Patent ID: 6696408
Filing Date: 2004-02-24
Classification: A61K,A61P,C07K

Abstract:
A method for treating a disorder in an individual which comprises administering a therapeutically effective amount of an active agent to an individual in need of treatment of the disorder to effect treatment of said disorder, said disorder selected from the group consisting of seizure, epilepsy, convulsion, and psychosis, said active agent selected from the group consisting of:(a) contulakin-G comprising the amino acid sequence Xaa1-Ser-Glu-Glu-Gly-Gly-Ser-Asn-Ala-Thr-Lys-Lys-Xaa2-Tyr-Ile-Leu (SEQ ID NO: 1), where Xaa1 is pyro-Glu, Xaa2 is proline or hydroxyproline and T10 is modified to contain an O-glycan; (b) a generic contulakin-G having the following general formula Xaa1-Xaa2-Xaa3-Xaa3-Gly-Gly-Xaa2-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa7-Xaa9-Xaa10-Ile-Leu (SEQ ID NO:2), where Xaa1 is pyro-Glu, Glu, Gln or &ggr;-carboxy-Glu; Xaa2 is Ser, Thr or S-glycan modified Cys; Xaa3 is Glu or &ggr;-carboxy-Glu; Xaa4 is Asn, N-glycan modified Asn or S-glycan modified Cys; Xaa5 is Ala or Gly; Xaa6is Thr, O-glycan modified Thr, Ser, O-glycan modified Ser, S-glycan modified Cys, Tyr or any hydroxy containing unnatural amino acid; Xaa7 is Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Arg, omithine, homoarginine or any unnatural basic amino acid; Xaa8 is Ala, Gly, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Arg, ornithine, homoarginine, any unnatural basic amino acid or X-Lys where X is (CH2)n, phenyl, â€”(CH2)mâ€”(CH&boxH;CH)â€”(CH2)mH or â€”(CH2)mâ€”(C&boxH;C)â€”(CH2)mH in which n is 1-4 and m is 0-2; Xaa9 is Pro or hydroxy-Pro; and Xaa10 is Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Trp, D-Trp, bromo-Trp, bromo-D-Trp, chloro-Trp, chloro-D-Trp, Phe, L-neo-Trp, or any unnatural aromatic amino acid, with the proviso that the generic contulakin-G is not desglycosylated contulakin-G; (c) a generic contulakin-G of (b) which is modified to contain an O-glycan, an S-glycan or an N-glycan; (d) a contulakin-G analog which comprises an N-terminal truncation of from 1 to 9 amino acids of the generic contulakin-G of (b); (e) a contulakin-G analog of (c), wherein an Ser-O-glycan, Thr-O-glycan or Cys-S-glycan is substituted for the amino acid residue at the truncated N-terminus; (f) a contulakin-G analog of (c), wherein an Ser-O-glycan, Thr-O-glycan or Cys-S-glycan is substituted for a residue at positions 2-9 of the generic contulakin-G; and (g) a contulakin-G analog which comprises an N-terminal truncation of 10 amino acids of the generic contulakin-G of (b) which is further modified to contain a Lys-N-glycan at residue 11 of the generic contulakin-G.