Dimeric antigen receptors

Patent metadata

Field	Value
Publication number	US-12180294-B2
Application number	US-202017013359-A
Country	US
Kind code	B2
Filing date	Sep 4, 2020
Priority date	Mar 9, 2018
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

The present disclosure provides dimeric antigen receptors (DAR) constructs comprising a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. The dimeric antigen receptors can be used for directed cell therapy.

First claim

What is claimed:

1. A nucleic acid encoding a precursor polypeptide comprising ten regions ordered from the amino terminus to the carboxyl terminus: (1) a heavy chain leader sequence, (2) an antibody heavy chain variable region comprising a CD38 antibody heavy chain variable region which comprises the amino acid sequence of SEQ ID NO:1, (3) an antibody heavy chain constant region, (4) an optional hinge region, (5) a transmembrane region, (6) an intracellular signaling region, (7) a T2A cleavage sequence, (8) a light chain leader sequence, (9) an antibody light chain variable region comprising a CD38 antibody light chain variable region which comprises the amino acid sequence of SEQ ID NO:3, and (10) an antibody light chain constant region.

2. The nucleic acid of claim 1 , comprising (4) the hinge region.

3. The nucleic acid of claim 1 , wherein (1) the heavy chain leader sequence comprises the amino acid sequence of SEQ ID NO: 10; (3) the antibody heavy chain constant region comprises a CD38 antibody heavy chain constant region which comprises the amino acid sequence of SEQ ID NO:2; (4) the hinge region is selected from a group consisting of a CD28 hinge region comprising the amino acid sequence of SEQ ID NO:5, a CD8 hinge region comprising the amino acid sequence of SEQ ID NO:21, and a hinge region comprising a CD28 hinge region comprising the amino acid sequence of SEQ ID NO:5 and a CD8 hinge region comprising the amino acid sequence of SEQ ID NO:21; (5) the transmembrane region comprises a CD28 transmembrane region which comprises the amino acid sequence of SEQ ID NO:6; (6) the intracellular signaling region comprises any one or any combination of two or more signaling sequences selected from a group consisting of 4-1BB signaling sequence comprising the amino acid sequence of SEQ ID NO:7, CD28 signaling sequence comprising the amino acid sequence of SEQ ID NO:8, CD3zeta (long) signaling sequence comprising the amino acid sequence of SEQ ID NO:9 and/or CD3zeta (short) signaling sequence having an ITAM 3 motif and comprising the amino acid sequence of SEQ ID NO:20; (7) the T2A cleavage sequence comprises the amino acid sequence of SEQ ID NO:12; (8) the light chain leader sequence comprises the amino acid sequence of SEQ ID NO: 11; and (10) the antibody light chain constant region comprises a CD38 antibody light chain constant region which comprises the amino acid sequence of SEQ ID NO:4.

4. A vector operably linked to the nucleic acid of claim 1 .

5. A host cell or a population of host cells harboring the vector of claim 4 .

6. The host cell of claim 5 , wherein the vector is an expression vector, and wherein the expression vector directs transcription and/or translation (expression) of the nucleic acid.

7. The host cell or the population of host cells of claim 5 , wherein the host cell or the population of host cells comprise T lymphocytes (T cells, regulatory T cells, gamma-delta T cells or cytotoxic T cells), NK (natural killer) cells, macrophages, dendritic cells, mast cells, eosinophils, B lymphocytes or monocytes.

8. A method for treating a subject having a disease, disorder or condition associated with detrimental expression of a tumor antigen in the subject, comprising: administering to the subject the host cell or the population of host cells of claim 5 .

9. The method of claim 8 , wherein the disease is a hematologic cancer selected from the group consisting of non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), B chronic lymphocytic leukemia (B-CLL), B and T acute lymphocytic leukemia (ALL), T cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's Lymphoma (HL), chronic myeloid leukemia (CML) and multiple myeloma (MM).

10. A method for treating a subject having a disease, disorder or condition associated with detrimental expression of a tumor antigen in the subject, comprising: administering to the subject the host cell or the population of host cells of claim 6 .

Assignees

• Sorrento Therapeutics Inc
• Vivasor Inc

Inventors

• Ji Henry Hongjun
• Guo Wenzhong
• Zhang Yanliang
• Kaufmann Gunnar F
• Ding Bei Bei

Classifications

• A61K2039/5158

  Antigen-pulsed cells, e.g. T-cells · CPC title

• A61K2039/5156

  expressing foreign proteins · CPC title

• A61K35/17

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title

• A61K40/4222

  CD38 not IgG · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title