US 11,753,475 B2
Bispecific-Fc molecules
Luis G. Borges, Redwood City, CA (US); Patrick A. Baeuerle, Gauting (DE); Wei Yan, Sammamish, WA (US); and Mark L. Michaels, Encino, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US)
Filed by AMGEN INC., Thousand Oaks, CA (US)
Filed on Feb. 1, 2018, as Appl. No. 15/885,998.
Application 15/885,998 is a continuation of application No. 14/210,178, filed on Mar. 13, 2014, abandoned.
Claims priority of provisional application 61/791,424, filed on Mar. 15, 2013.
Prior Publication US 2018/0230220 A1, Aug. 16, 2018
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); C07K 16/00 (2006.01); C07K 16/32 (2006.01); C07K 16/46 (2006.01); C07K 16/40 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2863 (2013.01) [C07K 16/00 (2013.01); C07K 16/28 (2013.01); C07K 16/2803 (2013.01); C07K 16/2809 (2013.01); C07K 16/32 (2013.01); C07K 16/40 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (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 2317/71 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2319/00 (2013.01)] 8 Claims
 
1. A bispecific-Fc molecule (Bi-Fc) monomer which mediates cytolysis of a cancer cell by a T cell, wherein the Bi-Fc comprises a polypeptide chain comprising an amino acid sequence having the following formula: V1-L1-V2-L2-V3-L3-V4-L4-Fc or Fc-L4-V1-L1-V2-L2-V3-L3-V4; wherein two of V1, V2, V3, and V4 are heavy chain variable (VH) regions and the other two are light chain variable (VL) regions; wherein one VH region and one VL region binds CD3 epsilon on a T cell and one VH region and one VL region binds HER2 on the cancer cell; wherein Fc is a human IgG Fc polypeptide chain; wherein L1, L2, L3, and L4 are linkers; wherein L4 can be present or absent; and wherein the Bi-Fc monomer comprises a single chain anti-HER2/CD3 epsilon antibody comprising the amino acid sequence of SEQ ID NO: 9.