Multivalent antigen-binding proteins
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsGeorge D. YANCOPOULOS, Nicholas J. PAPADOPOULOS, Neil STAHL, Samuel DAVIS, Andrew J. MURPHY, Lynn MACDONALD
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Abstract
Multivalent antigen-binding proteins comprising two or three or four or more immunoglobulin heavy chain variable domain binding domains are provided, as are methods for making them, nucleic acid constructs, and cell lines for making them. Proteins comprising two or three or four or more different heavy chain variable domains that lack an immunoglobulin variable domain are provided. Proteins comprising two or three or four or more different heavy chain variable domains that associate with the same immunoglobulin light chain variable domain are also provided.
Claims13
A multivalent antigen-binding protein comprising no more than three immunoglobulin heavy chain variable domains, wherein no more than one of the no more than three immunoglobulin variable domains specifically binds an effector cell, and at least one of the three immunoglobulin variable domains binds a target on a cell that is not the same as the effector cell.
A multivalent antigen-binding protein comprising:
- a first polypeptide that comprises an immunoglobulin single heavy chain variable domain (VH1sd) fused directly or through a linker to a second immunoglobulin heavy chain variable domain (VH2), fused directly or through a linker to a CH1 region, which is fused directly or through a linker or hinge to a multimerizing component M1;
- a second polypeptide comprising a third immunoglobulin single heavy chain variable domain (VH3sd) fused directly or through a linker to a fourth immunoglobulin heavy chain variable domain (VH4) that is fused directly or through a linker to a CH1 region, which is fused directly or through a linker to a multimerizing component M2;
- and,
- a third polypeptide comprising a light chain variable domain fused directly or through a linker to a light chain constant region.
A multivalent antigen-binding protein comprising:
- a first polypeptide comprising a first immunoglobulin heavy chain single variable domain (VL1sd) fused directly or through a linker to a light chain variable domain (VL2), which is fused directly or through a linker to a light chain constant region;
- a second polypeptide comprising (or consisting essentially of) a second heavy chain variable domain (VH2) fused directly or through a linker to a CH1 region, which is fused directly or through a linker to a first multimerizing component M1;
- and a third polypeptide comprising a fourth heavy chain variable domain (VH4) fused directly or through a linker to a CH1 region that is fused directly or through a linker to a second multimerizing component M2.
A multivalent antigen-binding protein comprising:
- a first polypeptide that comprises a first immunoglobulin heavy chain variable domain fused directly or through a linker to a second immunoglobulin heavy chain variable domain, which is fused directly or through a linker to a CH1 region, which is attached directly or through a linker to a first multimerizing component;
- a second polypeptide comprising a heavy chain single immunoglobulin variable domain (VH3sd) fused directly or through a linker to a second multimerizing component;
- and, a third polypeptide comprising a first light chain variable domain fused directly or through a linker to a second immunoglobulin light chain variable domain (VL2), which is fused directly or through a linker to a light chain constant domain.
A multivalent antigen-binding protein comprising:
- a first polypeptide that comprises a first single immunoglobulin heavy chain variable domain (VH1sd), a second heavy chain single immunoglobulin variable domain (VH2sd), and a first multimerizing component (M1), wherein the first polypeptide lacks an immunoglobulin CH1 domain;
- a second polypeptide that comprises a third single immunoglobulin heavy chain variable domain (VH3sd), a fourth immunoglobulin heavy chain variable domain (VH4sd) and a second multimerizing component (M2), wherein the second polypeptide lacks an immunoglobulin CH1 domain;
- wherein the first polypeptide associates with the second polypeptide by multimerizing components M1 and M2.
A multivalent antigen-binding protein comprising a first multimerizing component M1 fused with two single light chain immunoglobulin variable domains, and a second multimerizing component M2 fused with one or two single light chain immunoglobulin variable domains.
Dependencies are inferred from the claim text.