# US 10,308,719 B2 · IL13Rα2 binding agents and use thereof in cancer treatment

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- Number: US 10,308,719 B2
- Document ID: US10308719B2
- Status: Granted
- Kind: B2
- Application number: 15/545,945
- Filed: 2016-01-26
- Published: 2018-05-17
- Granted: 2019-06-04
- Earliest claimed: 2015-01-26
- Assignees: The University of Chicago
- Applicants: The University of Chicago
- Inventors: Irina V. Balyasnikova; Maciej S. Lesniak
- Web page: https://patentgrep.com/patent/US10308719B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- 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 40/4217: {Receptors for interleukins [IL]}
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70521: {CD28, CD152}
- C07K 14/7155: {for interleukins [IL]}
- C07K 16/3053: {Skin, nerves, brain}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- G01N 33/52: Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)}
- G01N 33/532: Production of labelled immunochemicals
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/13: Antibody-based
- A61K 2239/47: Brain; Nervous system
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/21: containing a His-tag
- C07K 2319/41: containing a Myc-tag
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- G01N 33/5091: {for testing the pathological state of an organism}
- G01N 2333/71: for growth factors; for growth regulators
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided are specific binding molecules, or fragments thereof, that bind to an epitope of IL13Rα2, a receptor polypeptide preferentially found on the surface of cancer cells rather than healthy cells. Exemplary specific binding molecules are bispecific binding molecules that comprise a fragment of an IL13Rα2 binding molecule and a peptide providing a second function providing a signaling function of the signaling domain of a T cell signaling protein, a peptide modulator of T cell activation, or an enzymatic component of a labeling system. Also provided are polynucleotides encoding such a specific binding molecule (e.g., bispecific binding molecule), vectors, host cells, pharmaceutical compositions and methods of preventing, treating or ameliorating a symptom associated with a cancer disease such as a solid tumor disease (e.g., glioblastoma multiforme).

## Claims

### Claim 1

An IL13Rα2 binding agent comprising each of the amino acid sequences of:
(a) complementarity determining region 1 (NYLMN (SEQ ID NO: 1));
(b) complementarity determining region 2 (RIDPYDGDIDYNQNFKD (SEQ ID NO: 2));
(c) complementarity determining region 3 (GYGTAYGVDY (SEQ ID NO: 3));
(d) complementarity determining region 4 (RASESVDNYGISFMN (SEQ ID NO: 4));
(e) complementarity determining region 5 (AASRQGSG (SEQ ID NO: 5)); and
(f) complementarity determining region 6 (QQSKEVPWT (SEQ ID NO: 6)).

### Claim 2 (depends on 1)

The IL13Rα2 binding agent of claim 1, comprising one or both of the amino acid sequences of SEQ ID NO: 7 and/or SEQ ID NO: 8.

### Claim 3 (depends on 2)

The IL13Rα2 binding agent of claim 2, wherein the amino acid sequence of SEQ ID NO: 7 is fused to the amino acid sequence of SEQ ID NO: 8 through a linker comprising the amino acid sequence of SEQ ID NO:10.

### Claim 4 (depends on 3)

The IL13Rα2 binding agent of claim 3, comprising the amino acid sequence of SEQ ID NO: 13.

### Claim 5 (depends on 1)

The IL13Rα2 binding agent of claim 1 further comprising an amino acid sequence of SEQ ID NO: 28, an amino acid sequence which is at least 90% identical to SEQ ID NO: 28, an amino acid sequence of SEQ ID NO: 30, or an amino acid sequence that is at least 90% identical to SEQ ID NO: 30.

### Claim 6 (depends on 1)

The IL13Rα2 binding agent of claim 1, which is an antibody, an antigen-binding fragment thereof that comprises the amino acid sequences of SEQ ID NOs: 1-6, or an antigen binding fragment thereof that is a single chain variable fragment (scFv).

### Claim 7 (depends on 6)

The IL13Rα2 binding agent of claim 6, wherein the binding agent is the scFv and wherein the binding agent further comprises an Ig kappa leader sequence of METDTLLLWVLLLWVPGSTGD (SEQ ID NO: 9).

### Claim 8 (depends on 7)

The IL13Rα2 binding agent of claim 7, further comprising a linker sequence of EEGEFSEAR (SEQ ID NO 10), a Myc tag sequence of GGPEQKLISEEDLN (SEQ ID NO: 11), or a His tag sequence of HHHHHH (SEQ ID NO: 12).

### Claim 9 (depends on 7)

The IL13Rα2 binding agent of claim 7, comprising the amino acid sequence of SEQ ID NO: 14.

### Claim 10 (depends on 1)

The IL13Rα2 binding agent of claim 1, which binds to human IL13Rα2 but does not bind to human IL13Rα1.

### Claim 11 (depends on 1)

The IL13Rα2 binding agent of claim 1 having an equilibrium dissociation constant (KD) for human IL13Rα2 which is no greater than about 1.39×10-9 M.

### Claim 12 (depends on 1)

The IL13Rα2 binding agent of claim 1, wherein the binding agent is covalently linked to an effector domain in a conjugate.

### Claim 13 (depends on 12)

The conjugate of claim 12, wherein the effector domain is a cytotoxin, an apoptosis tag, a T-cell signaling domain, or a label.

### Claim 14 (depends on 13)

The conjugate of claim 13, wherein the apoptosis tag is a TRAIL protein, or a portion thereof, optionally, wherein the apoptosis tag comprises the amino acid sequence of SEQ ID NO: 27.

### Claim 15 (depends on 1)

A nucleic acid encoding the IL13Rα2 binding agent of claim 1.

### Claim 16 (depends on 15)

The nucleic acid of claim 15, comprising the sequence of SEQ ID NO: 15 or SEQ ID NO: 16, or both SEQ ID NOs: 15 and 16.

### Claim 17 (depends on 15)

The nucleic acid of claim 15, wherein the nucleic acid is localized in a vector.

### Claim 18 (depends on 15)

The nucleic acid of claim 15 wherein the polynucleotide is Ad5FFscFv47.

### Claim 19 (depends on 17)

The vector of claim 17, wherein the vector is localized in a host cell.

### Claim 20 (depends on 1)

The binding agent of claim 1, wherein the binding agent is combined with a pharmaceutically acceptable carrier in a pharmaceutical composition.

### Claim 21 (depends on 1)

A method of treating glioblastoma multiforme or colon cancer in a subject, comprising administering to the subject a binding agent of claim 1, in an amount effective to treat the cancer in the subject.