Abstract: The present invention relates to binding moieties that specifically bind to a conformational epitope of C5a, in particular human C5a. Preferred binding moieties are anti-C5a antibodies that bind to this conformational epitope. The binding moieties described herein are useful as active agents in pharmaceutical compositions for the treatment and prevention of various acute and chronic diseases, in particular acute inflammatory diseases, such as the systemic inflammatory response syndrome (SIRS), and different degrees of sepsis including sepsis, severe sepsis, and septic shock.

Abstract: The present provides fusion proteins comprising PDGF and VEGF binding portions, and recombinant viral particles encoding the fusion proteins. Compositions comprising the fusion proteins and viral particles as well as methods of using the same are also provided.

Abstract: Compositions and methods for the diagnosis, treatment and prevention of prostate cancer, well as for treatment selection.

Abstract: The number of midbody derivatives in a cell may be modulated by modulating autophagy induced by NBR1. Exemplary methods include modulating the amount or activity of NBR1 in the cell, potentiating or inhibiting binding between NBR1 and Cep55 in the cell, or modulating the amount of Cep55 in the cell. These methods can be used in the treatment of cancers or in methods of reprogramming cells.

Abstract: The invention relates to a recombinant factor VIII that includes one or more mutations at an interface of A1 and C2 domains of recombinant factor VIII. The one or more mutations include substitution of one or more amino acid residues with either a cysteine or an amino acid residue having a higher hydrophobicity. This results in enhanced stability of factor VIII. Methods for making the recombinant factor VIII, pharmaceutical compositions containing the recombinant factor VIII, and use of the recombinant factor VIII for treating hemophilia A are also disclosed.

Abstract: The invention relates to methods and reagents for the treatment of immunological diseases. In particular, the invention relates to isoforms of the C4b-binding protein (C4BP) lacking beta chains as well as to fragments and peptides derived thereof and to the uses of these polypeptides for the treatment of immunological diseases such as immunoinflammatory disease, sepsis, an autoimmune disease, transplant rejection, graft-versus-host disease and a hypersensitivity disease. Moreover, the invention relates also the use of factor H for the treatment of immunological diseases. In addition, the invention relates to tolerogenic dendritic cells obtained using the C4BP isoform lacking beta chain, the peptides and fragments thereof and factor H and to the therapeutic uses of said cells.

Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Abstract: The present invention relates to B7-H4-specific chimeric antigen receptor compositions and methods of use thereof.

Abstract: This invention concerns HY epitopic polypeptides specifically presented by the HLA-DR7 molecule, a method for preparing these epitopic polypeptides, isolated T-lymphocytes capable of specifically recognizing an epitope from these polypeptides or from a polypeptide comprising the complete sequence of the protein encoded by the RPS4Y gene and presented by the HLA-DR7 molecule expressed on the surface of antigen-presenting cells, a method for preparing these T-lymphocytes, as well as the use of these epitopic polypeptides and these T-lymphocytes as medicaments, in particular for the treatment of cancers of immune cells.

Abstract: The present invention refers to the use of protein kinase inhibitors and more specifically to the use of inhibitors of the protein kinase c-Jun amino terminal kinase, JNK inhibitor (poly-)peptides, chimeric peptides, or of nucleic acids encoding same as well as pharmaceutical compositions containing same, for the treatment of dry eye syndrome.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: Disclosed herein are compositions of transcription activator-like effectors transcription factors and methods of using said compositions for inducing gene expression of mammalian genes.

Abstract: A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain by delivering a definite concentration of recombinant neurotrophin, into a targeted region of the brain using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. Growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated is provided.

Abstract: The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with dysregulated expression of mesothelin. In one embodiment, the invention relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target mesothelin.

Abstract: Methods, biomarkers, and expression signatures are disclosed for assessing the disease progression of Alzheimer's disease (AD). In one embodiment, BioAge (biological age), NdStress (neurodegenerative stress), Alz (Alzheimer), and Inflame (inflammation) are used as biomarkers of AD progression. In another aspect, the invention comprises a gene signature for evaluating disease progression. In still another embodiment, methods for evaluating disease progression are provided. In yet another embodiment, the invention can be used to identify animal models for use in the development and evaluation of therapeutics for the treatment of AD.

Abstract: The present invention relates to anti-FGFR2 and FGFR4 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

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: This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their ?1-?2 platform domain, to the intended target cell specifically. The ?1-?2 domain is contiguous with a heterologous ?3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the ?3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified ?3 domain of a MIC protein.

Abstract: In one embodiment, the present invention provides a new isoform of human PD1 (?42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain. ?42PD1 does not engage PD-L1/PD-L2, and can induce the production of pro-inflammatory cytokines In one embodiment, ?42PD1 can be used as an intramolecular adjuvant to develop a fusion DNA vaccine for enhancing antigen-specific CD8+ T cell immunity and for prevention of pathogenic infection and/or cancer. In one embodiment, soluble ?42PD1 protein could be a therapeutic target for autoimmune diseases. In other embodiments, proteins or peptides or nucleic acids encoding proteins or peptides containing ?42PD1 could be used as immunogens for developing antibodies binding specifically to ?42PD1. In yet another embodiment, neutralizing antibodies could block s?42PD1 function and accordingly could be used as treatment for autoimmune disorders.

Abstract: Provided are pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. Further provided are conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. Further provided are methods of using and making the conjugates.

Abstract: The present invention relates to the proline rich transmembrane protein 2 (PRRT2) gene, and the identification of mutations and variations in PRRT2 that give rise to seizure and movement disorders. Accordingly, the present invention provides methods for the diagnosis or prognosis of such disorders by identifying alterations in the PRRT2 gene. Identification of alterations in the PRRT2 gene also enables the identification of subjects with an increased likelihood of having an offspring predisposed to such disorders. The present invention also provides an isolated nucleic acid molecule comprising an alteration in the PRRT2 gene, wherein said alteration produces a seizure and/or movement disorder phenotype. Also provided is an isolated PRRT2 polypeptide that comprises an alteration which produces a seizure and/or movement disorder phenotype.

Abstract: Compositions for modulating the expression of a protein in a target cell comprising at least one RNA molecule which comprises at least one modification conferring stability to the RNA, as well as related methods, are disclosed.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention relates to the field of blood clotting. Specifically, the invention relates to particular inhibitors of artificial activation of the blood clotting process through contact with foreign surfaces.

Abstract: The invention provides isolated nucleic acid molecules, designated TANGO 228 nucleic acid molecules, which encode secreted proteins with homology to the rat MCA-32 protein, isolated nucleic acid molecules, designated TANGO 240 nucleic acid molecules, which encode secreted proteins with homology to the Mycobacterium tuberculosis hypothetical protein Rv0712, and isolated nucleic acid molecules, designated TANGO 243 nucleic acid molecules, which encode proteins with homology to human PLAP (phospholipase A2-activating protein). The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies.

Abstract: The present invention provides vectors that contain and express in vivo or in vitro sand fly Lu. longipalpis salivary antigens that elicit an immune response in animal or human against Leishmania, vaccine compositions comprising said vectors and/or Lu. longipalpis salivary polypeptides, methods of vaccination against Leishmania, and kits for use with such methods and compositions.

Abstract: A bioassay for the quantification of peptide fragments comprising a neo-epitope formed by cleavage of a titin protein by a proteinase comprises contacting a sample with an antibody specifically binding said neo-epitope and determining the level of binding.

Abstract: The present invention relates to antimicrobial peptides, isolated and purified from extracts of tilapia (Oreochromis niloticus) gills. Such peptides may be produced by chemical synthesis or by expression in heterologous systems, such as bacteria and yeasts, by conventional molecular biology techniques. These peptides show antimicrobial activity against various organisms, including Gram positive bacteria, Gram negative bacteria, fungi and viruses. The invention also includes compositions to for controlling pathogens comprising these antimicrobial peptides. The use of such peptides in vaccine preparations, as molecular adjuvants, is also part of the invention.

Abstract: The present invention relates to non-catalytic carbohydrate-binding modules (CBM) belonging to a new family of CBM's. A CBM of the invention was found attached to a glycosyl hydrolase family 61 (GH61) polypeptide and was shown to have little homology with known CBM's indicating that it is the first known member of a new family of CBM's. The present invention further relates to CBM's preferably exhibiting binding affinity for cellulose; to a method of producing such CBM's; and to methods for using such CBM's in the textile, detergent and cellulose fiber processing industries, for purification of polypeptides, immobilization of active enzymes, baking, manufacturing of biofuel, modification of plant cell walls.

Abstract: Lentiviral vectors modified at the 5? LTR or both the 5? and 3? LTR's are useful in the production of recombinant lentivirus vectors. Such vectors can be produced in the absence of a functional tat gene. Multiple transformation of the host cell with the vector carrying the transgene enhances virus production.

Abstract: The present disclosure provides immunogenic compositions comprising the N-domain of carcinoembryonic antigen (CEA). These compositions are useful for inducing or enhancing an immune response, for inhibiting tumor cell growth and for treating cancer.

Abstract: The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 200 bp having at least 70% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Abstract: The present invention claims an isolated nucleotide sequence characterized by encoding the PFR1 protein of Leishmania infantum or a fragment thereof. This PFR1 protein or a fragment thereof comprises at least a selected immunodominant epitope between the following group: SEQ ID No: 1, SEQ ID No: 2, SEQ ID No: 3, SEQ ID No: 4, SEQ ID No: 5, SEQ ID No: 6, SEQ ID No: 7 and SEQ ID No: 8, where the immunodominant epitope is able to induce an antigen-specific T cell cytotoxic immune response in an animal, against the kinetoplastids causing the leishmaniasis disease. The immunodominant epitopes are cytotoxic T-lymphocyte activators and they present a high binding affinity for A2 type MHC Class I molecule.

Abstract: The present technology provides methods and compositions for the treatment of inflammatory and/or tissue damage conditions. In particular, the use of Smad7 compositions delivered locally or systemically to a site of inflammation and/or tissue damage is described. Other specific embodiments concern treatment or prevention of side effects caused by radiation and/or chemotherapy, including but not limited to oral and gastric mucositis. Also provided are codon-optimized nucleic acids encoding for Smad7 fusion proteins.

Abstract: The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Abstract: The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

Abstract: Compositions and methods are disclosed that relate to novel plasmin-inhibiting polypeptides that are structural variants of a human TFPI-2 Kunitz-type proteinase first inhibitor domain (KD1). The polypeptides are potent plasmin inhibitors and in certain embodiments have anti-fibrinolytic activity and/or decreased anti-coagulation activity relative to wild-type TFPI-2 KD1 and are not highly immunogenic. The plasmin-inhibiting polypeptides will find uses as anti-cancer agents, as antifibrinolytic agents, as protease inhibitors, and in other contexts.

Abstract: The present invention relates to silk proteins which can be used to produce silk with a collagen-like structure, as well as nucleic acids encoding such proteins. The present invention also relates to recombinant cells and/or organisms which synthesize silk proteins. Silk proteins of the invention can be used for a variety of purposes such as in the production of personal care products, plastics, textiles, and biomedical products.

Abstract: The present disclosure provides a DNA molecule capable of replication in Mycobacteria having a nucleic acid sequence as disclosed in SEQ ID NO: 1, a shuttle vector constructed using it and a transformed cells containing the present vector. The vector of about 18 kb of the present disclosure contains 16 ORFs, a replication origin and a rep-like protein essential for replication. Therefore, the plasmid of the present disclosure can be utilized as a gene delivery system/research, and also in a therapeutic system such as immune therapeutics by effectively delivering proteins or heterologous DNA and expressing the encoded DNA in cells.

Abstract: This invention concerns improved methods, uses, and kits for treating chronic wounds through the administration of anti-connexin agents, particularly anti-connexin 43 antisense polynucleotides. The methods, uses, and kits of the invention are based on the surprising and unexpected discovery that chronic wounds that do not increase or decrease in size by more than a pre-determined amount during a pre-treatment phase are more amenable to successful treatment than wounds whose size varies outside the target range during the pre-treatment phase.

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: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer.

Abstract: Disclosed are immunomodulatory polypeptides that elicit an unusual induced cytokine profile, compositions comprising such polypeptides, compositions comprising antibodies that specifically bind to such polypeptides, and methods of using the same, including in cancer treatment, in the treatment of autoimmune diseases, in organ transplantation and for reducing graft rejection, for promoting fertility, and for identifying a neutrophil subset and/or other cellular subset including by flow cytometry. Pharmaceutical compositions and kits, and treatment methods are also disclosed.

Abstract: A family of novel feline bitter taste receptors, referred to as feline TAS2R (fTAS2R), are disclosed herein. Isolated polynucleotides encoding the novel feline bitter taste receptors and chimeric polypeptides are also disclosed, as are expression vectors and host cells for expression of the novel feline bitter taste receptors. Methods of identifying compounds that bind to the novel feline bitter taste receptors and modulate their activity are disclosed.

Abstract: The present invention comprises methods and compositions for controlling nematode parasitism in host plant. The present invention comprises novel polynucleotides and polypeptides encoded by such polynucleotides comprising one or more nucleic acid sequences disclosed herein having a nucleotide sequence comprising any one of SEQ ID NOs: 1-142, a fragment or variant thereof, or a complement thereof, or a polypeptide sequence comprising any one of SEQ ID NOs: 143-159, a fragment or variant thereof.

Abstract: The present invention provides Fibroblast Growth Factor Receptor-Like (FGFR-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing FGFR-L polypeptides. The inventio further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with FGFR-L polypeptides.

Abstract: Described herein are methods of screening for compounds that bind to conformational isomers of CD20 polypeptides. Also described are antibodies that bind to conformational isomers of CD20 polypeptides.

Abstract: A method for inhibiting tumor cell migration or metastasis of a cancer in a mammalian subject comprises one or more of the steps of administering to a subject a therapeutically effective amount of a composition comprising a molecule that: suppresses focal adhesion kinase (FAK) activity or phosphorylation; suppresses ULK1 kinase activity; suppresses activation or signaling of the mTORC1 (Ser757) pathway; activates AMPK; activates FIP200; or activates LKB1, in a cancer cell. Still another method of inhibiting tumor cell migration involves inhibiting phosphorylation of ULK1 on Ser757 in subjects with lung cancer. Suppressing activation or signaling of the mTORC1 (Ser757) pathway in subjects is in one aspect useful in treating lung cancer.

Abstract: Immunologically active agents are described, including isolated Pneumocystis A 12 protein or polypeptides; immunogenic conjugates containing Pneumocystis A 12 protein or polypeptide of the present invention; antibodies recognizing the Pneumocystis A 12 protein or polypeptide or the immunogenic conjugates of the present invention; and nucleic acid molecules that encode the Pneumocystis A 12 protein or polypeptide of the present invention, as well as DNA constructs, expression vectors, and host cells that contain the nucleic acid molecules. Disclosed uses of the antibodies, immunogenic conjugates, and DNA constructs include inducing passive or active immunity to treat or prevent pathogen infections, particularly by a Pneumocystis organism, in a subject.