US 9,526,786 B2 · Thermostabilization of proteins

Thermostabilization of proteins

AssigneesThe Trustee of Columbia University in the City of New York, The Regents of the University of Michigan

InventorsDonald W. Landry, James H. Woods, Roger K. Sunahara, Diwahar L. Narasimhan, Joanne MacDonald, Milan N. Stojanovic, John J. Tesmer, Remy L. Brim

Life of this patent

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Abstract

Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.

Claims17

Dependent claims

A method of treating a cocaine-induced condition, the method comprising:

administering to a mammalian subject in need thereof an effective amount of a composition comprising
a cocaine esterase (CocE) polypeptide comprising an amino acid sequence at least 85% identical to SEQ ID NO:
1 having esterase activity;
and
at least one thermostabilization compound selected from
wherein,
the CocE in the presence of the compound is more thermostable than the CocE in the absence of the compound and
the subject is diagnosed with, or at risk for, a cocaine-induced condition selected from the group consisting of cocaine overdose, cocaine toxicity, cocaine addiction, or cocaine dependence.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application

14/166,619Filed 28 Jan 2014 · continuation

Priority

10 Jul 2007

Published

US 2014/0348813 A127 Nov 2014

Granted

27 Dec 2016

Term ends

Not estimatedThe source records don’t support an estimate.

Classification23 codes

A61K 38/465
Hydrolases: acting on ester bonds , e.g. lipases, ribonucleases
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 31/505
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrimidines; Hydrogenated…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Application60/948,976Us provisional application · filed 10 Jul 2007

Application60/987,661Us provisional application · filed 13 Nov 2007

PCT/US2008/069659Parent of this continuation · filed 10 Jul 2008

US 2014/0348813 A1Pre-grant publication · published 27 Nov 2014

Application12/667,895Parent of this continuation

US 8,637,009 B2Parent of this continuation

US 2011/0142816 A1Published application

US 9,526,786 B2This patent

From the US filing history. Foreign family members aren’t listed.