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 . A method for treating or diagnosing a disease or disorder in a human or animal subject, the method comprising:
 administering to the subject a pharmaceutical composition comprising a mixture of two or more non-identical antibodies and a suitable carrier,   wherein at least two different heavy chains and a common light chain are represented in the mixture, and wherein the at least two different heavy chains are able to pair with the common light chain.   
     
     
         94 . The method according to  claim 93 , wherein the mixture is recombinantly produced from a clone derived from a single host cell comprising an exogenously introduced polynucleotide encoding a common immunoglobulin light chain and an exogenously introduced polynucleotide or polynucleotides encoding at least two different immunoglobulin heavy chains. 
     
     
         95 . The method according to  claim 94 , wherein at least one of the exogenously introduced polynucleotides is integrated into the host cell's genome. 
     
     
         96 . The method according to  claim 94 , wherein an exogenously introduced polynucleotide encoding a common immunoglobulin light chain is integrated in the host cell's genome. 
     
     
         97 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture bind to different antigens. 
     
     
         98 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture bind to different epitopes on the same target antigen or bind to different antigen molecules present in one antigen comprising mixture. 
     
     
         99 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture have different specificities for the same target antigen. 
     
     
         100 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture have different affinities for the same target epitope. 
     
     
         101 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture bind to non-overlapping epitopes on Her-2. 
     
     
         102 . The method according to  claim 93 , wherein the disease or disorder is selected from the group of auto-immune diseases, graft-versus-host rejection, and cancer, including solid tumors of the brain, head- and neck, breast, prostate, colon, lung, hematologic tumors, B-cell tumors, neoplastic disorders including leukemias, lymphomas, sarcomas, carcinomas, neural cell tumors, squamous cell carcinomas, germ cell tumors, metastases, undifferentiated tumors, seminomas, melanomas, myelomas, neuroblastomas, mixed cell tumors, and neoplasias caused by infectious agents. 
     
     
         103 . The method according to  claim 93 , wherein the disease or disorder is caused by a bacteria, virus, or fungi, including multidrug resistant  Staphylococcus aureus, Candida albicans, Aspergillus  species, yeast. Lyssavirus, rabies virus, Varicella-Zoster Virus, Adenovirus, Respiratory Syncitium Virus, Human Immunodeficiency Virus, Human Metapneumovirus, Influenza virus, West Nile Virus, Severe Acute Respiratory Syndrome (SARS),  Bacillus anthracis, Clostridium botulinum  toxin,  Clostridium perfringens  epsilon toxin,  Yersinia pestis, Francisella tulariensis, Coxiella burnetii, Brucella species, Staphylococcus  enterotoxin B, Variola major, alpha viruses causing meningoencephalitis syndromes (EEEV, VEEV, and WEEV), viruses known to cause hemorrhagic fevers such as Ebola, Marburg and Junin virus, Nipah virus, Hantaviruses, Tick-borne encephalitis virus, Yellow fever virus, toxins, and/or Ricin toxin from  Ricinus communis.    
     
     
         104 . The method according to  claim 93 , wherein the disease or disorder is caused by a unicellular or multicellular parasite. 
     
     
         105 . The method according to  claim 93 , wherein the targets for said two or more non-identical antibodies are selected from HER-2/Neu receptor, VEGFR1 receptor, VEGFR2 receptor, a B-cell marker, a T-cell marker, a cytokine, an interleukin and a cytokine receptor. 
     
     
         106 . The method according to  claim 93 , wherein the mixture comprises three or more non-identical antibodies. 
     
     
         107 . The method according to  claim 93 , wherein the mixture comprises at least one bispecific antibody. 
     
     
         108 . The method according to  claim 93 , wherein the 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. 
     
     
         109 . The method according to  claim 93 , wherein the two or more non-identical antibodies from the mixture are of isotype IgG1, IgG2, IgG3 or IgG4. 
     
     
         110 . The method according to  claim 93 , wherein the at least two non-identical antibodies from the mixture are of IgG isotype. 
     
     
         111 . The method according to  claim 93 , wherein the two or more non-identical antibodies from the mixture comprise constant regions of isotype IgG1. 
     
     
         112 . The method according to  claim 93 , wherein at least two non-identical antibodies from the mixture are of different isotype. 
     
     
         113 . The method according to  claim 112 , wherein the different isotypes comprise at least an IgG and an IgA.