Abstract: The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

Abstract: Methods and compositions for treating hemophagocytic lymphohistiocytosis (HLH) are provided. The disclosure also relates generally to methods and compositions for diagnosing and treating disorders associated with elevated levels of CXCL9, elevated levels of total IFN?, and other biomarkers. The disclosure also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder in patients with elevated levels of CXCL9 elevated levels of total IFN?, and other biomarkers using agents that interfere with or otherwise antagonize interferon gamma (IFN?) signaling, including neutralizing anti-IFN? antibodies.

Abstract: The present invention provides a single domain specific binding molecule having the structure FW1-CDR1-FW2-HV2-FW3a-HV4-FW3b-CDR3-FW4 in which the Framework Regions FW1, FW2, FW3a, FW3b, and FW4, the Complementarity Determining Regions CDR1 and CDR3, and the Hypervariable Regions HV2, and HV4 have amino acid sequences as defined which provide a high affinity anti-human serum albumin (HSA) binding domain.

Abstract: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human MAGE-A1 epitopes), T cells expressing such high affinity antigen-specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

Abstract: The present invention provides recombinant antigen-binding regions, antibodies and functional fragments thereof that are specific for GM-CSF, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, inflammatory diseases such as rheumatoid arthritis. Antibodies of the invention also can be used in the diagnostics field, as well as for further investigating the role of GM-CSF in the progression of various disorders. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

Abstract: The invention pertains to methods of isolating a Treg from a subject, the method comprising the steps of analyzing a sample of cells obtained from the subject to determine the level of expression of polypeptides and/or polynucleotides corresponding to proteins CD 127, CD4, CD25, and CD226 and isolating, as the Treg, a cell which expresses CD4 and CD25, expresses low levels of CD 127 or does not express CD 127, and expresses low levels of CD226 or does not express CD226. The Treg isolated from a subject can be proliferated in vitro. Accordingly, the invention also provides compositions comprising Treg isolated/proliferated according to the methods of the invention and pharmaceutically acceptable carrier and/or excipient. The pharmaceutical compositions can be used to treat and/or prevent inflammation mediated disease, for example, autoimmune diseases, such as, systemic lupus erythmatosus, rheumatoid arthritis, Multiple Sclerosis, type 1 diabetes, or inflammatory bowel disease.

Abstract: It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Abstract: Humanized or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to and neutralize human CD47, and find use in various therapeutic methods. Preferred are non-activating antibodies. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid sequences of the antibodies.

Abstract: The present invention relates to antibodies binding to 5T4, including bispecific antibodies binding to 5T4 and CD3. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

Abstract: The present invention provides an EndoS mutant enzyme having an amino acid sequence of EndoS D233Q and further having a particular additional mutation and exhibiting a reduced hydrolysis activity, in comparison with the activity of EndoS D233Q, to an N-linked sugar chain (N297-linked sugar chain) linked to Asn at position 297 in IgG and a gene encoding the same.

Abstract: The invention provides stabilized aqueous pharmaceutical etanercept compositions suitable for long-term storage of etanercept, methods of manufacture of these compositions, methods of administration, and kits containing same.

Abstract: This disclosure relates to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4 or CTLA-4) antibodies, antigen-binding fragments, and the uses thereof.

Abstract: The invention relates to multispecific antigen-binding proteins for engaging natural killer (NK) cells for triggering NK cell cytotoxicity by engaging the CD16A (Fc?RIIIA) expressed on NK cells, wherein the antigen-binding protein comprises at least two CD16A antigen-binding moieties and at least a further target antigen-binding moiety. The CD16A antigen-binding moiety comprises light chain and heavy chain variable regions linked one after another in a polypeptide chain and the variable region at the N-terminus of the polypeptide chain comprising the CD16A antigen-binding moiety is a light chain variable region.

Abstract: An antibody-drug conjugate (ADC) or a pharmaceutically acceptable salt thereof, is provided. The ADC includes a tetravalent monoclonal antibody conjugated to a cytotoxic drug by a chemical linker. The monoclonal antibody includes two long chains and four short chains. Each of the long chains includes a first segment and a second segment, the first segment located proximal to the N-terminus of the long chain, and the second segment located proximal to the C-terminus of the long chain. Each of the first segment and second segment pairs with one of the short chains to form an antigen-binding fragment domain, therefore forming four antigen-binding fragment domains having specificity toward the same antigen. Pharmaceutical composition including the ADC and methods of treating diseases using the compositions are also provided.

Abstract: The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.

Abstract: The disclosure is directed to an antibody-drug conjugate (ADC) comprising a monoclonal antibody, or an antigen-binding fragment thereof, directed against B-cell maturation antigen (BCMA) conjugated to a cytotoxin. The disclosure also provides compositions comprising the antibody-drug conjugate and methods of killing multiple myeloma cells (including multiple myeloma stems cells) that express BCMA by contacting multiple myeloma cells with the ADC.

Abstract: The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain consisting of one antibody variable domain capable of binding to an epitope of the human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to an epitope of a human and a non-chimpanzee primate tumor target antigen. The invention further relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3? (epsilon) chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain consisting of one antibody variable domain capable of binding to an epitope of a human and a non-chimpanzee primate tumor target antigen.

Abstract: Methods of treating liver diseases are provided. Accordingly there is provided a method of treating a liver disease selected from the group consisting of fatty liver disease and chronic liver rejection in a subject in need thereof, wherein said liver disease is not associated with genetic alpha-1 anti-trypsin (AAT) deficiency, the method comprising administering to the subject a therapeutically effective amount of AAT.

Abstract: A method for promoting expression of calreticulin in at least one kind of eukaryotic cell, and a synthetic peptide useful in this method are provided. In the method provided by the present invention, a culture of target cells is prepared, and a calreticulin expression-promoting peptide having calreticulin expression-promoting activity is supplied at least once to that culture.

Abstract: The present invention relates to the treatment of Pin1-associated disorders (e.g., disorders characterized by elevated Pin1 activity) with arsenic trioxide, optionally in combination with a retinoic acid compound. Pin1-associated disorders may include, for example, proliferative disorders (e.g., cancers), inflammatory conditions, and autoimmune disorders associated with aberrant levels of Pin1 activity.

Abstract: Provided herein is a pharmaceutical composition comprising an isoflavonoid derivative and a cyclodextrin. Also provided herein are methods of treating cancer, sensitizing cancer cells, and inducing apoptosis in cancer cells by administering such compositions. In specific instances, provided herein are intravenous compositions and therapies.

Abstract: A method of designing a pharmaceutical composition for providing the liver of a person or animal, as a therapeutic target, with a predetermined concentration of a sulfate or sulfonate of a pharmacologically active agent, during a predetermined period, includes determining the correlation between the solubility of a sulfate and/or sulfonate of a pharmacologically active agent of the formula Dn+(R1SO3)?n or Dn+(R2OSO3)?n for various carbon chain lengths X, Y in an aqueous solvent and the expected concentration of the pharmaceutically active agent D in the therapeutic target upon administration of the pharmacologically active agent D to the person or animal, defining a target solubility of the sulfate or sulfonate based on a desired concentration of said pharmaceutically active substance D in the therapeutic target, and determining the carbon chain length(s) X, Y corresponding to the target solubility.

Abstract: The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Abstract: The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell.

Abstract: Aspects of the invention include isolated anti-PD-L1 antibodies, as well as compositions containing such antibodies, and methods of using the same in the treatment of diseases or conditions that are mediated by PD-L1 signaling.

Abstract: Methods to create chemically-induced dimerizing (CID) protein systems and uses thereof are described. The methods utilize antibody binding domain dimerizing proteins. The created systems can be used to regulate cellular events such as gene expression, receptor signaling and cell death to effectuate a variety of clinically relevant treatment outcomes.

Abstract: The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and eribulin or a pharmaceutically acceptable salt thereof, and the use of the combination therapies for the treatment of cancer.

Abstract: This invention relates to crystals of the human Gremlin-1 protein, and the human Gremlin-1 protein in complex with an inhibitory antibody. The invention also relates to the structure of human Gremlin-1 (on its own, or in complex with the antibody) and uses of these structures in screening for agents which modulate Gremlin-1 activity. The invention further provides antibodies which bind an allosteric inhibitory site on Gremlin-1, together with pharmaceutical compositions and medical uses of such antibodies and agents identified by the screening methods.

Abstract: The present inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column based on the difference in isoelectric points between the H chains of two types of antibodies, wherein the difference is introduced by modifying the amino acids present on the surface of the antibody variable regions of two types of antibodies that constitute a bispecific antibody. Furthermore, the inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column by linking respective antigen binding sites (heavy chain variable regions) to the antibody constant regions having different isoelectric points, and then coexpressing these antibodies.

Abstract: The present invention relates to a new anti-BARF1 monoclonal antibody.

Abstract: This disclosure relates to anti-OX40 (TNF Receptor Superfamily Member 4, or TNFRSF4) antibodies, antigen-binding fragments, and the uses thereof.

Abstract: Compositions specific for TNF-receptor superfamily member 25 (TNFRSF25, DR3) modulate the immune re-sponse by regulating T regulatory cells.

Abstract: The present invention provides a combination epigenetic factors and bispecific compounds targeting CD33 and CD3 in the treatment of myeloid leukemia, wherein the epigenetic factor is selected from the group consisting of histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) I inhibitors, hydroxyurea, Granulocyte-Colony Stimulating Factor (G-CSF), histone demethylase inhibitors and ATRA (All Trans-retinoic acid). Accordingly, the invention provides a pharmaceutical composition comprising a CD33 targeting compound and at least one epigenetic factor and an epigenetic factor for use in the amelioration and/or treatment of a myeloid leukemia, wherein the epigenetic factor increases the responsiveness of a patient to a CD33 targeting compound.

Abstract: The present invention provides new, fully human EphA4 monoclonal antibodies with distinct binding characteristics. Also disclosed are antigen binding fragments of these antibodies, bispecific forms of these antibodies, and conjugates of these antibodies. In addition, nucleic acids encoding these antibodies, antigen binding fragments, bispecific antibodies and conjugates are disclosed. These monoclonal antibodies, antigen binding fragments, bispecific antibodies, conjugates, nucleic acids and vectors are of use for identifying and treating a subject with a disease or condition involving abnormal EphA4-mediated signaling.

Abstract: The invention provides stable aqueous pharmaceutical formulations comprising a therapeutic antibody, trehalose, a buffer, and optional surfactant, and having a pH in the range of about 5.5 to about 7.0. The invention also provides methods for making such formulations and methods of using such formulations.

Abstract: Humanized, mouse or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to human glycosylated and deglycosylated CD47 with an optimized Koff value, they disrupt the human CD47-SIRP? interaction, and find use in various therapeutic, preventive or diagnostic methods. The invention includes isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid and nucleotide sequences of the antibodies.

Abstract: The present invention provides caninized murine anti-human PD-1 antibodies that have specific sequences and a high binding affinity for canine PD-1. The invention also relates to use of these antibodies in the treatment of dogs.

Abstract: The present invention relates to methods and pharmaceutical composition for the treatment of cancer. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen for cancer, the method comprising: administering a pharmaceutically effective amount of a TNF? blocking agent to a subject in combination with the immune checkpoint inhibitor.

Abstract: The present invention is based on the finding that administration of polypeptides comprising at least one Immunoglobulin single variable domains against vWF to human TTP patients provides a significant decrease in the time to response. The invention provides a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) against von Willebrand Factor (vWF) for use in treating a vWF-related disease in a human in need thereof. The invention further relates to dosage unit forms, kits and medical uses for treating TTP.

Abstract: Disclosed herein are methods and compositions related to single chain antibody fragments which specifically bind sialyl-Tn epitope of tumor-associated glycoprotein 72 (TAG-72).

Abstract: A chemotherapeutic drug composition, prepared by combination of Everolimus, one of the drugs used in the treatment of the metastatic renal cell carcinoma (RCC) comprising 2-3% of the malignant tumors, with the anti-apoptotic Bcl-2 inhibitor ABT-737 for the treatment of RCC tumors that developed drug resistance. The effect of Everolimus and ABT-737 drug composition on cell survival and cell death in Everolimus-resistant RCC cell lines overexpressing Bcl-2 protein was shown by in vitro and in vivo experiments and the mechanism of the effect of the drug composition on RCC has been examined from a molecular point of view. Navitoclax (ABT-263), an orally available analog of ABT-737, and other Bcl-2 inhibitors alone or in combination with Everolimus, which is administered once a day at a dose of 10 mg, for the use in the treatment of Everolimus-resistant RCC.

Abstract: The present application provides an antibody or antibody fragment capable of binding to a lung-specific X protein and being used to treat a tumor, and a use thereof. The antibody or antibody fragment includes heavy chain CDRs having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 and light chain CDRs having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. Alternatively, the antibody or antibody fragment includes heavy chain CDRs having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 7, and SEQ ID NO: 3 and light chain CDRs having amino acid sequences of SEQ ID NO: 8, SEQ ID NO: 5, and SEQ ID NO: 6. The antibody is a chimeric antibody.

Abstract: Provided herein are methods and kits for determining receptivity status of an endometrium for embryonic implantation.

Abstract: The instant disclosure provides antibodies that specifically bind to TIM-3 (e.g., human TIM-3) and antagonize TIM-3 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 disclosure provides methods for inhibiting and/or reducing self-reactive IgE and/or basophils, thereby treating or preventing lupus, lupus nephritis, and lupus-related disorders.

Abstract: The invention provides conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein. These agents specifically target HCC tumors and treat the HCC. The invention also provides methods of using these conjugates, such as methods of treating HCC by administering the conjugates provided by the invention or compositions provided by the invention, such as pharmaceutical compositions.

Abstract: The present invention provides methods, compositions, reaction mixtures, and kits for detecting cancer biomarkers in a bodily fluid from a subject. Also provided are methods for selecting cancer biomarkers for use in detecting one or more types of cancer in a subject.

Abstract: The present invention relates to a therapeutic agent for an ophthalmic disease comprising a vascular endothelial growth factor (VEGF) receptor inhibitor or an epidermal growth factor (EGF) receptor inhibitor in a nanoparticle form, having a property to be retained in a posterior eye tissue when systemically administered.

Abstract: Antibody and other Fc-containing molecules with variations in the Fc region with reduced binding to Fc gamma receptors and resulting activity and can be used in the treatment of various diseases and disorders.

Abstract: The present invention relates to the field of pharmaceutical formulations of antibodies. Specifically, the present invention relates to a stable liquid antibody formulation and its pharmaceutical preparation and use. This invention is exemplified by an aqueous formulation of an anti-vascular endothelial growth factor (VEGF) antibody.