Abstract: Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for targeting prostate cancer cells. Also described herein are compositions containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

Abstract: Provided are antisense oligonucleotides and other agents that target and modulate IL-17 and/or IL-23 signaling activity in a cell, compositions that comprise the same, and methods of use thereof. Also provided are animal models for identifying agents that modulate 17 and/or IL-23 signaling activity.

Abstract: The invention provides compositions and methods for therapeutic and diagnostic applications.

Abstract: The invention provides a method of identifying an inhibitor of LtaS comprising: (a) providing bacteria which comprise a mutation in the mbl gene or homologue thereof; (b) culturing the bacteria of (a) in the presence of a test substance under conditions of low magnesium; (c) monitoring the growth of the bacteria; wherein growth or more rapid growth of the bacteria compared to growth in the absence of the test substance is indicative that the test substance is an inhibitor of LtaS.

Abstract: The invention provides functionalized monosaccharides and disaccharides suitable for use in synthesizing a lipid A derivative, as well as methods for synthesizing and using a synthetic lipid A derivative.

Abstract: The invention discloses highly purified daptomycin and to pharmaceutical compositions comprising this compound. The invention discloses a method of purifying daptomycin comprising the sequential steps of anion exchange chromatography, hydrophobic interaction chromatography and anion exchange chromatography. The invention also discloses a method of purifying daptomycin by modified buffer enhanced anion exchange chromatography. The invention also discloses an improved method for producing daptomycin by fermentation of Streptomyces roseosporus. The invention also discloses high pressure liquid chromatography methods for analysis of daptomycin purity. The invention also discloses lipopeptide micelles and methods of making the micelles. The invention also discloses methods of using lipopeptide micelles for purifying lipopeptide antibiotics, such as daptomycin. The invention also discloses using lipopeptide micelles therapeutically.

Abstract: Provided is a process for purifying a vancomycin wet body, comprising: dissolving a wet body obtained from a microorganism-fermented solution containing vancomycin into a water soluble solvent to a concentration of about 1 to 40 g/L and carrying out reverse osmosis filtration; and carrying out lyophilization of the filtered vancomycin. The process for purifying a vancomycin wet body provides high-purity vancomycin, while avoiding degradation of stability during a drying step.

Abstract: The invention relates to the fields of materials sciences and medicine and relates to an agent, which can be used, for example, as a contrast medium for the localization of cancer cells. The object of the present invention is to disclose an agent which sensitively and selectively recognizes the site and the type of the molecules or cells to be examined. The object is attained through an agent composed at least of bio-shuttle molecules to which endohedral fullerenes are coupled by way of peptide-based molecules, wherein the endohedral fullerenes are hydrophobic and correspond to the formula A3-xMxZ@C2n in which x=0 to 3 and n?34, A means rare earths and/or transuranic elements, M means metals, Z means non-metals and C means carbon. The object is further attained through a method in which hydrophobic endohedral fullerenes are coupled with bio-shuttle molecules by way of an irreversible Diels-Alder reaction with an inverse electron demand (DARinv).

Abstract: The present invention relates to prodrugs of vascular disrupting agents comprising a vascular disrupting agent (VDA) associated with a MMP proteolytic cleavage site and to the use of such prodrugs in the targeted treatment of cancer.

Abstract: The present invention is directed to methods of transfecting cells with siRNA, by contacting a transfection complex with one or more cells, where the transfection complex includes a transport polymer and siRNA. The transport polymer may include for example, H3K8b and/or structurally similar compounds. The invention is also directed to such transfection complexes, and to compositions that include such transfection complexes. The invention is further directed to methods of treating patients using the transfection complexes of the present invention.

Abstract: This invention relates to a method of modulating the expression of a target gene in an organism comprising administering an iRNA agent, wherein the iRNA comprises at least one 2?-deoxy-2?-fluoro (2?-F) nucleotide in the antisense strand and at least one modified nucleotide in the sense strand. The invention also relates to compositions comprising a single-stranded oligonucleotide that contains at least one 2?-deoxy-2?-fluoro (2?-F) nucleotide. siRNA molecule containing these oligonucleotides have decreased immunogenicity.

Abstract: The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for CD38, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, hematological malignancies such as multiple myeloma. Antibodies of the invention also can be used in the diagnostics field, as well as for investigating the role of CD38 in the progression of disorders associated with malignancies. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

Abstract: Provided are compositions and methods for delivery of therapeutic agents, such as chemically stabilized antisense oligonucleotides useful in RNA silencing. The compositions include interfering nanoparticles (iNOPs) associated with one or more agents. Several functional iNOP derivatives are provided which allow for targeted delivery of agents to specific cell types as well as exhibiting reduced cellular toxicity.

Abstract: Described herein are methods for analyzing polymer molecules. These methods are employed for the high throughput readout of DNA and RNA molecules with single molecule sensitivity. The method of the present invention comprises (1) the electrically controlled unzipping of DNA (or RNA) double strands, and (2) the readout of the molecule's identity (or code) using one or more molecule signal detection.

Abstract: The subject invention pertains to a conjugate comprising: (a) a first region comprising the homeodomain of antennapedia or a variant thereof; and (b) a second region not naturally associated with the first region. In one embodiment, the second region of the conjugate comprises a protein of at least 100 amino acids.

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: Aspects of the invention provide compositions and methods for delivering nucleic acids to target cells.

Abstract: Multiligand constructs and intermediate multivalent constructs for use in their preparation are described. The multiligand constructs have utility in diagnostic and therapeutic applications.

Abstract: The present invention discloses compositions and methods for delivery of biomolecules into cells. Compositions comprise peptidomimetic macrocycles complexed or conjugated to biomolecules such as nucleic acids.

Abstract: A first aspect of the invention relates to a conjugate comprising: (i) mannan; and (ii) at least one epitope comprising a peptide fragment of a protein selected from myelin basic protein (MBP), myelin oligodentrocyte glycoprotein (MOG) and proteolipid protein (PLP), said peptide fragment being in linear or cyclic form; wherein said epitope is linked to mannan via a [(LyS-GIy)n] bridge, where n is an integer from 1 to 10. Further aspects of the invention relate to pharmaceutical compositions comprising said conjugates, and their use in the preparation of a medicament for treating an immune disorder.

Abstract: According to the present invention, there is provided a process for the preparation of a first compound selected from peptides, oligonucleotides and peptide nucleic acids. The process comprises synthesising the first compound and then separating the first compound formed in step (i) from a second compound, which is a reaction by-product of the synthesis of the first compound and/or an excess of a reagent used for the synthesis of a first compound by a process of diafiltration. The membrane used for the diafiltration process is stable in organic solvents and provides a rejection for the first compound which is greater than the rejection for the second compound.

Abstract: A contrast agent for MRI imaging includes: (a) one cyclodextrin, whose truncated-cone-shaped structure defines a central axis, a first and a second openings along the axis, (b) one paramagnetic element, located on the cyclodextrin axis, outside the structure and proximate to the first opening, (c) one or several coordination ligand(s) of the paramagnetic element which coordinate(s) the paramagnetic element, (d) one arm covalently bound to the cyclodextrin, proximate to the second opening, which is able to form an inclusion complex with the cyclodextrin.

Abstract: Disclosed are derivatives of glycopeptide compounds having at least one substituent of the formula: —Ra—Y—Rb—(Z)x where Ra, Rb, Y, Z and x are as defined, and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

Abstract: A non-enzymatically self cleaving dipeptide element is provided that can be linked to known medicinal agents via an amide bond. The dipeptide will spontaneously be cleaved from the medicinal agent under physiological conditions through a reaction driven by chemical instability. Accordingly, the dipeptide element provides a means of linking various compounds to known medicinal agents wherein the compounds are subsequently released from the medicinal agent after a predetermined time of exposure to physiological conditions. For example, the dipeptide can be linked to an active site of a drug to form a prodrug and/or the dipeptide may comprise a depot polymer to sequester an injectable composition comprising the complex at the point of administration.

Abstract: The invention provides methods for preparing a peptide useful in generating an antibody specific for the glycosylated form of a glycopolypeptide wherein the glycosylated portion is isolated and a peptide corresponding to amino acids adjacent to a glycosylated N-linked glycosylation site is prepared.

Abstract: Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-? activity or activity of the relevant ligand. Reducing TNF-? activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-? activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.

Abstract: The present invention is directed to nucleic acids delivery systems and methods of modulating an expression of a target gene using the same. In particular, the invention relates to nucleic acids conjugates containing an endosomal release-promoting moiety. The nucleic acids conjugates further contain a nuclear localization signal moiety, and/or a cell targeting moiety.

Abstract: There is provided a novel target recognition molecule. The target recognition molecule has a specific reactivity, and can be densely self-assembled and immobilized reversibly or irreversibly at a predetermined site in a microfluidic device. And The target recognition molecule including: (1) a target recognition peptide segment having an amino acid sequence which specifically interacts with a target substance capable of causing an immune reaction; and (2) an electrostatically-charged segment which is provided with three or more electrostatically-charged functional groups capable of being electrically charged to the same polarity in the same solution.

Abstract: Disclosed herein is a class of linkable tetrasaccharide compounds that includes the amino phenyl glycoside of sialyl Lewis X (SLeX) and related analogs. These compounds have conjugatable nucleophilic groups, making them useful in preparing multimeric SLeX compositions. In particular, the disclosed SLeX compounds can be used to prepare selectin binding ligand con-jugatcs by linking them to a reporter moiety, such as a contrast agent, a radiodiagnostic agent, or a cytotoxic or chemotherapeutic agent. The SLeX compounds and conjugates of the invention exhibit binding to selectin that is similar to native Sialyl LeX, and are, therefore, useful for diagnosing and treating selectin-mediated disorders and related conditions.

Abstract: Glycopeptide conjugates, and methods of making and using such conjugates are disclosed. Certain glycopeptide conjugates comprise tumor associated carbohydrate antigens and peptide epitopes. Certain glycopeptide conjugates comprise cyclic peptide scaffolds that display carbohydrate antigens in a clustered fashion. The immunogenicity of select glycopeptide conjugates is demonstrated.

Abstract: The invention relates to using a combination of DNA-expression constructs for producing a drug for immunisation against leishmania infections and a corresponding vaccine. The DNA-expression construct is also disclosed. According to said invention the immunogene P36 LACK is used in combination with a leishmania infantum thiol-specific antioxidant protein gene (TSA), leishmania infantum kinetoplastid membrane protein 11 (KMP-11) and with a leishmania infantum GP63 antigen for producing an immune response. Plasmides, preferably minimalist immunologically defined gene-expression constructs (MIDGE) can be used in the form of the DNA-expression construct. The inventive DNA-expression construct makes it possible to produce a vaccine for treating leishmania infectious diseases and is used in the form of a component of said vaccine.

Abstract: The present invention relates to a nucleic acid molecule and a pharmaceutical or diagnostic composition for the therapeutic and/or prophylactic treatment or diagnosis of cancer and/or metastasis thereof, comprising a nucleic acid molecule, or an amino acid sequence related to Trim71 and/or its mammalian and non mammalian orthologs and/or a nucleic acid sequence of the gene encoding for Trim71 and/or its mammalian and non mammalian orthologs.

Abstract: According to the present invention, there is provided a process for synthesis of a first compound selected from peptides, oligonucleotides, and peptide nucleic acids, which comprises synthesis of the first compound linked to a soluble support, wherein the soluble support is degraded following the synthesis so that it can be separated from the first compound.

Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Abstract: Provided are antisense oligonucleotides and other agents that target and modulate nuclear hormone receptors (NHRs) such as the glucocorticoid receptor (GR), compositions that comprise the same, and methods of use thereof.

Abstract: In accordance with the present invention, it has been discovered that the uptake of negatively charged entities into cells can be enhanced by noncovalently associating such charged entities with molecular entities comprising an amphiphilic core with positively charged arms, wherein a plurality of lipophilic (e.g., bile acid) moieties are covalently attached to the positively charged arms. The molecular entities form well defined stoichiometric complexes with negatively charged entities. Various compositions and methods for stabilizing anionic charged entities and for enhancing the cellular uptake of any anionic charged entities, e.g. double-stranded or hairpin nucleic acid, are provided.

Abstract: A method for the determination of the responsiveness of an individual to mistletoe lectin or to (an) mistletoe lectin single chain(s), wherein the expression of a membrane-bound receptor for mistletoe lectin is characteristic of a corresponding responsiveness.

Abstract: Disclosed are a nanoparticle sensor for measuring protease activity, for protease imaging, and a method for preparing the same. More specifically, the present invention relates to a nanoparticle sensor for measuring protease activity in which a fluorophore- and a quencher-conjugated peptide substrate is conjugated to a biocompatible polymer nanoparticle. The peptide substrate is specifically lysed by a protease. The sensor according to the present invention is capable of inhibiting emission of fluorescence with high extinctive activity of the quencher on a fluorescent material. But strong fluorescence is specifically emitted only if the peptide substrate is lysed by a specific protease. Therefore, the sensor is especially useful as a method for screening a novel drug such as a protease overexpression inhibitor, and early diagnosis of incurable diseases and various diseases such as autoimmune diseases including cancer, osteoarthritis, rheumatoid arthritis and dementia.

Abstract: A nucleic acid probe set includes (A) a fluorescent probe and (B) a binding probe. The fluorescent probe (A) is formed of an oligonucleotide, which includes (a) a nucleotide unit labeled with (d) a fluorescent substance. The binding probe (B) is formed of an oligonucleotide having (b1) a fluorescent probe binding region, which can hybridize to the fluorescent probe (A), and (b2) a target nucleic acid binding region, which can hybridize to a target nucleic acid sequence (C). The fluorescent substance (d) is a fluorescent substance which changes in fluorescent character upon interaction with guanine. At least one of nucleotide units which constitute the fluorescent probe (A) is an artificial nucleotide unit having a function to raise a dissociation temperature between the probe (A) and the fluorescent probe binding region (b1). The nucleic acid probe is provided with an improved fluorescence quenching efficiency.

Abstract: The present invention relates to a system for intracellular delivery of a cargo comprising at least one component A chosen from aliphatic linear or branched moieties with at least 4 carbon atoms and/or cyclic ring systems comprising 2-4 rings which may contain several hetero atoms chosen from N, S, O and P, wherein component(s) A is (are) attached to a cell penetrating peptide B and/or a non-peptide analogue thereof. It also relates to methods of using the system in diagnosis of diseases, as research tool and as a targeting system, a composition comprising the system and especially a pharmaceutical composition a material covered with the system and a material having the delivery systems into the material. Finally it relates to novel peptides.

Abstract: The present invention relates to complexes of small-interfering nucleic acids (siNA). Compositions of siNA suited for administration to a patient are described. Methods for delivering the compositions are also described.

Abstract: A first or second polypeptide for use in a method of treating or preventing a disorder by tolerisation, wherein said method comprises administration of the first and second polypeptide; and wherein both first and second polypeptides: i) are of 7 to 30 amino acids in length; ii) comprise at least one MHC Class Il-binding T cell epitope; and iii) are a fragment of a protein allergen or a homologous variant of said fragment; wherein said first polypeptide induces the release of an amount of IL-10 that is greater than the amount of IL-10 released in response to the whole protein allergen from which the first polypeptide derives; wherein said disorder is characterised by an inappropriate immune response to the protein allergen from which the second polypeptide derives.

Abstract: The invention relates to a new type of polysaccharide-block-polypeptide diblock copolymer which is bioresorbable or biodegradable and biocompatible, to a method for preparing same, to the micellar vesicles constituted of this copolymer, and to the use thereof for encapsulation, transport, vectorization, and targeting of molecules of interest.

Abstract: Novel peptides derived from antibody complementarity determining regions (CDRs) that enhance delivery of macromolecules into cells, particularly when used in combination with cationic lipids, are provided. The peptides can be combined with cationic lipids, and compositions of cationic lipids associated with enhancer elements, to provide reagents that can complex with macromolecules such as nucleic acids, proteins and peptides and permit introduction of these macromolecules into a variety of cells and tissues in vitro or in vivo with greatly enhanced efficiency compared to other lipid-based reagents. Methods for delivering macromolecules into target cells and tissues using the lipids and enhancer elements are provided.

Abstract: The present invention pertains in general to Bromelain and particularly to the active compounds contained in this complex mixture of proteins. The present invention provides recombinant expressed Bromelain inhibitor precursor and Bromelain inhibitors, which are found in Bromelain. It has been found that the recombinant expressed inhibitors have superior effects in terms of treatment of disorders and conditions than Bromelain or its protein fractions from plant extracts.

Abstract: Compounds relating to attachment chemistries for binding biomolecules to a substrate surface are described. These include compounds of the following structure: The biomolecule includes a single nucleic acid, oligonucleotides, polynucleotides, DNAs, RNAs, proteins, peptides, enzymes, antibodies, CNAs (cyclohexyl nucleic acids), p-MeNAs (methyl or methoxy phosphate nucleic acids), peptide nucleic acids (PNAs), and pyranosyl RNAs (p-RNAs).

Abstract: Disclosed is a water-soluble high-molecular weight conjugate of physiologically active substances which enable medicament to release without depending on the enzymes in a living body and which is expected to have a useful therapeutic effect. A high-molecular weight conjugate of a physiologically active substance has a substituent group represented by a general formula (1) bonded to a side-chain carboxy group of a block copolymer which has a polyethylene glycol moiety and either a polyaspartic acid moiety or a polyglutamic acid moiety.

Abstract: The invention provides methods, nucleic acids and kits for detecting metastasis of colon cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of metastasis of colon cell proliferative disorders, thereby enabling the improved diagnosis and treatment of patients.

Abstract: The present invention relates, in general, to RNA silencing and, in particular, to a method of effecting targeted delivery of an RNA silencing moiety using a targeting moiety that binds to a cell surface receptor and mediates internalization of the RNA silencing moiety to be accessible to Dicer. Also provided is a chimeric nucleic acid molecule comprised of a targeting moiety and an RNA silencing moiety, wherein the targeting moiety is an aptamer and the RNA silencing moiety comprises a Dicer substrate.