# US 6,296,843 B1 · Mutagenized IL 13-based chimeric molecules

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- Number: US 6,296,843 B1
- Document ID: US6296843B1
- Status: Granted
- Kind: B1
- Application number: 09/054,711
- Filed: 1998-04-03
- Granted: 2001-10-02
- Earliest claimed: 1998-04-03
- Assignees: The Penn State Research Foundation
- Inventors: Waldemar Debinski
- Web page: https://patentgrep.com/patent/US6296843B1

## CPC

- C07K 14/21: from Pseudomonadaceae (F)
- A61P 35/00: Antineoplastic agents
- C07K 14/5437: {IL-13}
- 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)
- C07K 2319/00: Fusion polypeptide
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

This invention provides mutagenized interleukin 13 molecules that show improved specificity for the restricted (IL4 independent) IL13 receptor and reduced cross-reactivity with the IL4/IL4 shared receptor. The mutagenized IL13 molecules include one or more mutations in a domain that interacts with the 140 kDa hIL4Rβ or the hIL13Rα1 subunit. These mutagenized IL13 molecules provide effective targeting moieties in chimeric molecules (e.g. fusion proteins) that specifically deliver effector molecules (e.g. cytotoxins) to cells overexpressing IL13 receptors (e.g. cancer cells such as gliomas).

## Claims

### Claim 1

A chimeric molecule having the formula:
R1—(L)j—(R2)n
wherein R1 is a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
j is 0 or 1;
n is at least 1;
R2 is a cytotoxin; and
L is a linker.

### Claim 2 (depends on 1)

The chimeric molecule of claim 1, wherein said cytotoxin is selected from a group consisting of PE4E and PE38QQR.

### Claim 3 (depends on 1)

The chimeric molecule of claim 1, wherein said linker is a peptide linker.

### Claim 4 (depends on 1)

The chimeric molecule of claim 1, wherein L or R2, if present, are attached to the carboxyl terminus of R1.

### Claim 5 (depends on 1)

The chimeric molecule of claim 1, wherein L or R2, if present, are attached to the amino terminus of R1.

### Claim 6

A method of delivering an effector molecule to a cell bearing an interleukin 13 receptor (IL13R), said method comprising the step of contacting said cell with a chimeric molecule comprising said effector molecule attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.

### Claim 7 (depends on 6)

The method of claim 6, wherein said effector molecule is a cytotoxin selected from a group consisting of PE4E and PE38QQR.

### Claim 8

A method of inhibiting the growth of a cell expressing an IL13 receptor (IL13R), said method comprising contacting said cell with a cytotoxic molecule comprising a cytotoxin covalently attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.

### Claim 9 (depends on 8)

The method of claim 8, wherein said cytotoxin is selected from the group consisting of PE38QQR and PE4E.

### Claim 10 (depends on 8)

The method of claim 8, wherein said cell is a neoplastic cell.

### Claim 11

A pharmaceutical composition comprising
a pharmacologically acceptable excipient; and
a cytotoxic molecule comprising a cytotoxin covalently attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.

### Claim 12 (depends on 11)

The composition of claim 11, wherein said cytotoxin is selected from the group consisting of PE38QQR and PE4E.