Abstract: The present invention pertains to novel analgesics useful for treating mechanical pain. The invention suggests the use of inhibitors of ?-tubulin acetylation for inhibition of neurological sensations that are mediated by sensory neurons. The perception of mechanical pain is can be modulated by altering the ?-tubulin acetylation, in context of the invention in particular by modulation of the expression and/or activity of the enzyme ?-tubulin acetyltransferase (Atat). The invention provides the medical application of ?-tubulin acetyltransferase inhibitors as analgesics and a screening method for the identification of compounds useful in the treatment of pain.

Abstract: The present invention relates to methods for the in vitro diagnosis of esophageal cancer, and to compositions and methods for the prevention or the treatment of esophageal cancer. Disclosed are said compositions that include an antibody binding to progastrin and disclosed are methods that include the use of an antibody binding to progastrin.

Abstract: It has been discovered that disrupting the stromal capsule restores a better vasculature/tumor perfusion and improve T cells infiltration inside the core of a melanoma. The invention relates to the use of drugs or immunoconjugates that target the transmembrane protease ADAM12 and deplete the cells that express it. Since ADAM12 protein is specifically expressed by stromal cells of the tumor stromal capsule and around vessels in models for prostate cancer, neuroendocrine pancreatic cancer and melanoma, an ADAM12 inhibitor is useful in anti-tumor therapies as an adjuvant. The invention encompasses methods, compositions, and kits containing ADAM12 inhibitors for use in the depletion of ADAM12+ stromal cells in cancer patient, particularly together with anti-tumor compounds and treatments.

Abstract: Aspects of the disclosure relate to improved methods for predicting whether a prostate tissue biopsy obtained from a subject will contain detectable prostate cancer.

Abstract: The present invention relates to methods for the in vitro diagnosis of ovarian cancer, and to compositions and methods for the prevention or the treatment of ovarian cancer. Disclosed are compositions that include an antibody binding to progastrin and disclosed are methods that include the use of an antibody binding to progastrin.

Abstract: The present disclosure relates to compositions and methods that enable the formation of pharmaceutically relevant particles that can be used for therapy. In particular, the methods disclosed herein allow the controlled formation of circular particles having low internal void spaces comprising bioactive therapeutic agents.

Abstract: Methods are disclosed for the mobilization of marrow infiltrating cells (MILs) using E-selectin antagonists for the treatment of disorders such as cancer. Methods for treating or preventing cancers using MILs mobilized by E-selectin antagonists are further disclosed.

Abstract: This invention relates to compositions of chimeric and humanized antibodies that bind to the human CTLA4 molecule and their use in cancer immunotherapy and for reduction of autoimmune side effects compared to other immunotherapeutic agents.

Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to treat fibrotic disorders.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. The antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of the antibodies in medicine are also described.

Abstract: The invention provides methods of treating an allergic inflammatory condition characterized by inflammation of the squamous epithelium of a target tissue by administering to the subject a pharmaceutical composition comprising a kallikrein 5 (KLK5) inhibitor, and a pharmaceutically acceptable carrier.

Abstract: Provided are methods and compositions for treatment of angiogenic disorders using anti-VEGF agents. The anti-VEGF agents comprise VEGF binding domains and have the ability to bind vitreous. Provided are exemplary embodiments of Fc-IgG fusion proteins with VEGF binding domains with strong heparin-binding characteristics, strong inhibition of VEGF mitogenic activity, and improved pharmacokinetics, namely longer half-lives of the anti-VEGF agents and consequently less frequent dosing.

Abstract: Disclosed herein are anti-IgE antibodies having low binding affinity to human IgE and compositions and methods thereof. In some embodiments, the present invention provides a composition comprising one or more humanized low affinity anti-IgE antibodies (hLAAIGEs) and a pharmaceutically acceptable carrier. In some embodiments, the present invention provides a method of treating a subject for an IgE-mediated disorder, which comprises administering to the subject one or more hLAAIGEs or a composition thereof. In some embodiments, the IgE-mediated disorder is an allergic reaction.

Abstract: The present disclosure provides compositions and methods for treating a disease or condition in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a composition comprising a plurality of particles comprising at least one therapeutic biologic suspended in a pharmaceutically acceptable liquid carrier.

Abstract: The present invention relates to methods and kits or articles of manufacture related thereto that may find use, inter alia, in assessing responsiveness of cancers to MUC16 antagonists by monitoring HE4 expression. In some embodiments, the methods include measuring the level of expression of HE4 in a sample from a subject; comparing the level of expression of HE4 in the sample with the level of expression of HE4 in a sample previously obtained from the subject; and, optionally, administering to the subject a therapeutically effective amount of a MUC16 antagonist.

Abstract: Specific binder-drug conjugates (ADCs) of kinesin spindle protein inhibitors, effective metabolites of these ADCs, processes for preparing these ADCs, the use of these ADCs for the treatment and/or prevention of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases, are described.

Abstract: Methods are provided for determining prognosis of multiple myeloma in a patient by measuring expression of BCMA in a sample. Also provided are methods for treating multiple myeloma by measuring expression of BCMA in a sample and administering an effective amount of an antigen binding protein that binds BCMA. Also provided are kits for measuring BCMA expression in a sample.

Abstract: The invention provides antibodies against Fibroblast Activation Protein (FAP) and methods of using the same.

Abstract: Provided herein are monoclonal antibodies (e.g., human antibodies) binding to human Growth Differentiation Factor 15 protein (hereinafter, sometimes referred to as “GDF15”), and pharmaceutical compositions and methods of treatment comprising the same.

Abstract: Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

Abstract: Embodiments of the invention provide shaped masses comprising one or more drugs such as proteins or polypeptides and methods for forming such shaped masses. One embodiment provides a shaped mass comprising a drug such as a protein or polypeptide having a biological activity in the body of a mammal. The shaped mass is formed by compression of a precursor material comprising the drug wherein an amount of biologically active drug in the mass is a preserved above a minimum level. Drugs which may be incorporated into the shaped mass may include one or more glucose regulating proteins such as insulin, incretins; and immunoglobulins such as TNF-inhibiting antibodies or interleukin neutralizing antibodies. Embodiments of the shaped mass may be incorporated into a tissue penetrating member which is inserted into the intestinal wall allowing for the oral delivery of proteins and peptides which would otherwise be degraded in the intestinal tract.

Abstract: Provided are anti-epidermal growth factor receptor (EGFR) antibodies, aglycosylated CDR-H2 anti-EGFR antibodies, and antigen binding fragments thereof. Also provided are isolated nucleic acid molecules that encode the anti-EGFR antibodies or antigen binding fragments thereof, related expression vectors, and host cells. Provided are methods of making anti-epidermal growth factor receptor (EGFR) antibodies, aglycosylated CDR-H2 anti-EGFR antibodies, and antigen binding fragments thereof. Also provided are related pharmaceutical compositions and methods of their use to treat subjects.

Abstract: Methods of prohibiting Xist-dependent silencing of X chromosome genes include targeting the required Xist silencing complex components including SHARP, SMRT, HDAC3, SAF-A, LBR, and the respective binding sites of SHARP, LBR, and SAF-A on Xist, thereby prohibiting Xist repression, allowing for reactivation of the silenced X chromosome genes.

Abstract: The present invention relates generally to a method of prognosing the survival of a patient with a breast neoplasm, more particularly a patient with a breast neoplasm which is estrogen receptor-/progesterone receptor-/HER-2-(“triple-negative”). The method of the present invention more particularly provides a method for prognosing breast cancer patient survival, in particular risk of metastatic spread, by screening for IRF9 expression. In a related aspect, the present invention provides a method of therapeutically or prophylactically treating patients with a triple-negative breast neoplasm, in particular those patients with triple-negative breast neoplasia which is characterised by a poor survival prognosis, still more particularly a high risk of metastatic spread, by upregulating type I IFN levels.

Abstract: The present invention concerns markers of multiple sclerosis, their use, and treatment with IL-17 antagonists, including IL-17 antibodies, of subjects with increased levels of such markers.

Abstract: The present disclosure provides methods of treating diuretic resistance by administering an IL-6 antagonist to patients who require diuresis. In typical embodiments, the patient has heart failure. Optionally, the patient has elevated urine levels of IL-6, plasma levels of IL-6, or both urine and plasma levels of IL-6.

Abstract: Described here are methods and compositions for treating tumors and metastases that improve anti-angiogenesis therapy. By inhibiting these mechanisms in a biological system with an anti-beta one integrin composition in combination with an antiangiogenic composition, tumors and metastases may be deprived of an adequate blood supply, thereby resulting in tumor cell growth arrest and possibly regression, including tumor cell death. The present compositions comprise an anti-beta one integrin agent in combination with an anti-VEGF agent, in a pharmaceutical composition or compositions. Methods of treatment and of imaging are also described.

Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the apolipoprotein C3 (APOC3) gene, and methods of using such RNAi agents to inhibit expression of APOC3 and methods of treating subjects having an APOC3 associated disorder, e.g., hypertriglyceridemia.

Abstract: A method is provided for reversibly modifying a protein or peptide on its glutamine residue(s) by performing a reaction, such as a transglutaminase-catalyzed reaction, between the protein or peptide and an amine-containing reagent, whereby the reagent is linked through its amine function to a side chain of the glutamine residue. Subjecting the modified protein to an appropriate stimulus regenerates the protein or peptide in its original form.

Abstract: Methods of treating ischemic tissue injury or kidney disease, e.g., delayed graft function, that include administering a Nicotinamide adenine dinucleotide (NAD)/niacinamide (NAM) pathway agonist.

Abstract: This disclosure relates to a chimeric antigen receptor for binding with a tumor specific target antigen. The chimeric antigen receptor comprises at least one antigen specific targeting region evolved from a parent protein or a fragment thereof and having a decrease in activity in the assay at the normal physiological condition compared to the activity in the assay under the aberrant condition. A method for producing the chimeric antigen receptor is also provided.

Abstract: The instant disclosure provides antibodies that specifically bind to CD137 (e.g., human CD137) and increases CD137 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: The present invention provides a method for evaluating the risk of occurrence of cancer in an individual.

Abstract: In alternative embodiments, provided are compositions, including e.g., isolated, synthetic or recombinant peptides or polypeptides, for: expanding regulatory T cells (Treg) populations; or, for treating, ameliorating, preventing or reversing a vascular inflammation, and Kawasaki disease (KD) or a pediatric acute vasculitis of the coronary arteries, including vascular coronary abnormalities and the same or similar types of acute or chronic vascular inflammatory abnormalities, and methods for making and using them.

Abstract: The technology described herein is directed to methods and compositions for the treatment of hypertension, e.g. pulmonary arterial hypertension, relating to inhibition of TGF?1, TGF?3, and/or GDF-15.

Abstract: The present invention provides a method for generating bispecific shark variable antibody domains (vNAR domains) and uses thereof. The present invention further provides fusion proteins comprising the inventive bispecific vNAR domains as well as polynucleotide libraries for use in the generation of the inventive bi-specific vNARs. Furthermore, the invention provides pharmaceutical compositions comprising the inventive bispecific vNARs or fusion proteins comprising bi-specific vNAR domains for use in the treatment of pathological conditions in an individual. The invention also provides kits of parts comprising the bispecific vNAR domains or fusion proteins.

Abstract: Methods of treating proliferative disorders are described. In particular, combination treatment with a GITR agonist and a PD-1 antagonist are provided.

Abstract: The present invention relates to an IL-1? binding antibody or a functional fragment thereof for use in preventing or reducing risk of experiencing a recurrent cardiovascular (CV) event or a cerebrovascular event in a patient that has suffered of a qualifying CV event.

Abstract: Lipid conjugates for enhanced delivery of cargo to the lymph nodes are disclosed. The lipid conjugates typically include three domains: a lipophilic domain that binds to albumin, a polar block domain, and a cargo such as a molecular adjuvant or immunostimulatory compound (such as an oligonucleotide) or antigenic peptide. Depending on the cargo, the length and compositions of the polar block can be tailored to push the equilibrium toward albumin binding, stable micelle formation, or cell insertion. The conjugates can be administered to a subject, for example, a subject with cancer or an infection, to induce or enhance a robust immune response in the subject.

Abstract: An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

Abstract: The invention relates to the use of adenosine monophosphate deaminase 2 (AMPD2) inhibitors alone or in combination with various agents to treat a wide variety of diseases including, but not limited to, sugar craving, salt craving, umami craving, and addictions including drug, tobacco, nicotine and alcohol addictions. Embodiments of the invention may also relate to stimulation of AMPD2 activity to treat anorexia nervosa or stimulate food intake in a subject.

Abstract: NK cells and NK cell lines are modified to increase cytotoxicity, wherein the cells and compositions thereof have a use in the treatment of cancer. Production of modified NK cells and NK cell lines is via genetic modification to add mutant (variant) TRAIL ligand expression.

Abstract: A method of treating a hemolytic disorder in a subject in need thereof includes administering to the subject a therapeutically effective amount of an antibody that binds to a component of alternative pathway C3 convertase and selectively inhibits C3a, C5a, C3b, C5b, and C5b-9 produced exclusively by the alternative pathway, without inhibiting any of the classical pathway's ability to produce C3a, C5a, C3b, C5b, and C5b-9.

Abstract: The present invention relates to a monoclonal antibody platform designed to be coupled to therapeutic peptides to increase the half-life of the therapeutic peptide in a subject. The invention also relates to pharmaceutical compositions and methods for use thereof.

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: The invention relates to compounds derived from the EGF(A) domain of LDL-R, in particular compounds comprising a peptide analogue of the wild-type EGF(A) (LDL-R(293-332)) sequence and at least one substituent comprising at least one fatty acid group. The invention also relates to a pharmaceutical composition thereof and use a medicament. The novel EGF(A) compounds of the invention are useful as treatment e.g. in the field of cholesterol lowering, dyslipidaemia and cardiovascular disease.

Abstract: The present invention provides methods for treating inflammatory diseases, or conditions associated with, or resulting in part from, elevated levels of IL-33 and IL-4, in particular inflammatory lung disorders. The methods of the present invention comprise administering to a subject in need thereof one or more therapeutically effective doses of an IL-33 antagonist alone or in combination with one or more therapeutically effective doses of an IL-4R antagonist. In certain embodiments, the methods of the present invention include use of the antagonists to treat any inflammatory disease or condition mediated in part by enhanced IL-33-mediated signaling and IL-4-mediated signaling.

Abstract: The invention provides a three-step chromatography process for small and large-scale purification of proteins, specifically monoclonal antibodies, using only four buffer solutions made from a mother solution.

Abstract: The present invention relates to antibody molecules, in particular antibody molecules that bind Transforming Growth Factor beta (TGF?), and uses thereof. More particularly, the invention relates to antibody molecules that bind and preferably neutralise TGF?1, TGF?2 and TGF?3, so-called “pan-specific” antibody molecules, and uses of such antibody molecules. Preferred embodiments within the present invention are antibody molecules, whether whole antibody (e.g. IgG, such as IgG1 or IgG4) or antibody fragments (e.g. scFv, Fab, dAb).

Abstract: Techniques are described for determining the quality of a nerve graft by assessing quantitative structural characteristics of the nerve graft. Aspects of the techniques include obtaining an image identifying laminin-containing tissue in the nerve graft; creating a transformed image using a transformation function of an image processing application on the image; using an analysis function of the image processing application, analyzing the transformed image to identify one or more structures in accordance with one or more recognition criteria; and determining one or more structural characteristics of the nerve graft derived from a measurement of the one or more structures.