Antibody specific to alpha-toxin of Staphylococcal aureus and uses thereof
Inventors
CHAO, TZU-YUAN • Chang, Ching-Wen • Tsao, Eric
Assignees
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Publication Number
US-11530256-B2
Publication Date
2022-12-20
Expiration Date
Abstract
The present disclosure relates to an antibody or antigen-binding fragment thereof that specifically bind to α-toxin of Staphylococcal aureus. The present disclosure also relates to a pharmaceutical composition, a method for treating and/or preventing diseases and/or disorders caused by Staphylococcal aureus infection in a subject in need, and a method for detecting α-toxin of Staphylococcal aureus in a sample.
Core Innovation
The invention provides an antibody or antigen-binding fragment thereof that specifically binds an epitope in b1-toxin of Staphylococcal aureus or a fragment thereof. The antibody or antigen-binding fragment comprises complementarity determining regions (CDRs) of a heavy chain variable region and complementarity determining regions of a light chain variable region, including CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3. The document further identifies murine clone 25A1 and humanized variants.
The CDRH1 region comprises the amino acid sequence consisting of SEQ ID NO: 1; the CDRH2 region comprises the amino acid sequence consisting of SEQ ID NO: 3; and the CDRH3 region comprises the amino acid sequence consisting of SEQ ID NO: 7. The CDRL1 region comprises the amino acid sequence consisting of SEQ ID NO: 10; the CDRL2 region comprises the amino acid sequence consisting of SEQ ID NO: 14; and the CDRL3 region comprises the amino acid sequence consisting of SEQ ID NO: 16.
The invention states functional uses including neutralizing b1-toxin for passive immunotherapy, including in pneumonia/sepsis/bacteremia models. It also provides detecting b1-toxin in samples by antibody contact and detection kits, and supports high-affinity binding with inhibition of cytotoxicity and hemolysis in vitro and survival benefits in vivo.
Claims Coverage
The independent claim covers one inventive feature: an antibody or antigen-binding fragment that specifically binds an epitope in Staphylococcal aureus b1-toxin, with defined heavy- and light-chain CDR sequence requirements. Additional inventive features are covered in dependent claims by adding an antibody-type limitation, a binding affinity constraint, and downstream uses including prophylactic/therapeutic treatment and detection/kit formats.
Defined epitope-binding antibody or antigen-binding fragment with specified CDR sequences
The antibody or antigen-binding fragment specifically binds an epitope in b1-toxin of Staphylococcal aureus, and comprises CDRs of a heavy chain variable region and a light chain variable region with CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences consisting of specified SEQ ID NOs.
KD binding affinity range for b1-toxin
The antibody or antigen-binding fragment binds b1-toxin with a dissociation constant (KD) ranging from 1d710^-27 to 1d710^-2210 M.
Antibody or antigen-binding fragment is a defined antibody type
The antibody or antigen-binding fragment is a monoclonal antibody, chimeric antibody, humanized antibody or human antibody.
Treating, prophylactically treating, and/or preventing disease caused by Staphylococcal aureus infection
A method of treating, prophylactically treating, and/or preventing diseases or disorders in a subject caused by Staphylococcal aureus infection by administering the antibody or antigen-binding fragment.
Detecting b1-toxin in a sample using the antibody
A method of detecting b1-toxin of Staphylococcus aureus in a sample by contacting the sample with the antibody or antigen-binding fragment.
Detection kit comprising the antibody
A kit comprising the antibody or antigen-binding fragment for detecting b1-toxin of Staphylococcus aureus in a sample.
Overall claim coverage centers on a specifically binding antibody or antigen-binding fragment with specified heavy- and light-chain CDR sequences, optionally constrained by a stated KD range and specific antibody types, and further extends to prophylactic or therapeutic use and to detection formats including methods and kits for detecting b1-toxin in samples.
Stated Advantages
Neutralization of b1-toxin for passive immunotherapy.
Inhibition of cytotoxicity in vitro, including A549 cytolysis and RBC hemolysis inhibition.
Improved survival benefits in vivo in murine and rabbit infection models.
Synergy with standard antibiotics such as vancomycin and linezolid.
Detection of b1-toxin in samples using antibody contact and detection kits.
Documented Applications
Passive immunotherapy for neutralizing Staphylococcus aureus b1-toxin, including pneumonia/sepsis/bacteremia models.
Detecting b1-toxin of Staphylococcus aureus in a sample by contacting the sample with the antibody or antigen-binding fragment.
Using a kit for detecting b1-toxin of Staphylococcus aureus in a sample.
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