Toxins and radionuclides coupled to IGF-1 receptor ligands for treatment of cancer
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Publication Number
US-8017102-B2
Publication Date
2011-09-13
Expiration Date
Abstract
The invention provides an insulin-like growth factor-1 (IGF-1) receptor ligand carrying a therapeutic radionuclide for treatment of cancer is provided. A method of treating cancer using the IGF-1 receptor ligand carrying a therapeutic radionuclide is also provided. An anti-cancer therapeutic agent containing an IGF-1 receptor ligand linked to a toxin is also provided, as are methods of using the toxin conjugates for treatment of cancer.
Core Innovation
The document describes anti-cancer therapeutic agents that target the insulin-like growth factor-1 (IGF-1) receptor by linking an IGF-1 receptor ligand to a toxin. The IGF-1 receptor ligand is defined by specific polypeptide sequence identities, and the toxin is defined by specified residue regions or a specific toxin chain.
In particular, the conjugates include an IGF-1 receptor ligand comprising a polypeptide sequence at least 90% identical to SEQ ID NO:1 linked to a toxin comprising Clostridium perfringens enterotoxin residues 45-116 of SEQ ID NO:4. Alternative embodiments include an IGF-1 receptor ligand comprising SEQ ID NO:2 linked to Clostridium perfringens enterotoxin residues 45-116 of SEQ ID NO:4.
Additional embodiments described in the document include an IGF-1 receptor ligand comprising a polypeptide sequence at least 90% identical to SEQ ID NO:1 linked to diphtheria toxin residues 1-193 of SEQ ID NO:5, and an IGF-1 receptor ligand comprising at least 90% sequence identity to SEQ ID NO:1 linked to ricin chain A. The document further describes embodiments where the IGF-1 receptor ligand comprises SEQ ID NO:2 linked to ricin chain A, and where SEQ ID NO:2 is linked to diphtheria toxin residues 1-193 of SEQ ID NO:5.
Claims Coverage
The provided claim set includes six independent claims. Each independent claim is directed to an anti-cancer therapeutic agent comprising an IGF-1 receptor ligand linked to a toxin, with inventive structure defined by IGF-1 ligand sequence identity or exact sequence ID and by specific toxin residue ranges or toxin chain identity.
IGF-1 receptor ligand with at least 90% identity to SEQ ID NO:1 linked to Clostridium perfringens enterotoxin residues 45-116
An anti-cancer therapeutic agent comprising an insulin-like growth factor-1 (IGF-1) receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises a polypeptide sequence at least 90% identical to SEQ ID NO:1, and wherein the toxin comprises Clostridium perfringens enteroxin residues 45-116 of SEQ ID NO:4.
IGF-1 receptor ligand comprising SEQ ID NO:2 linked to Clostridium perfringens enterotoxin residues 45-116
An anti-cancer therapeutic agent comprising an insulin-like growth factor-1 (IGF-1) receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises SEQ ID NO:2, and wherein the toxin comprises Clostridium perfringens enteroxin residues 45-116 of SEQ ID NO:4.
IGF-1 receptor ligand with at least 90% identity to SEQ ID NO:1 linked to diphtheria toxin residues 1-193
An anti-cancer therapeutic agent comprising an insulin-like growth factor-1 (IGF-1) receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises a polypeptide sequence at least 90% identical to SEQ ID NO:1, and wherein the toxin comprises diphtheria toxin residues 1-193 of SEQ ID NO:5.
IGF-1 receptor ligand with at least 90% identity to SEQ ID NO:1 linked to ricin chain A
An anti-cancer therapeutic agent comprising an IGF-1 receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises a polypeptide sequence at least 90% identical to SEQ ID NO:1, and wherein the toxin comprises ricin chain A.
IGF-1 receptor ligand comprising SEQ ID NO:2 linked to diphtheria toxin residues 1-193
An anti-cancer therapeutic agent comprising an insulin-like growth factor-1 (IGF-1) receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises SEQ ID NO:2, and wherein the toxin comprises diphtheria toxin residues 1-193 of SEQ ID NO:5.
IGF-1 receptor ligand comprising SEQ ID NO:2 linked to ricin chain A
An anti-cancer therapeutic agent comprising an IGF-1 receptor ligand linked to a toxin, wherein the IGF-1 receptor ligand comprises SEQ ID NO:2, and wherein the toxin comprises ricin chain A.
Across all independent claims, the inventive concept is an anti-cancer therapeutic agent in which an IGF-1 receptor ligand, defined by at least 90% identity to SEQ ID NO:1 or by SEQ ID NO:2, is linked to a toxin defined by specific toxin residue ranges of Clostridium perfringens enterotoxin or diphtheria toxin, or by ricin chain A.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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