Eli Lilly and Company

Hybritech Incorporated

James P McDonough

Thomas C Furman

Gerald W Becker

Warren C MacKellar

Richard M Bartholomew

Rodney A Jue

This disclosure relates to new compounds and to a process for the controlled conversion of such compounds to produce a Protein that comprises an amino acid sequence which is useful as a precursor to human insulin or to a modified human insulin, the amino terminus portion of which sequence does not define a cathepsin C dipeptide removal stop point. The compounds have the formula Met-Y-Protein in which Y is Tyr or Arg.

Enzymatic removal of a protein amino-terminal sequence

Novel methods for reducing the heterogeneity of secreted monoclonal antibodies are disclosed. The first method comprises incubating the heterogeneous antibodies at low pH for a length of time sufficient to convert the heterogeneous forms of antibodies into substantially homogeneous forms. Another method produces the same result using ascites fluid, while yet another method produces the same result using carboxypeptidase. The homogeneous antibodies can then be purified in high yield.

Method for the reduction of heterogeneity of monoclonal antibodies

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Indianapolis, IN, United States of America

James P McDonough