Multi-valent human immunodeficiency virus antigen binding molecules and uses thereof

Inventors

Keyt, Bruce Alan • Stinchcomb, Dan T. • Olsen, Ole A.

Assignees

IGM Biosciences Inc

Abstract

This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an 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 HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.

Core Innovation

The invention relates to multimeric binding molecules comprising multiple bivalent antibody binding units assembled with a modified J-chain. Each binding unit includes two antibody heavy chain constant regions or fragments thereof, each associated with an antigen binding domain, and at least one antigen binding domain specifically binds a human immunodeficiency virus (HIV) antigen expressed on the surface of HIV viral particles, on the surface of HIV-infected cells, or on a combination thereof.

In described embodiments, the multimeric binding molecule includes two or five bivalent binding units together with a modified J-chain that comprises a J-chain or functional fragment or variant and a heterologous polypeptide directly or indirectly fused to the J-chain or its variant or fragment. The described architectures include IgA dimer and IgM pentamer or hexamer assemblies that use antibody constant regions linked to HIV spike glycoprotein binding.

An isolated IgM antibody is also disclosed that includes a modified J-chain and five binding units assembled into a pentameric IgM that can specifically bind to the CD4 binding site of the HIV spike glycoprotein. In this pentameric IgM, the modified J-chain includes a J-chain or functional fragment or variant fused to an antigen binding scFv antibody fragment that binds CD3 directly or indirectly.

Claims Coverage

The document provides two independent claims. These claims define multimeric HIV-binding molecules and an isolated pentameric IgM antibody with modified J-chains fused to heterologous polypeptides, where HIV binding is directed to HIV antigens on viral particle surfaces and/or HIV-infected cell surfaces, and where certain embodiments specifically bind the CD4 binding site of the HIV spike glycoprotein and additionally bind CD3 via a fused scFv.

Across the independent claims, the inventive concept is centered on multimeric HIV-binding molecules, including pentameric IgM formats, that use a modified J-chain fused to a heterologous binding component, combined with antigen-binding domains that specifically bind HIV antigens on viral particle surfaces and/or HIV-infected cell surfaces, including binding to the CD4 binding site of the HIV spike glycoprotein.

Stated Advantages

Documented Applications