Compositions and methods for treating and preventing Staphylococcus aureus infections

• US 10,577,410 B2
• Filed: 01/07/2019
• Issued: 03/03/2020
• Est. Priority Date: 06/03/2014
• Status: Active Grant

• Current Assignee: XBiotech Inc.
• Original Assignee: XBiotech Inc.
• Inventors: Simard, John
• Primary Examiner(s): Baskar, Padmavathi
• Application Number:
  US16/241,809
• Publication Number:
  US 20190127449A1
• Time in Patent Office: 421 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61K 39/085 Staphylococcus
• CPC Class Codes: A61K 39/40 bacterial
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/1271 from Micrococcaceae (F), e.g. Staphylococcus
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/30 characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Antibodies having Fab regions that specifically bind to Staphylococcus aureus protein A are capable of mediating opsinization of Staphylococcus aureus bacteria despite their expression of antibody-neutralizing protein A. These antibodies and antigen-binding fragments thereof can be used in methods of treating and/or preventing Staphylococcus aureus infections.

Claims

1. A method for displacing human IgG immunoglobulins bound to Staphylococcus aureus protein A (SpA) via their Fc regions, the method comprising the step of contacting a human IgG-SpA complex with a purified monoclonal antibody which specifically binds SpA with a K_D of less than 1×

10<sup>−

10</sup> M via its Fab region paratope whereby the purified monoclonal antibody displaces the human IgG immunoglobulins bound to SpA.

2. The method of claim 1, wherein the human IgG-SpA complex is located on a Staphylococcus aureus bacterium.

3. The method of claim 2, wherein the Staphylococcus aureus bacterium is located in a human being.

4. The method of claim 1, wherein the purified monoclonal antibody is a human or humanized IgG3 monoclonal antibody.

5. The method of claim 1, wherein the purified monoclonal antibody is a human monoclonal antibody.

6. The method of claim 4, wherein the human IgG-SpA complex is located on a Staphylococcus aureus bacterium and the Staphylococcus aureus bacterium is located in a human being.

7. The method of claim 5, wherein the human IgG-SpA complex is located on a Staphylococcus aureus bacterium and the Staphylococcus aureus bacterium is located in a human being.

8. The method of claim 1, wherein the monoclonal antibody is able to mediate opsonization of SpA-expressing Staphylococcus aureus bacteria in the presence of at least 1 mg/ml of IgG immunoglobulins which bind SpA via their Fc regions.

9. The method of claim 1, wherein the purified monoclonal antibody binds to an epitope present in the extracellular domain of SpA.

10. The method of claim 1, wherein the purified monoclonal antibody binds to an IgG binding domain of SpA.

11. The method of claim 1, wherein the purified monoclonal antibody binds to an X_R repeat region of SpA.