Abstract: The present invention relates to antisense oligonucleotide (ASO) compositions and particularly to compositions and methods for the cytosolic delivery of antisense oligonucleotides (ASOs). Hybrid ASOs, part single-stranded and part double-stranded, are provided, hybridizing to form a double-stranded region that can non-covalently bond to nucleic-acid-binding protein regions. In this way, ASO::protein complexes may be produced that facilitate delivery of antisense DNA into target cells. Such complexes may be used to down-regulate gene expression in cells.

Abstract: A polypeptide with improved alkaline stability, which polypeptide comprises a mutant of a B or C domain of Staphylococcus Protein A, as specified by SEQ ID NO 1 or SEQ ID NO 2, or of Protein Z, as specified by SEQ ID NO 3, wherein at least the glutamine residue at position 9 has been mutated to an amino acid other than asparagine. The invention also discloses multimers of said polypeptide, as well as separation matrices comprising the multimers or polypeptides.

Abstract: An immobilized enzymatic reactor can include a wall defining a chamber having an inlet and an outlet; a solid stationary phase covalently linked to an enzyme and disposed within the chamber; and a pressure modulator in fluid communication with the chamber and adapted to support continuous flow of a liquid sample comprising a polymer analyte through the inlet, over the solid stationary phase, and out of the outlet under a pressure between about 2,500 and 35,000 psi. In one example, the solid stationary phase includes inorganic/organic hybrid particles in an ultra performance liquid chromatography system, the enzyme is a protease, and the polymer analyte is a polypeptide. The immobilized enzymatic reactor can prepare an analyte for applications such as for hydrogen deuterium exchange mass spectrometry.

Abstract: The invention relates to an immunological method for detecting an extra renal active infection by JC virus in a patient candidate for a treatment with an immunosuppressive treatment or during the course of this treatment.

Abstract: A method for inhibiting cartilage degradation comprising administering to a subject a therapeutically effective amount of a polypeptide comprising or consisting of a Link_TSG6 polypeptide is disclosed.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for the neonatal Fc receptor (in the following referred to as FcRn), and provides an FcRn binding polypeptide comprising the sequence EX2X3X4AX6X7 EIRWLPNL X16X17X18QRX21 AFIX25X26LX28X29 (SEQ ID NO: 1075). The present disclosure also relates to the use of such an FcRn binding polypeptide as an agent for modifying pharmacokinetic and pharmacodynamic properties and as a therapeutic agent.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: A method of treating breast cancer is described, in which a peptide having cancer selective translocation function-doxoribicin conjugate is administered. The conjugate includes doxorubicin chemically linked to the N-terminus or C-terminus of a VEGF-binding protein transduction domain (VPTD) peptide represented as SEQ ID NO: 1, wherein the VPTD peptide and doxorubicin are linked to each other by a disulfide bond, and wherein the VPTD peptide binds specifically to vascular endothelial growth factor (VEGF) in tumor cells or tumor tissues.

Abstract: The invention relates to complement inhibitors that inhibit both the classical and alternative complement pathways. In particular, the invention relates to complement inhibitors derived from the salivary glands of haematophagous arthropods that inhibit both the classical and alternative complement pathways. The invention also relates to the use of the complement inhibitors in the treatment and prevention of diseases.

Abstract: Systems, methods and computer-readable media are described herein for determining a protein's most-likely structural alignment. A maximum likelihood algorithm is utilized that compares possible input protein structural translocations with a template protein. It then calculates the optimally superimposed position for each input protein utilizing a distance-based probability scoring algorithm that accurately manages extreme distances.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: The present invention relates to a composition for treatment or metastasis suppression of cancers which includes a p34 expression inhibitor or activity inhibitor as an active ingredient. According to the present invention, the p34 protein knock-down causes monoubiquitination of PTEN and accordingly nuclear localization of PTEN is induced, as a result, an Akt pathway which is related to survival, proliferation, invasive properties and metastatic properties of tumors is inhibited, and thus there is an effect of significantly reducing clonogenic potential and tumor forming potential of various cancer cells which simultaneously express PTEN and NEDD4-1. Consequently, the p34 gene expression inhibitor or p34 protein activity inhibitor according to the present invention can be effectively used as a treatment agent or a metastasis suppression agent for cancers.

Abstract: A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.

Abstract: A conjugate consisting of an insulin-like growth factor-1 (IGF-I) variant and one or two poly(ethylene glycol) group(s), characterized in that said IGF-I variant has an amino acid alteration at up to three amino acid positions 27, 37, 65, 68 of the wild-type IGF-I amino acid sequence so that one or two of said amino acids is/are lysine and amino acid 27 is a polar amino acid but not lysine, is conjugated via the primary amino group(s) of said lysine(s) and said poly(ethylene glycol) group(s) have an overall molecular weight of from 20 to 100 kDa is disclosed. This conjugate is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.

Abstract: A compound represented by the formula (I) (R1 represents hydrogen atom or a monovalent substituent; R2 and R3 represent hydrogen atom, an alkyl group, or a halogen atom; R4 and R5 represent an alkyl group or an aryl group; R6 and R7 represent hydrogen atom, an alkyl group, or a halogen atom; R8 represent hydroxy group or a dialkoxyboranetriyl group; and X represents silicon atom, germanium atom, or tin atom), which is a novel fluorophore usable as a mother nucleus of an off/on type fluorescent probe not utilizing the intramolecular photoinduced electron transfer.

Abstract: The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The alanines at positions 21 and 30, in wild type amyloid beta peptide amino acid sequence, are according to the invention replaced by cysteins, which results in an intra molecular disulphide bond. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.

Abstract: The present invention provides a bifunctional catalyst of the formula (1): wherein: each R1 is independently selected from an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aralkyl group and an optionally substituted alkaryl group; Z represents a divalent organic linking moiety optionally containing one or more stereocenters; and EWG represents an electron-withdrawing group.

Abstract: The invention features immunoconjugates for impeding weight gain and treating obesity in a subject. The immuno-conjugates comprise particular ghrelin polypeptides and a suitable carrier moiety.

Abstract: Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Abstract: The present invention is related to compositions and methods to treat, ameliorate and/or prevent morbidity and/or mortality from microbial infections. In particular, bacterial infections that are associated with the production and release of bacterial toxins. For example, many Clostridia bacteria, such as Clostridium difficile, release toxins resulting in tissue and organ damage and death, even after antibiotic therapy that either reduces or eliminates the bacteria. In particular, various peptides, polypeptides, and proteins are disclosed herein that either inactivate Clostridium difficile toxin and/or reduce Clostridium difficile toxin production.

Abstract: Isolated LY6K-derived epitope peptides having Th1 cell inducibility are disclosed herein. Such peptides can be recognized by MHC class II molecules and induce Th1 cells. In preferred embodiments, such a peptide of the present invention can be promiscuously bind to MHC class II molecules and induce LY6K-specific cytotoxic T lymphocytes (CTLs) in addition to Th1 cells. Such peptides are thus suitable for use in enhancing immune response in a subject, and accordingly find use in cancer immunotherapy, in particular, as cancer vaccines. Also disclosed herein are polynucleotides that encode any of the aforementioned peptides, APCs and Th1 cells induced by such peptides and methods of induction associated therewith. Pharmaceutical compositions that comprise any of the aforementioned components as active ingredients find use in the treatment and/or prevention of cancers or tumors.

Abstract: The present invention provides a microporous membrane for detecting at least one target analyte in a sample. The membrane includes an array that comprises at least one capture element and the at least one control element printed on the membrane surface, the at least one capture element corresponding to and being able to bind a target analyte, the plurality of control elements, when present including: i) at least one fiduciary marker, ii) at least one negative control to monitor background signal, iii) at least one negative control to monitor assay specificity, iv) at least one positive colorimetric control, v) at least one positive control to monitor assay performance or any combination thereof.

Abstract: The invention relates to the use of a peptide comprising a six-member ring created by the disulfide bond between two cysteines in the increase of biomass of a photosynthetic organism, for its application in the wood industry, in obtaining energy coming from renewable sources and in agriculture.

Abstract: Disclosed herein are methods for large-scale, high-throughput identification of protein-protein interactions and the topologies thereof under physiologically relevant conditions. In one aspect, the disclosure provides methods for identifying one or a plurality of interacting peptides within a biological system comprising obtaining a population of proteins cross-linked with a cleavable protein interaction reporter (PIR) cross-linker, cleaving the PIR crosslinker to produce released peptides and cleaved reporter ions, and analyzing the population of released peptides to identify interacting peptides. Also disclosed are methods for identifying candidate drug compounds, as well as methods of data processing and visualization of protein-protein interactions.

Abstract: Synthetic design of drug-incorporated novel dendrimer structures for quantitatively controlled drug delivery. The dendritic drugs have better control and thus a quantitative drug release can be obtained. There are no prior art dendritic drugs that control release both sequentially and quantitatively like the dendritic drugs disclosed herein. The dendritic drugs are formed by incorporating multiple same type drug units or more than two different drug types into a dendritic cascade structure to form a dendrimer drug.

Abstract: Antagonist peptide of the bond between CD47 and a protein belonging to the thrombospondin family has the sequence S1 R1-R2-R3-S-Q-L-L-K-G-R4-R5-R6 and interacts specifically with the C-terminal end of the TSP, at the site of the bond between the TSP and the CD47 receptor. Interaction between the CD47 receptor and the protein is prevented. The peptide can be used in the context of cancer treatments.

Abstract: An atomic layer deposition method is disclosed for preparing polypeptides. The method comprises providing a solid-phase support comprising a reactive amine monolayer in an atomic layer deposition (ALD) chamber. The solid-phase support is contacted with a first protected amino acid substituted with a protecting group by atomic layer deposition, wherein the protecting group is bonded to a non-side chain amino group of the protected amino acid. A carboxylic acid group of the first protected amino acid is reacted with the reactive amine monolayer, thereby coupling the first protected amino acid to the solid-phase support to produce a coupled-product.

Abstract: The present invention provides methods for treating and improving the symptoms of osteogenesis imperfecta (OI) in a subject by administering to the subject a therapeutically effective amount of a binding agent that binds to transforming growth factor beta (TGF?).

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 present invention relates to ligation agents and their use in making an amide ligation product. Methods of making the ligation agents are also disclosed.

Abstract: Disclosed herein are immunogenic compositions for preventing infection with influenza viruses wherein the immunogenic compositions comprises an immunogen such as a hemagglutinin of an influenza virus, and an immunopotentiator such as an Fc fragment of human IgG and optionally a stabilization sequence. The immunogen is linked to the stabilization sequence which in turn is linked to the immunopotentiator.

Abstract: The present invention is directed to variants of antigens comprising folate binding protein epitopes as a composition associated with providing immunity against a tumor in an individual. The variant is effective in inducing cytotoxic T-lymphocytes but preferably not to the extent that they become sensitive to silencing by elimination, such as by apoptosis, or by anergy, as in unresponsiveness.

Abstract: A therapeutic particle comprises a particle comprising one or more therapeutic agents and one or more fibrin-avid peptide variants attached to the surface of the particle. A method for magnetically targeting a therapeutic agent toward a device in a subject, such as a temporarily introduced magnetizable catheter or an implanted stent, comprises administering the therapeutic particles to the subject and generating a magnetic field, which targets the magnetic particles toward the device. The affinity peptide-modified therapeutic particles may comprise an effective amount of an anti-proliferative agent, such as paclitaxel, to inhibit or prevent in-stent restenosis.

Abstract: The instant invention comprises a process of preparing a composition comprising directed sequence polymer (DSP) mixtures that act as epitopes and useful as vaccines, such DSP synthesized according to a set of rules regarding the identity and the frequency of occurrence of amino acids that substitute a base or native amino acid of a known epitope. The resulting composition is a mixture of related peptides for therapeutic use as a vaccine, preferably for infectious agents that are immune evasive.

Abstract: Described herein are melanocortin analogs having enhanced activity and transport.

Abstract: The present invention provides antibodies that bind to human GFR?3 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GFR?3. The antibodies of the invention are useful for the treatment of diseases and disorders associated with one or more GFR?3 biological activities, including the treatment of acute or chronic pain conditions, or inflammatory conditions.

Abstract: Provided herein are compositions and methods for targeted drug delivery to prevent restenosis in the cardiovascular system. In particular, provided herein are nanoscale delivery vehicles for drugs that prevent proliferation and neointimal hyperplasia.

Abstract: Polypeptides comprising variant vascular endothelial growth factor sequences are provided. The polypeptides are useful in cancer imaging, cancer diagnosis, monitoring and treatment as well as treatment of diseases characterized by excessive neovascularization.

Abstract: Provided herein are compounds, conjugates and methods for making lipid-chemically self-assembled nanorings (Lipid-CSANs) and using them to treat diseases and modify cell surfaces.

Abstract: A medicinal composition for suppressing or preventing the metastasis of a malignant tumor, the composition comprising, as an active ingredient, at least one kind of vasoprotective agent selected from the following (i) to (iv): (i) angiotensin II receptor antagonist, (ii) HMG-CoA reductase inhibitor, (iii) ghrelin or its derivative, and (iv) adrenomedullin or its derivative; or a pharmacologically acceptable salt thereof.

Abstract: A novel convenient method for evaluating the function of a phagocyte is provided. The method assays sCD14-ST, which is a humoral factor specifically produced in phagocytosis by the phagocyte and which is stable enough for use in an assay. Also provided is a method for detecting diseases associated with the phagocytosis by the phagocyte.

Abstract: Populations of polypeptide variants based on a common scaffold, each polypeptide in the population comprising the scaffold amino acid sequence EXXXAXXEIX XLPNLTXXQX XAFIXKLXDD PSQSSELLSE AKKLNDSQ (SEQ ID NO: 1) or AKYAKEXXXAXX EIXXLPNLTX XQXXAFIXKL XDDPSQSSEL LSEAKKLNDS Q (SEQ ID NO:2), wherein each X individually corresponds to an amino acid residue which is varied in the population are disclosed. Also populations of polynucleotides, wherein each member encodes a member of a polypeptide population are disclosed. Furthermore, combinations of such polypeptide populations and such polynucleotide populations are disclosed, wherein each member of polypeptide population is physically or spatially associated with the polynucleotide encoding that member via means for genotype-phenotype coupling.

Abstract: The application provides Fc fusion proteins having novel arrangements. In one embodiment, the application provides Fc fusion proteins comprising a 10Fn3 domain. In another embodiment, the application provides Fc fusion proteins comprising linkers derived from the naturally occurring C-terminal tail regions of membrane bound or secretory immunoglobulins.

Abstract: The invention relates to curcumin derivatives having the formula I: wherein: Z represents: H3CO A represents —CH2—CH2— or —CH?CH—; L represents —C(O)—(NH)n1—R—(NH)n2—C(O)—; R represents a saturated or unsaturated, branched or unbranched hydrocarbyl chain having a minimum of 3 carbon atoms in the chain; wherein the maximum number of carbon atoms in the chain is 24; and wherein the carbon atoms of the chain can be replaced by at least one heteroatom, wherein the heteroatoms are independently —O— or —NH2—, with the proviso that each heteroatom is separated from each other heteroatom by at least two carbon atoms; n1 and n2 independently represent 0 or 1; and Y represents an antibody that binds specifically to a target antigen of a tumor cell. The invention further relates to methods of method of inhibiting the growth of tumors in a human by administering an effective amount of the curcumin derivative, and to methods of producing the curcumin derivative.

Abstract: The present invention relates to synthetic lung surfactant compositions that contain one or more of phospholipase-resistant phospho-glycerol derivatives, phospholipase-resistant phospho-choline derivatives, and surface active proteins or peptides, more preferably a combination of at least two or all three of these materials. Novel phospholipase-resistant phospho-glycerol derivatives, phospholipase-resistant phospho-choline derivatives, and surface active peptides are also disclosed herein. Uses of the surfactant compositions of the present invention to treat endogenous surfactant dysfunctional or deficient lung tissue, to prepare synthetic peptides for use in the surfactant compositions, and to deliver therapeutic agents are also disclosed.

Abstract: The present invention relates to methods and compositions for treating and reducing the risk of Acute Myelogenous Leukemia (AML). In particular, the invention provides methods for identifying novel treatments for AML based on reproducible and detectable changes in AML1-ETO acetylation. The present invention further provides methods of using these treatments.

Abstract: The present invention is directed to an inventive composition or vaccine composition comprising a) an adjuvant component comprising or consisting of at least one immunostimulatory nucleic acid sequence, complexed with a complexing agent; b) an antigen, preferably a protein or peptide antigen and/or a nucleic acid sequence encoding said antigen; and c) a carrier molecule for combined packaging the adjuvant component and the antigen. The present invention is also directed to the first medical use of such an inventive composition or vaccine composition and to the second medical use of such an inventive composition or vaccine composition or components thereof for the treatment of diseases, such as infectious or cancer or tumor diseases as defined herein. The present invention furthermore discloses kits comprising such a composition or vaccine composition.

Abstract: The invention relates to peptides, and peptide variants thereof, in which substantially all of the amino acids in the amino sequence of said peptide are the same, for use as antibacterial agents.

Abstract: Replicons of genotype 6 hepatitis C virus (HCV) are provided. These replicons contain adaptive mutations giving rise to the HCV's capability to replicate in vitro. Methods of preparing genotype 6 replicons and methods of using these replicons to screen antiviral agents are also provided.

Abstract: Chemoattractant polypeptide compounds for progenitor cells and compositions and drug products comprising the compounds are provided herein. Methods for attracting progenitor cells to a location in or on a patient also are provided along with methods of growing and repairing bone.