Multi-valent hepatitis B virus antigen binding molecules and uses thereof
AssigneeIGM Biosciences, Inc.
InventorsStephen F. Carroll, Ramesh Baliga, Dean Ng, Bruce Keyt
Life of this patent
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Abstract
This disclosure provides a multimeric hepatitis B virus (HBV) protein binding molecule, e.g., a dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HBV antigen binding domain. The disclosure also provides compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.
Claims18
A multimeric antibody comprising at least two bivalent binding units;
- wherein each binding unit comprises two IgM or IgA antibody heavy chain constant regions, each associated with an antigen binding domain;
- wherein the antigen binding domains specifically bind to a hepatitis B virus (HBV) antigen expressed on the surface of infectious viral particles, on the surface of HBV infected cells, or a combination thereof, and
- wherein the binding molecule is more potent than a reference IgG antibody comprising the antigen binding domain that specifically binds to the HBV antigen.
An isolated IgM antibody comprising a modified J-chain and five binding units, each comprising two heavy chains and two light chains, wherein each heavy chain comprises a human Mu constant region, and the heavy chain variable region amino acid sequence SEQ ID NO:
- 62, and wherein each light chain comprises a human kappa constant region and the light chain variable region amino acid sequence SEQ ID NO:
- 6;
- wherein the antibody can assemble into a pentameric IgM antibody that can specifically bind to the pre-S1 region of HBV surface antigen, and wherein the modified J-chain comprises the amino acid sequence SEQ ID NO:
- 68 (V15J) or SEQ ID NO:
- 71 (J15V).
Dependencies are inferred from the claim text.