Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.

Abstract: The present invention provides a method of treating cognitive impairment of Hunter syndrome. Among other things, the present invention provides a method comprising a step of administering intrathecally to a subject in need of treatment a recombinant iduronate-2-sulfatase (I2S) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce declining of one or more cognitive, adaptive, motor, and/or executive functions relative to a control.

Abstract: Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

Abstract: The present invention provides a method of making a proteinase-engineered cancer vaccine for treating a cancer patient, especially for cancer patient at advanced/metastatic stage. The cancer vaccine comprises dead cancer cells with unbroken plasma membrane wherein the extracellular proteins and extracellular portion of membrane proteins are cleaved by proteinase digestion. The cancer vaccine may be derived from cancer cell lines or patients' cancer cells. The present invention provides a method of treating a cancer patient by administrating an effective amount of the cancer vaccine to the patient. In a clinical trial with 35 cancer patients, the cancer vaccine therapy brings cancer-free lives (no detectable tumor, micro tumor or cancer cells after treatments of customized cancer vaccines) back to 40% of these patients. The present invention further provides a method of obtaining cancer-specific immune components from blood of individuals treated with the cancer vaccine.

Abstract: Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

Abstract: Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

Abstract: Model and method of treating inflammatory diseases. Traditional treatments for such diseases include administering to the patient toxic anti-inflammatory drugs. Following stabilization of the symptoms, the drug doses are tapered down to minimize side effects, as a result of which inflammation remains high and the disease is rarely cured. A chemistry-based disease model concludes that irrespective of the role that inflammation plays in the disease, inflammation reduction will impede disease initiation and progression. Managing and controlling inflammatory diseases requires reducing inflammation to acceptable normal values. Non-toxic ways such as non-steroidal anti-inflammatory drugs, anti-inflammatory diets, and regular exercise allow such reduction in inflammation to normal values, thereby slowing down or arresting disease progression and allowing the discontinuation or reduction of toxic anti-inflammatory therapy while maintaining low inflammation using non-toxic therapy.

Abstract: The present invention provides, among other things, compositions, kits and methods for subcutaneous delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention provides methods for treating Hunter syndrome by subcutaneous administration of a replacement iduronate-2-sulfatase (I2S) protein. In some embodiments, the present invention provides a kit comprising an arrangement of components for subcutaneously administering iduronate-2-sulfatase (I2S) protein.

Abstract: A recombinant polypeptide is described including at least one PUF RNA-binding domain capable of specifically binding to a cytosine RNA base. The PUF RNA-binding domain of the polypeptide includes at least one RNA base-binding motif of the general formula X1X2X3X4X5X6X7X8X9X10X11 wherein X1 is selected from a defined group and wherein the RNA base-binding motif is operably capable of specifically binding to a cytosine RNA base.

Abstract: The invention relates to a method for assaying plasminogen in a sample comprising a step consisting in particular of reacting a streptokinase (R1), and a streptokinase activator, with a control solution or a diluted plasma sample, in which the streptokinase activator is selected from the group comprising a fibrin DD fragment and/or at least one DD fragment derivative. The invention also relates to a liquid composition, a plasminogen assay kit for implementing this method and the use of a streptokinase activator selected from the group comprising a fibrin DD fragment and/or at least one DD fragment derivative.

Abstract: The present invention relates to stable aqueous formulations comprising at least 5 mg/mL CD-RAP and a charged amino acid, said amino acid preferably having a net charge at a pH between about 6 and 8. The ingredients of the formulation preferably provide stability over repeated freeze-thaw cycles. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory disorders, preferably osteoarthritis. Furthermore, a kit comprising the formulation of the invention is provided.

Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.

Abstract: The invention provides reagents and methods for enzyme replacement therapy using chemically modified species of human cystathionine ?-synthase (CBS) to treat homocystinuria and other related diseases and disorders.

Abstract: The present invention provides chimeric polypeptides comprising myotubularin 1 (MTMI) polypeptides and an internalizing moiety, wherein, the moiety can be an antibody, and is preferably monoclonal antibody 3E10, a functional variant or a fragment thereof. One aspect of the present invention provides compositions comprising these chimeric polypeptides together with a pharmaceutically acceptable carrier, and optionally, a further therapeutic agent. Another aspect of the present invention provides methods of treating Myotubular Myopathy comprising administering the polypeptides or compositions comprising the polypeptides to a subject in need.

Abstract: A product containing papain, bromelain or mixtures thereof is intended for use as a medicinal product at a dosage of at least 5000 mg administered for at least one day in a single dose. This dosage relates to papain powder having a titer of 3 U/mg and bromelain powder having a titer of 2 U/mg, and to a patient with a body weight of 55 kg. In the case of variations of the titer and/or of the patient's weight, the dosage must be varied in proportion to said variations.

Abstract: The invention belongs to the field of functional proteomics and, more particularly, to the field of protein aggregation. Described are methods for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as interferor, that has a specificity for a target protein and that induces aggregation upon contact with the target protein. The invention also discloses such interferer molecules and their use in therapeutic applications.

Abstract: The present invention relates to chimeric polypeptides comprising a first portion, which comprises a bacteriocin cell wall-binding domain (CBD) and a second portion, which comprises an enzymatic active domain (EAD) selected from the lytic domain of a bacteriophage lysin, a bacteriocin and a bacterial autolysin. Provided are such chimeric polypeptides and variants and fragments thereof, nucleic acids encoding the same, vectors carrying such nucleic acids and host cells transformed or transfected with such vectors. The chimeric polypeptides of the present invention are useful for the reduction of certain bacterial populations, including methods and compositions for the treatment of various bacterial infections. For example, chimeric polypeptides of the present invention have been shown to effectively kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), as well as other human pathogens.

Abstract: The present invention relates to methods for producing N-terminal derivatives of proteins in which a polysaccharide, preferably having at least terminal sialic units, and preferably consisting essentially only of sialic acid units, is reacted at the N-terminus of a protein or peptide under controlled conditions to produce an N-terminal derivative. The controlled conditions include use of acidic pH for the derivatisation step and a higher pH for purification. The derivatives are useful for improving pharmacokinetics and pharmacodynamics of proteins and peptides.

Abstract: The invention provides compositions and methods for targeted controlled drug release. The compositions and methods can be used for treating or imaging vascular stenosis, stenotic lesions, occluded lumens, embolic phenomena, thrombotic disorders and internal hemorrhage.

Abstract: The invention provides reagents and methods for enzyme replacement therapy using chemically modified species of human cystathionine ?-synthase (CBS) to treat homocystinuria and other related diseases and disorders.

Abstract: A method of reducing or treating parainfluenza or influenza virus infection in an immunocompromised patient by administering to the respiratory tract of the patient a composition comprising a therapeutically effective amount of protein having sialidase activity.

Abstract: Conjugates between Factor IX and PEG moieties. are disclosed in the present application. The conjugates are linked via a glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. Conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

Abstract: The present invention relates to the development of new derivatives of a bacterial plasminogen activator, Staphylokinase (SAK), having one or more amino acid residues with single or multiple cysteines at the amino and/or carboxy terminal ends and their conjugation with PEG (Polyethylene Glycol), resulting in new Staphylokinase derivatives that display altered oligomeric states, enhanced thermal and protease stability and extended plasma half-life. Also included is the cloning and expression in a suitable bacterial host; purification of Staphylokinase derivatives to homogeneity and their chemical modification by integrating a PEG molecule to create new biologically active Staphylokinases having higher protein stability and improved in vivo plasma half life, that may enhance the clinical potential of Staphylokinase in thrombolytic therapy for the treatment of cardiovascular diseases.

Abstract: The present invention is directed to compounds useful in stabilizing thrombin activity, thrombin compositions comprising the compounds, methods of using the compounds and methods of identifying compounds capable of stabilizing thrombin activity. The compounds are preferably isolated peptides comprising or interacting with the gamma loop of thrombin.

Abstract: Methods and therapeutic treatments of diseases such as viral infections are provided including applying peg-Arginase I. Methods are provided that treat inflammation mediated diseases with peg-Arginase I.

Abstract: Methods for rapidly obtaining a nanoscale apolipoprotein bound phospholipid bilayer (NABB) associated with at least one membrane protein are provided. Also disclosed are methods for rapidly obtaining a NABB not associated with membrane proteins. Immunogenic compositions comprising NABBs with native conformational epitopes are also provided along with their methods of use.

Abstract: The present invention provides albumin-binding probes capable of reversibly linking to short-lived amino-containing drugs and non-covalently associating with albumin in-vivo, thereby converting said drugs into inactive reactivable prodrugs having prolonged lifetime in-vivo. The invention further provides conjugates of said probes with amino-containing drugs, as well as pharmaceutical compositions and uses thereof.

Abstract: A composition is provided that includes a fish spawn protein isolate. A natural product extract is also present that includes unsaturated fatty acids and sterols. An emulsifier is provided to form a mixture of the isolate and the extract. A composition is also provided that includes an egg hatching protein isolate and at least one biocide protective of isolate activity. An emulsifier forms a mixture with the isolate that has an aqueous phase buffered to a pH of between 5.6 and 7.9. A process of producing such a cosmetic has an emulsion or an aqueous phase that is buffered to a pH of between 5.5 and 7.9 prior to the addition of isolate to the emulsion. A process of improving skin appearance is provided that includes the application of the cosmetic to the skin at least three times per week to achieve the improvement of the skin appearance.

Abstract: Methods and dosage formulations are provided for subcutaneous administration in which therapeutic agents are modified to increase the hydrophilicity and molecular dimensions in relation to the native state of the therapeutic agent, in which the Cmax:Caverage ratio is lower than the Cmax:Caverage ratio of the agent when delivered intravenously.

Abstract: The present invention provides methods of dosing Factor VIII or Factor IX chimeric and hybrid polypeptides.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotropin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: The present invention provides further improved compositions and methods for efficient lysosomal targeting based on the GILT technology. Among other things, the present invention provides methods and compositions for targeting lysosomal enzymes to lysosomes using furin-resistant lysosomal targeting peptides. The present invention also provides methods and compositions for targeting lysosomal enzymes to lysosomes using a lysosomal targeting peptide that has reduced or diminished binding affinity for the insulin receptor.

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with improved specificity and methods for generating and using such TALEs.

Abstract: A method and composition are presented for enhancing the dissolution and bioavailable properties of CoQ10 nutritional supplements and/or therapeutic agents for a human being and other mammals. The method includes preparing an anhydrous self-microemulsifying base composition by combining: CoQ10, a water-immiscible, and a non-ionic surfactant, containing polyethylene glycol. For an orally administered CoQ10 nutritional supplement in a capsule formulation, a unit dosage from the composition is added to a dissolvable capsule, preferably a soft gelatin capsule, in order to form the nutritional supplement. When a capsule containing the self-microemulsifying composition enters the digestive tract, the temperature of the body's digestive juices warms the composition, causing any of the CoQ10 that may have re-crystallized out of the composition to become re-dissolved into the composition before the capsule dissolves. The re-dissolution of CoQ10 is bioavailable when the capsule dissolves.

Abstract: The invention provides methods for the synthesis of oligosaccharides comprising an aminooxy group. The invention further provides oligosaccharides comprising an aminooxy group, methods for coupling oligosaccharides comprising an aminooxy group to glycoproteins, and oligosaccharide-protein conjugates. Also provided are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-protein conjugate.

Abstract: Novel hybrid polymers are disclosed that have a structure represented by the following wherein Abiotic oligomer, Polypeptide, X, Y, and R1 are as described herein. The methods to prepare the hybrid polymers via novel oxazolidinyl compounds are also described.

Abstract: Provided are liquid compositions comprising inactive biopesticide precursors comprising a glucosinolate concentrate, a plant material comprising a myrosinase enzyme complex, and a water soluble polyol. Further provided are methods of making and using such compositions.

Abstract: The invention relates to a controlled release delivery compositions and methods of using them for pathologies associated with Otorhinolaryngology and Head and Neck. Specifically, the invention relates to regulating drug delivery by the use of chitosan based matrices together with chitosanases.

Abstract: Antimicrobial compositions based upon stabilized angiogenin compositions also contain osteopontin and antimicrobial proteins such as lactoperoxidase (LPO), myeloperoxidase (MPO), salivary peroxidase (SPO) and lysozyme.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidised polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: The present invention provides a site-directed mutated arginase and the preparation method thereof, and the use of said site-directed mutated arginase in preparing a medicament for treating an arginase-related disease. The present invention also provides a site-directed pegylated arginase and the preparation method thereof, and the use of said pegylated arginase in preparing a medicament for treating an arginase-related disease.

Abstract: The invention relates to compositions of vault complexes containing recombinant cytokine fusion proteins that include a cytokine and a vault targeting domain, and methods of using the vault complexes to deliver the cytokines to a cell or subject, and methods for using the compositions to treat cancer, such as lung cancer.

Abstract: Provided herein are methods and compositions for treating a subject suffering from a deficiency in arylsulfatase A in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an arylsulfatase A.