Abstract: The present invention relates to novel Anilinopiperazine Derivatives of Formula (I), compositions comprising the Anilinopiperazine Derivatives, and methods for using the Anilinopiperazine Derivatives for treating or preventing a proliferative disorder, cancer, an anti-proliferative disorder, inflammation, arthritis, a central nervous system disorder, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral disease, a fungal infection, or a disorder related to the activity of a protein kinase.

Abstract: Connective tissue regenerative compositions and methods of repairing and regenerating connective tissue using such compositions are provided. The compositions generally comprise a bioactive hydrogel matrix comprising a polypeptide, such as gelatin, and a long chain carbohydrate, such as dextran. The hydrogel matrix may further include polar amino acids, as well as additional beneficial additives. Advantageously, the compositions include further components, such as osteoinductive or osteoconductive materials, medicaments, stem or progenitor cells, and three-dimensional structural frameworks. The compositions are useful for regenerating connective tissue, and can be administered to an area having injury to, or a loss of, connective tissue, such as bone, cartilage, tendon, and ligament.

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: The invention provides a method of modulating a T cell immune response by modulating DR3 function in the T cell, wherein the T cell response causes a symptom of inflammatory lung disease. The invention also provides a method of treating a reactive airway disease in an animal subject by administering to the subject an agent which modulates at least one functional activity of CD30. The invention additionally provides a method for treating an inflammatory lung disease by administering an agent that decreases the activity of DR3 or CD30, whereby IL-13 expression is decreased.

Abstract: Methods and kits for preventing or reducing the likelihood of implantation failure or spontaneous abortion in a recipient of FET, ICSI, GIFT or ZIFT are provided. The methods include administering into a recipient of FET, ICSI, GIFT or ZIFT in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

Abstract: Novel mutants of human monocyte chemoattractant protein 1 (MCP-1) with increased glycosaminoglycan (GAG) binding affinity and knocked-out or reduced GPCR activity compared to wild type MCP-1, and their use for therapeutic treatment of inflammatory diseases.

Abstract: Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

Abstract: Disclosed are solid and frozen haemostatic materials and dressings consisting essentially of a fibrinogen component and a fibrinogen activator. Also disclosed are methods of treating internal wounded tissue in a mammal by applying one or more of these haemostatic materials and dressings.

Abstract: Disclosed herein are methods and compositions comprising interferon-? (IFN-?) and anti-CD74 or anti-HLA-DR antibodies. In preferred embodiments, the IFN-? increases the expression of CD74 and/or HLA-DR in target cells and increases the sensitivity of the cells to the cytotoxic effects of the anti-CD74 or anti-HLA-DR antibodies. The compositions and methods are of use to treat diseases involving CD74+ and/or HLA-DR+ cells, such as cancer cells, autoimmune disease cells or immune dysfunction disease cells.

Abstract: Disclosed herein are polypeptides which comprise all or part of an antibody linked to all or part of a cytokine. The cytokine sequences of the polypeptides have a modified heparin binding region which disrupts, inhibits, or reduces the ability of the cytokine to bind a heparin compound as compared to a corresponding cytokine having an unmodified heparin binding region. Also disclosed are methods of treating cancer, inducing cell proliferation, and reducing the non-specific binding and/or non-specific localization of the polypeptides.

Abstract: Stabilized pharmaceutical compositions comprising substantially monomeric interferon-beta (IFN-?) and methods useful in their preparation are provided. The compositions comprise the IFN-? solubilized in a low-ionic-strength formulation that maintains the composition at a pH of about 3.0 to about 5.0. Methods for preparing these compositions, and for increasing solubility of IFN-? in pharmaceutical compositions, are provided.

Abstract: Methods and kits for preventing or reducing the likelihood of implantation failure or miscarriage in a recipient of artificial insemination are provided. The methods include administering into a recipient of artificial insemination in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

Abstract: The present disclosure relates to methods for the modulation of autophagy and the treatment of autophagy-related diseases, including cancer, neurodegenerative diseases and pancreatitis.

Abstract: The present invention relates to the discovery of novel T cell epitopes of the human HER-2/Neu protein that is promiscuous for at least 25 different HLA-DR alleles. The invention also relates to compositions that contain one of the novel epitopes or a fusion peptide of such a epitope and a heterologous polypeptide. Further disclosed herein is the use of the epitopes or their fusion peptides, and compositions containing the epitopes or their fusion peptides.

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: Described herein are compositions and methods for treating, preventing and ameliorating diseases and conditions characterized by a lower than normal white blood cell count, such as leukopenia and neutropenia. The compositions and methods include recombinant human albumin-human granulocyte colony stimulating factor. Pharmaceutical formulations including the recombinant fusion protein, and methods of making such formulations are also described.

Abstract: The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.

Abstract: The invention relates to a compound of formula: which may be in base form or in the form of a hydrate or a solvate, in combination with prednisone or prednisolone, for its use as a medicament in the treatment of prostate cancer, particularly metastatic prostate cancer, especially for patients who are not catered for by a taxane-based treatment.

Abstract: The invention relates to a human or veterinary pharmaceutical composition (B) for the stimulation of stem cells, comprising at least two stem-cells-stimulating-agents and at least one pharmaceutically acceptable excipient.

Abstract: The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HW).

Abstract: The present invention relates to a vaccine for increasing the immunogenicity of a tumor antigen thus allowing treatment of cancer, as well as a vaccine that increases the immunogenicity of a viral antigen, thus allowing treatment of viral infection, including immunodeficiency virus (HIV) infection. In particular, the present invention provides a fusion protein comprising a viral chemokine fused to either a tumor antigen or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing viral infection.

Abstract: The disclosure relates to treating muscle wasting-associated disorders in a patient, using a therapeutically effective amount of an antagonist of Fbxo40, wherein the antagonist reduces the expression, level or activity of Fbxo40. The Fbxo40 antagonist increases muscle mass, or prevents, limits or reduces muscle mass loss, in the patient. The Fbxo40 antagonist can be a low molecular weight (LMW) compound, a protein, an antibody, or an inhibitory nucleic acid, such as a siRNA. The disclosure also relates to methods of screening for antagonists of Fbxo40, and methods of diagnosing or monitoring levels of muscle mass maintenance, loss or increase.

Abstract: Disclosed is a liquid formulation which allows long-acting G-CSF conjugates, that have improved in vivo duration and stability, to be stable when stored for a long period of time. It comprises a stabilizer composition characterized by buffer and mannitol. Being free of human serum albumin and other potential factors harmful to the body, the liquid formulation is free of concerns about viral infections and guarantees excellent storage stability to long-acting G-CSF conjugates.

Abstract: Novel acoustically sensitive drug carrying particles comprising low concentrations of phosphatidylethanolamine are disclosed, as well as uses and methods thereof. The drug carrying particles accumulate in the diseased target tissue and efficiently release their payload upon exposure to acoustic energy.

Abstract: A method including introducing a treatment agent at a treatment site within a mammalian host; and introducing a bioerodable gel material at the treatment site. An apparatus including a first annular member having a first lumen disposed about a length of the first annular member and a first entry port at a proximal end of the first annular member, and a second annular member coupled to the first annular member having a second lumen disposed about a length of the second annular member and a second entry port at a proximal end of the second annular member, wherein the first annular member and the second annular member are positioned to allow a combining of treatment agents introduced through each annular member at the treatment site.

Abstract: A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and/or increase in one or more tryptophan metabolites within the local macrophage microenvironment Expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and other types of transplantation. Inhibitors of IDO can be used to activate T cells. Inhibiting tryptophan degradation, or supplementing tryptophan concentration, can be used in addition to, or in place of, inhibitors of IDO. Increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. One can manipulate local tryptophan concentrations, and/or modulate the activity of the high affinity tryptophan transporter, and/or administer tryptophan degrading enzymes.

Abstract: Methods and compositions for the use of long-acting hematopoietic factor protein analogs for accelerating hematopoietic recovery in subjects who have been or will be exposed to radiation are disclosed.

Abstract: New chiral and achiral oxy-substituted cyclopentyl pyridinone diketocarboxamides and their derivatives and methods for their preparations are disclosed. The compounds include tautomers, regioisomers and geometric isomers. These complex carboxamides are designed as inhibitors of HIV replication through inhibition of HIV integrase. The compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

Abstract: The present invention relates to the ability of adipose tissue-derived adult stem cells to migrate, and more particularly to the novel use of adipose tissue-derived adult stem cells primed with a specific chemokine or growth factor and their specific secretory products, which more effectively migrate to a disease site in vivo. The inventive composition containing either adipose-derived adult stem cells or adipose tissue-derived adult stem cells primed with a specific chemokine or growth factor can be administered by a simple method such as intravenous administration and are able to induce the targeting of the stem cells to a disease site. Thus, the composition is useful as a cell therapeutic agent.

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. Also disclosed are therapeutic methods for using the cysteine variants of the invention.

Abstract: Disclosed are fusion proteins comprising a biologically active molecule and an immunoglobulin (Ig) Fc domain which is linked to the biologically active molecule. The Fc domain is a hybrid human Fc domain of (i) IgG1, IgG2 or IgG4 or (ii) IgG4 and IgD. The hybrid Fc is useful as a carrier of biologically active molecules.

Abstract: The present invention relates generally to the field of inflammation. More particularly, the present invention relates to reducing release of pro-inflammatory cytokines induced to MUC1 activity. In one aspect, the present invention provides a method of modulating (inhibiting or promoting) an inflammatory response wherein modulation of the inflammatory response is desired, comprising administering an effective amount of an agent which inhibits or promotes MUC-1 function to an individual.

Abstract: The present invention provides compositions, kits and methods for the prevention of spontaneous abortion or implantation failure during assisted reproduction. The compositions, kits and methods provide an effective amount of granulocyte colony stimulating factor to prevent spontaneous abortion or implantation failure of an embryo. The present invention also provides compositions, kits and methods for the treatment or prevention of preeclampsia and preterm labor.

Abstract: The present invention provides a method of improving a therapeutic response to a cancer treatment, in a subject, the method comprising administering an effective amount of an agent that enhances the expression of microRNA-140-5p or an agent that mimics the effects of microRNA-140-5p. Further provided is a method of treating a cancer in a subject in need of such treatment comprising the step of administering an effective amount of a microRNA-140-5p or an agent that enhances the expression of microRNA-140-5p.

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H? function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

Abstract: The invention relates to diazo bicyclic Smac mimetics that are tethered through a covalent linker to give a bivalent species. Bivalent diazo bicyclic Smac mimetics function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs). The invention also relates to the use of bivalent diazo bicyclic Smac mimetics for inducing or sensitizing cells to the induction of apoptotic cell death. Thus, compounds of the invention are useful in the treatment, amelioration, or prevention of hyperproliferative diseases such as cancer.

Abstract: Methods and kits for preventing or reducing the likelihood of implantation failure or miscarriage in a recipient of artificial insemination are provided. The methods include administering into a recipient of artificial insemination in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

Abstract: A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.

Abstract: The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided. The conjugates are formed by a reductive amination reaction between at least one aldehyde group or keto group or hemiacetal group of the hydroxyalkyl starch or of a derivative of the hydroxyalkyl starch, and at least one amino group of the protein, so that the hydroxyalkyl starch or the derivative thereof is covalently linked to the protein via an azomethine linkage or a amino linkage. Methods of producing these conjugates and specific uses of the conjugates also are provided.

Abstract: The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

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: The present invention provides novel peptide immunogens comprising influenza virus matrix 2 protein epitopes and related compositions and methods. The present invention relates to a composition comprising a peptide immunogen useful for the prevention and treatment of an influenza virus-mediated disease. The invention also relates to vaccines, immunogenic products and immunogenic compositions containing the peptide immunogens.

Abstract: The present invention provides combinations of (a) an immunoconjugate comprising at least one antigen-binding moiety and an effector moiety, and (b) an antibody engineered to have increased effector function, for use in treating a disease in an individual in need thereof. Further provided are pharmaceutical compositions comprising the combinations, and methods of using them.

Abstract: Compositions and methods are provided for promoting organ development in warm blooded animals, and in particular in certain aspects a premature infant or fetus. Compositions and methods are also provided for the administration of at least one colony stimulating factor-1 protein (CSF-1), precursor, variant, analogue, derivative thereof, or combinations thereof, or otherwise, at least one nucleic acid molecule encoding colony stimulating factor-1 protein (CSF-1), precursor, variant, analogue, derivative thereof, or combinations thereof.

Abstract: Cellulose and sulfated cellulose fibrous meshes exhibiting robust structural and mechanical integrity in water were fabricated using a combination of electrospinning, thermal-mechanical annealing and chemical modifications. The sulfated fibrous mesh exhibited higher retention capacity for human recombinant bone morphogenetic protein-2 than the cellulose mesh, and the retained proteins remained biologically active for at least 7 days. The sulfated fibrous mesh also more readily supported the attachment and osteogenic differentiation of rat bone marrow stromal cells in the absence of osteogenic growth factors. These properties combined make the sulfated cellulose fibrous mesh a promising bone tissue engineering scaffold.

Abstract: The present invention provides methods for preventing, attenuating neuronal damage or stimulating neuronal repair prior or following central nervous system injury.

Abstract: The present invention provides polypeptides including MCP1 fused, optionally, by a linker, to an immunoglobulin. Methods for using the polypeptides to treat medical disorders are also covered.

Abstract: A method of increasing hematopoietic stem cell production is disclosed. The method includes administering a TPO mimetic compound to a subject. Pharmaceutical compositions including a TPO mimetic compound and a pharmaceutically acceptable carrier are also disclosed.

Abstract: Methods and compositions for treating obesity and related disorders. The methods include the use of BMP-2, -4, -6 and -7.