US 7,462,354 B2
Method and system for optimizing minigenes and peptides encoded thereby
Alessandro Sette, La Jolla, Calif. (US); Robert Chesnut, Cardiff-by-the-Sea, Calif. (US); Brian D. Livingston, San Diego, Calif. (US); Denise Marie Baker, San Diego, Calif. (US); and Mark J. Newman, Carlsbad, Calif. (US)
Assigned to Pharmexa Inc., San Diego, Calif. (US)
Filed on Jun. 27, 2001, as Appl. No. 9/894,018.
Application 09/894018 is a continuation in part of application No. PCT/US00/35568, filed on Dec. 28, 2000.
Claims priority of provisional application 60/173390, filed on Dec. 28, 1999.
Claims priority of provisional application 60/284221, filed on Apr. 16, 2001.
Prior Publication US 2002/0119127 A1, Aug. 29, 2002
Int. Cl. A61K 39/00 (2006.01); C07K 14/00 (2006.01); G06F 19/00 (2006.01)
U.S. Cl. 424—184.1  [424/185.1; 424/192.1; 702/19; 702/20; 530/350] 20 Claims
 
1. A method for designing an optimized multi-epitope polypeptide comprising:
(i) selecting ten or more epitopes that contain human leukocyte antigen (HLA) allele-specific motifs or supermotifs, wherein said epitopes are HLA class I cytotoxic T lymphocyte (CTL) epitopes;
(ii) sorting said ten or more epitopes to minimize the number of junctional epitopes, and
(iii) incorporating said ten or more CTL epitopes into a multi-epitope polypeptide, wherein, during the incorporation step (iii):
at least one flanking or spacer amino acid residue is introduced at the C-terminus of one or more of said ten or more CTL epitopes; wherein said flanking or spacer amino acid residue is selected from the group consisting of lysine (K), arginine (R), asparagine (N), glutamine (Q), glycine (G), alanine (A), serine (S), cysteine (C), and threonine (T); and
wherein said flanking or spacer amino acid residue prevents the occurrence of a CTL junctional epitope.