Non-human primate Fc receptors and methods of use

Abstract

The invention provides isolated non-human primate Fc receptor polypeptides, the nucleic acid molecules encoding the Fc receptor polypeptides, and the processes for production of recombinant forms of the Fc receptor polypeptides, including fusions, variants, and derivatives thereof. The invention also provides methods for evaluating the safety, efficacy and biological properties of Fc region containing molecules using the non-human primate Fc receptor polypeptides.

1 - 43 . (cancelled)  
     
     
         44 . A method for evaluating at least one biological property of an Fc region containing molecule comprising: 
 a) contacting an isolated non-human primate Fc receptor polypeptide with an Fc region containing molecule; and    b) determining the effect of the contact on at least one biological property of the Fc region containing molecule.    
     
     
         45 . A method according to  claim 44 , wherein the Fc region containing molecule is an antibody.  
     
     
         46 . A method according to  claim 45 , wherein the antibody is a humanized antibody.  
     
     
         47 . A method according to  claim 46 , wherein the antibody is an antibody variant.  
     
     
         48 . A method according to  claim 47 , wherein the non-human primate Fc receptor polypeptide is a soluble receptor.  
     
     
         49 . A method according to  claim 48 , wherein the non-human primate receptor polypeptide is selected from the group consisting of FcγRI α-chain, FcγRIIA, FcγRIIB, FcγRIIA α-chain, FcRn α-chain and mixtures thereof.  
     
     
         50 . A method according to  claim 44 , wherein the non-human primate receptor polypeptide is expressed on a cell.  
     
     
         51 . A method according to  claim 44 , wherein the biological property is the binding affinity of the Fc region containing molecule for the non-human primate receptor polypeptide.  
     
     
         52 . A method according to  claim 44 , wherein the biological property is the toxicity of the Fc region containing molecule.  
     
     
         53 . A method according to  claim 44 , wherein the isolated non-human primate Fc receptor polypeptide is a FcRn α-chain and the biological property is the half-life of the Fc region containing molecule.  
     
     
         54 . A method according to  claim 44 , wherein the non-human primate Fc receptor polypeptide comprises an amino sequence of 1 to 265 of SEQ ID NO: 65.  
     
     
         55 . A method according to  claim 44 , wherein the non-human primate Fc receptor polypeptide comprises an amino acid sequence of 1 to 172 of SEQ ID NO: 66.  
     
     
         56 . A method according to  claim 44 , wherein the non-human primate Fc receptor polypeptide comprises an amino acid sequence of 1 to 174 of SEQ ID NO: 68.  
     
     
         57 . A method according to  claim 47 , wherein the non-human primate receptor polypeptide comprises an amino acid sequence of amino acids 1 to 172 of SEQ ID NO: 69.  
     
     
         58 . A method according to  claim 44 , wherein the non-human primate Fc receptor polypeptide comprises an amino acid sequence of amino acids 1 to 171 of SEQ ID NO: 67.  
     
     
         59 . A method for evaluating at least one biological property of an Fc region containing molecule comprising: 
 a) contacting a Fc region containing molecule with a cell transformed with an isolated nucleic acid encoding a nonhuman primate Fc receptor polypeptide; and    b) determining the effect of the contact on at least one biological property of the Fc region containing molecule.    
     
     
         60 . A method according to  claim 59 , wherein the Fc region containing molecule is an antibody or antibody variant.  
     
     
         61 . A method according to  claim 59 , wherein the biological property is the binding affinity of the Fc region containing molecule for the non-human primate Fc receptor polypeptide.  
     
     
         62 . A method according to  claim 59 , wherein the cell is transformed with at least two nucleic acids according to claim  1 .  
     
     
         63 . A method according to  claim 62 , wherein the nucleic acids comprise a nucleic acid that encodes a cynomolgus FcγRI α-chain of SEQ ID NO: 9 and a nucleic acid that encodes a cynomolgus FcγR gamma chain of SEQ ID NO: 11.  
     
     
         64 . A method according to  claim 62 , wherein the nucleic acids comprise a nucleic acid that encodes a cynomolgus FcγRIII α-chain of SEQ ID NO: 20 and a nucleic acid that encodes a cynomolgus FcγR gamma chain of SEQ ID NO: 11.  
     
     
         65 . A method according to  claim 62 , wherein the nucleic acids comprise a nucleic acid that encodes a cynomolgus FcγR α-chain of SEQ ID NO: 29 and a nucleic acid sequence that encodes a cynomolgus β-2 microglobulin of SEQ ID NO:25.  
     
     
         66 . A method for identifying an agent that has an increased affinity for at least one cynomolgus Fc receptor polypeptide with an ITAM region compared to human Fc receptor polypeptide comprising: 
 a) determining the binding affinity of the agent to at least one cynomolgus Fc receptor polypeptide associated a polypeptide with an ITAM region;    b) determining the binding affinity of the agent to the corresponding human Fc receptor polypeptide; and    c) selecting agents that have an increased affinity for the cynomolgus Fcγ receptor polypeptide associated with a polypeptide with an ITAM region compared to the corresponding human Fc receptor.    
     
     
         67 . A method according to  claim 66 , wherein the agent is an antibody.  
     
     
         68 . A method according to  claim 67 , wherein the agent is an IgG antibody.  
     
     
         69 . A method according to  claim 67 , wherein the Fc receptor polypeptide is selected from the group consisting of FcγR1 α-chain, FcγRIIA, FcγRIIIA α-chain and mixtures thereof.  
     
     
         70 . A method for identifying an agent that has an altered affinity for a cynomolgus Fc receptor polypeptide with an ITIM region compared to corresponding human Fc receptor polypeptide comprising: 
 a) determining a binding affinity for the agent to be at least one cynomolgus FcγRIIB receptor polypeptide;    b) determining a binding affinity of the agent to corresponding human FcγRIIB receptor polypeptide; and    c) selecting agents with altered affinity for a cynomolgus FcγRIIB receptor polypeptide with an ITIM region compared to corresponding human FcγRIIB polypeptide.    
     
     
         71 . A method according to  claim 70 , wherein the agent is an antibody.  
     
     
         72 . A method for identifying an agent with increased binding affinity for a cynomolgus Fc receptor polypeptide with an ITAM region and decreased affinity for a cynomolgus Fc receptor polypeptide with an ITIM region comprising: 
 a) determining a binding affinity of the agent for at least one cynomolgus Fc receptor polypeptide associated with an ITAM region and a binding affinity of the agent to the corresponding human Fc receptor polypeptide;    b) determining the binding affinity of the agent for at least one cynomolgus Fc receptor polypeptide with an ITIM region and a binding affinity of the agent for the corresponding human Fc receptor polypeptide; and    c) selecting an agent with enhanced binding for a cynomolgus Fc receptor polypeptide with an ITAM region and a decreased affinity for a cynomolgus Fc receptor polypeptide with an ITIM region compared to the corresponding human Fc receptor polypeptides.    
     
     
         73 . A method according to  claim 72 , wherein the Fcγ receptor with an ITAM region is an Fcγ receptor IIA and the Fcγ receptor with an ITIM region is a Fcγ receptor IIB.  
     
     
         74 . A method according to  claim 73 , wherein the agent is an antibody.  
     
     
         75 - 90 . (cancelled)