Composition and method for treating lupus nephritis

Abstract

The present invention provides novel isolated BFLP1698 polynucleotides and polypeptides encoded by the BFLP1698 polynucleotides. Also provided are the antibodies that immunospecifically bind to a BFLP1698 polypeptide or any derivative (including fusion derivative), variant, mutant or fragment of the BFLP1698 polypeptide, polynucleotide or antibody. The invention additionally provides methods in which the BFLP1698 polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, as well as to other uses.

1 . An isolated nucleic acid molecule encoding a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule encodes a polypeptide that binds rapamycin.  
     
     
         3 . The isolated nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule encodes a polypeptide at least 98% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein said molecule hybridizes under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule comprising nucleotides 1-3486 of SEQ ID NO:1.  
     
     
         5 . The isolated nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         6 . The isolated nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises nuclebtides 1-3486 of SEQ ID NO:1.  
     
     
         7 . A vector comprising the nucleic acid molecule of  claim 1 .  
     
     
         8 . A cell including the vector of  claim 7 .  
     
     
         9 . A substantially purified polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         10 . The polypeptide of  claim 9 , wherein said polypeptide binds rapamycin.  
     
     
         11 . The polypeptide of  claim 9 , wherein the amino acid sequence of said polypeptide is at least 98% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         12 . The polypeptide of  claim 9 , wherein the amino acid sequence of said polypeptide is at least 99% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         13 . The polypeptide of  claim 9 , wherein the amino acid sequence of said polypeptide comprises the amino acid sequence of SEQ ID NO:2.  
     
     
         14 . The polypeptide of  claim 9 , wherein the amino acid sequence of said polypeptide consists of the amino acid sequence of SEQ ID NO:2.  
     
     
         15 . A fusion polypeptide comprising the polypeptide of  claim 9  operably linked to a non-BFLP1698 polypeptide.  
     
     
         16 . The fusion polypeptide of  claim 9 , wherein said non-BFLP1698 polypeptide comprises at least one member selected from the group consisting of an Fc region of an immunoglobulin molecules or a FLAG epitope, a HIS tag, and a MYC tag.  
     
     
         17 . A polypeptide comprising a rapamycin-binding domain of the amino acid sequence of SEQ ID NO:2.  
     
     
         18 . A polypeptide at least 993 amino acids in length comprising at least five contiguous amino acids of SEQ ID NO:2, provided that said polypeptide comprises an amino acid sequence other than SEO ID NO:21.  
     
     
         19 . The polypeptide of  claim 18 , wherein said polypeptide comprises a rapamycin-binding domain.  
     
     
         20 . A polypeptide comprising at least five contiguous amino acids of SEQ ID NO:15.  
     
     
         21 . The polypeptide of  claim 20 , wherein said polypeptide comprises a rapamycin-binding domain.  
     
     
         22 . The polypeptide of  claim 20 , wherein said polypeptide is at least 50 amino acids in length.  
     
     
         23 . The polypeptide of  claim 20 , wherein said polypeptide is at least 100 amino acids in length.  
     
     
         24 . The polypeptide of  claim 20 , wherein said polypeptide is at least 220 amino acids in length.  
     
     
         25 . A pharmaceutical composition comprising the polypeptide of  claim 17  and a pharmaceutically acceptable carrier.  
     
     
         26 . A fusion polypeptide comprising a rapamycin-binding domain of a BFLP1698 polypeptide operably linked to a non-BFLP1698 polypeptide.  
     
     
         27 . The fusion polypeptide of  claim 26 , wherein said non-BFLP1698 polypeptide comprises at least one member selected from the group consisting of an Fc region of an immunoglobulin molecules or a FLAG epitope, a HIS tag, and a MYC tag.  
     
     
         28 . A pharmaceutical composition comprising the fusion polypeptide of  claim 26  and a pharmaceutically acceptable carrier.  
     
     
         29 . An antibody that binds selectively to the polypeptide of  claim 9 .  
     
     
         30 . The antibody of  claim 29 , wherein said antibody inhibits binding of a BFLP1698 polypeptide to rapamycin.  
     
     
         31 . The antibody of  claim 29 , wherein said antibody is a polyclonal antibody.  
     
     
         32 . The antibody of  claim 29 , wherein said antibody is a monoclonal antibody.  
     
     
         33 . The monoclonal antibody of  claim 32 , wherein said monoclonal antibody is selected from the group consisting of a murine monoclonal antibody, and a humanized monoclonal antibody.  
     
     
         34 . A method of producing a BFLP1698 polypeptide, said method comprising culturing a cell including the nucleic acid molecule of  claim 1  under conditions allowing for expression of a BFLP1698 polypeptide encoded by said nucleic acid molecule.  
     
     
         35 . A method of detecting the presence of a BFLP1698 nucleic acid molecule in a biological sample, the method comprising: 
 contacting the sample with a nucleic acid probe that binds specifically to a BFLP1698 nucleic acid; and    identifying the bound probe, if present, thereby detecting the presence of BFLP1698 nucleic acid molecule in said sample.    
     
     
         36 . A method of detecting the presence of a BFLP1698 polypeptide in a sample, the method comprising: 
 contacting the sample with a compound that selectively binds to said polypeptide under conditions allowing for formation of a complex between said polypeptide and said compound; and    detecting said complex, if present, thereby identifying said polypeptide in said sample.    
     
     
         37 . The method of  claim 36 , wherein said compound is rapamycin.  
     
     
         38 . The method of  claim 36 , wherein said compound is an anti-BFLP1698 antibody.  
     
     
         39 . A method for determining the presence of or predisposition to lupus nephritis in a subject, the method comprising: 
 a) measuring the amount of a BFLP1698 nucleic acid molecule in a sample from said subject; and    b) comparing the amount of said nucleic acid in step to the amount of the nucleic acid present in a control sample from a subject without lupus nephritis,    wherein an increase in the level of said BLP 1698 nucleic acid in step (a) as compared to the level of the nucleic acid in the control sample indicates the presence of or predisposition to lupus nephritis in said subject.    
     
     
         40 . The method of  claim 39 , wherein said subject is a human.  
     
     
         41 . A method for determining the presence of or predisposition to lupus nephritis in a subject, the method comprising: 
 a) measuring the amount of a BFLP1698 polypeptide in a sample from said subject; and    b) comparing the amount of said polypeptide to the amount of the nucleic acid present in a control sample from a subject without lupus nephritis,    wherein an increase in the level of said BFLP1698 polypeptide as compared to the level of the polypeptide in the control sample indicates the presence of or predisposition to lupus nephritis in said subject.    
     
     
         42 . The method of  claim 41 , wherein said subject is a human.  
     
     
         43 . A method for screening for a therapeutic agent for treating an autoimmune disorder, the method comprising: 
 contacting a test compound with a BFLP1698 polypeptide; and    determining if said test compound binds to said BFLP1698 polypeptide, wherein binding of said test compound to said polypeptide indicates the test compound is a therapeutic agent for an autoimmune disorder.    
     
     
         44 . The method of  claim 43 , wherein said immune disorder is an autoimmune disorder.  
     
     
         45 . The method of  claim 44 , wherein said autoimmune disorder is lupus.  
     
     
         46 . The method of  claim 44 , wherein said autoimmune disorder is lupus lephritis.  
     
     
         47 . The method of  claim 43 , wherein said BFLP1698 is provided in a cell-free extract.  
     
     
         48 . The method of  claim 43 , wherein said BFLP1069 is provided in a cell.  
     
     
         49 . A method of treating lupus nephritis in a subject, the method comprising administering to said subject a therapeutically effective amount of an agent that inhibits activity of a BFLP1698 polypeptide in said subject.  
     
     
         50 . The method of  claim 49 , wherein said subject is a human.  
     
     
         51 . The method of  claim 49 , wherein said agent is an anti-BFLP1698 antibody.  
     
     
         52 . A pharmaceutical composition comprising an agent that inhibits activity of a BFLP1698 polypeptide in a subject and a pharmaceutically acceptable carrier.  
     
     
         53 . The pharmaceutical composition of  claim 52 , wherein said agent is an anti-BFLP1698 antibody.