Botulinum Toxin Research Associates, Inc.

Other

Revance Therapeutics, Inc.

Associated Synapse Biologics

Wisconsin Alumni Research Foundation

Gary E Borodic

Martin Andrew Acquadro

Eric Arthur Johnson

David James Beebe

William Howard Tepp

Sabine Pellett

Michael C Goodnough

Amy Paguirigan

A composition of botulinum toxin is claimed which can penetrate into the ocular surface inclusive of a penetration through a conjunctiva, cornea, and other structures. This composition allows for a maximal penetration of a topical preparation of botulinum toxin which serves to reduce the need for frequent allergy drops for the treatment of ocular surface disease and other conditions causing ocular surface inflammation or deep ocular inflammation. No puncture of the needle is necessary for the administration. Herein describes a novel composition using several principles based on composition, method of application, which enhances the effectiveness of the penetration.

Topical ocular preparation of botulinum toxin for use in ocular surface disease

Formulations and methods of treatment are disclosed for prevention and/or treatment of visual loss from age-related macular degeneration. The disclosed formulations include botulinum neurotoxin (e.g., botulinum neurotoxin or a fragment thereof, either in pure form or with one or more peptide fragments and/or neurotoxin associated proteins). In some embodiments, the disclosed formulations also include one or more anti-VEGF agents. The disclosed formulations may be applied to an intraocular or extraocular region of a patient. If applied to an extra ocular region of a patient, the botulinum-based pharmaceutical formulation may be transported to the intra-ocular region of the patient via axoplasmic transport, thereby allowing the active ingredient(s) to penetrate into the choroid, neuro-retina, and/or retinal pigment epithelium without direct injection into the eye, allowing for improved therapeutic safety by eliminating risk of retinal detachment, retinal break, retinal hemorrhage, and blindness associated with direct injection into the eye.

Method of treating macular degeneration using botulinum toxin-based pharmaceuticals

Formulations and methods of treatment are disclosed for prevention and/or treatment of visual loss from age-related macular degeneration. The disclosed formulations include botulinum neurotoxin (e.g., botulinum neurotoxin or a fragment thereof, either in pure form or with one or more peptide fragments and/or neurotoxin associated proteins. In some embodiments, the disclosed formulations are applied to the para orbital or periorbital region of a patient to delay or stop the progression of dry macular degeneration. The methods described herein do not involve a direct injection into the eye or subconjunctival region, thus significantly easing both comfort and administration related complications and further preserving barrier functions of retinal layers while also delaying or ceasing the degenerative process to wet conversion.

Formulations and methods of treatment are disclosed for prevention and/or treatment of visual loss from age-related macular degeneration. The disclosed formulations include botulinum neurotoxin. The disclosed formulations may be applied to an intraocular or extraocular region of a patient. If applied to an extra ocular region of a patient, the botulinum-based pharmaceutical formulation may then be transported to the intra-ocular region of the patient, allowing the active ingredient(s) to penetrate into the choroid, neuro-retina, and/or retinal pigment epithelium without direct injection into the eye, eliminating risk of retinal detachment, retinal break, retinal hemorrhage, and blindness. The methods described herein allow for increased blood flow to the choroid, which improves removal of metabolites and intra retinal fluid and also serves to arrest, reverse and/or delay early and later stages of age-related macular degeneration.

Methods of using botulinum toxin based pharmaceuticals are disclosed. The methods cause vasodilatation and decreased flow resistance of certain vascular beds for the purpose of increasing blood flow to a region in order to positively impact deterioration from a number of diseases.

Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds

A method of treating circadian rhythm disorders includes identifying a subject with a circadian rhythm disorder or at least one symptom of a circadian rhythm disorder and administering an effective amount of a composition comprising a botulinum toxin and a pharmaceutically acceptable carrier to said subject thereby reducing at least one symptom of a circadian rhythm disorder.

Botulinum toxin and the treatment of primary disorders of mood and affect

An extended duration pharmaceutical composition including a botulinum neurotoxin, an adhesive agent, and a stabilizing macromolecule is disclosed. The composition effectively has all the properties to cause chemodenervation through a facial muscle, or other muscle, that predecessor botulinum toxin preparations have had as well as agents which create a fibrotic adhesion on the under surface of facial muscles (or other muscles) to the facial bone (or other bones) so that the facial bone tethers the under surface of the facial muscle, thereby causing fibrosis to the underlying fat pad. The composition can be used to treat various disorders. Methods of modifying facial contour for functional or cosmetic purposes in a human patient are disclosed which involve injecting a therapeutically effective amount of the disclosed compositions. A method of quantifying the extended duration of the compositions is also disclosed.

Extended length botulinum toxin formulation for human or mammalian use

An extended duration pharmaceutical composition including a botulinum neurotoxin, an adhesive agent, and a stabilizing macromolecule. The composition effectively has all the properties to cause chemodenervation through a facial muscle, or other muscle, that predecessor botulinum toxin preparations have had as well as agents which create a fibrotic adhesion on the under surface of facial muscles (or other muscles) to the facial bone (or other bones) so that the facial bone tethers the under surface of the facial muscle, thereby causing fibrosis to the underlying fat pad. The composition can be used to treat various disorders. Methods of modifying facial contour for functional or cosmetic purposes in a human patient are disclosed which involve injecting a therapeutically effective amount of the disclosed compositions. A method of quantifying the extended duration of the compositions is also disclosed.

A highly sensitive method of analyzing a sample for the presence or activity of botulinum neurotoxin (BoNT) or antibodies specific for botulinum neurotoxin is disclosed. In one embodiment, the method comprises the steps of preparing primary non-human mammalian or avian spinal cord cells, and exposing the cells to a test sample, in parallel with a control sample, and examining the extent of cleavage of the intracellular neuronal target protein in both the test and control sample.

Method of detecting botulinum neurotoxin and antibodies that neutralize botulinum neurotoxin action

The invention provides methods for treating primary disorders of mood and affect, including depressive disorders, anxiety and sleep disorders and CNS disorders comprising the administration of a neurotoxin.

The present invention provides methods for treating sinus-evoked headaches using botulinum toxin injected or applied in multiple subcutaneous locations over divisions of the trigeminal nerve in soft tissues and dermatomes overlying the corresponding effected sinuses implicated in the etiology of the pain.

Treatment of sinusitis related chronic facial pain and headache with botulinum toxin injections

The present invention provides improved formulations of botulinum toxin that increase delivery of the botulinum toxin to neural and associated tissues and exhibit a higher specific neurotoxicity and higher potency (in LDUnits) than available formulations of botulinum toxins. These improved formulations enable physicians to treat a wide variety of pathological conditions with a lower toxin load that reduces the risk of inducing an immune response against the toxin and its associated proteins that may ultimately lead to the development of toxin resistance. These benefits are particularly important in the treatment of conditions that require high-dose or chronic administration of botulinum toxin. Additionally, the decreased in LDUnit doses of inventive formulations allows for controlled administration limits diffusion. The present invention also provides methods of treating neuromuscular diseases and pain, using low-dose botulinum toxin.

High-potency botulinum toxin formulations

This invention relates to a composition of botulinum based pharmaceuticals used for therapeutic and cosmetic treatment. This invention offers an improvement on the prior art by eliminating the potential of blood-borne contamination with botulinum based pharmaceuticals. Recombinant serum albumin is taught for use in the place of human serum albumin as a stabilizing or enhancing agent.

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Canton, MA, United States of America

Gary E Borodic