Patent ID: 8808694
Filing Date: 2014-08-19
Classification: A61K,A61P,C07K

Abstract:
1. A method of selecting a peptidomimetic macrocycle that generates a reduced antibody response capable of being used in therapy to treat a cell proliferative disorder, comprising: a) preparing a peptidomimetic macrocycle by forming a cross-linker connecting two amino acid residues of a polypeptide to stabilize a secondary structure of the peptidomimetic macrocycle; b) testing the peptidomimetic macrocycle for a reduced antibody response in an in vivo assay as compared to a corresponding uncross-linked polypeptide; and c) selecting the tested peptidomimetic macrocycle as the peptidomimetic macrocycle that generates the reduced antibody response capable of being used in therapy to treat a cell proliferative disorder if the tested peptidomimetic macrocycle has the reduced antibody response; and wherein the peptidomimetic macrocycle that generates the reduced antibody response is of Formula (I): wherein: each A, C, D, and E, is independently a natural or non-natural amino acid; B is a natural or non-natural amino acid, amino acid analog, [—NH-L 3 -CO—], [—NH-L 3 -SO 2 —], or [—NH-L 3 -]; R R L is a macrocycle-forming linker of the formula -L L each R each K is independently O, S, SO, SO each R each R R R each of v and w is independently an integer from 1-1000; each of x, y, and z, is independently an integer from 0-10; u is an integer from 1-10; and n is an integer from 1-5.