IP Library › Granted Patent US 12,258,409
Granted Patent B2
US 12,258,409 · App. 17/934,441 · Granted Mar 25, 2025

Method of assessing the efficacy of a test agent for modulating programmed death 1 (PD-1) signaling by using anti-phosphotyrosinylated PD-1 monoclonal antibodies

Inventors: Gordon J. Freeman (Brookline, MA); Vassiliki A. Boussiotis (Brookline, MA); Xia Bu (Brookline, MA); Vikram R. Juneja (Boston, MA); Arlene H. Sharpe (Brookline, MA); Nikolaos Patsoukis (Boston, MA); Jessica Weaver (Brighton, MA); Laura Strauss (Boston, MA)
Assignees: Dana-Farber Cancer Institute, Inc.; Beth Israel Deaconess Medical Center; President and Fellows of Harvard College
C07K16/2818C07K16/44G01N33/5011G01N33/57492C07K2317/33C07K2317/34C07K2317/76C07K2317/92G01N2333/70596G01N2440/14G01N2500/04G01N2500/10G01N2500/20G01N2800/52
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Quick Facts
Patent No.
US 12,258,409
App. No.
17/934,441
Granted
Mar 25, 2025
Kind
B2
Abstract

The present invention is based, in part, on the discovery of monoclonal and polyclonal antibodies that specifically bind to phosphorylated PD-1, as well as immunoglobulins, polypeptides, nucleic acids thereof, and methods of using such antibodies for diagnostic, prognostic, and therapeutic purposes.

Claims (25)

1. A method of assessing the efficacy of a test agent for modulating PD-1 signaling, the method comprising:

a) contacting a cell expressing PD-1 with a test agent; and

b) determining the ability of the test agent to modulate the level of phosphorylated PD-1 using at least one monoclonal antibody, or antigen-binding fragment thereof, that binds to a phosphorylation site at tyrosine residue 248 of human PD-1, wherein the monoclonal, or antigen-binding fragment thereof, comprises:

i) a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 6, CDR-L2 having the sequence of SEQ ID NO: 9, and CDR-L3 having the sequence of SEQ ID NO: 12, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 19, CDR-H2 having the sequence of SEQ ID NO: 22, and CDR-H3 having the sequence of SEQ ID NO: 25;

ii) a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 34, CDR-L2 having the sequence of SEQ ID NO: 38, and CDR-L3 having the sequence of SEQ ID NO: 43, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 52, CDR-H2 having the sequence of SEQ ID NO: 56, and CDR-H3 having the sequence of SEQ ID NO: 60;

iii) a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 70, CDR-L2 having the sequence of SEQ ID NO: 74, and CDR-L3 having the sequence of SEQ ID NO: 78, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 88, CDR-H2 having the sequence of SEQ ID NO: 92, and CDR-H3 having the sequence of SEQ ID NO: 96; or

iv) a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 106, CDR-L2 having the sequence of SEQ ID NO: 110, and CDR-L3 having the sequence of SEQ ID NO: 114, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 124, CDR-H2 having the sequence of SEQ ID NO: 128, and CDR-H3 having the sequence of SEQ ID NO: 132;

wherein a modulated level of phosphorylated PD-1 resulting from contacting with the test agent identifies the test agent as a modulator of PD-1 signaling.

2. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 6, CDR-L2 having the sequence of SEQ ID NO: 9, and CDR-L3 having the sequence of SEQ ID NO: 12, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 19, CDR-H2 having the sequence of SEQ ID NO: 22, and CDR-H3 having the sequence of SEQ ID NO: 25.

3. The method of claim 2 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising a sequence at least 90% identical to SEQ ID NO: 1 and a heavy chain comprising a sequence at least 90% identical to SEQ ID NO: 14.

4. The method of claim 3 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising the sequence of SEQ ID NO: 1 and a heavy chain comprising the sequence of SEQ ID NO: 14.

5. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 34, CDR-L2 having the sequence of SEQ ID NO: 38, and CDR-L3 having the sequence of SEQ ID NO: 43, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 52, CDR-H2 having the sequence of SEQ ID NO: 56, and CDR-H3 having the sequence of SEQ ID NO: 60.

6. The method of claim 5 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising a sequence at least 90% identical to SEQ ID NO: 30 and a heavy chain comprising a sequence at least 90% identical to SEQ ID NO: 46.

7. The method of claim 6 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising the sequence of SEQ ID NO: 30 and a heavy chain comprising the sequence of SEQ ID NO: 46.

8. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 70, CDR-L2 having the sequence of SEQ ID NO: 74, and CDR-L3 having the sequence of SEQ ID NO: 78, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 88, CDR-H2 having the sequence of SEQ ID NO: 92, and CDR-H3 having the sequence of SEQ ID NO: 96.

9. The method of claim 8 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising a sequence at least 90% identical to SEQ ID NO: 64 and a heavy chain comprising a sequence at least 90% identical to SEQ ID NO: 82.

10. The method of claim 9 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising the sequence of SEQ ID NO: 64 and a heavy chain comprising the sequence of SEQ ID NO: 82.

11. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising CDR-L1 having the sequence of SEQ ID NO: 106, CDR-L2 having the sequence of SEQ ID NO: 110, and CDR-L3 having the sequence of SEQ ID NO: 114, and a heavy chain comprising CDR-H1 having the sequence of SEQ ID NO: 124, CDR-H2 having the sequence of SEQ ID NO: 128, and CDR-H3 having the sequence of SEQ ID NO: 132.

12. The method of claim 11 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising a sequence at least 90% identical to SEQ ID NO: 100 and a heavy chain comprising a sequence at least 90% identical to SEQ ID NO: 118.

13. The method of claim 12 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain comprising the sequence of SEQ ID NO: 100 and a heavy chain comprising the sequence of SEQ ID NO: 118.

14. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, is chimeric, humanized, murine, or rabbit.

15. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, is detectably labeled.

16. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises an effector domain.

17. The method of claim 1 , wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises an Fc domain.

18. The method of claim 1 , wherein the antigen-binding fragment thereof, is selected from the group consisting of Fv, Fav, F (ab′)2), Fab′, dsFv, scFv, sc (Fv)2, and diabodies fragments.

Assignments (4)
CONFIRMATORY LICENSE Recorded Jan 29, 2024
From: DANA-FARBER CANCER INST
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066377/0563 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2023
From: FREEMAN, GORDON J.; BU, XIA
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 062689/0822 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2023
From: BOUSSIOTIS, VASSILIKI A.; PATSOUKIS, NIKOLAOS; WEAVER, JESSICA; STRAUSS, LAURA
To: BETH ISRAEL DEACONESS MEDICAL CENTER
Reel/Frame 062689/0839 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2023
From: JUNEJA, VIKRAM R.; SHARPE, ARLENE H.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 062689/0847 →
Continuity (3)
Division 16603894
Provisional Application 62487808 · Apr 20, 2017
Related Publication 20230331847A1 · Oct 19, 2023
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