IP Library › Granted Patent US 12,202,886
Granted Patent B2
US 12,202,886 · App. 17/855,553 · Granted Jan 21, 2025

Neutralizing antibodies to GP120 and their use

Inventors: Mark Connors (Bethesda, MD); Jinghe Huang (Derwood, MD); Byong Ha Kang (Rockville, MD); John Mascola (Rockville, MD); Elise Ishida (Chevy Chase, MD); Tongqing Zhou (Boyds, MD); Peter Kwong (Washington, DC); Anqi Zheng (Boyds, MD)
Assignee: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services
C07K16/1063A61P31/18C07K16/2809C07K16/468G01N33/56988A61K2039/505A61K2039/545C07K2317/21C07K2317/31C07K2317/52C07K2317/76G01N2333/162G01N2800/26
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Quick Facts
Patent No.
US 12,202,886
App. No.
17/855,553
Granted
Jan 21, 2025
Kind
B2
Abstract

Antibodies and antigen binding fragments that specifically bind to gp120 and neutralize HIV-1 are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

Claims (16)

1. An isolated monoclonal antibody, comprising

a heavy chain variable region (V H ) comprising the amino acid sequence of SEQ ID NO: 1;

a light chain variable region (V L ) comprising the amino acid sequence of SEQ ID NO: 2; and

an IgG constant domain comprising M428L and N434S mutations, wherein the antibody binds to CD4 binding site on HIV-1 gp120.

2. The isolated monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody specifically binds to HIV-1 gp120 and neutralizes HIV-1.

3. The isolated monoclonal antibody of claim 1 , wherein the isolated monoclonal antibody neutralizes at least 50% of the following HIV-1 isolates: 6540.v4.c1, 620345.c1, T278-50, 6322.V4.C1, DU422.01, X2088.c9, 6545.V4.C1, 242-14, T250-4, 7165.18, BL01.DG, HO86.8, 6471.V1.C16, 6631.V3.C10, TVI.29, TZA125.17, CAP210.E8, and DU172.17, with an inhibitory concentration (IC 50 ) of <50 μg/ml.

4. A method of treating an HIV-1 infection in a subject, comprising administering to the subject a therapeutically effective amount of the isolated monoclonal antibody of claim 1 , thereby treating the HIV-1 infection.

5. The method of claim 4 , further comprising administering to the subject an additional antibody, an additional antigen binding fragment, or a nucleic acid encoding the additional antibody or additional antigen binding fragment, wherein the additional antibody or additional antigen binding fragment specifically binds to HIV-1 Env and neutralizes HIV-1 infection.

6. The method of claim 4 , wherein the subject is a human subject.

7. The method of claim 6 , wherein the subject is a pregnant female.

8. The method of claim 7 , further comprising administering to the subject an effective amount of an anti-retroviral therapy.

9. The method of claim 8 , wherein the anti- retroviral therapy is a nucleoside analog reverse-transcriptase inhibitor, a nucleotide reverse transcriptase-inhibitor, a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, a viral entry or fusion inhibitor, a maturation inhibitor, or IL-15.

10. A pharmaceutical composition for use in treating an HIV-1 infection, comprising:

a therapeutically effective amount of the isolated monoclonal antibody of claim 1 ; and

a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is sterile and/or is in unit dosage form or a multiple thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2022
From: CONNORS, MARK; HUANG, JINGHE; KANG, BYONG HA; MASCOLA, JOHN; ISHIDA, ELISE; ZHOU, TONGQING; KWONG, PETER; ZHENG, ANQI
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 060400/0888 →
Continuity (6)
Continuation 17358522 · Jun 25, 2021
Continuation 16786267 · Feb 10, 2020
Continuation 15559791
Provisional Application 62250378 · Nov 3, 2015
Provisional Application 62136228 · Mar 20, 2015
Related Publication 20230060304A1 · Mar 2, 2023
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US 12,545,719