Excipient stabilization of polypeptides treated with organic solvents

• US 5,804,557 A
• Filed: 09/24/1996
• Issued: 09/08/1998
• Est. Priority Date: 02/23/1993
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Cleland, Jeffrey L., Jones, Andrew J. S.
• Primary Examiner(s): Davenport, Avis M.
• Application Number:
  US08/719,196
• Time in Patent Office: 714 Days
• Field of Search: 514/12, 514/21, 530/351, 530/324, 530/399, 424/85.7
• US Class Current: 514/11.3
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

Methods and compositions for excipient stabilization of dry or aqueous polypeptides treated with organic solvents are disclosed, wherein the polypeptide is admixed with a polyol having a molecular weight less than about 70,000 kD.

Claims

1. A method of increasing solubility of a polypeptide in an aqueous formulation comprising a polyol excipient, said method comprising:

admixing the polypeptide with the polyol excipient, wherein the polyol excipient is trehalose,

wherein said increasing is at least 2-fold relative to solubility of the polypeptide in the formulation lacking excipient.

2. The method of claim 1 wherein the trehalose and polypeptide are present in a mass ratio of 1:

20 polyol excipient;

polypeptide.

3. The method of claim 1 wherein the trehalose and polypeptide are present in a mass ratio of 1:

4 polyol excipient;

polypeptide.

4. The method of claim 1 wherein the trehalose and polypeptide are present in a mass ratio of 1:

2 polyol excipient;

polypeptide.

5. A composition comprising a polypeptide admixed in an aqueous formulation with a polyol excipient, wherein the polyol excipient is trehalose,

wherein the solubility of the polypeptide in the formulation is increased by at least 2-fold relative to solubility of the polypeptide in the formulation lacking excipient.

6. The composition of claim 5 wherein the trehalose and polypeptide are present in a mass ratio of 1:

20 polyol excipient;

polypeptide.

7. The composition of claim 5 wherein the trehalose and polypeptide are present in a mass ratio of 1:

4 polyol excipient;

polypeptide.

8. The composition of claim 5 wherein the trehalose and polypeptide are present in a mass ratio of 1:

2 polyol excipient;

polypeptide.