Monoclonal antibodies against human protein Mcm3, process for their production, and their use

Abstract

The present invention relates to monoclonal antibodies against the human Mcm3 protein, hybridoma cell lines, that produce such antibodies, procedures for the production and their use, pharmaceutical compositions comprising a monoclonal antibody according to the present invention, their use for the prevention and treating of certain diseases and well as methods relating to the prevention and treatment of diseases associated with Mcm3 expression. Monoclonal antibodies according to the invention detect and bind human Mcm3 monospecifically both in immunohistological and immunobiochemical detection systems. The process for the production of these monoclonal antibodies comprises an initial screening of excess hybridoma supernatant with immunobiochemical methods followed by a second screening of positive hybridoma by means of an immunohistochemical method.

What is claimed is:  
     
         1 . A method for detecting a proliferating cell, a cancer cell or a neoplastic cell in a sample using a monoclonal antibody which binds specifically to human Mcm3, in which said monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.  
     
     
         2 . A method according to  claim 1 , wherein said monoclonal antibody binds to human Mcm3 both immunohistologically and immunobiochemically.  
     
     
         3 . A method according to  claim 1 , wherein said monoclonal antibody is selected from the group consisting of: a recombinant antibody, a chimeric antibody, a humanized antibody, a synthetic antibody and a genetically altered antibody.  
     
     
         4 . A method according to  claim 1 , wherein said monoclonal antibody is labeled with a detectable substance.  
     
     
         5 . A method according to  claim 4 , wherein said detectable substance comprises a fluorescent, radioactive, enzymatic or luminescent label.  
     
     
         6 . A method according to  claim 1 , wherein said monoclonal antibody is produced by the hybridoma cell line with the deposit number DSM ACC2388.  
     
     
         7 . A method according to  claim 1 , wherein the proliferating, cancer or neoplastic cell is detected immunohistologically, immunocytologically or immunobiochemically.  
     
     
         8 . A method according to  claim 1 , wherein the sample is selected from the group consisting of: serum, a blood sample, sputum, urine, liquor, a tissue, a biopsy, a gynaecological sample and a fine needle aspiration.  
     
     
         9 . A method according to  claim 1 , further comprising detecting Ki-67 and p27.  
     
     
         10 . A method according to  claim 9 , wherein Ki-67 and p27 are detected by the use of antibodies thereto.  
     
     
         11 . A method of exposing a cell to a monoclonal antibody which specifically binds to human Mcm3 for disrupting or preventing the cell cycle of a cell, DNA replication by a cell, or proliferation of a cell, in which the monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.  
     
     
         12 . A method according to  claim 11 , wherein said monoclonal antibody is selected from the group consisting of: a recombinant antibody, a chimeric antibody, a humanized antibody, a synthetic antibody and a genetically altered antibody.  
     
     
         13 . A method according to  claim 11 , wherein said monoclonal antibody is produced by the hybridoma cell line with the deposit number DSM ACC2388.  
     
     
         14 . A method for the treatment or prevention of an Mcm3 associated disease, the method comprising administering to an individual in need of such treatment a therapeutically effective amount of a monoclonal antibody which specifically binds to human Mcm3, in which the monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.  
     
     
         15 . A method according to  claim 14 , wherein said disease is selected from the group consisting of: tumours, allergies, auto-immunopathies, scar formation, inflammation, rheumatic diseases and the suppression of defence reactions of transplantations.  
     
     
         16 . A method according to  claim 14 , wherein said monoclonal antibody is selected from the group consisting of: a recombinant antibody, a chimeric antibody, a humanized antibody, a synthetic antibody and a genetically altered antibody.  
     
     
         17 . A method according to  claim 14 , wherein said monoclonal antibody is produced by the hybridoma cell line with the deposit number DSM ACC2388.  
     
     
         18 . A pharmaceutical composition comprising a monoclonal antibody which specifically binds to human Mcm3, wherein said monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388, together with a pharmaceutically acceptable carrier, adjuvant or additive.  
     
     
         19 . A method for the production of a hybridoma expressing a monoclonal antibody which specifically binds to human Mcm3, comprising the steps of: 
 (a) immunizing an animal with human Mcm3;    (b) obtaining a lymphocyte from the animal immunized with human Mcm3;    (c) immortalizing the lymphocyte to produce a hybridoma; and    (d) selecting a hybridoma which expresses a monoclonal antibody which reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.    
     
     
         20 . A method according to  claim 19 , in which a hybridoma is selected which expresses a monoclonal antibody which reacts both immunobiochemically and immunohistochemically with human Mcm3.  
     
     
         21 . A method for the production of a monoclonal antibody comprising expressing the antibody from a hybridoma obtained by a process according to  claim 19 .  
     
     
         22 . A method for the production of a monoclonal antibody comprising expressing the antibody from a hybridoma obtained by a process according to  claim 20 .  
     
     
         23 . A monoclonal antibody capable of specific binding to human Mcm3 in which the monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.  
     
     
         24 . A monoclonal antibody according to  claim 23 , wherein said monoclonal antibody is labeled with detectable substance.  
     
     
         25 . A monoclonal antibody according to  claim 24 , wherein the detectable substance comprises a fluorescent, radioactive, enzymatic or a luminescent label.  
     
     
         26 . A monoclonal antibody according to  claim 23 , which is capable of binding to human Mcm3 both immunohistologically and immunobiochemically.  
     
     
         27 . A monoclonal antibody according to  claim 23 , wherein said antibody is selected from the group consisting of: a recombinant antibody, a chimeric antibody, a humanized antibody, a synthetic antibody and a genetically altered antibody.  
     
     
         28 . A monoclonal antibody according to  claim 23 , wherein said antibody is produced by the hybridoma cell line with the deposit number DSM ACC2388.  
     
     
         29 . A hybridoma cell line expressing a monoclonal antibody which binds to human Mcm3, in which the monoclonal antibody reacts with the same epitope of human Mcm3 as the monoclonal antibody obtainable from the hybridoma cell line with deposit number DSM ACC2388.