The present invention relates to a fusion protein comprising a protein transduction domain capable of introducing the fusion protein into a mammalian cell and an anti-apoptotic protein comprising the amino acid of the sequence of SEQ ID NO:1 or an anti-apoptotically active variant or fragment thereof. The invention also relates to a pharmaceutical composition comprising such a fusion protein, in particular for blocking apoptosis in a patient in need thereof. The invention also provides a polynucleotide encoding such a fusion protein, an expression vector comprising the polynucleotide and a host cell comprising the expression vector. In a further aspect, the invention relates to the use of any of theses materials for the preparation of a medicament for blocking apoptosis in a patient in need thereof.

The invention features isolated mRNAs encoding fusion polypeptides comprising a Stefm A (SteA) scaffold polypeptide and one or more binding polypeptides, such as one or more Bc1-2 homology 3 (BH3) domains, including mRNAs comprising one or more modified nucleobase, and methods of using the same, for example, for inducing apoptosis and/or treating cancer (e.g., liver cancer or colorectal cancer).

The present invention relates to compounds of Formula I, IA, II, IIA, III, or IIIA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

The present invention includes a composition and method of modulating a dysregulated gut-derived inflammation following a thermal injury comprising: identifying a mammal in need of treatment for the dysregulated gut-derived inflammation following the thermal injury; and providing the mammal with a recombinant Cystatin 9 (CST9) and Cystatin C (CSTC) in a synergistic amount sufficient to restrain or prevent a life-threatening, unrestrained systemic dysregulated gut-derived inflammation in the mammal caused by the thermal injury.

The invention relates to a polypeptide, such as an Affimer polypeptide, comprising an amino acid sequence having at least 80% identity to amino acid residues 1 to 11, 13 to 15, 17 to 19, 21 to 25, 27 to 28, 35 to 37, 39, 41, 43 to 44, 46 to 47, 49 to 50, 52 to 53, 55 to 58, 63 to 64, 66, 68 to 82, 84 to 85, and 87 to 98 of SEQ ID NO: 1; characterized in that said polypeptide comprises one or mutations relative to SEQ ID NO: 1. The invention also relates to various methods and nucleic acids.

Disclosed herein is a protein fusion technology that allows the combination of one or more cancer vaccine epitopes with scaffold domains. Also disclosed herein are polypeptide and polynucleic acid compositions encompassed by the protein fusion technology and the methods of using the same.

The present invention relates to a cathepsin inhibitor comprising or consisting of Formula (I) (X.sub.1)(X.sub.2)(X.sub.3)(X.sub.4)(Y)(X.sub.5)(X.sub.6)(X.sub.7) Formula (I) wherein (X.sub.1) is an amino acid selected from K, L, F and M; (X.sub.2) is an amino acid selected from L, A, D, E, F, G, H, I, K, M, N, S, W, Y, Q and R; (X.sub.3) is an amino acid selected from R, A and L; (X.sub.4) is an amino acid selected from M, I, K, V and Y; (X.sub.5) is an amino acid selected from P, A, I, L, V, W and Y; (X.sub.6) is an amino acid selected from K, A, E, F, G, I, L, M, N, Q, S, T, V, W, Y and Q; (X.sub.7) is an amino acid selected from D, A, E, F, G, I, L, M, N, P, T, V, W, Y, Q and R; and (Y) is a Michael acceptor.

The present disclosure provides methods and compositions for the treatment of diseases and genetic disorders linked to CSTB loss and/or misfunction. The methods and compositions of the present disclosure include rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules encoding CSTB polypeptides.

The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease).

The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and Huntington's disease.