The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Methods and compositions related to the engineering of a protein with MTA/ADO-degrading enzyme activity are described. For example, in certain aspects there may be disclosed an MTase capable of degrading MTA/ADO. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer or SCID with an MTase using the disclosed proteins or nucleic acids.

The present invention provides compositions and methods comprising interleukin-2 (TL-2) polypeptide conjugates. Also described are IL-2 conjugates for the treatment of diseases or conditions including cancer.

The present invention provides a covalent conjugate. The conjugate includes an antibody or antibody derivative, at least two LL37-derived polypeptides, and a payload. The antibody or antibody derivative targets a cell that has phosphatidylserine in its outer leaflet. The payload includes: a small molecule cytotoxic drug of less than 3 kDa, or a plurality thereof; or a peptide or protein of less than 100 kDa. Uses and methods of using these covalent conjugates are also provided, related to enhancing delivery of the antibody/derivative or the payload, e.g. to enhance therapeutic or diagnostic effectiveness.

The disclosure provides multimeric proteins comprising three, four, or more monomer polypeptides, each comprising a first 4-1BB-targeting moiety, an oligomerization moiety, and optionally a linker. The monomer polypeptide may further comprise one or more additional targeting moieties. The oligomerization moiety promotes the trimerization, tetramerization, or higher state of oligomerization of the monomer polypeptides. Such multimeric proteins can be used in many pharmaceutical applications, for example, as anti-cancer agents and/or immune modulators. The present disclosure also concerns methods of making the multimeric proteins described herein as well as compositions comprising such multimeric proteins. The present disclosure further relates to nucleic acid molecules encoding such multimeric proteins and methods for the generation of such multimeric proteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of such multimeric proteins as well as compositions comprising one or more of such multimeric proteins.

The present disclosure relates to genetically modified non-human animals that express a fusion protein including B2M and FcRn, and methods of use thereof. In some embodiments, the animals can have a B-NDG background. In some embodiments, the endogenous B2M gene is knocked out in the animals.

Provided are activatable proprotein heterodimers comprising at least two separate polypeptide chains, one chain comprising an IL-2 protein fused to an IL-15 binding protein such as IL-15Rα, and another chain comprising an IL-15 protein fused to an IL-2 binding protein such as IL-2Rα, among other features including binding moieties and cleavable linkers, and related pharmaceutical compositions and methods of use thereof.

It is an object of the preset invention to provide a usefultool for treating or preventing infections disease. According to the present invention, provided is a therapeutic or preventive agent for infections disease, comprising, as an active ingridient, a fusion protein of (a) at least one polypeptide comprising an amino acid sequence that is identical to or substantially identical to the amino acid sequence of the N-terminal domain of pertraxin 3 capable of binding to a bistone to form a polypeptide aggregate and (b) the Fe portion of an immunoglobulin, or a pharmacologically acceptable salt thereof.

The present disclosure includes compositions and methods for treating, ameliorating, and/or preventing immune mediated pathology associated with a bacterial and/or viral infection.