US 11,891,454 B2
Production of T cell retargeting hetero-dimeric immunoglobulins
Stanislas Blein, La Chaux-de-Fonds (CH); Romain Ollier, La Chaux-de-Fonds (CH); Darko Skegro, La Chaux-de-Fonds (CH); and Samuel Hou, La Chaux-de-Fonds (CH)
Assigned to Ichnos Sciences SA, La Chaux-de-Fonds (CH)
Filed by Ichnos Sciences SA, La Chaux-de-Fonds (CH)
Filed on Jul. 17, 2020, as Appl. No. 16/931,506.
Application 16/931,506 is a continuation of application No. 15/984,822, filed on May 21, 2018.
Application 15/984,822 is a continuation of application No. 15/190,268, filed on Jun. 23, 2016, abandoned.
Application 15/190,268 is a continuation of application No. 14/532,923, filed on Nov. 4, 2014, granted, now 9,493,563, issued on Nov. 15, 2016.
Claims priority of application No. 13191386 (EP), filed on Nov. 4, 2013.
Prior Publication US 2021/0171661 A1, Jun. 10, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/46 (2006.01); C07K 16/28 (2006.01); C07K 16/32 (2006.01); C07K 16/42 (2006.01)
CPC C07K 16/468 (2013.01) [C07K 16/2803 (2013.01); C07K 16/2809 (2013.01); C07K 16/2863 (2013.01); C07K 16/2878 (2013.01); C07K 16/2887 (2013.01); C07K 16/2896 (2013.01); C07K 16/32 (2013.01); C07K 16/4291 (2013.01); C07K 2317/14 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/52 (2013.01); C07K 2317/526 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/622 (2013.01); C07K 2317/71 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 15 Claims
 
1. A hetero-dimeric immunoglobulin or fragment thereof, comprising:
(a) a first polypeptide that binds to Protein A comprising an epitope binding region that binds a first epitope and an immunoglobulin constant region; and
(b) a second polypeptide comprising a VH3 based epitope binding region that binds a second epitope and an immunoglobulin constant region;
wherein the VH3 based epitope binding region of the second polypeptide has a modified VH3 domain with reduced binding to Protein A compared to an unmodified VH3 domain;
wherein the first and second polypeptides comprise an engineered immunoglobulin constant region with a modified CH3 domain having a protein-protein interface, wherein the protein-protein interface of the first polypeptide comprises an amino acid substitution at a position selected from the group consisting of: 3, 5, 7, 20, 22, 26, 27, 79, 81, 84, 84.2, 85.1, 86, 88 and 90, IMGT numbering, and wherein the protein-protein interface of the second polypeptide comprises an amino acid substitution at a position selected from the group consisting of 3, 5, 7, 20, 22, 26, 27, 79, 81, 84, 84.2, 84.4, 85.1, 86, 88 and 90, IMGT numbering;
wherein the epitope binding region of the first polypeptide binds the CD3 protein complex and the epitope binding region of the second polypeptide binds CD38 or wherein the epitope binding region of the first polypeptide binds CD38 and the epitope binding region of the second polypeptide binds the CD3 protein complex.