Compositions and methods related to antibodies to Staphylococcal protein A

Patent metadata

Field	Value
Publication number	US-10047149-B2
Application number	US-201615377050-A
Country	US
Kind code	B2
Filing date	Dec 13, 2016
Priority date	Aug 15, 2011
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

Embodiments concern methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. Aspects include methods and compositions for providing a passive immune response against the bacteria. In certain embodiments, the methods and compositions involve an antibody that binds Staphylococcal protein A (SpA).

First claim

What is claimed is:

1. A purified chimeric polypeptide comprising an amino acid sequence comprising CDR1, CDR2 and CDR3 of both the light and heavy chains of a 5A10 monoclonal antibody (SEQ ID NO: 16-18, 11-13, respectively), 8E2 monoclonal antibody (SEQ ID NO: 26-28, 21-23, respectively), 3F6 monoclonal antibody (SEQ ID NO: 56-58, 51-53, respectively), 1F10 monoclonal antibody (SEQ ID NO: 66-68, 61-63, respectively), 3D11 monoclonal antibody (SEQ ID NO: 86-88, 81-83, respectively) or 2F2 monoclonal antibody (SEQ ID NO: 101-103, 96-98, respectively), wherein the polypeptide is capable of specifically binding at least two Spa IgG binding domains A, B, C, D and E of a Staphylococcal protein A (SpA) polypeptide variant that lacks non-specific Ig-binding activity, and wherein each of CDR1, CDR2, and CDR3 have up to one amino acid substitution.

2. The polypeptide of claim 1 , wherein the SpA polypeptide that lacks non-specific Ig-binding activity is SpA KKAA .

3. The polypeptide of claim 1 , wherein the polypeptide competes for binding of SpA KKAA polypeptide with the 5A10, 8E2, 3F6, 1F10, 3D11, 2F2, monoclonal antibody.

4. The polypeptide of claim 1 , wherein the polypeptide has an association constant for the SpA KKAA polypeptide of between about 0.5 and 100×10 9 M −1 , 1.0 and 100×10 9 M −1 , or 2.0 and 100×10 9 M −1 as measured by ELISA.

5. The polypeptide of claim 1 , wherein the polypeptide is a single domain antibody.

6. The polypeptide of claim 1 , wherein the polypeptide is a humanized monoclonal antibody.

7. The polypeptide of claim 1 , wherein the polypeptide is recombinant.

8. The polypeptide of claim 1 , wherein the recombinant polypeptide comprises six CDR domains from a SpA-binding antibody and a scaffold from a polypeptide selected from the group consisting of an immunoglobulin, a fibronectin, a lipocalin or a S. aureus protein Z.

9. The polypeptide of claim 1 , wherein the purified polypeptide is operatively coupled to a second recombinant polypeptide that specifically binds to a second Staphylococcal protein.

10. The polypeptide of claim 1 , wherein the polypeptide is a 5A10, 8E2, 3F6, 1F10, 3D11, 2F2, monoclonal antibody.

11. The polypeptide of claim 1 , wherein the polypeptide is an antibody comprising (a) a heavy chain comprising said VH region, and a human hinge, CH1, CH2, and CH3 regions from an IgG1, IgG2, IgG3 or IgG4 subtype; and (b) a light chain comprising said VL region, and either a human kappa CL or human lambda CL.

12. A pharmaceutical composition comprising a purified chimeric polypeptide comprising CDR1, CDR2 and CDR3 of both the light and heavy chains of a 5A10 monoclonal antibody (SEQ ID NO: 16-18, 11-13, respectively), 8E2 monoclonal antibody (SEQ ID NO: 26-28, 21-23, respectively), 3F6 monoclonal antibody (SEQ ID NO: 56-58, 51-53, respectively), 1F10 monoclonal antibody (SEQ ID NO: 66-68, 61-63, respectively), 3D11 monoclonal antibody (SEQ ID NO: 86-88, 81-83, respectively) or 2F2 monoclonal antibody (SEQ ID NO: 101-103, 96-98, respectively), wherein the polypeptide is capable of specifically binding at least two Spa IgG binding domains A, B, C, D and E of a Staphylococcal protein A (SpA) polypeptide variant that lacks non-specific Ig-binding activity, and wherein each of CDR1, CDR2, and CDR3 have up to one amino acid substitution.

13. The pharmaceutical composition of claim 12 , comprising a single unit dose of the purified polypeptide in a sealed container.

14. The pharmaceutical composition of claim 12 , comprising at least a second anti-bacterial agent.

15. The pharmaceutical composition of claim 14 , wherein the second anti-bacterial agent is an antibiotic, a Staphylococcal vaccine composition or a polypeptide that specifically binds to a second Staphylococcal protein.

16. The pharmaceutical composition of claim 12 further comprising one or more physiologically acceptable excipients.

Assignees

• Univ Chicago

Inventors

• Schneewind Olaf
• Missiakas Dominique M
• Kim Hwan Keun
• Emolo Carla
• Dedent Andrea

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07K2317/51

  Complete heavy chain or Fd fragment, i.e. VH + CH1 · CPC title

• A61K2039/505

  comprising antibodies · CPC title