Abstract: The present invention relates to fusion proteins in which a pharmaceutically active component is fused to an antibody mimetic. The invention specifically concerns fusion proteins comprising interferons or biologically active muteins thereof and modified hetero-dimeric ubiquitin proteins as specific targeting domain. The invention further relates to these fusion proteins for use in medicine, in particular for use in the treatment of cancer or infectious diseases. The invention is further directed to pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with such fusion proteins, and in combination with cancer therapeutic agents. Moreover, the invention relates to a method for the generation of said fusion proteins.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

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 invention relates to suppressors of endogenous human interferon-gamma (INF-?) applicable in treatment of diseases associated with impaired activity of endogenous IFN-?. The suppressors of the invention are useful in treating autoimmune diseases and for prevention of graft arteriosclerosis and rejection of organs in allograft transplanted patients. The invention includes inactive analogues or variants of IFN-? having preserved affinity to the IFN-? receptor, genetically modified in the domain responsible for triggering the signal transduction pathway.

Abstract: The present invention relates generally to antibodies cross-reactive with IL-17A and IL-17F, and bispecific anti-IL-17A/F and their uses.

Abstract: The present invention relates to a method for increasing the expression of a protein in cells, preferably in eukaryotic cells, by reducing the number of RNase L cleavage sites in the coding and/or non-coding region of the nucleic acid sequence of said protein. Furthermore, it relates to nucleic acid sequences exhibiting a reduced number of RNase L cleavage sites as well as to the proteins translated from such sequences.

Abstract: Monoclonal antibodies to the IL-21 receptor and multimeric complexes comprising the IL-21 receptor; including monoclonal antibodies to the heterodimeric receptor, IL-21/IL-2R?; have been prepared. The invention also describes a method of producing said antibodies. And, the invention also describes a method of treatment comprising using said antibodies to suppress an immune response.

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: Reagents and methods for functionalizing polypeptides with moieties poly (alkylene glycol) molecules and glycan groups are disclosed that are based on a functionalizing reagent which comprises a nitrogen containing heterocyclic aromatic ring having a vinyl substituent that is capable of reacting with one or more thiol groups that are naturally present, or have been introduced into, the polypeptide, for example by employing a thiol group of one or more cysteine residues. The functionalizing reagent is covalently linked to a poly (alkylene glycol) molecule, such as a polyethylene glycol (PEG) molecule, or a glycan group so that the reaction between the vinyl group and the thiol group in the polypeptide covalently links the polypeptide to the poly (alkylene glycol) molecule and/or the glycan group.

Abstract: A recombinant fusion interferon for animals. The recombinant fusion interferon comprises an animal interferon and a Fc region of an animal immunoglobulin G (IgG). The animal interferon and the Fc region of the animal immunoglobulin G can be further joined by a linker. A polynucleotide that encodes the recombinant fusion interferon for animals, a method for producing the recombinant fusion interferon, and the use of the recombinant fusion interferon.

Abstract: Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analogue, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

Abstract: The monofunctional branched poly(ethylene glycol) (PEG) has a general formula shown in formula (1), and the bio-related substance modified by the monofunctional branched PEG has a general fomula shown in formula (2), wherein X1 and X2 are each independently a hydrocarbon group having 1 to 20 carbon atoms, n1 and n2 are each independently an integer selected from 1 to 1000, n3 is an integer selected from 11 to 1000, L1, L2 are each independently a linking group, p is 0 or 1, q is 0 or 1, R1 is a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms, D is a bio-related substance, Z is a linking group, and Z can react with the bio-related substance to form a residue group L3. The PEG-modified bio-related substance maintains good biological activity, and has better solubility and a longer half-life in vivo.

Abstract: The invention relates to derivatives of recombinant proteins, comprising homo-multimers of genetically fused recombinant biologically active protein monomer units, connected via selected peptide linker moiety; and the method of preparation thereof. Derivative of recombinant protein is preferably dimer of human granulocyte colony-stimulating factor, characterised by increased circulation time in vivo.

Abstract: The present invention is related to a nucleic acid molecule binding to SDF-1, whereby the nucleic acid molecule influences migration of cells.

Abstract: This invention provides fully human monoclonal antibodies that recognize IL-17F, the IL-17F homodimer, IL-17A, the IL-17A homodimer, and/or the heterodimeric IL-17A/IL-17F protein complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: The invention relates, in part, to compositions and methods that utilize a peptide tag that binds to hemagglutanin (HA). The HA tag can be linked to a molecule such as a protein or nucleic acid which, when administered to the eye, results in an increase in ocular half-life and/or mean residence time, and or a decrease in ocular clearance of the protein or nucleic acid. The invention also encompasses methods for treating ocular disease, including retinal vascular disease, by administering a protein or nucleic acid linked to an HA peptide tag.

Abstract: Purified genes encoding a cytokine referred to as interleukin-B30 (IL-B30) from a mammal, and reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using the reagents and diagnostic kits are also provided.

Abstract: Homogeneous preparations of IL-28A, IL-28B, and IL-29 have been produced by mutating one or more of the cysteine residues in the polynucleotide sequences encoding the mature proteins. The cysteine mutant proteins can be shown to either bind to their cognate receptor or exhibit biological activity. One type of biological activity that is shown is an antiviral activity.

Abstract: Chemokine binding activity of viral TNF receptors and related proteins. The invention relates to a C-terminal domain (CTD) of viral tumor necrosis factor receptors (vTNFRs) CrmB or CrmD or CTD homologues (CTD1, CTD2 and CTD3) from poxvirus and their functional homologues, including derivatives, and fragments, for use in binding chemokines and their analogues and/or to enhance the immunomodulatory properties of TNFRs or in blocking binding of chemokines to their corresponding cell surface receptors and/or to modulate chemokine biological activity.

Abstract: The present invention relates generally to polypeptides whose primary sequence has high sequence homology with human interleukin 2 (IL-2) with some punctual mutations in the sequence of native IL-2. The polypeptides of the present invention have an immunomodulatory effect on the immune system, which is selective/preferential on regulatory T cells. The present invention also relates to specific polypeptides whose amino acid sequence is disclosed herein. In another aspect the present invention relates to pharmaceutical compositions comprising as active ingredient the polypeptides disclosed. Finally, the present invention relates to the therapeutic use of the polypeptides and pharmaceutical compositions disclosed due to their immune modulating effect on diseases such as cancer and chronic infectious diseases.

Abstract: Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

Abstract: Bispecific antibodies which comprise antigen-binding regions binding to two different epitopes of human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods of preparing and using the antibodies are also disclosed.

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: Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

Abstract: Conjugate comprising interleukin-12 (IL-12) and a single chain targeting portion comprising two antigen binding sites. The targeting portion may comprise an antibody fragment such as a single chain diabody. The conjugate may be a single chain fusion protein. Use of single chain bivalent IL-12 immunocytokine for targeting the extra-cellular matrix (ECM) of tissues, particularly tumour neovasculature antigens, for example fibronectin. Use for treating cancer or pathological angiogenesis in a patient.

Abstract: Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [125I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.

Abstract: The invention relates to methods and kits for the differential diagnosis of Alzheimer's disease (AD) versus frontotemporal dementia (FTD), using biomarkers TNF-?, FAS-L and CK18, taken from a biological sample. Differences in biomarker levels can be used to distinguish between AD and FTD The invention is based on a discovered correlation between FTD and markers FAS-L and CK18. Therefore the invention also relates to the diagnosis of FTD using FAS-L and CK18. The serum concentrations of these biomarkers can further be used as an index of the severity of disease, and may occur in conjunction with clinical-based diagnostic testing and neuro-imaging assessment.

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 relates to a compound which is a polysaccharide derivative of GCSF, or of a GCSF like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for albumin. It also relates to new methods and uses that exploit binding by these and other compounds to albumin in different contexts, some of which have significance for treatment or diagnosis of disease in mammals including humans.

Abstract: Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.

Abstract: Homogeneous preparations of IL-28A, IL-28B, and IL-29 have been produced by mutating one or more of the cysteine residues in the polynucleotide sequences encoding the mature proteins. The cysteine mutant proteins can be shown to either bind to their cognate receptor or exhibit biological activity. One type of biological activity that is shown is an antiviral activity.

Abstract: Disclosed are peptides having activity against receptor CXCR3 are disclosed that exhibit activity in preventing the formation of new vessels and activity in mediating the dissociation of newly-formed vessels and resolving of wounds in the later stages of wound healing. Preferred peptides are derived from the ?-helix portion IP-10 (CXCL10) or from IP-9 (CXCL11), are nontoxic, and smaller than naturally occurring peptides, making them useful in therapies against diseases or disease states marked by unwanted angiogenesis, including tumorogenic diseases such as cancers, and in healing of chronic wounds.

Abstract: The present invention relates to methods for obtaining a polypeptide in a monomeric form, the method comprising a) providing a solution containing the polypeptide in monomeric form and in aggregated form, wherein the ratio of monomeric to aggregated form is 4:1 or less, as determined by size exclusion chromatography, b) performing mixed-mode chromatography in bind-and-elute mode, or hydrophobic interaction chromatography in flow-through mode, or a size-exclusion chromatography, and c) performing a weak cation exchange chromatography in bind-and-elute mode or flow-through mode, and thereby obtaining the polypeptide in monomeric form.

Abstract: The present invention provides a polypeptide adjuvant composition with thermostability, which is designed from wild-type chicken interleikin-1? to construct a new chicken interleikin-1?, named CP-interleikin-1?. The CP-interleikin-1? having improved heat resistance keeps the original biological activity, and which helps to develop protein adjuvant with high efficiency and uses in medical application. The present invention also provides a method of manufacturing such polypeptide adjuvant composition.

Abstract: Methods to derive novel hybrid type 1 interferons that are broadly active against highly pathogenic viruses of biodefense significance are described. Libraries of hybrid interferon genes were produced using gene shuffling, the proteins were expressed, and screened for activity against viruses of interest. Sequences of several broadly active hybrid interferons are described.

Abstract: The present invention provides a polypeptide adjuvant composition with thermostability, which is designed from wild-type chicken interleikin-1? to construct a new chicken interleikin-1?, named CP-interleikin-1?. The CP-interleikin-1? having improved heat resistance keeps the original biological activity, and which helps to develop protein adjuvant with high efficiency and uses in medical application. The present invention also provides a method of manufacturing such polypeptide adjuvant composition.

Abstract: The present invention is related to fragments of human melanotransferrin (p97). In particular, this invention relates to treatment of diseases through the introduction of the melanotransferrin fragment conjugated to a therapeutic or diagnostic agent to a subject.

Abstract: The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases.

Abstract: Described herein are cell lines and methods for preparing antibodies that bind RANKL, including cell lines that produce blocking antibodies to human RANKL.

Abstract: This invention provides fully human monoclonal antibodies that recognize IL-17F, the IL-17F homodimer, IL-17A, the IL-17A homodimer, and/or the heterodimeric IL-17A/IL-17F protein complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: A novel IFN-?/? independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated IFN-?1, IFN-?2, IFN-?3, based, inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN-? proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-?R1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-?R1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection.

Abstract: The present invention provides for biopolymer conjugates of an IL-11 analog (mIL-11) and a biocompatible polymer. The mIL-11 of the invention displays an enhanced resistance to acidolysis and shows increased stability as compared to rhIL-11. The conjugates of the present invention are characterized by a longer serum half-life and exhibit essentially no loss of activity as compared to the corresponding unconjugated mIL-11.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and/or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.

Abstract: A process for producing an interferon alpha 5 (IFNa5) protein by expression in an IFNa5 producing Escherichia coli host cell, wherein incorporation of an extra methionine residue in the N-terminal end of the polypeptide chain is minimized as well as the generation of its oxidized species is disclosed. The IFNa5 protein can be purified by an efficient process to render a biologically active IFNa5.

Abstract: The invention relates to the use of notch regulators for modulating IL-22 production in T-cells, by influencing the activity or activation of the notch signal path. The invention further relates to the use of modulating the immune response, primarily in case of infection reactions. The invention in particular relates to the use for treating illnesses associated with infections. The invention further relates to the use for reducing IL-22 production in T-cells.

Abstract: Provided is a method of obtaining biologically active recombinant human G-CSF from inclusion bodies, wherein the solubilization and refolding process can be performed at ambient temperature and the purification step comprises reversed phase chromatography (RP), in particular RP-HPLC. The G-CSF preparation so obtained is characterized by high purity and homogeneity.

Abstract: The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to engineered fusion molecules comprising an antibody (Ab) which can target tumor cells (e.g., RITUXIN®), fused to one or more biologic moieties capable of inducing apoptosis in tumor cells, e.g., tumor necrosis factor super family (TNFSF) member ligands such as TNF-?, CD40L, CD95L (also “FasL/Apo-1L”) and TRAIL/Apo-2L. Importantly, the engineered fusion molecules of the present invention retain the death-inducing properties of the biologic moiety at optimum concentrations and with reduced systemic toxicities, thus improving the therapeutic index of the engineered fusion molecules.

Abstract: IL-17 Receptor binding proteins, including non-naturally occurring and recombinantly modified proteins, methods of making and using such molecules as therapeutic, prophylactic and diagnostic agents are provided.