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-9359428-B2
Publication Date
2016-06-07
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 anti–Staphylococcus enterotoxin B (SEB) antibodies and antigen-binding fragments. The antibodies are defined by specific heavy chain CDR1, CDR2, and CDR3 amino acid sequences and specific light chain CDR1, CDR2, and CDR3 amino acid sequences, as provided by SEQ ID numbers. The disclosed antibodies bind SEB with a dissociation constant (KD) of less than 3×10⁻28 M.
The document further discloses nucleic acids encoding the antibodies and antigen-binding fragments, together with host/expression cells. The antibody-containing materials are presented as recombinant antibodies or antigen-binding fragments that retain antigen binding to SEB, with binding characterized through reported affinity and binding properties. SEB binding is described in the context of epitope competition/binding and binding kinetics/competition.
The patent also describes therapeutic and preventive methods based on administration of antibody-containing compositions. The compositions include the antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier to treat SEB-mediated diseases. The description includes characterization of antibody performance such as inhibition of SEB-mediated PBMC proliferation/cytokine production, and in vivo mouse challenge model survival.
Claims Coverage
The independent claim covers a recombinant antibody or antigen-binding fragment with specified heavy- and light-chain CDR amino acid sequences that binds Staphylococcus enterotoxin B with a dissociation constant (KD) of less than 3×10⁻28 M. Dependent claims refine the covered antibodies by specifying alternative full heavy/light chain amino acid sequence identities and by adding a pharmaceutical composition limitation.
Recombinant antibody defined CDR sequences with high-affinity SEB binding
A recombinant antibody comprising a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 132, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 106, or an antigen-binding fragment thereof, that binds Staphylococcus enterotoxin B with a dissociation constant (KD) of less than 3×10⁻28 M.
Alternative full heavy/light chain variable-domain identities for the antibody
An antibody or antigen-binding fragment thereof in which the heavy chain variable domain and the light chain variable domain contain amino acid sequence identities specified by SEQ ID NO: 204 and SEQ ID NO: 200, and alternatively by SEQ ID NO: 232 and SEQ ID NO: 186, as stated in the dependent claims.
Pharmaceutical composition comprising the antibody with a pharmaceutically acceptable carrier
A pharmaceutical composition comprising the antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier.
Overall, the claim set is focused on recombinant anti-SEB antibodies or antigen-binding fragments defined by particular heavy- and light-chain CDR sequences that bind SEB with KD < 3×10⁻28 M, further narrowed by alternative specified variable-domain sequence identities and by inclusion of a pharmaceutically acceptable carrier in a pharmaceutical composition.
Stated Advantages
The antibodies bind Staphylococcus enterotoxin B with a dissociation constant (KD) of less than 3×10⁻28 M.
The disclosed antibodies are characterized as neutralizing SEB, including inhibition of SEB-mediated PBMC proliferation and cytokine production.
The disclosed therapeutic approach includes treating SEB-mediated diseases and is described with in vivo mouse challenge model survival.
Documented Applications
Therapeutic and preventive methods involving administration of an antibody-containing composition to treat SEB-mediated diseases.
Neutralization and functional characterization against SEB, including inhibition of SEB-mediated PBMC proliferation and cytokine production.
In vivo mouse challenge model survival to assess performance against SEB.
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