The present invention relates to Protoxin-II variants, polynucleotides encoding them, and methods of making and using the foregoing.

Provided are a labelling agent including a compound of the following Formula 1, a labelling composition, a method of labelling a protein with the labelling agent, and a method of detecting the protein using the labelling agent: ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.8 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, R.sub.7 is H or —NR.sub.9R.sub.10, R.sub.9 and R.sub.10 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, X is —NR.sub.11, —O, or S, R.sub.11 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, Y is —OR.sub.12 or —NR.sub.13R.sub.14, R.sub.12 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, and R.sub.13 and R.sub.14 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl.

Provided are a labelling agent including a compound of the following Formula 1, a labelling composition, a method of labelling a protein with the labelling agent, and a method of detecting the protein using the labelling agent: ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.8 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, R.sub.7 is H or —NR.sub.9R.sub.10, R.sub.9 and R.sub.10 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, X is —NR.sub.11, —O, or S, R.sub.11 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, Y is —OR.sub.12 or —NR.sub.13R.sub.14, R.sub.12 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, and R.sub.13 and R.sub.14 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl.

Fusion proteins containing a half-life extension protein, a linker, and a GDF15 protein are described. Also described are nucleic acids encoding the fusion proteins, recombinant cells thereof, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing metabolic diseases, disorders or conditions.

Fusion proteins containing a half-life extension protein, a linker, and a GDF15 protein are described. Also described are nucleic acids encoding the fusion proteins, recombinant cells thereof, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing metabolic diseases, disorders or conditions.

Described herein are compositions and kits that comprise an engineered TL1A ligand that displays high stability, minimal binding to decoy receptor DcR3 while retaining functional activity via binding to its cell surface receptor, DR3, and the ability to activate T cells in vitro and in vivo. Methods of making an engineered TL1A ligand and methods of treating a disease or disorder in a subject by administering an engineered TL1A ligand are also provided.

Described herein are compositions and kits that comprise an engineered TL1A ligand that displays high stability, minimal binding to decoy receptor DcR3 while retaining functional activity via binding to its cell surface receptor, DR3, and the ability to activate T cells in vitro and in vivo. Methods of making an engineered TL1A ligand and methods of treating a disease or disorder in a subject by administering an engineered TL1A ligand are also provided.

The present invention relates to isolated protein sequences that correspond to cell binding peptides, fragments, neo-structures and/or neo-epitopes of a normally occurring serum protein present in human tissue, wherein the peptide, fragment, neo-structure and/or neo-epitope has an immunoregulatory activity and is the result of either an enhanced proteolytic activity and/or conformational changes in a tissue, or a malignant tumor. In the present patent application, a common structure of several of these peptides, fragments, neo-structures and/or neo-epitopes, having immunoregulatory activity by binding to receptors on immune cells, has been identified. The present invention further also relates to monoclonal and/or polyclonal antibodies directed to a cell binding fragment of a normally occurring serum protein present in human tissue, as described above.

The present invention relates to isolated protein sequences that correspond to cell binding peptides, fragments, neo-structures and/or neo-epitopes of a normally occurring serum protein present in human tissue, wherein the peptide, fragment, neo-structure and/or neo-epitope has an immunoregulatory activity and is the result of either an enhanced proteolytic activity and/or conformational changes in a tissue, or a malignant tumor. In the present patent application, a common structure of several of these peptides, fragments, neo-structures and/or neo-epitopes, having immunoregulatory activity by binding to receptors on immune cells, has been identified. The present invention further also relates to monoclonal and/or polyclonal antibodies directed to a cell binding fragment of a normally occurring serum protein present in human tissue, as described above.

The present invention relates to a polypeptide binding to human serum albumin and comprising or consisting of an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDY(X.sup.1)(X.sup.2)(X.sup.3)(X.sup.4)(X.sup.5) (X.sup.6)D(X.sup.7)SFHKGEKFQIL(X.sup.8)(X.sup.9)(X.sup.10)(X.sup.11)(X.sup.12)G(X.sup.13)(X.sup.14)W(X.sup.15)(X.sup.16)RSLTTG(X.sup.17)(X.sup.18)G(X.sup.19)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein (X.sup.1) is A, V, I, L, M, G, P, S, T, N, Q, C, R, H, K, D or E; (X.sup.2) is R, H, K, A, V, I, L, M, G, P, S, T, N, Q or C; (X.sup.3) is R, H, K, S, T, N, Q, C, F, Y, W, A, V, I, L, M, G or P; (X.sup.4) is S, T, N, Q, C, A, V, I, L, M, G, P, R, H, K, F, Y, W, D or E; (X.sup.5) is S, T, N, Q, C, D, E, F, Y, W, A, V, I, L, M, G, P, R, H or K; (X.sup.6) is F, Y, W, A, V, I, L, M, G, P, R, H, K, S, T, N, Q or C; (X.sup.7) is A, V, I, L, M, G, P, R, H or K; (X.sup.8) is S, T, N, Q, C, D or E; (X.sup.9) is S, T, N, Q, C, D, E, A, V, I, L, M, G, P, F, Y or W; (X.sup.10) is A, V, I, L, M, G or P; (X.sup.11) is F, Y, W, R, H or K; (X.sup.12) is S, T, N, Q, C, F, Y or W; (X.sup.13) is F, Y, W, R, H, K, S, T, N, Q, C, D, E, A, V, I, L, M, G or P; (X.sup.14) is F, Y, W, A, V, I, L, M, G or P; (X.sup.15) is D, E, A, V, I, L, M, G or P; (X.sup.16) is A, V, I, L, M, G or P; (X.sup.17) is D, E, A, V, I, L, M, G, P, R, H or K; (X.sup.18) is S, T, N, Q, C, A, V, I, L, M, G or P; (X.sup.19) is F, Y, W, S, T, N, Q or C; and (b) an amino acid sequence which is at least 90% identical to the amino acid sequence of (a), wherein the identity determination excludes amino acid positions (X.sup.1) to (X.sup.19).