The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

A complex comprising a GDF15 polypeptide is described. Methods of treating individuals with a metabolism disorder, such as, glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

A complex comprising a GDF15 polypeptide is described. Methods of treating individuals with a metabolism disorder, such as, glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

The present invention relates to the treatment of muscular diseases.

Provided herein are methods and compositions relating to modified proteins of Anti-Müllerian hormone (AMH) for regulating folliculogenesis in a woman, and in particular regulating follicle activation and maturation and immature (primordial) follicle depletion. In certain embodiments, regulating or inhibiting folliculogenesis in a woman treats ovarian senescence, pauses or slows down ovarian aging and/or delays the onset of menopause and/or the symptoms related to menopause, premature ovarian decline induced by gonadotoxic treatment, or diseases or conditions caused by genetic mutations in genes regulating folliculogenesis and ovarian biology.

Provided herein are methods and compositions relating to modified proteins of Anti-Müllerian hormone (AMH) for regulating folliculogenesis in a woman, and in particular regulating follicle activation and maturation and immature (primordial) follicle depletion. In certain embodiments, regulating or inhibiting folliculogenesis in a woman treats ovarian senescence, pauses or slows down ovarian aging and/or delays the onset of menopause and/or the symptoms related to menopause, premature ovarian decline induced by gonadotoxic treatment, or diseases or conditions caused by genetic mutations in genes regulating folliculogenesis and ovarian biology.

The present invention relates to a human Lefty A protein variant with improved productivity and stability, a fusion protein comprising the protein variant, and a composition for preventing and/or treating neuromuscular disease comprising the protein variant or the fusion protein. According to the present invention, a human Lefty A protein variant and a fusion protein comprising the variant are constructed, which have better stability than naturally occurring human Lefty A protein, and thus are expressed at high levels and produced in high yield in animal cells. In addition, administration of the constructed human Lefty A protein variant or fusion protein can restore the nerve and motor functions of nerve disease model animals. Accordingly, the use of the human Lefty A protein variant or fusion protein can effectively prevent or treat various nerve diseases and muscle diseases.

The present invention relates to a human Lefty A protein variant with improved productivity and stability, a fusion protein comprising the protein variant, and a composition for preventing and/or treating neuromuscular disease comprising the protein variant or the fusion protein. According to the present invention, a human Lefty A protein variant and a fusion protein comprising the variant are constructed, which have better stability than naturally occurring human Lefty A protein, and thus are expressed at high levels and produced in high yield in animal cells. In addition, administration of the constructed human Lefty A protein variant or fusion protein can restore the nerve and motor functions of nerve disease model animals. Accordingly, the use of the human Lefty A protein variant or fusion protein can effectively prevent or treat various nerve diseases and muscle diseases.