Eli Lilly and Company

Jose M Hanquier

Jeffrey C Baker

Robert T Shuman

Aidas V Kriauciunas

Warren E Shrader

Victor J Chen

Brian A Moser

The present invention relates to the field of diabetes. More particularly, the invention relates to a monomeric insulin analog wherein the A chain is the naturally occurring sequence of the human insulin A chain and the B chain is modified at either position B28 and B29 or both. The analog is mono-acylated at the N-terminal of the A chain or B chain or at the lysine. The acylated insulin analogs have an extended duration of action.

Acylated Insulin Analogs

Acylated insulin analogs

The present invention relates to the acylation of proteins. More particularly, the invention relates to a one-step process for selectively acylating the free .epsilon.-amino group of insulin, insulin analog, or proinsulin in the presence of a free .alpha.-amino group.

Selective acylation of epsilon-amino groups

A method for processing a fatty acid-acylated protein, especially N-palmitoyl Lys.sup.B29 human insulin, to reduce the incidence of gelation by conducting such processing in the presence of a citrate buffering agent as the primary buffer which method allows such processing to be conducted at higher protein concentrations and with less temperature control than would otherwise be possible in the absence of the citrate buffer.

Reducing gelation of a fatty acid-acylated protein

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Martinsville, IN, United States of America

Jose M Hanquier