Abstract: The present invention relates to interferon-?2b modified with Y-shaped branched polyethylene glycol (PEG) at a single Lys residue and the preparation thereof. The peglated IFN-?2b can be used for the preparation of a medicament for treating a disease, e.g. viral infections such as Hepatitis C.

Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.

Abstract: Methods for treatment of diseases, including human immunideficiency virus infection, are provided. The disease are treated by administering conjugates containing as a ligand a chemokine receptor targeting agents, such as a chemokine, and a targeted agent, such as a toxin.

Abstract: The present invention refers to single-chain fusion proteins comprising three soluble TNF superfamily (TNFSF) cytokine domains and nucleic acid molecules encoding these fusion proteins. The fusion proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and/or research applications.

Abstract: The use of interleukin 17E to inhibit tumour growth in a subject is provided. The interleukin 17E can be provided to the subject exogenously, as an interleukin 17E polypeptide or a polynucleotide encoding an interleukin 17E polypeptide, or it can be provided by stimulating production of endogenous interleukin 17E. Also provided is the use of interleukin 17E in combination with one or more anti-cancer therapeutics for inhibiting tumour growth in a subject. Anti-cancer therapeutics include, for example, standard chemotherapeutic drugs, immunotherapeutics, radiation, gene therapy, hormone manipulation and antisense therapy.

Abstract: The present invention relates to the identification of an epitope in human Interleukin-15 (IL-15) that is responsible for binding to the interleukin-15 receptor ?-chain. Two IL-15 regions are involved in the formation of this epitope: the first region (44LLELQVISL52, peptide 1) corresponds to a sequence located in the B helix and the second (64ENLII68, peptide 2 or 64ENLIIL69, peptide 2a) to a sequence located in helix C. Muteins displaying agonist or antagonist properties are described, and may be useful as therapeutic agents.

Abstract: The invention provides methods of chemically synthesizing chimeric proteins comprising at least a portion of an immunoglobulin constant region and a biologically active molecule.

Abstract: This invention provides a crystalline recombinant interferon (rSIFN-co) having (i) the same amino acid sequence as that of human consensus interferon, and (ii) altered three-dimensional structure as compared to IFN-?2b. The interferon of the present invention exhibits enhanced biological activities. The present invention also provides a structure model of said interferon useful for drug screening and/or drug design and the mimetic of said interferon.

Abstract: The present invention relates to viral interleukin-6 (v-IL-6), which can be obtained by recombinant expression of the DNA of human herpesvirus type 8 (HHV-8), and which may be used in diagnosis and treatment of human diseases such as kaposi sarcoma, Castleman's disease, multiple myeloma, kidney cell carcinoma, mesangial proliferative glomerulonephritis or B cell lymphoma.

Abstract: A conjugate protein comprising an IL-2 and a soluble TGF-beta type II receptor type B and its use in cancer immunotherapy are described.

Abstract: The present invention relates generally to the field of crystallography. More particularly, the present invention provides crystalline forms of a complex between granulocyte macrophage-colony stimulating factor (GM-CSF) and its receptor (GM-CSFR). The present invention further provides methods for the design and selection of modulators of GM-CSF/GM-CSFR interaction and signaling as well as signaling of other cytokines.

Abstract: A method of stimulating an immune response in a subject including administering a micrometer-sized particle coupled with an antigen to the subject, wherein increasing the aspect ratio of the micrometer-sized particle increases the immune response. A method of stimulating an immune response in a subject including administering to the subject a plurality of particles, wherein each particle is coupled with an immuno stimulating agent and a protein. A vaccine particle composition including a plurality of particles configured to release a first protein at a first rate and a second protein at a second rate and configured to provide priming and boosting capability in a single dose.

Abstract: Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Abstract: The present invention relates to a novel member of the TNF-Ligand superfamily. More specifically, isolated nucleic acid molecules are provided encoding a human Apoptosis Inducing Molecule II (AIM II). AIM II polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of AIM II activity. Also provided are therapeutic methods for treating lymphadenopathy, aberrant bone development, autoimmune and other immune system diseases, graft versus host disease, rheumatoid arthritis, osteoarthritis and to inhibit neoplasia, such as tumor cell growth.

Abstract: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.

Abstract: Thioloated taxane derivatives are linked to colloidal metal particles such as gold nanoparticles for use as antitumor agents. The antitumor agents may be targeted to tumors.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc.

Abstract: Protease resistant modified interferon-beta polypeptides, pharmaceutical compositions and methods of treatment by administering the compositions are provided. The modified interferon-beta polypeptides are orally available; hence pharmaceutical compositions formulated for oral administration also are provided.

Abstract: The present invention provides technology for making large (e.g., greater than 50 amino acids), semi-synthetic, stapled or stitched proteins. The method essentially involves ligating a synthetically produced stapled or stitched peptide to a larger protein. Modified version of IL-13 and MYC are provided as illustrative examples.

Abstract: This disclosure provides peptides, polypeptides, fusion polypeptides, compositions, and methods for enhancing or increasing the stability of a polypeptide (e.g., Taq polymerase). Such peptides, polypeptides, fusion polypeptides, or compositions include polypeptides linked to a peptide tag that enhances the stability of the polypeptide. The peptides, polypeptides, fusion polypeptides, compositions may also enhance the activity, specificity, and/or fidelity of other polypeptides in a reaction mixture. The disclosure also provides methods of using such peptides, polypeptides, fusion polypeptides, compositions.

Abstract: A method is provided for introducing a GAG binding site into a protein comprising the steps: identifying a region in a protein which is not essential for structure maintenance introducing at least one basic amino acid into said site and/or deleting at least one bulky and/or acidic amino acid in said site, whereby said GAG binding site has a GAG binding affinity of Kd?10 ?M, preferably ?1 ?M, still preferred ?0.1 ?M, as well as modified GAG binding proteins.

Abstract: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.

Abstract: The present invention provides biologically active variants of human ?-2b-interferon. The variants contain carboxy terminus truncations when compared with the amino acid sequence of full-length human ?-2b-interferon. It is the novel finding of the present invention that these truncated variants have the biological activity of full-length human ?-2b-interferon. The invention encompasses these biologically active variant ?-interferons, as well as polynucleotides encoding these interferons. Expression cassettes comprising these polynucleotides and host cells comprising the expression cassettes are also provided. The invention also provides compositions comprising variant ?-interferon polypeptides and a pharmaceutically acceptable carrier.

Abstract: Methods for treating mammals with infections, particularly viral infections using molecules that have an IL-21 functional activity are described. The molecules having IL-21 functional activities include polypeptides that have homology to the human IL-21 polypeptide sequence and proteins fused to a polypeptide with IL-21 functional activity. The molecules can be used as a monotherapy or in combination with other known antimicrobial or antiviral therapeutics.

Abstract: The invention is directed to a fusion protein which includes a first portion including an immunoglobulin (Ig) chain and a second portion including interleukin-7 (IL-7).

Abstract: A transmembrane fusion protein including ubiquitin or a ubiquitin-like protein, a membrane translocation sequence linked to the C-terminus of the ubiquitin or ubiquitin-like protein, and a biologically active molecule linked to the C-terminus of the membrane translocation sequence is disclosed herein. A polynucleotide encoding the transmembrane fusion protein, a recombinant expression vector including the polynucleotide sequence, a cell transformed by the recombinant expression vector, and a method of delivering the biologically active molecule into a cell using the transmembrane fusion protein are also disclosed.

Abstract: The invention relates to suppressor of the endogenous human interferon-gamma (hlFN-?) applicable in treatment of diseases associated with impaired activity of endogenous hlFN-?, especially autoimmune diseases and for prevention of graft arteriosclerosis and rejection of organs in allograft transplanted patients. It is based on inactive analogues of the hlFN-? with pre-served affinity to the hlFN-? receptor, genetically modified in the domain responsible for triggering the signal transduction pathway.

Abstract: Purified genes encoding a cytokine or composite cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: Methods of diagnosing, detecting or treating cancer where the cancer expresses a tumor cell antigen that is elevated relative to the normal adjacent tissue, by administering an antibody or antibody fragment which binds to that tumor cell antigen. The methods involve the use of antibodies that bind to the tumor cell antigens KIAA1815, LOC157378, FU20421, DSCD75, GPR160, GPCR41, and SLC1A5.

Abstract: Disclosed are interferons of Rhesus and Cynomolgus origin and methods of production and use thereof.

Abstract: Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.

Abstract: The present invention provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) in which the antibody or fragment thereof is conjugated to a pharmaceutically active moiety. The invention also provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (Gil) and a detectable label. The invention further provides the use of such compositions in medicine, in particular for the treatment of an arthropathy, and in methods of diagnosis.

Abstract: A method for inducing differentiation of ES cells into cardiomyocytes, which comprises contacting the ES cells with an agonist for G-CSF receptor.

Abstract: This invention relates to compositions and methods comprising “lymphotoxin-?-receptor blocking agents”, which block lymphotoxin-? receptor signalling. Lymphotoxin-? receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-?.receptor extracellular domain that act as lymphotoxin-? receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-?. receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-? receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-? receptor signalling is provided.

Abstract: The present invention relates to IL-2 mutants with increased affinity for the IL-2 alpha-receptor subunit (IL-2R?). The invention thus includes IL-2 mutants with improved biological potency. The invention also includes methods for directed evolution of IL-2? using yeast surface display to generate mutants with increased affinity for IL-2R?.

Abstract: The present invention is directed to novel polypeptides having homology to the IL-1-like family of proteins and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention, and methods for producing the polypeptides of the present invention.

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: The present invention provides a chimeric protein capable of killing or modifying a cell expressing abnormally high levels of a ligand of a receptor of the TNF/NGF family, comprising the amino acid sequence of at least one polypeptide consisting of an extracellular portion of said receptor connected to an effector molecule. In addition the invention provides pharmaceutical compositions comprising said chimeric protein and use thereof.

Abstract: A conjugate protein comprising a GM-CSF or a fragment thereof and a truncated CCL2 is described. The conjugate protein has unexpected immune suppressive, anti-obesity and tumoricidal properties and is useful in a variety of therapeutic applications.

Abstract: The present invention relates to novel methods of making soluble proteins having free cysteines in which a host cell is exposed to a cysteine blocking agent. The soluble proteins produced by the methods can then be modified to increase their effectiveness. Such modifications include attaching a PEG moiety to form pegylated proteins.

Abstract: Novel polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zyctor17, a novel cytokine receptor. The polypeptides may be used within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The polynucleotides encoding zyctor17, are located on chromosome 5, and can be used to identify a region of the genome associated with human disease states. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Abstract: The invention provides TGF-?3s, or fragments or derivatives thereof, wherein the alpha-helix-forming domain between amino acid residues (58) and (67) of full-length wild type TGF-?3 comprises at least one alpha-helix-stabilizing substitution. The invention also provides TGF-?3s, or fragments or derivatives thereof, wherein the Glycine residue at position (63) of full-length wild type TGF-?3 is replaced with Proline. Further still, the invention provides TGF-?3s, or fragments or derivatives thereof, comprising a substitution of the Glutamic acid residue at position (12) of full-length wild type TGF-?3 and/or the Arginine residue at position (52) of full-length wild type TGF-?3. The invention also provides medicaments and methods of treatment using such TGF-?3s.

Abstract: The present invention provides for IL-17 receptor like polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, agonists and antagonists (including selective binding agents), and methods for producing IL-17 receptor like polypeptides. Also provided for are methods for treatment, diagnosis, amelioration, or prevention of diseases with IL-17 receptor like polypeptides.

Abstract: A method for precipitating casein from a suspension comprising milk is disclosed. The method includes the following steps: adding a phosphate solution to a suspension; mixing the phosphate solution with the suspension to form a mixture having a phosphate concentration greater or equal to 40 mM; freezing the mixture having a phosphate concentration greater or equal to 40 mM to obtain a frozen mixture; and thawing the frozen mixture to obtain casein-containing aggregates in the mixture, in which the phosphate solution is buffered at a pH value of no less than 4.4.

Abstract: The current invention provides methods for producing a polypeptide as inclusion bodies in bacterial host cells. The present methods are carried out by forming a gene construct comprising the genetic sequence encoding a polypeptide operatively linked to that of an inclusion partner protein, such as E. coli thioredoxin or a modified E. coli thioredoxin, such that host cells comprising the gene construct produce the polypeptide as intracellular inclusion bodies. The methods of the present invention facilitate the rapid isolation and purification of recombinant proteins. In addition, the present methods may be useful for producing polypeptides or proteins which are small and are typically difficult to express, as well as those proteins that are toxic to host cells such as E. coli. The present invention also provides plasmids, vectors and host cells to be used in the present invention for production of polypeptides, and methods of production of polypeptides using these vectors and host cells.

Abstract: Disclosed are water soluble polymeric reagents comprising the structure POLY-[Y—S—W]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, and S—W is a thiol, protected thiol, or thiol-reactive derivative. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are conjugates of such polymeric reagents with pharmaceutically relevant molecules, and methods of their formation and use.

Abstract: Compositions, kits and methods for the prevention of, for example, spontaneous abortion, preeclampsia, preterm labor or implantation failure during assisted reproduction are provided. The compositions, kits and methods provide an effective amount of granulocyte colony stimulating factor to prevent, for example, spontaneous abortion, preeclampsia, preterm labor or implantation failure of an embryo.

Abstract: Methods and compositions for modulating the mobilization of stem cells, particularly for promoting or increasing the mobilization of hematopoietic stem cells from the bone marrow to the peripheral blood are disclosed. In particular, the invention relates to the use of adrenergic agonists that act in concert with a mobilization compound or agent. The mobilization agent(s) may act to decrease the expression or function of the chemokine, CXCL12, or may act to block or antagonize CXCR4. The invention also relates to methods of using these compounds or agents for enhancing the mobilization of hematopoietic stem cells when harvesting of the stem cells is necessary for the treatment of diseases, disabilities or conditions whereby transplantation of such cells would be beneficial in ameliorating the symptoms associated with such diseases, disabilities or conditions. Methods of screening for novel agents and pharmaceutical compositions comprising these agents are also disclosed.

Abstract: Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of Il-12 for bone marrow preservation or recovery.

Abstract: The present invention relates to the use of the compound according to formula (I), below for the treatment of tumors, cancer and hyperproliferative diseases, among other conditions or disease states: Where X is H or F; R1 and R2 are independently H, an acyl group, a C1-C20 alkyl or ether group, a phosphate, diphosphate, triphosphate or a phosphodiester group, a (A) or (B) group; Where Nu is a radical of a biologically active compound such as an anticancer, antiviral or antihyperproliferative compound such that an amino group or hydroxyl group from said biologically active agent forms a phosphate, phosphoramidate, carbonate or urethane group with the adjacent moiety; each R8 is independently H, or a C1-C20 alkyl or ether group, preferably a C1-C12 alkyl group; k is 0-12, preferably, 0-2; and pharmaceutically acceptable salts thereof.