Chlorotoxin polypeptides and conjugates and uses thereof
Inventors
Sentissi, Abdellah • Jacoby, Douglas B.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10183975-B2
Publication Date
2019-01-22
Expiration Date
Abstract
Reduced lysine chlorotoxin polypeptides that may be used to generate single species conjugates of chlorotoxin. Conjugates comprising such chlorotoxin polypeptides and pharmaceutical compositions thereof. Methods of using such compositions and/or conjugates.
Core Innovation
The invention relates to reduced-lysine chlorotoxin polypeptides based on SEQ ID NO: 1, in which the modified chlorotoxin peptide comprises a single lysine residue and is at least 90% sequence identity with SEQ ID NO: 1. By reducing lysine availability, the chlorotoxin system enables production of single-species chlorotoxin conjugates rather than mixed conjugate populations.
The modified chlorotoxin peptide comprises a single lysine residue located at a lysine position corresponding to positions 15, 23, or 27 of SEQ ID NO: 1, and substitutions at specified lysine positions generate reduced-lysine variants. The conjugates are covalently coupled to a conjugated agent using linkers or chemistries associated with attachment via the single lysine residue, and in some cases using termini-based attachment.
The reduced-lysine chlorotoxin conjugates are described for targeting cancer, where cancer is treated by contacting the cancer with a chlorotoxin conjugate comprising the modified chlorotoxin peptide and an anti-cancer agent. The described anti-cancer agents include anti-cancer drug entities, nucleic acids, photosensitizers, radiosensitizers and radioisotopes, superantigens, prodrug-activating enzymes, and pharmaceutical composition concepts for administration.
Claims Coverage
The independent claim covers a cancer-treatment method by contacting cancer with a chlorotoxin conjugate that combines a modified chlorotoxin peptide with at least 90% sequence identity to SEQ ID NO: 1, a reduced-lysine design having a single lysine residue, and covalent coupling to an anti-cancer agent.
Single-lysine modified chlorotoxin peptide with sequence identity to SEQ ID NO: 1
A chlorotoxin conjugate comprises a modified chlorotoxin peptide having at least 90% sequence identity with SEQ ID NO: 1, and the modified chlorotoxin peptide comprises a single lysine residue.
Covalent coupling to an anti-cancer agent
The single-lysine modified chlorotoxin peptide is covalently coupled to an anti-cancer agent, and the method comprises contacting the cancer with the chlorotoxin conjugate.
Overall claim coverage is anchored on a chlorotoxin conjugate in which the modified chlorotoxin peptide is engineered to include a single lysine residue and is covalently coupled to an anti-cancer agent for treating cancer by contacting the cancer with the conjugate.
Stated Advantages
Enables generation of single-species chlorotoxin conjugates rather than mixed conjugate populations.
Documented Applications
Treating cancer by contacting cancer with a chlorotoxin conjugate comprising a modified chlorotoxin peptide and an anti-cancer agent.
Targeting neuroectodermal tumors, wherein the neuroectodermal tumor is a glioma.
Interested in licensing this patent?