Abstract: Long-acting compstatin analogs comprising a clearance-reducing moiety attached to two compstatin analog moieties, each compstatin analog moiety comprising a cyclic peptide extended by a lysine residue or a sequence comprising a lysine residue at the N-terminus, C-terminus, or both, wherein the lysine residue is separated from the cyclic portion of the peptide by a rigid or flexible spacer comprising an oligo(ethylene glycol) moiety, the clearance reducing moiety comprises a linear polymer, wherein each end of the linear polymer is linked to one of the compstatin analog moieties by way of a carbamate, wherein (i) the spacer comprises —(CH2)m— and —(O—CH2-CH2—)n joined covalently, wherein m is between 1 and 10 and n is between 1 and 10; and/or (ii) the spacer comprises 8-amino-3,6-dioxaoctanoic acid (AEEAc) or 11-amino-3,6,9-trioxaundecanoic acid.

Abstract: The present application relates to methods for the functionalization of antibodies using transglutaminase, in particular antibodies lacking Fc regions. Also disclosed herein are peptide tags for transglutaminase, linking reagents, functionalized antibodies, multi-specific antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: The present invention relates to the field of medicine and the treatment of diabetes or hyperglycemia within that field. More particularly, the invention relates to a compound that lowers blood glucose, pharmaceutical compositions containing such a compound, and therapeutic uses of such a compound. The compound claimed herein comprises an A chain and a B chain, wherein the amino acid sequence of the A chain is SEQ ID NO: 1 and the amino acid sequence of the B chain is SEQ ID NO: 2.

Abstract: The present invention provides methods for improving the efficacy of a vaccine in the treatment of cancer. The methods of the invention comprise the administration of at least two doses of an agent that interferes with DNA replication prior to vaccination with a survivin vaccine. Also provided are compositions for use in the methods of the invention.

Abstract: T cell receptors (TCRs) that have higher affinity for the Survivin antigen are provided. The high affinity TCRs were engineered through the generation of mutational libraries of TCRs in a single-chain format, followed by selection for improved stability and affinity on the surface of yeast (i.e. directed evolution). In embodiments, the engineered TCRs can be used in soluble form for targeted delivery in vivo, or as genes introduced into T cells in an adoptive T cell setting.

Abstract: The present disclosure relates to a method of inhibiting tumor growth. More specifically, the present disclosure relates to the use of monoclonal antibodies for targeting truncated O-glycans on glycoproteins to inhibit activation of pro-survival ceil signaling pathways, to inhibit tumor growth. For example, monoclonal antibody AR9.6 may be used to target truncated O-glycans on the MUC16 glycoprotein, thereby inhibiting the phosphatidyiinositol 3-kinase/Akt (Pi3K/Akt) signaling pathway.

Abstract: Methods and compositions for regulating fatty acid uptake and/or decreasing gastric motility in an animal are provided. The method comprises administering an antagonist of integrin ?v?3 or ?v?5 to an animal in an amount sufficient to reduce fatty acid uptake in the animal, thereby reducing fatty acid uptake in the animal. In some embodiments, the antagonist is an antibody. Also provided is a method of increasing fatty acid uptake and/or gastric motility in an animal.

Abstract: The present invention relates generally to the identification of patients suffering from cancer whether they will respond to specific therapies. More particularly the invention relates to a method and means for identifying responder to a therapy TLR-9 agonists.

Abstract: Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4+ T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

Abstract: The present invention provides methods and systems for the rapid determination of the intact mass of non-covalently associated antibody heavy chains (HC) and light chains (LC) which result from the attachment of drug conjugates to interchain cysteine residues. By analyzing the antibody-drug conjugate (ADC) using native desalting conditions, the intact-bivalent structure of the ADC, which ordinarily would decompose as a consequence of denaturing chromatographic conditions typically used for LCMS, is maintained. The mass of the desalted ADC is subsequently determined using desolvation and ionization ESI-MS conditions. The methods described herein provide for direct measurement of the intact mass of an ADC conjugated at interchain cysteine residues. The methods described herein also provide for the relative quantitation of the individual ADC species.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for carbonic anhydrase IX (CAIX), and provides a CAIX binding polypeptide comprising the sequence EX2X3X4AX6X7EIX10X11LPN?LX16X17X18QX20?X21AFIX25X26LWD. The present disclosure also relates to the use of such a CAIX binding polypeptide as a diagnostic, prognostic agent and/or therapeutic agent.

Abstract: The present invention provides a pharmaceutical composition formulated for oral delivery, comprising a particulate non-covalently associated mixture of pharmacologically inert silica nanoparticles having a hydrophobic surface, a polysaccharide, and a biologically active protein or peptide suspended in an oil. The present invention further provides methods of manufacturing same and therapeutic methods utilizing same for oral delivery of a therapeutic protein or peptide.

Abstract: The present invention provides methods for reducing glycoprotein aggregation by optimizing the number of O-linked glycosylation sites.

Abstract: The present disclosure provides a human antibody or antigen binding fragment thereof or an antibody construct comprising a human binding domain or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell. The disclosure relates to a nucleic acid sequence encoding the antibody or antigen binding fragment thereof contained in the antibody construct, a vector comprising the nucleic acid sequence and a host cell transformed or transfected with the vector. Furthermore, the disclosure relates to a process for the production of the antibody construct of the disclosure, a medical use or a method of treatment using the antibody construct and a kit comprising the antibody or antigen binding fragment thereof or the antibody construct.

Abstract: Provided are compositions for repairing an injured tissue. The composition includes carboxymethylcellulose conjugated to an extracellular matrix derived peptide, and a methylcellulose. Also provided are kits and methods for using the subject compositions.

Abstract: The present invention relates to a microarray device for the screening or the finding of protein inhibitors, to a method for the production thereof, and to a corresponding method for screening or finding protein inhibitors. The microarray device according to the invention comprises a solid supporting element having a support material, at least one protein immobilized thereon for which inhibitors are to be screened or found, and at least one known inhibitor of the at least one protein, the inhibitor being bound to the at least one protein and comprising a detectable label.

Abstract: Methods and therapeutic compositions for treating respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and devices for administering the therapeutic compositions. Methods for treatment include producing a protein solution, producing a concentrated bone marrow aspirate (cBMA), optionally combining the protein solution and cBMA to form an therapeutic composition, and optionally saturating the autologous therapeutic composition with hydrogen gas, and administering the therapeutic composition to a subject in need thereof. The present methods, compositions and devices are useful for treating COPD and the progression of COPD.

Abstract: The present invention features inter alia nucleic acid molecules which encode polypeptides comprising a single chain Fc region and the polypeptides they encode. The Fc moieties of these constructs are linked by a cleavable scFc linker which is adjacent to at least one enzymatic cleavage site, e.g., an intracellular processing site. The resulting processed molecules comprise two polypeptide chains and substantially lack the extraneous amino acid sequence found in single chain Fc linker molecule. Methods of making and using these dimeric molecules are also described.

Abstract: The present invention provides p97-antibody conjugates and related compositions and methods, which may be used in any of a variety of therapeutic methods, including methods for the treatment of cancers such as Her2/neu-expressing and Her1/EGFR-expressing cancers.

Abstract: The present invention relates to humanized antibodies that specifically bind to CXCR5 and can, for example, inhibit CXCR5 function. The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders.

Abstract: The present invention has the object of providing a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or polymer thereof is introduced, and a method for producing the cell. The invention relates to a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or a polymer thereof is introduced, a method for producing the cell, and a method of screening for a compound inhibiting an intracellular accumulation of a protein containing fibril structures, wherein the method comprises bringing a candidate substance into contact with the cell.

Abstract: In various embodiments chimeric moieties (constructs) are provided that show significant efficacy against cancers. In certain embodiments the constructs comprise a targeting moiety that specifically binds CD138 attached to an interferon or to a mutant interferon. In certain embodiments, the constructs comprise anti-CD138 antibody attached to an interferon alpha (IFN-?) or to a mutant interferon alpha.

Abstract: The invention provides humanized antibodies that specifically bind to LIV-1. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting LIV-1.

Abstract: The invention relates to molecules inhibiting biologically active compounds and further comprising moieties specifically cleavable by a reagent produced by a target cell. More specifically, the invention relates to inhibitors that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent. Inhibitors comprise at least one moiety that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent and at least one moiety that can be cleaved specifically by a reagent produced by target cells. The cleavage deactivates the inhibitor. Following cleavage, the active agent is liberated into the local environment. Administration of the inhibitor alone or together with the active agent suppress the compound's activity until it reaches the proximity of a target cell. This targeted specific release enables the agent concentration in a site to reach levels that have desired therapeutic effects without systemic toxicity.

Abstract: Described are prodrug conjugates that release a chemotherapeutic agent upon activation by caspase, and methods using such prodrug conjugates to induce apoptosis, amplify apoptosis, and treat cancer.

Abstract: The invention generally relates to synthetic mimics of cell penetrating peptides. More particularly, the invention relates to certain novel monomers, oligomers and polymers (e.g., co-polymers) that are useful for the preparation of synthetic mimics of cell penetrating peptides, their compositions, preparations and use.

Abstract: The present invention relates to a compound of formula (I) and to compositions comprising said compound, as well as the use of said compound and/or said compositions to prevent fungal and/or bacterial growth.

Abstract: The present invention relates to methods and compositions for treating disease related to disorders of bone remodeling. In particular, the present invention relates to compositions and methods for treating rheumatoid arthritis.

Abstract: The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8 or 10 mg/kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

Abstract: A conjugate of water soluble polymer-amino acid oligopeptide-drug of Formula (I) below and a pharmaceutical composition comprising the conjugate are provided. In the conjugate, P is a water soluble polymer; X is a linking group, wherein the linking group links P and A1; each of A1, A2 and A3 is independently same or different amino acid residue or amino acid analogue residue; each of D1 and D2 is independently same or different drug molecule residue; a is 0 or 1; b is an integer of 2-12; c is an integer of 0-7; d is 0 or 1. The conjugate could improve drug load capacity, water solubility, stability and activity of the drug.

Abstract: N-acyl modified sialic acid (?-(2?6))-D-aminopyranose derivatives, their synthesis methods and uses are disclosed. Sialic acid (?-(2?6))-D-aminopyranose derivatives represented by formula 1 are synthesized by using D-aminogalactose (glucose) and sialic acid as raw materials, which are coupled with carrier proteins or polypeptides to obtain glycoprotein (glycopeptide) conjugates. Acetyl is replaced by derivative acyl in the structures of said compounds, therefore the compounds show good activity in antitumor vaccines.

Abstract: The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.

Abstract: The present invention discloses a compound comprising the formula: wherein R is hydrogen or an alkyl group having from one to ten carbon atoms, or a compound of the formula wherein the S is replaced by CH2, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof. A method of treating a patient having cancer or a disease comprising administering to a patient an effective amount of the compound or pharmaceutically acceptable salt, hydrate, or solvate thereof.

Abstract: A novel bio-based superabsorbent polymer material based on a proteinaceous natural polymer is introduced herein. There is further disclosed a method for the manufacture of such a bio-based crosslinked superabsorbent polymer material. The method includes, but not limited to, introducing polymerizable unsaturated groups onto the natural polymer or its derivative so as to yield a macromonomer. The macromonomer can be formed by covalently binding unsaturated carbon-carbon double bonds to a proteinaceous substrate through a reaction of a selected chemical compound and the amino group on the proteinaceous substrate. The macromonomer is then copolymerized with unsaturated co-monomer(s) to form a crosslinked superabsorbent material.

Abstract: Fibrinolytic nanoparticles including a polymeric core having a surface that is functionalized with a cationic amphiphilic compound, and a fibrinolytic agent dispersed within the core, are described herein. The fibrinolytic nanoparticles can be used in method of dissolving a blood clot in a subject by administering to the subject a therapeutically effective amount of fibrinolytic nanoparticles.

Abstract: The disclosure provides binding proteins that specifically bind to IL-1? and IL-1?. These binding proteins can be organized into DVD-Igs. These proteins can be used to modulate the activity of IL-1? and/or IL-1? and can be used for the treatment immunological diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, multiple sclerosis, and other autoimmune diseases. In addition, their uses in the amelioration and/or treatment of pain in an individual suffering from a disease or disorder associated with IL-1 accumulation.

Abstract: Provided herein are attenuated Salmonella bacteria for expressing autoantigen alone or in combination with an immunomodulator, as well as methods of using these bacteria to treat various autoimmune disorders.

Abstract: This application discloses a BBB-selective antibody. The BBB-selective antibody comprises a protein encoded by a DNA sequence comprising SEQ ID NO:7 (CDRH1 of scFv 15), SEQ ID NO:8 (CDRH2 of scFv 15), SEQ ID NO:9 (CDRH3 of scFv 15), SEQ ID NO:10 (CDRL1 of scFv 15), SEQ ID NO:11 (CDRL2 of scFv 15) and SEQ ID NO:12 (CDRL3 of scFv 15) or a DNA sequence comprising SEQ ID NO:19 (CDRH1 of scFv 38), SEQ ID NO:20 (CDRH2 of scFv 38), SEQ ID NO:21 (CDRH3 of scFv 38), SEQ ID NO:22 (CDRL1 of scFv 38), SEQ ID NO:23 (CDRL2 of scFv 38) and SEQ ID NO:24 (CDRL3 of scFv 38). Preferably, the BBB-selective antibody comprises a protein encoded by SEQ ID NO:1 or 3.

Abstract: Protease inhibitors together with protease sensitive therapeutics or diagnostics are provided, which may be ionically or covalently bound, or unbound. The protease inhibitors and/or protease sensitive moiety may be provided in monomeric, homopolymeric, heteropolymeric (for each of the protease and agent) and/or block copolymeric (combining polymers of agent and inhibitor) form. The inhibitors may be native active or e.g., protease activated. Multiple protease inhibitor peptides may be used in-frame with multiple protease cleavage signals (polymeric protease activated protease inhibitors). Combination with the protease inhibitors with the protease sensitive therapeutic enhances the intact, active molecule local-regional or targeted cell or tissue concentration, peak concentration and/or duration of the therapeutic exposure, thereby increasing its therapeutic efficacy. The protease inhibitors are particularly useful for tumor-targeted therapies and for vaccines.

Abstract: The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

Abstract: The present invention relates to complexes of a) bi-specific antibodies and antibody fragments against a target protein and b) a digoxigenin conjugated to a therapeutic or diagnostic agent, methods for their production, their use as a delivery platform for therapeutic or diagnostic agents, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human ?-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.

Abstract: The invention is related to methods of producing rod-derived cone viability factor (RdCVF). This invention also relates to the treatment of an ocular disease in a mammal using RdCVF. Also provided are expression vectors for high secreted expression of RdCVF of using nucleotide sequences encoding heterologous signal proteins and optionally markers for furin cleavage.

Abstract: The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin/biotin or streptavidin/biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.

Abstract: The present invention relates to compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders in mammals, particularly in humans. More particularly, the present invention provides for compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders using, inter alia, a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin.

Abstract: This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-?R) agonist and/or a tumor necrosis factor alpha receptor (TNF-?R) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g.

Abstract: The invention includes compositions, methods and kits for the in vivo identification of an enzyme that binds to a substrate. The invention comprises, in part, a photoreactive moiety to aid in identification of such an enzyme.

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: Disclosed are a combination of active components inducing synergistic effects of multi-targeting and a use thereof. More particularly, disclosed are a functional food composition, a cosmetic composition, a pain-suppressive composition, and a composition for treatment or prevention of pruritus or atopic dermatitis, which comprise as active components, two or more components selected from a group consisting of (a) a 5-hydroxytryptamine subtype 2 (5-HT2) receptor antagonist; (b) a P2X receptor antagonist; and (c) any one of a glycine receptor agonist, a glycine transporter (GlyT) antagonist, a gamma-aminobutyric acid (GABA) receptor agonist, and a GABA transporter 1 (GAT1) antagonist.

Abstract: A novel bio-based superabsorbent polymer material based on a proteinaceous natural polymer is introduced herein. There is further disclosed a method for the manufacture of such a bio-based crosslinked superabsorbent polymer material. The method includes, but not limited to, introducing polymerizable unsaturated groups onto the natural polymer or its derivative so as to yield a macromonomer. The macromonomer can be formed by covalently binding unsaturated carbon-carbon double bonds to a proteinaceous substrate through a reaction of a selected chemical compound and the amino group on the proteinaceous substrate. The macromonomer is then copolymerized with unsaturated co-monomer(s) to form a crosslinked superabsorbent material.