# US 12,110,326 B2 · Anti-ILT3 antibodies and antibody drug conjugates

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- Number: US 12,110,326 B2
- Document ID: US12110326B2
- Status: Granted
- Kind: B2
- Application number: 17/585,815
- Filed: 2022-01-27
- Published: 2022-07-21
- Granted: 2024-10-08
- Earliest claimed: 2017-02-09
- Assignees: Bluefin BioMedicine, Inc.
- Applicants: Bluefin BioMedicine, Inc.
- Inventors: Jaime Rene Darce; Scott Michael Lonning; Nels Eric Pederson; Klarisa Rikova; Aleksandr Tkachev
- Web page: https://patentgrep.com/patent/US12110326B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 47/6825: {Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61K 2039/507: {Comprising a combination of two or more separate 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 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/77: Internalization into the cell
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are anti-immunoglobulin-like transcript-3 (ILT3) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.

## Claims

### Claim 1

An isolated antibody, or antigen binding portion thereof, that binds to immunoglobulin-like transcript 3 (ILT3), wherein the antibody, or antigen binding portion thereof, comprises:
a heavy chain variable region that is at least 95% identical to SEQ ID NO: 81 and a light chain variable region that is at least 95% identical to SEQ ID NO: 84;
a heavy chain variable region that is at least 95% identical to SEQ ID NO: 1 and a light chain variable region that is at least 95% identical to SEQ ID NO: 5;
a heavy chain variable region that is at least 95% identical to SEQ ID NO: 53 and a light chain variable region that is at least 95% identical to SEQ ID NO: 57;
a heavy chain variable region that is at least 95% identical to SEQ ID NO: 74 and a light chain variable region that is at least 95% identical to SEQ ID NO: 78; or
a heavy chain variable region that is at least 95% identical to SEQ ID NO: 104 and a light chain variable region that is at least 95% identical to SEQ ID NO: 100.

### Claim 2 (depends on 1)

The isolated antibody, or antigen binding portion thereof, of claim 1, wherein
the antibody, or antigen binding portion thereof, comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 48, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 83, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 82, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 52, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 73, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 50;
the antibody, or antigen binding portion thereof, comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 2, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6;
the antibody, or antigen binding portion thereof, comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 56, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 55, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 54, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 60, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 59, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 58;
the antibody, or antigen binding portion thereof, comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 76, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 75, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 60, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 73, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 50; or
the antibody, or antigen binding portion thereof, comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 106, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 105, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 62, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 60, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 73, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 50.

### Claim 3 (depends on 1, 2)

An isolated nucleic acid encoding the antibody, or antigen binding portion thereof, of claim 1 or claim 2.

### Claim 4 (depends on 1, 2)

A pharmaceutical composition comprising the antibody, or antigen binding portion thereof, of claim 1 or claim 2, and a pharmaceutically acceptable carrier.

### Claim 5 (depends on 1, 2)

An antibody, or antigen binding portion thereof, of claim 1 or claim 2, conjugated to at least one drug.

### Claim 6 (depends on 5)

The antibody, or antigen binding portion thereof, of claim 5, wherein the at least one drug is selected from the group consisting of an anti-apoptotic agent, a mitotic inhibitor, an anti-tumor antibiotic, an immunomodulating agent, a nucleic acid for gene therapy, an anti-angiogenic agent, an anti-metabolite, a boron-containing agent, a chemoprotective agent, a hormone agent, an anti-hormone agent, a corticosteroid, a photoactive therapeutic agent, an oligonucleotide, a radionuclide agent, a radiosensitizer, a topoisomerase inhibitor, and a tyrosine kinase inhibitor.

### Claim 7 (depends on 5)

The antibody, or antigen binding portion thereof, of claim 5, wherein the at least one drug is conjugated to the antibody, or antigen-binding portion thereof, via a linker.

### Claim 8 (depends on 5)

The antibody, or antigen binding portion thereof, of claim 5, wherein the antibody, or antigen binding portion thereof, is an IgG1 or IgG4 isotype.

### Claim 9 (depends on 1, 2)

A method for treating cancer, comprising administering a therapeutically effective amount of the antibody, or antigen binding portion thereof, of claim 1 or claim 2 to a subject in need thereof.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cancer is triple negative breast cancer (TNBC), acute myeloid leukemia, prostate cancer, breast cancer, lung cancer, colon cancer, colorectal cancer, melanomas, bladder cancer, brain/CNS cancer, cervical cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lymphomas, ovarian cancer, pancreatic cancer, or sarcomas.

### Claim 11 (depends on 9)

The method of claim 9, wherein the antibody, or antigen binding portion thereof, is administered in combination with an immune checkpoint inhibitor.

### Claim 12 (depends on 1, 2)

A method for inhibiting or decreasing solid tumor growth in a subject having a solid tumor, said method comprising administering an effective amount of the antibody or antigen binding portion thereof of claim 1 or claim 2, to the subject having the solid tumor, such that the solid tumor growth is inhibited or decreased.

### Claim 13 (depends on 12)

The method of claim 12, wherein the antibody or antigen binding portion thereof is administered in combination with an additional agent or an additional therapy.

### Claim 14 (depends on 13)

The method of claim 13, wherein the additional agent is an immune checkpoint inhibitor.

### Claim 15 (depends on 1, 2)

A method for upregulating an immune response in a subject, comprising administering a therapeutically effective amount of the antibody or antigen binding portion thereof of claim 1 or claim 2 to the subject, thereby upregulating the immune response in the subject.

### Claim 16 (depends on 15)

The method of claim 15, wherein the antibody, or antigen binding portion thereof, is administered in combination with an additional agent or an additional therapy.

### Claim 17 (depends on 16)

The method of claim 16, wherein the additional agent is an immune checkpoint inhibitor.

### Claim 18 (depends on 15)

The method of claim 15, wherein the subject has cancer.

### Claim 19 (depends on 1, 2)

A method for increasing T cell activation in a subject, comprising administering a therapeutically effective amount of the antibody, or antigen binding portion thereof, of claim 1 or claim 2 to the subject, thereby increasing T cell activation in the subject.

### Claim 20 (depends on 19)

The method of claim 19, wherein the antibody, or antigen binding portion thereof, is administered in combination with an additional agent or an additional therapy.

### Claim 21 (depends on 20)

The method of claim 20, wherein the additional agent is an immune checkpoint inhibitor.

### Claim 22 (depends on 19)

The method of claim 19, wherein the subject has cancer.
