Abstract: The present disclosure relates to IL-7 polypeptides, compositions comprising IL-7 polypeptides, methods of making the same, and methods of using the IL-7 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the IL-7 polypeptides. In some embodiments, the disclosed IL-7 polypeptides comprise at least one modification at an amino acid residue which reduces the affinity of the IL-7 polypeptide to the IL-7 receptor. Also provided herein are synthetic IL-7 polypeptides and methods of manufacture thereof. Further provided herein are immunocytokines comprising immune checkpoint inhibitor molecules, such as anti-PD-1 antibodies, couple to the IL-7 polypeptides provided herein.

Abstract: The present disclosure relates to modified anti-TNF? polypeptides, compositions comprising modified anti-TNF? polypeptides, methods of making the same, and methods of using the modified anti-TNF? polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of inflammatory disorders using the modified anti-TNF? polypeptides.

Abstract: The present disclosure relates activatable immunocytokines targeted to immune checkpoint molecules such as PD-1, compositions comprising the activatable immunocytokines, and methods of use thereof. The present disclosure also relates activatable IL-2 polypeptides linked to anti-PD-1 polypeptides (e.g., anti-PD-1 antibodies).

Abstract: The present disclosure relates to cleavable peptides, including multi-protease cleavable peptides, and methods of use thereof. The cleavable peptides are useful in a variety of applications, including as conditional linkers between two groups and as conditional activators of proteins. The present disclosure also relates to a composition of conditionally regulated proteins with cleavable peptides for treatment of diseases including but not limited to cancer. The conditional activation of proteins is based on cleavable polypeptides that regulate the protein activity.

Abstract: The present disclosure relates to activatable proteins which comprise cleavable moieties attached thereto which display an altered activity upon cleavage of the cleavable moieties. The present disclosure also relates to activatable IL-2 polypeptides which comprise cleavable moieties, as well as compositions and methods of use thereof. The present disclosure further relates to cleavable peptides which can be cleaved by multiple proteases, as well as to polypeptides incorporating said cleavable peptides.

Abstract: The present disclosure relates to modified anti-PD-1 polypeptides linked to IL-7, pharmaceutical compositions comprising modified anti-PD-1 polypeptides linked to IL-7, methods of making anti-PD-1 polypeptides linked to IL-7, and methods of using the modified anti-PD-1 polypeptides linked to IL-7 for treatment of diseases. In one aspect, the disclosure relates to methods of treating cancer in a subject using the modified anti-PD-1 polypeptides linked to IL-7. Also provided herein is synthetic IL-7 and methods of manufacture thereof.

Abstract: The present disclosure relates to bifunctional cytokine compositions comprising first and second cytokines connected by a linker, as well as methods of making bifunctional cytokine compositions. The disclosure also relates to bifunctional cytokine compositions comprising interleukins, including interleukin-2, interleukin-7, and interleukin-18, as well as derivatives thereof.

Abstract: The present disclosure relates to activatable IL-18 polypeptides, compositions comprising activatable IL-18 polypeptides, methods of making the same, and methods of using the activatable IL-18 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the activatable IL-18 polypeptides.

Abstract: The present disclosure relates to modified immunocytokine compositions comprising antibodies or antigen binding fragments specific for immune cell antigens and IL-18 polypeptides. Also provided herein are methods of treatment with and methods of manufacture of immunocytokine compositions.

Abstract: The present disclosure relates a modified interleukin 18 (IL-18) polypeptide, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases including cancer. The modified IL-18 polypeptide can exhibit an ability to induce interferon gamma (IFN?) production when in contact with a cell, exhibit a diminished ability to be inhibited by IL-18 binding protein (IL-18BP) compared to wild type IL-18 (WT IL-18), and exhibit a ratio of half-maximal inhibitory concentration (IC50) by IL-18BP to half-maximal effective concentration (EC50) to induce IFN? production which is greater than that of WT IL-18.

Abstract: The present disclosure relates to modified IL-2 polypeptides, compositions comprising modified IL-2 polypeptides, methods of making the same, and methods of using the modified IL-2 polypeptides for treatment of diseases including autoimmune diseases. In one aspect, the disclosure relates to the treatment of autoimmune diseases using the modified IL-2 polypeptides. In some embodiments, the disclosed IL-2 polypeptides exhibit enhanced binding to IL-2 receptor ? and/or reduced binding to IL-2 receptor ?. In another aspect, the modified IL-2 polypeptides exhibit enhanced ability to activate T regulatory cells compared to T effector cells.

Abstract: The present disclosure relates to modified anti-PD-1 polypeptides, pharmaceutical compositions comprising modified anti-PD-1 polypeptides, methods of making anti-PD-1 polypeptides, and methods of using the modified anti-PD-1 polypeptides for treatment of diseases. In one aspect, the disclosure relates to methods of treating cancer in a subject using the modified anti-PD-1 polypeptides.

Abstract: The present disclosure relates to modified anti-CD20 polypeptides, compositions comprising modified anti-CD20 polypeptides, methods of making the same, and methods of using the modified anti-CD20 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the modified anti-CD20 polypeptides.

Abstract: The present disclosure relates to conjugate compositions comprising an antibody or an antigen binding fragment, a synthetic protein, and a linker. The disclosure further relates to methods of making the conjugate compositions and to methods of using the conjugate compositions for the treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the conjugate compositions.

Abstract: The present disclosure relates to modified anti-TNF? polypeptides, compositions comprising modified anti-TNF? polypeptides, methods of making the same, and methods of using the modified anti-TNF? polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of inflammatory disorders using the modified anti-TNF? polypeptides.

Abstract: The present disclosure relates to modified anti-PD-L1 polypeptides, compositions comprising modified anti-PD-L1 polypeptides, methods of making the same, and methods of using the modified anti-PD-L1 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the modified anti-PD-L1 polypeptides.

Abstract: The present disclosure relates to modified IL-18 polypeptides, compositions comprising modified IL-18 polypeptides, methods of making the same, and methods of using the modified IL-18 polypeptides for treatment of diseases. In one aspect, the disclosure relates to the treatment of cancer using the modified IL-18 polypeptides. In some embodiments, the disclosed IL-18 polypeptides induce the production of IFN?. In some embodiments, the disclosed IL-18 polypeptides induce the production of IFN? without being neutralized by IL-18 binding protein.

Abstract: The present invention relates to substituted imidazoquinoxaline compounds of general formula (I) as inhibitors of Mps-1 Kinase or TTK, and being active against inflammation and cancer.

Abstract: The present invention relates to substituted imidazoquinoxaline compounds of general formula (I) as inhibitors of Mps-1 Kinase or TTK, and being active against inflammation and cancer.