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US 6,203,794 B1Granted
Modification of clostridial toxins for use as transport proteins
AssigneeAllergan Sales, Inc.
InventorsJames Oliver Dolly, Kei Roger Aoki, Larry Allen Wheeler, Michael Elwood Garst
Life of this patent
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Abstract
A chemical conjugate for treating a nerve cell related disorder is provided. The conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.
Claims14
A composition comprising,
- a) an inactive Clostridial neurotoxin comprising
- i) a light chain containing one or more amino acid sequence mutation as compared to the amino acid sequence of the light chain of a wild-type Clostridial neurotoxin of the same type and from the same species, wherein said light chain is inactivated by at least one said amino acid mutation, and
- ii) an unaltered Clostridial neurotoxin heavy chain which has binding specificity for a target nerve cell;
- and
- b) a drug or other bioactive molecule joined to the inactivated light chain of said inactive neurotoxin,
- wherein said inactive neurotoxin is internalizable by said target nerve cell.
3 more elements
A pharmaceutical composition for treatment of a neuromuscular dysfunction in a mammal, comprising:
- a) an inactive Clostridial neurotoxin comprising
- i) a light chain containing one or more amino acid sequence mutation as compared to the amino acid sequence of the light chain of a wild-type Clostridial neurotoxin of the same type and from the same species, wherein said light chain is inactivated by at least one said amino acid mutation, and
- ii) an unaltered Clostridial neurotoxin heavy chain which has binding specificity for a target nerve cell;
- and
- b) a drug or other bioactive molecule joined to the inactivated light chain of said inactive neurotoxin,
- wherein said inactive neurotoxin is internalizable by said target nerve cell, and a pharmaceutically acceptable excipient.
3 more elements
A method for treating a mammal having acute botulinum poisoning, comprising:
- introducing into said mammal an effective quantity of a pharmaceutically active solution comprising
- a) an inactive Clostridial neurotoxin comprising
- i) a light chain containing one or more amino acid sequence mutation as compared to the amino acid sequence of the light chain of a wild-type Clostridial neurotoxin of the same type and from the same species, wherein said light chain is inactivated by at least one said amino acid mutation, and
- ii) an unaltered Clostridial neurotoxin heavy chain which has binding specificity for a target nerve cell;
- and
- b) a drug or other bioactive molecule joined to the inactivated light chain of said inactive neurotoxin,
- wherein said inactive neurotoxin is internalizable by said target nerve cell, thereby lessening the effects of said acute botulinum poisoning.
4 more elements
Dependencies are inferred from the claim text.