IP Library › Granted Patent US 11,066,461
Granted Patent B2
US 11,066,461 · App. 15/779,189 · Granted Jul 20, 2021

Method for preventing or treating nosocomial pneumonia

Inventors: Hasan Jafri (Gaithersburg, MD); Antonio Digiandomenico (Gaithersburg, MD); Michael McCarthy (Gaithersburg, MD); Xiang-Qing Yu (Gaithersburg, MD); Charles K. Stover (Gaithersburg, MD); Brian Bishop (Gaithersburg, MD)
Assignee: MEDIMMUNE LIMITED
C07K16/1214A61K39/40A61K45/06A61P31/04C07K16/468A61K2039/505C07K2317/21C07K2317/31C07K2317/76
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Quick Facts
Patent No.
US 11,066,461
App. No.
15/779,189
Granted
Jul 20, 2021
Kind
B2
Abstract

A method for preventing or treating nosocomial diseases, e.g., diseases caused by Pseudomonas aeruginosa , is provided. The method includes administering to a susceptible human subject a specified dose of a bispecific antibody that specifically binds Pseudomonas aeruginosa Psl and PcrV.

Claims (12)

1. A method of treating a Pseudomonas aeruginosa infection in a susceptible human subject comprising administering to the subject 1500 mg or 3000 mg of a bispecific antibody that specifically binds Pseudomonas aeruginosa Psl and PcrV,

wherein the bispecific antibody comprises a binding domain which specifically binds to P. aeruginosa Psl comprising a set of complementarity determining regions (CDRs): HCDR1-Psl, HCDR2-Psl, HCDR3-Psl, LCDR1-Psl, LCDR2-Psl, and LCDR3-Psl, wherein HCDR1-Psl has the amino acid sequence of SEQ ID NO: 10, HCDR2-Psl has the amino acid sequence of SEQ ID NO: 11, HCDR3-Psl has the amino acid sequence of SEQ ID NO: 12, LCDR1-Psl has the amino acid sequence of SEQ ID NO: 13, LCDR2-Psl has the amino acid sequence of SEQ ID NO: 14, and LCDR3-Psl has the amino acid sequence of SEQ ID NO: 15; and a binding domain which specifically binds to P. aeruginosa PcrV comprising a set of CDRs: HCDR1-PcrV, HCDR2-PcrV, HCDR3-PcrV, LCDR1-PcrV, LCDR2-PcrV, and LCDR3-PcrV, wherein HCDR1-PcrV has the amino acid sequence of SEQ ID NO: 2, HCDR2-PcrV has the amino acid sequence of SEQ ID NO: 3, HCDR3-PcrV has the amino acid sequence of SEQ ID NO: 4, LCDR1-PcrV has the amino acid sequence of SEQ ID NO: 6, LCDR2-PcrV has the amino acid sequence of SEQ ID NO: 7, and LCDR3-PcrV has the amino acid sequence of SEQ ID NO: 8, and

wherein the subject maintains a serum concentration of the bispecific antibody of at least 1.7 μg/mL through 7 days following administration of the bispecific antibody.

2. The method of claim 1 , wherein the infection is pneumonia, bacteremia, bone infection, joint infection, skin infection, burn infection, wound infection, or any combination thereof.

3. The method of claim 2 , wherein the infection is pneumonia.

4. The method of claim 1 , wherein the subject maintains a serum concentration of the bispecific antibody of at least 1.7 μg/mL through 21 days following administration of the bispecific antibody.

5. The method of claim 1 , wherein the binding domain which specifically binds to P. aeruginosa Psl comprises an scFv comprising the amino acid sequence of SEQ ID NO:9.

6. The method of claim 1 , wherein the binding domain which specifically binds to P. aeruginosa PcrV comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a variable light chain comprising the amino acid sequence of SEQ ID NO:5.

7. The method of claim 1 , wherein the bispecific antibody comprises

(i) a heavy chain of the formula VH-CH1-H1-L1-S-L2-H2-CH2-CH3, wherein VH is an anti- P. aeruginosa PcrV heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 1; CH1 is a heavy chain constant region domain 1; H1 is a first heavy chain hinge region fragment; L1 is a first linker; S is an anti- P. aeruginosa Psl ScFv molecule comprising the amino acid sequence of SEQ ID NO: 9; L2 is a second linker; H2 is a second heavy chain hinge region fragment; CH2 is a heavy chain constant region domain-2; and CH3 is a heavy chain constant region domain-3; and

(ii) a light chain of the formula VL-CL, wherein VL is an anti- P. aeruginosa PcrV light chain variable domain comprising the amino acid sequence of SEQ ID NO: 5, and CL is an antibody light chain kappa constant region or an antibody light chain lambda region.

8. The method of claim 1 wherein the infection is a nosocomial infection.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 9, 2018
From: MEDIMMUNE, LLC
To: MEDIMMUNE LIMITED
Reel/Frame 046593/0895 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 9, 2018
From: JAFRI, HASAN; DIGIANDOMENICO, ANTONIO; STOVER, CHARLES K; MCCARTHY, MICHAEL; YU, XIANG-QING; BISHOP, BRIAN
To: MEDIMMUNE, LLC
Reel/Frame 046751/0358 →
Continuity (2)
Provisional Application 62260935 · Nov 30, 2015
Related Publication 20180355026A1 · Dec 13, 2018
Cited By (1)
US 12,428,473