Antibody immune cell inhibitor fusion proteins
AssigneeAlexion Pharmaceuticals, Inc.
InventorJulian Chandler
Life of this patent
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Abstract
The disclosure provides antibody immune cell inhibitor fusion proteins comprising four polypeptide chains that form two antigen binding sites and at least two immune cell receptor binding sites that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure also provides antibody immune cell inhibitor fusion proteins comprising two polypeptide chains that form one antigen binding site and at least one immune cell receptor binding site that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure further provides pharmaceutical compositions and kits that comprise such antibody immune cell inhibitor fusion proteins, and methods of treatment using such proteins.
Claims17
An antibody immune cell inhibitor fusion protein comprising four polypeptide chains that form two antigen binding sites and at least two immune cell receptor binding sites;
- wherein two polypeptide chains have a structure represented by the formula II1-VL-CL-II2, and two polypeptide chains have a structure represented by the formula II3-VH-CH1-Fc-II4;
- wherein:
- VL is an immunoglobulin light chain variable domain;
- VH is an immunoglobulin heavy chain variable domain;
- CL is an immunoglobulin light chain constant domain;
- CH1 is the immunoglobulin CH1 heavy chain constant domain;
- Fc is the immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains;
- and
- II1, II2, II3, and II4 are each independently an immune cell inhibitor domain of an immunoglobulin superfamily member or are absent;
- wherein at least one of II1, II2, II3, and II4 is an immune cell inhibitor domain of an immunoglobulin superfamily member;
- and
- wherein the antibody immune cell inhibitor fusion protein inhibits or diminishes activation of an immune effector cell only when bound to a target antigen at one or both of the antigen binding sites.
An antibody immune cell inhibitor fusion protein comprising four polypeptide chains that form two antigen binding sites and at least two immune cell receptor binding sites;
- wherein two polypeptide chains have a structure represented by the formula II1-L1-VL-CL-L2-II2, and two polypeptide chains have a structure represented by the formula II3-L3-VH-CH1-Fc-L4-II4;
- wherein:
- VL is an immunoglobulin light chain variable domain;
- VH is an immunoglobulin heavy chain variable domain;
- CL is an immunoglobulin light chain constant domain;
- CH1 is the immunoglobulin CH1 heavy chain constant domain;
- Fc is the immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains;
- L1, L2, L3 and L4 are each independently a linker domain or are absent;
- and
- II1, II2, II3, and II4 are each independently an immune cell inhibitor domain of an immunoglobulin superfamily member or are absent;
- wherein at least one of L1, L2, L3 and L4 is a linker domain and at least one of II1, II2, II3, and II4 is an immune cell inhibitor domain of an immunoglobulin superfamily member;
- and
- wherein the antibody immune cell inhibitor fusion protein inhibits or diminishes activation of an immune effector cell only when bound to a target antigen at one or both of the antigen binding sites.
An antibody immune cell inhibitor fusion protein comprising two polypeptide chains that form one antigen binding site and at least one immune cell receptor binding site;
- wherein one polypeptide chain has a structure represented by the formula II1-VL-CL-II2, and one polypeptide chain has a structure represented by the formula II3-VH-CH1-II4;
- wherein:
- VL is an immunoglobulin light chain variable domain;
- VH is an immunoglobulin heavy chain variable domain;
- CL is an immunoglobulin light chain constant domain;
- CH1 is the immunoglobulin CH1 heavy chain constant domain;
- and
- II1, II2, II3, and II4 are each independently an immune cell inhibitor domain of an immunoglobulin superfamily member or are absent;
- wherein at least one of II1, II2, II3, and II4 is an immune cell inhibitor domain of an immunoglobulin superfamily member;
- and
- wherein the antibody immune cell inhibitor fusion protein inhibits or diminishes activation of an immune effector cell only when bound to a target antigen at the antigen binding site.
An antibody immune cell inhibitor fusion protein comprising two polypeptide chains that form one antigen binding site and at least one immune cell receptor binding site;
- wherein one polypeptide chain has a structure represented by the formula II1-L1-VL-CL-L2-II2, and one polypeptide chain has a structure represented by the formula II3-L3-VH-CH1-L4-II4;
- wherein:
- VL is an immunoglobulin light chain variable domain;
- VH is an immunoglobulin heavy chain variable domain;
- CL is an immunoglobulin light chain constant domain;
- CH1 is the immunoglobulin CH1 heavy chain constant domain;
- L1, L2, L3 and L4 are each independently a linker domain or are absent;
- and
- II1, II2, II3, and II4 are each independently an immune cell inhibitor domain of an immunoglobulin superfamily member or are absent;
- wherein at least one of L1, L2, L3 and L4 is a linker domain and at least one of II1, II2, II3, and II4 is an immune cell inhibitor domain of an immunoglobulin superfamily member;
- and
- wherein the antibody immune cell inhibitor fusion protein inhibits or diminishes activation of an immune effector cell only when bound to a target antigen at the antigen binding site.
Dependencies are inferred from the claim text.