Methods of using 18903 to treat pain and pain-related disorders

Abstract

The invention provides isolated nucleic acid molecules, designated COE-2 nucleic acid molecules, which encode novel carboxylesterase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing COE-2 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a COE-2 gene has been introduced or disrupted. The invention still further provides isolated COE-2 proteins, fusion proteins, antigenic peptides and anti-COE-2 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

1 . An isolated nucleic acid molecule selected from the group consisting of: 
 (a) a nucleic acid molecule comprising a nucleotide sequence which is at least 93% identical to the nucleotide sequence of SEQ ID NO:1 or 3, or a complement thereof;    (b) a nucleic acid molecule comprising at least 828 nucleotides of the nucleotide sequence of SEQ ID NO:1 or 3, or a complement thereof;    (c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least about 63% identical to the amino acid sequence of SEQ ID NO:2; and    (d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising at least 273 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2.    
     
     
         2 . An isolated nucleic acid molecule comprising the nucleic acid molecule of  claim 1 , and a nucleotide sequence encoding a heterologous polypeptide.  
     
     
         3 . A vector comprising the nucleic acid molecule of claims  1 .  
     
     
         4 . The vector of  claim 3 , which is an expression vector.  
     
     
         5 . A host cell transfected with the expression vector of  claim 4 .  
     
     
         6 . A method of producing a polypeptide comprising culturing the host cell of  claim 5  in an appropriate culture medium to, thereby, produce the polypeptide.  
     
     
         7 . An isolated polypeptide selected from the group consisting of: 
 a) a fragment of a polypeptide comprising at least 273 contiguous amino acids of SEQ ID NO:2;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to the complement of a nucleic acid molecule consisting of SEQ ID NO:1 or 3 under stringent conditions;    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 93% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1 or 3; and    d) a polypeptide comprising an amino acid sequence which is at least 63% identical to the amino acid sequence of SEQ ID NO:2.    
     
     
         8 . The polypeptide of  claim 7 , further comprising heterologous amino acid sequences.  
     
     
         9 . An antibody which selectively binds to a polypeptide of  claim 7 .  
     
     
         10 . A method for detecting the presence of a polypeptide of  claim 7  in a sample comprising: 
 a) contacting the sample with a compound which selectively binds to the polypeptide; and    b) determining whether the compound binds to the polypeptide in the sample to thereby detect the presence of a polypeptide of  claim 7  in the sample.    
     
     
         11 . The method of  claim 10 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         12 . A kit comprising a compound which selectively binds to a polypeptide of  claim 7  and instructions for use.  
     
     
         13 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample comprising: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and    b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample to thereby detect the presence of a nucleic acid molecule of  claim 1  in the sample.    
     
     
         14 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         15 . A method for identifying a compound which binds to a polypeptide of  claim 7  comprising: 
 a) contacting the polypeptide, or a cell expressing the polypeptide with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         16 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 7  comprising: 
 a) contacting a polypeptide of  claim 7  with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.    
     
     
         17 . A method of identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder comprising: 
 a) contacting a sample obtained from said subject comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of a nucleic acid molecule of  claim 1;  and    b) detecting the presence of a nucleic acid molecule in said sample that hybridizes to said probe, thereby identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder.    
     
     
         18 . A method of identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder comprising: 
 a) contacting a sample obtained from said subject comprising nucleic acid molecules with a first and a second amplification primer, said first primer comprising at least 25 contiguous nucleotides of SEQ ID NO:1 and said second primer comprising at least 25 contiguous nucleotides from the complement of SEQ ID NO:1;    b) incubating said sample under conditions that allow nucleic acid amplification; and    c) detecting the presence of a nucleic acid molecule in said sample that is amplified, thereby identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder.    
     
     
         19 . A method of identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder comprising: 
 a) contacting a sample obtained from said subject comprising polypeptides with a substance that binds a polypeptide of  claim 7;  and    b) detecting the presence of a polypeptide in said sample that binds to said substance, thereby identifying a subject having an inflammatory or pain disorder, or at risk for developing an inflammatory or pain disorder.    
     
     
         20 . A method for identifying a compound capable of treating an inflammatory or pain disorder characterized by aberrant activity of a polypeptide of  claim 7  or aberrant expression of a nucleic acid molecule encoding a polypeptide of  claim 7 , comprising assaying the ability of the compound to modulate nucleic acid expression of a nucleic acid molecule encoding a polypeptide of  claim 7  or activity of a polypeptide of  claim 7 , thereby identifying a compound capable of treating an inflammatory or pain disorder characterized by aberrant activity of a polypeptide of  claim 7  or aberrant expression of a nucleic acid molecule encoding a polypeptide of  claim 7.