Abstract: Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-? conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-?, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

Abstract: The present invention relates to hydroxyalkylstarch (HAS)-polypeptide-conjugate (HAS-polypeptide) comprising one or more HAS molecules, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety or a thioether as well as to methods for the production thereof. In a preferred embodiment, the polypeptide is erythropoietin (EPO).

Abstract: The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.

Abstract: The present invention provides compositions and methods relating to IL-1Rrp2 requiring proteins.

Abstract: The present invention provides fusion proteins comprising a mucin-domain polypeptide covalently linked to an active protein that has improved properties (e.g. pharmacokinetic and/or physicochemical properties) compared to the same active protein not linked to mucin-domain polypeptide, as well as methods for making and using the fusion proteins of the invention.

Abstract: The invention provides compound of the general formula: in which each X independently represents a polymer chain; n represents an integer greater than 1; Q represents a linker; Y represents an amide group; and Z represents either —CH.(CH2L)2 or —C(CH2L)(?CH2), in which each L independently represents a leaving group. The compounds are useful reagents for the conjugation of polymers to proteins, the resulting conjugates being novel and also forming part of the invention.

Abstract: A method for measuring the proliferation status of a cell present in a biological sample, comprising the step of measuring in the said cell the loss of BACH2 by Fluorescence after In Situ Hybridization (FISH) analysis and mRNA quantification or by Comparative Genomic Hybridization (CGH) and corresponding kit and applications.

Abstract: The present invention provides fusion polypeptides comprising polypeptide ligands that are modified by circular permutation and fused to at least one polypeptide fusion partner wherein such fusion polypeptides have new, improved or enhanced biological functions or activities. Such improvements include, but are not limited to, increased binding affinity, increased activity, increased agonist activity (super agonist), antagonist activity, increased accessibility, increased flexibility of the active site, increased stability, broader and/or changed substrate specificity, and combinations thereof.

Abstract: The invention provides fusion proteins having improved bioactivity comprising a first polypeptide fusion partner and a second polypeptide fusion partner wherein the first fusion partner is linked to the second fusion partner by a mucin-domain polypeptide linker and wherein the bioactivity of the fusion protein of the invention is improved as compared to fusion of the first polypeptide fusion partner and the second polypeptide fusion partner in the absence of the mucin-domain polypeptide linker. Mucin-domain polypeptide linkers comprise a mucin domain that is rich in potential glycosylation sites, and has a high content of serine and/or threonine and proline, which can represent greater than 40% of the amino acids within the mucin domain and further comprise at least about 60% of its mass due to the glycans.

Abstract: This invention provides fully human monoclonal antibodies that recognize IL-17F and/or the heterodimeric IL-17A/IL-17F complex, but do not recognize IL-17A. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: The present invention relates to blocking, inhibiting, reduceing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, hybridomas that produce the antibodies, and methods of using the same in inflammation.

Abstract: The present invention provides, among other things, polymeric reagents suitable for reaction with biologically active agents to form conjugates, the polymeric reagents comprising one or more polymer chains and a plurality of hydroxyapatite-targeting moieties, and optionally the reagents include one or more degradable linkages that serve to divide the polymer chains into polymer segments having a molecular weight suitable for renal clearance.

Abstract: Disclosed herein are novel proteins that have reduced binding to the interleukin-7 receptor, compositions containing such proteins, and methods of using the same.

Abstract: Cosmetic methods for treating skin and/or hair, including steps of (a) applying to skin and/or hair a cosmetic composition comprising interleukin-1 for 3 to 70 days, followed by (b) withdrawing application of the composition for 14 to 70 days, and (c) repeating steps (a)-(b) at least once.

Abstract: The present invention relates to interferon (IFN)-?2a modified at a specific Lys residue with Y-shaped branched polyethylene glycol (PEG) derivative and the preparation thereof, as well as the use of the prepared IFN-?2a modified by PEG at a single amino acid residue in medicines.

Abstract: Modified, furin resistant human TSLP polypeptides and polynucleotides encoding the modified human TSLP polypeptides are provided. Pharmaceutical compositions, B and T cell activation agents, assays and methods of use are also described.

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

Abstract: The present invention relates to a polypeptide having interleukin-10 function, comprising two interleukin-10 monomer subunits covalently linked by a linker. The present invention further relates to a nucleic acid molecule encoding the polypeptide of the invention, a vector comprising said nucleic acid molecule, a non-human host transformed with the nucleic acid molecule or the vector of the invention as well as a method for the production of a recombinant polypeptide of the invention. The present invention further relates to a pharmaceutical composition as well as to the polypeptide, the nucleic acid molecule, the vector or the host or host cell of the invention for use in treating and/or preventing inflammatory diseases.

Abstract: Disclosed are methods for the treatment and/or prevention of Type 2 diabetes, insulin resistance and disease states and conditions characterized by insulin resistance, obesity, hyperglycemia, hyperinsulinemia and Type 1 diabetes, comprising administering to a subject an effective amount of anti-IL-1? antibody or fragment thereof.

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: The present invention provides a new stable pharmaceutical composition of granulocyte-colony stimulating factor (G-CSF).

Abstract: Provided are MUC18 targeting peptides which may be used, e.g., to therapeutically target B-1 lymphocytes to reduce the influence of these cells on the metastatic potential of melanoma cells and/or to target cancerous cells, including certain melanoma and leukemia cells. MUC18 targeting peptides may be comprised in fusion constructs, imaging constructs, and/or therapeutic constructs such as fusion constructs which may be used for diagnosing or treating a cancer.

Abstract: The present invention relates to a novel drug delivery system comprising a drug(s)-protein-polymer triple conjugate. The triple conjugate employs a (i) protein moiety capable of binding selectively to a particular target site possessed by a cell/affected organ, (ii) a polymer moiety, covalently linked to the protein and (iii) an active drug moiety that includes one or more drug(s) covalently linked to either said polymer moiety or to a protein moiety. The conjugates of the present invention have target specificity and better selectivity to a defined population of cells/organs(s). The present invention further relates to methods of preparation and methods of treatment comprising administering said conjugate as a single unit. The conjugates of the present invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic applications.

Abstract: Disclosed is a newly identified secreted molecule, identified herein as “monocyte, granulocyte, and dendritic cell colony stimulating factor” (MGD-CSF), the polypeptide sequence, and polynucleotides encoding the polypeptide sequence. Also provided is a procedure for producing the polypeptide by recombinant techniques employing, for example, vectors and host cells. Additionally, procedures are described to modify the disclosed novel molecules of the invention to prepare fusion molecules. Also disclosed are methods for using the polypeptides and active fragments thereof for treatment of a variety of diseases, including, for example, cancer, autoimmune and inflammatory diseases, infectious diseases, and recurrent pregnancy loss.

Abstract: IFN-alpha mutants are obtained by substituting Cys for Tyr at position 85 or 86 in existing IFN-alpha. Their polyethylene glycol derivatives with high in vitro antiviral activity and prolonged in vivo half-life are also provided, wherein a polyethylene glycol moiety is covalently bound to the free Cys residue of an IFN-alpha mutant. The preparation methods of PEG derivatives of IFN-alpha mutants and medical compositions comprising the derivatives are also provided. The test results showed that the IFN-alpha mutants of the present invention are ready to prepare and have high activity; their polyethylene glycol derivatives have extended lifetime in the body and low clearance rate.

Abstract: Disclosed are a protein conjugate with improved in vivo duration and stability and the use thereof. The protein conjugate includes a physiologically active polypeptide, a non-peptide polymer and an immunoglobulin Fc fragment. Since the three components are covalently linked, the protein conjugate has extended in vivo duration and enhanced stability for the physiologically active polypeptide. The protein conjugate maintains the in vivo activity at relatively high levels and remarkably increases the serum half-life for the physiologically active polypeptide, with less risk of inducing undesirable immune responses. Thus, the protein conjugate is useful for developing long-acting formulations of various polypeptide drugs.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: Disclosed are water soluble polymeric conjugates comprising the structure POLY-[Y—S—S-A]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 2, S—S is a disulfide group attached to an sp3 hybridized carbon of Y; and A is a covalently linked residue of a pharmacologically active molecule. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are polymeric reagents useful to prepare such conjugates, and methods of their formation and use.

Abstract: This invention provides a set of methods for modulating protein spatial configuration. First, select the amino-acid codon for encoding the target protein according to host codon usage. Second, choose combinations which can modulate the spatial configuration and construct into different vectors which can transfect a series of hosts. Third, choose the vector promoter by monitoring a combination of base pairs after combining the code sequence of the promoter and the target protein. Finally, choose the appropriate expression host to express the target protein, refold and purify, measure the activity and spatial configuration.

Abstract: Provided are pharmaceutical liquid formulations of G-CSF, which are stable over a long time period and substantially free of excipients, as well as ready-to-use syringes containing such formulations and corresponding kits.

Abstract: Novel chimeric moieties that show significant efficacy against cancers are provided. In certain embodiments the chimeric moieties comprise a targeting moiety attached to an interferon. In certain embodiments, the chimeric moieties comprise fusion proteins where an antibody that specifically binds to a cancer marker is fused to interferon alpha (IFN-?) or interferon beta (IFN-?).

Abstract: The present invention provides an antibody comprising an antigen binding domain which binds to human IL-12 and human IL-23. The antibody binds human IL-12p40 existing as a monomer (human IL-12p40) and as a homodimer (human IL-12p80) and the antibody inhibits the binding of human IL-12 to human IL-12R ?2 and human IL-23 to human IL-23R but does not inhibit the binding of human IL-12 or human IL-23 or human IL-12p40 or human IL-12p80 to human IL-12R?1.

Abstract: Disclosed are Fc-interferon-beta (Fc-IFN-?) fusion proteins and nucleic acid molecules encoding them. The Fc-IFN-? fusion proteins include variants of the interferon-beta (IFN-?) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and/or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

Abstract: The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, hybridomas that produce the antibodies, and methods of using the same in inflammation.

Abstract: This invention provides a recombinant interferon (rSIFN-co) and its equivalent with changed spatial configuration, high efficacy and low side effects. Therefore, high dose of rSIFN-co may be used. The cytotoxic effect of rSIFN-co is only one-eighth (?) of currently clinically available interferons but its anti-viral effect is approximately five to twenty (5-20) times higher, and when used in vivo it has a broader spectrum of clinical applications and longer biofeedback response. This invention further provides methods of using the recombinant interferon to treat proliferative disorders such as cancer or viral diseases.

Abstract: Disclosed are methods and materials for inhibiting (e.g., treating or preventing) uveitis in a subject, including treatment refractory uveitis, using anti-IL-1? binding molecules (e.g., IL-1? binding antibodies or binding fragment thereof).

Abstract: A fusion protein comprising domain (a) which is a functional fragment of hTRAIL protein sequence, which fragment begins with an amino acid at a position not lower than hTRAIL95, or a homolog of said functional fragment having at least 70% sequence identity; and domain (b) which is a sequence of an immunostimulating effector peptide, wherein the sequence of domain (b) is attached at the C-terminus or N-terminus of domain (a). The fusion protein can be used for the treatment of cancer diseases.

Abstract: An HA-protein conjugate in which an HA-aldehyde derivative, in which an aldehyde group is introduced to a hyaluronic acid or a salt thereof, is conjugated to the N-terminus of a protein, and a method for preparing the same are provided. The HA-protein conjugate includes a protein drug exhibiting an excellent bioconjugation efficiency and long-term medicinal effects, and has excellent protein drug activities since the hyaluronic acid is specifically conjugated to the N-terminus of the protein. Also, since liver-targeting properties of the hyaluronic acid can be freely controlled by changing an aldehyde substitution rate of the HA-aldehyde derivative, the HA-protein conjugate can be effectively used as a protein drug for treating liver diseases, and also be useful in enabling long-term medicinal effects of a protein drug required to bypass the liver. Accordingly, the HA-protein conjugate can be effectively used for a drug delivery system of proteins.

Abstract: A method, and system, to induce remission in diseases characterized by excess production of sTNR and interleukin 2 has been developed. In the most preferred embodiment, the system consists of antibodies to sTNFR1, sTNFR2 and sIL2R immobilized in a column containing a material such as SEPHAROSE™. The patient is connected to a pheresis machine which separates the blood into the plasma and red cells, and the plasma is circulated through the column until the desired reduction in levels of sTNFR1, sTNFR2, and IL2 is achieved, preferably to less than normal levels. In the preferred method, patients are treated three times a week for four weeks. This process can be repeated after a period of time. Clinical studies showed reduction in tumor burden in patients having failed conventional chemotherapy and radiation treatments.

Abstract: Provided herein are IL-18 receptor antigen binding proteins and polynucleotides encoding the same. Expression vectors and host cells comprising the same for production of the antigen binding proteins are also provided. In addition, provided are compositions and methods for diagnosing and treating diseases mediated by IL-18 receptor.

Abstract: Aspects and embodiments of the instant disclosure provide therapeutic methods and compositions comprising interleukin 12 (IL-12) useful for treating radiation-induced damage in a subject. In particular, the instant disclosure provides methods and compositions for radiation protection and/or radiation toxicity mitigation for the treatment of acute radiation syndrome and radiation induced toxicity associated with the treatment of cutaneous T-cell lymphoma.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

Abstract: The production of soluble HLA class II molecules, as well as methods of using the soluble HLA class II molecules so produced, are described herein.

Abstract: The invention pertains to methods of treating cardiovascular disease by modulating inflammatory and immunoregulatory responses associated with such pathological conditions. Embodiments of the invention provide methods for the treatment of cardiovascular disease in a subject having cardiovascular disease comprising administering an effective amount of one or more IL-17 antagonists, IL-18 antagonists, 4-1BB antagonists, CD30 antagonists, OX40 antagonists and/or CD39 alone or in any combination. This abstract is provided for the sole purpose of enabling the reader to quickly ascertain the subject matter of the technical disclosure and is not intended to be used to interpret or limit the scope or meaning of the claims. 37 CFR 1.72(b).

Abstract: The invention relates to a method for the preparation of a hydroxyalkyl starch derivative which comprises reacting hydroxyalkyl starch (HAS) via the optionally oxidised reducing end of the HAS with the amino group M of a crosslinking compound which, apart from the amino group, comprises a specifically protected carbonyl group, namely an acetal group or a ketal group.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen array, wherein the antigen is an IL-1 protein, an IL-1 mutein or an IL-1 fragment. More specifically, the invention provides a composition comprising a virus-like particle, and at least one IL-1 protein, IL-1 mutein or at least one IL-1 fragment linked thereto. The invention also provides a process for producing the composition. The compositions of the invention are useful in the production of vaccines for the treatment of inflammatory diseases, and chronic autoimmune diseases, genetic diseases and cardiovascular diseases. The composition of the invention efficiently induces immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

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 fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-?) mutant molecule. The engineered Ab-IFN-? mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-? fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-? fusion molecules.

Abstract: The present application discloses new PEG-interferon lambda 1 conjugates (PEG-IFN?1), processes for their preparation, pharmaceutical compositions containing these conjugates and processes for making the same. These conjugates have increased blood half-lives and persistence time compared to IFN?1 and are effective in the treatment of hepatitis B and hepatitis C.

Abstract: The present invention relates to blocking the activity of IL-TIF polypeptide molecules. IL-TIF is a cytokine involved in inflammatory processes and human disease. The present invention includes anti-IL-TIF antibodies and binding partners, as well as methods for antagonizing IL-TIF using such antibodies and binding partners in IL-TIF-related human inflammatory diseases, amongst other uses disclosed.