IP Library › Granted Patent US 12,344,670
Granted Patent B2
US 12,344,670 · App. 18/389,914 · Granted Jul 1, 2025

Anti-ILT4 antibodies and antigen-binding fragments

Inventors: Milan Blanusa (Jena, DE); Barbara Joyce-Shaikh (San Jose, CA); Andrea Claudia Schuster (Jena, DE); Kornelia Schultze (Jena, DE); Luis A. Zuniga (Mountain View, CA)
Assignees: Agenus Inc.; Merck Sharp & Dohme LLC
C07K16/2803A61P35/00C07K16/2818C07K16/2896A61K2039/505C07K2317/21C07K2317/33C07K2317/56C07K2317/565C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,344,670
App. No.
18/389,914
Granted
Jul 1, 2025
Kind
B2
Abstract

The present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 (immunoglobulin-like transcript 4) and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject; and methods of making such antibodies and fragments.

Claims (121)

1. A method for detecting an ILT4 peptide or fragment thereof in a sample, comprising contacting the sample with an antibody or antigen-binding fragment thereof that binds human ILT4, wherein the antibody or antigen-binding fragment thereof comprises:

(1) a heavy chain variable domain comprising:

CDR-H1: GYYWS (SEQ ID NO: 16),

CDR-H2: EINHXGSTNYNPSLKS wherein X is S or A (SEQ ID NO: 17), and

CDR-H3: LPTRWVTTRYFDL (SEQ ID NO: 18); and,

a light chain variable domain comprising:

CDR-L1: TGSSSNIGAGYDVH (SEQ ID NO: 19),

CDR-L2: GX1X2NRPS, wherein X1 is N, Q, E or D and X2 is S or A (SEQ ID NO: 20), and

CDR-L3: QSFDNSLSAYV (SEQ ID NO: 21);

(2) a heavy chain variable domain comprising:

CDR-H1: SYAIS (SEQ ID NO: 22),

CDR-H2: GIIPIFGTANYAQKFOG (SEQ ID NO: 23), and

CDR-H3: YFX1X2SGWYKGGAFDI, wherein X1 is D or S and X2 is S or A (SEQ ID NO: 24); and,

a light chain variable domain comprising:

CDR-L1: TLRSGINVDTYRIH (SEQ ID NO: 25),

CDR-L2: YKSDSDKHOGS (SEQ ID NO: 26), and

CDR-L3: AIWYSSTWV (SEQ ID NO: 27);

(3) a heavy chain variable domain comprising:

CDR-H1: SYAMH (SEQ ID NO: 28),

CDR-H2: VISYDGSNKYYADSVKG (SEQ ID NO: 29), and

CDR-H3: VGEWIQLWSPFDY (SEQ ID NO: 30); and,

a light chain variable domain comprising:

CDR-L1: RASQGISSWLA (SEQ ID NO: 31),

CDR-L2: AASSLOS (SEQ ID NO: 32), and

CDR-L3: QQYNSYPPT (SEQ ID NO: 33); or

(4) a heavy chain variable domain comprising:

CDR-H1: ELSMH (SEQ ID NO: 34),

CDR-H2: GFDPEDGETIYAQKFOG (SEQ ID NO: 35), and

CDR-H3: AGPLYTIFGVVIIPDNWFDP (SEQ ID NO: 36); and,

a light chain variable domain comprising:

CDR-L1: TGSSSNIGAGYDVH (SEQ ID NO: 37),

CDR-L2: GNSNRPS (SEQ ID NO: 38), and

CDR-L3: QSYDSSLSGSGVV (SEQ ID NO: 39), and detecting the presence of a complex between the antibody or antigen-binding fragment thereof and the ILT4 peptide or fragment thereof; wherein detection of the complex indicates the presence of the ILT4 peptide or fragment thereof.

2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:

a heavy chain variable domain comprising:

CDR-H1: GYYWS (SEQ ID NO: 16),

CDR-H2: EINHAGSTNYNPSLKS (SEQ ID NO: 48), and

CDR-H3: LPTRWVTTRYFDL (SEQ ID NO: 18); and,

a light chain variable domain comprising:

CDR-L1: TGSSSNIGAGYDVH (SEQ ID NO: 19),

CDR-L2: GDSNRPS (SEQ ID NO: 52), and

CDR-L3: QSFDNSLSAYV (SEQ ID NO: 21).

3. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, 11, 13, 15, or 45, and/or a heavy chain having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:1, 2, 8, 9, 10, 12, 14, 44, 79, 80, 81, 82, 83, 84, 85, or 86.

4. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain variable domain having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:70, 71, 72, 73, 58, 74, 75, 76, or 77, and/or

a heavy chain comprising a heavy chain variable domain having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:63, 57, 64, 65, 66, 67, 68, or 69.

5. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 3, 4, 5, 6, 7, 11, 13, 15, or 45; and/or

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1, 2, 8, 9, 10, 12, 14, 44, 79, 80, 81, 82, 83, 84, 85, or 86.

6. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 70, 71, 72, 73, 58, 74, 75, 76, or 77, and/or

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:63, 57, 64, 65, 66, 67, 68, or 69.

7. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:

(1)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1 or 79; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 3;

(2)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2 or 80; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 4;

(3)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2 or 80; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 5;

(4)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2 or 80; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 6;

(5)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2 or 80; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 7;

(6)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2 or 80; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 3;

(7)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 8 or 82; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11;

(8)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 9 or 83; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11;

(9)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 10 or 84; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 11;

(10)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 12 or 85; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 13; or

(11)

a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 14 or 86; and

a light chain comprising the amino acid sequence set forth in SEQ ID NO: 15.

8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:

(1)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:63; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:70;

(2)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:71;

(3)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:72;

(4)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:73;

(5)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:58;

(6)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:70;

(7)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:64; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:74;

(8)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:65; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:74;

(9)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:66; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:74;

(10)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:67; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:75; or

(11)

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:68; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:76;

a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57; and

a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:58.

9. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 2; and a light chain comprising the amino acid sequence set forth in SEQ ID NO:7.

10. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 80; and a light chain comprising the amino acid sequence set forth in SEQ ID NO:7.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2023
From: BLANUSA, MILAN; SCHUSTER, ANDREA CLAUDIA; SCHULTZE, KORNELIA
To: AGENUS SWITZERLAND INC.
Reel/Frame 065918/0172 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2023
From: AGENUS SWITZERLAND INC.
To: AGENUS INC.
Reel/Frame 065918/0395 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2023
From: ZUNIGA, LUIS A.; JOYCE-SHAIKH, BARBARA
To: MERCK SHARP & DOHME CORP.
Reel/Frame 065918/0523 →
MERGER Recorded Dec 20, 2023
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 065918/0574 →
Continuity (4)
Continuation 17338566 · Jun 3, 2021
Division 15945779 · Apr 5, 2018
Provisional Application 62483019 · Apr 7, 2017
Related Publication 20240228614A1 · Jul 11, 2024
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