Claims for Patent: 8,586,340

Summary for Patent: 8,586,340

Title:	Selective posttranslational modification of phage-displayed polypeptides
Abstract:	The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2] cycloaddition reactions and Staudinger modifications.
Inventor(s):	Tsao; Meng-Lin (San Diego, CA), Tian; Feng (San Diego, CA), Schultz; Peter (La Jolla, CA)
Assignee:	The Scripps Research Institute (La Jolla, CA)
Application Number:	11/580,223
Patent Claims:	1. A purified or isolated phage comprising a phage-displayed polypeptide, wherein the polypeptide comprises an unnatural amino acid that comprises: ##STR00004## and wherein the purified or isolated phage is viable; ##STR00005## and wherein the purified or isolated phage is viable; or, ##STR00006## 2. A purified or isolated phage comprising a polypeptide, wherein the polypeptide comprises an unnatural amino acid residue selected from the group consisting of: a) an unnatural amino acid residue comprising an amide moiety and a phosphine oxide moiety, wherein the phage is viable, and b) an unnatural amino acid residue comprising a triazole linkage. 3. A purified or isolated post-translationally modified phage produced by a process comprising the steps of: a) providing a phage comprising a polypeptide, wherein the polypeptide comprises a p-propargyloxyphenylalanine or a p-azidophenylalanine; b) reacting the p-propargyloxyphenylalanine or p-azidophenylalanine acid via Staudinger ligation or [3+2] cycloaddition; and c) producing the purified or isolated post-translationally modified phage by covalent modification of the p-propargyloxyphenylalanine or p-azidophenylalanine acid; wherein the purified or isolated post-translationally modified phage is viable when the p-propargyloxyphenylalanine or p-azidophenylalanine acid is reacted via Staudinger ligation. 4. The phage of claim 1, 2, or 3, wherein said phage is a filamentous phage. 5. The phage of claim 1, 2, or 3, wherein said phage is a recombinant M13 phage. 6. The phage of claim 1, 2, or 3, wherein said polypeptide is a phage-displayed fusion polypeptide. 7. The phage of claim 6, wherein said fusion polypeptide comprises a peptide linker that comprises an amino acid sequence that can be recognized and cleaved by a protease. 8. The phage of claim 7, wherein said protease is selected from Factor Xa, Factor XIa, Kallikvein, thrombin, Factor XIIa, collagenase and enterokinase. 9. The phage of claim 3, wherein said aryl-azide unnatural amino acid residue is a para-azido-L-phenylalanine residue. 10. The phage of claim 1, 2, or 3, wherein said phage or said polypeptide is immobilized to a solid support.

Details for Patent 8,586,340

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2025-10-12