Anti-O2 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-12312397-B2
Application number	US-202217819199-A
Country	US
Kind code	B2
Filing date	Aug 11, 2022
Priority date	Aug 5, 2016
Publication date	May 27, 2025
Grant date	May 27, 2025

Abstract

The present disclosure provides binding proteins (e.g., antibodies or antigen binding fragments thereof) that specifically bind to Klebsiella pneumoniae 02 and induce opsonophagocytic killing of Klebsiella (e.g., Klebsiellapneumoniae) and/or protects mice from a lethal Klebsiella challenge. The present disclosure also provides methods of reducing Klebsiella (e.g., Klebsiella pneumoniae ) or treating or preventing Klebsiella (e.g., Klebsiella pneumoniae ) infection in a subject comprising administering the Klebsiella pneumoniae 02 binding proteins, (e.g., antibodies or antigen-binding fragments thereof) to the subject.

First claim

What is claimed is:

1. A method for treating or ameliorating a Klebsiella infection in a subject in need thereof comprising administering to said subject an effective amount of an antigen binding protein that specifically binds to Klebsiella pneumoniae O2 antigen and comprises a set of Complementarity-Determining Regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of:
SEQ. ID. NOs: 10-13, DVN or SEQ ID NO: 15, and SEQ ID NO:16, respectively;
SEQ. ID. NOs: 19-22, DVN or SEQ ID NO: 24, and SEQ ID NO: 25, respectively;
SEQ. ID. NOs: 28-31, DAS or SEQ ID NO: 33, and SEQ ID NO: 34, respectively;
SEQ. ID. NOs: 37-40, DMS or SEQ ID NO: 42, and SEQ ID NO: 43, respectively;
SEQ. ID. NOs: 46-49, DVN or SEQ ID NO: 51, and SEQ ID NO: 52, respectively;
SEQ. ID. NOs: 166-168, 175, DVN or SEQ ID NO: 177, and SEQ ID NO: 178, respectively;
SEQ. ID. NOs: 169-171, 179, DVN or SEQ ID NO: 181, and SEQ ID NO: 182, respectively;
SEQ. ID. NOs: 55-58, DMS or SEQ ID NO: 60, and SEQ ID NO: 61, respectively;
SEQ. ID. NOs: 64-67, AAS or SEQ ID NO: 69, and SEQ ID NO: 70, respectively;
SEQ. ID. NOs: 73-78, respectively;
SEQ. ID. NOs: 82-85, EVS or SEQ ID NO: 87, and SEQ ID NO: 88, respectively;
SEQ. ID. NOs: 91-94, DNN or SEQ ID NO: 96, and SEQ ID NO: 97, respectively;
SEQ. ID. NOs: 100-103, ENN or SEQ ID NO: 105, and SEQ ID NO: 106, respectively;
SEQ. ID. NOs: 109-112, ENN or SEQ ID NO: 114, and SEQ ID NO: 115, respectively;
SEQ. ID. NOs: 118-121, EVN or SEQ ID NO: 123, and SEQ ID NO: 124, respectively;
SEQ. ID. NOs: 127-130, GAS or SEQ ID NO: 132, and SEQ ID NO: 133, respectively; or
SEQ. ID. NOs: 172-174, 183, EVN or SEQ ID NO: 185, and SEQ ID NO: 186, respectively.

2. A method for inhibiting the growth of Klebsiella , or reducing the number of Klebsiella in a subject infected with Klebsiella comprising administering to a subject in need thereof an antigen binding protein that specifically binds to Klebsiella pneumoniae O2 antigen and comprises a set of Complementarity-Determining Regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of:
SEQ. ID. NOs: 10-13, DVN or SEQ ID NO: 15, and SEQ ID NO:16, respectively;
SEQ. ID. NOs: 19-22, DVN or SEQ ID NO: 24, and SEQ ID NO: 25, respectively;
SEQ. ID. NOs: 28-31, DAS or SEQ ID NO: 33, and SEQ ID NO: 34, respectively;
SEQ. ID. NOs: 37-40, DMS or SEQ ID NO: 42, and SEQ ID NO: 43, respectively;
SEQ. ID. NOs: 46-49, DVN or SEQ ID NO: 51, and SEQ ID NO: 52, respectively;
SEQ. ID. NOs: 166-168, 175, DVN or SEQ ID NO: 177, and SEQ ID NO: 178, respectively;
SEQ. ID. NOs: 169-171, 179, DVN or SEQ ID NO: 181, and SEQ ID NO: 182, respectively;
SEQ. ID. NOs: 55-58, DMS or SEQ ID NO: 60, and SEQ ID NO: 61, respectively;
SEQ. ID. NOs: 64-67, AAS or SEQ ID NO: 69, and SEQ ID NO: 70, respectively;
SEQ. ID. NOs: 73-78, respectively;
SEQ. ID. NOs: 82-85, EVS or SEQ ID NO: 87, and SEQ ID NO: 88, respectively;
SEQ. ID. NOs: 91-94, DNN or SEQ ID NO: 96, and SEQ ID NO: 97, respectively;
SEQ. ID. NOs: 100-103, ENN or SEQ ID NO: 105, and SEQ ID NO: 106, respectively;
SEQ. ID. NOs: 109-112, ENN or SEQ ID NO: 114, and SEQ ID NO: 115, respectively;
SEQ. ID. NOs: 118-121, EVN or SEQ ID NO: 123, and SEQ ID NO: 124, respectively;
SEQ. ID. NOs: 127-130, GAS or SEQ ID NO: 132, and SEQ ID NO: 133, respectively; or
SEQ. ID. NOs: 172-174, 183, EVN or SEQ ID NO: 185, and SEQ ID NO: 186, respectively.

3. The method of claim 1 , wherein the Klebsiella is antibiotic-resistant.

4. The method of claim 3 , wherein the Klebsiella is resistant to cephalosporin, quinolone, carbapenem, meropenem, fluoroquinolone, tetracycline, chloramphenicol, trimethoprim, sulfonamide, and/or colistin.

5. The method of claim 1 , further comprising administering an antibiotic.

6. The method of claim 5 , wherein the antigen binding protein and the antibiotic provide a synergistic therapeutic effect.

7. The method of claim 5 , wherein the antibiotic is meropenem, carbapenems, fluoroquinolone, tetracycline, chloramphenicol, trimethoprim, sulfonamide, and/or colistin.

8. The method of claim 3 , wherein antigen binding protein also specifically binds Klebsiella pneumoniae O1 antigen.

9. The method of claim 3 , wherein the antigen binding protein that specifically binds to Klebsiella pneumoniae O2 antigen is an antibody or antigen binding fragment thereof.

10. The method of claim 1 , wherein the Klebsiella is K. pneumoniae, K. oxytoca, K. planticola, K. ozaenae, K. rhinosclermoatis and/or K. granulomatis.

11. The method of claim 10 , wherein the Klebsiella is K. pneumoniae.

12. The method of claim 1 , wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ. ID. NOs: 109-112, ENN, and SEQ ID NO: 115, respectively; and wherein the antigen-binding protein is an antibody.

13. The method of claim 12 , wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 116 and a VL comprising the amino acid sequence of SEQ ID NO: 117.

14. The method of claim 2 , wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ. ID. NOs: 109-112, ENN, and SEQ ID NO: 115, respectively; and wherein the antigen-binding protein is an antibody.

15. The method of claim 14 , wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 116 and a VL comprising the amino acid sequence of SEQ ID NO: 117.

Assignees

• Medimmune Llc
• Humabs Biomed Sa

Inventors

• Wang Qun
• Pennini Meghan
• Xiao Xiaodong
• Corti Davide
• Cameroni Elisabetta
• Beltramello Martina
• Kaplan Gilad
• Demarco Anna
• Stover Charles K

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title