Compositions and methods for treating and preventing Staphylococcus aureus infections

• US 10,214,581 B2
• Filed: 08/18/2017
• Issued: 02/26/2019
• 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:
  US15/680,533
• Publication Number:
  US 20170349648A1
• Time in Patent Office: 557 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 pharmaceutical composition comprising a pharmaceutically acceptable carrier and a purified monoclonal antibody which specifically binds Staphylococcus aureus protein A (SpA) with a K_D of less than 1×

10<sup>−

10</sup> M via its Fab region paratope, wherein the monoclonal antibody is able to displace human IgG immunoglobulins bound to SpA on Staphylococcus aureus bacteria via their Fc regions, wherein the monoclonal antibody specifically binds to an amino acid sequence selected from the group of amino acid sequences consisting of SEQ ID NO;

1, SEQ ID NO;

82, SEQ ID NO;

83, SEQ ID NO;

84, and SEQ ID NO;

85.

2. The pharmaceutical composition of claim 1, wherein the monoclonal antibody is a human or humanized IgG3 monoclonal antibody.

3. The pharmaceutical composition of claim 1, wherein the monoclonal antibody is a human or humanized IgG3 monoclonal antibody, 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.

4. A method of treating a Staphylococcus aureus infection in a subject, the method comprising administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a purified monoclonal antibody which specifically binds Staphylococcus aureus protein A (SpA) with a K_D of less than 1×

10<sup>−

10</sup> M via its Fab region paratope, wherein the monoclonal antibody is able to displace human IgG immunoglobulins bound to SpA on Staphylococcus aureus bacteria via their Fc regions, and wherein the monoclonal antibody specifically binds to an amino acid sequence selected from the group of amino acid sequences consisting of SEQ ID NO;

1, SEQ ID NO;

82, SEQ ID NO;

83, SEQ ID NO;

84, and SEQ ID NO;

85.

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

6. The method of claim 4, 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.

7. The method of claim 4, wherein the Staphylococcus aureus infection is bacteremia.

8. The method of claim 4, wherein the Staphylococcus aureus infection is caused by methicillin-resistant Staphylococcus aureus.

9. The method of claim 4, wherein the monoclonal antibody is administered to the subject intravenously.

10. The method of claim 4, wherein vancomycin is co-administered with the monoclonal antibody.