US 11,725,065 B2
Assembly of bispecific antibodies
Glen Giese, Belmont, CA (US); Amy Lim, Palo Alto, CA (US); Josefine Persson, Half Moon Bay, CA (US); Justin Scheer, Half Moon Bay, CA (US); and Ambrose Williams, Redwood City, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Mar. 16, 2020, as Appl. No. 16/820,660.
Application 15/789,775 is a division of application No. 14/251,428, granted, now 9,862,778, previously published as PCT/US2012/059810, filed on Oct. 11, 2012.
Application 16/820,660 is a continuation of application No. 15/789,775, filed on Oct. 20, 2017, granted, now 10,626,189.
Claims priority of provisional application 61/545,863, filed on Oct. 11, 2011.
Claims priority of provisional application 61/546,503, filed on Oct. 12, 2011.
Claims priority of provisional application 61/560,704, filed on Nov. 16, 2011.
Claims priority of provisional application 61/676,837, filed on Jul. 27, 2012.
Prior Publication US 2020/0317820 A1, Oct. 8, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/46 (2006.01)
CPC C07K 16/468 (2013.01) [C07K 2317/31 (2013.01); C07K 2317/522 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/53 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01)] 20 Claims
 
1. A method of producing a heteromultimeric protein, said method comprising:
a. obtaining a first half-antibody, wherein the first half-antibody comprises a heterodimerization domain;
b. obtaining a second half-antibody, wherein the second half-antibody comprises a heterodimerization domain;
c. adjusting pH of each half-antibody to between pH 4 and 9;
d. mixing the first and second half-antibodies to obtain an assembly mixture;
e. adding a 50-400x molar excess of glutathione (GSH) to the assembly mixture; and
f. incubating the assembly mixture to form a heteromultimeric protein comprising the first half-antibody and the second half-antibody.