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US 11,891,454 B2Granted
Production of T cell retargeting hetero-dimeric immunoglobulins
AssigneeIchnos Sciences SA
InventorsStanislas Blein, Romain Ollier, Darko Skegro, Samuel Hou
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Abstract
The present invention describes hetero-dimeric immunoglobulins or fragments thereof which bind to CD3 and a disease associated antigen. These hetero-dimeric immunoglobulins have been engineered to promote hetero-dimer formation during expression and can be purified to a high degree using a Protein A differential purification technique.
Claims15
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.
4 more elements
A hetero-dimeric immunoglobulin or fragment thereof that binds to:
- i) the CD3 protein complex and CD38, wherein the first polypeptide has an amino acid sequence of SEQ ID NO:
- 169 and is assembled with a cognate light chain of amino acid sequence of SEQ ID NO:
- 119 and binds CD38, and wherein the second polypeptide has an amino acid sequence of SEQ ID NO:
- 162 and binds CD3 epsilon;
- ii) the CD3 protein complex and CD38, wherein the first polypeptide has an amino acid sequence of SEQ ID NO:
- 170 and is assembled with a cognate light chain of amino acid sequence of SEQ ID NO:
- 138 and binds CD38, and wherein the second polypeptide has an amino acid sequence of SEQ ID NO:
- 171 and binds CD3 epsilon;
- iii) the CD3 protein complex and CD38, wherein the first polypeptide has an amino acid sequence of SEQ ID NO:
- 176 and is assembled with a cognate light chain of amino acid sequence of SEQ ID NO:
- 119 and binds CD38, and wherein the second polypeptide has an amino acid sequence of SEQ ID NO:
- 177 and binds CD3 epsilon;
- or
- iv) the CD3 protein complex and CD38, wherein the first polypeptide has an amino acid sequence of SEQ ID NO:
- 178 and is assembled with a cognate light chain of amino acid sequence of SEQ ID NO:
- 128 and binds CD38, and wherein the second polypeptide has an amino acid sequence of SEQ ID NO:
- 179 and binds CD3 epsilon.
14 more elements
Dependencies are inferred from the claim text.