Abstract: The present invention relates to interleukin-4 receptor binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 receptor binding protein moiety joined to a pro-apoptotic Bcl-2 family member protein moiety.

Abstract: The invention provides fusion proteins comprising antigens of infectious disease agents and cancer cells linked to multiple-trimer forms of TNF SuperFamily (TNFSF) ligands. The TNFSFs serve as vaccine adjuvants for increasing the immune response to the antigens. In particular, a fusion polypeptide strand that self-assembles inside cells into a multiple-trimer form of CD40 ligand (CD40L, TNFSF5) is provided. Other similar fusion proteins are also disclosed. The fusion proteins can be delivered to a host as isolated proteins, as nucleic acids used directly in DNA vaccination or carried and expressed by a viral vector such as adenovirus. In addition to use as a vaccine to prevent or ameliorate disease caused by an infectious agent, compositions of the invention may be used for the treatment of ongoing infection or for cancer immunotherapy.

Abstract: The present invention relates to peptides, in particular dodecapeptide-containing coating agents, adhesion promoters or adhesives for oxidic surfaces, a multilayer composite or a coated substrate, containing compounds which are formed entirely or in part of dodecapeptides as adhesion promoters between at least two adjacent layers of the composite or between the coating and the substrate, and to dodecapeptides that can be used as coating agents, adhesion promoters or adhesives for oxidic surfaces.

Abstract: A method of inducing mitochondrial biogenesis in a mammal is provided. The method comprises the step of administering to the mammal an interleukin-15 or nucleic acid encoding an interleukin-15 to the mammal.

Abstract: Described herein are compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a subject, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the composition and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

Abstract: In one embodiment, the invention provides a method of inhibiting cAMP efflux and increasing intracellular cAMP in a subject who suffers from, or who is at risk of developing, a cancer by administering to the subject a therapeutically-effective amount of a cAMP efflux inhibitor. Novel compounds, pharmaceutical compositions, diagnostics and screening methods are also provided.

Abstract: Disclosed are methods of treating a chemotherapy-resistant cancer, of treating a cholangiocarcinoma, of treating a metastatic carcinoma, and of treating a transition cell urothelial carcinoma by administering a therapeutically effective amount of an endothelin B (ETB) receptor agonist and a chemotherapeutic agent to a subject afflicted with such a cancer.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Provided are polypeptides comprising a variant IgG Fc domain, wherein the polypeptides exhibit reduced or ablated effector functions (e.g., ADCC and/or CDC) and increased stability and plasma half-life compared to a parent polypeptide. Also provided are compositions, methods of treatment, and methods to diminish Fc-induced effector function in a parent polypeptide.

Abstract: A novel combination comprising a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl; -2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and a PD-1 antagonist; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or immune modulation through PD-1 is beneficial, e.g., cancer.

Abstract: Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided, More particularly, the present disclosure relates to optimized dosing parameters to achieve and maintain efficacy in the treatment and/or prevention of metabolic diseases, disorders and conditions in a subject, while minimizing the adverse effects associated therewith. Particular embodiments are directed to the treatment and/or prevention of abnormally high levels of cholesterol and/or manifestation(s) of hypercholesterolemia in as subject.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: The present invention provides suppressive and/or regulative human CD4+CD25+ T cells, a method for expanding same, and the use of the suppressive and/or regulative human CD4+CD25+ T cells and the expanded T cells as regulatory agent.

Abstract: Provided herein are compounds and related composition and methods that may be used to raise an antibody response to nicotinic compounds, in some embodiments.

Abstract: Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.

Abstract: The present invention provides a fusion polypeptide which can bind to a cell surface binding moiety (e.g., a carbohydrate) and serve as a ligand for a cell surface polypeptide, as well as a vector comprising a nucleic acid encoding for such a fusion polypeptide, and a host cell comprising such nucleic acid. The present invention also provides a composition comprising an antigen bearing target and such a fusion polypeptide, as well as a composition comprising a virus or a cell and such a fusion polypeptide. The present invention further relates to a method of modulating an immune response in an animal using such compositions.

Abstract: The present invention relates to the use of secreted proteins from mesenchymal stem cells and other cells for the treatment of myocardial infarction. In particular, the invention provides compositions and methods based on secreted proteins from mesenchymal stem cells and the genes encoding them.

Abstract: Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent diseases, disorders or conditions, or to improve a subject's heath or wellbeing.

Abstract: Novel self-assembling peptide complexes comprising a charged peptide and a polysaccharide, methods of producing them and uses therefore are described. The novel self-assembling peptide complexes have particular utility in the restoration of biomechanical or biochemical function of a variety of biological tissues, for example and without limitation, in degenerated spinal discs, osteoarthritic joints, damaged cartilage, meniscus, ligaments, tendons, dental, ophthalmic and cardiovascular and blood vessel tissues. Methods of repairing and or restoring biomechanical or biochemical function of biological tissues and scaffolds for the support of cell growth are also described.

Abstract: The present invention is directed to compounds, compositions and methods for treating or preventing hepatitis C virus (HCV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.

Abstract: Certain embodiments are directed to recombinant vesiculovirus encoding a heterologous polynucleotide and methods of using the same.

Abstract: The present application relates to treatment of cutaneous wounds using IL-12. The methods of the invention result in improved wound closure. The methods comprise treating cutaneous wounds using topical, subcutaneous, and/or intramuscular administration of IL-12.

Abstract: Methods of optimizing mRNA sequences for expression in host cells are provided. Methods of determining the stability of a protein are also provided. Methods of determining the affinity of a ligand for a protein are also provided.

Abstract: The present invention relates to anti-IL-1 beta antibodies and in particular to monovalent high potency IL-1 beta-binding antibody fragments being highly stable. Such antibodies can be used in the treatment of inflammatory and other diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.

Abstract: The peptide of the present invention performs a function, which is the same as or similar to that of natural interleukin (IL)-3, and has superior skin permeability due to the small size thereof. In addition, the peptide of the present invention suppresses the activation of NF-?B and nuclear transition by inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK signaling pathway, and suppresses the expression of a RANKL or an inflammatory cytokine-induced tartrate-resistant acid phosphatase (TRAP), cathepsin K, or TNF receptor type 1 or type 2, thereby inhibiting osteoclast differentiation depending on the treatment concentration. Moreover, the peptide of the present invention can contribute to osteoblast differentiation by promoting the expression of osteoblast differentiation markers such as osteocalcin (CON), osteoprotegerin (OPG), bone sialoprotein (BSP), or osteopontin (OPN).

Abstract: Described herein is the finding that activators of CXCR3, such as proteins that bind CXCR3 (e.g., IP-9, IP-10 and PF4), enhance the density of goblet cells in the eye. Goblet cells in the conjunctiva are the primary source of tear mucus. Accordingly, the present disclosure describes methods of treating dry eye syndrome by administering an activator of CXCR3. Also described are methods of increasing goblet cells density, such as goblet cell density in the conjunctiva.

Abstract: This disclosure relates to compositions for use in treatment of a retinal degenerative disease, such as age related macular degeneration. The described compositions include agents for activating p38 and/or JNK signaling through the activation of TAK1 in the retinal pigment epithelium of a subject diagnosed with the disease. Methods of treatment of a retinal degenerative disease using the described compositions are also provided.

Abstract: The present invention relates to cell specific therapeutic modality by using a region of the PLAP Promoter. The invention further relates to specific expression of therapeutically PLAP useful sequences for specific transcriptional activation of this gene. The invention also relates to the PLAP region which may be used alone or in combination with other regions like enhancer sequences that augment cell or tumour specific gene expression.

Abstract: Provided herein are methods for the treatment of metastatic pancreatic cancer comprising administration of a composition comprising nanoparticles comprising a taxane (such as paclitaxel) and a carrier protein in combination with gemcitabine.

Abstract: The present invention relates to methods of treating cancer with a combination of extended-PK IL-2 and one or more therapeutic agents, such as a therapeutic antibody. The methods of the invention are applicable across any type of cancer.

Abstract: This disclosure relates to methods of treatment using compound (1) or analogs thereof, and pharmaceutically acceptable salts thereof. Also disclosed are compounds of formula (10): as defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the same. Methods of treatment, such as for cancer, are provided that comprise administering the compounds and their salts to a subject in need of such treatment.

Abstract: The invention provides a dual VEGF/PDGF antagonist comprising a VEGF antagonist linked to a PDGF antagonist. The VEGF antagonist is an antibody to a VEGF or VEGFR or is a VEGFR extracellular trap segment (i.e., a segment from the extracellular region of one or more VEGFR receptors that inhibits binding of at least one VEGFR to at least one VEGF). The PDGF antagonist is an antibody to a PDGF or PDGFR or is a PDGFR extracellular trap segment (i.e., segment from the extracellular region of one or more PDGFRs, which inhibits binding of at least one PDGFR and at least one PDGF). The dual antagonist is preferably conjugated to a half-life extending moiety, such as a HEMA-PC polymer. The dual antagonist is particularly useful for treating wet aged related macular degeneration.

Abstract: This invention relates to the contributions of the bone marrow—and adipose tissue—derived mesenchymal stem cells applied following the maxillary expansion—a frequently used method for the orthodontic treatment—to the healing of the expanded bone tissues. In the invention, adipose tissue and bone marrow-derived stem cell applications increased the healing and quality of the bones following the maxillary expansion and the applied stem cells were involved in the bone structure. Thus, the relapse following the maxillary expansion treatment was avoided. This application will shorten the treatment period for patients undergoing the maxillary expansion treatment and the patients will not have to use apparatus for a long period of time.

Abstract: The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and the CDK inhibitor dincaciclib, and the use of the combination therapies for the treatment of cancer, and in particular for treating cancers that express PD-L1.

Abstract: OX40 is a potent immune stimulating target. Provided herein are methods for the treatment of cancer patients using (3X40 agonists methods to predict clinical outcome of the treatment by correlation of the treatment and an increase in OX40-induced T cell proliferation.

Abstract: The invention discloses isolated endotoxemia marker polynucleotides selected from any one of 163 different polynucleotide sequences, or variants thereof. Endotoxemia related conditions are diagnosed in a test subject by aberrant expression of at least one of the endotoxemia markers or variants thereof. Of practical use, is the early diagnosis of disease, determining those animals at risk of developing endotoxemia, monitoring of an animals immune response to the disease and the enablement of better treatments. Of particular interest is the diagnosis of laminitis in hoofed animals, including horses.

Abstract: Deuterated diaminopyrimidine compounds and pharmaceutical compositions containing such compounds are described. In particular, disclosed are deuterated diaminopyrimidine compounds of formula (I), and pharmaceutical compositions containing such compounds or crystal forms, pharmaceutically acceptable salt, hydrates or solvates thereof. The disclosed deuterated diaminopyrimidine compounds can be used for treating and/or preventing protein kinase-associated diseases, such as cell proliferative disease, cancer, immune disease and the like.

Abstract: Compound represented by formula 1: or a pharmaceutically acceptable salt, a hydrate, a crystalline form, or a stereoisomer thereof, wherein: R1 is hydrogen, tert-butoxycarbonyl, where R11 is an optionally substituted C1-C6 alkyl, an optionally substituted C3-C6 cycloalkyl, or an optionally substituted C1-C6 alkyloxy, and arrows (?) indicate the position of substituents attachment; R2 is hydrogen, halogen, or C1-C4alkyl; R3 is an optionally substituted aryl, an optionally substituted aryloxy, an optionally substituted arylsulfanyl, an optionally substituted arylamino, or an optionally substituted nitrogen hetaryl; where R41 is an optionally substituted C1-C6 alkyl, an optionally substituted C3-C6 cycloalkyl, or an optionally substituted C1-C6 alkyloxy; X is buta-1,3-diynylene or 1,4-phenylene; arrows (?) indicate the position of substituents attachment.

Abstract: Provided are nanoparticles comprising heparin, chitosan, and at least one immunomodulatory agent, e.g. a cytokine. The cytokine can be selected from the group consisting of TNF, IL-12, IL-2, IL-23, IL-1?, IL-10, IL-18, and combinations thereof. Further provided are methods of making a nanoparticle comprising mixing a first composition comprising heparin with a second composition comprising chitosan in the presence of at least one cytokine to form a third composition. Further provided are methods of modulating an immune response comprising co-administering to a subject an antigen or vaccine with nanoparticles comprising heparin, chitosan, and at least one cytokine.

Abstract: The present invention relates to a method for treating a GD2 positive cancer by administering a preparation comprising an anti-GD2 antibody to a patient as a continuous intravenous infusion over 24 hours per day.

Abstract: Described herein are immunosuppressive molecules including immunosuppressive variants of IL-2, and use of such molecules to treat inflammatory and autoimmune disorders.

Abstract: The present invention relates to Bispecific antibodies against human TWEAK and human IL17 (bispecific TWEAK-IL17 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder—Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.

Abstract: This invention provides compositions and methods to treat a condition or disease without the use of exogenous targeting sequences or chemical compositions. The present invention relates to single-domain antibodies (sdAbs), proteins and polypeptides comprising the sdAbs that are directed against intracellular components that cause a condition or disease. The invention also includes nucleic acids encoding the sdAbs, proteins and polypeptides, and compositions comprising the sdAbs. The invention includes the use of the compositions, sdAbs, and nucleic acids encoding the sdAbs for prophylactic, therapeutic or diagnostic purposes.

Abstract: The current application teaches methods and compositions useful for the treatment of cancer through administration of an antioxidant together with an immune stimulator at concentrations sufficient to augment antitumor immunity while simultaneously preventing inhibition of T cell function as a result of tumor secreted oxidative stress. Compositions such as toll like receptor agonists in combination with antioxidants are disclosed. In further embodiments, the application teaches the use of antioxidants to prevent immunotherapy associated oxidative stress, of which, one manifestation is vascular leak syndrome. In one specific embodiment, the application teaches the use of intravenous ascorbic acid as a means of reducing IL-2 associated toxicity.

Abstract: The present invention relates in essence to use of a compound, which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by a therapy which comprises re-directing of T-cells against target cells in a patient. Such a therapy includes, but is not limited to, treatment with an antibody comprising a CD3 binding domain, such as a CD20×CD3 or a CD19×CD3 bispecific single chain antibody, e.g., blinatumomab (MT-103). Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated, as are methods of identifying a compound for administration in the methods of prophylaxis, amelioration and/or treatment.

Abstract: A composition comprising a synthetic growth factor analog comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor and an osteoconductive material where the synthetic growth factor analog is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.