Claims for Patent: 8,725,421

Summary for Patent: 8,725,421

Title:	In vitro estimation of in vivo half-life binding proteins
Abstract:	The present invention discloses methods used to estimate the in vivo half-life of a binding protein of interest. The disclosed methods involve (a) determining for a binding protein of interest and for each of at least two different reference binding proteins an in vitro half-life using an in vitro protease reaction assay, wherein said reference binding proteins have known different in vivo half-lives, (b) determining the correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of each of the reference binding proteins, and (c) estimating from said correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of the reference binding proteins the in vivo half-life of the binding protein of interest that correlates with the in vitro proteolytic half-life of the binding protein of interest.
Inventor(s):	Talanian; Robert V. (Harvard, MA)
Assignee:	Abbvie Inc. (North Chicago, IL)
Application Number:	12/386,332
Patent Claims:	1. A method for estimating the in vivo human half-life of a monoclonal antibody of interest comprising: (a) determining an in vitro proteolytic half-life in an in vitro protease reaction assay for each of at least four different reference monoclonal antibodies and for said antibody of interest, wherein said reference antibodies have different known in vivo human half-lives and wherein said in vitro protease reaction assays are performed under identical conditions, (b) determining a correlation between the known in vivo human half-lives and the in vitro proteolytic half-lives of the reference antibodies, (c) estimating from the correlation in (b) between the known in vivo human half-lives and the in vitro proteolytic half-lives of the reference antibodies the in vivo human half-life of the antibody of interest that correlates with the in vitro proteolytic half-life of the antibody of interest. 2. The method according to claim 1, wherein said correlation is a linear correlation. 3. The method of claim 1, wherein said protease is selected from the group consisting of thermolysin, elastase, pepsin, trypsin, chymotrypsin, papain, and combinations thereof. 4. The method according to claim 3, wherein said protease is thermolysin. 5. The method according to claim 2, wherein said correlation is linear and represented by the formula: y=mx+b wherein "y" is the in vivo human half-life, "m" is the observed slope of the linear correlation between the in vivo human half-life and the in vitro protease-mediated proteolytic half-life, "x" is the in vitro half-life as determined in a proteolytic reaction assay, and the constant "b" is the y-intercept corresponding to an in vitro proteolytic half-life of zero (x =0) along the linear correlation. 6. The method according to claim 1, wherein said at least four reference antibodies are selected from the group consisting of infliximab, trastuzumab, rituximab, palivizumab, daclizumab, and basiliximab. 7. The method of claim 1, wherein said correlation is linear and represented by the formula: y=0.27x+2.79 wherein "y" is the in vivo human half-life in days, "0.27" is the slope of the linear correlation between in vivo human half-life and in vitro thermolysin proteolytic half-life, "x" is in vitro half-life in an in vitro thermolysin proteolysis assay, and the constant "2.79" is the in vivo human half-life corresponding to an in vitro proteolytic half-life of zero (0 days) along the linear correlation.

Details for Patent 8,725,421

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2028-04-18
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2028-04-18
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2028-04-18
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	05/12/1998		2028-04-18
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	01/02/2003		2028-04-18
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	For Injection	103770	06/19/1998		2028-04-18
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	Injection	103770	07/23/2004		2028-04-18