US2002115155A1PendingUtilityA1

Human neuropeptide receptor

55
Priority: May 5, 1995Filed: Feb 20, 2002Published: Aug 22, 2002
Est. expiryMay 5, 2015(expired)· nominal 20-yr term from priority
Inventors:Daniel SoppetYi LiCraig Rosen
C12N 2799/026C12N 2799/027G01N 2333/726C07K 14/70571A61P 43/00G01N 2333/70571A61K 38/00C07K 16/286G01N 2500/10
55
PatentIndex Score
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Cited by
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References
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Claims

Abstract

Human neuropeptide receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the neuropeptide receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the neuropeptide receptor nucleic acid sequences and an altered level of the soluble form of the receptors.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide as set forth in SEQ ID NO:2;    (b) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (c) a polynucleotide fragment of the polynucleotide of (a) or (b).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 97128;    (b) a polynucleotide encoding the polypeptide expressed by the DNA contained in ATCC Deposit No. 97128;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a) or (b); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).    
     
     
         4 . A vector containing the DNA of  claim 2 .  
     
     
         5 . A host cell transformed or transfected with the vector of  claim 4 .  
     
     
         6 . A process for producing a polypeptide comprising: 
 expressing from the host cell of  claim 5  the polypeptide encoded by said DNA.    
     
     
         7 . A process for producing cells capable of expressing a polypeptide comprising transforming or transfecting the cells with the vector of  claim 4 .  
     
     
         8 . A receptor polypeptide comprising a member selected from the group consisting of: 
 (i) a polypeptide having the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof; and    (ii) a polypeptide encoded by the cDNA of ATCC Deposit No. 97128 and fragments, analogs and derivatives of said polypeptide.    
     
     
         9 . The polypeptide of  claim 8  wherein the polypeptide has the deduced amino acid sequence of SEQ ID NO:2.  
     
     
         10 . An antibody against the polypeptide of  claim 8 .  
     
     
         11 . A compound which activates the polypeptide of  claim 8 .  
     
     
         12 . A compound which inhibits activation the polypeptide of  claim 8 .  
     
     
         13 . A method for the treatment of a patient having need to activate a neuropeptide receptor comprising: 
 administering to the patient a therapeutically effective amount of the compound of  claim 11 .    
     
     
         14 . A method for the treatment of a patient having need to inhibit a neuropeptide receptor comprising: 
 administering to the patient a therapeutically effective amount of the compound of  claim 12 .    
     
     
         15 . The method of  claim 13  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said agonist and expressing said agonist in vivo.  
     
     
         16 . The method of  claim 14  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said antagonist and expressing said antagonist in vivo.  
     
     
         17 . A method for identifying compounds which bind to and inhibit or activate the polypeptide of  claim 8  comprising: 
 contacting a cell expressing on the surface thereof the receptor polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor polypeptide; and  
 determining whether the ligand binds to the polypeptide and detecting the presence or absence of a signal generated from the interaction of the compound with the polypeptide.  
 
     
     
         18 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of the polypeptide of  claim 8  comprising: 
 determining a mutation in the nucleic acid sequence encoding said polypeptide.  
 
     
     
         19 . The polypeptide of  claim 8  wherein the polypeptide is a soluble fragment of the polypeptide and is capable of binding a ligand for the receptor.  
     
     
         20 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 18  in a sample derived from a host.    
     
     
         21 . An isolated antibody or portion thereof that specifically binds to a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of amino acid residues 1-46 of SEQ ID NO:2;    (b) a protein whose sequence consists of amino acid residues 190-213 of SEQ ID NO:2;    (c) a protein whose-sequence comprises at least 30 contiguous amino acid residues of SEQ ID NO:2; and    (d) a protein whose sequence comprises at least 50 contiguous amino acid residues of SEQ ID NO:2, 
 wherein said antibody or portion thereof specifically binds to the amino acid sequence of SEQ ID NO:2.  
   
     
     
         22 . The antibody or portion thereof of  claim 21  that specifically binds protein (a).  
     
     
         23 . The antibody or portion thereof of  claim 21  that specifically binds protein (b).  
     
     
         24 . The antibody or portion thereof of  claim 21  that specifically binds protein (c).  
     
     
         25 . The antibody or portion thereof of  claim 21  that specifically binds protein (d).  
     
     
         26 . The antibody or portion thereof of  claim 21 , wherein said protein specifically bound by said antibody or portion thereof is glycosylated.  
     
     
         27 . The antibody or portion thereof of  claim 21  which is a monoclonal antibody.  
     
     
         28 . The antibody or portion thereof of  claim 21  which is a polyclonal antibody.  
     
     
         29 . The antibody or portion thereof of  claim 21  which is a chimeric antibody.  
     
     
         30 . The antibody or portion thereof of  claim 21  which is a humanized antibody.  
     
     
         31 . The antibody or portion thereof of  claim 21  which is a human antibody.  
     
     
         32 . The antibody or portion thereof of  claim 21  which is a single chain antibody.  
     
     
         33 . The antibody or portion thereof of  claim 21  which is a Fab fragment.  
     
     
         34 . The antibody or portion thereof of  claim 21  which is labeled.  
     
     
         35 . The antibody of  claim 34 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         36 . A composition comprising the antibody or portion thereof of  claim 21  and a carrier.  
     
     
         37 . The composition of  claim 36 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         38 . The composition of  claim 36 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         39 . The composition of  claim 36 , wherein the antibody or portion thereof is a humanized antibody.  
     
     
         40 . The composition of  claim 36 , wherein the antibody or portion thereof is a human antibody.  
     
     
         41 . The composition of  claim 36 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         42 . The composition of  claim 36 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         43 . The composition of  claim 36 , wherein the antibody or portion thereof is labeled.  
     
     
         44 . The composition of  claim 43 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         45 . An isolated cell that produces the antibody of  claim 21 .  
     
     
         46 . A hybridoma that produces the antibody of  claim 21 .  
     
     
         47 . A hybridoma that produces the antibody of  claim 27 .  
     
     
         48 . A method of detecting Human Neuropeptide Receptor protein in a biological sample comprising: 
 (a) contacting the biological sample with the antibody or portion thereof of claim  21 ; and    (b) detecting the Human Neuropeptide Receptor protein in the biological sample.    
     
     
         49 . The method of  claim 48 , wherein the antibody is a monoclonal antibody.  
     
     
         50 . The method of  claim 48 , wherein the antibody is a polyclonal antibody.  
     
     
         51 . The method of  claim 48 , wherein the antibody is a chimeric antibody.  
     
     
         52 . The method of  claim 48 , wherein the antibody is a humanized antibody.  
     
     
         53 . The method of  claim 48 , wherein the antibody is a human antibody.  
     
     
         54 . The method of  claim 48 , wherein the antibody is a single chain antibody.  
     
     
         55 . The method of  claim 48 , wherein the antibody is a labeled antibody.  
     
     
         56 . The method of  claim 55 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         57 . An isolated antibody or portion thereof produced by immunizing an animal with a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of amino acid residues 1-46 of SEQ ID NO:2;    (b) a protein whose sequence consists of amino acid residues 190-213 of SEQ ID NO:2;    (c) a protein whose sequence comprises at least 30 contiguous amino acid residues of SEQ ID NO:2; and    (d) a protein whose sequence comprises at least 50 contiguous amino acid residues of SEQ ID NO:2,    wherein said antibody or portion thereof specifically binds to the amino acid sequence of SEQ ID NO:2.    
     
     
         58 . The antibody or portion thereof of  claim 57  produced by immunizing an animal with protein (a).  
     
     
         59 . The antibody or portion thereof of  claim 57  produced by immunizing an animal with protein (b).  
     
     
         60 . The antibody or portion thereof of  claim 57  produced by immunizing an animal with protein (c).  
     
     
         61 . The antibody or portion thereof of  claim 57  produced by immunizing an animal with protein (d).  
     
     
         62 . An isolated antibody or portion thereof that specifically binds to a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of the amino acid sequence of the full length polypeptide encoded by the cDNA in ATCC Deposit No. 97128;    (b) a protein whose sequence consists of amino acid residues 1 to 402 of SEQ ID NO:2;    (c) a protein whose sequence consists of amino acid residues 1 to 369 of SEQ ID NO:4; and    (d) a protein whose sequence consists of amino acid residues 1 to 372 of SEQ ID NO:6.    
     
     
         63 . The antibody or portion thereof of  claim 62  that specifically binds protein (a).  
     
     
         64 . The antibody or portion thereof of  claim 62  that specifically binds protein (b).  
     
     
         65 . The antibody or portion thereof of  claim 62  that specifically binds protein (c).  
     
     
         66 . The antibody or portion thereof of  claim 62  that specifically binds protein (d).  
     
     
         67 . The antibody or portion thereof of  claim 62  wherein said protein specifically bound by said antibody or portion thereof is glycosylated.  
     
     
         68 . The antibody or portion thereof of  claim 62  which is a monoclonal antibody.  
     
     
         69 . The antibody or portion thereof of  claim 62  which is a polyclonal antibody.  
     
     
         70 . The antibody or portion thereof of  claim 62  which is a chimeric antibody  
     
     
         71 . The antibody or portion thereof of  claim 62  which is a humanized antibody.  
     
     
         72 . The antibody or portion thereof of  claim 62  which is a human antibody.  
     
     
         73 . The antibody or portion thereof of  claim 62  which is a single chain antibody.  
     
     
         74 . The antibody or portion thereof of  claim 62  which is a Fab fragment.  
     
     
         75 . The antibody or portion thereof of  claim 62  which is labeled.  
     
     
         76 . The antibody of  claim 75 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         77 . A composition comprising the antibody or portion thereof of  claim 62  and a carrier.  
     
     
         78 . The composition of  claim 77 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         79 . The composition of  claim 77 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         80 . The composition of  claim 77 , wherein the antibody or portion thereof is a humanized antibody.  
     
     
         81 . The composition of  claim 77 , wherein the antibody or portion thereof is a human antibody.  
     
     
         82 . The composition of  claim 77 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         83 . The composition of  claim 77 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         84 . The composition of  claim 77 , wherein the antibody or portion thereof is labeled.  
     
     
         85 . The composition of  claim 84 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         86 . An isolated cell that produces the antibody of  claim 62 .  
     
     
         87 . A hybridoma that produces the antibody of  claim 62 .  
     
     
         88 . A hybridoma that produces the antibody of  claim 68 .  
     
     
         89 . A method of detecting Human Neuropeptide Receptor protein in a biological sample comprising: 
 (a) contacting the biological sample with the antibody or portion thereof of claim  62 ; and    (b) detecting the Human Neuropeptide Receptor protein in the biological sample.    
     
     
         90 . The method of  claim 89 , wherein the antibody is a monoclonal antibody.  
     
     
         91 . The method of  claim 89 , wherein the antibody is a polyclonal antibody.  
     
     
         92 . The method of  claim 89 , wherein the antibody is a chimeric antibody.  
     
     
         93 . The method of  claim 89 , wherein the antibody is a humanized antibody.  
     
     
         94 . The method of  claim 89 , wherein the antibody is a human antibody.  
     
     
         95 . The method of  claim 89 , wherein the antibody is a single chain antibody.  
     
     
         96 . The method of  claim 89 , wherein the antibody is a labeled antibody.  
     
     
         97 . The method of  claim 96 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         98 . An isolated antibody or portion thereof produced by immunizing an animal with a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of the amino acid sequence of the full length polypeptide encoded by the cDNA in ATCC Deposit No. 97128;    (b) a protein whose sequence consists of amino acid residues 1 to 402 of SEQ ID NO:2;    (c) a protein whose sequence consists of amino acid residues 1 to 369 of SEQ ID NO:4; and    (d) a protein whose sequence consists of amino acid residues 1 to 372 of SEQ ID NO:6.    
     
     
         99 . The antibody or portion thereof of  claim 98  produced by immunizing an animal with protein (a).  
     
     
         100 . The antibody or portion thereof of  claim 98  produced by immunizing an animal with protein (b).  
     
     
         101 . The antibody or portion thereof of  claim 98  produced by immunizing an animal with protein (c).  
     
     
         102 . The antibody or portion thereof of  claim 98  produced by immunizing an animal with protein (d).  
     
     
         103 . An isolated antibody or portion thereof that specifically binds to a protein expressed on the surface of a cell, wherein said protein is selected from the group consisting of: 
 (a) a protein whose sequence consists of the amino acid sequence of the full length polypeptide encoded by the cDNA in ATCC Deposit No. 97128;    (b) a protein whose sequence consists of amino acid residues 1 to 402 of SEQ ID NO:2;    (c) a protein whose sequence consists of amino acid residues 1 to 369 of SEQ ID NO:4; and    (d) a protein whose sequence consists of amino acid residues 1 to 372 of SEQ ID NO:6.    
     
     
         104 . The antibody or portion thereof of  claim 103  that specifically binds protein (a).  
     
     
         105 . The antibody or portion thereof of  claim 103  that specifically binds protein (b).  
     
     
         106 . The antibody or portion thereof of  claim 103  that specifically binds protein (c).  
     
     
         107 . The antibody or portion thereof of  claim 103  that specifically binds protein (d).  
     
     
         108 . The antibody or portion thereof of  claim 103  which is a monoclonal antibody.  
     
     
         109 . The antibody or portion thereof of  claim 103  which is a chimeric antibody.  
     
     
         110 . The antibody or portion thereof of  claim 103  which is a humanized antibody.  
     
     
         111 . The antibody or portion thereof of  claim 103  which is a human antibody.  
     
     
         112 . The antibody or portion thereof of  claim 103  which is a single chain antibody.  
     
     
         113 . The antibody or portion thereof of  claim 103  which is a Fab fragment.  
     
     
         114 . The antibody or portion thereof of  claim 103  which is labeled.  
     
     
         115 . The antibody of  claim 114 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         116 . A composition comprising the antibody or portion thereof of  claim 103  and a carrier.  
     
     
         117 . The composition of  claim 116 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         118 . The composition of  claim 116 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         119 . The composition of  claim 116 , wherein the antibody or portion thereof is a humanized antibody.  
     
     
         120 . The composition of  claim 116 , wherein the antibody or portion thereof is a human antibody.  
     
     
         121 . The composition of  claim 116 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         122 . The composition of  claim 116 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         123 . The composition of  claim 116 , wherein the antibody or portion thereof is labeled.  
     
     
         124 . The composition of  claim 116 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.    
     
     
         125 . An isolated cell that produces the antibody of  claim 103 .  
     
     
         126 . A hybridoma that produces the antibody of  claim 103 .  
     
     
         127 . A hybridoma that produces the antibody of  claim 108 .  
     
     
         128 . A method of detecting Human Neuropeptide Receptor protein in a biological sample comprising: 
 (a) contacting the biological sample with the antibody or portion thereof of claim  103 ; and    (b) detecting the Human Neuropeptide Receptor protein in the biological sample.    
     
     
         129 . The method of  claim 128 , wherein the antibody is a monoclonal antibody.  
     
     
         130 . The method of  claim 128 , wherein the antibody is a polyclonal antibody.  
     
     
         131 . The method of  claim 128 , wherein the antibody is a chimeric antibody.  
     
     
         132 . The method of  claim 128 , wherein the antibody is a humanized antibody.  
     
     
         133 . The method of  claim 128 , wherein the antibody is a human antibody.  
     
     
         134 . The method of  claim 128 , wherein the antibody is a single chain antibody.  
     
     
         135 . The method of  claim 128 , wherein the antibody is a labeled antibody.  
     
     
         136 . The method of  claim 135 , wherein the label is selected from the group consisting of: 
 (a) an enzyme label;    (b) a radioisotope; and    (c) a fluorescent label.

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