# US 10,308,717 B2 · Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor

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- Number: US 10,308,717 B2
- Document ID: US10308717B2
- Status: Granted
- Kind: B2
- Application number: 15/182,775
- Filed: 2016-06-15
- Published: 2017-01-12
- Granted: 2019-06-04
- Earliest claimed: 2013-02-20
- Assignees: Novartis AG; The Trustees of the University of Pennsylvania; University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: Novartis AG; The Trustees of the University of Pennsylvania; University of Pittsburgh—of the Commonwealth System of Higher Education
- Inventors: Jennifer Brogdon; Laura Alexandra Johnson; Carl H. June; Andreas Loew; Marcela Maus; John Scholler; Hideho Okada
- Web page: https://patentgrep.com/patent/US10308717B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- 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 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 40/4204: {Epidermal growth factor receptors [EGFR]}
- A61K 40/4255: {Mesothelin [MSLN]}
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/3053: {Skin, nerves, brain}
- 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 2239/47: Brain; Nervous system
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- 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: 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

The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

## Claims

### Claim 1

A humanized anti-EGFRvIII binding domain comprising:
(a) a heavy chain immunoglobulin variable region comprising:
(i) a CDR1 comprising the sequence DYYIH (SEQ ID NO: 22);
(ii) a CDR2 comprising the sequence RIDPENDETKYGPIFQG (SEQ ID NO: 23); and
(iii) a CDR3 comprising the sequence RGGVY (SEQ ID NO: 24); and
(b) a light chain immunoglobulin variable region comprising:
(i) a CDR1 comprising the sequence KSSQSLLDSDGKTYLN (SEQ ID NO: 26);
(ii) a CDR2 comprising the sequence LVSKLDS (SEQ ID NO: 27); and
(iii) a CDR3 comprising the sequence WQGTHFPGT (SEQ ID NO: 28).

### Claim 2 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises an amino acid sequence with 99% sequence identity to SEQ ID NO:68.

### Claim 3 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises the amino acid sequence of SEQ ID NO:68.

### Claim 4 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises an scFv domain.

### Claim 5 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises a Fab domain.

### Claim 6 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises an amino acid sequence with 95% sequence identity to SEQ ID NO:68.

### Claim 7 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises an amino acid sequence having at least one, two or three modifications but not more than 10 modifications of an amino acid sequence of SEQ ID NO:68.

### Claim 8 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises the amino acid sequence of SEQ ID NO:50.

### Claim 9 (depends on 1)

The humanized anti-EGFRvIII binding domain of claim 1, wherein the humanized anti-EGFRvIII binding domain comprises the amino acid sequence of SEQ ID NO:80.