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.

1 .- 92 . (canceled) 
     
     
         93 . An isolated host cell comprising an exogenously introduced nucleic acid sequence encoding an immunoglobulin common light chain that is capable of paring with two or more different immunoglobulin heavy chains, wherein the exogenously introduced nucleic acid sequence is stably integrated in the host cell genome. 
     
     
         94 . The host cell of  claim 93 , further comprising two or more exogenously introduced nucleic acid sequences encoding two or more immunoglobulin heavy chains. 
     
     
         95 . The host cell of  claim 94 , wherein the nucleic acid sequences encoding the immunoglobulin heavy chains are stably integrated in the host cell genome. 
     
     
         96 . The host cell of  claim 94 , wherein the immunoglobulin heavy chains have identical constant regions. 
     
     
         97 . The host cell of  claim 94 , wherein the immunoglobulin heavy chains have different specificities and/or affinities. 
     
     
         98 . The host cell of  claim 97 , wherein the immunoglobulin heavy chains bind to different epitopes on the same antigen. 
     
     
         99 . The host cell of  claim 97 , wherein the immunoglobulin heavy chains bind to different antigens. 
     
     
         100 . The host cell of  claim 94 , wherein the nucleic acid sequences are introduced into the host cell consecutively. 
     
     
         101 . The host cell of  claim 94 , wherein the nucleic acid sequence are introduced into the host cell concomitantly. 
     
     
         102 . The host cell of  claim 93 , wherein the nucleic acid sequence encoding the immunoglobulin common light chain is stably integrated in a predetermined position. 
     
     
         103 . The host cell of  claim 102 , wherein the integration is performed using homologous recombination or site-specific recombinases. 
     
     
         104 . The host cell of  claim 95 , wherein the nucleic acid sequences encoding the two or more immunoglobulin heavy chains are stably integrated in predetermined positions. 
     
     
         105 . The host cell of  claim 94 , wherein the two or more immunoglobulin heavy chains are capable of paring with the immunoglobulin common light chain to form two or more non-identical antibodies that bind antigen. 
     
     
         106 . The host cell of  claim 105 , wherein the two or more non-identical antibodies are of different isotypes. 
     
     
         107 . The host cell of  claim 106 , wherein the isotype is independently selected from the group consisting of: IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE, and IgM. 
     
     
         108 . The host cell of  claim 105 , wherein the two or more non-identical antibodies comprise at least one bispecific antibody. 
     
     
         109 . The host cell of  claim 93 , which is present in a non-human animal. 
     
     
         110 . A cell culture comprising the host cell of  claim 105  and a culture medium. 
     
     
         111 . The cell culture of  claim 110 , which produces two or more non-identical antibodies for more than 20 population doublings.