Abstract: The present invention provides a tnaluronidase. The hyaluronidase can be produced by the strain Streptomyces aitinocidm 77, Exemplary characteristics of the hyaluronidase include specific C-terminal or other amino acid sequences, including full-length sequences, and improved physico-chemical and actix itj properties as compared to known h> al?ronidase preparatkiiis. Described are also various uses of the hyaiur?nidasc, including topical administration of the h> aiuronidasc to improve skin penetration of a co-administered active substance.

Abstract: Soluble PH20 polypeptides are provided, including extended soluble PH20 polypeptides, and uses thereof. Also provided are other C-terminally truncated PH20 polypeptides and partially deglycosylated PH20 polypeptides and uses thereof.

Abstract: One aspect of the present invention relates to mutants of chondroitinase ABCI. Such chondroitinase ABCI mutants exhibit altered chondroitin lyase activity or increased resistance to inactivation from stressors including exposure to UV light or heat. Methods of using chondroitinase ABCI mutant enzymes are also provided.

Abstract: The present invention relates to protein and nucleic acid mutants of chondroitinase ABCI. Such chondroitinase ABCI mutant enzymes exhibit altered chondroitin lyase activity or increased resistance to inactivation from stressors including UV light or heat. Methods of using chondroitinase ABCI mutant enzymes are also provided.

Abstract: The present invention relates to the use of hyaluronidase for the prevention and/or treatment of arterial hypertension or cardiac insufficiency. In addition, the present invention provides a composition and a combined preparation each comprising hyaluronidase and at least one further antihypertensive, and a method of prevention and/or treating arterial hypertension or cardiac insufficiency in a patient in need thereof, wherein the patient is administered a therapeutically effective amount of hyaluronidase.

Abstract: This invention addresses the pharmaceutical composition for topical corticosteroid use in association with diffusing enzyme for treatment of phimosis. A pharmaceutical composition for treatment of phimosis using topical corticosteroid characterized by including around 0.025 to 5 percent in weight in relation to the total weight of the mixture composition of one or more corticosteroids and/or hormone steroids, whether or not associated with non-hormonal anti-inflammatory agents and around 25 UTR to 4000 UTR/g of one or more proteolytic diffusing enzymes in proper medium, in different pharmaceutical forms, accompanied with additives known to the technical man. Topical corticosteroid application in association with diffusing enzyme for treatment of phimosis in which 90 percent of the patients had improvements over their clinical complaints, with the prepuce being easily retracted.

Abstract: The present invention relates to treatment methods and methods for sustained delivery of one or more exogenous factors to desired nervous system sites. In certain embodiments, the invention relates to the use of biodegradable microspheres to deliver exogenous factors, such as the morphogenic factor, sonic hedgehog (Shh), to the site of spinal cord injury. In certain embodiments, the Shh-releasing microspheres are administered together with stem cells, which may be spinal cord neural stem cells. In certain embodiments, the invention relates to regrowth of neural cells in both the central and peripheral nervous systems.

Abstract: Methods and combinations are provided for controlling the duration of action, in vivo, of matrix-degrading enzymes. The methods and combinations permit temporary in-vivo activation of matrix-degrading enzymes upon administration to the extra cellular matrix (or “ECM”). Matrix-degrading enzymes having a controlled duration of action can be used to treat ECM-mediated diseases or disorders characterized by increased deposition or accumulation of one or more ECM components.

Abstract: Provided are combinations, compositions and kits containing a hyaluronan degrading enzyme, such as a soluble hyaluronidase, for treatment of hyaluronan-associated conditions, diseases and disorders. In one example, the products include an additional agent or treatment. Such products can be used in methods for administering the products to treat the hyaluronan-associated diseases and conditions, for example, hyaluronan-associated cancers, for example, hyaluronan-rich tumors. The methods include administration of the hyaluronan degrading enzyme composition alone or in combination with other treatments. Also provided are methods and compositions for providing sustained treatment effects in hyaluronan-associated diseases and conditions.

Abstract: Provided are combinations, compositions and kits containing a bisphosphonate composition and a soluble hyaluronidase composition formulated for subcutaneous administration. Such products can be used in methods of treating bisphosphonate-treatable diseases or conditions. Also provided are methods for subcutaneous administration of a bisphosphonate compound whereby the dosing regimen is substantially the same as for intravenous administration of the same dosage for treatment of the same bisphosphonate-treatable disease or condition.

Abstract: Provided are combinations, compositions and kits containing an fast-acting insulin composition and a hyaluronan degrading enzyme composition formulated for parenteral administration. Such products can be used in methods of treating insulin-treatable diseases or conditions. Also provided are methods for administration of a fast-acting insulin and a hyaluronan degrading enzyme.

Abstract: Tissue engineering devices and methods are provided for the reconstruction, repair, augmentation, or replacement of a luminal organ or tissue structure involving the use of a biodegradable polymer matrix conforming to a portion of a laminarly arranged luminal organ, the processing of autologous, allogeneic or xenogeneic tissue comprising multiple cell populations to obtain a minced tissue composition, the seeding of the matrix with the composition, and the implanting of the seeded polymer matrix into a patient.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The invention is directed to a method of delivering a gene product to an animal. The method comprises administering an expression vector comprising a nucleic acid sequence operably linked to a promoter and encoding a gene product, and upregulating transcription of the nucleic acid sequence in the ocular cell. The expression vector can be an adenoviral vector. The invention further provides a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a neurotrophic agent. In one aspect, the method further comprises upregulating transcription of the nucleic acid sequence. Preferably, if 2×108 adenoviral particles of the inventive method are administered to a mouse, the level of expression of the nucleic acid sequence is not diminished more than ten-fold at 28 days post-administration.

Abstract: One aspect of the present invention relates to mutants of chondroitinase ABCI. Such chondroitinase ABCI mutants exhibit altered chondroitin lyase activity or increased resistance to inactivation from stressors including exposure to UV light or heat. Methods of using chondroitinase ABCI mutant enzymes are also provided.

Abstract: This disclosure relates to compositions capable of use in the treatment of spinal cord injuries and related disorders of the central nervous system (CNS), and in particular, compositions including proteoglycan degrading molecules and compositions capable of blocking and/or over coming the activity of neuronal growth inhibitory molecules, as well as fusion proteins which includes a proteoglycan degrading domain and a domain capable of blocking and or over coming the activity of neuronal growth inhibitory molecules.

Abstract: Methods and devices are provided for delivering a drug to or withdrawing a fluid from a biological tissue, such the skin, sclera, cornea, and conjunctiva. One method includes the steps of inserting at least one microneedle into the biological tissue; partially retracting the at least one microneedle from the tissue; and then delivering at least one drug formulation into the biological tissue via the partially retracted at least one microneedle. The microneedle deforms and penetrates the biological tissue during the insertion step, and the retraction step at least partially relaxes the tissue deformation while maintaining at least part of the tissue penetration, facilitating drug delivery or fluid withdrawal.

Abstract: The present invention is directed to compositions and processes related to use of hyaluronidase in combination with plasmin for the induction of posterior vitreous detachment.

Abstract: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, and cholecystitis for example.

Abstract: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, for example.

Abstract: Disclosed herein are methods for treating mucositis (e.g., Alternaria-activated mucositis) that involves the direct mucoadministration of an active agent that is antifungal and antibacterial in an amount and for a duration effective to treat mucositis.

Abstract: The invention relates to use of the enzyme hyaluronidase in a dosage of at least 6,000 units per day for prevention and/or treatment of cardiovascular diseases whereby the hyaluronidase is administered intra venam over a period of at least four weeks. Hyaluronidase is particularly suited to treating coronary heart diseases as well as for preventive purposes in patients at risk of heart infarctions.

Abstract: This invention provides compositions of highly phosphorylated lysosomal enzymes, their pharmaceutical compositions, methods of producing and purifying such compounds and compositions and their use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases.

Abstract: Methods of reversing local anesthesia are disclosed. The methods comprise administering a local anesthetic and alpha adrenergic receptor agonist to induce local anesthesia followed by reversing anesthesia with a low dose of an alpha adrenergic receptor antagonist. Also disclosed are kits comprising a local anesthetic, an alpha adrenergic receptor agonist and a low dose of an alpha adrenergic receptor antagonist.

Abstract: A method comprising administering by ocular route a dose of a glycol ether effective to induce retinal detachment.

Abstract: The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

Abstract: The present invention relates to the isolation, purification and characterization of a hyaluronidase which derives from the tropical leech Hirudinaria manillensis. Therefore, according to this invention, the enzyme was called “manillase”. The invention is furthermore concerned with the recombinant method of production of manillase which includes the disclosure of DNA and amino acid sequences as well as of expression vectors and host systems. Finally, the invention relates to the use of manillase for therapeutic purposes, for example, for the treatment of myocardial diseases, thrombotic events and tumors.

Abstract: The present invention describes pharmaceutically effective substances from the poison of spiders of the family of Sicariidae as well as their preparation and their use in medicine.

Abstract: The present invention relates to a Bacillus sp. strain producing a mannanase which is highly active in the neutral and the acidic media. The Bacillus sp. WL-1 strain (KCTC 0800BP), which is isolated from the soil, produces in large scale the mannanase in the culture medium containing lactose and bran, wherein the mannanase is highly active in the neutral and the acidic media so said mannanase is useful as an additive for feeds and is helpful in the decomposition of hemicellulose.

Abstract: Hyaluronic acid, a polymer found in the trabecular meshwork of the eye, has a polymeric structure that is broken down by the enzyme hyaluronidase. A method is provided for reducing elevated intraocular pressure in an eye of a patient, such as a patient suffering from glaucoma, by administering modified hyaluronidase to the surface of the eye as a drop, spray, ointment, sustained-release or non-sustained release unit, and allowing the hyaluronidase to remain within the anterior chamber of the eye. The hyaluronidase is modified to enhance penetration through the corneal barrier, and is administered in an amount effective to reduce an elevated intraocular pressure. The method thus reduces the elevated intraocular pressure in the eye of a glaucoma patient without undesirable side effects.

Abstract: A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a ?-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.

Abstract: A method of treating prostate cancer in a living mammal includes local administration of a composition that includes a therapeutically effective concentration of collagenase. In one embodiment, a method of treating prostate cancer in a living mammal includes local administration of a composition that includes a therapeutically effective concentration of collagenase and at least one of a glycosidase, a protease, a nuclease, a lipase, an esterase, a plasminogen activator, a streptokinase, and combinations thereof. Preferably a glycosidase, such as, for example, hyaluronidase, is administered. Compositions used in methods for treating prostate cancer can also include or be administered with calcium ions, a nonionic surfactant, such as, for example, Triton® X-100, and an antibiotic, such as, for example, gentamicin. Another method of treating prostate cancer in a living mammal includes activating PSA in vivo by, for example, locally administering calcium ions.

Abstract: A highly specific and easily purified form of hyaluronidase is described for use in ophthalmic treatments. The enzyme, from Streptomyces hyalurolyticus is specific for hyaluronidase and carries out an elimination reaction that results in the production of double bonds at the nonreducing end of hyaluronic acid. Hyaluronidase from Streptomyces hyalurolyticus has a higher activity than comparable enzymes from other species. The enzyme is now capable of being purified in what is essentially a protease-free form making it applicable to medical treatments. The use of this source of hyaluronidase in ophthalmic treatments is now made possible by its high activity, specificity for hyaluronidase and purity.

Abstract: Methods of reversing local anesthesia are disclosed. The methods comprise administering a local anesthetic and alpha adrenergic receptor agonist to induce local anesthesia followed by reversing anesthesia with a low dose of an alpha adrenergic receptor antagonist. Also disclosed are kits comprising a local anesthetic, an alpha adrenergic receptor agonist and a low dose of an alpha adrenergic receptor antagonist.

Abstract: An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

Abstract: A method of performing intra-articular therapy and a dilution resistant viscoelastic composition are disclosed. One embodiment of the dilution resistant composition comprises a hyaluronate-based viscoelastic agent and a low viscosity, polymer-containing solution. The hyaluronate-based viscoelastic can be an aqueous solution sodium hyaluronate having an average molecular weight greater than 750,000 Daltons and a concentration by weight between 0.5% and 3%. The polymer-containing solution can contain a polymer selected from the group consisting of chondroitin sulfate and hydroxypropylmethylcellulose. One embodiment can comprise a polymer-containing solution containing hydroxypropylmethylcellulose at a concentration by weight from about 0.05% to about 5.0% and chondroitin sulfate at a concentration by weight from about 0.1 to about 7%.

Abstract: Use of an extract of bacterium from the family Pseudomonadaceae in the production of cosmetic compositions in particular for combating ageing of the skin.

Abstract: Methods of modifying total MMP activity levels in the vitreous of an eye are provided. In a preferred embodiment, the method results in reduced MMP activity and comprises introducing plasmin into the vitreous of the eye. Enzyme assisted vitrectomy procedures are also provided, and comprise introducing plasmin into the vitreous in an amount sufficient to induce posterior detachment of the vitreous, mechanically detaching the vitreous from the eye, introducing a replacement fluid into the eye, and introducing plasmin into the eye in an amount sufficient to decrease the total MMP activity in vitreous. Considering the purported roles of MMPs in a variety of vitreal pathologies, the present invention provides methods of inhibiting the progression of various disease conditions, including prolifertaive diabetic retinopathy.

Abstract: Methods of reversing local anesthesia are disclosed. The methods comprise administering a local anesthetic and alpha adrenergic receptor agonist to induce local anesthesia followed by reversing anesthesia with a low dose of an alpha adrenergic receptor antagonist. Also disclosed are kits comprising a local anesthetic, an alpha adrenergic receptor agonist and a low dose of an alpha adrenergic receptor antagonist.

Abstract: The invention disclosed herein relates to biochemical methods for the elimination of corneal collagen fiber disorganization to improve vision. Disorganization of corneal collagen fibers is seen in corneal scars, corneal opacification and corneal haze. In addition, the invention relates to biochemical methods for the elimination of corneal collagen fiber disorganization resulting from accidental traumatic injury to the cornea and from refractive surgery for such as radial keratotomy (RK), photorefractive keratectomy (PRK), and laser in situ keratomileusis (LASIK) so as to improve visual acuity and quality of vision.

Abstract: The invention relates to an agent for treating skin diseases and/or functional disorders of the skin on the basis of different medicaments and/or auxiliary substances through promotion of penetration from topical formulations into the skin. According to the invention, the agent is composed of a hyaluronate lyase produced by microbial means and a medicament, preferably a hydrophilic medicament and/or auxiliary substances in different galenic formulations including colloidal carrier systems. The areas of application for the invention in human and veterinary medicament relate to the treatment, prophylaxis and/or metaphylaxis of skin diseases, functional disorders of the skin, the processes of skin ageing and dry skin conditions.

Abstract: A polypeptide selected from the group of lysosomal enzymes and lysosomal enzyme activators, comprising at least one introduced glycosylation site as compared to a corresponding parent enzyme or activator. By introducing additional glycosylation sites the resulting glycosylated lysosomal enzyme or activator obtains improved in vivo activity and thereby provides for improved treatment of lysosomal storage diseases.

Abstract: This invention provides a Dioscorea polysaccharide extract prepared by the method of this invention, which enhances the immunological activities by regulating the gene expression of cytokines. This invention further provides a Dioscorea polysaccharide extract, which has a synergistic effect with an oral vaccine and is capable of eliminating oral tolerance.

Abstract: A unique clone of a Polistinae venom enzyme, recombinantly produced Polistinae venom enzymes, and methods of using the recombinant enzymes are provided. In a specific example, both phospholipase and hyaluronidase cDNA from Polistes annulares contain apparent “intronic” sequences. In still a further embodiment, genetic engineering permits the construction of the “intronic” sequences to yield a useful coding sequence for expression of mature Polistinae venom enzyme proteins.

Abstract: Water-soluble polymer conjugates of antimicrobial agents retaining at least a portion of the antimicrobial activity of the agent, pharmaceutical compositions containing the polymer conjugates, and methods for treating microbial infections with the pharmaceutical compositions.

Abstract: The invention as described herein relates to the efficient production of recombinant, clinically effective lysosomal enzymes using a transformed insect cell expression system. For example, to create the expression system of the invention, any insect cell can be transfected with a plasmid comprised of a gene encoding the human glucocerebrosidase gene and genetic elements that enhance its expression. The insect cell transfected with the plasmid encoding glucocerebrosidase secretes synthesized glucocere-brosidase into its growth media. The recombinantly produced clinically effective glucocerebrosidase produced by the insect cell expression system can be used to treat Gaucher's disease.

Abstract: An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to the retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

Abstract: This invention involves the new use of a diagnostic test to determine the risk of atherosclerotic diseases such as myocardial infarction and stroke, particularly among individuals with no signs or symptoms of current disease and among nonsmokers. Further, this invention involves the new use of a diagnostic test to assist physicians in determining which individuals at risk will preferentially benefit from certain treatments designed either to prevent first or recurrent myocardial infarctions and strokes, or to treat acute and chronic cardiovascular disorders. Methods for treatment also are described.