Eli Lilly and Company

Other

Ronald E Chance

Bruce H Frank

John A Galloway

Richard Dennis DiMarchi

James E Shields

James A Hoffmann

Recombinant processes for preparing insulin analogs modified at position 29 of the B-chain and, optionally, at other positions are claimed. The analogs produced using the claimed processes have modified physico-chemical properties and are useful in treating hyperglycemia.

Process for preparing insulin analogs

Analogs of human insulin modified at position 29 of the B chain thereof and, optionally, at other positions, have modified physico-chemical and pharmacokinetic properties and are useful in the treatment of hyperglycemia.

Insulin analogs modified at position 29 of the B chain

A pharmaceutical composition which comprises human proinsulin in association with a pharmaceutically acceptable carrier is useful in controlling a diabetic condition and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Human proinsulin pharmaceutical formulations

A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin and human proinsulin in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Pharmaceutical formulations comprising human insulin and human proinsulin

A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin, human C-peptide, and human proinsulin, said human C-peptide being present in a molar ratio, human insulin to human C-peptide, of from about 1:4 to about 4:1, and said human proinsulin being present in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Pharmaceutical formulations comprising human insulin, human C-peptide,

Production of insulin or an insulin analog is provided by combination of an A-chain and a B-chain, which comprises bringing the S-sulfonated form of the A-chain, the S-sulfonated form of the B-chain, and a thiol reducing agent together in an aqueous medium under conditions which produce a mixture having (1) a pH of from about 8 to about 12, (2) a total protein concentration of from about 0.1 to about 50 milligrams per milliliter, and (3) an amount of thiol reducing agent which affords a total of from about 0.4 to about 2.5 --SH groups per each --SSO.sub.3.sup.- group present in the total amount of A- and B-chain S-sulfonates, and allowing formation of insulin or an insulin analog to occur by maintaining the mixture at a temperature of from about 0.degree. C. to about 25.degree. C. and in an environment which provides a source of oxygen.

Growing community of inventors

Westfield, IN, United States of America

Ronald E Chance