US2004235102A1PendingUtilityA1

Novel ABCB9 transporter and uses thereof

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Assignee: ACTIVE PASS PHARMACEUTICALS INPriority: Nov 29, 1999Filed: Mar 17, 2004Published: Nov 25, 2004
Est. expiryNov 29, 2019(expired)· nominal 20-yr term from priority
Inventors:Victor LingMichelle PollardBruce ConnopFang Zhang
A01K 2217/05C07K 14/705C07K 2319/00
38
PatentIndex Score
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Cited by
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References
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Claims

Abstract

The invention provides isolated nucleic acid molecules, designated ABCB9 transporter nucleic acid molecules, which encode novel ABC transporter family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing ABCB9 transporter nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which an ABCB9 transporter gene has been introduced or disrupted. The invention still further provides isolated ABCB9 transporter proteins, fusion proteins, antigenic peptides, anti-ABCB9 transporter antibodies, and screening assays for ABCB9 transporter modulators. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . An isolated ABCB9 transporter polypeptide selected from the group consisting of 
 (a) an isolated ABCB9 transporter polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least 92% identical to a nucleotide sequence set forth in SEQ ID NO: 1 or 3, wherein the polypeptide retains an ABCB9 transporter activity;    (b) an isolated ABCB9 transporter polypeptide comprising an amino acid sequence at least 96% identical to the amino acid sequence set forth in SEQ ID NO: 2, wherein the ABCB9 polypeptide retains an ABCB9 transporter activity; and    (c) an isolated ABCB9 transporter polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.    
     
     
         2 . The ABCB9 transporter polypeptide according to  claim 1  comprising a heterologous amino acid sequence.  
     
     
         3 . The ABCB9 transporter polypeptide according to  claim 1  wherein the ABCB9 transporter activity is the ability to transport β-amyloid across a membrane.  
     
     
         4 . An isolated antibody or fragment thereof that specifically binds to an ABCB9 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.  
     
     
         5 . An isolated antibody or fragment thereof that specifically binds to a ABCB9 transporter polypeptide comprising an amino acid sequence at least 96% identical to the amino acid sequence set forth in SEQ ID NO:2, wherein the ABCB9 transporter polypeptide retains an ABCB9 transporter activity.  
     
     
         6 . An isolated antibody or fragment thereof that specifically binds to a ABCB9 transporter polypeptide encoded by a nucleic acid molecule that comprises a nucleotide sequence at least 92% identical to SEQ ID NO: 1 or 3, wherein the ABCB9 transporter polypeptide retains an ABCB9 transporter activity.  
     
     
         7 . A method for identifying a compound that binds to an ABCB9 transporter polypeptide comprising: 
 (a) contacting a test compound with an ABCB9 transporter polypeptide according to  claim 1  or a cell expressing the ABCB9 transporter polypeptide under conditions that permit interaction between the ABCB9 transporter polypeptide and the test compound; and    (b) determining the ability of the test compound to bind to the ABCB9 transporter polypeptide.    
     
     
         8 . The method of  claim 7 , wherein the binding of the test compound to the ABCB9 transporter polypeptide is detected by a method selected from the group consisting of 
 (a) detection of binding by direct detection of binding of the test compound to the ABCB9 transporter polypeptide;    (b) detection of binding using a competition binding assay; and    (c) detection of binding using an assay for ABCB9 transporter activity.    
     
     
         9 . The method according to  claim 7  wherein the compound is an antibody that binds specifically to the ABCB9 transporter polypeptide.  
     
     
         10 . The method according to  claim 7  wherein the compound is selected from the group consisting of a small molecule, a polypeptide, a peptide, and a peptidomimetic.  
     
     
         11 . A method for modulating the activity of an ABCB9 transporter polypeptide, comprising contacting an ABCB9 transporter polypeptide according to  claim 1  or a cell expressing the ABCB9 transporter polypeptide with a compound identified according to the method of  claim 7  that binds to the ABCB9 transporter polypeptide, thereby modulating the activity of the ABCB9 transporter polypeptide.  
     
     
         12 . A method for identifying a compound that modulates an activity of an ABCB9 transporter polypeptide comprising: 
 a) contacting a test compound with an ABCB9 transporter polypeptide according to  claim 1  or a cell that expresses the ABCB9 transporter polypeptide under conditions that permit interaction between the ABCB9 transporter polypeptide and the test compound; and    b) determining the level of the activity of the ABCB9 transporter polypeptide in the presence of the test compound relative to a level of the activity of the ABCB9 transporter polypeptide in the absence of the test compound, and thereby identifying a compound that modulates the activity of the ABCB9 transporter polypeptide.    
     
     
         13 . The method according to any one of claims  7 ,  11 , and  12  wherein the cell is a brain cell.  
     
     
         14 . The method according to any one of claims  7 ,  11 , and  12  wherein the ABCB9 transporter polypeptide is a membrane-bound form of the isolated ABCB9 transporter polypeptide.  
     
     
         15 . The method according to either  claim 11  or  claim 12  wherein the activity of the ABCB9 transporter is the ability to transport a substrate across a membrane.  
     
     
         16 . The method according to  claim 15  wherein the substrate is β-amyloid.  
     
     
         17 . The method according to either  claim 11  or  claim 12  wherein the activity is the ability to act as an ATP dependent pump.  
     
     
         18 . The method according to either  claim 11  or  claim 12  wherein the activity is the ability to bind ATP.  
     
     
         19 . The method according to  claim 15  wherein the ability to transport a substrate is the ability to catalyze ATP-dependent transport of the substrate.  
     
     
         20 . The method according to either  claim 11  or  claim 12  wherein the activity is decreased.  
     
     
         21 . A method for identifying a compound that modulates the ability of an ABCB9 transporter polypeptide to bind to a substrate comprising: 
 (a) contacting a test compound with an ABCB9 transporter polypeptide according to  claim 1  or a cell that expresses the ABCB9 transporter polypeptide, and an ABCB9 transporter polypeptide substrate under conditions that permit interaction between the substrate and the ABCB9 transporter polypeptide; and    (b) determining the level of binding of the ABCB9 transporter polypeptide to the substrate of the ABCB9 transporter polypeptide in the presence of the test compound relative to the level of binding of the ABCB9 transporter polypeptide to the substrate in the absence of the test compound, and thereby identifying a compound that modulates the ability of an ABCB9 transporter polypeptide to bind to a substrate.    
     
     
         22 . The method of  claim 21  wherein the ABCB9 transporter polypeptide is a membrane-bound form of an isolated ABCB9 polypeptide.  
     
     
         23 . The method of  claim 21  wherein the substrate is β-amyloid.  
     
     
         24 . A method for identifying a compound that modulates expression of an ABCB9 transporter polypeptide comprising: 
 (a) contacting a test compound with a cell that expresses an ABCB9 transporter polypeptide according to  claim 1;  and    (b) determining the level of expression of an mRNA that encodes the ABCB9 transporter polypeptide in the presence of the test compound relative to the level of expression of an mRNA that encodes the ABCB9 transporter polypeptide in the absence of the test compound, and therefrom identifying a compound that modulates expression of the ABCB9 transporter polypeptide.    
     
     
         25 . A method for identifying a compound that modulates expression of an ABCB9 transporter polypeptide comprising: 
 (a) contacting a test compound with a cell that expresses an ABCB9 transporter polypeptide according to  claim 1;  and    (b) determining the level of the ABCB9 transporter polypeptide expressed in the presence of the test compound relative to the level of the ABCB9 transporter polypeptide expressed in the absence of the test compound, and thereby identifying a compound that modulates expression of the ABCB9 transporter polypeptide.    
     
     
         26 . The method according to  claim 25  wherein the test compound is an antisense nucleic acid molecule comprising a nucleotide sequence that is complementary to the sequence set forth in SEQ ID NO: 1 or 3.  
     
     
         27 . The method according to any one of claims  21 ,  24 , and  25  wherein the cell is a brain cell.

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