Abstract: The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to form an inclusion complex. A therapeutic composition of the invention may be used to deliver the therapeutic agent and to treat various disorders. Both the polymer of the particulate composite and the complexing agent may be used to introduce functionality into the therapeutic composition. The invention also relates to a method of preparing a composition. The method combines a therapeutic agent, a polymer having host or guest functionality, and a complexing agent having guest or host functionality to form the therapeutic composition. The complexing agent forms an inclusion complex with the polymer. The invention also relates to a method of delivering a therapeutic agent.

Abstract: The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a transferrin receptor (TfR). Therapeutic uses for the conjugates are also provided.

Abstract: The invention provides fusion proteins comprising an exendin-4 fused to a transferrin (Tf) via a polypeptide linker, as well as corresponding nucleic acid molecules, vectors, host cells, and pharmaceutical compositions. The invention also provides the use of the exendin-4/Tf fusion proteins for treatment of Type II diabetes, obesity, and to reduce body weight.

Abstract: The present invention relates to isolation of whey proteins and the preparation of a whey product and a whey isolate. In particular the present invention relates to the isolation of a ?-lactoglobulin product and the isolation of an ?-enriched whey protein isolate from whey obtained from an animal. The ?-enriched whey protein isolate provided by the present invention is besides from being low in ?-lactoglobulin also high in ?-lactalbumin and immunoglobulin G.

Abstract: Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission.

Abstract: The present invention provides a micelle comprising an amphiphilic block copolymer, said amphiphilic block copolymer consisting of (a) a hydrophobic polymer attached to the 5? end of a first nucleic acid molecule, wherein said first nucleic acid molecule is hybridized with a second nucleic acid molecule, wherein a targeting unit capable of selectively binding to a specific cell type and/or tissue is attached to the 5? end of said second nucleic acid molecule; and/or (b) a hydrophobic polymer attached to the 3? end of a first nucleic acid molecule, wherein said first nucleic acid molecule is hybridized with a second nucleic acid molecule, wherein a targeting unit capable of selectively binding to a specific cell type and/or tissue is attached to the 3? end of said second nucleic acid molecule.

Abstract: The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.

Abstract: Based on the three-dimensional structure of transferrin, the inventors have designed variant polypeptides (muteins) which have one or more Cysteine residues with a free thiol group (hereinafter referred to as thiotransferrin). The variant polypeptide may be conjugated through the sulphur atom of the Cysteine residue to a bioactive compound.

Abstract: An anticancer agent containing BL-angiostatin as an active ingredient; and a process for producing the same. Also a method for treating cancer comprising administering to a mammal a pharmaceutically effective amount of BL-angiostatin.

Abstract: Fusion proteins comprising a transferrin moiety and integrin binding domain and peptide libraries thereof are disclosed. The present invention includes a method of screening transferrin and integrin peptide libraries displayed in fusion proteins expressed by host cells. The fusion proteins of the present invention include transferrin fusion proteins capable of expression in yeast.

Abstract: Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

Abstract: [Problems] The differential diagnosis of Alzheimer's disease as distinguished from other type of dementia and the diagnosis of Alzheimer's disease at such an early stage where neural cell death has not proceeded yet are important for the treatment of Alzheimer's disease. On the other hand, it is difficult to differentially diagnose Alzheimer's disease at an earlier stage by a diagnosis mainly made by questioning by a doctor or a diagnostic technique using phosphorylated tau or amyloid-? protein as an indicator. Thus, the development of a novel diagnostic technique has been demanded. [Means for Solving Problems] An attention is focused on transferrin having a sugar chain attached thereto. Thus, disclosed are a diagnostic kit, a diagnostic marker and a detection method for differentially diagnosing the disease condition of Alzheimer's disease at an earlier stage.

Abstract: The invention relates to peptides which bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates to methods of using and methods of making the peptides of the invention.

Abstract: The present invention relates to single domain proteins that bind to epidermal growth factor receptor (EGFR). The invention also relates to single domain proteins for use in diagnostic, research and therapeutic applications. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative proteins.

Abstract: The invention relates to the use of Factor H for the manufacture of a medicament to treat both chronic nephropathies which are not causally associated with proteinuria and chronic nephropathies which are causally associated with proteinuria. The invention also relates to large scale purification methods for Factor H.

Abstract: The present invention relates to a multi-conjugate of small interfering RNA (siRNA) and a preparing method of the same, more precisely a multi-conjugate of siRNA prepared by direct binding of double stranded sense/antisense siRNA monomers or indirect covalent bonding mediated by a cross-linking agent or a polymer, and a preparing method of the same. The preparing method of a siRNA multi-conjugate of the present invention is characterized by simple and efficient reaction and thereby the prepared siRNA multi-conjugate of the present invention has high molecular weight multiple times the conventional siRNA, so that it has high negative charge density, suggesting that it has excellent ionic interaction with a cationic gene carrier and high gene delivery efficiency.

Abstract: The present invention provides methods for treating or preventing diseases and disorders caused by iron-dependent pathogenic microorganisms, such as bacteria, fungi, and parasites, by applying a gallium compound to an affected area. In particular, the present invention provides methods for treating or preventing dental caries, vaginal infections, skin infections, and so forth. Gallium compounds can be formulated as toothpaste, mouthwash, cream, ointment, gel, solution, eye drops, suppository, and the like. Furthermore, the invention provides methods for controlling microbial growth on environmental surfaces, including those of toothbrush, denture, dental retainer, contact lens, catheter, food stuff, and so forth. In addition, the present invention provides animal feeds which contain gallium compounds that promote the animal growth and prevent the animals from infections as well as protect consumers from post processing infections.

Abstract: The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3?-position, their bioconjugates and their uses are described. 1,3?-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1?-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups.

Abstract: An agent for thermally stabilizing lactoferrin, which comprises a nucleic acid as an active ingredient, can be added to lactoferrin to impart thermal stability to lactoferrin. Thermally stabilized lactoferrin can be heat-sterilized at a pH value around a neutral pH value while keeping its activity.

Abstract: A method that accurately and conveniently detects a compound shown by the formula (I) in a human sample is disclosed. An antibody that reacts with the compound shown by the formula (I), but does not cross-react with the N-oxide metabolite and the desmethyl levofloxacin metabolite of the compound shown by the formula (I) is prepared using an antigen produced by binding bovine serum albumin to the compound shown by the formula (I) through the 6-position carboxyl group. Immunoassay that measures the compound shown by the formula (I) that has not been metabolized is implemented using the above antibody.

Abstract: A method for destroying harmful cells is provided, applicable in treating proliferative diseases. The cells are destroyed by a combined treatment with a chemiluminescent agent and with a ligand-photosensitizer conjugate. The chemiluminescent agent emits light on reacting with oxygen species present in situ, the conjugate binds to the cell through its ligand and is activated by the emitted light, thereby destroying the cell. The method is demonstrated on a conjugate of transferrin-hematoporphyrin, which destroys cancerous cells in the presence of luminol.

Abstract: An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.

Abstract: Hydrolyzate compositions comprising at least one milk protein or whey hydrolyzed with at least one proteolytic enzyme are provided. The hydrolyzates reduce the immunogenicity of the milk or whey protein in a subject predisposed to having an immune reaction to the protein. Methods for making the compositions are also provided, as food products and nonfood products comprising the compositions.

Abstract: The present invention provides novel fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of a homologue of native IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2-homologue/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for the preparation of a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.

Abstract: The present invention provides a recombinant protein comprising the sequence of a transferrin mutant, wherein Ser415 is mutated to an amino acid which does not allow glycosylation at Asn413 and/or wherein Thr613 is mutated to an amino acid which does not allow glycosylation as Asn611. It also provides polynucleotides encoding the same and methods of making and using said recombinant protein.

Abstract: A process for isolation and purification of a target protein by chromatography wherein the chromatography removes or depletes prions (PrPSC), comprising the steps of contacting a potentially PrPSC contaminated sample comprising a target protein with a multimodal chromatographic material; setting buffer conditions so that the target protein is bound to the multimodal chromatographic material and whereas PrPSC is not binding to the multimodal chromatographic material; followed by elution of the target protein. a process for isolation and purification of a target protein free of prion protein (prpSC).

Abstract: The invention relates to compositions and methods for modulating the expression of alpha-ENaC, and more particularly to the downregulation of alpha-ENaC expression by chemically modified oligonucleotides.

Abstract: A method for destroying harmful cells is provided, applicable in treating proliferative diseases. The cells are destroyed by a combined treatment with a chemiluminescent agent and with a ligand-photosensitizer conjugate. The chemiluminescent agent emits light on reacting with oxygen species present in situ, the conjugate binds to the cell through its ligand and is activated by the emitted light, thereby destroying the cell. The method is demonstrated on a conjugate of transferrin-hematoporphyrin, which destroys cancerous cells in the presence of luminol.

Abstract: Methods of producing properly refolded recombinant plasminogen and plasmin polypeptide are provided. Denatured recombinant plasminogen polypeptide is refolded by first solubilizing the polypeptide with a chaotroph and reducing and oxidizing agents at high pH, followed by refolding in the presence of reduced concentration of chaotroph and reducing and oxidizing agents and in the presence of arginine.

Abstract: A process for enhancing the recovery yield of proteins, especially plasma proteins, from sources containing the proteins, wherein the sources containing the proteins are frozen at temperatures of ??70° C., and the proteins from a frozen source after thawing are further processed in a per se known manner.

Abstract: Compositions and methods for decreasing the viability of cells, particularly aberrant non-healthy cells, and most particularly cancer cells, are disclosed. The primary agent that causes cell death is a toxic metal atom or ion. Embodiments of the invention provide compositions and methods to ensure that the toxic metal is directed to the desired cell or tissue. In one embodiment, the metal is bound to a sulfur-rich peptide or protein carrier containing a targeting moiety. Such metal-protein complex is targeted to the selected cells or tissues to enrich the cell or tissue site with the metal-containing peptide or protein molecules followed by administering a dithiocarbonyl which carries the metal from the protein inside the cells to induce cell death.

Abstract: The present invention provides innovative proteins that bind to insulin-like growth factor-I receptor (IGF-IR), as well as other important proteins. The invention also provides innovative proteins in pharmaceutical preparations and derivatives of such proteins and the uses of same in diagnostic, research and therapeutic applications. The invention further provides cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins.

Abstract: Chromophore probes that are capable of being taken up by, retained by or bound to a biocompatible molecule to form an imaging construct are provided. Various activation strategies of the resulting imaging construct are also provided.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural ? amyloid peptides (?-AP). In a preferred embodiment, the ? amyloid modulator compounds of the invention are comprised of an A? aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural ? amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural ?-AP aggregation when the natural ?-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.

Abstract: Fusion proteins comprising a transferrin moiety, a stalk moiety, and cell wall linking member and peptide libraries thereof are disclosed. The present invention includes a method of screening peptide libraries displayed in fusion proteins expressed by host cells. The fusion proteins of the present invention include transferrin fusion proteins capable of expression in yeast.

Abstract: Fusion proteins comprising a first protein fused to hemopexin are provided, said fusion proteins exhibit an increased circulation time.

Abstract: The invention provides a method for delivering a nucleic acid to a cell using a targeting molecule that is bound non-covalently to the nucleic acid. Compositions and kits are also provided.

Abstract: A biocompatible block copolymer having a hydrophobic segment composed of amino acid and hydroxycarboxylic acid and a hydrophilic segment composed of polyalkylene oxide, wherein the terminal not bonded to the hydrophilic segment of the hydrophobic segment is composed of an amino acid unit.

Abstract: The invention provides fusion proteins comprising an exendin-4 fused to a transferrin (Tf) via a polypeptide linker, as well as corresponding nucleic acid molecules, vectors, host cells, and pharmaceutical compositions. The invention also provides the use of the exendin-4/Tf fusion proteins for treatment of Type II diabetes, obesity, and to reduce body weight.

Abstract: The present invention provides transferrin (Tf) conjugates of anti-cancer agents with increased cellular association and increased cellular internalization. The present invention also provides methods of treating cancer comprising administration of a Tf conjugate with increased cellular association to a subject with cancer. The present invention additionally provides methods of making, as well as screening for, Tf conjugates with increased cellular association or cellular internalization. The present invention also provides Tf conjugates with increased cellular association and internalization for delivering nucleic acids to cancer cells.

Abstract: The present invention relates to fusion proteins. The invention specifically relates to compositions and methods of Tf-based fusion proteins that demonstrate a high-level expression of transferrin (Tf)-based fusion proteins by inserting a helical linker between two protein domains.

Abstract: A method for producing an oligomeric form of ?-lactalbumin which is in the molten globule-like state is described. The method suitably comprises exposing a source of ?-lactalbumin in which the ?-lactalbumin is preferably in the molten globule-like state, to an ion exchange medium which has been pre-treated with casein or an active component thereof, such as oleic acid, and recovering ?-lactalbumin in an oligomeric form therefrom. Pre-treatment of the ion exchange medium, particularly with casein derived from human milk, has been found to significantly improve yields of the oligomeric form of ?-lactalbumin and mean that it can readily isolated from readily available sources such as bovine ?-lactalbumin. This form of ?-lactalbumin is useful therapeutically, in particular as an antibacterial agent and also as an anti-cancer therapeutic.

Abstract: Compounds comprising an angiopoietin-like protein 6 (Angptl6) peptide for use in the treatment of metabolic syndrome, in particular, obesity and insulin resistance are described.

Abstract: Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

Abstract: The present invention provides a method for increasing the yield of a protein produced by cultivating eukaryotic cells and adding an ionic substance to the culture medium prior to harvest of the protein. Suitable ionic substances are the salts of the Hofmeister series, amino acids and peptone.

Abstract: A polypeptide comprising a G-CSF domain operably linked to a Tf domain, wherein the ability of the polypeptide to be transported into a cell expressing a TfR gene or the ability of the polypeptide to be transported across a cell expressing a TfR gene via transcytosis is higher than that of the G-CSF domain alone.

Abstract: A polypeptide comprising a first protein domain, a second protein domain, and a dithiocyclopeptide spacer containing at least one protease cleavage site, wherein the dithiocyclopeptide is exogenous relative to the first or second protein domain, and wherein the first and second protein domains are operably linked by the dithiocyclopeptide. Also disclosed are methods of producing the polypeptide and delivering the protein domains into a cell.