Abstract: The present invention relates to modified recombinant human MIS protein which has improved cleavage and increased bioactivity and increased potency as compared to wild-type human MIS protein. Other aspects of the invention relate to methods to prevent and treat cancers, such as cancers that express the MIS receptor type II (MISRII) by administering to a subject a composition comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen. Another aspect provides pharmaceutical compositions and kits and methods for use comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with the recombinant MIS protein that lowers the effective dose of the chemotherapeutic agent.

Abstract: This invention relates to polypeptides, including variants of interleukin-37 (IL-37), and related therapeutics and compositions. The invention also relates to the use of the polypeptides and compositions in methods of treating inflammatory diseases or conditions. The present invention provides a monomeric anti-inflammatory polypeptide comprising an amino acid sequence of an IL-37 monomer, the amino acid sequence having a mutation or modification for preventing the anti-inflammatory peptide from forming a homodimer.

Abstract: The disclosure provides chimeric antigen receptors (CARs), T cells comprising such CARs, nucleic acids that encode such CARS, and methods of use thereof, e.g., to treat cancer such as B cell malignancies.

Abstract: The invention provides antibodies immunoreactive with human OX40 and methods of using the same. The antibodies are reactive with a portion of the C-terminus of the human OX40 protein that includes amino acids 266-277. The antibodies are useful for detecting OX40 protein expression in human tissue samples, including by immunohistochemistry, immunofluorescence, or immunoblot.

Abstract: Disclosed herein are anti-Factor XIIa antibodies and methods of using such for treating diseases associated with Factor XII, including diseases associated with contact system activation, plasma prekallikrein signaling (e.g., hereditary angioedema), and ocular diseases.

Abstract: The invention provides for methods of treating obesity or an obesity-associated disorder.

Abstract: The invention relates to a human Interleukin-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (KD)?7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (Koff)?1×10?4 s?1 and/or the antibody displays no measurable cross-reactivity to murine IL-2.

Abstract: Provided are anti-GM-CSF antibodies or fragments thereof including humanized antibodies and fragments. Also provided are uses of the antibodies and fragments for therapeutic, diagnostic and prognostic purposes. Therapeutic uses of the antibodies and fragments, for example include the treatment of inflammatory and autoimmune diseases and disorders.

Abstract: The present invention provides novel, single chain Fc fusion proteins having improved properties. The invention provides single chain fusions of soluble proteins fused to the Fc region of an immunoglobulin via a novel linker comprising a constant region of an immunoglobulin light chain linked to a CH1 constant region of an immunoglobulin heavy chain. This novel linker confers favorable properties on the Fc fusion proteins of the invention such as improved bioactivity and increased half-life as compared to non-Fc fusion counterparts or as compared to prior art Fc fusion proteins. The novel Fc fusion protein scaffold as described herein may be designed to include soluble proteins of interest capable of binding or interacting with any target of interest. Preferably, the Fc fusion protein of the invention is a dimer. The dimer preferably forms via a disulfide bond between free cysteine residues in the hinge region of two monomeric Fc fusion proteins of the invention.

Abstract: In the methods of the invention, an agent that increases phagocytosis and/or efferocytosis of cellular components of coronary plaque is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce aneurysm disease in the individual.

Abstract: This invention pertains to methods and compositions for the diagnosis and treatment of cardiovascular conditions. More specifically, the invention relates to isolated molecules that can be used to diagnose and/or treat cardiovascular conditions including cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure.

Abstract: Methods of modulating immune responses are provided, including contacting SLAT or IP3R1 with an agent that modulates binding of SLAT to IP3R1. Methods of modulating activation or differentiation of CD4+ T cells are also provided, including contacting SLAT or IP3R1 with an agent that modulates binding of SLAT to IP3R1. Peptides and fragments of an IP3R1 amino acid sequence that binds to a SLAT amino acid sequence, and peptides and fragments of a SLAT amino acid sequence that binds to am IP3R1 amino acid sequence, are further provided.

Abstract: The invention provides an improved pan-TGF-? antibody for treatment of conditions that are mediated by TGF-?, including autoimmune diseases, fibrotic conditions, and cancers. Also provided are methods and uses of the antibody in conjunction with other immunomodulatory agents such as an anti-PD-1 antibody.

Abstract: Antibodies or antigen-binding fragments thereof are engineered to bind Transforming Growth Factor-? (TGF?). TGF?-isoform selective antibodies or antigen-binding fragments thereof may selectively bind human TGF?1, compared to human TGF?2 and human TGF?3, or may selectively bind human TGF?3, compared to human TGF?1 and human TGF?2. The design of the antibodies or antigen-binding fragments thereof is facilitated by a co-crystal structure of a recombinant Fab fragment of GC1008 bound to TGF?2 and by another co-crystal structure of the scFv version of GC1008 bound to TGF?1.

Abstract: The present inventors discovered that neural invasion is suppressed by inhibiting IL-6 in a model for neural invasion of pancreatic cancer, and completed the present invention. The present inventors also demonstrated that: an IL-6 receptor is expressed in cells of human pancreatic cancer cell lines; and IL-6 enhances the chemotactic and migratory activities and intracellular signaling of pancreatic cancer cells; and thus pancreatic cancer can be treated by inhibiting IL-6. Furthermore, the present inventors found that neural invasion of human pancreatic cancer can be suppressed, from the results of administering IL-6 inhibitors to neural invasion model mice.

Abstract: The invention provides novel methods of determining or comparing potency of a test interferon relative to rSIFN-co (an interferon having therapeutic effects on solid tumors); methods of establishing substantial equivalence between a test interferon and rSIFN-co; methods for down-regulation of expression of Wnt-related receptors or co-receptors, such as LRP6/FZD6; down-regulation of expression of Wnt-related target genes, such as, Axin2, CD24, Survivin and/or ID2; inhibition of beta-catenin/TCF transcriptional activities; suppression of expression of beta-catenin; up-regulation of tumor suppressor genes, such as DKK-3, BATF2 and/or KLF4; inhibition of tumor cell viability in vitro; inhibition of tumor growth and metastases in vivo; inhibition of tumor cell migration, pseudopod formation, and colony formation in vitro; as well as methods for determining potency of a test interferon, kits for determination of such methods, and an interferon or an interferon substitute having said activities.

Abstract: Provided are anti-GM-CSF antibodies or fragments thereof including humanized antibodies and fragments. Also provided are uses of the antibodies and fragments for therapeutic, diagnostic and prognostic purposes. Therapeutic uses of the antibodies and fragments, for example include the treatment of inflammatory and autoimmune diseases and disorders.

Abstract: The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

Abstract: Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF-? superfamily of proteins.

Abstract: The present invention provides a method for treating multiple sclerosis (MS), and for reducing flu-like symptoms associated with administration of an interferon to a patient with MS. The method involves intramuscularly administering the interferon to the MS patient according to an escalating dosing regimen in weeks 1 to 3, and a full therapeutically effective dose of interferon in week 4. In one embodiment of the invention, the escalating dosing regimen comprises administering one quarter of the therapeutically effective dose in week 1, half of the therapeutically effective dose in week 2, and three-quarters of the therapeutically effective dose in week 3. Also provided are titration packages for enabling compliance with a regimen of changing dosage of an interferon over a period of time.