Bifunctional molecules

Abstract

A chimeric antibody conjugate comprising an antigen binding region of a non-human antibody and an immunoglobulin constant region which comprises at least one CH domain or epitope thereof, with the proviso that the constant region is not a naturally occurring FC fragment. A bifunctional molecule for use in labelling an antibody derived from a first species, the bifunctional molecule comprising a binding-region which binds to the antibody of the first species or to one or more groups provided thereon, and a constant region derived from an antibody of a second species, the constant region comprising at least one CH domain or an epitope thereof. The present invention relates to bifunctional molecules and complexes which are useful as positive control reagents in antibody based diagnostic tests. The present invention also relates to polynucleotides encoding these bifunctional molecules, and to diagnostic assays involving the use of these molecules.

1 - 90 . (canceled)  
     
     
         91 . A method for detecting presence of an antibody in a biological sample obtained from a test species, the method comprising: 
 a) performing an antibody based diagnostic test on the biological sample;    b) performing the antibody based diagnostic test on a positive control, wherein the positive control shows a positive reaction; and    c) comparing results of step a) with results of step b), whereby the presence of an antibody in the biological sample is detected by a positive reaction in step a);    wherein the positive control comprises a complex formed between (i) an antibody or biologically active fragment thereof from a first species, wherein the first species is different from the test species and (ii) a bifunctional molecule, the bifunctional molecule comprising a binding region that binds to the antibody of the first species, and a constant region from an antibody of the test species, the constant region comprising at least one CH domain or an epitope thereof.    
     
     
         92 . The method according to  claim 91 , wherein the bifunctional molecule binds to the constant region of the antibody of the first species.  
     
     
         93 . The method according to  claim 91 , wherein the binding region of the bifunctional molecule is of non-antibody origin.  
     
     
         94 . The method according to  claim 93 , wherein the binding region is a protein selected from the group consisting of Streptococcal protein G, Staphylococcal aureus protein A, and  Peptostreptococcus magnus  protein L, or a fragment thereof.  
     
     
         95 . The method according to  claim 93 , wherein the binding region comprises fragment B of  Staphylococcus aureus  protein A.  
     
     
         96 . The method according to  claim 93 , wherein the binding region comprises a mouse Fc y receptor or fragment thereof.  
     
     
         97 . The method according to  claim 93 , wherein the binding region comprises histidine rich glycoprotein.  
     
     
         98 . The method according to  claim 91 , wherein the binding region has a K D  for the antibody of the first species of less than 10 −6  M.  
     
     
         99 . The method according to  claim 91 , wherein the binding region has a K D  for the antibody of the first species of less than 10 −8  M.  
     
     
         100 . The method according to  claim 91 , wherein the binding region binds to one or more non-naturally occurring group(s) provided on the constant region of the antibody of the first species.  
     
     
         101 . The method according to  claim 100 , wherein the group(s) is a biotin molecule and the binding region comprises streptavidin or a fragment thereof.  
     
     
         102 . The method according to  claim 91 , wherein the constant region from the antibody of the test species comprises one or more constant domains from an IgM antibody.  
     
     
         103 . The method according to  claim 102 , wherein the constant region from the antibody of the test species comprises one or more C H 3μ domains.  
     
     
         104 . The method according to  claim 91 , wherein the constant region from the antibody of the test species comprises one or more constant domains from an IgG antibody.  
     
     
         105 . The method according to  claim 104 , wherein the constant region from the antibody of the test species comprises one or more C H 3γ domains.  
     
     
         106 . The method according to  claim 91 , wherein the constant region from the antibody of the test species comprises one or more constant domains from an IgA antibody.  
     
     
         107 . The method according to  claim 91 , wherein the constant region from the antibody of the test species comprises or consists of a non-naturally occurring combination of immunoglobulin C H  domains or epitopes thereof.  
     
     
         108 . The method according to  claim 91 , wherein the constant region from an antibody of the test species consists of a single C H  domain.  
     
     
         109 . The method according to  claim 91 , wherein the binding region and the constant region from the antibody of the test species are linked directly or are separated by a linker molecule of between 1 and 20 amino acids in length.  
     
     
         110 . The method according to  claim 91 , wherein the first species is a rat or mouse.  
     
     
         111 . The method according to  claim 91 , wherein the test species is a human.  
     
     
         112 . The method according to  claim 91 , wherein the antibodies to be detected are antibodies characteristic of a disease selected from the group consisting of dengue fever, Japanese encephalitis, rubella, spotted fever, herpes infection, parvovirus infection, melioidosis, typohid, leptospirosis, malaria, yellow fever, whooping cough, systemic candidiasis/thrush, chicken pox, shingles, ADS, hepatitis, liver cancer, cervical cancer, infectious mononucleosis, nasopharyngeal carcinoma, Ross River fever,  brucella , exanthum subitum (sixth disease/roseola infantum), erythema infectiosum (fifth disease), Q fever, cold sores, genital herpes, spotted fever and scrub typhus.  
     
     
         113 . The method according to  claim 91 , wherein the antibody based diagnostic test is selected from the group consisting of ELISA, immunochromatography, particle agglutination ELISA and biosensor assays.