# US 11,111,297 B2 · Antibodies specific for immunoglobulin-like transcript 3 (ILT3) and uses thereof

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- Number: US 11,111,297 B2
- Document ID: US11111297B2
- Status: Granted
- Kind: B2
- Application number: 16/191,485
- Filed: 2018-11-15
- Published: 2019-05-23
- Granted: 2021-09-07
- Earliest claimed: 2017-11-17
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme Corp.
- Inventors: Michael A. Meehl; Philip E. Brandish; Laurence Fayadat-Dilman; Veronica Juan; Carl Mieczkowski; Latika Singh
- Web page: https://patentgrep.com/patent/US11111297B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- 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

Humanized, non-promiscuous monoclonal antibodies specific for immunoglobulin-like transcript 3 (ILT3), also known as Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), are described.

## Claims

### Claim 1

An antibody or antigen binding fragment that binds the extracellular domain of human immunoglobulin-like transcript 3 (ILT3) having amino acids 1-238 of SEQ ID NO: 1, wherein the antibody or antigen binding fragment comprises
(a) a heavy chain complementarity determining region 1 (HC-CDR1), wherein the HC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 17; an HC-CDR2, wherein the HC-CDR2 has the amino acid sequence set forth in SEQ ID NO: 19, 20, or 21; an HC-CDR3, wherein the HC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 23; and
(b) a light chain complementarity determining region 1 (LC-CDR1), wherein the LC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 34, 35, 36, 37, 38, 39, 40, 41, or 42; an LC-CDR2, wherein the LC-CDR2 has the amino acid sequence set forth in SEQ ID NO: 43; and an LC-CDR3, wherein the LC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 2 (depends on 1)

The antibody or antigen binding fragment of claim 1, wherein
(a) the HC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 17; the HC-CDR2 has the amino acid sequence set forth in SEQ ID NO:20; and the HC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 23; and
(b) the LC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 41; the LC-CDR2 has the amino acid sequence set forth in SEQ ID NO:43; and, the LC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 3 (depends on 2)

The antibody or antigen binding fragment of claim 2, wherein the antibody comprises:
(i) a VH having a framework selected from the group consisting of human VH1, VH2, VH3, VH4, VHS, and VH6 and a human IgG1 or IgG4 HC constant domain or variant thereof comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof compared to the amino acid sequence of the native IgG1 or IgG4 isotype HC constant domain; and,
(ii) a VL having a framework selected from the group consisting of human Vκ1, Vκ2, Vκ3, Vκ4, Vκ5, Vκ6, Vλ1, Vλ2, Vλ3, Vλ4, Vλ5, Vλ6, Vλ7, Vλ8, Vλ9, and Vλ10 and a human kappa or lambda LC constant domain or variant thereof comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof compared to the amino acid sequence of the native human kappa or lambda LC constant domain.

### Claim 4 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the antibody comprises a heavy chain (HC) constant domain comprising the amino acid sequence set forth in SEQ ID NO: 9, 10, 11, 12, or 13.

### Claim 5 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the antibody comprises a light chain (LC) constant domain comprising the amino acid sequence set forth in SEQ ID NO: 14.

### Claim 6 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence set forth in SEQ ID NO: 142, 143, 144, 148, 149, 150, 167, 168, 169, 170, 174, 175, 176, 177, 178, 182, 183, 184, 185, 186, 187, 191, 192, or 193.

### Claim 7 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the antibody comprises a light chain (LC) comprising the amino acid sequence set forth in SEQ ID NO: 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, or 166.

### Claim 8 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence set forth in SEQ ID NO: 143 and a light chain (LC) comprising the amino acid sequence set forth in SEQ ID NO: 165, and variants thereof wherein the HC lacks a C-terminal Lysine residue or a C-terminal glycine-lysine.

### Claim 9 (depends on 1)

The antibody or antigen binding fragment of claim 1, wherein the VH comprises a framework selected from the group consisting of human VH1, VH2, VH3, VH4, VH5, and VH6, and variants thereof having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof; and, the VL comprises a framework selected from the group consisting of human Vκ1, Vκ2, Vκ3, Vκ4, Vκ5, Vκ6, Vλ1, Vλ2, Vλ3, Vλ4, Vλ5, Vλ6, Vλ7, Vλ8, Vλ9, and Vλ10, and variants thereof having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof.

### Claim 10 (depends on 9)

The antibody or antigen binding fragment of claim 9, wherein the antibody or antigen binding fragment comprises a VH and a VL having the amino acid sequences set forth in SEQ ID NO: 15 and SEQ ID NO: 16, respectively; SEQ ID NO:45 and SEQ ID NO: 46, respectively; SEQ ID NO: 53 and SEQ ID NO: 54, respectively; SEQ ID NO: 61 and SEQ ID NO: 62, respectively; SEQ ID NO: 69 and SEQ ID NO: 70, respectively; SEQ ID NO: 77 and SEQ ID NO: 78, respectively; SEQ ID NO: 85 and SEQ ID NO: 86, respectively; SEQ ID NO: 93 and SEQ ID NO: 94, respectively; or SEQ ID NO:101 and SEQ ID NO: 102, respectively.

### Claim 11 (depends on 9)

The antibody or antigen binding fragment of claim 9, wherein the antibody or antigen binding fragment comprises a VH having the amino acid sequence set forth in SEQ ID NO: 117, 118, 119, 123, 124, or 125 and a VL having the amino acid sequence set forth in SEQ ID NO: 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141.

### Claim 12 (depends on 11)

The antibody or antigen binding fragment of claim 11, wherein the antibody or antigen binding fragment comprises a VH having the amino acid sequence set forth in SEQ ID NO: 118 and a VL having the amino acid sequence set forth in SEQ ID NO: 140.

### Claim 13 (depends on 1)

The antibody or antigen binding fragment of claim 1, wherein the antibody comprises an HC having a human IgG1, IgG2, IgG3, or IgG4 HC constant domain or variant thereof having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof compared to the amino acid sequence of the native IgG1, IgG2, IgG3, or IgG4 isotype constant domain.

### Claim 14 (depends on 13)

The antibody or antigen binding fragment of claim 13, wherein the antibody comprises an LC having a human kappa or lambda LC constant domain or variant thereof comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, additions, deletions, or combinations thereof compared to the amino acid sequence of the native human kappa or lambda light chain constant domain.

### Claim 15 (depends on 1)

A composition comprising:
an antibody or antigen binding fragment of claim 1 and a pharmaceutically acceptable carrier.

### Claim 16

An antibody or antigen binding fragment that binds the extracellular domain of human immunoglobulin-like transcript 3 (ILT3) having amino acids 1-238 of SEQ ID NO: 1, wherein the antibody or antigen binding fragment comprises
(a) a heavy chain complementarity determining region 1 (HC-CDR1), wherein the HC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 17; an HC-CDR2, wherein the HC-CDR2 has the amino acid sequence set forth in SEQ ID NO: 20; an HC-CDR3, wherein the HC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 23; and
(b) a light chain complementarity determining region 1 (LC-CDR1), wherein the LC-CDR1 has the amino acid sequence set forth in SEQ ID NO: 41; an LC-CDR2, wherein the LC-CDR2 has the amino acid sequence set forth in SEQ ID NO: 43; and an LC-CDR3, wherein the LC-CDR3 has the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 17 (depends on 16)

The antibody or antigen binding fragment of claim 16, wherein the antibody or antigen binding fragment comprises a VH and a VL having the amino acid sequences set forth in SEQ ID NO: 118 and SEQ ID NO: 140, respectively.

### Claim 18 (depends on 17)

The antibody or antigen binding fragment of claim 17, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence set forth in SEQ ID NO: 143 and a light chain (LC) comprising the amino acid sequence set forth in SEQ ID NO: 165, and variants thereof wherein the HC lacks a C-terminal Lysine residue or a C-terminal glycine-lysine.

### Claim 19 (depends on 16)

A composition comprising:
an antibody or antigen binding fragment of claim 16 and a pharmaceutically acceptable carrier.

### Claim 20 (depends on 17)

A composition comprising:
an antibody or antigen binding fragment of claim 17 and a pharmaceutically acceptable carrier.

### Claim 21 (depends on 18)

A composition comprising:
an antibody or antigen binding fragment of claim 18 and a pharmaceutically acceptable carrier.