Abstract: Described are novel variants of APRIL that modulate signaling via receptor-specific agonist activity, and nucleic acids encoding these variant proteins. Further described is the use of these novel proteins in the treatment of APRIL-associated disorders, in particular, pathologies of the immune system and oncological disorders.

Abstract: Methods for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of cerebral hemorrhage and subarachnoid hemorrhage. Therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). An effective amount of DFO may be administered to the upper third of the nasal cavity of a patient at risk for, or diagnosed with, cerebral hemorrhage and subarachnoid hemorrhage. The effective amount of DFO is delivered directly to the patient's central nervous system for preconditioning, preventing and/or treating the cerebral hemorrhage and subarachnoid hemorrhage.

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: This invention relates to compositions and methods for immunotherapy of cancer. Specifically, a method of cancer immunotherapy is described which results in the systemic liquidation of both solid and metastatic tumors whereever they reside in the body. The compositions include activated allogeneic Th1 cells that when administered appropriately lead to liquidation of tumors. The method includes administering priming doses of the therapeutic composition, ablation of a selected tumor lesion along with intratumoral injection of the composition and then infusion of the therapeutic composition. These steps enable the systemic liquidation of tumors secondary to immune cell infiltration and leads to immune-mediated tumor eradication.

Abstract: Provided herein are methods and compositions for modulating energy metabolism and weight in mammals, in particular by modulating thermogenesis associated with brown fat, including thermogenesis by brown fat or brown fat cells, adaptive thermogenesis by brown fat or brown fat cells, thermogenic capacity of brown fat or brown fat cells, or a combination thereof. More specifically, methods and compositions provided herein for treating or preventing obesity, or methods and compositions for identifying compounds effective for treating or preventing obesity are taught in connection with ligands such as B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), their receptors, and molecules that modulate the interactions between the ligands and receptors.

Abstract: The methods and compositions disclosed herein are effective in the promoting the reattachment of delaminated cartilage to bone. The methods (and related compositions) comprise the removal of the acellular layer of the delaminated cartilage thereby exposing the underlying chondrocyte cells thereby allowing the promotion of the reattachment of the delaminated cartilage.

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 invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.

Abstract: The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

Abstract: The present invention provides micelles having a polynucleotide encapsulated therein, the micelle comprising copolymers comprising hydrophobic moieties in a cationic complexing block. The invention further provides methods of preparing and using said micelles, and compositions thereof.

Abstract: A method of promoting wound healing or connective tissue reconstruction and a method of treating ischemia in a subject in need thereof are disclosed. The methods comprising topically administering to the subject about 10-30 mg per cm2 wound tissue of Erythropoietin and about 100-300 mg per cm2 wound tissue of Fibronectin, thereby promoting wound healing or connective tissue reconstruction or treating ischemia in the subject. Unit dosage forms, pharmaceutical compositions, cosmetic compositions and formulations comprising Erythropoietin and/or Fibronectin are also disclosed.

Abstract: The present invention relates to a composition and methods of treatment for inflammation comprising of adult stem cells and inflammatory cytokines. The invention further relates to the treatment of inflammation associated with autoimmune disorders, allergies, sepsis, cancer as well as to preventing, reducing or treating transplant rejection and/or graft-versus-host disease (GvHD).

Abstract: Disclosed is the use of Volasertib or a salt or a hydrate thereof for treating patients suffering from acute myeloid leukemia (AML) comprising administering a high dose of Volasertib in combination with fludarabine, cytarabine and Granulocyte colony-stimulating factor (GCSF) or in combination with fludarabine, cytarabine, GCSF and a daunorubicin citrate liposome injection.

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: Compounds having the formula (I) wherein R1, R2, R3 and X are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

Abstract: The present invention relates to compositions and methods relating to an interleukin18-inducible cytokine termed tumor necrosis factor-alpha inducing factor (TAIF) or interleukin-32 (IL-32). In particular, the present invention provides compositions and methods for treating autoimmune diseases and cancer, in part by regulation of tumor necrosis factor-alpha expression.

Abstract: Provided herein are chimeric nucleic acid sequences encoding chimeric polypeptides. Also provided herein are chimeric polypeptides. Further provided herein are methods of treating a subject with or at risk of developing a cancer. The methods comprise selecting a subject with or at risk of developing a cancer, and administering to the subject an effective amount of the chimeric polypeptides provided herein.

Abstract: Humanized antibodies are provided that specifically bind HLA-DR. The antibodies recognize the epitope recognized by the murine monoclonal antibody L243. Processes for preparing such antibodies, pharmaceutical compositions containing such antibodies, and clinical therapeutic and diagnostic, as well as research-related uses for such antibodies, are provided.

Abstract: The pharmaceutically acceptable salts of bicycle-substituted pyrazolon azo derivatives represented by the general formula (I), their preparation methods, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor. The definitions of substituents in the general formula (I) are the same as the description.

Abstract: A synthetic, flexible tissue matrix and methods for repairing hyaline cartilage defects in a joint using the flexible tissue matrix are described. The flexible tissue matrix includes a high molecular weight polycaprolactone polymer entangled with a polysaccharide such as hyaluronic acid. In the methods, autologous bone mesenchymal stem cells are introduced to a joint by a microfracturing technique, and a membrane made of the flexible matrix is applied to the joint. Cartilage which forms in the joint is hyaline cartilage rather than fibrocartilage.

Abstract: Biomaterial systems, e.g., gel scaffolds, are used in vivo to recruit immune cells and promote their activation towards a non-inflammatory phenotype, thereby leading suppression of inflammation. The compositions and methods are useful to reduce the severity of autoimmunity, chronic inflammation, allergy, and periodontal disease.

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 relates to injecting a high specificity cytokine antagonist into a diseased intervertebral disc.

Abstract: A method of regulating the immune system of a subject that involves removing antigen presenting cells from subject and loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject.

Abstract: The present invention describes oxidized avidin, suitable for inhalation, for conditioning the lung affected by inoperable/diffuse diseases, enabling the targeted delivery of biotinylated therapeutic agents to it.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpaha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

Abstract: The invention provides small molecule mimics of the Smac peptide that are dimer-like or trimer-like compounds having two or three amide-containing domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders.

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: This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

Abstract: Provided herein are methods of inducing tolerance or reducing an immune response to a foreign antigen in a human subject. The methods include administering anti-CD4 antibodies or CD4-binding fragments thereof or CD4-binding molecules, and the foreign antigen to the human subject.

Abstract: The invention provides polymer compositions for cell and drug delivery.

Abstract: System and methods for isolation of collagen and other fibrous tissue from adipose tissue are described herein. The method of the present invention isolates the collagen from adipose tissue by sonication. The tissue to be sonicated is placed in a container or a flow cell transparent to ultrasound waves. After sonication the sonicated material is filtered out through the bottom of the flow cell and the sonicated collagen is trapped in the filter, which may be taken for further processing. The isolated collagen can then be combined with a suitable carrier for re-injection to correct various tissue defects such as wrinkles, to form a carrier for the stem cells, a filler, and matrix for new collagen production by injecting into the desired area of the host.

Abstract: Androgen receptor-based vaccines for eliciting an immune reaction in vivo against cells expressing androgen receptor are disclosed. The vaccines are useful in the treatment of prostate cancer. Also disclosed are methods for inducing immune reaction to androgen receptor or treating prostate cancer in a mammal, using the vaccines and pharmaceutical compositions comprising the vaccines.

Abstract: The present invention includes compositions, methods of making and using the compositions for modulating the immune response in a subject by providing a vaccine composition having a pollen/spore disposed in a pharmaceutical carrier for delivery to a subject, wherein the pollen/spore comprises multiple pores that connect an outer surface of the pollen/spore to an inner cavity and one or more antigens disposed on the outer surface, in the inner cavity, in the multiple pores, or a combination thereof, wherein the one or more antigens modulate an immune responses in the subject.

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: A flowable biomedical implant for application to a bone defect to promote bone growth is provided. The flowable biomedical implant comprises a carrier matrix including a biodegradable polysaccharide and ceramic material. An impermeable membrane can be integrally formed at the surface of the carrier matrix by applying a crosslinking agent to the biodegradable polysaccharide mixed with ceramic materials.

Abstract: The present invention relates to topical ophthalmic compositions for treating or preventing epithelial lesions or ophthalmic disorders, including dry eye or keratoconjunctivitis sicca.

Abstract: A medical device that is at least partially formed of a novel metal alloy, which novel metal alloy improves the physical properties of the medical device.

Abstract: This invention relates to stable aminosterol phosphate compositions. The aminosterol phosphate compositions permit administration without associated tissue damage and achieve a sustained release effect.

Abstract: Provided are electrokinetically-altered aqueous fluids (e.g., gas-enriched electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide modulation of at least one of cellular membrane potential and cellular membrane conductivity, and therapeutic compositions and methods for use in treating an irritation, infection or inflammatory eye condition, comprising administering to, by contacting the eye of a subject in need thereof a therapeutically effective amount of an electrokinetically-altered aqueous fluid. The electrokinetically-altered fluids or therapeutic compositions and methods include electrokinetically-altered ioinic aqueous fluids optionally in combination with other therapeutic agents. Other embodiments include particular routes of administration or formulations for the electrokinetically-altered fluids (e.g.

Abstract: The present invention provides a recombinant fusion protein which stimulates the rejuvenation and reactivation of skin and epidermal cells for improving skin appearance, smoothing wrinkles and freckles, and whitening skin. Particularly, the present invention provides various types of products for improving skin, which contain recombinant fusion protein of human serum albumin (HSA) with cytokine peptides (EGF, FGF, KGF, HGH, HGF, PDGF, GCSF, interferon, IL-11 or IGF) by genetic engineering technology. The fusion protein can be used independently or in a combination or combination with yeast fermentation products, or with varied emulsifiers, thickeners, moisturizer, preservatives, yeasts and ferments.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Abstract: Systems and methods for inhibiting bone loss using FoxP3+ CD8 T-cells (TcREG). Osteoclasts are induced to produce FoxP3+ CD8 T-cells (TcREG) either in vivo or ex vivo. The FoxP3+ CD8 T-cells (TcREG) are provided to the patient to subsequently regulate osteoclast function, thereby establishing a bi-directional regulatory loop between osteoclasts and FoxP3+ CD8 T-cells(TcREG).

Abstract: Compositions and methods for diagnosing and treating tumors using myeloid derived suppressor cells (MDSCs) are provided. More particularly, the compositions contain labeled MDSCs or MDSCs in combination with oncolytic viruses, nano-particles or other anti-tumor agents.

Abstract: The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

Abstract: A method of inducing or promoting hair growth on the scalp of a subject, comprising the steps of (i) providing an ECM composition including at least one ECM material, (ii) administering inciting event means to a target location on the scalp of the subject to induce an inciting event at the target scalp location, and (iii) administering a therapeutically effective amount of said ECM composition to the target scalp location. In some embodiments, the ECM composition includes at least one additional biologically active agent.

Abstract: The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

Abstract: Disclosed herein are immunoglobulin constructs comprising at least one immunoglobulin domain or fragment thereof; and a therapeutic polypeptide or derivative or variant thereof attached to or inserted into said immunoglobulin domain. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a knob domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said knob domain of the CDR3H. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a stalk domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said stalk domain of the CDR3H. Also described herein are methods and compositions comprising the immunoglobulin constructs described herein for treatment and prevention of a disease or condition in a subject.

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.