US 10,889,653 B2
Heterodimeric antibodies that bind CD3 and tumor antigens
Matthew J. Bernett, Monrovia, CA (US); Gregory Moore, Azusa, CA (US); John Desjarlais, Pasadena, CA (US); Seung Chu, Cypress, CA (US); Rumana Rashid, Temple City, CA (US); Umesh Muchhal, Monrovia, CA (US); and Sung-Hyung Lee, San Gabriel, CA (US)
Assigned to Xencor, Inc., Monrovia, CA (US)
Filed by Xencor, Inc., Monrovia, CA (US)
Filed on Nov. 25, 2015, as Appl. No. 14/952,714.
Claims priority of provisional application 62/085,117, filed on Nov. 26, 2014.
Claims priority of provisional application 62/084,908, filed on Nov. 26, 2014.
Claims priority of provisional application 62/085,027, filed on Nov. 26, 2014.
Claims priority of provisional application 62/085,106, filed on Nov. 26, 2014.
Claims priority of provisional application 62/159,111, filed on May 8, 2015.
Claims priority of provisional application 62/251,005, filed on Nov. 4, 2015.
Claims priority of provisional application 62/250,971, filed on Nov. 4, 2015.
Prior Publication US 2016/0229924 A1, Aug. 11, 2016
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); C07K 16/46 (2006.01); C07K 16/30 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/468 (2013.01) [C07K 16/2809 (2013.01); C07K 16/2818 (2013.01); C07K 16/2896 (2013.01); C07K 16/30 (2013.01); C07K 16/3061 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/515 (2013.01); C07K 2317/52 (2013.01); C07K 2317/522 (2013.01); C07K 2317/526 (2013.01); C07K 2317/528 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/60 (2013.01); C07K 2317/622 (2013.01); C07K 2317/64 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 4 Claims
 
1. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first heavy chain comprising:
1) a first variable heavy domain;
2) a first constant heavy chain comprising a first Fc domain;
3) a scFv comprising a scFv variable light domain, an scFv linker and a scFv variable heavy domain; wherein said scFv is covalently attached to the C-terminus of said Fc domain using a domain linker;
b) a second monomer comprising a second heavy chain comprising a second variable heavy domain and a second constant heavy chain comprising a second Fc domain; and
c) a common light chain comprising a variable light domain and a constant light domain;
wherein said first and said second Fc domains have a set of amino acid substitutions selected from the group consisting of S364K/E357Q:L368D/K370S; L368D/K370S:S364K; L368E/K370S:S364K; T411E/K360E/Q362E:D401K; L368D/K370S:S364K/E357L and K370S:S364K/E357Q,
wherein said first variable heavy domain and said variable light domain bind a first target tumor antigen (TTA), said second variable heavy domain and said variable light domain bind said first TTA, and said scFv binds human CD3, and
wherein said heterodimeric antibody is a trivalent antibody.