Abstract: The discovery of clonally pure populations of serosal cancer stem cells (CSCs) as well as methods of producing CSCs, culturing the CSCs and using them in screening assays, has lead to the development of methods of treating serosal and ovarian cancers by targeting removal or inhibition of the glycocalyx coat surrounding such cells, and includes combination therapies using particular chemotherapeutics in conjunction with glycocalyx inhibitors, as well as the same new chemotherapy treatments without targeting the glycocalyx, where the chemotherapeutic agent is any one of LBH-589 (Panobinostat), NVP-AUY922, LAQ824 (NVP-LAQ824, Dacinostat), colchicine, brefeldin A, diphenyleneiodonium chloride, any combination thereof or another agent identified herein. These treatment methods of the invention can also be used in combination with radiation treatment or other conventional cancer therapy.

Abstract: The invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum. The protein binds specifically to nerve cells with a higher affinity as the native neurotoxin. The invention also relates to a method for the production of transport protein, the nucleic acids coding for the transport protein, the transport protein containing pharmaceutical and cosmetic compositions and use thereof.

Abstract: Methods for treating skin disorders by local administration of a Clostridial toxin, such as a botulinum toxin, to a patient with a skin disorder.

Abstract: The invention relates to recombinant nucleic acid and polypeptides encoding collagenase I and collagenase II, methods for the preparation thereof and methods for the use thereof. The invention also encompasses methods related to releasing a composition comprising collagenase prior to therapeutic administration.

Abstract: A pest-combating composition including sodium lauryl sulfate and one or more of C6-12 fatty acids, preferably lauric and/or capric and/or caprylic acid, soy methyl ester, and 2-undecanone, and methods of combating pests utilizing same, are disclosed. The compositions can include a carrier oil such as silicon oil, soy methyl ester, or a vegetable oil, and can be in the form of an emulsion. The composition may be constituted as a spray composition, an aerosol, a lotion, a paste, or another compositional form. Pests that may be usefully combated with such composition include flying insects, including flies, mosquitoes, and wasps, ants, including arthropods such as fire ants, ticks, fleas, cockroaches, silver fish, thrips, gnats, aphids, Japanese beetles, and agricultural and horticultural arthropods and insects including beetles (potato and bean), flea beetles, fleahoppers, squash bugs, slugs, leaf hoppers, harlequin bugs, milk weed bugs, spiders, mites, lice, rodents, and deer.

Abstract: There are provided a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals. The lyophilized preparation of botulinum toxin according to the present invention can maintain an activity of botulinum toxin, and also exhibit excellent long-term storage stability even under conditions of high temperature, which may occur when botulinum toxin is stored, delivered, and processed.

Abstract: This invention relates to a novel method for producing di-chain proteins for use in humans from single-chain precursors, including di-chain clostridial neurotoxins. The method comprises the step of expressing a nucleic acid sequence encoding a single-chain precursor comprising a thrombin-cleavage site and the step of cleaving the single-chain precursor with a human factor Xa or a human thrombin, particularly a human thrombin drug product authorized for human therapeutic use. The invention further relates to novel di-chain clostridial neurotoxins and nucleic acid sequences encoding such novel di-chain clostridial neurotoxins.

Abstract: The present invention concerns new compositions containing hyaluronic acid or the derivatives thereof in association with the proteolytic enzyme collagenase (and relative pharmaceutical formulations) for the preparation of a dressing for topical treatment of various kinds of wounds, burns of varying depth, pressure sores, vascular ulcers and diabetic foot ulcers as well as for the treatment of hypertrophic and keloid scars.

Abstract: Devices and methods of altering protein concentrations in cerebrospinal fluid and/or brain interstitial fluid are disclosed. Devices include a support having at least one protease attached to the support. The device may further include a housing. Devices may be implantable for use in an in vivo active flow system or for use in an in vivo passive system. Devices may also be used in an ex vivo active flow system. Devices may also be used in a passive system to treat cerebrospinal fluid and/or brain interstitial fluid that is withdrawn, or in a passive system that is implanted surgically. Methods include contacting cerebrospinal fluid and/or brain interstitial fluid with a support including at least one protease attached to the support. Proteins contained in the cerebrospinal fluid and/or brain interstitial fluid are cleaved by the protease resulting in the reduction of protein in cerebrospinal fluid and/or brain interstitial fluid.

Abstract: Methods and compositions are provided for increasing responsiveness to therapeutic metalloproteases including increasing and/or maximizing responsiveness and preventing botulinum and tetanus toxin resistance due to a functional deficiency of zinc. Also provided are methods for zinc replacement or supplement in lacking individuals comprising the administration of a zinc supplement for a loading period and/or administration of a phytase supplement together with the zinc supplement. Also provided are methods for standardization of botulinum toxin potency assays that provide for greater certainty and margins of safety in the use of products from different manufacturers.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: The present invention concerns new compositions containing hyaluronic acid or the derivatives thereof in association with the proteolytic enzyme collagenase (and relative pharmaceutical formulations) for the preparation of a dressing for topical treatment of various kinds of wounds, burns of varying depth, pressure sores, vascular ulcers and diabetic foot ulcers as well as for the treatment of hypertrophic and keloid scars.

Abstract: The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.

Abstract: The present invention provides a therapeutic agent for Alzheimer's disease. The therapeutic agent contains membrane vesicles (exosomes) of adipose tissue-derived mesenchymal stem cells, and the membrane vesicles (exosomes) contain neprilysin. Through the research by the inventors of the present invention, it was revealed that exosomes secreted by human adipose tissue-derived mesenchymal stem cells contain neprilysin, which degrades amyloid-? as a pathogenic protein of Alzheimer's disease. When exosomes secreted by human adipose tissue-derived mesenchymal stem cells were administered to the brains of Alzheimer's disease model mice, the generation of amyloid-? was inhibited.

Abstract: This invention provides methods of preventing or treating cardiac ischemia-reperfusion injury in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to a subject in need thereof wherein the peptide is D-Arg-26-Dmt-Lys-Phe-NH2 (SS-31).

Abstract: Treatment and procedures for treating bodily conduits involves deactivating, killing, or otherwise treating smooth muscle tissue of the conduit.

Abstract: The present invention is directed to a method of treating or reducing EFP in a patient comprising administering one or multiple low dose injections of collagenase to an area affected by EFP. The invention encompasses methods wherein the dose of collagenase per injection is between about 50 to about 200 ABC units and/or wherein the concentration of collagenase is between about 50 to about 2000 ABC units/milliliter (ml).

Abstract: The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production.

Abstract: Provided is a growth factor anchoring type bone graft material, wherein a bone graft substrate exposing at least a collagen fiber is bound to a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide. The same can be produced by mixing a bone graft substrate and a collagen-binding-site-containing growth factor which contains a growth factor receptor agonist peptide and a collagen-binding peptide, and is also superior in osteogenic ability.

Abstract: The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

Abstract: Methods for treatment of arterial or venous thrombosis in patients undergoing an endovascular intervention or a surgical procedure, and more particularly, administering alfimeprase directly into the thrombus or adjacent to the thrombus in a coronary, cerebral, or peripheral vessel.

Abstract: Ophthalmic conditions such as presbyopia, myopia, and astigmatism can be corrected by the use of a molding contact lens in combination with a pharmaceutical composition suitable for delivery to the eye. The molding contact lenses are preferably commercially available and are not specifically designed for orthokeratology. The agents in the pharmaceutical compositions such as hyaluronase allow the cornea of the eye to be molded in order to correct the refractive error of the eye. The contact lenses and the pharmaceutical composition induce a change in the radius of curvature of the anterior surface of the cornea, thereby correcting the refractive error of the eye. One advantage of the inventive technique is that the patient with his or her own individual visual needs guides the treatment until the patient near and far visual needs are met.

Abstract: The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: Provided herein are methods and compositions for treating ischemia or a disease or disorder that causes ischemia comprising contacting a subject with cysteamine, a cysteamine derivative, cystamine or a cystamine derivative. The disclosure also provides methods of modulating adiponectin levels in a subject comprising contact a subject with cysteamine, a cysteamine derivative, cystamine or a cystamine derivative.

Abstract: Disclosed are pharmaceutical compositions and methods for digesting atherosclerotic plaques in a patient in need thereof. The compositions include and the methods utilize a mixture of collagenases for digesting plaques and optionally may include or utilize additional agents such as cyclodextrins, chelating agents, and tissue plasminogen activator.

Abstract: The invention relates to an active ingredient and/or to a composition having beneficial effect on neurological and cognitive functions.

Abstract: Methods for treating or alleviating symptoms associated with femoroacetabular impingement (FAI) by local administration of a clostridial derivative, such as a botulinum toxin, to the hip capsule and surrounding muscle.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a neurotoxin polypeptide exhibiting a reduced duration of the biological effect in a subject, wherein said polypeptide comprises at least one E3 ligase recognition motif in the light chain, wherein said E3 ligase recognition motif is preferably a binding motif for the E3 ligase MDM2. The invention further pertains to polypeptides encoded by the polynucleotide of the invention as well as polypeptides comprising one or more amino acid substitutions. Further encompassed by the present invention are vectors and host cells comprising the said polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising said polynucleotides and polypeptides, as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

Abstract: The present invention is concerned with modified neurotoxins. Specifically, it relates to a modified biologically active neurotoxin polypeptide comprising at least one poly-Glycine domain. Also contemplated is a polynucleotide encoding the modified neurotoxin polypeptide having a poly-Glycine domain fused to the N-terminus, to the C-terminus or to both of the heavy and/or light chain of the mature neurotoxin polypeptide, vector comprising it and a host cell comprising such a polynucleotide or a vector. Moreover, envisaged are the aforementioned compounds for use as a medicament for treating various diseases.

Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumour cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalised and inhibits secretion from said tumour cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract: Botulinum neurotoxin formulated with a hyaluronic acid carrier with increased residency time of the botulinum toxin at a subdermal location and fewer botulinum toxin induced complications or side effects.

Abstract: The present invention relates to methods of reducing, delaying, preventing and/or inhibiting the progression of a Cryptococcus infection into the central nervous system (CNS) of a subject by inhibiting the activity of a M36 fungalysin metalloprotease (e.g., MPR1) secreted by the Cryptococcus. The invention further provides methods of increasing, promoting and/or enhancing delivery of a therapeutic agent across the blood-brain-barrier, comprising systemically administering the therapeutic agent in conjunction with a M36 fungalysin metalloprotease (e.g., MPR1), or an enzymatically active fragment thereof.

Abstract: According to this invention, compositions and methods for increasing the extent of penetration of a biologically active substance into the tissues and organs are proposed, the methods comprising administration of the biologically active substance in combination with one or more chaotropic agents, e.g., ammonium sulfate.

Abstract: The invention includes liquid formulations of botulinum toxin, including hydrogel formulations that are stable to storage in liquid form at standard refrigerator temperatures for at least 1-2 years and to storage at higher temperatures for at least 6 months. The invention also includes methods of treatment using such formulations for various therapeutic and cosmetic purposes.

Abstract: Provided herein are methods of treatment of migraine headaches comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual in need thereof.

Abstract: A headache can be treated more effectively by co-administration of a botulinum toxin and a triptan drug to a patient and/or the effectiveness of a triptan medication can be increased. The botulinum toxin can be botulinum toxin type A and the botulinum toxin can be administered to or to the vicinity of where a patient experiences or is predisposed to experience pain or a headache.

Abstract: The present invention relates to ADAMTS-1 and uses thereof. The present invention also relates to fragments of ADAMTS-1 and methods of inhibiting cell growth and metastasis. The present invention also provide methods of identifying inhibitors and activators relating to the function of ADAMTS-1.

Abstract: The present invention relates to new biphenyl-3-carboxylic acid modulators of beta-3-adrenoceptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The disclosure relates to methods for detecting PNH Type II cell populations in biological samples as well as methods for determining whether a patient is at an increased risk for developing thrombocytopenia or thrombosis based on the percentage of PNH Type II cells in the patient's blood. The disclosure also features reagents and conjugates for use in the methods.

Abstract: The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: Provided herein are novel biomarkers for the identification, prediction or monitoring of fibrotic pulmonary diseases (e.g. idiopathic pulmonary fibrosis (IPF)). The biomarkers provided herein may further be used for therapeutic treatment of IPF.

Abstract: This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

Abstract: The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.

Abstract: This invention provide novel compositions, methods and devices for sustained drug delivery. The microencapsulated sustained drug delivery compositions are deposited using oscillating needle apparatus oscillating at 10-12000 minutes per minutes. The injected compositions may undergo variety of physical chemical changes upon deposition. The physical and chemical changes enables improved drug encapsulation and sustained drug release. Also described are new methods to form polymer microparticles or polymer films/implants in situ inside the tissue. The invention also describes colored biodegradable microparticle based compositions wherein the compositions comprise drug encapsulated microparticles and coloring agent encapsulated microparticles mixed in any proportion. Medical applications of the compositions and methods described in this invention are also described.

Abstract: The present invention relates to composition(s) comprising collagen, calcium ions and alginate, wherein the composition polymerizes in situ when contacted with blood. The composition may further comprise an erythrocyte aggregation agent and/or a platelet activation agent. The composition may be formulated into two separate formulations. The first formulation comprises collagen in a calcium-containing solution and a second formulation comprises an aqueous alginate solution. The two formulations can be mixed prior to the contact with blood or mixed coincident with the contact with blood.

Abstract: A pest-combating composition including sodium lauryl sulfate and one or more of C6-12 fatty acids, preferably lauric and/or capric and/or caprylic acid, soy methyl ester, and 2-undecanone, and methods of combating pests utilizing same, are disclosed. The compositions can include a carrier oil such as silicon oil, soy methyl ester, or a vegetable oil, and can be in the form of an emulsion. The composition may be constituted as a spray composition, an aerosol, a lotion, a paste, or another compositional form. Pests that may be usefully combated with such composition include flying insects, including flies, mosquitoes, and wasps, ants, including arthropods such as fire ants, ticks, fleas, cockroaches, silver fish, thrips, gnats, aphids, Japanese beetles, and agricultural and horticultural arthropods and insects including beetles (potato and bean), flea beetles, fleahoppers, squash bugs, slugs, leaf hoppers, harlequin bugs, milk weed bugs, spiders, mites, lice, rodents, and deer.

Abstract: The present invention provides methods for improving gut health. In particular, the invention provides methods for improving gut health by improving the digestibility of dietary proteins, decreasing the flow of protein to the lower gastrointestinal tract, and/or decreasing the levels of Clostridium bacteria the upper intestinal tract of a subject. The methods comprise administering to the subject a supplement consisting essentially of at least one protease.

Abstract: The present invention provides for a pharmaceutical composition that includes tetrabenazine and a release-retarding agent; and a method of treating a hyperkinetic movement disorder (e.g., Huntington's disease, chorea associated with Huntington's disease, hemiballismus, senile chorea, tic disorders, tardive dyskinesia, myoclonus, dystonia and/or Tourette's syndrome). The method includes administering an effective amount of the pharmaceutical composition, for a period of time effective to treat the hyperkinetic movement disorder.