 0.7 molecules of zinc for each molecule of GLP-1.
Parent Case Info
[0001] This application is a continuation-in-part of Galloway et al., U.S. Ser. No. 08/164,277, filed Dec. 9, 1993.
Divisions (3)
|
Number |
Date |
Country |
Parent |
09348136 |
Jul 1999 |
US |
Child |
09573809 |
May 2000 |
US |
Parent |
08927227 |
Sep 1997 |
US |
Child |
09348136 |
Jul 1999 |
US |
Parent |
08407831 |
Mar 1995 |
US |
Child |
08927227 |
Sep 1997 |
US |
Continuations (2)
|
Number |
Date |
Country |
Parent |
09975905 |
Oct 2001 |
US |
Child |
10125255 |
Apr 2002 |
US |
Parent |
09573809 |
May 2000 |
US |
Child |
09975905 |
Oct 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08164277 |
Dec 1993 |
US |
Child |
08407831 |
Mar 1995 |
US |