Abstract: The present invention relates to a cell permeable fusion protein for strengthening regenerative potential of stem cells, and more particularly to a cell permeable fusion protein for strengthening regenerative potential of stem cells for stimulating the differentiation of stem cells, inhibiting apoptosis, maintaining the functionality of stem cells and restoring the stress-inhibited functionality of stem cells.

Abstract: Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. In these methods, the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). The bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen. Methods of treating collagenopathies using a composition including a collagen-binding polypeptide and a PTH/PTHrP receptor agonist are also provided. In addition, methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. Finally, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided.

Abstract: The invention relates to the use of peptides corresponding to dermaseptin B2 or fragments thereof for treating proliferative diseases such as cancer or ocular lesions, and to pharmaceutical compositions containing such peptides.

Abstract: The present invention provides methods and compositions to reduce growth of microbial colonies, including infections, and includes therapeutic compositions, methods for treatment of infections, and methods for identifying additional such compositions.

Abstract: Novel biologically active compounds of the general formula (I) in which one of X and X? represents a polymer, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; or, if X? represents a polymer, X-Q-W— together may represent an electron withdrawing group; and in addition, if X represents a polymer, X? and electron withdrawing group W together with the interjacent atoms may form a ring; each of Z1 and Z2 independently represents a group derived from a biological molecule, each of which is linked to A and B via an amine group; or Z1 and Z2 together represent a single group derived from a biological molecule which is linked to A and B via two amine groups; A is a C1-5 alkylene or alkenylene chain; and B is a bond or a C1-4 alkylene or alkenylene chain; are formed by conjugating a suitable polymer to a suitable biologically active molecule via amine groups in sai

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 present invention relates to a pharmaceutical or veterinary or nutritional or personal care composition comprising coenzyme Q10 (CoQ10), reduced CoQ10, or mixtures thereof and oxygenated dibenzo-?-pyrone or an amino acyl ester thereof. The composition of the present invention is able to support and/or provide therapy to individuals at risk and/or under treatment for dysfunctions of energy metabolism, and specifically, for mitochondrial diseases.

Abstract: The present invention relates generally to the field of prevention of diseases caused by enveloped viruses. More particularly, this invention concerns a composition for inactivating an enveloped virus comprising at least one non phospholipid Lipid Vesicle (nPLV) able to interact with said enveloped virus and an agent that enhances the lipid exchange between said nPLV and the membrane of said enveloped virus.

Abstract: The present invention is related to a compound that includes a lysosomal enzyme and a targeting moiety, for example, where compound is a fusion protein including iduronate-2-sulfatase and Angiopep-2. In certain embodiments, these compounds, owning to the presence of the targeting moiety can crossing the blood-brain barrier or accumulate in the lysosome more effectively than the enzyme alone. The invention also features methods for treating lysosomal storage disorders (e.g., mucopolysaccharidosis Type II) using such compounds.

Abstract: A hydrolytic enzyme is stabilized in a liquid surfactant preparation using a component that stabilizes the hydrolytic enzyme and includes a phenylalkyldicarboxylic acid.

Abstract: A hydrolytic enzyme is stabilized in a liquid surfactant preparation using a component that stabilizes the hydrolytic enzyme and encompasses an oligoaminobiphenyl oligocarboxylic acid.

Abstract: The present invention relates to compositions comprising factor VII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of coagulation factor-related diseases, disorders, and conditions.

Abstract: The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of a target cell by a pathogen, such as a virus. The present invention also comprises therapeutic compositions having sialidase activity, including protein-based compounds having sialidase catalytic domains. Compounds of the invention can be used for treating or preventing pathogen infection, and for treating and reducing allergic and inflammatory responses. The invention also provides compositions and methods for enhancing transduction of target cells by recombinant viruses. Such compositions and methods can be used in gene therapy.

Abstract: Methods and therapeutic treatments of ocular diseases are provided including applying peg-Arginase I to affected eyes. Methods are provided that simultaneously treat inflammation and neovascularization of eyes while promoting healing. Methods are provided to treat lesions or infections of an eye.

Abstract: Modified Factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Abstract: The present invention relates to chimeric (preferably, bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds preferably covalently bind to the urokinase receptor and recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and/or antibody-dependent cellular cytotoxicity (ADCC) against a large number and variety of cancers, thus providing cancer cell death and/or an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.

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

Abstract: Described herein are methods of making targeting peptides conjugated to recombinant lysosomal enzymes by modifying the amino (N)-terminus and one or more lysine residues on recombinant human lysosomal enzymes using a first crosslinking agent to give rise to first crosslinking agent modified recombinant human lysosomal enzymes, modifying the first amino acid within a short linker at the amino (N)-terminus on a variant IGF-2 peptide using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short linker. Also described herein are conjugates synthesized characterized as having higher affinities for the IGF2/CI-MPR receptor and cellular uptake using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, ?-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

Abstract: The present invention provides a novel fusion polypeptide containing a catalytic portion of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

Abstract: The present invention relates to polypeptides for use in suppressing cancer and cancer disorders. The treatment employs use of a non-cytotoxic protease, which is targeted to the cancer cell, and, when so delivered, the protease is internalised and inhibits secretion from the cancer cell.

Abstract: The present disclosure provides complexes comprising an FGF-10 portion and a heterologous protein or peptide, as well as methods of using such complexes.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Abstract: The invention provides methods, compositions, systems, and kits that include an enzyme/substrate co-delivery system. The liquid delivery system includes at least one enzyme encapsulated in a water-soluble polymeric matrix and a substrate for the enzyme in a carrier liquid in which the polymeric matrix is insoluble. When water is added, the polymeric matrix is solubilized and enzyme is released from the matrix, permitting catalytic action upon the substrate.

Abstract: The present invention provides chimeric polypeptides comprising myotubularin 1 (MTMI) polypeptides and an internalising 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: The present invention provides PEGylated tyrosyl-tRNA synthetase (YRS) polypeptides, compositions comprising the same, and methods of using such polypeptides and compositions for treating or diagnosing a variety of conditions. The PEGylated YRS polypeptides of the invention have improved controlled release properties, stability, half-life, and other pharmacokinetic properties compared to non-PEGylated YRS polypeptides.

Abstract: A peptide for synthesizing silica and use thereof are provided. The peptide for synthesizing silica can polymerize silica from a silica precursor in an aqueous solution having conditions of normal temperature, normal pressure and near-neutral weak base. The peptide for synthesizing silica can form a self-assembled structure during silica synthesis, and thus can be used as various biomaterials such as a silica-based protein immobilizer, a biosensor, and a drug delivery system.

Abstract: Thrombopoietic compositions are provided comprising tyrosyl tRNA synthetase polypeptides, including truncations and/or variants thereof. Also provided are methods of using such compositions in the treatment of conditions that benefit from increased thrombopoiesis, such as thrombocytopenia.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases.

Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of autoimmune disease, inflammatory disease, or cancer. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

Abstract: A chimeric toxin is disclosed comprising a peptide ligand specifically targeting neurons involved in pain processing; and a clostridial neurotoxin light chain, wherein the ligand is linked to the light chain. The methods of preparing such chimeric toxin and the method of using the chimeric toxin to regulate pain transmission are also disclosed.

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: There is provided a method of producing a stabilized catalase enzyme. In the method, a substrate is thoroughly mixed with phosphate borate and catalase, rinsed with water and the solids dried. The dried solid may be mixed with polyvinyl alcohol and dried for further stabilization. The stabilized powder may be mixed with various skin solutions (lotions, ointments and the like). The catalase enzyme can catalyze the reaction of peroxide to oxygen.

Abstract: The present invention relates to B-domain truncated Factor VIII molecules with a modified circulatory half life, said molecule being covalently conjugated with a hydrophilic polymer. The invention furthermore relates to methods for obtaining such molecules as well as use of such molecules.

Abstract: The present invention relates to new aminopyrimidine inhibitors of tyrosine kinase activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The use of tPA to treat hemorrhagic transformation, neurotoxicity has been limited to short treatment time windows because a high dose of tPA required to generate sufficient amounts of the enzyme plasmin for clot lysis. The present invention combines tPA with recombinant Annexin A2 resulting in thrombolysis without hemorrhagic transformation at delayed times after stroke. This embodiment allows the administration of a lower, non-neurotoxic, tPA dose. Our results suggest this novel combination for stroke therapy may greatly improve both efficacy and safety, and prolong tPA therapeutic time window.

Abstract: The invention relates to methods of targeted drug delivery of compounds, including, chemical agents, (poly)peptides and nucleic acid based drugs (like DNA vaccines, antisense oligonucleotides, ribozymes, catalytic DNA (DNAzymes) or RNA molecules, siRNAs or plasmids encoding thereof). Furthermore, the invention relates to targeted drug delivery of compounds to extravascular and intracellular target sites within cells, tissues and organs, in particular to target sites within the central nervous system (CNS), into and across the blood-brain barrier, by targeting to glutathione transporters present on these cells, tissues and organs. Thereto, the compounds, or the pharmaceutical acceptable carrier thereof, are conjugated to glutathione-based ligands that facilitate the specific binding to and internalization by these glutathione transporters.

Abstract: Orally administrable pharmaceutical compositions of lipase-containing products, particularly pancreatin and pancreatin-containing products, or of enzyme products which contain at least one lipase of non-animal, especially microbial origin, which improve the lipolytic activity and particularly result in stabilization of the lipase in the acidic pH range. These oral pharmaceutical compositions contain a system which includes at least one surfactant and one co-surfactant and optionally a lipophilic phase, and are self-emulsifiable on contact with a hydrophilic and a lipophilic phase. The compositions according to the invention are suitable for treating or inhibiting maldigestion, especially maldigestion due to chronic exocrine pancreatic insufficiency, in mammals and humans.

Abstract: The present invention relates to a method for suppressing or treating cancer, in particular to a method for suppressing or treating one or more of colorectal cancer, breast cancer, prostate cancer and/or lung cancer. The therapy employs use of a non-cytotoxic protease, which is targeted to a growth hormone-secreting cell such as to a pituitary cell. When so delivered, the protease is internalised and inhibits secretion/transmission of growth hormone from said cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract: Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.

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: Peptidoglycan hydrolases are an effective new source of antimicrobials. A chimeric fusion protein of the Ply187 endopeptidase domain and LysK SH3b cell wall binding domain is a potent agent against Staphylococcus aureus in three functional assays.

Abstract: This invention relates to methods of modifying pyridoxal 5? phosphate (PLP) dependent enzymes to extend the serum half-life of the enzyme, extend the in vivo period of methionine depletion in a host, and decrease the immunogenicity of the enzyme. A preferred PLP-dependent enzyme to be modified is a methioninase, preferably a recombinant methioninase (rMETase). The invention further relates to compositions comprising a modified PLP-dependent enzyme and methods of using the same.

Abstract: Reagents and methods for functionalizing polypeptides with moieties poly (alkylene glycol) molecules and glycan groups are disclosed that are based on a functionalizing reagent which comprises a nitrogen containing heterocyclic aromatic ring having a vinyl substituent that is capable of reacting with one or more thiol groups that are naturally present, or have been introduced into, the polypeptide, for example by employing a thiol group of one or more cysteine residues. The functionalizing reagent is covalently linked to a poly (alkylene glycol) molecule, such as a polyethylene glycol (PEG) molecule, or a glycan group so that the reaction between the vinyl group and the thiol group in the polypeptide covalently links the polypeptide to the poly (alkylene glycol) molecule and/or the glycan group.

Abstract: The present invention provides an aqueous pharmaceutical composition comprising the fusion protein whose amino acid sequence is set forth as SEQ ID No:1 and an aqueous solution comprising 40 to 60 mM sodium phosphate. The present invention further provides a lyophilized pharmaceutical composition, an reconstituted solution, a sealed package comprising the lyophilized pharmaceutical composition, and a vial comprising the lyophilized pharmaceutical or the reconstituted solution. The present invention also provides a method of producing the lyophilized pharmaceutical composition and the sealed package. The present invention also provides a method of treating a human having cocaine seeking behavior, and methods of using the aqueous pharmaceutical composition and lyophilized pharmaceutical composition.

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: Disclosed is an invention which relates to synthesizing immobilized and crosslinked proteases derived from plants for use as skin care agents. The resulting stabilized protease will minimally penetrate the skin because of its immobilized nature. It will retain activity because of its crosslinked nature and, in certain embodiments, due to its stabilization via physical additives. The present invention relates in particular to a linked papain product used in topical skin applications.

Abstract: Methods for evaluating responsiveness of a subject having cancer to treatment with an activin receptor-like kinase 1 (ALK1) antagonist are provided. Methods for selecting a subject for treatment with an ALK1 antagonist based on the subject being identified as responsive to such treatment are also provided. Some of the diagnostic methods provided herein are based on detecting an ALK1 agonist, e.g., an ALK1 ligand such as BMP9 or BMP10, in a sample obtained from the subject. Diagnostic reagents and kits for determining whether a subject is responsive to treatment with an ALK1 antagonist are also provided.

Abstract: The disclosure provides targeted cargo proteins that are useful for targeting cancer stem cells, and methods of their use in treating cancer.