Abstract: The present invention relates to a conjugate of a protein or peptide with a polyethylene glycol derivative having catechol, wherein the protein or peptide is mono-PEGylated at the N-terminal with the polyethylene glycol derivative, and to a preparation method thereof. According to the invention, the catechol-PEG derivative can be site-specifically conjugated with the N-terminal amine group of a protein or peptide, so that a homogeneous polyethylene glycol-protein or -peptide conjugate can be obtained in high yield. Unlike a prior art conjugate, the conjugate obtained according to the invention allows the decrease in the activity of the protein to be minimized without chemically modifying the protein, and thus the conjugate has an excellent pharmacological effect. Also, because the conjugate is homogeneous, the process for preparing the conjugate can be simplified. Moreover, the conjugate has uniform biological efficacy in vivo and shows strong resistance to hydrolysis and thus a long in vivo duration time.

Abstract: The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

Abstract: Purified genes encoding a T cell surface antigen from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this antigen are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Chimeric molecules that contain at least one pathogen-detection domain and at least one effector domain, and their methods of use in preventing or treating a pathogen infection in a cell or organism are described. The pathogen-detection domain and effector domain of the chimeric molecules are domains not typically found in nature to be associated together. Agents are also described herein having at least one pathogen-interacting molecular structure and at least one effector-mediating molecular structure, the agent being one that is non-naturally-occurring in a cell. The methods of prevention and treatment described herein are effective for a broad spectrum of pathogens and exhibit little or no toxic side-effects. Assays for the detection of a pathogen, pathogen component, or product produced or induced by a pathogen, are also provided.

Abstract: The present invention relates to a method for capturing virus-like particles of interest from a mixture comprising the use of an expanded bed of adsorbent; suitably wherein said method comprises the steps of: (a) providing an expanded bed of adsorbent; (b) contacting the mixture with the adsorbent such that the constituents of the mixture contact the expanded bed of adsorbent; (c) optionally washing the adsorbent; and (d) optionally eluting the particle of interest from the adsorbent.

Abstract: The present invention is directed to a bio-functionalized stimulus-responsive dissolvable PEG-hydrogel. This inventive stimulus-responsive dissolvable PEG-hydrogel comprises a matrix of PEG-polymers, which are modified to contain at least one multifunctional fusion protein, the multifunctional fusion protein preferably comprising as components a substrate binding peptide (SBP), preferably a repetitive RGD-binding peptide and/or a ZZ-binding domain, preferably a tag for purification, and at least one N- and/or C-terminal linker. The present invention is furthermore directed to the use of such inventive stimulus-responsive dissolvable PEG-hydrogels in the treatment of lesions, in surgical dressings, for wound treating, for soft and hard tissue regeneration, for the treatment of wounds in the oral cavity, in the field of ophthalmology, in the field of periodontal defects, etc. The invention also describes a method of treatment for such diseases.

Abstract: The present invention relates to a process for improving pegylation reaction yield of r-metHuG-CSF comprising conjugating r-metHuG-CSF to a PEG aldehyde at a free amine moiety at the N terminal end on the G-CSF in presence of a reducing agent in a pegylation buffer solution comprising a polyol having the formula CnH2n+2On where n is from 3 to 6, or a carbohydrate, or a derivative thereof wherein the concentration of said polyol or carbohydrate or derivative thereof is in the range of 0.1% to 10% w/w.

Abstract: Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.

Abstract: The present invention relates generally to a novel method of introducing property modifying groups to a protein. In particular, the present invention relates to the derivatization of lysine residues, as well as new conjugates of growth hormones with improved pharmacological properties, and methods for their preparation and use in therapy.

Abstract: Thermostabilization of a protein where the protein contains access routes and wherein at least one amino acid in the bottleneck of the access route is mutated, includes identifying the amino acids of the bottleneck and the amino acids control exchange of the solvent between a buried protein core and surrounding environment and/or in the packing of the amino acids inside the access route. Modification of the amino acids are determined so that the packing of the amino acids inside the tunnel is improved and the access route prevents access of undesired solvent molecules to the protein core, while allowing passage of the compounds necessary at the protein core to enable the protein to perform its biological function.

Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

Abstract: Described are specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins include muteins of a lipocalin protein, such as lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

Abstract: The present invention relates to a cobalamin acquisition protein, compositions containing the cobalamin acquisition protein, and the use of such compositions.

Abstract: An object of the present invention is to provide a cell-adhesive material for biological tissues, in which the surface of a material for biological tissues (particularly metallic material) is modified strongly with a large amount of a cell-adhesive artificial peptide (P) that retains a biological activity. The present invention provides a cell-adhesive material for biological tissues including a cell-adhesive artificial peptide (P) and a material for biological tissues, wherein the cell-adhesive artificial peptide (P) is immobilized on the surface of the material for biological tissues through an electrochemical reaction. The cell-adhesive artificial peptide (P) is preferably a peptide (P1) that is synthesized by a genetic recombinant microorganism and has at least one cell-adhesive minimal amino acid sequence (X) in one molecule. The number of the cell-adhesive minimal amino acid sequences (X) in one molecule of the polypeptide (P1) is preferably 3 to 50.

Abstract: Ligand Drug conjugate compounds comprising a ?-glucuronide-based linker and methods of using such compounds are provided.

Abstract: Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Each compound has the formula: wherein: Z is a trityl derivative; X, the reactivity function, covalently binds to amino acid side chains of proteins; Y, the selectivity function, modulates binding of X to the amino acid side chains in proteins such that X binds to fewer proteins when Y is present than in its absence; and Q permits separation or immobilization of the capture compound. Automated systems for performing the methods also are provided.

Abstract: A novel gene, dubbed “YS68”, involved in primitive hematopoiesis was successfully isolated from cDNA derived from mouse yolk sacs. In addition, a human gene corresponding to this gene was successfully isolated. Expression characteristics of these genes suggested their involvement in primitive hematopoiesis. The proteins of this invention and genes encoding the proteins may be utilized as tools for drug development against diseases, such as hematological disorders.

Abstract: Anti-FAP-antibodies and immunoconjugates, pharmaceutical compositions containing such conjugates, and their use in cancer therapy.

Abstract: A method for differentiating between a post-translationally modified peptide and a peptide contained in a sample, comprising: (a) contacting the sample with a peptide attachment surface to create a peptidized surface, wherein the sample includes at least one functional group; (b) contacting the peptidized surface with a recognition reagent that selectively binds or forms a complex with the post-translationally modified peptide in the sample to provide an incubated surface; and (c) contacting a liquid crystal with the incubated surface and detecting presence of post-translationally modified peptide in the sample with the liquid crystal.

Abstract: A system and method for preventing protein aggregation is developed by covalent modification of proteins with organic molecules that can preserve the native protein folding. Proteins are covalently modified with sugar alcohols or cyclodextrins (organic Kosmotropes) or other small molecule drugs by water-driven bioorganic reactions in water. In the water-driven bioorganic reactions, the reagent is stable in water and can modify lysine residues or cysteine residue of a protein at physiological conditions with high yield and fast rate. Proteins and antibodies will be modified by non-natural sugar alcohols. As a result, the efficacy of protein drugs (reduction in aggregation and enzymatic degradation, and increase in blood stream life time) may be improved.

Abstract: Provided herein are polymeric ?-hydroxy aldehyde or ?-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the ?-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Abstract: A DNA vaccine comprising hyperglycosylated mutant HA gene, which is derived from avian influenza virus, is provided. A DNA vaccine composition comprising: (a) the DNA vaccine; and (b) a booster is also provided. An influenza virus-like particle comprising adjuvant-fused M2 protein is further provided.

Abstract: The present invention relates to a method for labeling proteins in a sample prior to separation thereof using a protein reactive dye, comprising the following steps a) dissolving the proteins in, or diluting the proteins with, or exchanging an existing protein buffer with, a labeling buffer comprising a dye-reactant (reacting with the protein reactive dye) to form a mixture, b) adding protein reactive dye to said mixture, c) incubating said mixture wherein the labeling of said proteins with said dye can be completed within 5 minutes, and wherein both the proteins and the dye-reactant form measurable reaction products with said dye, and d) separating said reaction products. The invention also relates to a kit for pre-labeling of proteins, comprising a labeling buffer, a dye, a molecular weight marker, and a sample gel loading buffer.

Abstract: The invention relates generally to G protein coupled receptors and in particular to agonists and antagonists of G protein receptors and methods of using the same.

Abstract: Provided herein are Parathyroid hormone (PTH) peptides and parathyroid hormone-related protein (PTHrP) peptides (e.g., PTH analogs, PTHrP analogs), and related variants, chemical derivatives, fusion polypeptides, multimeric polypeptides, and peptidomimetics, peptoids, the like. Also provided are their use in methods for activating the PTH receptor in a cell (e.g., an osteoblast), methods of treating a subject with bone loss (e.g., by administration of a PTH peptide or PTHrP peptide (e.g., a PTH analog or PTHrP analog)), methods of ameliorating a symptom associated with osteoporosis in a subject, methods of retarding the progression of osteoporosis in a subject, and methods of regenerating bone in a subject.

Abstract: The present invention relates to a method of separating one or more immunoglobulin containing proteins from a liquid. The method includes first contacting the liquid with a separation matrix comprising ligands immobilised to a support; allowing the immunoglobulin containing proteins to adsorb to the matrix by interaction with the ligands; followed by an optional step of washing the matrix containing the immunoglobulin containing proteins adsorbed thereon; and recovering said immunoglobulin containing proteins by contacting the matrix with an eluent which releases the proteins. The method improves upon previous separation methods in that each of the ligands comprises one or more of a protein A domain (E, D, A, B, C), or protein Z, or a functional variant thereof, with at least one of the monomers having a substitution of the Asparagine at the position corresponding to N28 of B domain of Protein A or Protein Z, and wherein the ligand provides an increase in elution pH compared to non-substituted ligand.

Abstract: The present invention provides luminescent complexes between a lanthanide ion and an organic ligand which contains 1,2-hydroxypyridinone units. The complexes of the invention are stable in aqueous solutions and are useful as molecular probes, for example in medical diagnostics and bioanalytical assay systems. The invention also provides methods of using the complexes of the invention.

Abstract: Provided herein are carbohydrate complement-modified bifunctional glycoproteins, and their use in tumor-selective therapy. The bifunctional glycoproteins comprise a first component that specifically binds to a tumor-specific antigen and a second component having enzymatic activity by means of which a non-toxic prodrug is cleaved into a cytotoxic drug. The carbohydrate complement comprises at least one exposed carbohydrate residue selected from the group consisting of mannose, galactose, N-acetylglucosamine, N-acetyllactose, glucose and fucose. The modified carbohydrate complement contributes to increased relative concentration of the glycoproteins at the site of the tumor, and enhanced clearance from the general circulation and non-tumor sites.

Abstract: Multifunctional probes are synthesized in a single step using peptide scaffold-based multifunctional single-attachment-point reagents. To obtain multifunctional probes using the methods of the invention, a substrate (e.g., a nanoparticle, polymer, antibody, protein, low molecular weight compound, drug, etc.) is reacted with a multifunctional single-attachment-point (MSAP) reagent. The MSAP reagents can include three components: (i) a peptide scaffold, (ii) a single chemically reactive group on the peptide scaffold for reaction of the MSAP with a substrate having a complementary reactive group, and (iii) multiple functional groups on the peptide scaffold. The peptide scaffold can include any number of residues; however, for ease of synthesis and reproducibility in clinical trials, it is preferred to limit the residues in the peptide to 20 or less.

Abstract: The present invention relates to a liquid pharmaceutical composition comprising a granulocyte colony stimulating factor polypeptide conjugated with a polymer, the composition having a pH value in the range of 4.5 to 5.5. The composition further comprises a surfactant and optionally one or more other pharmaceutically acceptable excipients. Further, the composition of the invention is free from tartaric acid or salts thereof and from succinic acid and salts thereof as buffering agents and does not contain amino acids as stabilizer. The composition has a good storage stability and is especially useful for the prophylaxis and treatment of disorders and medical indications where granulocyte colony stimulating factor preparations are considered as useful remedies.

Abstract: The invention relates to fusion constructs, methods of using fusion constructs and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies.

Abstract: The present invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A) or of a biologically active fragment of HMGB1 Box-A. Further, the invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A). Moreover, the present invention concerns the use of said polymer conjugates of polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and/or associated with an increased expression of RAGE.

Abstract: This application is directed to chemokine-immunoglobulin fusion polypeptides and chemokine-polymer conjugates. The fusion polypeptides and conjugates can be used for treating chemokine receptor-mediated disorders and modulating inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival.

Abstract: The present invention relates generally to the treatment of an interleukin-11 (IL-11)-mediated condition. More particularly, the present invention provides the use of modified forms of IL-11 which modulate IL-11 signaling in the treatment of IL-11-mediated conditions.

Abstract: The present invention provides variants of fluorescent proteins, which are improved with regard to their properties for use as reporter proteins and/or in analytics. In particular, variants of fluorescent proteins are provided, which fluoresce brighter, show improved quantum yield and/or have shifted excitation or emission spectra. The fluorescent proteins according to the invention comprise in their LOV domain besides the substitution of a cysteine with an amino acid that does not covalently bind FMN at least one further point mutation.

Abstract: A novel type of particle platform for application in biotechnology is provided by the present invention. Said platforms comprise RNA-free particles generated by thermal denaturation and structural remodeling of helical plant viruses. Tobamovir-uses and, in particular, tobacco mosaic virus (TMV) coat protein (CP) subunits, denatured, at high temperatures are specifically self-assembled by two-stage assembly into the spherical particles (SPs) of similar shape and varying size including nanoparticles (SNPs) with a diameter up to 100-150 nm and spherical microparticles (SMPs) with a diameter up to 800 nm and more. The size of said SPs depends on the virus concentration used and, therefore can be controlled. Said SPs are biologically safe, highly stable and highly immunogenic. Said SNPs and SMPs are structurally distinct from viruses presently known. They are unique, having no protein nano-particle analogs in the nature.

Abstract: A process for producing a substrate having an adhesive surface, which process comprises: (a) contacting the substrate with a carbene precursor, which carbene precursor is a compound of the following formula (1): whose substituent groups are defined herein, provided that when R is aryl or heteroaryl, said aryl or heteroaryl may be substituted by one, two, three, four or five groups, which groups are independently selected from various groups including -LB-WB; and (b) either: (i) when WA or WB comprises an adhesive functional group, generating a carbene reactive intermediate from the carbene precursor so that it reacts with the substrate to functionalise the surface, thereby yielding said substrate having an adhesive surface; or (ii) when WA or WB comprises a group which is a precursor of an adhesive functional group, generating a carbene reactive intermediate from the carbene precursor so that it reacts with the substrate to functionalise the surface, and (c) converting said group which is a precursor into an

Abstract: The present invention relates to granulocyte colony stimulating factor (G-CSF) modified with Y-shaped branched polyethylene glycol (YPEG-G-CSF) at a specific lysine (Lys 17) and the preparation thereof, as well as the pharmaceutical composition comprising YPEG-G-CSF and use thereof.

Abstract: An imaging probe can include a photoluminescent carbon nanostructure configured to emit a wavelength of light detectable through living tissue, and a targeting moiety including a first binding partner configured to interact with a second binding partner.

Abstract: Compositions and methods for the therapy and diagnosis of Inflammatory Bowel Disease (IBD), including Crohn's Disease and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of IBD.

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

Abstract: The present invention provides, in part, MCP1-Ig fusion polypeptides exhibiting surprisingly beneficial properties as well as methods for treating various diseases (e.g., inflammatory diseases) by administering any of such fusions.

Abstract: A method for in situ formation of a medical device on biological tissue includes attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue, and providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members on the surface of the biological tissue with the complimentary reactive members on the fibers, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the fibers to the tissue. The fibers can incorporate functionalities which may cause them to bind to one another.

Abstract: Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive animation of oxidized sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

Abstract: It is an object of the present invention to provide a method for chemically modifying biopolymer and polypeptide with a hydrophobic compound or a compound which causes degradation or reaction under basic condition. The present invention provides a method for producing a chemically modified biopolymer or polypeptide, wherein a biopolymer or polypeptide is chemically modified in a reaction solution containing an organic fluorine compound.

Abstract: The invention provides soluble fusion protein complexes having at least two soluble fusion proteins. The first fusion protein is a biologically active polypeptide covalently linked to an interleukin-15 (IL-15) polypeptide or a functional fragment thereof. The second fusion protein is a second biologically active polypeptide covalently linked to a soluble interleukin-15 receptor alpha (IL-15R?) polypeptide or a functional fragment thereof. In the complexes of the invention, one or both of the first and second fusion proteins further includes an immunoglobulin Fc domain or a functional fragment thereof; and the first fusion protein binds to the soluble IL-15R? domain of the second fusion protein to form a soluble fusion protein complex. The invention further provides methods for making and using the complexes of the invention.

Abstract: The invention features compositions and methods for site-specific modification of proteins by incorporation of an aldehyde tag. Enzymatic modification at a sulfatase motif of the aldehyde tag through action of a formylglycine generating enzyme (FGE) generates a formylglycine (FGly) residue. The aldehyde moiety of FGly residue can be exploited as a chemical handle for site-specific attachment of a moiety of interest to a polypeptide.

Abstract: The present invention provides a method for enhancing an immune response in a mammal to facilitate the elimination of a chronic pathology. The method involves the removal of immune system inhibitors such as soluble TNF receptor from the circulation of the mammal, thus, enabling a more vigorous immune response to the pathogenic agent. The removal of immune system inhibitors is accomplished by contacting biological fluids of a mammal with one or more binding partner(s) such as TNF? muteins capable of binding to and, thus, depleting the targeted immune system inhibitor(s) from the biological fluids. Particularly useful in the invention is an absorbent matrix composed of an inert, biocompatible substrate joined covalently to a binding partner, such as a TNF? mutein, capable of specifically binding to a targeted immune system inhibitor such as soluble TNF receptor.

Abstract: The present invention provides a method of treating cancer involving administering an insulin-like growth factor-1 receptor (IGF-1 receptor) agonist and an anti-cancer chemotherapeutic agent. Also provided are compounds for treating cancer comprising an IGF-1-receptor ligand coupled to an anti-cancer chemotherapeutic agent. Also provided are compounds for treating cancer comprising an insulin-receptor ligand coupled to an anti-cancer chemotherapeutic agent.

Abstract: Methods for producing biomolecule-polymer conjugates, such as polypeptide-polymer conjugates, include attachment of an initiator agent to a biomolecule and in situ polymerization of a polymer from defined sites on the biomolecule. The conjugates may have desirable pharmacological properties and may be used therapeutically.