Claims for Patent: 6,312,708

Summary for Patent: 6,312,708

Title:	Botulinum toxin implant
Abstract:	A controlled release system for multiphasic, in vivo release of therapeutic amounts of botulinum toxin in a human patient over a prolonged period of time. The controlled release system can comprise a plurality of botulinum toxin incorporating polymeric microspheres.
Inventor(s):	Donovan; Stephen (Capistrano Beach, CA)
Assignee:	Allergan Sales, Inc. (Irvine, CA)
Application Number:	09/624,003
Patent Claims:	1. A pulsatile release botulinum toxin delivery system, comprising: (a) a carrier; (b) a botulinum toxin associated with the carrier, thereby forming a pulsatile release botulinum toxin delivery system, wherein therapeutic amounts of the botulinum toxin can be released from the carrier in a plurality of pulses in vivo upon subdermal implantation of the delivery system in a human patient without a significant immune system response. 2. The delivery system of claim 1, wherein the carrier comprises a plurality of polymeric microspheres. 3. The delivery system of claim 1, wherein substantial amounts of the botulinum toxin has not be transformed into a botulinum toxoid prior to association of the botulinum toxin with the carrier. 4. The delivery system of claim 1, wherein significant amounts of the botulinum toxin associated with the carrier have a toxicity which is unchanged relative to the toxicity of the botulinum toxin prior to association of the botulinum toxin with the carrier. 5. The delivery system of claim 1, wherein the carrier comprises a polymeric matrix. 6. The delivery system of claim 1, wherein the botulinum toxin can be released from the carrier over of a period of time of from about 10 days to about 6 years. 7. The delivery system of claim 1, wherein the carrier is comprised of a substance which is biodegradable. 8. The delivery system of claim 1, wherein the botulinum toxin is selected from the group consisting of botulinum toxin types A, B, C.sub.1, D, E, F and G. 9. The delivery system of claim 1, wherein the botulinum toxin is a botulinum toxin type A. 10. The delivery system of claim 1, wherein the quantity of the botulinum toxin associated with the carrier is between about 1 unit and about 50,000 units of the botulinum toxin. 11. The delivery system of claim 1, wherein the quantity of the botulinum toxin is between about 10 units and about 2,000 units of a botulinum toxin type A. 12. The delivery system of claim 1, wherein the quantity of the botulinum toxin is between about 100 units and about 30,000 units of a botulinum toxin type B. 13. A controlled release system, comprising: (a) a biodegradable polymer; (b) between about 10 units and about 100,000 units of a botulinum toxin encapsulated by the polymer carrier, thereby forming a controlled release system, wherein therapeutic amounts of the botulinum toxin can be released from the carrier in a pulsatile manner in vivo upon subdermal implantation of the controlled release system in a human patient over a prolonged period of time extending from about 2 months to about 5 years without a significant immune system response. 14. A method for making a controlled release system, the method comprising the steps of: (a) dissolving a polymer in a solvent to form a polymer solution; (b) mixing or dispersing a botulinum toxin in the polymer solution to form a polymer-botulinum toxin mixture, and; (c) allowing the polymer-botulinum toxin mixture to set or cure, thereby making a controlled release system for pulsatile release of the botulinum toxin without a significant immune system response. 15. The method of claim 14, further comprising the step after the mixing step of evaporating solvent. 16. A method for using a pulsatile drug delivery system, the method comprising injection or implantation of a controlled release system which includes a polymeric matrix and a botulinum toxin, thereby treating a movement disorder or a disorder influenced by cholinergic innervation by local administration of a botulinum toxin without a significant immune system response. 17. A pulsatile release botulinum toxin delivery system, comprising: (a) a carrier comprising a polymer selected from the group of polymers consisting of polylactides, polyglycolides and polyanhydrides, wherein the carrier further comprises a plurality of discrete sets of polymeric, botulinum toxin incorporating microspheres, each set of polymers having a different polymeric composition; (b) a stabilized botulinum toxin associated with the carrier, thereby forming a pulsatile release botulinum toxin delivery system, wherein the botulinum toxin comprises: (a) a first element comprising a binding element able to specifically bind to a neuronal cell surface receptor under physiological conditions, (b) a second element comprising a translocation element able to facilitate the transfer of a polypeptide across a neuronal cell membrane, and (c) a third element comprising a therapeutic element able, when present in the cytoplasm of a neuron, to inhibit exocytosis of acetylcholine from the neuron, wherein the therapeutic element can cleave a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), thereby inhibiting the exocytosis of acetylcholine from the neuron, and, wherein therapeutic amounts of the botulinum toxin can be released from the carrier in a plurality of pulses in vivo upon subdermal implantation of the delivery system in a human patient without a significant immune system response. 18. The delivery system of claim 17, wherein the carrier comprises a plurality of discrete sets of polymeric, botulinum toxin incorporating microspheres, wherein each set of polymers has a different polymeric composition. 19. The delivery system of claim 18, wherein the SNARE is selected from the group consisting of syntaxin, a 25 kilo Dalton synaptosomal associated protein (SNAP-25) and a vesicle associated membrane protein (VAMP). 20. The delivery system of claim 18, wherein the neuron is a presynaptic, cholinergic, peripheral motor neuron.

Details for Patent 6,312,708

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Solstice Neurosciences, Llc	MYOBLOC	rimabotulinumtoxinb	Injection	103846	12/08/2000		2020-06-02