Recombinant production of mixtures of antibodies

Abstract

Provided is methods for producing mixtures of antibodies from a single host cell clone, wherein, a nucleic acid sequence encoding a light chain and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The recombinantly produced antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen-binding domains. Mixtures of the recombinantly produced antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.

What is claimed is: 
     
       1. A composition comprising a mixture of two or three non-identical antibodies and a suitable pharmaceutically acceptable carrier,
 wherein two different heavy chains and a common immunoglobulin light chain able to pair with the two different heavy chains are present in the mixture of the two or three non-identical antibodies, and 
 wherein the mixture of two or three non-identical antibodies comprises:
 a bispecific antibody and at least one monospecific antibody, and 
 
 wherein at least one of the two different heavy chains is modified as compared to wild-type. 
 
     
     
       2. The composition of  claim 1 , wherein the mixture comprises a bispecific antibody and two different monospecific antibodies. 
     
     
       3. The composition of  claim 1 , wherein the two or three non-identical antibodies have differing specificities for the same target antigen. 
     
     
       4. The composition of  claim 1 , wherein the two or three non-identical antibodies have differing affinity for the same target epitope. 
     
     
       5. The composition of  claim 1 , wherein the two or three non-identical antibodies bind to different epitopes on the same target antigen. 
     
     
       6. The composition of  claim 1 , wherein the two or three non-identical antibodies bind to different antigens. 
     
     
       7. The composition of  claim 1 , wherein the two or three non-identical antibodies are independently selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE, and IgM. 
     
     
       8. The composition of  claim 1 , wherein the different immunoglobulin heavy chains are of IgG isotype. 
     
     
       9. A composition comprising a mixture of two or three non-identical antibodies that have been produced in the same host cells,
 wherein two different heavy chains and a common immunoglobulin light chain are present in the mixture of the two or three non-identical antibodies,   wherein the two different heavy chains are able to pair to said common light chain,   wherein the two different heavy chains have different binding specificities, and   wherein said heavy chains further differ in their constant regions sufficiently so that the amount of bispecific antibodies is decreased as compared to the theoretical percentage of bispecific antibodies, and   wherein the mixture of two or three non-identical antibodies comprises two different monospecific antibodies.   
     
     
       10. A composition comprising a mixture of two or three non-identical antibodies and a suitable carrier,
 wherein only two different heavy chains are present in the two or three antibodies,   wherein a common immunoglobulin light chain able to pair with the two different heavy chains is present in the mixture of the two or three non-identical antibodies, and   wherein the mixture of two or three non-identical antibodies comprises:
 a bispecific antibody and at least one monospecific antibody. 
   
     
     
       11. A composition comprising a mixture of two or three non-identical antibodies and a suitable carrier,
 wherein two different heavy chains are present in the two or three antibodies,   wherein only a common immunoglobulin light chain able to pair with the two different heavy chains is present in the mixture of the two or three antibodies, and   wherein the mixture of two or three non-identical antibodies comprises:
 a bispecific antibody and at least one monospecific antibody. 
   
     
     
       12. A composition comprising a mixture of two or three non-identical antibodies and a suitable pharmaceutically acceptable carrier,
 wherein only two different heavy chains are present in the two or three antibodies, and 
 wherein a common immunoglobulin light chain able to pair with the two different heavy chains is present in the mixture of the two or three non-identical antibodies, and 
 wherein the mixture of two or three non-identical antibodies comprises a monospecific antibody and a bispecific antibody, and 
 wherein at least one of the two different heavy chains is modified as compared to wild-type. 
 
     
     
       13. A composition comprising a mixture of two or three non-identical antibodies and a suitable pharmaceutically acceptable carrier,
 wherein two different heavy chains are present in the two or three antibodies, and 
 wherein only a common immunoglobulin light chain able to pair with the two different heavy chains is present in the mixture of the two or three antibodies, and 
 wherein the mixture of two or three non-identical antibodies comprises a monospecific antibody and a bispecific antibody, and 
 wherein at least one of the two different heavy chains is modified as compared to wild-type. 
 
     
     
       14. A composition comprising at least a first antibody and a second antibody,
 wherein the first and second antibodies have a common light chain, 
 wherein the first antibody comprises two copies of a first heavy chain, 
 wherein the second antibody comprises one copy of the first heavy chain and one copy of a second heavy chain, and 
 wherein the first heavy chain and the second heavy chain are different from one another, and 
 wherein at least one of the two different heavy chains is modified as compared to wild-type. 
 
     
     
       15. The composition of claim 1, wherein the mixture comprises three non-identical antibodies. 
     
     
       16. The composition of claim 1, wherein the common light chain is identical in each light chain/heavy chain pair of the two or three non-identical antibodies. 
     
     
       17. The composition of claim 1, wherein the common light chain is the only light chain present in the composition. 
     
     
       18. The composition of claim 1, wherein the two different heavy chains differ in their variable region. 
     
     
       19. The composition of claim 1, wherein the two different heavy chains differ in both the variable region and constant region. 
     
     
       20. The composition of claim 1, wherein the mixture of two or three non-identical antibodies has been produced in the same host cells. 
     
     
       21. The composition of claim 1, wherein:
 the mixture comprises three non-identical antibodies;   the common light chain is identical in each light chain/heavy chain pair of the two or three non-identical antibodies;   the common light chain is the only light chain present in the composition;   the three non-identical antibodies have been produced in the same host cells; and   the two different heavy chains differ in their variable region.   
     
     
       22. The composition of claim 1, wherein the mixture of two or three non-identical antibodies has been isolated from the host cells which produce the antibodies. 
     
     
       23. The composition of claim 1, wherein the light chain is able to pair with one of the two heavy chains present in the mixture. 
     
     
       24. The composition of claim 1 wherein the two or three non-identical antibodies have a different affinity for the same target epitope. 
     
     
       25. The composition of claim 24 wherein the different affinity is analyzed by surface plasmon resonance. 
     
     
       26. The composition of claim 1, wherein the two or three non-identical antibodies have been isolated separately or as a mixture from a culture of the host cell.