Abstract: In one aspect, the present disclosure provides a formulation comprising a hyaluronidase enzyme and a therapeutically effective amount of an active ingredient. In another aspect, the present disclosure provides a method of administering a high volume of the formulation in a single administration to treat a disease or disorder in a subject.

Abstract: Embodiments described herein provide a surgical duration estimation system for continuously predicting real-time remaining surgical duration (RSD) of a live surgical session of a given surgical procedure based on a real-time endoscope video of the live surgical session. In one aspect, the process receives a current frame of the endoscope video at a current time of the live surgical session, wherein the current time is among a sequence of prediction time points for making continuous RSD predictions during the live surgical session. The process next randomly samples N?1 additional frames of the endoscope video corresponding to the elapsed portion of the live surgical session between the beginning of the endoscope video corresponding to the beginning of the live surgical session and the current frame corresponding to the current time. The process then combines the N?1 randomly sampled frames and the current frame in the temporal order to obtain a set of N frames.

Abstract: The disclosure relates to compositions and methods for treating infection, allergic reactions, colitis, IBD, contact dermatitis, psoriasis, atopic dermatitis, graft vs. host disease and disorders and other disease and disorders comprising dendritic cell activation as well as compositions and method to improve allergen sensitization.

Abstract: Disclosed herein are methods for the generation of highly accurate oligonucleic acid libraries encoding for predetermined variants of a nucleic acid sequence. The degree of variation may be complete, resulting in a saturated variant library, or less than complete, resulting in a selective library of variants. The variant oligonucleic acid libraries described herein may designed for further processing by transcription or translation. The variant oligonucleic acid libraries described herein may be designed to generate variant RNA, DNA and/or protein populations. Further provided herein are method for identifying variant species with increased or decreased activities, with applications in regulating biological functions and the design of therapeutics for treatment or reduction of disease.

Abstract: Methods of generating conditionally active biologic proteins, in particular therapeutic or diagnostic proteins, which are more active at an aberrant condition than at a normal physiological condition. The methods include discovery methods using libraries of proteins and assays employing physiological concentrations of components of bodily fluids. The conditionally active biologic proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety. Criteria for selecting starting proteins for the discovery methods, as well as formats of the proteins are also disclosed.

Abstract: Apparatus are described for providing support and maintenance of facial structures using facial support members that include internal silicone gel pads that are encased in an elastomeric casing and are dimensioned to apply downward pressure to tissues underlying the facial support members.

Abstract: The present invention relates to the dual, independent cistron expression system in a single vector for the production of protein of interest proteins and peptides expressed as insoluble inclusion bodies formed in the bacteria E. coli. The present invention also provides the process for the expression of protein of interest using said bicistronic vector.

Abstract: Provided are methods and kits for reducing the severity of muscle stiffness. The method comprises delivering to one or more specific locations in the deep fascia of an affected muscle a composition comprising a therapeutically effective amount of hyaluronidase.

Abstract: Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.

Abstract: The subject invention pertains to compositions and methods for promoting repair of damaged nerve tissue. The compositions and methods of the subject invention can be employed to restore the continuity of nerve interrupted by disease, traumatic events or surgical procedures. Compositions of the subject invention comprise one or more chondroitin sulfate proteoglycan (CSPG)-degrading enzymes that promote axonal penetration into damaged nerve tissue. The invention also concerns methods for promoting repair of damaged nerve tissue using the present compositions and nerve tissue treated according to such methods. The invention also pertains to kits for nerve repair.

Abstract: A method of treating or preventing a disorder, or a complication of a disorder, of an eye of a subject comprising contacting a vitreous and/or aqueous humor with a composition comprising a truncated form of plasmin comprising a catalytic domain of plasmin (TPCD). TPCDs include, but are not limited to, miniplasmin, microplasmin and derivatives and variants thereof. The methods of the invention can be used to reduce the viscosity of the vitreous, liquefy the vitreous, induce posterior vitreous detachment, reduce hemorrhagic blood from the eye, clear or reduce materials toxic to the eye, clear or reduce intraocular foreign substances from the eye, increase diffusion of a composition administered to an eye, reduce extraretinal neovascularization and any combinations thereof. The method can be used in the absence of, or as an adjunct to, vitrectomy.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

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: This invention relates to methods of enhancing the permeability of blood vessels to therapeutic agents.

Abstract: The present invention relates to pharmaceutical preparations comprising Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders. The invention further relates to the combined use of a Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the treatment and prevention of bleeding disorders, and to a method for increasing the bioavailability after non-intravenous administration of Factor VIII by co-adminstration of a sulfated glycosaminoglycan and a hyaluronidase.

Abstract: Modified PH20 hyaluronidase polypeptides that exhibit stability and activity under thermal stress conditions are provided. Also provided are compositions and formulations and uses thereof.

Abstract: An anesthetic composition for use e.g. in the administration of a local anesthetic by injection comprises a first component, which comprises hyaluronidase, and a second component which comprises an anesthetic preparation. The composition is both effective and highly shelf stable, and has as an advantage that it may be stored and administered at room temperature. In a particular embodiment, the hyaluronidase is prepared in dry powder form, as by lyophilization. The anesthetic component may be selected from a group of known anesthetics, such as lidocaine, polocaine, xylocaine, novocaine, procaine, prilocaine, bupivacaine, mepivacaine, carbocaine, etidocaine and chincocaine. The composition may be prepared in unit dosage forms, including a single dosage form, for a variety of purposes, and such unit dosage forms may be prepared in a plural chambered syringe or like dispenser, whereby the components are not mixed until administration.

Abstract: An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (e.g., a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device. The device may be rigid, or flexible, in which case a flexible device can be attached to a bio-degradable support scaffold that provides sufficient structural rigidity for insertion of the device into the target tissue.

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: A composition useful for the treatment of degenerative brain disease. A pharmaceutical composition comprising an effective amount of apamin as an active ingredient and an effective amount of at least another compound including a permeability enhancer and/or carrier molecule.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: A method of treating keloid scars, hypertrophic scars or burn scars with contracture includes administering low molecular weight hyaluronic acid to the keloid scar, hypertrophic scar or burn scar with contracture.

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 technology relates to the use of a proteolytic enzyme, for example hyaluronidase, for the treatment of abnormal protein collection in a patient's lymphatic system. In addition, the present technology provides a composition and a combined preparation each comprising hyaluronidase and at least one further proteolytic enzyme, and a method of prevention and/or treating primary or secondary edema in a patient in need thereof, wherein the patient is administered a therapeutically effective amount of hyaluronidase.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: Effective devices and methods using a chemical denervation agent are provided for treating chronic back pain. The devices and methods comprise a chemical denervation agent to degrade or to shrink at least a portion of a nerve associated with back pain e.g. basivertebral nerve of the lumbar. In some embodiments, the methods and devices are configured to immediately release an effective amount of the chemical denervation agent within 24 hours and provide sustained release of the chemical denervation agent or other therapeutic agent over a period of up to one year to treat chronic back pain.

Abstract: Methods for delivering an effective amount of insulin to the central nervous system to treat Social Communication Disorder while minimizing systemic exposure to the administered insulin. The present invention provides these advantages by administering at least an effective amount of insulin and/or pharmaceutical composition(s) thereof, to the upper third of the nasal cavity, thereby bypassing the blood-brain barrier and delivering an effective amount of insulin and/or pharmaceutical compound(s) thereof directly to the CNS. Further methods comprise administering an at least an effective amount of therapeutic agents to the amniotic fluid surrounding a fetus with a treatable neurologic agent or a preventable neurologic condition. For example, administering the at least effective amount of insulin to the amniotic fluid of a fetus with a mother diagnosed with gestational diabetes may prevent the fetus from developing Social Communication Disorder or autism.

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 form 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 present invention relates to methods for making a stabilized powder formulation for inhalation comprising a macromolecule in lyophilized form, a crystalline carrier material, and magnesium stearate.

Abstract: The present invention provides a tnaluronidase. The hyaiuronidase 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>aluronidase preparatkiiis. Described are also various uses of the hyaiuronidase, including topical administration of the h>aiuronidase to improve skin penetration of a co-administered active substance.

Abstract: Provided are 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. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: The methods and compositions disclosed herein are effective in the promoting the reattachment of delaminated cartilage to bone. The methods (and related compositions) comprise the removal of the acellular layer of the delaminated cartilage thereby exposing the underlying chondrocyte cells thereby allowing the promotion of the reattachment of the delaminated cartilage.

Abstract: Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.

Abstract: Provided herein are diagnostic methods for identifying subjects susceptible to treatment with a hypoxia-activated agent, and related methods. Also provided herein are methods of monitoring treatments with anti-hyaluronan agents, and related methods.

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: Bee venom may be administered in a standardized formulation with or without relatively small amounts of anesthetic. In particular, the results of the combination of venom and anesthetic dramatically decreased pain and discomfort for patients undergoing apitherapy.

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 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 form 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 compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

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 form 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: Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.

Abstract: Provided are compositions and formulations or co-formulations containing a hyaluronan degrading enzyme. The compositions, formulations or co-formulations can also contain another therapeutic agent, such as one that is suitable for treatment of Benign Prostatic Hyperplasia, for example, a 5-alpha reductase inhibitor. The compositions and formulations can be used for the treatment of Benign Prostatic Hyperplasia. The compositions and formulations can be provided in combinations with one or more other agents for the treatment of Benign Prostatic Hyperplasia.

Abstract: Bee venom may be administered in a standardized formulation with or without relatively small amounts of anesthetic. In particular, the results of the combination of venom and anesthetic dramatically decreased pain and discomfort for patients undergoing apitherapy.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: The present invention relates to an agent for use as a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation, a method of diagnosing or monitoring apoptosis-factor-associated conditions or disorders as well as a method of identifying a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation. Preferably, the invention relates to TRAIL-induced cell death and/or TRAIL-induced apoptosis. Preferably the agents are used to stimulate and/or enable TRAIL-induced cell death or to inhibit TRAIL-induced cell death. The preferable use of the diagnostic tools is to diagnose sensitivity or resistance to TRAIL-induced cell death or induction of sensitivity or resistance to TRAIL-induced cell death by an agent.

Abstract: The present invention provides a tnaluronidase. The hyaiuronidase 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 hyaiuronidase, including topical administration of the h>aiuronidase to improve skin penetration of a co-administered active substance.

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 disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.