Broadly neutralizing antibodies against HIV
Inventors
SAJADI, Mohammad • Lewis, George K. • DEVICO, Anthony • Kim, Dongkyoon • Cavet, Guy
Assignees
University of Maryland Baltimore • US Department of Veterans Affairs
Publication Number
US-12331105-B2
Publication Date
2025-06-17
Expiration Date
2038-06-22
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Abstract
The present invention provides broadly neutralizing antibodies against HIV, compositions comprising the same and methods of use thereof.
Core Innovation
The invention provides non-naturally occurring, broadly neutralizing antibodies against HIV, as well as compositions comprising these antibodies and methods of their use. The antibodies are capable of neutralizing a wide range of HIV viruses, including at least 95% or even 100% of the HIV viral strains listed in detailed panels, with high potency measured by low IC50 values. The antibodies are defined by specific heavy and light chain variable region sequences, including their complementarity-determining regions (CDRs), and can be further identified by unique combinations of sequence motifs and structural features as described in the claims and detailed description.
The problem addressed by the invention is the insufficient breadth and potency of previously isolated anti-HIV antibodies, which have not been able to neutralize all circulating strains, particularly those resistant to other broadly neutralizing antibodies. Many existing methods did not yield detailed understanding or isolation of the most effective neutralizing antibody species from circulation, and there is a continuing need to develop new therapies for treatment and prevention of HIV infection in patients.
This invention addresses the limitations by isolating and characterizing highly potent, broadly neutralizing anti-HIV antibodies from human sources with exceptional neutralization breadth. The invention includes antibodies with unique structural features such as the ability to bypass the CD4-binding site Phe43 cavity while engaging highly conserved regions of the gp120 inner domain – a feature demonstrated by structural and functional assays. The antibodies are produced and characterized with defined sequence motifs and binding properties, providing tools for HIV treatment, prevention, and research applications.
Claims Coverage
The patent contains one independent claim comprising a multi-part list of main inventive features for non-naturally occurring anti-HIV antibodies defined by specific CDR sequences and chain compositions.
Non-naturally occurring anti-HIV antibodies defined by specific CDR sequences and variable regions
The inventive feature covers anti-HIV antibodies, each defined by specific heavy chain and light chain variable region CDR sequences. For example, a claim describes an antibody with a heavy chain variable region where CDR H1 comprises GYKFPDYI (SEQ ID NO:405), CDR H2 comprises INPMGGQV (SEQ ID NO:406), and CDR H3 comprises VRDRSNGSGRRFESSN (SEQ ID NO:407); and a light chain variable region where CDR L1 comprises HNL, CDR L2 comprises DFN, and CDR L3 comprises WAYEA (SEQ ID NO:408). Each antibody variant is further limited by its specific CDR combinations and is expressly not an antibody consisting of the corresponding full-length amino acid sequences referenced in the claim. Additional variants are described by other precise CDR sequence pairings in both heavy and light chains, with the structure of the claim repeating this format for each recited antibody pair.
In summary, the claims provide broad coverage for non-naturally occurring anti-HIV antibodies strictly defined by specified heavy and light chain CDR motifs and variable region characteristics, distinguishing them from naturally occurring or previously reported full-sequence antibodies.
Stated Advantages
The antibodies are capable of neutralizing all or nearly all HIV viral strains in an extensive multi-clade panel with high potency, often neutralizing viruses resistant to other broadly neutralizing antibodies.
The antibodies are defined by specific molecular features allowing them to target highly conserved regions of the HIV gp120 inner domain and bypass resistance mechanisms associated with CD4-binding site variants.
The invention provides antibody structures and sequences that can be used to inform and improve HIV treatment, prevention, and research strategies by allowing for precise targeting and broad neutralization of diverse HIV strains.
Documented Applications
Use of these antibodies for treatment of HIV infection in subjects.
Use in pharmaceutical compositions comprising the anti-HIV antibodies.
Methods for preventing HIV infection in patients through administration of the antibodies.
Methods for functionally curing HIV infection by administering effective amounts of the composition.
Use of the antibodies in research for HIV detection, antigen binding studies, and selection or purification of HIV proteins or trimers.
Use of the antibodies for passive immunotherapy, gene therapy delivery (via nucleic acid constructs or viral vectors), and possible incorporation into engineered immune cells.
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