# US 11,897,956 B2 · Anti-ILT4 antibodies and antigen-binding fragments

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- Number: US 11,897,956 B2
- Document ID: US11897956B2
- Status: Granted
- Kind: B2
- Application number: 17/338,566
- Filed: 2021-06-03
- Published: 2022-01-06
- Granted: 2024-02-13
- Earliest claimed: 2017-04-07
- Assignees: Merck Sharp & Dohme Corp.; Agenus Inc.
- Applicants: Merck Sharp & Dohme LLC; Agenus Inc.
- Inventors: Milan Blanusa; Barbara Joyce-Shaikh; Andrea Claudia Schuster; Kornelia Schultze; Luis A. Zuniga
- Web page: https://patentgrep.com/patent/US11897956B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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

### Claim 1

A polynucleotide comprising a nucleotide sequence encoding a VH, a VL, both a VH and a VL, a heavy chain immunoglobulin, a light chain immunoglobulin, or both a heavy chain and a light chain immunoglobulin of an antibody or antigen-binding fragment thereof that binds human ILT4, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain comprising: a CDR-H1 having an amino acid sequence of GYYWS (SEQ ID NO: 16), a CDR-H2 having an amino acid sequence of EINHSGSTNYNPSLKS (SEQ ID NO: 47) or EINHAGSTNYNPSLKS (SEQ ID NO: 48), and a CDR-H3 having an amino acid sequence of LPTRWVTTRYFDL (SEQ ID NO: 18); and a light chain variable domain comprising: a CDR-L1 having an amino acid sequence of TGSSSNIGAGYDVH (SEQ ID NO: 19), a CDR-L2 having an amino acid sequence of GNSNRPS(SEQ ID NO: 49), GQSNRPS(SEQ ID NO: 50), GESNRPS(SEQ ID NO: 51), GDSNRPS(SEQ ID NO: 52), GNANRPS(SEQ ID NO: 53), GQANRPS(SEQ ID NO: 54), GEANRPS(SEQ ID NO: 55), or GDANRPS(SEQ ID NO: 56), and a CDR-L3 having an amino acid sequence of QSFDNSLSAYV (SEQ ID NO: 21).

### Claim 2 (depends on 1)

The polynucleotide of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:58, 70, 71, 72, 73, or 77, and a heavy chain variable domain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:57, 63, or 69.

### Claim 3 (depends on 1)

The polynucleotide 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:58, 70, 71, 72, 73, or 77, and a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57, 63, or 69.

### Claim 4 (depends on 1)

The polynucleotide of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, or 45, and a heavy chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:1, 2, 79, 80, or 81.

### Claim 5 (depends on 1)

The polynucleotide 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, or 45, and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:1, 2, 79, 80, or 81.

### Claim 6

A polynucleotide comprising a nucleotide sequence encoding a VH, a VL, both a VH and a VL, a heavy chain immunoglobulin, a light chain immunoglobulin, or both a heavy chain and a light chain immunoglobulin of an antibody or antigen-binding fragment thereof that binds human ILT4, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain comprising: a CDR-H1 having an amino acid sequence of GYYWS (SEQ ID NO: 16), a CDR-H2 having an amino acid sequence of EINHAGSTNYNPSLKS (SEQ ID NO: 48), and a CDR-H3 having an amino acid sequence of LPTRWVTTRYFDL (SEQ ID NO: 18); and a light chain variable domain comprising: a CDR-L1 having an amino acid sequence of TGSSSNIGAGYDVH (SEQ ID NO: 19), a CDR-L2 having an amino acid sequence of GDSNRPS (SEQ ID NO: 52), and a CDR-L3 having an amino acid sequence of QSFDNSLSAYV (SEQ ID NO: 21).

### Claim 7 (depends on 6)

The polynucleotide of claim 6, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:58, and a heavy chain variable domain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:57.

### Claim 8 (depends on 6)

The polynucleotide of claim 6, 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:58 and a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO:57.

### Claim 9 (depends on 6)

The polynucleotide of claim 6, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:7 and a heavy chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:2.

### Claim 10 (depends on 6)

The polynucleotide of claim 6, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO:7 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:2.

### Claim 11 (depends on 6)

The polynucleotide of claim 6, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO:7 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:80.

### Claim 12 (depends on 6)

The polynucleotide of claim 6, the nucleotide sequence encodes a light chain comprising the amino acid sequence set forth in SEQ ID NO:7.

### Claim 13 (depends on 6)

The polynucleotide of claim 6, the nucleotide sequence encodes a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:2.

### Claim 14 (depends on 6)

The polynucleotide of claim 6, the nucleotide sequence encodes a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:80.

### Claim 15 (depends on 6)

The polynucleotide of claim 6, comprising the nucleotide sequence set forth in SEQ ID NO:87.

### Claim 16 (depends on 6)

The polynucleotide of claim 6, comprising the nucleotide sequence set forth in SEQ ID NO:88.

### Claim 17 (depends on 6)

A vector comprising the polynucleotide of claim 6.

### Claim 18 (depends on 17)

A host cell comprising the vector of claim 17.