US 12,331,132 B2
Multispecific polypeptide constructs having constrained CD3 binding and related methods and uses
Brendan P. Eckelman, La Jolla, CA (US); Michael D. Kaplan, La Jolla, CA (US); Katelyn M. Willis, La Jolla, CA (US); and John C. Timmer, La Jolla, CA (US)
Assigned to Inhibrx Biosciences, Inc., La Jolla, CA (US)
Filed by Inhibrx Biosciences, Inc., La Jolla, CA (US)
Filed on Jun. 6, 2023, as Appl. No. 18/206,354.
Application 18/206,354 is a continuation of application No. 16/380,963, filed on Apr. 10, 2019, abandoned.
Claims priority of provisional application 62/656,331, filed on Apr. 11, 2018.
Prior Publication US 2023/0295336 A1, Sep. 21, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/30 (2006.01); A61P 35/00 (2006.01); C07K 1/14 (2006.01)
CPC C07K 16/30 (2013.01) [A61P 35/00 (2018.01); C07K 1/14 (2013.01); C07K 2317/31 (2013.01); C07K 2317/522 (2013.01); C07K 2317/55 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2317/624 (2013.01); C07K 2317/64 (2013.01); C07K 2317/66 (2013.01); C07K 2317/732 (2013.01); C07K 2317/734 (2013.01); C07K 2317/75 (2013.01); C07K 2317/92 (2013.01)] 21 Claims
 
1. A multispecific polypeptide construct, the multispecific polypeptide construct comprising a first component comprising an immunoglobulin Fc region and a second component comprising a CD3-binding region, wherein:
the CD3 binding region is an anti-CD3 disulphide-stabilized Fv antibody fragment (dsFv) comprising a variable heavy chain region (VH) and a variable light chain region (VL);
the Fc region is a heterodimeric Fc comprising a first Fc polypeptide and a second Fc polypeptide and the VH and VL of the anti-CD3 antibody or antigen binding fragment are linked to opposite polypeptides of the heterodimeric Fc;
the first and second components are coupled by a non-cleavable linker, wherein the Fc region is linked to the N-terminus of the CD3-binding region;
the first component comprises at least one antigen binding domain that bind a tumor associated antigen (TAA), wherein the at least one antigen binding domain is linked to the N-terminus of the Fc region and wherein the at least one antigen binding domain is an sdAb.