Methods of treating HIV-1 infection utilizing broadly neutralizing human immunodeficiency virus type 1 (HIV-1) GP120-specific monoclonal antibodies

Inventors

Chan-Hui, Po-Ying • Doores, Katherine • Huber, Michael • Kaminsky, Stephen • Frey, Steven • Olsen, Ole • Mitcham, Jennifer • Moyle, Matthew • Phogat, Sanjay K. • Burton, Dennis R. • Walker, Laura Marjorie • Poignard, Pascal Raymond Georges • Koff, Wayne • Simek-Lemos, Melissa Danielle De Jean De St. Marcel

Assignees

Scripps Research Institute • International AIDS Vaccine Initiative Inc • Theraclone Sciences Inc

Abstract

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

Core Innovation

The invention relates to passive immunization or treating an HIV-1 infection by administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof. The antibody is defined by specified complementarity determining regions in both the light chain variable region and the heavy chain variable region, with amino acid sequences identified by SEQ ID NOS.

For the light chain variable region, the invention requires three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 150, 151, and 152. For the heavy chain variable region, the disclosed sets include SEQ ID NOS: 143, 144, and 145 in one set, and SEQ ID NOS: 90, 265, and 143 in another set.

The provided description includes detailed amino acid and nucleotide sequence information for multiple PGT-family anti-HIV-1 antibodies, including Kabat and Chothia CDR definitions and SEQ ID NO mappings for polynucleotides and polypeptides. The disclosed sequence information supports defined non-naturally occurring PGT-121 monoclonal antibodies and antigen binding portions used in the stated passive immunization or HIV-1 treatment methods.

Claims Coverage

The provided independent claim set includes two independent claims. Across these claims, the inventive features focus on administering a non-naturally occurring PGT-121 monoclonal antibody or antigen-binding portion defined by specific light-chain and heavy-chain variable region CDR amino-acid sequences for passive immunization or treating an HIV-1 infection.

Overall, the claim coverage is anchored in methods of passive immunization or treating an HIV-1 infection by administering a therapeutically effective composition containing non-naturally occurring PGT-121 monoclonal antibodies whose light- and heavy-chain complementarity determining regions are constrained to specific SEQ ID-defined amino acid sequences.

Stated Advantages

Documented Applications