Recombinant pseudomonas exotoxin with increased activity
AssigneeNational Institutes of Health
InventorsIra H. Pastan, David J. Fitzgerald
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Abstract
This invention relates to the production and use of recombinant Pseudomonas-derived toxins modified to increase their toxicity and potency in therapy. More particularly, the invention relates to certain deletions in domain II of the amino acid sequence of Pseudomonas exotoxin the domain which relates to the toxin's natural proteolytic processing.
Claims13
An isolated and purified recombinant Pseudomonas exotoxin (PE) fusion protein wherein a ligand binding agent is fused to a PE molecule in which domain Ia is deleted and from 1 to 28 amino acids from the amino terminal end of domain II are deleted.
An isolated and purified recombinant Pseudomonas exotoxin (PE) fusion protein wherein a ligand binding agent is fused to a PE molecule in which:
- (a) domain Ia is deleted;
- (b) from 1 to 28 amino acids from the amino terminal end of domain II are deleted;
- and,
- (c) a methionine residue is inserted at the resultant amino terminus of said molecule;
- (d) wherein the fusion protein is further characterized in that it is at least twenty times more cytotoxic to target cells bound by the ligand binding agent in a cytotoxicity assay when compared with an unmodified PE40 fused to the ligand binding agent.
Dependencies are inferred from the claim text.