IP Library › Granted Patent US 8,877,191
Granted Patent B2
US 8,877,191 · App. 13/271,146 · Granted Nov 4, 2014

Antibodies to the PcrV antigen of

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Quick Facts
Patent No.
US 8,877,191
App. No.
13/271,146
Granted
Nov 4, 2014
Kind
B2
Abstract

The current invention provides high-affinity antibodies to the Pseudomonas aeruginosa PcrV protein that have reduced immunogenicity when administered to treat Pseudomonas aeruginosa infections.

Claims (20)

1. A method of treating a P. aeruginosa infection in a patient, the method comprising administering a therapeutically effective amount of an anti-PcrV antibody that selectively binds PcrV to a patient infected with P. aeruginosa , wherein the antibody has a K D of less than 50 nM when assayed as a Fab and comprises:

a V L region that has a CDR3 having a sequence Q(Q/H)FWGTPYT (SEQ ID NO:41); a CDR1 having a sequence RASEGVDRWLA (SEQ ID NO:69) or RASQSISRWVA (SEQ ID NO:68); and a CDR2 having a sequence, DASTLQS (SEQ ID NO:73) or DASSLKS (SEQ ID NO:71); and

a V H region that has a CDR3 having a sequence NRGDIYYDFTYA(M/F)DX 1 (SEQ ID NO:42), wherein X 1 is I, Q, Y or S; a CDR1 having a sequence NYPMH (SEQ ID NO:54) or SYPLH (SEQ ID NO:53); and a CDR2 having a sequence VISYDGSEKWYADSVKG (SEQ ID NO:57) or FISYDGSEKYYASSVKG (SEQ ID NO:56).

2. The method of claim 1 , wherein the V H region comprises a FR4 that has at least 90% identity to the FR4 region of the human JH3 or human JH6 segment and the V L region comprises a FR4 that has at least 90% identity to the FR4 region of the human JK2 germline gene segment or at least 90% identity to the JL2 germline sequence.

3. The method of claim 2 , wherein the FR4 of the V H region has the sequence of the corresponding FR4 region of human germline JH3; and the FR4 of the V L region has the sequence of the corresponding FR4 region of human germline Jκ2.

4. The method of claim 1 , wherein the antibody is a Fab′.

5. The method of claim 4 , wherein the antibody is PEGylated.

6. The method of claim 5 , wherein the antibody is di-PEGylated.

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

8. The method of claim 1 , wherein the anti-PcrV antibody is administered by insufflation, intravenous injection, or sub-cutaneous bolus injection.

9. The method of claim 1 , wherein the anti-PcrV antibody retains at least 75% of the Type III secretion pathway antagonist activity of Mab166.

10. The method of claim 1 , wherein the patient has cystic fibrosis.

11. The method of claim 1 , wherein the V H region has a CDR3 having a sequence NRGDIYYDFTYAMDI (SEQ ID NO:99), a CDR1 having a sequence NYPMH (SEQ ID NO:54) or SYPLH (SEQ ID NO:53); and a CDR2 having a sequence VISYDGSEKWYADSVKG (SEQ ID NO:57) or FISYDGSEKYYASSVKG (SEQ ID NO:56).

12. The method of claim 11 , wherein the V H region has a CDR3 having a sequence NRGDIYYDFTYAMDI (SEQ ID NO:99), a CDR1 having a sequence NYPMH (SEQ ID NO:54), and a CDR2 having a sequence VISYDGSEKWYADSVKG (SEQ ID NO:57); or a CDR3 having a sequence NRGDIYYDFTYAMDI (SEQ ID NO:99), a CDR1 having a sequence SYPLH (SEQ ID NO:53) and a CDR2 having a sequence FISYDGSEKYYASSVKG (SEQ ID NO:56).

13. The method of claim 1 , wherein the V L region has a CDR3 having a sequence QHFWGTPYT (SEQ ID NO:110), a CDR1 having a sequence RASEGVDRWLA (SEQ ID NO:69) or RASQSISRWVA (SEQ ID NO:68), and a CDR2 having a sequence DASTLQS (SEQ ID NO:73) or DASSLKS (SEQ ID NO:71).

14. The method of claim 13 , wherein the V L region has a CDR3 having a sequence QHFWGTPYT (SEQ ID NO:110), a CDR1 having a sequence RASEGVDRWLA (SEQ ID NO:69) and a CDR2 having a sequence DASTLQS (SEQ ID NO:73); or the V L region has a CDR3 having a sequence QHFWGTPYT (SEQ ID NO:110), a CDR1 having a sequence RASQSISRWVA (SEQ ID NO:68), and a CDR2 having a sequence DASSLKS (SEQ ID NO:71).

15. The method of claim 1 , wherein the V H region has a CDR3 having a sequence NRGDIYYDFTYAMDI (SEQ ID NO:99), a CDR1 having a sequence NYPMH (SEQ ID NO:54), and a CDR2 having a sequence VISYDGSEKWYADSVKG (SEQ ID NO:57); and the V L region has a CDR3 having a sequence QHFWGTPYT (SEQ ID NO:1 10), a CDR1 having a sequence RASEGVDRWLA (SEQ ID NO:69), and a CDR2 having a sequence DASTLQS (SEQ ID NO:73).

16. The method of claim 1 , wherein the V H region has a V-segment sequence of a V-segment of SEQ ID NO:13, 19, 23, 25, 26, or 35; and the V L region has a V-segment sequence of a V-segment of SEQ ID NO:24, 12, 4, or 37.

17. The method of claim 16 , wherein the V H region has a sequence of SEQ ID NO:13, 19, 23, 25, 26, or 35; and the V L region has a sequence of SEQ ID NO:24 or 37.

18. The method of claim 17 , wherein the V H region has a sequence of SEQ ID NO:26 and the V L region has a sequence of SEQ ID NO:24.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Mar 30, 2018
From: BLACK HORSE CAPITAL MASTER FUND LTD.
To: KALOBIOS PHARAMECUTICALS, INC.
Reel/Frame 045788/0148 →
RELEASE OF SECURITY INTEREST Recorded Mar 30, 2018
From: BLACK HORSE CAPITAL MASTER FUND LTD.
To: KALOBIOS PHARAMECUTICALS, INC.
Reel/Frame 045855/0533 →
SECURITY INTEREST Recorded May 23, 2016
From: KALOBIOS PHARMACEUTICALS, INC.
To: BLACK HORSE CAPITAL, LP
Reel/Frame 038788/0266 →