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-8895704-B2
Publication Date
2014-11-25
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 isolated human monoclonal antibodies and antigen-binding fragments that bind and neutralize Staphylococcus enterotoxin B (SEB). The antibodies comprise defined heavy chain and light chain CDRs, including a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148, together with a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140. The binding is specified by a dissociation constant (K_D) that is less than 3×10^-8 M.
The disclosure further supports alternative heavy chain variable-domain and light chain variable-domain sequence assignments using additional defined SEQ ID NOs for the variable domains. It also specifies nucleic acids, vectors, and host cells that encode or express the antibodies or antigen-binding fragments, including cells that produce recombinant antibody binding to SEB.
The invention additionally provides pharmaceutical composition context in which the antibody or antigen-binding fragment is formulated with a pharmaceutically acceptable carrier. It frames use in SEB-neutralizing therapeutic or preventive methods, and it characterizes antibody effects using in vitro/in vivo-related context, including PBMC proliferation and cytokine inhibition, with discussion of IFN-γ and TNF-α inhibition and antibody competition/epitope overlap relationships.
Claims Coverage
The independent claim defines a recombinant antibody or antigen-binding fragment by specific heavy- and light-chain CDR amino acid sequences together with a binding dissociation-constant threshold. Dependent claims further constrain the antibody sequence assignments, tighten binding/affinity thresholds, and add a pharmaceutical composition element with a pharmaceutically acceptable carrier.
Recombinant antibody with defined heavy- and light-chain CDRs and K_D threshold
A recombinant antibody comprising a heavy chain CDR1 comprising SEQ ID NO: 144, a heavy chain CDR2 comprising SEQ ID NO: 146, and a heavy chain CDR3 comprising SEQ ID NO: 148, and a light chain CDR1 comprising SEQ ID NO: 136, a light chain CDR2 comprising SEQ ID NO: 138, and a light chain CDR3 comprising SEQ ID NO: 140, or an antigen-binding fragment thereof, that binds Staphylococcus enterotoxin B with a dissociation constant (K_D) of less than 3×10^-8 M.
Alternative defined heavy- and light-chain variable domains
The antibody or antigen-binding fragment is defined by a heavy chain variable domain with amino acid sequence SEQ ID NO: 230 and a light chain variable domain with amino acid sequence SEQ ID NO: 228.
Alternative defined heavy- and light-chain sequences
The antibody or antigen-binding fragment is defined by a heavy chain with amino acid sequence SEQ ID NO: 216 and a light chain with amino acid sequence SEQ ID NO: 214.
Affinity constraint of less than about 1×10^-9 M
The antibody or an antigen-binding fragment thereof has an affinity less than about 1×10^-9 M.
Affinity constraint of less than about 3×10^-10 M
The antibody or an antigen-binding fragment thereof has an affinity less than about 3×10^-10 M.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition that includes the antibody or an antigen-binding fragment together with a pharmaceutically acceptable carrier.
Across the independent and dependent claims, the patent covers SEB-binding recombinant antibodies defined by specific CDR amino acid sequences and related variable-domain sequence assignments with dissociation or affinity requirements, and also covers pharmaceutical compositions including a pharmaceutically acceptable carrier.
Stated Advantages
SEB-neutralizing therapeutic or preventive methods are supported.
Documented Applications
Therapeutic and preventive methods using SEB-neutralizing antibodies or antigen-binding fragments.
In vitro/in vivo-related characterization context including PBMC proliferation and cytokine inhibition, including IFN-γ and TNF-α inhibition.
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