Reagents for use as calibrators and controls

• US 6,015,662 A
• Filed: 01/23/1996
• Issued: 01/18/2000
• Est. Priority Date: 01/23/1996
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Hackett, John R. Jr., Golden, Alan M., Ostrow, David H., Hoff, Jane A.
• Primary Examiner(s): Wortman, Donna C.
• Assistant Examiner(s): Brumback, Brenda G.
• Application Number:
  US08/589,939
• Time in Patent Office: 1,456 Days
• Field of Search: 435/5, 435/7.2, 435/7.22, 435/7.31, 435/7.32, 435/7.34, 436/548
• US Class Current: 435/5
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/6857 Antibody fragments
• CPC Class Codes: G01N 33/96 involving blood or serum control standard

Abstract

The present invention relates to the use of a reagent that binds specifically to a predetermined ligand, contains one or more antibody constant region epitopes, and is uniform in specificity and affinity. The reagent can be produced continually, in the manufacture of calibrators (standards) and/or controls for diagnostic kits designed to qualitatively or quantitatively measure antibodies specific for a desired ligand. For example, the present invention encompasses recombinant mouse-human chimeric antibodies which may be used as calibrators (standards) and/or positive controls in assays and kits which measure human antibodies. Any species may be used in creating the chimeric antibodies, and the presence of any corresponding species of antibody may be detected.

Claims

1. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with antigen specific for said antibody for a time and under conditions sufficient to allow the formation of antigen/antibody complexes, (B) detecting the presence of said antibody which may be present in said test sample and employing, as a control or calibrator, a reagent which binds to said antigen, wherein the improvement comprises employing, as said control or calibrator, a chimeric antibody comprising murine heavy and light chain variable regions genetically fused to human or a species immunologically cross0reactive with human heavy and light chain constant regions, wherein said chimeric antibody binds to said antigen and is homogeneous with respect to specificity and affinity.

4. The method of claim 1 or 3 wherein said chimeric antibody is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive to human constant regions.

5. The method of claim 1 or 3 wherein said chimeric antibody binds specifically to Toxoplasma gondii.

6. The method of claim 5 wherein said chimeric antibody binds specifically to protein P30 or protein P66 of Toxoplasma gondii.

7. The method of claim 1 or 3 wherein said murine heavy chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO:

2 and said murine light chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO;

4.

8. The method of claim 1 or 3 wherein said murine heavy chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO:

1 and said murine light chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO;

3.

9. The method of claim 1 or 3 wherein said murine heavy chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO:

6 and said murine light chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO;

8.

10. The method of claim 1 or 3 wherein said murine heavy chain variable region of said chimeric monoclonal antibody has the amino acid sequence of SEQ ID NO:

5 and said murine light chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO;

7.

17. The method of claim 1, 2, 3, or 11 wherein said antibody to be detected in said test sample is selected from the group consisting of IgA, IgD, IgE, IgG, and IgM.

18. The method of claim 1, 2, 3, or 11 wherein said antigen is selected from the group consisting of an infectious agent, an autoantigen, an allergen, and a pharmaceutical compound.

19. The method of claim 18 wherein said infectious agent is selected from the group consisting of a parasite, a bacterium, a fungus, a yeast and a virus.

20. The method of claim 19 wherein said virus is selected from the group consisting of:

human immunodeficiency virus-1, human immunodeficiency virus-2, human T-cell leukemia virus-1, human T-cell leukemia virus-2, cytomegalovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis GB virus, respiratory syncytial virus, and Rubella virus, said parasite is selected from the group consisting of Toxoplasma gondii and Trypanosoma cruzi, said fungus is selected from the group consisting of Histoplasma capsulatum and Cryptococcus neoformans, and said bacterium is selected from the group consisting of Helicobacter pylon and Streptococcus pyogenes.

2. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with at least one antigen specific for said antibody for a time and under conditions sufficient to allow the formation of antigen/antibody complexes, (B) detecting the presence of said antibody which may be present in said test sample, and employing, as a control or calibrator, two or more reagents which bind to said at least one antigen, wherein the improvement comprises employing, as said control or calibrator, in place of said test sample, two or more chimeric antibodies, wherein each is homogeneous with respect to specificity and affinity and each comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross0reactive with human heavy and light chain constant regions, whereineach of said two or more chimeric antibodies binds to an antigen comprising more than one epitope wherein:

a) said antigen and said two or more chimeric antibodies are present in a single container or

b) said antigen and said two or more chimeric antibodies are present in separate containers such that said antigen is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) two of said different antigen and said two or more chimeric antibodies are present in a single container or

b) each of said two different antigens and said two or more chimeric antibodies are present in separate containers such that each of said two different antigens is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different antigens may be from one source or from different sources.

3. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with antigen specific for said antibody for a time and under conditions sufficient to allow the formation of antigen/antibody complexes, (B) adding a direct or indirect conjugate to said resulting antigen/antibody complexes for a time and under conditions sufficient to allow said conjugate to bind to said bound antibody, wherein said conjugate comprises an antibody attached to a signal generating compound capable of generating a detectable signal, (C) detecting the presence of said antibody which may be present in said test sample by detecting the signal generating by said signal generating compound, and employing, as a control or calibrator, a reagent which binds to said antigen, wherein the improvement comprises employing, as said control or calibrator, a chimeric antibody comprising murine heavy and light chain variable regions genetically fused to human or a species immunologically cross0reactive with human heavy and light chain constant regions, wherein said chimeric antibody binds to said antigen and is homogeneous with respect to specificity and affinity.

11. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with at least one antigen specific for said antibody for a time and under conditions sufficient to allow the formation of antigen/antibody complexes, (B) adding a direct or indirect conjugate to said resulting antigen/antibody complexes for a time and under conditions sufficient to allow said conjugate to bind to said bound antibody, wherein said conjugate comprises an antibody attached to a signal generating compound capable of detecting a detectable signal, (C) detecting the presence of said antibody which may be present in said test sample by detecting the signal generated by said signal generating compound, and employing, as a control or calibrator, two or more reagents which bind to said at least one antigen, wherein the improvement comprises employing, as said control or calibrator, in place of said test sample, two or more chimeric antibodies, wherein each is homogeneous with respect to affinity and specificity and each comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, whereineach of said two or more chimeric antibodies binds to an antigen comprising more than one epitope wherein:

a) said antigen and said two or more chimeric antibodies are present in a single container or

b) said antigen and said two or more chimeric antibodies are present in separate containers such that said antigen is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) two of said different antigen and said two or more chimeric antibodies are present in a single container or

b) each of said two different antigens and said two or more chimeric antibodies are present in separate containers such that each of said two different antigens is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different antigens may be from one source or from different sources.

12. The method of claim 2 or 11 wherein each of said two or more chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.

13. The method of claims 2 or 11 wherein each of said two or more chimeric antibodies binds specifically to Toxoplasma gondii.

14. The method of claim 13 wherein each of said two or more chimeric antibodies binds specifically to protein P30 or protein P66 of Toxoplasma gondii.

15. The method of claims 2 or 11 wherein said murine heavy chain variable region of said chimeric antibody representing one of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO:

2 and said murine light chain variable region of said chimeric antibody representing said one of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

4, and said murine heavy chain variable region of said chimeric monoclonal antibody representing another of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

6 and said murine light chain variable region of said another of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

8.

16. The method of claim 2 or 11 wherein said murine heavy chain variable region of said chimeric antibody representing one of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO:

1 and said murine light chain variable region of said chimeric antibody representing said one of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

3, and said murine heavy chain variable region of said chimeric antibody representing another of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

5 and said murine light chain variable region of said another of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

7.

21. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with anti-antibody specific for said antibody for a time and under conditions sufficient to allow for the formation of anti-antibody/antibody complexes, (B) detecting the presence of said antibody which may be present in said test sample, and employing, as a control or calibrator, a reagent which binds to said anti-antibody, wherein the improvement comprises employing, as said control or calibrator, a chimeric antibody comprising murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, wherein said chimeric antibody binds to said antigen and is homogeneous with respect to specificity and affinity.

24. The method of claim 21 or 23 wherein said chimeric antibody is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with to human constant regions.

25. The method of claim 21 or 23 wherein said chimeric antibody binds specifically to Toxoplasma gondii.

26. The method of claim 25 wherein said chimeric antibody binds specifically to protein P30 or protein P66 of Toxoplasma gondii.

27. The method of claim 21 or 23 wherein said murine heavy chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO:

2 and said murine light chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO;

4.

28. The method of claim 21 or 23 wherein said murine heavy chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO:

1 and said murine light chain variable region of said chimeric monoclonal antibody has the amino acid sequence of SEQ ID NO;

3.

29. The method of claim 21 or 23 wherein said murine heavy chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO:

6 and said murine light chain variable region of said chimeric antibody is encoded by the nucleotide sequence of SEQ ID NO;

8.

30. The method of claim 21 or 23 wherein said murine heavy chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO:

5 and said murine light chain variable region of said chimeric antibody has the amino acid sequence of SEQ ID NO;

7.

37. The method of claim 21, 22, 23, or 31 wherein said antibody to be detected in said test sample is selected from the group consisting of IgA, IgD, IgE, IgG, and IgM.

38. The method of claim 21, 22, 23, or 31 wherein said antigen selected from the group consisting of an infectious agent, an autoantigen, an allergen, and a pharmaceutical compound.

39. The method of claim 38 wherein said infectious agent is selected from the group consisting of a parasite, a bacterium, a fungus, a yeast and a virus.

40. The method of claim 39 wherein said virus is selected from the group consisting of:

human immunodeficiency virus-1, human immunodeficiency virus-2, human T-cell leukemia virus-1, human T-cell leukemia virus-2, cytomegalovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis GB virus, respiratory syncytial virus, and Rubella virus, said parasite is selected from the group consisting of Toxoplasma gondii and Trypanosoma cruzi, said fungus is selected from the group consisting of Histoplasma capsulatum and Cryptococcus neoformans, and said bacterium is selected from the group consisting of Helicobacter pylon and Streptococcus pyogenes.

22. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with at least one anti-antibody specific for said antibody for a time and under conditions sufficient to allow the formation of anti-antibody/antibody complexes, (B) detecting the presence of said antibody which may be present in said test sample, and employing, as a control or calibrator, two or more reagents which bind to said at least one anti-antibody, wherein the improvement comprises employing, as said control or calibrator, in place of said test sample, two or more chimeric antibodies, wherein each is homogeneous with respect to specificity and affinity and each comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, whereineach of said two or more chimeric antibodies binds to an anti-antibody comprising more than one epitope wherein:

a) said anti-antibody and said two or more chimeric antibodies are present in a single container or

b) said anti-antibody and said two or more chimeric antibodies are present in separate containers such that said anti-antibody is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different anti-antibody, said different antigen comprising one or more epitopes wherein;

a) two of said different anti-antibody and said two or more chimeric antibodies are present in a single container or

b) each of said two different anti-antibodies and said two or more chimeric antibodies are present in separate containers such that each of said two different anti-antibodies is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different antigens may be from one source or from different sources.

32. The method of claim 22 or 31 wherein each of said two or more chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.

33. The method of claim 22 or 31 wherein each of said two or more chimeric antibodies binds specifically to Toxoplasma gondii.

34. The method of claim 33 wherein each of said two or more chimeric antibodies binds specifically to protein P30 or protein P66 of Toxoplasma gondii.

35. The method of claim 22 or 31 wherein said murine heavy chain variable region of said chimeric monoclonal antibody representing one of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO:

2 and said murine light chain variable region of said chimeric antibody representing said one of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

4, and said murine heavy chain variable region of said chimeric antibody representing another of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

6 and said [L] murine light chain variable region of said another of said two or more chimeric antibodies is encoded by the nucleotide sequence of SEQ ID NO;

8.

36. The method of claim 22 or 31 wherein said murine heavy chain variable region of said chimeric antibody representing one of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO:

1 and said murine light chain variable region of said chimeric antibody representing said one of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

3, and said murine heavy chain variable region of said chimeric antibody representing another of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

5 and murine light chain variable region of said another of said two or more chimeric antibodies has the amino acid sequence of SEQ ID NO;

7.

23. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with anti-antibody specific for said antibody for a time and under conditions sufficient to allow the formation of anti-antibody/antibody complexes, (B) adding a conjugate to said resulting anti-antibody/antibody complexes for a time and under conditions sufficient to allow said conjugate to bind to said bound antibody, wherein said conjugate comprises an antigen attached to a signal generating compound capable of generating a detectable signal, (C) detecting the presence of said antibody which may be present in said test sample by detecting the signal generating by said signal generating compound, and employing, as a control or calibrator, a reagent which comprises antibody bound by said anti-antibody, wherein the improvement comprises employing, as said control or calibrator, a chimeric antibody comprising murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, wherein said chimeric antibody binds to said antigen and is homogeneous with respect to specificity and affinity.

31. A method for detecting the presence of antibody which may be present in a test sample wherein said method comprises (A) contacting said test sample suspected of containing said antibody with at least one anti-antibody specific for said antibody for a time and under conditions sufficient to allow the formation of anti-antibody/antibody complexes, (B) adding a conjugate to said resulting anti-antibody/antibody complexes for a time and under conditions sufficient to allow said conjugate to bind to said bound antibody, wherein said conjugate comprises an antigen attached to a signal generating compound capable of generating a detectable signal, (C) detecting the presence of said antibody which may be present in said test sample by detecting the signal generated by said signal generating compound, and employing, as a control or calibrator, two or more chimeric reagents which bind to said at least one anti-antibody, wherein the improvement comprises employing, as said control or calibrator, in place of said test sample, two or more chimeric antibodies each comprising murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, wherein each of said two or more chimeric antibodies binds to different epitopes on said anti-antibody and has a unique specificity and affinity, whereineach of said two or more chimeric antibodies binds to an anti-antibody comprising more than one epitope wherein:

a) said anti-antibody and said two or more chimeric antibodies are present in a single container or

b) said anti-antibody and said two or more chimeric antibodies are present in separate containers such that said anti-antibody is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different anti-antibody, said different anti-antibody comprising one or more epitopes wherein;

a) two of said different anti-antibody and said two or more chimeric antibodies are present in a single container or

b) each of said two different anti-antibodies and said two or more chimeric antibodies are present in separate containers such that each of said two different anti-antibodies is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different anti-antibodies may be from one source or from different sources.

41. A method for detecting the presence of antibodies, developed against more than one antigen, which may be present in a test sample, wherein said method comprises (A) contacting said test sample suspected of containing said antibodies with antigens specific for said antibodies, respectively, for a time and under conditions sufficient to allow the formation of antigen/antibody complexes, (B) adding direct or indirect conjugates to said antigen/antibody complexes for a time and under conditions sufficient to allow said conjugates to bind to said bound antibodies, wherein said conjugates comprise an antibody attached to a signal generating compound capable of generating a detectable signal, (C) detecting the presence of said antibodies which may be present in said test sample by detecting the signal generating by said signal generating compound, and employing, as controls or calibrators, reagents which bind to said antigens, wherein the improvement comprises employing, as said controls or calibrators, in place of said test sample, chimeric antibodies, wherein each is homogeneous with respect to specificity and affinity and each comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, whereineach of said chimeric antibodies binds to an antigen comprising more than one epitope wherein:

a) each of said antigens and said chimeric antibodies are present in a single container or

b) said antigens and said chimeric antibodies are present in separate containers such that one of said antigens is present with one of said chimeric antibodies in one container;

or

2) each of said chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) all of said different antigen and said chimeric antibodies are present in a single container or

b) each of said different antigen and said chimeric antibodies are present in separate containers such that each of said different antigen is present with one of said chimeric antibodies in one container of said separate containers, wherein each of said different antigen may be from one source or from different sources.

42. The method of claim 41 wherein each of said chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.

43. A kit for determining the presence of antibody in a test sample comprising:

(A) at least one antigen specific for said antibody;

and

(B) a control or calibrator comprising two or more chimeric antibodies wherein each of said two or more chimeric antibodies comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, binds to different epitopes on said at least one antigen, and is homogeneous with respect to specificity and affinity wherein

1) each of said two or more chimeric antibodies binds to an antigen comprising more than one epitope wherein;

a) said antigen and said two or more chimeric antibodies are present in a single container or

b) said antigen and said two or more chimeric antibodies are present in separate containers such that said antigen is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) two of said different antigen and said two or more chimeric antibodies are present in a single container or

b) each of said two different antigens and said two or more chimeric antibodies are present in separate containers such that each of said two different antigens is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different antigens may be from one source or from different sources.

46. The kit of claim 43 or 44 wherein said antibody to be detected in said test sample is selected from the group consisting of IgA, IgD, IgE, IgG, and IgM.

47. The kit of claim 43 or 44 wherein said antigen is selected from the group consisting of an infectious agent, an autoantigen, an allergen, and a pharmaceutical compound.

44. A kit for determining the presence of antibody in a test sample comprising:

(A) at least one antigen specific for said antibody;

(B) a direct or indirect conjugate comprising an antibody attached to a signal generating compound capable of generating a detectable signal; and

(C) a control or calibrator comprising two or more chimeric antibodies wherein each of said two or more chimeric antibodies comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, binds to different epitopes on said at least one antigen, and is homogeneous with respect to specificity and affinity wherein

1) each of said two or more chimeric [reagents] antibodies binds to an antigen comprising more than one epitope wherein;

a) said antigen and said two or more chimeric antibodies are present in a single container or

b) said antigen and said two or more chimeric are present in separate containers such that said antigen is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) two of said different antigen and said two or more chimeric antibodies are present in a single container or

b) each of said two different antigens and said two or more chimeric antibodies are present in separate containers such that each of said two different antigens is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said different antigens may be from one source or from different sources.

45. The kit of claim 44 wherein each of said two or more chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.

48. A kit for determining the presence of antibody in a test sample comprising:

a) an antigen specific for said antibody; and

b) a control or calibrator comprising a chimeric antibody, and may further comprise c) a direct or indirect conjugate comprising an antibody attached to a signal generating compound capable of generating a detectable signal, wherein said chimeric antibody is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to human heavy and light chain constant regions, binds to said antigen, and is homogenous with respect to specifically and affinity.

49. A kit for determining the presence of antibody in a test sample comprising:

(A) at least one anti-antibody specific for said antibody;

(B) at least one antigen specific for said antibody;

and

(C) a control or calibrator comprising two or more chimeric antibodies wherein each of said two or more chimeric antibodies comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, binds to different epitopes on said at least one antigen, and is homogeneous with respect to specificity and affinity wherein

1) each of said two or more chimeric antibodies binds to an antigen comprising more than one epitope wherein;

a) said antigen and said two or more chimeric antibodies are present in a single container or

b) said antigen and said two or more chimeric antibodies are present in separate containers such that said antigen is present with one of said two or more chimeric antibodies in one container;

or

2) each of said two or more chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) one or more of said different antigen and said two or more chimeric antibodies are present in a single container or

b) each of said one or more different antigen and said two or more chimeric antibodies are present in separate containers such that each of said one or more different antigen is present with one of said two or more chimeric antibodies in one container of said separate containers, wherein each of said one or more different antigen may be from one source or from different sources.

50. The kit of claim 49 wherein each of said two or more chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.

51. The kit of claim 49 wherein said antibody to be detected in said test sample is selected from the group consisting of IgA, IgD, IgE, IgG and IgM.

52. The kit of claim 49 wherein said antigen is selected from the group consisting of an infectious agent, an autoantigen, an allergen, and a pharmaceutical compound.

53. A kit for determining the presence of antibody in a test sample comprising:

a) an anti-antibody specific for said antibody;

b) an antigen specific for said antibody; and

c) a control or calibrator;

or

a) an anti-antibody specific for said antibody;

b) a direct or indirect conjugate comprising an antigen attached to a signal generating compound capable of generating a detectable signal; and

c) control or calibrator comprising a chimeric antibody wherein said chimeric antibody is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to human heavy and light chain constant regions, binds to said antigen, and is homogeneous with respect to specificity and affinity.

54. A kit for determining the presence of antibodies, developed against more than one antigen, which may be present in a test sample, comprising:

(A) antigens specific for said antibodies, respectively;

(B) direct or indirect conjugates each comprising an antibody attached to a signal generating compound capable of generating a detectable signal; and

(C) controls or calibrators comprising chimeric antibodies wherein each of said chimeric antibodies comprises murine heavy and light chain variable regions genetically fused to human or a species immunologically cross-reactive with human heavy and light chain constant regions, binds to said respective antigens, and is homogeneous with respect to specificity and affinity wherein

1) each of said chimeric antibodies binds to an antigen comprising more than one epitope wherein;

a) each of said antigens and said chimeric antibodies are present in a single container or

b) said antigens and said chimeric antibodies are present in separate containers such that one of said antigens is present with one of said chimeric antibodies in one container;

or

2) each of said chimeric antibodies binds to a different antigen, said different antigen comprising one or more epitopes wherein;

a) all of said different antigen and said chimeric antibodies are present in a single container or

b) each of said different antigen and said chimeric antibodies are present in separate containers such that each of said different antigen is present with one of said chimeric antibodies in one container of said separate containers, wherein each of said different antigen may be from one source or from different sources.

55. The kit of claim 54 wherein each of said chimeric antibodies is a chimeric monoclonal antibody comprising murine heavy and light chain variable regions genetically fused to constant regions derived from a species immunologically cross-reactive with human constant regions.