# US 12,180,294 B2 · Dimeric antigen receptors

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- Number: US 12,180,294 B2
- Document ID: US12180294B2
- Status: Granted
- Kind: B2
- Application number: 17/013,359
- Filed: 2020-09-04
- Published: 2020-12-24
- Granted: 2024-12-31
- Earliest claimed: 2018-03-09
- Assignees: Vivasor, Inc.
- Applicants: Sorrento Therapeutics, Inc.
- Inventors: Henry Hongjun Ji; Wenzhong Guo; Yanliang Zhang; Gunnar F. Kaufmann; Bei Bei Ding
- Web page: https://patentgrep.com/patent/US12180294B2

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4222: {CD38 not IgG}
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C12N 5/0636: {T lymphocytes}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- A61K 2039/5156: {expressing foreign proteins}
- A61K 2039/5158: {Antigen-pulsed cells, e.g. T-cells}
- A61K 2039/572: {cytotoxic response}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/53: Hinge
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/50: containing protease site
- C12N 2510/00: Genetically modified cells
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 4)

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

### Claim 6 (depends on 5)

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.

### Claim 7 (depends on 5)

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.

### Claim 8 (depends on 5)

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.

### Claim 9 (depends on 8)

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).

### Claim 10 (depends on 6)

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.