Advanced Immuni T, Inc.

Peptide Technology Limited

Carlsberg Biotechnology Ltd. A/s

Drug Royalty Corporation

Anders Jorgen Andersen

Deborah Ann Rathjen

Roger Aston

Fred Widmer

David James Phipps

Douglas Kevin MacFadden

Penelope Reed Doob

Peter Louis Carlen

A method of treating inflammation in patients in need of such treatment by administering an effective amount of I-A-B-C-D-E-F-G-H-II (General Formula), wherein A is Ala, Gly, Val, Ser, Thr or absent, B is Ala, Gly, Val, Ser, Thr, or absent, C is Ser, Thr or absent, D is Ser, Thr, Asn, Glu, Arg, Ile, Leu or absent, E is Ser, Thr, Asp or absent, F is Ser, Thr, Asp or absent, G is Tyr or absent, H is Thr, Arg, Gly, Met, Met(O), Cys, Thr, Gly or absent and I is Cys or absent II is Cys, an amide group, an ester group or absent. At least one of the amino acids optionally is substituted by a monomeric or polymeric carbohydrate or derivative thereof, such substitution being accomplished through hydroxyl and/or amino acid and/or amido groups of the amino acids, and wherein the peptide composes at least 4 amino acid residues, and a pharmaceutically acceptable salt thereof.

Peptide T and related peptides in the treatment of inflammation, including multiple sclerosis

A method of treating or preventing multiple sclerosis in a patients in need of such treatment by administering an effect amount of the peptide: I-A-B-C-D-E-F-G-H-II (General Formula) wherein A is Ala, Gly, Val, Ser, Thr or absent, B is Ala, Gly, Val, Ser, Thr or absent, C is Ser, Thr or absent, D is Ser, Thr, Asn, Glu, Arg, IIe, Leu or absent, E is Ser, Thr, Asp or absent, F is Thr, Ser, Asn, Glu, Lys, Trp or absent, G is tyr or absent; H is Thr, Arg, Gly, Met, Met(O), Gys, Thr, Gly or absent, I is Cys or absent, II is Cys, an amide group, substituted amide group, an ester group or absent.

Peptide T and related peptides in the treatment of inflammation,

Pentapeptides having the formula H-Asp-Ser-C-Pro-Arg-OH, where Asp, Ser, Pro and Arg may have L- or D-configuration, and C denotes Asp or Asn in L or D configuration, are synthesized by reacting in an aqueous medium Y.sub.2 -Pro-OH, wherein Y.sub.2 is a protective group, with Arg-Ro, wherein Ro is OH or is as defined below for R.sub.1 below, to form Y.sub.2 -Pro-Arg-Ro, which is deprotected, if necessary under conversion to Pro-Arg-R.sub.1, wherein R.sub.1 is an enzymatically cleavable .alpha.- carboxy substituting group selected form esters, amides, anilides, hydrazides or L-amino acid esters, and thereafter reacting Y.sub.3 -C(Z.sub.3)-OH with Pro-Arg-R.sub.1 to form Y.sub.3 -C(Z.sub.3)-Pro-Arg-R.sub.1 which is deprotected to C-Pro-Arg-R.sub.1, and then reacting Y.sub.4 -Ser-OH with C-Pro-Arg-R.sub.1 to form Y.sub.4 -Ser-C-Pro-Arg-R.sub.1, which is deprotected to Ser-C-Pro-Arg-R.sub.1, and reacting Y.sub.5 -Asp(Z.sub.5)-OH with Ser-C-Pro-Arg-R.sub.1 to form Y.sub.5 -Asp(Z.sub.5)-Ser-C-Pro-Arg-R.sub.1, which is deprotected to the intermediate Asp-Ser-C-Pro-Arg-R.sub.1, and finally removing the group R.sub.1 with an enzyme, preferably trypsin to form Asp-Ser-C-Pro-Arg, or removing R.sub. 1 from Y.sub.5 -Asp(Z.sub.5)-Ser-C-Pro-Arg-R.sub.1 before deprotection to Asp-Ser-C-Pro-Arg-OH. The groups Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5, Z.sub.3 and Z.sub.5 are protective groups which apart from Y.sub.2 are removable by catalytic hydrogenation. The employed synthesis strategy based on the combination hydrogenation/enzyme, both proceeding under mild conditions, leads to the peptides, in particular HEPP, in good yield without risk of formation of .beta.-aspartyl peptides and cleavage of Asp-Pro bonds.

Process for producing pentapeptides and intermediates for use in the

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Kokkedal, Denmark

Anders Jorgen Andersen