Eli Lilly and Company

Jeffrey C Baker

Jose M Hanquier

Theodore Arsay Sheliga

Lihua Huang

Andrew David Carlson

Warren E Shrader

Brian A Moser

Robert T Shuman

Bruce H Frank

Victor J Chen

Aidas V Kriauciunas

Nancy Delores Jones

Nancy D Carter

Bradley M Roberts

The present invention is directed at a method of processing an aqueous solution of protein C into a state suitable for storage, handling, and recovery. The present invention provides aqueous activated protein C solutions and an improved method of processing such solutions into cryogranules.

Cryogranulation of activated protein C

The present invention is broadly directed to a method for reducing autodegradation of activated protein C during processing and purification. The present invention provides aqueous activated protein C solutions and an improved method of processing of such solutions, comprising conducting such processing at an ionic strength of greater than 150 mM and at a pH of about 5.5 to less than 6.3.

Activated protein C formulations

Methods for processing activated protein C

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

A method for recovering an acylated protein as a powder, especially in cases where said acylated protein is one that resists isolation by isoelectric precipitation from aqueous solutions of the protein, said method comprising in combination adjusting said aqueous solution to near the isoelectric pH of the protein and providing a suitable alcohol concentration to cause precipitation of the protein in the form of filterable particles at said pH.

Preparation of an acylated protein powder

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

The present invention discloses a process of preparing a crystalline alkali metal or ammonium salt of Lys.sup.B28 Pro.sup.B29 -human insulin. The process is useful in the purification and manufacture of Lys.sup.B28 Pro.sup.B29 -human insulin. Lys.sup.B28 Pro.sup.B29 -human insulin is useful in the treatment of diabetes.

Preparation of stable insulin analog crystals

The present invention discloses a process of preparing a crystalline insulin analog. The process is useful in the purification and manufacture of Lys.sup.B28 Pro.sup.B29 -human insulin. Lys.sup.B28 Pro.sup.B29 -human insulin is useful in the treatment of diabetes.

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Indianapolis, IN, United States of America

Jeffrey C Baker