This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Novel polypeptides, polynucleotides, expression vectors and novel immunogenic compositions derived from Staphylococcus aureus, in particular novel polypeptides, polynucleotides, expression vectors and compositions derived from/related to the SpA, Hla, Aur and LukE polypeptides. Also disclosed is methods of immunity induction utilising the polypeptides, polynucleotides, expression vectors, and immunogenic compositions.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase 1 and the CMPD is protein transduction domain of the HIV-1 Tat protein.

A method of treating acute myocardial infarction in a patient by administering to the patient a combination of r-SAK and an antiplatelet agent such as ticagrelor. The acute myocardial infarction can be ST-elevation myocardial infarction. The patient can be one who is expected to receive percutaneous coronary intervention within 120 minutes from his or her first medical contact, e.g., one who is expected to receive percutaneous coronary intervention within 120 minutes from his or her first medical contact but more than 30 minutes from his or her first medical contact. A pharmaceutical composition for use in treating acute myocardial infarction in a patient is also provided which include r-SAK and an antiplatelet agent.