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Anti-Cocaine Compositions and Treatment Donald Landry University of Kentucky UKnowledge Pharmaceutical Sciences Faculty Patents Pharmaceutical Sciences 12-1-2015 Anti-Cocaine Compositions and Treatment Donald Landry Chang-Guo Zhan University of Kentucky, [email protected] James H. Woods Roger Sunahara Diwahar L. Narasimhan See next page for additional authors Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/ps_patents Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Landry, Donald; Zhan, Chang-Guo; Woods, James H.; Sunahara, Roger; Narasimhan, Diwahar L.; MacDonald, Joanne; Yang, Victor; Ko, Mei-Chuan Holden; Deng, Shi-Xian; Tesmer, John J.; Lee, Tien-Yi; Kwon, Young Min; and Gao, Daquan, "Anti-Cocaine Compositions and Treatment" (2015). Pharmaceutical Sciences Faculty Patents. 60. https://uknowledge.uky.edu/ps_patents/60 This Patent is brought to you for free and open access by the Pharmaceutical Sciences at UKnowledge. It has been accepted for inclusion in Pharmaceutical Sciences Faculty Patents by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Authors Donald Landry, Chang-Guo Zhan, James H. Woods, Roger Sunahara, Diwahar L. Narasimhan, Joanne MacDonald, Victor Yang, Mei-Chuan Holden Ko, Shi-Xian Deng, John J. Tesmer, Tien-Yi Lee, Young Min Kwon, and Daquan Gao This patent is available at UKnowledge: https://uknowledge.uky.edu/ps_patents/60 111111 1111111111111111111111111111111111111111111111111111111111111 US009200265B2 c12) United States Patent (10) Patent No.: US 9,200,265 B2 Landry et al. (45) Date of Patent: *Dec. 1, 2015 (54) ANTI-COCAINE COMPOSITIONS AND C07K 1100 (2006.01) TREATMENT A61K 38/00 (2006.01) (52) U.S. Cl. (71) Applicants: The Trustees of Columbia University CPC ........... C12N9/18 (2013.01); C12Y 301101084 in the City of New York, New York, NY (2013.01);A61K 38/00 (2013.01) (US); The Regents of the University of (58) Field of Classification Search Michigan, Ann Arbor, MI (US); The CPC ... A61K 38/00; C12Y 301/01084; C12N 9/18 University of Kentucky Research Foundation, Lexington, KY (US) USPC ................ 424/94.6, 94.1; 435/197, 196, 195, 435/69.1, 91.1; 536/23.1, 23.2; 530/350 (72) Inventors: Donald Landry, New York, NY (US); See application file for complete search history. Chang-Guo Zhan, Lexington, KY (US); James H. Woods, Ann Arbor, MI (US); (56) References Cited Roger Sunahara, Ann Arbor, MI (US); U.S. PATENT DOCUMENTS Diwahar L. Narasimhan, Ann Arbor, MI (US); Joanne MacDonald, New 5,462,868 A 10/1995 Britt et al. York, NY (US); Victor Yang, Ann Arbor, 5,730,985 A 3/1998 Barber et a!. MI (US); Mei-Chuan Holden Ko, Ann 5,977,314 A 1111999 Landry et al. Arbor, MI (US); Shi-Xian Deng, White 8,318,156 B2 * 1112012 Landry et al ................. 424/94.6 2002/0048271 A1 4/2002 Rastinejad et a!. Plains, NY (US); John J. Tesmer, Ann 201110142816 A1 6/2011 Landry et al. Arbor, MI (US); Tien-Yi Lee, Ann Arbor, MI (US); Young Min Kwon, Ann FOREIGN PATENT DOCUMENTS Arbor, MI (US); Daquan Gao, Louisville, KY (US) GB 2257972 111993 wo W02008008358 1/2008 (73) Assignees: The Trustees of Columbia University OTHER PUBLICATIONS in the City of New York, New York, NY (US); The Regents of the University of Sen, et a!., Developments in Directed Evolution for Improving Michigan, Ann Arbor, MI (US); Enzyme Functions. Appl. Biochem. Biotechnol., 2007, vol. 143: pp. University of Kentucky Research 212-223. Foundation, Lexington, KY (US) Sun, et a!., Cocaine Metabolism Accelerated by a Re-Engineered Human Butyrylcholinesterase, J. Pharmacol. Exp. Ther., 2002, pp. ( *) Notice: Subject to any disclaimer, the term of this 710-716, vol. 302, No.2. patent is extended or adjusted under 35 Sun, et al., Re-Engineering Butyrylcholinesterase as a Cocaine U.S.C. 154(b) by 173 days. Hydrolase, Molecular Pharmacology, 2002., pp. 220-224, vol. 62, No.2. This patent is subject to a terminal dis­ Turner, eta!., Biochemical Characterization and Structural Analysis claimer. of a Highly Proficient Cocaine Esterase, Biochemistry, 2002, pp. 12297-12307, vol. 41. (21) Appl. No.: 13/676,324 Uchiyama, eta!., Directed Evolution to Improve the Thermo stability of Prolyl Endopeptidase, Journal of Biochemistry, 2000, pp. 441- (22) Filed: Nov. 14, 2012 447,vol. 128, Tokyo. Veronese and Harris, Introduction and Overview of Peptide and (65) Prior Publication Data Protein Pegylation, Advanced Drug Delivery Reviews, 2002, pp. 453-456, vol. 54. US 2013/0136728 Al May 30,2013 (Continued) Related U.S. Application Data Primary Examiner- Ganapathirama Raghu (74) Attorney, Agent, or Firm- Dentons US LLP (63) Continuation of application No. 12/373,510, filed as application No. PCTIUS2007/015762 on Jul. 10, (57) ABSTRACT 2007, now Pat. No. 8,318,156. Embodiments of the invention disclosed herein generally (60) Provisional application No. 60/819,569, filed on Jul. relate to anti-cocaine therapeutics. Specifically, some 10, 2006. embodiments of the invention relate to highly efficient, ther­ mostable, and long-lasting cocaine esterase (CocE) mutants (51) Int. Cl. that can protect against the toxic and reinforcing effects of A61K 38146 (2006.01) cocaine in subjects. Provided herein are mutant CocE A61K 38143 (2006.01) polypeptides displaying thermostable esterase activity. Also C12N9/18 (2006.01) provided are methods of treating cocaine-induced conditions C12N9/16 (2006.01) in a subject in need via administration of mutant CocE as well C12N9/14 (2006.01) as methods for high-throughput screening of candidate C12P 21106 (2006.01) esterase polypeptides. C12P 19134 (2006.01) C07H 21104 (2006.01) 19 Claims, 36 Drawing Sheets US 9,200,265 B2 Page 2 (56) References Cited Carroll, et a!., Pharmacotherapies for treatment of Cocaine Abuse: Preclinical Aspects J. Med. Chern., Jul. 29, 1999, pp. 2721-2736, vol. OTHER PUBLICATIONS 42, No. 15. Chica, et a!., Semi-rational Approaches to Engineering Enzyme Whisstock, et a!., Prediction of Protein Function from Protein Activity: Combining the Benefits of Directed Evolution and Rational Sequence, Q. Rev. Biophysics., 2003. vol. 36 (3): pp. 307-340. Design, Curr. Opi, Biotechnol., 2005, vol. 16: pp. 378-384. White, eta!., Improved Thermo stability of the North American Fire­ Cooper, eta!., Inhibition of Cocaine Toxicity by Cocaine Esterase in fly Luciferase: Saturation Mutagenesis at Position 354, Biochemistry the Rat. FASEB Journal, 2005, p. A512, abstract No. 311.6. Journal, 1996, pp. 343-350, vol. 319. Cooper, eta!., Rapid and Robust Protection Against Cocaine-Induced Wishart, eta!., A Single Mutation Converts a Novel Phosphotyrosine Lethality in Rats by the Bacterial Cocaine Esterase, Mol. Pharmacol, Binding Domain into a Dual-Specificity Phosphatase. J. Bioi. Chern., pp. 1885-1891, vol. 70, No.6, 2006. 1995, vol. 270(45): pp. 26762-26785. Deng, eta!., Anticocaine Catalytic Antibiodies, J. Immunol. Meth­ Witkowski, et al., Conversion of B-ketoacyl Synthase to a Malonyl ods, 2002, pp. 299-301, vol. 269. Decarboxylase by Replacement of the Active Cysteine with Devos, eta!., Practical Limits ofF unction Prediction. Proteins: Struc­ Glutamine. Biochemistry, 1999, vol. 38: pp. 11643-11650. ture, Function, and Genetics. 2000, vol. 41: pp. 98-107. Xie, eta!., An Improved Cocaine Hydrolase: The A328Y Mutant of Duysen, et a!., Wild-type and A328W Mutant Human Human Butyrylcholinesterase is 4-Fold More Efficient, Mol. Butyrylcholinesterase Tetramers Expressed in Chinese Hamster Pharmacol., 1999, pp. 83-91, vol. 55. Obary Cells Have a 16-Hour Half-Life in the Circulation and Protect Zhan, et a!., Fundamental Reaction Mechanism for Cocaine Mice from Cocaine Toxicity, J. Pharrnacol. Expt. Ther., 2002, pp. Hydrolysis in Human Butyrylcholinesterase, Journal of the Ameri­ 751-758, vol. 302, No.2. can Chemical Society, 2003, pp. 2462-2474, vol. 125. Flores and Ellington, Increasing the Thermal Stability of an Supplemental European Search Report dated Jan. 13, 2010 Issued in Oligomeric Protein, Beta-Glucoronidase, Journal of Molecular Biol­ the related European Application No. EP07810316.5 filed Jul. 10, ogy, 2002, pp. 325-337, vol. 315. 2007, 8 pages. Gao and Brimijoin, An Engineered Cocaine Hydrolase Blunts and Cooper, et a!., Cocaine Esterase Blocks Cocaine-Induced Seizures Reverse Cardiovascular Responses to Cocaine in Rates. J. and Cardiovascular Effects in the Rat, FASEB Journal, 2005, p. Pharmacol. Exp. Ther., 2004, pp. 1046-1052, vol. 310, No.3. A512, abstract311.7. Gao, eta!., Gene Transfer of Cocaine Hydrolase Suppresses Cardio­ Chinese Office Action dated Jun. 1, 2011 in related Application No. vascular Responses to Cocaine in Rats, Molecular Pharmacology, 200780033496, includes English translation, 10 pages. 2005, pp. 204-211, vol. 67, No. 1. 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