IP Library › Granted Patent US 12,312,397
Granted Patent B2
US 12,312,397 · App. 17/819,199 · Granted May 27, 2025

Anti-O2 antibodies and uses thereof

Inventors: Qun Wang (Gaithersburg, MD); Meghan Pennini (Gaithersburg, MD); Xiaodong Xiao (Gaithersburg, MD); Davide Corti (Bellinzona, CH); Elisabetta Cameroni (Bellinzona, CH); Martina Beltramello (Bellinzona, CH); Gilad Kaplan (Gaithersburg, MD); Anna DeMarco (Bellinzona, CH); Charles K. Stover (Gaithersburg, MD)
Assignees: MedImmune, LLC; Humabs BioMed SA
C07K16/1228A61K31/407A61K39/40A61P31/04A61K2039/505A61K2039/545C07K2317/565C07K2317/73C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,312,397
App. No.
17/819,199
Granted
May 27, 2025
Kind
B2
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.

Claims (49)

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.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 22, 2023
From: WANG, QUN; STOVER, CHARLES KEN; PENNINI, MEGHAN; XIAO, XIAODONG; KAPLAN, GILAD
To: MEDIMMUNE, LLC
Reel/Frame 064992/0676 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 22, 2023
From: CORTI, DAVIDE; CAMERONI, ELISABETTA; BELTRAMELLO, MARTINA; DE MARCO, ANNA
To: HUMABS BIOMED SA
Reel/Frame 064992/0741 →
Continuity (3)
Division 16323185
Provisional Application 62371402 · Aug 5, 2016
Related Publication 20230079661A1 · Mar 16, 2023
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