High affinity antibodies that neutralize Staphylococcus enterotoxin B
Inventors
Sass, Philip M. • Nicolaides, Nicholas C. • Grasso, Luigi • Berger, Marc • Sai, Tao
Assignees
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Publication Number
US-10364284-B2
Publication Date
2019-07-30
Expiration Date
Abstract
Provided herein are antibodies that specifically bind and neutralize Staphylococcus enterotoxin B. In addition, nucleic acids encoding such antibodies, and cells that express such antibodies are provided. Also provided are methods for treating diseases mediated by, and for neutralizing Staphylococcus enterotoxin B.
Core Innovation
The invention relates to high-affinity human monoclonal antibodies and antigen-binding fragments that specifically bind and neutralize Staphylococcus enterotoxin B (SEB). The antibodies comprise defined heavy chain CDR1, CDR2, and CDR3 amino acid sequences, together with defined light chain CDR1, CDR2, and CDR3 amino acid sequences, and binding to SEB is defined by a dissociation constant (K_D) of less than 3×10^-8 M.
The disclosed antibody variants are characterized by competition and epitope relationships, including antibody competition and epitope overlap. Binding kinetics and affinity are described using binding kinetics and competition measurements, including reported K_D values and related high-affinity behavior, and multiple antibody variants are identified, including 79G9, 100C9, 154G12, F10, E12, F6, and C5.
The document further describes nucleic acids encoding the antibodies and cells expressing the antibodies. The described rationale and evidence include antigen-specific binding panels and functional inhibition, including PBMC proliferation and cytokine inhibition assays, and in vivo evidence is described using mouse SEB challenge studies. Antibody-producing hybridoma cell lines are deposited.
Claims Coverage
The partial content identifies one independent claim covering a recombinant antibody or antigen-binding fragment defined by specific heavy-chain and light-chain CDR amino-acid sequences and a binding affinity threshold to Staphylococcus enterotoxin B via K_D. Dependent claims refine the antibody sequence identities and, for one dependent claim, a pharmaceutical composition.
Recombinant antibody with defined SEB-binding CDR sequences and high affinity (K_D<3×10^-8 M)
A recombinant antibody comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or an antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B with a dissociation constant (K_D) of less than 3×10^-8 M.
The claim coverage focuses on antibodies or antigen-binding fragments with specified heavy- and light-chain CDR sequence sets and an explicit K_D threshold for binding to SEB, with further refinements to alternative full heavy/light chain sequence identities and a pharmaceutical composition including a pharmaceutically acceptable carrier.
Stated Advantages
High-affinity binding to Staphylococcus enterotoxin B with a dissociation constant (K_D) of less than 3×10^-8 M.
Neutralization of SEB is described for the antibodies and antigen-binding fragments.
Documented Applications
Preventing and/or treating SEB-mediated disease, including rationale supported by in vitro inhibition and in vivo mouse SEB challenge studies.
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