Patched-2 antibodies

Abstract

The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, antibodies, vectors and host cells expressing, immunoadhesins, agonists and antagonists to patched-2.

What is claimed is:  
     
         1 . Isolated nucleic acid comprising DNA having at least a 95% sequence identity to (a) a DNA molecule encoding a patched-2 polypeptide comprising the sequence of amino acids 1 to about 1203 of FIG. 1 (SEQ ID NO:2), and encoding a polypeptide having patched-2 biological activity.  
     
     
         2 . An isolated nucleic acid comprising DNA having at least a 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 209778 designation:, or (b) the complement of the DNA molecule of (a).  
     
     
         3 . The isolated nucleic acid of  claim 5  comprising human patched-2 encoding sequence of the cDNA in ATCC deposit No. 209778 designation:, or a sequence which hybridizes thereto under stringent conditions.  
     
     
         4 . A vector comprising the nucleic acid of  claim 1 .  
     
     
         5 . The vector of  claim 4  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         6 . A host cell transformed with the vector of  claim 4 .  
     
     
         7 . The host cell of  claim 6  which is mammalian.  
     
     
         8 . The host cell of  claim 7  wherein said cell is a CHO cell.  
     
     
         9 . The host cell of  claim 6  which is prokaryotic.  
     
     
         10 . The host cell of  claim 9  wherein said cell is an  E. coli.    
     
     
         11 . The host cell of  claim 7  wherein said cell is a yeast cell.  
     
     
         12 . The host cell of  claim 11  which is  Saccharomyces cerevisiae.    
     
     
         13 . A process for producing patched-2 polypeptides comprising culturing the host cell of  claim 9  under conditions suitable for expression of vertebrate patched-2 and recovering patched-2 from the cell culture.  
     
     
         14 . Isolated native sequence human patched-2 polypeptide comprising amino acid residues 1 to 1203 of FIG. 1 (SEQ ID NO:2).  
     
     
         15 . Isolated native sequence human patched-2 polypeptide encoded by the nucleotide deposited under accession number ATCC 209778 Designation having patched-2 biological activity.  
     
     
         16 . A chimeric molecule comprising vertebrate patched-2 polypeptide patched-2 to a heterologous amino acid sequence.  
     
     
         17 . The chimeric molecule of  claim 16  wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         18 . The chimeric molecule of  claim 17  wherein said heterologous amino acid sequence is a constant region of an immunoglobulin.  
     
     
         19 . An antagonist of patched-2 which blocks, prevents, inhibits and/or neutralizes the Dhh function in the Dhh signaling pathway.  
     
     
         20 . The antagonist of  claim 19  which is a small bioorganic molecule.  
     
     
         21 . The antagonist of  claim 19  which is an antisense nucleotide.  
     
     
         22 . An agonist of patched-2 with stimulates or enhances the normal functioning of patched-2 in the Dhh signaling pathway.  
     
     
         23 . The agonist of  claim 22  which prevents Smo (SEQ ID NO:17) inactivation of Ptch-2 (SEQ ID NO:2).  
     
     
         24 . The agonist of  claim 22  which is a small bioorganic molecule.  
     
     
         25 . The agonist of  claim 24  which is a small bioorganic molecule.  
     
     
         26 . A method of screening for antagonists or agonists of patched-2 biological activity comprising: 
 (a) exposing patched-2 expressing target cells in culture to a candidate compound and Dhh; and    (b) analyzing cells for binding of Dhh to patched-2; or    (c) scoring phenotypic or functional changes in the treated cells;    and comparing the results to control cells which were not exposed to the candidate compound.    
     
     
         27 . A method of screening for antagonist or agonist molecule of patched-2 biological activity comprising: 
 (a) exposing a patched-2 ligand and a compound having patched-2 biological activity to a candidate antagonist or agonist; and    (b) analyzing the substrate for binding of the ligand to the compound; and    comparing the results to control reactions which were not exposed to the candidate molecule.    
     
     
         28 . A method of diagnosing to determine whether a particular disorder is modulated by Dhh signaling, comprising: 
 (a) culturing test cells or tissues;    (b) administering a compound which can inhibit patched-2 modulated Dhh signaling; and    (c) analyzing the level of Dhh binding to patched-2 or Dhh mediated phenotypic effects in the test cells.