Arenavirus monoclonal antibodies and uses

Inventors

Branco, Luis M. • Garry, Robert F. • Robinson, James E. • SAPHIRE, Erica O. • HASTIE, Kathryn M. • Geisbert, Thomas W.

Assignees

Zalgen Labs LLC • Scripps Research Institute • Tulane University • The University of Texas System

Abstract

Disclosed herein are compositions comprising arenavirus monoclonal antibodies, as well as therapeutic, diagnostic, and preventative methods using the novel antibodies. Preventative methods include preparation of vaccines, as well as factors (e.g. small molecules, peptides) that inhibit Old World arenavirus infectivity, including LASV and LCMV. In some embodiments, the antibodies provide pan-arenavirus protection against a number of arenavirus types and strains. Diagnostic and therapeutic antibodies including neutralizing antibodies for the prevention and treatment of infection by LASV and other arenaviruses are also disclosed, as well as new tools and methods for the design, production, and use of arenavirus monoclonal antibodies, including expression in engineered bacterial- and mammalian-based systems.

Core Innovation

The invention relates to an antigen-binding composition comprising a neutralizing human monoclonal antibody or neutralizing antigen-binding antibody fragment specific to Lassa virus glycoprotein targets, including glycoprotein 1 (GP1), glycoprotein precursor (GPC), or full-length glycoprotein (GP). The compositions are defined by specified heavy chain variable region (VH) and light chain variable region (VL), each comprising complementarity determining regions associated with SEQ ID NOs and a light chain CDR2 sequence Gly Ala Ser.

In one embodiment, the neutralizing antibody or antibody fragment comprises a VH CDR1 of SEQ ID NO: 98, a VH CDR2 of SEQ ID NO: 99, a VH CDR3 of SEQ ID NO: 100, a VL CDR1 of SEQ ID NO: 135, a VL CDR2 of sequence Gly Ala Ser, and a VL CDR3 of SEQ ID NO: 136. In another embodiment, the neutralizing human monoclonal antibody or antibody fragment comprises a VH of SEQ ID NO: 44 and a VL of SEQ ID NO: 60.

The documented content further describes use of LASV/LCMV antibodies in diagnostics via immunoassay formats such as ELISA and detectable labelling groups, as well as DNA-based and antibody-based vaccines with adjuvants and administration routes. The document also provides pharmaceutical compositions comprising pharmaceutically acceptable carriers, and kit packaging and labeling with container types including vials, bottles, jars, and flexible packaging containers.

Claims Coverage

The partial content provides two independent claims, each defining a neutralizing human monoclonal antibody or neutralizing antigen-binding antibody fragment specific to LASV glycoprotein targets with specified variable-region CDR or variable-region SEQ ID assignments.

Overall, the claim coverage is centered on neutralizing human monoclonal antibodies or neutralizing antigen-binding antibody fragments that bind LASV glycoproteins (GP1, GPC, or full-length GP), with specificity determined by the listed VH/VL and CDR/SEQ ID assignments.

Stated Advantages

Documented Applications