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US 10,519,242 B2Granted
Targeting regulatory T cells with heterodimeric proteins
AssigneeXencor, Inc.
InventorsSeung Chu, Matthew Bernett, Dilki Wickramarachchi, John Desjarlais
Life of this patent
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Abstract
The present invention provides methods and compositions comprising a heterodimeric antibody comprising a first monomer comprising a first variant heavy chain constant region and an anti-CD4 binding moiety. The heterodimeric antibody also comprises a second monomer comprising: a second variant heavy chain constant region and an anti-CD25 binding moiety. In some cases, the pIs of the first and second variant heavy chain constant regions are at least 0.5 logs apart.
Claims17
A composition comprising a heterodimeric antibody comprising:
- a) a first monomer comprising:
- i) a first variant Fc domain;
- ii) an anti-CD4 binding moiety;
- and
- b) a second monomer comprising:
- i) a second variant Fc domain;
- ii) an anti-CD25 binding moiety, wherein one of said first variant Fc domain and second variant Fc domain comprises amino acid substitutions L368E/K370S and the other of said first variant Fc domain and second variant Fc domain comprises amino acid substitution S364K, wherein said numbering is according to the EU index as in Kabat.
4 more elements
A composition comprising a heterodimeric antibody comprising:
- a) a first monomer comprising:
- i) a first variant Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds CD4 comprising a first variable heavy chain, a first variable light chain and a scFv linker, wherein said an scFv linker covalently attaches said first variable heavy chain and said variable light chain;
- and
- b) a second monomer comprising a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain and CH2-CH3 is a second variant Fc domain;
- and
- c) a light chain comprising a second variable light chain, wherein said second variable heavy chain and second variable light chain form a CD25 binding moiety;
- and
- wherein one of said first variant Fc domain and second variant Fc domain comprises amino acid substitutions L368E/K370S and the other of said first variant Fc domain and second variant Fc domain comprises amino acid substitution S364K, wherein said numbering is according to the EU index as in Kabat.
7 more elements
A composition comprising a heterodimeric antibody comprising:
- a) a first monomer comprising:
- i) a first variant Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds CD25 comprising a first variable heavy chain, a first variable light chain and a scFv linker, wherein said an scFv linker covalently attaches said first variable heavy chain and said variable light chain;
- and
- b) a second monomer comprising a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain and CH2-CH3 is a second variant Fc domain;
- and
- c) a light chain comprising a second variable light chain, wherein said second variable heavy chain and second variable light chain form a CD4 binding moiety;
- and
- wherein one of said first variant Fc domain and second variant Fc domain comprises amino acid substitutions L368E/K370S and the other of said first variant Fc domain and second variant Fc domain comprises amino acid substitution S364K, wherein said numbering is according to the EU index as in Kabat.
7 more elements
A composition comprising a heterodimeric antibody comprising:
- a) a first monomer comprising a first VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a first variable heavy chain and CH2-CH3 is a first variant Fc domain;
- b) a second monomer comprising a second VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain and CH2-CH3 is a second variant Fc domain;
- c) a first light chain comprising a first variable light chain;
- and
- d) a second light chain comprising a second variable light chain,
- wherein said first variable heavy chain and said first variable light chain form an anti-CD4 binding moiety,
- wherein said second variable heavy chain and said second variable light chain form an anti-CD25 binding moiety, and
- wherein one of said first variant Fc domain and second variant Fc domain comprises amino acid substitutions L368E/K370S and the other of said first variant Fc domain and second variant Fc domain comprises amino acid substitution S364K, wherein said numbering is according to the EU index as in Kabat.
5 more elements
A composition comprising a heterodimeric antibody comprising:
- a) a first monomer comprising:
- i) a first variant Fc domain;
- ii) an anti-CD4 binding moiety;
- and
- b) a second monomer comprising:
- i) a second variant Fc domain;
- ii) an anti-CD25 binding moiety;
- wherein the pIs of said first and second variant heavy chain constant regions are at least 0.5 logs apart, wherein one of said first variant Fc domain and second variant Fc domain comprises amino acid substitutions L368E/K370S and the other of said first variant Fc domain and second variant Fc domain comprises amino acid substitution S364K, wherein said numbering is according to the EU index as in Kabat.
5 more elements
Dependencies are inferred from the claim text.