# US 2022/0031748 A1 · Compositions and methods for treating cancer

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- Number: US 2022/0031748 A1
- Document ID: US20220031748A1
- Status: Published application
- Kind: A1
- Application number: 17/307,235
- Filed: 2021-05-04
- Published: 2022-02-03
- Earliest claimed: 2020-05-05
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: David DiLillo; Thomas Craig Meagher
- Web page: https://patentgrep.com/patent/US20220031748A1

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 16/30: from tumour cells
- 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 40/4245: {Tyrosinase or tyrosinase related proteinases [TRP-1 or TRP-2]}
- A61K 40/4268: {MAGE}
- A61K 40/4269: {NY-ESO}
- A61P 35/00: Antineoplastic agents
- 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)}
- C07K 16/085: Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- 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 2039/876: {Skin, melanoma}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/57: Skin; melanoma
- 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 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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: 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

Disclosed are compositions and methods for targeted treatment of cancer. The present disclosure provides chimeric antigen receptors and cells expressing such chimeric antigen receptors. In certain embodiments, engineered cells expressing the chimeric antigen receptors are specific for a low density cancer antigen or peptide in groove antigen.

## Claims

### Claim 1

A CAR polypeptide comprising:
a) at least one intracytoplasmic/costimulatory region comprising a cluster of differentiation 28 zeta (CD28/ζ) domain,
b) at least one intracytoplasmic signaling region comprising a cluster of differentiation 3 zeta (CD3/ζ) domain, and
c) an antigen binding domain specific for a peptide in groove cancer antigen.

### Claim 2 (depends on 1)

The CAR polypeptide of claim 1, wherein
(i) the intracytoplasmic/costimulatory region of the CAR polypeptide further comprises a 4-1BB domain,
(ii) the hinge/spacer region of the CAR comprises at least one cluster of differentiation 28 zeta (CD28/ζ) domain, or
(iii) the transmembrane region of the CAR comprises at least one cluster of differentiation 28 zeta (CD28/ζ) domain.

### Claim at position 3

3-4. (canceled)

### Claim 5 (depends on 1)

The CAR polypeptide of claim 1, wherein the CAR comprises at least one cluster of differentiation 28 zeta (CD28/ζ) amino acid sequence selected from the amino acid sequences set forth in SEQ ID NOs. 1 to 3.

### Claim 6 (depends on 5)

The CAR polypeptide of claim 5, wherein at least one cluster of differentiation 28 (CD28) amino acid sequence is part of the intracytoplasmic/costimulatory region, the transmembrane region, or the hinge/spacer region of the CAR.

### Claim at position 6

7-8. (canceled)

### Claim 9 (depends on 1)

The CAR polypeptide of claim 1, wherein the cancer antigen is a MAGEA4, Tyrosinase, HPV16 E7, or a NY-ESO peptide.

### Claim 10 (depends on 9)

The CAR polypeptide of claim 9, wherein the CAR is specific for an antigen comprising at least one epitope selected from MAGEA4230-239, MAGEA4286-294, Tyr369-377, HPV16E711-19 or NY-ESO-1157-165.

### Claim 11

A CAR polypeptide having antigenic specificity for a peptide in groove cancer antigen and the CAR comprises an amino acid sequence set forth in SEQ ID NOs: 7, 9, 11, 13, 30, or 34.

### Claim 12 (depends on 1)

The CAR polypeptide of claim 1, wherein the CAR polypeptide comprises
(i) a variable light chain comprising any one of the amino acid sequences set forth in SEQ ID NOs: 16 to 19, 31, or 37, or
(ii) a variable heavy chain comprising any one of the amino acid sequences set forth in SEQ ID NOs: 20 to 23, 32, or 38.

### Claim 13

(canceled)

### Claim 14 (depends on 1)

A composition comprising immune cells expressing the CAR of claim 1.

### Claim 15 (depends on 1)

A nucleic acid encoding the CAR polypeptide of claim 1.

### Claim 16

(canceled)

### Claim 17 (depends on 15)

The nucleic acid of claim 15, wherein the nucleic acid has a sequence set forth in SEQ ID NOs: 14, 15, 35 or 36.

### Claim at position 16

18-19. (canceled)

### Claim 20 (depends on 15)

An immune cell comprising the nucleic acid of claim 15.

### Claim 21 (depends on 1)

An immune cell expressing the CAR polypeptide of claim 1.

### Claim 22 (depends on 20)

The immune cell of claim 20, wherein the immune cell is a leukocyte, a lymphocyte, a monocyte, a macrophage, a dendritic cell, a mast cell, a neutrophil, a basophil, an eosinophil, an αβT cell, γδT cell, a Natural Killer (NK) cell, a Natural Killer T (NKT) cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, or a regulatory T cell.

### Claim at position 20

23-25. (canceled)

### Claim 26

A method of treating a tumor in a subject, the method comprising administering a composition comprising cells expressing a CAR polypeptide comprising:
a) at least one intracytoplasmic/costimulatory region comprising a cluster of differentiation 28 zeta (CD28/ζ) domain,
b) at least one intracytoplasmic signaling region comprising a cluster of differentiation 3 zeta (CD3/ζ) domain, and
c) an antigen binding domain specific for a peptide in groove antigen.

### Claim 27 (depends on 26)

The method of claim 26, wherein the CAR comprises at least one CD28/ζ domain in the hinge/spacer region or the transmembrane region of the CAR.

### Claim 28

(canceled)

### Claim 29 (depends on 26)

The method of claim 26, wherein at least one cluster of differentiation 28 zeta (CD28/ζ) amino acid sequence selected from the amino acid sequences set forth in SEQ ID NOs. 1 to 3.

### Claim 30 (depends on 26)

The method of claim 26, wherein the method further comprises conjointly administering to the subject a second CAR polypeptide comprising:
a) a 4-1BB domain in the costimulatory region of the CAR polypeptide, b) at least one intracytoplasmic signaling region comprising a cluster of differentiation 3 zeta (CD3/ζ) domain, and
c) an extracellular domain specific for a peptide in groove cancer antigen.

### Claim 31 (depends on 30)

The method of claim 30, wherein the second CAR polypeptide comprises a cluster of differentiation 8 alpha (CD8/α) peptide in the hinge/transmembrane region.

### Claim 32 (depends on 1)

A cell bank comprising cells for adoptive immunotherapy, wherein the cells express the CAR of claim 1.