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-9868780-B2
Publication Date
2018-01-16
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 recombinant human monoclonal anti–Staphylococcus enterotoxin B (SEB) antibodies and antigen-binding fragments. The antibodies comprise specified heavy chain CDR1, CDR2, and CDR3 amino acid sequences, and specified light chain CDR1, CDR2, and CDR3 amino acid sequences. The antibody or antigen-binding fragment binds to SEB with a dissociation constant (K_D) of less than 3×10^-8 M.
The disclosed embodiments provide antibody variants described as substantially-identical variants (≥90% identity) and include associated heavy chain and light chain variable-domain sequences. The disclosure also specifies multiple SEQ ID NOs for CDRs and variable-domain components, together with polynucleotides, vectors, and host cells associated with the recombinant antibodies.
The invention further includes characterization of SEB specificity and binding relationships and describes treatment and prevention of SEB-mediated disease by administration of anti-SEB antibodies. The document describes assessment of SEB specificity without cross-reactivity, binding kinetics and competition/epitope binding relationships, and in vivo protection in a mouse SEB/LPS challenge context.
Claims Coverage
Independent claim clm-00001 covers a recombinant antibody (or antigen-binding fragment) defined by specific heavy-chain and light-chain CDR amino-acid sequences that bind SEB with K_D < 3×10^-8 M. Dependent claims clm-00002 to clm-00004 narrow the antibody to particular full variable-domain or full chain amino-acid sequences and add a pharmaceutical composition limitation in one dependent claim.
CDR-defined recombinant antibody binding SEB with K_D < 3×10^-8 M
A recombinant antibody comprising a heavy chain CDR1 with the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 with the amino acid sequence of SEQ ID NO: 93, a heavy chain CDR3 with the amino acid sequence of SEQ ID NO: 94, and a light chain CDR1 with the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 with the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 with the amino acid sequence of SEQ ID NO: 82 (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.
Particular heavy and light variable-domain sequences
The antibody or antigen-binding fragment of the K_D-defined CDR set wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 160 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 158.
Particular heavy and light chain amino-acid sequences
The antibody or antigen-binding fragment of the K_D-defined CDR set wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 251 and the light chain comprises the amino acid sequence of SEQ ID NO: 249.
Pharmaceutical composition with pharmaceutically acceptable carrier
A composition comprising the antibody or antigen-binding fragment of the K_D-defined CDR set and a pharmaceutically acceptable carrier.
Overall, the claim set protects SEB-binding recombinant antibodies defined by specific heavy-chain and light-chain CDR amino-acid sequences achieving K_D < 3×10^-8 M, with optional narrowing to specified variable-domain or full chain sequences and a further limitation to a pharmaceutical composition containing a pharmaceutically acceptable carrier.
Stated Advantages
High-affinity binding to Staphylococcus enterotoxin B, with K_D less than 3×10^-8 M.
SEB specificity without cross-reactivity (as described in characterization/assays in the document).
In vivo protection in a mouse SEB/LPS challenge context (as described in the document).
Documented Applications
Treatment and prevention of SEB-mediated disease by administration of anti-SEB antibodies (as described in the document).
Protection in a mouse SEB/LPS challenge study context (as described in the document).
Characterization of SEB specificity and binding/competition/epitope binding relationships (as described in the document).
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