# US 10,870,705 B2 · Chimeric antigen receptors specific for carbonic acid anhydrase IX

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- Number: US 10,870,705 B2
- Document ID: US10870705B2
- Status: Granted
- Kind: B2
- Application number: 15/537,780
- Filed: 2015-12-21
- Published: 2018-02-01
- Granted: 2020-12-22
- Earliest claimed: 2014-12-19
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Dana-Farber Cancer Institute, Inc.
- Inventors: Wayne A. Marasco
- Web page: https://patentgrep.com/patent/US10870705B2

## CPC

- C07K 16/30: from tumour cells
- A61K 38/2013: {IL-2}
- 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 40/4244: {Enzymes}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/10: of the bladder
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70521: {CD28, CD152}
- C07K 16/40: against enzymes
- C12N 5/0636: {T lymphocytes}
- C12N 5/0637: {Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 9/88: Lyases (4.)
- C12Y 402/01001: Carbonate dehydratase (4.2.1.1), i.e. carbonic anhydrase
- A61K 2039/505: {comprising antibodies}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/56: Kidney
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/60: characterized by non-natural combinations of immunoglobulin fragments
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- 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)
- C12Y: ENZYMES

## Abstract

The present invention provides chimeric antigen receptor cells specific for carbonic anhydrase IX (CAIX) and methods of using same for treatment of CAIX expressing cancers such as renal cell carcinoma.

## Claims

### Claim 1

A chimeric antigen receptor (CAR) comprising an intracellular signaling domain, a transmembrane domain and an extracellular domain, wherein the extracellular domain comprises comprising a carbonic-anhydrase-IX (G250)-specific antibody or fragment thereof, wherein the intracellular signaling domain comprises a CD3 zeta chain.

### Claim 2 (depends on 1)

The CAR of claim 1, wherein the transmembrane domain further comprises a stalk region positioned between the extracellular domain and the transmembrane domain.

### Claim 3 (depends on 1)

The CAR of claim 1, wherein the transmembrane domain comprises CD28.

### Claim 4 (depends on 1)

The CAR of claim 1, further comprising one or more addition costimulatory molecules positioned between the transmembrane domain and the intracellular signaling domain.

### Claim 5 (depends on 4)

The CAR of claim 4, wherein the costimulatory molecules is CD28, 4-1BB, Inducible T cell costimulator (ICOS), or OX40.

### Claim 6 (depends on 1)

The CAR of claim 1, wherein the antibody is an Fab or scFV.

### Claim 7 (depends on 1)

The CAR of claim 1, wherein the antibody comprises (a) a heavy chain comprising
a CDR1 comprising an amino acid sequence SYAMS (SEQ ID NO: 55);
a CDR2 comprising an amino acid sequence AISANGGTTYYADSVKG (SEQ ID NO: 67); and
a CDR3 comprising an amino acid sequence NGNYRGAFDI (SEQ ID NO: 65); and (b)
a light chain with a CDR1 comprising an amino acid sequence TGSSSNIGAGFDVH (SEQ ID NO: 68), an amino acid sequence TGSSSNIGAGYDVH (SEQ ID NO: 61), or an amino acid sequence TGTSSNIGAGYDVH (SEQ ID NO: 81); a CDR2 comprising an amino acid sequence GNTNRPS (SEQ ID NO: 69), an amino acid sequence GNSNRPS (SEQ ID NO: 72), or an amino acid sequence GNNNRPS (SEQ ID NO: 62); and a CDR3 comprising an amino acid sequence QSYDSRLSAWV (SEQ ID NO: 70), an amino acid sequence QSYDRSLSWV (SEQ ID NO: 73), an amino acid sequence QSYDSTLRVWM (SEQ ID NO: 74), an amino acid sequence QSYDKSLTWV (SEQ ID NO: 76), an amino acid sequence QSYDKSLSWV (SEQ ID NO: 80), or an amino acid sequence QSYDSSLSAWV (SEQ ID NO: 82).

### Claim 8 (depends on 6)

The CAR of claim 6, wherein the scFv antibody has a heavy chain comprising an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs 1, 3-23, and wherein said scFv antibody has a light chain comprising an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs: 2 and 24-44.