Recombinant production of mixtures of antibodies
The invention provides 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.
1. A composition comprising three or more non-identical antibodies and a pharmaceutically acceptable carrier,
wherein said three or more non-identical antibodies comprise at least three antibodies comprising heavy chains having different immunoglobulin heavy chain sequences and one common light chain,
wherein at least three different heavy chain sequences are represented in the composition, and wherein the common light chain is paired with the at least three immunoglobulin heavy chains having different immunoglobulin heavy chain sequences to form functional antigen binding domains, and
wherein the three or more non-identical antibodies comprise constant regions of isotypes selected from the group consisting of IgG, IgA, IgD, IgE, IgM, and mixtures of any thereof.
2. A composition comprising three or more non-identical antibodies and a pharmaceutically acceptable carrier, wherein the three or more non-identical antibodies comprise at least three antibodies comprising heavy chains having different immunoglobulin heavy chain sequences and one common light chain, wherein at least three different heavy chain sequences are represented in the composition, and wherein the common light chain is paired with the at least three immunoglobulin heavy chains having different immunoglobulin heavy chain sequences to form functional antigen binding domains, and
wherein said three or more non-identical antibodies comprise at least one bispecific antibody.
3. The composition of claim 1 , wherein at least two of said three or more non-identical antibodies have differing specificities for the same target antigen.
4. The composition of claim 1 , wherein at least two of said three or more non-identical antibodies have differing affinity for the same target epitope.
5. The composition of claim 1 , wherein at least two of said three or more non-identical antibodies bind to different epitopes on the same target antigen.
6. The composition of claim 1 , wherein at least two of said three or more non-identical antibodies bind to different antigens.
7. The composition of claim 1 , wherein at least two of said three or more non-identical antibodies are of different isotypes.
8. The composition of claim 7 , wherein said different isotypes comprise at least an IgG and an IgA.
9. The composition of claim 7 , wherein said different isotypes comprise at least an IgG1 and an IgG3 antibody.
10. The composition of claim 1 , wherein the three or more non-identical antibodies are of isotype IgG1, IgG2, IgG3 or IgG4.
11. The composition of claim 10 , wherein the three or more non-identical antibodies comprise constant regions of isotype IgG1.
12. The composition of claim 1 , wherein said three or more non-identical antibodies comprise at least one bispecific antibody.
13. The composition of claim 2 , wherein said heavy chains differ in their constant regions sufficiently to reduce pairing between the different heavy chains.
14. The composition of claim 2 , wherein a first antibody binds CD22, a second antibody binds CD72, and a third antibody binds HLA-DR.
15. The composition of claim 2 , wherein a first antibody binds EP-CAM homotypic adhesion molecule and a second and third non-identical antibody binds CD46.
16. The composition of claim 5 , wherein a first, second, and third non-identical antibody binds to non-overlapping epitopes on Her-2.
17. The composition of claim 2 , wherein the targets for said antibodies are selected from HER-2Neu receptor, VEGFR1 receptor, VEGFR2 receptor, a B-cell marker, a T-cell marker, cytokines, interleukins, and cytokine receptors.