Abstract: This invention relates to methods and kits for safely removing and inactivating topical therapeutic or cosmetic compositions. The methods and kits according to the invention are particularly well suited for removing and inactivating highly toxic substances.

Abstract: The present invention provides a method for analysis methylation patterns in DNA and identifying aberrantly methylated genes in disease tissue. The invention also provides a method of identifying novel targets for therapeutic intervention and disease markers. Novel cancer targets are provided.

Abstract: Compounds of formula (I): wherein: R1 represents a hydrogen atom or a group of formula COR4, or R1 represents a group of formula (A): R2 represents a group of formula NR5R6, or R2 represents a nitrogen-containing heterocyclic group, an aryl group or a heteroaryl group, R3 represents a hydrogen atom or an alkyl group, m represents an integer between 1 and 6 inclusive, n represents 0, 1 or 2, their optical isomers, and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating and/or preventing thrombotic events.

Abstract: A method of controlling dysregulation of the dorsal cutaneous nerve of the clitoris and, in particular, a method for treating PGAD is provided. In one aspect, the method comprises administering a neurotoxin, such as a botulinum toxin, to the clitoral area of the human in need of treatment.

Abstract: Methods for treating ocular and periocular disorders by administration to a human patient of a therapeutically effective amount of a compound that modulates muscle action.

Abstract: The present invention provides methods of identifying the presence of or quantifying the amount of one or more of T helper (Th) cells and iTreg cells present in a sample by identifying the presence of an ADAM or the amount of an ADAM, such as ADAM12, present in a sample. The present invention also provides methods for increasing or decreasing signaling of a TGF such as TGF? by increasing or decreasing the biological activity or expression of an ADAM. Further, the present invention provides methods for inhibiting or stimulating, downregulating or upregulating, an immune response, and for treating diseases associated with an immune response such as cancer, viral, bacterial and fungal infections, autoimmune diseases and graft versus host diseases. Still further, the invention provides screening methods effective for identifying therapeutic agents, pharmaceutical compositions containing therapeutic agents, and vaccines.

Abstract: The present invention provides a method for producing a drug product comprising a combination of highly purified collagenase I and collagenase II from Clostridium histolyticum. The method utilizes an improved medium for the cultivation of Clostridium histolyticum which includes a non-meat-derived (i.e., non-mammalian) peptone or vegetable peptone. The method includes one or more of: (1) reducing glucose content in the meat-free or vegetable-derived media; and (2) increasing the salt concentration in the meat-free or vegetable-derived media. Also provided is a drug product which includes collagenase I and collagenase II at an optimized fixed mass ratio, and which has a purity of greater than at least 95%.

Abstract: The present invention relates to polypeptides comprising protease variants of wild type human neprilysin having an altered specificity and/or activity. In particular the present invention relates to polypeptides comprising protease variants derived from human neprilysin having an increased specificity and/or activity against certain substrates, in particular against amyloid beta.

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 compositions and methods for modulating one or more phenotypes of a macrophage-related cell, e.g., a macrophage. The invention further provides methods of treating disease by modulating macrophage phenotype. Representative phenotypes include pro-inflammatory, anti-inflammatory, immunogenic, tolerogenic, tissue-destructive, tissue restorative, cytotoxic, migratory, bone-resorbing, pro-angiogenic, anti-angiogenic, suppressor, antigen presentation, or phagocytic. Representative diseases include atherosclerosis, arthritis, and multiple sclerosis.

Abstract: The present invention relates to a clonally pure population of serosal cancer stem cells (CSCs) as well as methods of producing and culturing the CSCs and uses thereof. The CSCs form catenae (free floating chains of cells) which have a glycocalyx coat of hyaluronan and proteoglycans. This discovery has lead to the development of methods of treating serosal and ovarian cancers by targeting removal or inhibition of glycocalyx formation, including combination therapies using chemotherapeutics in conjunction with glycocalyx inhibitors. The invention also provides drug screening assays for identifying compounds effective against these CSCs as well as other serosal cancer cells. Methods to use catena gene signatures, protein and surface antigens are provided for monitoring patient samples for the presence of serosal cancer stem cells.

Abstract: The present specification discloses TVEMPs, compositions comprising such TVEMPs and methods of treating a disease or disorder associated with aberrant new blood vessel formation in a mammal using such TVEMP compositions.

Abstract: The present specification discloses TVEMPs, compositions comprising such TVEMPs and methods of treating a prostate cancer, a benign prostatic hyperplasia, and/or neovascularization or pathological angiogenesis associated with a cancer in a mammal using such TVEMP compositions.

Abstract: The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

Abstract: Embodiments of the invention provide treatment methods utilizing botulinum toxins. Certain methods describe specific time intervals between administration sessions. Administration sessions can include multiple administrations, for example, injections.

Abstract: A formulation comprising botulinum toxin (BT), lipid and surfactant, characterised in that the lipid and surfactant are in the form of macromolecular assemblies of less than 100 nm in diameter. The surfactant may have an HLB number of less than 20.

Abstract: Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is a single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent.

Abstract: A Clostridium histolyticum collagenase ColH (Glu451Asp) melts adipose tissue when injected into selected regions of the body. This protein product melts fat pads effectively in fat rat experiments, with very little side effects. Very little hemorrhage was observed. We also invent a new version of ColH mutant by linking a peptide motif CKGGRAKDC-G(varying from 2 to 6 Gs) (SEQ ID NO: 2) in front of ColH (Glu451Asp) (called topical ColH-FM), which can target to white fat vasculature. By combining with novel transdermal technology (such as Hydroxysome technology), we develop a topical protein cream that can melt fat. This product can be used as cellulite cream and for chemical liposuction. This topical ColH-FM can also be injected into adipose tissue as a replacement for liposuction or as an adjunct method with liposuction. Since raise scar is formed by overgrowth of collagen, our topical ColH-FM cream is shown to have application in scar reduction.

Abstract: The invention relates to systems and therapeutic methods to reduce plaque causing Peyronie's disease. One approach uses high pressure injection of collagenase-containing composition into a penile plaque. Plaque disruption is enhanced by the mechanical force of the high pressure, followed by the enzymatic action of collagenase. Another approach uses collagenase as a pretreatment, followed by addition of adipose-derived stem cells ADSCs. The initial collagenase injection breaks down collagen (often more type III than type I in Peyronie's) to provide short term benefit. The longer-term benefit is provided by introduction of ADSCs to the plaque, which can produce cytokines and other signals for revascularization and restoration of normal penile tissue. The resulting combination advantageously reduces the bulk of the plaque early on with ongoing reduction through the revascularization of the tissue. In addition, the treatment provides an advantageous shift of elastin and collagen ratios.

Abstract: Methods of using clostridial toxins and other biological agents to treat skin cosmesis in humans is provided. The disclosed methods provide beneficial effects in humans.

Abstract: Methods for prolongation of climax time in a patient in need thereof are presented, as are methods for treating premature ejaculation by local administration of a Clostridial neurotoxin, such a botulinum neurotoxin, to the patient, are provided.

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 a methods and compositions for treating a patient having a skin condition characterized by vascular hyper-reactivity, such as chronic or episodic flushing or blushing, and/or rosacea. The method comprises applying a topical composition to affected areas of the patient's skin. The topical composition comprises an effective amount of a botulinum neurotoxin for decreasing vasodilation in cutaneous microvasculature, and a carrier for effectively transporting the botulinum toxin to the cutaneous microvasculature. The invention thereby provides a safe, effective, comfortable, and/or convenient manner of treating vascular hyper-reactivity in skin.

Abstract: The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and/or heart.

Abstract: A method for reducing or maintaining platelet inhibition in a patient by administering cangrelor prior to an invasive procedure is described. The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.

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: A procedure for treating carpal tunnel syndrome can involve delivering a dehydrating agent into and/or near the carpal tunnel. The dehydrating agent can reduce swelling of the flexor tendons and/or the carpal ligament in the region, thereby reducing pressure on the median nerve that also runs through the carpal tunnel. Through the use of a dehydrating agent that affects proteoglycans without affecting collagen, localized dehydration can be induced without weakening the flexor tendons, carpal ligament, and any other structures in the carpal tunnel region.

Abstract: Liposomes are used for intravesical drug delivery, especially delivery of botulinum toxin (BoNT) to help improve lower urinary tract symptoms by decreasing bladder irritation and frequency. The system uses a lower and safer dose of BoNT with lower risk of urinary retention. A simple instillation of liposome-BoNT as a liquid formulation into the bladder, in a typical volume of 30-60 ml, will achieve efficacy similar to that currently achieved with cystscopic needle injection of BoNT. The dose may be lower than that done by injection, thereby causing significantly less risk of urinary retention. Liposome-BoNT can protect the BoNT from bladder and urine breakdown. Liposome-BoNT instillation is more comfortable for the patients and allows many more doctors' offices to offer this form of treatment that would otherwise be restricted to doctors skilled and certified in cystoscopic BoNT injection.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

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 discloses compounds of Formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases.

Abstract: The invention relates to compositions and methods for prion degradation, decontamination or disinfection. The composition comprises an oxidizing agent, one or more proteases and a surfactant such as an ionic surfactant/detergent. The method comprises contacting a prion contaminated entity with a prion-degrading composition comprising an effective amount of an oxidizing agent, an effective amount of at least one protease, and an effective amount of a surfactant. The components of the composition may be contacted with a prion-contaminated entity sequentially or simultaneously using an aqueous composition. Typically at least two different proteases are used for optimal efficacy. Preferably the oxidizing agent comprises peracetyl ions or a source thereof. The invention also relates to kits comprising the various reagents.

Abstract: The invention relates to the X-ray crystal structure of PfA-M1 aminopeptidase alone, and in complex with the phosphinate dipeptide analogue hPheP[CH2]Phe. More specifically the present invention provides the structure coordinates of PfA-M1 and PfA-M1 in complex with Co4. The invention also includes the use of the X-ray crystal structures as drug target models for anti-malarial drug design and a method for identifying or designing novel anti-malarial drugs, for example using high-throughput chemical screening and medicinal chemistry methods. The invention further provides anti-malarial drugs identified or designed according to the aforementioned method and their use for obstructing protein metabolism and synthesis in a parasite by blocking the entrance of Hb-derived peptides and/or blocking the exit of released amino acids at the active site of PfA-M1 protease.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases.

Abstract: This invention relates to the use of agents which are capable of the catabolism of components of cartilage extracellular matrix to promote cartilage regeneration within cartilage pathologies and to promote cartilage integration within focal defects.

Abstract: The present application discloses matrix compositions to support the repair of tissue defects such as an injury to tendon tissue, ligament tissue, vascular tissue, dermal tissue, or muscle tissue. A matrix described herein comprises a polyester polymer entangled with a polysaccharide polymer. Also disclosed are methods of preparing a matrix, and methods of using a matrix in the repair of tissue. In certain configurations, a matrix can comprise a polyester cross-linked with a polysaccharide, which can be an oxidized polysaccharide. In some configurations, a matrix can further comprise one or more additional components, such as a growth factor or an anti-infective agent. In some configurations, a matrix can be a viscous fluid or a paste, while in other configurations a matrix can be comprised by a solid such as a plug, a granule or a membrane.

Abstract: A drug product comprising a combination of highly purified collagenase I and collagenase II from Colostridium histolyticum is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product.

Abstract: A drug product comprising a combination of highly purified collagenase I and collagenase II from Colostridium histolyticum is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product.

Abstract: The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.

Abstract: The use of a collagenase containing formulation for degrading collagen within an occlusive atherosclerotic plaque in a chronic fibrotic occlusion, chronically occluded animal tube or cavity. A medical-related apparatus is provided comprising a medical-related device having provided thereto a therapeutic amount of a collagen degrading composition comprising a proteiolytic enzyme containing formulation A method is provided for treating chronically occluded animal tubes and cavities by administering a therapeutic effective amount of a proteolytic enzyme-containing formulation adjacent to an occluding atherosclerotic plaque, waiting for a pre-angioplasty waiting period, followed by crossing the plaque with an angioplasty guide wire.

Abstract: A pharmaceutical preparation comprising one of the botulinum neurotoxins from Clostridium botulinum of types A, B, C, D, E, F or G or a mixture of two or more of these neurotoxins, wherein the neurotoxin or the mixture of neurotoxins is free of the complexing proteins which naturally form the botulinum neurotoxin complexes together with the neurotoxins.

Abstract: Polypeptides which are related to the neprilysin enzyme family and have zinc metalloprotease activities and are referred to as IGS5, polynucleotides encoding such polypeptides, vectors containing such polynucleotides, host cells containing such vectors, processes for producing such polypeptides and/or polynucleotides, screening methods for identifying compounds which stimulate or inhibit IGS5 polypeptides and/or polynucleotides, and the use of such polypeptides and/or polynucleotides in therapy of various dysfunctions, disorders or diseases, particularly cardiovascular diseases, metabolic diseases such as diabetes mellitus type II, and neurodegenerative disorders, such as Parkinson's Disease.

Abstract: Disclosed are a composition and a method for treating skin disorders, including rosacea, pityriasis rosea, erythema, rhinophyma, and rosacea-associated disorders including pimples, papules, pustules, and telangiectasia.

Abstract: The present invention relates to the discovery of the Aegyptin gene and Aegyptin protein, a molecule that interacts with collagen and inhibits platelet adhesion, activation and aggregation. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

Abstract: A drug product comprising a combination of highly purified collagenase I and collagenase II from Colostridium histolyticum is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product.

Abstract: The present specification discloses modified Clostridial toxins, compositions comprising an integrated protease cleavage site-binding domain, polynucleotide molecules encoding such modified Clostridial toxins and compositions comprising di-chain forms of such modified Clostridial toxins.

Abstract: Physiologically acceptable anti-biofilm compositions comprising Serratia peptidase and optionally one or more of bromelain, papain and a fibrinolytic enzyme. Additional components can include antimicrobials, antibiotics, antifungals, herbals, chelating agents, lactoferrin and related compounds, minerals, surfactants, binders, and fillers useful for the inhibition and treatment of gastrointestinal biofilms in humans. Physiologically acceptable anti-biofilm compositions containing these enzymes are useful in the inhibition, reduction and/or treatment of biofilms such as in the ear, vagina, joints, bones, gut, surgical sites and other locations, and are useful for the inhibition, reduction and/or treatment of associated systemic symptoms caused by biofilm associated microorganisms.

Abstract: Physiologically acceptable anti-biofilm compositions comprising Serratia peptidase and optionally one or more of bromelain, papain and a fibrinolytic enzyme. Additional components can include antimicrobials, antibiotics, antifungals, herbals, chelating agents, lactoferrin and related compounds, minerals, surfactants, binders, and fillers useful for the inhibition and treatment of gastrointestinal biofilms in humans. Physiologically acceptable anti-biofilm compositions containing these enzymes are useful in the inhibition, reduction and/or treatment of biofilms such as in the ear, vagina, joints, bones, gut, surgical sites and other locations, and are useful for the inhibition, reduction and/or treatment of associated systemic symptoms caused by biofilm associated microorganisms.

Abstract: Physiologically acceptable anti-biofilm compositions comprising Serratia peptidase and optionally one or more of bromelain, papain and a fibrinolytic enzyme. Additional components can include antimicrobials, antibiotics, antifungals, herbals, chelating agents, lactoferrin and related compounds, minerals, surfactants, binders, and fillers useful for the inhibition and treatment of gastrointestinal biofilms in humans. Physiologically acceptable anti-biofilm compositions containing these enzymes are useful in the inhibition, reduction and/or treatment of biofilms such as in the ear, vagina, joints, bones, gut, surgical sites and other locations, and are useful for the inhibition, reduction and/or treatment of associated systemic symptoms caused by biofilm associated microorganisms.