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This invention claims species-independent agonists of A₃AR, specifically (N)-methanocarba adenine nucleosides and pharmaceutical compositions comprising such nucleosides. The A₃ adenosine receptor (A₃AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A₃AR subtype have been developed that are also selective for the mouse A₃AR while retaining selectivity for the human receptor.

The invention hereby offered for licensing is in the field of Immunotherapy and more specifically in therapy of autoimmune diseases such as Type I diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosis and immune mediated allergies such as asthma as well as in transplantation-related disorders, such as graft acceptance and graft-versus-host-disease (GVHD).

This invention includes methods for treating or ameliorating fibrosis by inhibiting the interaction between IL-21 Receptor (IL-21R) and IL-21 using either anti-IL-21R monoclonal antibodies (or binding fragments of anti-IL-21R mAbs), anti-IL-21 monoclonal antibodies (or binding fragments of anti-IL-21 mAbs) or soluble IL-21R (or binding fragments of IL-21R). It is believed that the TH2 immune response, induced by IL-21, plays a major role in the in the pathogenesis of tissue fibrosis.

Novel and potent caspase 1 inhibitors are available for licensing. In particular, this technology discloses potent and selective caspase 1 inhibitors that target the active site of the enzyme. Caspase 1 is known to play a pro-inflammatory role in numerous autoimmune and inflammatory diseases and therefore represents an excellent target for treatment of a broad range of diseases, including but not limited to Huntington's, amyotrophic lateral sclerosis, ischemia, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, and sepsis.

This technology describes monoclonal antibodies against mouse chemokine (C-X-C motif) ligand 9 (CXCL9), also known as Monokine induced by gamma interferon (Mig). CXCL9 is a secreted protein that functions to attract white cells and increased expression of CXCL9 has been linked to several diseases. The inventors at the NIH generated over 100 anti-mouse CXCL9 antibodies from a CLXL9/Mig knockout mouse and further characterized several antibodies to show neutralization of CXCL9.

The global market for cancer therapeutics is over $40 billion and is anticipated to continue to rise in the future. There remains a significant unmet need for therapeutics for cancers that affect blood, bone marrow, and lymph nodes and the immune system, such as leukemia, multiple myeloma, and lymphoma. The proteasome inhibitor bortezomib, which may prevent degradation of pro-apoptotic factors permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways, has been a successful mode of treatment for such cancers.

NIH Inventors have recently discovered a novel Leucine-rich repeat and calponin homology domain-containing protein 4 (Lrch4) in a proteomic screen of the plasma membrane of lipopolysaccharide (LPS)-exposed macrophages. Expression data by RT-PCR revealed that all Lrch family members (1-4) are expressed in macrophages, but only Lrch4 was recruited into lipid rafts (signaling microdomains of the plasma membrane) by LPS. Lrch4 is the most highly expressed Lrch family member in mouse tissues. It is a predicted single-spanning transmembrane protein that is encoded by the Lrch4 gene in humans.

The uses for human anti-HIV monoclonal antibody 10E8 and its variants include passive immunization, therapeutic vaccination, and the development of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing antibodies isolated and it neutralizes up to 98% of diverse HIV-1 strains. 10E8 is specific to the membrane-proximal external region (MPER) of the HIV envelope protein gp41 and 10E8 is orthogonal to other anti-HIV antibodies. In combination with other antibodies 10E8 may provide an antibody response that neutralizes nearly all strains of HIV-1.

This molecular probe may serve as a companion tool to identify and stratify patient populations based on the prevalence of the target A₃ adenosine receptors.

Small molecule drugs, A₃AR-selective agonists, are currently in advanced clinical trials for the treatment of hepatocellular carcinoma, autoimmune inflammatory diseases, such as rheumatoid arthritis, psoriasis, and dry eye disease, and other conditions.

The present invention is directed to novel small molecule agonists of the mammalian relaxin family receptor 1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: 1) vasodilation due to up-regulation of the endothelin system; 2) extracellular matrix remodeling; 3) moderation of inflammation by reducing levels of inflammatory cytokines; and 4) angiogenesis. Small molecule agonists of RXFP1 may be useful in treating acute heart failure (AHF), scleroderma, fibrosis, other conditions associated with the biology of relaxin, and in improving reproductive health and wound healing.