Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with dysregulated expression of mesothelin. In one embodiment, the invention relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target mesothelin.

Abstract: The invention provides single domain antibodies and derivatives thereof that bind antigens of interest, which are stable, soluble, and do not tend to aggregate. The invention also provides methods for constructing a dAb library and methods for screening dAb libraries to identify the dAb of the invention. The invention also provide methods of treating or preventing conditions by antigen neutralization by administering the dAbs of the invention.

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: The present invention relates to compositions comprising Wnt antagonists and methods of treating Wnt-associated diseases and disorders, such as cancer, inducing differentiation, and reducing the frequency of cancer stem cells, as well as novel methods of screening for such Wnt antagonists. In particular, the invention discloses soluble FZD, SFRP and Ror receptors and their use.

Abstract: The invention provides antibodies against the A2 domain of tenascin-C and methods of using the same.

Abstract: The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.

Abstract: The present invention provides Immunosuppressive compounds capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The present invention further provides peptide based compositions for treatment of cancer or treatment of infections via immunopotentiation caused by inhibition of immunosuppressive signalling induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient. Further, the invention provides pharmaceutical compositions comprising the Immunosuppressive peptide compounds or modified peptide moieties for preventive and/or therapeutic agents for cancer, cancer metastasis, immunodeficiency, an infectious disease or the like and an application of PD-1 or PD-L1 as a testing or diagnostic agent or a research agent for such a disease.

Abstract: Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Abstract: Provided herein are compositions, including pharmaceutical compositions, and methods for modulating, i.e., stimulating or inhibiting, activity of the alternative complement pathway, and methods of identifying factor H-binding proteins.

Abstract: This invention relates to fusion proteins that include a whey acidic protein (WAP) domain-containing polypeptide and a second polypeptide. Additionally, the invention relates to fusion proteins that include a WAP domain-containing polypeptide a second polypeptide, and a third polypeptide. The second and/or third polypeptides of the fusion proteins of the invention are a Fe polypeptide; an albumin polypeptide; a cytokine targeting polypeptide; or a serpin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Abstract: The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domain DOM7h-11, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts.

Abstract: A novel receptor in the TNF family is provided: BAFF-R. Chimeric molecules and antibodies to BAFF-R and methods of use thereof are also provided.

Abstract: The invention relates to the design of trimeric polypeptide complexes using polypeptide structural elements derived from the collagen XVIII protein, and their use in diagnostic and therapeutic systems in vivo and in vitro. The invention also relates to nucleic acids and vectors useful for producing said trimeric complexes.

Abstract: The present invention provides methods for preventing the allogeneic immune rejection of allogeneic cells, such as cells derived from human Embryonic Stem Cells (hESCs), without suppressing the entire immune system. Also provided a vector containing a CTLA4-Ig and PD-L1 expression cassette, and compositions containing a CTLA4-Ig and PD-L1 for use in preventing allogeneic immune rejection of allogeneic cells.

Abstract: The present invention provides a hemojuvelin (HJV) fusion protein (e.g., a human HJV.Fc) protein, polynucleotides and vectors encoding such proteins, and methods for making such proteins. Also provided are methods for treating iron-related disorders which include administration of a HJV fusion protein to a patient in need thereof.

Abstract: The present invention is further directed to methods and compositions for modulating the activity of the Toso protein. The invention further encompasses treatment of disorders associated with inflammation, autoimmune disorders, and cancer using compositions that include a soluble Toso protein.

Abstract: The invention relates to methods for controlling the glycosylation of a RAGE fusion protein. The invention also relates to compositions comprising an amount of a RAGE fusion protein where at least 0.5% of the amount of the RAGE fusion protein is aglycosylated and wherein no more than 53.2% of the amount of the RAGE fusion protein is aglycosylated.

Abstract: The present invention relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.

Abstract: The present invention provides methods comprising combination therapy for treating cancer. In particular, the present invention provides Wnt pathway inhibitors in combination with MAPK pathway inhibitors for the treatment of cancer and other diseases. In some embodiments, the MAPK pathway signaling activation is due to a mutation in a MAPK pathway component. In some embodiments, the MAPK pathway signaling component is Ras, Raf, MEK, or ERK.

Abstract: The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, e.g., to suppress or prevent an immune response and/or to treat or prevent an autoimmune disease.

Abstract: A monoclonal antibody against oncostatin M specific receptor beta subunit, a hybridoma capable of producing the same and a medicament for treating atopic dermatitis comprising the same.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: The invention provides stabilized aqueous pharmaceutical etanercept compositions suitable for long-term storage of etanercept, with substantial reduction in sub-visible particles, and methods of manufacture of these compositions, methods of administration, and articles of manufacture.

Abstract: The present invention provides affinity matured humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from mAb 1567 and recognizes the same epitope. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

Abstract: A chimeric ErbB ligand binding molecule is disclosed along with its pharmaceutically acceptable salt forms. The molecule is a protein that as part of its sequence includes the sequence of SEQ ID NOS: 1, 2, or 3. The molecule can be fused to an IgGFc and especially IgGFc containing cysteine to serine changes in the hinge region. For example, the fusion can be to IgG 1Fc DNA sequences that encode the binding molecules are also contemplated as well as vectors containing such DNA sequences and hosts that contain such vectors. Pharmaceutical compositions are contemplated that contain the binding molecule along with a pharmaceutically acceptable excipient.

Abstract: The invention relates to the use of a JAK1 kinase-selective inhibitor that has minimal inhibitory activity towards Jak2 kinase for treating a disease, such as an inflammatory disease (e.g., moderate to severe Rheumatoid Arthritis) and/or bone loss, either alone or in combination with a DMARD (disease modifying anti-rheumatic drug), such as methotrexate. The invention also provides pharmaceutical composition, dosage formulation, administration route, and dosage schedule thereof.

Abstract: The present invention relates to methods of using the expression of ILTL3 ligand or ILT3 on certain types of cancer cells as a diagnostic tool. Methods are provided for treating ILT3-ligand expressing cancers, such as T-cell acute lymphoblastic leukemia (T-cell acute lymphoblastic leukemia), for example by administering ILT3, the extracellular domain of ILT3 or ILT3Fc conjugated to a cytotoxic agent to kill the targeted cancer cell. Other methods are provided for treating cancers that express ILT3 on their surface, such as monocytic forms of AML, for example by administering anti-ILT3 antibodies conjugated to a cytotoxic agent.

Abstract: Compositions and methods relating to antibodies that specifically bind to TGF-beta binding proteins are provided. These methods and compositions relate to altering bone mineral density by interfering with the interaction between a TGF-beta binding protein sclerostin and a TGF-beta superfamily member, particularly a bone morphogenic protein. Increasing bone mineral density has uses in diseases and conditions in which low bone mineral density typifies the condition, such as osteopenia, osteoporosis, and bone fractures.

Abstract: Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.

Abstract: B7-H5 costimulatory polypeptides, nucleic acids encoding such polypeptides, and methods for using the polypeptides and nucleic acids to enhance a T cell response are provided herein.

Abstract: Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1?, TNF-?, TGF-beta, IFN-?, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.

Abstract: The invention relates to methods and compositions for treating undifferentiated arthritis (UA) and/or preventing the development of rheumatoid arthritis (RA) in subjects with UA by administering to a subject in need thereof an effective amount of soluble CTLA4 molecule.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Abstract: A method of treating, preventing, or delaying the progression of Type 1 diabetes mellitus autoimmunity by administering an effective amount of a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) molecule is provided herewith. The CTLA4 molecule may be a fusion protein of a CTLA4 extracellular region and an immunoglobulin, such as abatacept.

Abstract: Variants of cytotoxic T-lymphocyte antigen 4 (CTLA-4) with high affinity, potency and stability. Formulations of CTLA-4 variants at high concentration for subcutaneous or intravenous administration, e.g. at monthly or less frequent dosage intervals. Use of CTLA-4 variants for treating rheumatoid arthritis and other inflammatory disorders. Fusion of CTLA-4 with IgG Fc having improved stability and longer in vivo half-life.

Abstract: Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.

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 relates to a protein construct, comprising (i) a targeting moiety that is capable of binding to a target cell, and (ii) an effector immunogenic moiety that is capable of triggering an existing, vaccine-induced or natural, immune response. The protein construct, that is preferably in the form of a heteromultimeric protein, is useful for redirecting an immune response that was pre-existing in a patient, toward an undesired target cell.

Abstract: Disclosed is a recombinant fusion protein containing an amino-acid sequence which comprises: (a) the Fc section or part of an Fc section of an immunoglobulin as component (A) or a functional variant of component (A); (b) the extracellular part of a TNF ligand or a partial sequence of the extracellular part of a TNF ligand as component (B) or a functional variant of component (B); and optionally (c) a transition area between component (A) and component (B), containing a linker.

Abstract: The present invention relates to use of an antagonist of BIR1 (B cell immunoglobulin receptor 1) related to the present invention, a method for screening the antagonist, in addition to subtype polypeptides of BIR1, the polynucleotide encoding them and antibodies for the polypeptides. BIR1 functions as an immunosuppressive receptor, and the antagonist of BIR1 has immunopotentive activity, which is able to use for preventing and/or treating a cancer, an immunodeficiency disease or an infectious disease.

Abstract: The present invention aims to provide a lactoferrin fusion protein, which is configured to retain the biological activities of natural lactoferrin, to have a significantly prolonged in vivo lifetime, and to be more clinically useful than natural and gene recombinant lactoferrin, as well as a method for preparation thereof, etc. The present invention provides a fusion protein formed with a protein or peptide comprising an FcRn-binding region and lactoferrin or a biologically active fragment or peptide of lactoferrin, which is represented by: (LF-s-Y)n or (Y-s-LF)n [wherein LF represents lactoferrin or a biologically active fragment or peptide of lactoferrin, Y represents the protein or peptide comprising an FcRn-binding region, s represents any amino acid sequence of 0 to 10 residues, and n represents an integer of 1 to 10], or a variant thereof.

Abstract: Disclosed are methods of treating chronic nervous system diseases or injuries, e.g., chronic spinal cord injury, using Nogo receptor antagonists, including Nogo receptor-1 (NgR1) polypeptides, Nogo receptor-1 antibodies and antigen-binding fragments thereof, soluble Nogo receptors and fusion proteins thereof, and polynucleotides. Also disclosed are methods of noninvasively monitoring axonal growth during and after treatment with an axonal growth promoting agent.

Abstract: The invention provides anti-NRP1 antibodies and methods of using the same.

Abstract: The invention provides anti-polyubiquitin antibodies and methods of using the same.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat rheumatoid arthritis.

Abstract: Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit A class of Eph receptors, antagonize the effects of growth factors on the growth and survival of tumor cells, and which have minimal agonistic activity or are preferentially devoid of agonist activity. Said antibodies and fragments thereof may be used in the treatment of tumors that express elevated levels of A class of Eph receptors, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of A class of Eph receptors.