IP Library Granted Patent US 11,760,789
Granted Patent B2
US 11,760,789 · App. 16/725,596 · Granted Sep 19, 2023

Broadly neutralizing antibodies against HIV

Inventors: Mohammad Sajadi (Cockeysville, MD); George K. Lewis (Baltimore, MD); Anthony DeVico (Alexandria, VA)
Assignees: UNIVERSITY OF MARYLAND, BALTIMORE; THE UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS
C07K16/1063A61K39/42A61K45/06A61P31/18C07K16/1045C07K2317/34C07K2317/565C07K2317/732C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 11,760,789
App. No.
16/725,596
Granted
Sep 19, 2023
Kind
B2
Abstract

The present invention provides broadly neutralizing antibodies against HIV, compositions comprising the same and methods of use thereof.

Claims (35)

1. An isolated anti-HIV antibody, wherein the anti-HIV antibody is a non-naturally occurring antibody and is selected from the group consisting of:

a. an antibody comprising a heavy chain variable region, wherein CDR H1 comprises GYDFIDYV (SEQ ID NO:401), CDR H2 comprises MNPSGGGT (SEQ ID NO:402) and CDR H3 comprises VRDRANGSGRRRFESVNWFLDL (SEQ ID NO:403); and a light chain variable region, wherein CDR L1 comprises HNY, CDR L2 comprises DFN and CDR L3 comprises WAFEN (SEQ ID NO:404), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:1 and a light chain amino acid sequence of SEQ ID NO:2;

b. an antibody comprising a heavy chain variable region, wherein CDR H1 comprises GYRFPDYI (SEQ ID NO:497), CDR H2 comprises MNPMGGQV (SEQ ID NO:421) and CDR H3 comprises VRDRSNGSGKRFESSNWFLDL (SEQ ID NO:441); and a light chain variable region, wherein CDR L1 comprises HNL, CDR L2 comprises DFN and CDR L3 comprises WAYEA (SEQ ID NO:408), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:3 and a light chain amino acid sequence of SEQ ID NO:4;

c. an antibody comprising a heavy chain variable region, wherein CDR H1 comprises GYKFMDQL (SEQ ID NO:442), CDR H2 comprises MNPTYGQV (SEQ ID NO:443) and CDR H3 comprises ARGPSGENYPFHY (SEQ ID NO:444); and a light chain variable region, wherein CDR L1 comprises RHII (SEQ ID NO:445), CDR L2 comprises DDD and CDR L3 comprises NTYEF (SEQ ID NO:446), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:35 and a light chain amino acid sequence of SEQ ID NO:36; and

d. an antibody comprising a heavy chain variable region, wherein CDR H1 comprises GYTFTDYL (SEQ ID NO:409), CDR H2 comprises MNPVYGQV (SEQ ID NO:410) and CDR H3 comprises VRDTGDGSRRHFDSINWFLDL (SEQ ID NO:411); and a light chain variable region, wherein CDR L1 comprises HNY, CDR L2 comprises DFD and CDR L3 comprises WAFEA (SEQ ID NO:412), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:7 and a light chain amino acid sequence of SEQ ID NO:8.

2. The isolated anti-HIV antibody of claim 1 , wherein the anti-HIV antibody comprises a heavy chain or an antigen binding fragment thereof and a light chain or an antigen binding fragment thereof, wherein the heavy chain or antigen binding fragment thereof comprises a heavy chain variable (VH) region and the light chain or antigen binding fragment thereof comprises a light chain variable (VL) region; wherein the anti-HIV antibody is selected from the group consisting of:

a. an antibody wherein the VH region comprises amino acids 1-128 of SEQ ID NO:153 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; wherein the VL region comprises amino acids 1-99 of SEQ ID NO:155 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions;

b. an antibody wherein the VH region comprises amino acids 1-127 of SEQ ID NO:161 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; wherein the VL region comprises amino acids 1-99 of SEQ ID NO:163 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions;

c. an antibody wherein the VH region comprises amino acids 1-127 of SEQ ID NO:165 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; wherein the VL region comprises amino acids 1-99 of SEQ ID NO:167 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions;

d. an antibody wherein the VH region comprises amino acids 1-128 of SEQ ID NO:225 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; wherein the VL region comprises amino acids 1-99 of SEQ ID NO:227 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; and

e. an antibody wherein the VH region comprises amino acids 1-120 of SEQ ID NO:293 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions; wherein the VL region comprises amino acids 1-100 of SEQ ID NO:295 or a variant thereof comprising 1, 2, 3, or 4 conservative amino acid substitutions.

3. The anti-HIV antibody of claim 1 , wherein the anti-HIV antibody is selected from the group consisting of:

a. an antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO:153 or an antigen binding fragment thereof and a light chain amino acid sequence comprising SEQ ID NO:155 or an antigen binding fragment thereof;

b. an antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO:161 or an antigen binding fragment thereof and a light chain amino acid sequence comprising SEQ ID NO:163 or an antigen binding fragment thereof;

c. an antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO:165 or an antigen binding fragment thereof and a light chain amino acid sequence comprising SEQ ID NO:167 or an antigen binding fragment thereof;

d. an antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO:225 or an antigen binding fragment thereof and a light chain amino acid sequence comprising SEQ ID NO:227 or an antigen binding fragment thereof; and

e. an antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO:293 or an antigen binding fragment thereof and a light chain amino acid sequence comprising SEQ ID NO:295 or an antigen binding fragment thereof.

4. An isolated host cell expressing the antibody of claim 2 .

5. An engineered cell that expresses the antibody of claim 2 .

6. A pharmaceutical composition comprising one or more antibodies of claim 1 and a pharmaceutically acceptable carrier.

7. A method for treating or preventing HIV infection in a subject, comprising administering to the subject an effective amount of the composition of claim 6 .

8. The method of claim 6 , wherein the composition is administered in combination with another therapy.

9. The method of claim 8 , wherein the therapy is an anti-retroviral therapy.

10. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain variable region, wherein CDR H1 comprises GYDFIDYV (SEQ ID NO:401), CDR H2 comprises MNPSGGGT (SEQ ID NO:402) and CDR H3 comprises VRDRANGSGRRRFESVNWFLDL (SEQ ID NO:403); and a light chain variable region, wherein CDR L1 comprises HNY, CDR L2 comprises DFN and CDR L3 comprises WAFEN (SEQ ID NO:404), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:1 and a light chain amino acid sequence of SEQ ID NO:2.

11. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain variable region, wherein CDR H1 comprises GYRFPDYI (SEQ ID NO:497), CDR H2 comprises MNPMGGQV (SEQ ID NO:421) and CDR H3 comprises VRDRSNGSGKRFESSNWFLDL (SEQ ID NO:441); and a light chain variable region, wherein CDR L1 comprises HNL, CDR L2 comprises DFN and CDR L3 comprises WAYEA (SEQ ID NO:408), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:3 and a light chain amino acid sequence of SEQ ID NO:4.

12. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain variable region, wherein CDR H1 comprises GYKFMDQL (SEQ ID NO:442), CDR H2 comprises MNPTYGQV (SEQ ID NO:443) and CDR H3 comprises ARGPSGENYPFHY (SEQ ID NO:444); and a light chain variable region, wherein CDR L1 comprises RHII (SEQ ID NO:445), CDR L2 comprises DDD and CDR L3 comprises NTYEF (SEQ ID NO:446), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:35 and a light chain amino acid sequence of SEQ ID NO:36.

13. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain variable region, wherein CDR H1 comprises GYTFTDYL (SEQ ID NO:409), CDR H2 comprises MNPVYGQV (SEQ ID NO:410) and CDR H3 comprises VRDTGDGSRRHFDSINWFLDL (SEQ ID NO:411); and a light chain variable region, wherein CDR L1 comprises HNY, CDR L2 comprises DFD and CDR L3 comprises WAFEA (SEQ ID NO:412), wherein the antibody is not an antibody that consists of a heavy chain amino acid sequence of SEQ ID NO:7 and a light chain amino acid sequence of SEQ ID NO:8.

14. The isolated anti-HIV antibody of claim 10 , wherein the antibody comprises a heavy chain amino acid sequence that is at least 95% identical to SEQ ID NO:1 and a light chain amino acid sequence that is at least 95% identical to SEQ ID NO:2.

15. The isolated anti-HIV antibody of claim 11 , wherein the antibody comprises a heavy chain amino acid sequence that is at least 95% identical to SEQ ID NO:3 and a light chain amino acid sequence that is at least 95% identical to SEQ ID NO:4.

16. The isolated anti-HIV antibody of claim 12 , wherein the antibody comprises a heavy chain amino acid sequence that is at least 95% identical to SEQ ID NO:35 and a light chain amino acid sequence that is at least 95% identical to SEQ ID NO:36.

17. The isolated anti-HIV antibody of claim 13 , wherein the antibody comprises a heavy chain amino acid sequence that is at least 95% identical to SEQ ID NO:7 and a light chain amino acid sequence that is at least 95% identical to SEQ ID NO:8.

18. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain comprising SEQ ID NO:153 and a light chain comprising SEQ ID NO:155.

19. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain comprising SEQ ID NO:161 and a light chain comprising SEQ ID NO:163.

20. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain comprising SEQ ID NO:293 and a light chain comprising SEQ ID NO:295.

21. The isolated anti-HIV antibody of claim 1 , wherein the antibody comprises a heavy chain comprising SEQ ID NO:225 and a light chain comprising SEQ ID NO:227.

Assignments (3)
CONFIRMATORY LICENSE Recorded Aug 2, 2022
From: UNIVERSITY OF MARYLAND BALTIMORE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 060699/0241 →
ASSIGNMENT OF A JOINT UNDIVIDED RIGHT, TITLE, AND INTEREST Recorded Jan 16, 2020
From: UNIVERSITY OF MARYLAND, BALTIMORE
To: THE UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS
Reel/Frame 051619/0439 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 14, 2020
From: SAJADI, MOHAMMAD; LEWIS, GEORGE K.; DEVICO, ANTHONY
To: UNIVERSITY OF MARYLAND, BALTIMORE
Reel/Frame 051509/0646 →
Continuity (7)
Continuation PCTUS2018039162 · Jun 22, 2018
Provisional Application 62673607 · May 18, 2018
Provisional Application 62591244 · Nov 28, 2017
Provisional Application 62589614 · Nov 22, 2017
Provisional Application 62573764 · Oct 18, 2017
Provisional Application 62523437 · Jun 22, 2017
Related Publication 20200239551A1 · Jul 30, 2020
Cited By (1)
US 12,534,516