Claims for Patent: 7,452,539

Summary for Patent: 7,452,539

Title:	Stabilizing polypeptides which have been exposed to urea
Abstract:	Methods for stabilizing polypeptides, such as anti-HER2 antibodies, which have been exposed to urea.
Inventor(s):	Emery; Jefferson C. (Foster City, CA), McDonald; Paul J. (San Francisco, CA), O\'Leary; Rhona M. (San Francisco, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	10/316,694
Patent Claims:	1. A method for stabilizing an antibody from degradation upon exposure to urea comprising determining that said antibody shows degradation upon exposure to urea, exposing said antibody to urea in the presence of an amine containing solution comprising an amino acid, and confirming that degradation of said antibody has been prevented or reduced. 2. The method of claim 1 wherein the amino acid is glycine. 3. The method of claim 2 wherein the concentration of the glycine is from about 100 mM to about 400 mM. 4. The method of claim 1 wherein the antibody binds HER2, vascular endothelial growth factor (VEGF), IgE, CD20, CD40, CD11a, tissue factor (TF), prostate stem cell antigen (PSCA), interleukin-8 (IL-8), epidermal growth factor receptor (EGFR), HER3, HER4, .alpha.4.beta.7 or .alpha.5.beta.3. 5. The method of claim 1 wherein the antibody is Trastuzumab (HERCEPTIN.RTM.). 6. The method of claim 1 wherein the antibody is exposed to urea to inactivate viral contaminant(s) in a composition comprising the antibody and the viral contaminant(s). 7. The method of claim 1 wherein the amine containing solution comprising an amino acid is added to urea prior to the exposure to the antibody. 8. The method of claim 1 wherein the concentration of the amine containing solution comprising an amino acid is from about 10 mM to about 1M. 9. The method of claim 1 wherein the antibody has been subjected to a purification step prior to the exposure to the urea. 10. The method of claim 9 wherein the purification step is Protein A chromatography. 11. The method of claim 1 which reduces deamidation, aggregation and/or unfolding of the antibody. 12. A method of preparing a monoclonal antibody comprising treating a composition comprising the monoclonal antibody and one or more viral contaminants with urea to inactivate the viral contaminant(s), wherein said treatment is performed in the presence of an amine-containing solution comprising an amino acid as a cyanate scavenger. 13. A method of inactivating or reducing viral contamination in a composition comprising an anti-HER2 antibody and one or more viral contaminant(s) comprising treating the composition with urea, in the presence of an amine-containing solution comprising an amino acid as a cyanate scavenger. 14. The method of claim 13 wherein urea is added to the anti-HER2 antibody composition at a concentration from about 2M to about 4M. 15. The meted of claim 13 wherein the pH of the composition is from about 4 to about 6.5. 16. An isolated composition comprising an anti-HER2 antibody, and urea and an amino acid added to said antibody, wherein the concentration of said antibody in the composition is from about 1 mg/mL to about 10 mg/mL. 17. An isolated composition comprising a anti-HER2 antibody, and urea ad a amino acid added to said antibody, wherein the concentration of said urea in the composition is from about 2M to about 4M. 18. An isolated composition comprising an anti-HER2 antibody, and urea and an amino acid added to said antibody, wherein the concentration of the amino acid is from about 200 mM to about 400 mM. 19. A method of preparing a polypeptide comprising: (a) purifying the polypeptide by a first purification step; and (b) treating the polypeptide of step (a) with urea to inactivate viral contamination thereof, wherein said treatment is performed in to presence of a amine-containing solution comprising an amino acid as a cyanate scavenger. 20. The method of claim 19 wherein the amino acid is glycine. 21. The method of claim 19 wherein the polypeptide is an antibody and the purification step is Protein A Chromatography. 22. The method of claim 19 further comprising subjecting the polypeptide of step (b) to one or more additional purification step(s) which reduce the levels of urea and cyanate scavenger associated with the polypeptide.

Details for Patent 7,452,539

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2021-12-19
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2021-12-19
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2021-12-19