Methods and compositions relating to anti-ccr7 antigen binding proteins

Abstract

The present invention provides compositions and methods relating to antigen binding proteins against CCR7, including antibodies, nucleic acids, vectors, methods of making the antigen binding proteins, and methods of using the antigen binding proteins.

What is claimed is: 
     
         1 . An isolated CCR7 antigen binding protein, wherein said antigen binding protein comprises either:
 a. the light chain variable domain sequence of antibody 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8; or   b. the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, 6E1.2 HC G2V, 6E1.2 HC F80Y, 6E1.2 HC G2V F80Y or MAB22_HC_V1; or   c. a light chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8; or   d. a heavy chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, or MAB22_HC_V1; or   e. a light chain variable domain sequence that differs at no more than 15, 12, 10, 8, 5, or 3 amino acid positions from the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8; or   f. a heavy chain variable domain sequence that differs at no more than 15, 12, 10, 8, 5, or 3 amino acid positions from the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, or MAB22_HC_V1; or   g. a light chain variable domain sequence that is encoded by a nucleic acid sequence that is at least 90%, 95%, 97%, or 99% identical to the nucleic acid sequence encoding the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8 as provided in  FIG. 1 ; or   h. a heavy chain variable domain sequence that is encoded by a nucleic acid sequence that is at least 90%, 95%, 97%, or 99% identical to the nucleic acid sequence encoding the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, 6E1.2 HC G2V, 6E1.2 HC F80Y, 6E1.2 HC G2V F80Y or MAB22_HC_V1, as provided in  FIG. 1 ; or   i. a light chain variable domain sequence that is encoded by a nucleic acid sequence that hybridizes under moderately stringent, stringent, or highly stringent conditions to the nucleic acid sequence encoding the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8 as provided in  FIG. 1 ; or   j. a heavy chain variable domain sequence that is encoded by a nucleic acid sequence that hybridizes under moderately stringent, stringent, or highly stringent conditions to the nucleic acid sequence encoding the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, 6E1.2 HC G2V, 6E1.2 HC F80Y, 6E1.2 HC G2V F80Y or MAB22_HC_V1, as provided in  FIG. 1 ; or   k. CDR1, CDR2, and CDR3 of the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, or MAB22_KLC_V1; or   l. CDR1, CDR2, and CDR3 of the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, 6E1.2 HC G2V, 6E1.2 HC F80Y, 6E1.2 HC G2V F80Y, or MAB22_HC_V1; or   m. light chain variable domain CDR1, CDR2, and CDR3 sequences that each differs at no more than 3, 2, or 1 amino acid positions from the light chain variable domain CDR1, CDR2, and CDR3 sequences, respectively, of the light chain variable domain sequence of 6B4.1 LC, 6B5.1 LC, 6E1.2 LC, 6B4.1 LC desS, 6E1.2 LC H36Q, or MAB22_KLC_V1; or   n. heavy chain variable domain CDR1, CDR2, and CDR3 sequences that each differs at no more than 3, 2, or 1 amino acid positions from the heavy chain variable domain CDR1, CDR2, and CDR3 sequences, respectively, of the heavy chain variable domain sequence of 6B4.1 HC, 6B5.1 HC, 6E1.2 HC, 6E1.2 HC G2V, 6E1.2 HC F80Y, 6E1.2 HC G2V F80Y, or MAB22_HC_V1.   
     
     
         2 . The isolated CCR7 antigen binding protein of  claim 1 , comprising:
 a. the light chain variable domain sequence of 6B4.1 LC or of 6B4.1 LC desS, as shown in  FIG. 1 , and the heavy chain variable domain sequence of 6B4.1 HC, as shown in  FIG. 1 ; or   b. the light chain variable domain sequence of 6B5.1 LC, as shown in  FIG. 1 , and the heavy chain variable domain sequence of 6B5.1 HC, as shown in  FIG. 1 ; or   c. the light chain variable domain sequence of 6E1.2 LC or of 6E1.2 LC H36Q, as shown in  FIG. 1 , and the heavy chain variable domain sequence of 6E1.2, 6E1.2 HC G2V, 6E1.2 HC F80Y, or 6E1.2 HC G2V F80Y, as shown in  FIG. 1 ; or   d. the light chain variable domain sequence of MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V1, as shown in  FIG. 1 , and the heavy chain variable domain sequence of MAB22_HC_V1, as shown in  FIG. 2 ; or   e. the light chain CDR 1, 2, and 3 sequences of 6B4.1 LC or of 6B4.1 LC desS, as shown in  FIG. 1 , and the heavy chain CDR 1, 2, and 3 sequences of 6B4.1 HC, as shown in  FIG. 1 ; or   f. the light chain CDR 1, 2, and 3 sequences of 6B5.1 LC, as shown in  FIG. 1 , and the heavy chain CDR 1, 2, and 3 sequences of 6B5.1 HC, as shown in  FIG. 1 ; or   g. the light chain CDR 1, 2, and 3 sequences of 6E1.2 LC or of 6E1.2 LC H36Q, as shown in  FIG. 1 , and the heavy chain CDR 1, 2, and 3 sequences of 6E1.2, 6E1.2 HC G2V, 6E1.2 HC F80Y, or 6E1.2 HC G2V F80Y, as shown in  FIG. 1 ; or   h. the light chain CDR 1, 2, and 3 sequences of MAB22_KLC-V1, as shown in  FIG. 1 , and the heavy chain CDR 1, 2, and 3 sequences of MAB22_HC_V1, as shown in  FIG. 1 ; or   i. a light chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the light chain variable domain sequence of 6B4.1 LC or of 6B4.1 LC desS, as shown in  FIG. 1 , and a heavy chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the heavy chain variable domain sequence of 6B4.1 HC, as shown in  FIG. 1 ; or   j. a light chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the light chain variable domain sequence of 6B5.1 LC, as shown in  FIG. 1 , and a heavy chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the heavy chain variable domain sequence of 6B5.1 HC, as shown in  FIG. 1 ; or   k. a light chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the light chain variable domain sequence of 6E1.2 LC or of 6E1.2 LC H36Q, as shown in  FIG. 1 , and a heavy chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the heavy chain variable domain sequence of 6E1.2, 6E1.2 HC G2V, 6E1.2 HC F80Y, or 6E1.2 HC G2V F80Y, as shown in  FIG. 1 ; or   l. a light chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the light chain variable domain sequence of MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8, as shown in  FIG. 1 , and a heavy chain variable domain sequence that is at least 90%, 95%, 97%, or 99% identical to the heavy chain variable domain sequence of MAB22_HC_V1, as shown in  FIG. 1 ; or   m. the light chain sequence of 6B4.1 LC or of 6B4.1 LC desS, as shown in  FIG. 1 , and the heavy chain sequence of 6B4.1 HC, as shown in  FIG. 1 ; or   n. the light chain sequence of 6B5.1 LC, as shown in  FIG. 1 , and the heavy chain sequence of 6B5.1 HC, as shown in  FIG. 1 ; or   o. the light chain sequence of 6E1.2 LC or of 6E1.2 LC H36Q, as shown in  FIG. 1 , and the heavy chain sequence of 6E1.2, 6E1.2 HC G2V, 6E1.2 HC F80Y, or 6E1.2 HC G2V F80Y, as shown in  FIG. 1 ; or   p. the light chain sequence of MAB22_KLC-V1, MAB22_KLC_V2, MAB22_KLC_V3, MAB22_KLC_V4, MAB22_KLC_V5, MAB22_KLC_V6, MAB22_KLC_V7, or MAB22_KLC_V8, as shown in  FIG. 1 , and the heavy chain sequence of MAB22_HC_V1, as shown in  FIG. 1 .   
     
     
         3 . The isolated CCR7 antigen binding protein of  claim 1 , wherein said CCR7 antigen binding protein is an anti-CCR7 antibody, and wherein said antibody comprises the sequences:
 a. 6B4.1 LC and 6B4. HC;   b. 6B5.1 LC and 6B5.1 HC; or   c. MAB22_KLC_V1 and MAB22_HC_V1.   
     
     
         4 . The isolated CCR7 antigen binding protein of  claim 1 , wherein said antigen binding protein competes for binding to a human CCR7 with antibody 6B4.1, 6B5.1, or 6E1.2. 
     
     
         5 . The isolated CCR7 antigen binding protein of  claim 1 , wherein said antigen binding protein comprises either:
 a. a light chain variable domain that differs from the light chain variable domain of antibody 6B4.1, 6B5.1, or 6E1.2 only in that one or more non-germline amino acid residues are replaced with the corresponding germline residues;   b. a heavy chain variable domain that differs from the heavy chain variable domain of antibody 6B4.1, 6B5.1, or 6E1.2 only in that one or more non-germline amino acid residues are replaced with the corresponding germline residues; or   c. a light chain variable domain that differs from the light chain variable domain of antibody 6B4.1, 6B5.1, or 6E1.2 only in that one or more non-germline amino acid residues are replaced with the corresponding germline residues, and a heavy chain variable domain that differs from the heavy chain variable domain of the same antibody 6B4.1, 6B5.1, or 6E1.2 only in that one or more non-germline amino acid residues are replaced with the corresponding germline residues.   
     
     
         6 . The isolated CCR7 antigen binding protein of  claim 1  wherein said antigen binding protein comprises:
 a. a human antibody; 
 b. a humanized antibody; 
 c. a chimeric antibody; 
 d. a monoclonal antibody; 
 e. a polyclonal antibody; 
 f. a recombinant antibody; 
 g. an antigen-binding antibody fragment; 
 h. a single chain antibody; 
 i. a diabody; 
 j. a triabody; 
 k. a tetrabody; 
 l. a Fab fragment; 
 m. a F(ab′)2 fragment; 
 n. a domain antibody; 
 o. an IgD antibody; 
 p. an IgE antibody; 
 q. an IgM antibody; 
 r. an IgG1 antibody; 
 s. an IgG2 antibody; 
 t. an IgG3 antibody; 
 u. an IgG4 antibody; or 
 v. an IgG4 antibody having at least one mutation in a hinge region that alleviates a tendency to form intra-H chain disulfide bond. 
 
     
     
         7 . The isolated CCR7 antigen binding protein of  claim 1  wherein said antigen binding protein inhibits binding of CCL19 or CCL21 to CCR7. 
     
     
         8 . An isolated anti-CCR7 antibody, wherein said antibody binds to wild-type human CCR7, but does not bind to wild-type murine CCR7. 
     
     
         9 . The isolated anti-CCR7 antibody of  claim 8 , wherein said antibody also binds to a mutated human CCR7 polypeptide, wherein said mutated human CCR7 polypeptide differs from wild-type human CCR7 only by the mutation F44Y. 
     
     
         10 . The isolated anti-CCR7 antibody of  claim 9 , wherein said antibody binds to said mutated human CCR7 polypeptide at least as well as either antibody 6B4.1 or antibody 6B5.1. 
     
     
         11 . The isolated anti-CCR7 antibody of  claim 8 , wherein said antibody does not bind to a mutated murine CCR7, wherein said mutated murine CCR7 differs from wild-type murine CCR7 only by the mutations Y44F and V47L. 
     
     
         12 . The isolated anti-CCR7 antibody of  claim 8 , wherein said antibody binds better than antibody mAb197 to a mutated murine CCR7, wherein said mutated murine CCR7 differs from wild-type murine CCR7 only by the mutations K201R, N202S, G204S, T207A, and L208M. 
     
     
         13 . An isolated polynucleotide comprising a sequence that encodes the light chain, the heavy chain, or both of said isolated CCR7 antigen binding protein of  claim 1  or of the isolated anti-CCR7 antibody of  claim 8 . 
     
     
         14 . The isolated polynucleotide of  claim 13 , wherein said isolated polynucleotide comprises a light chain variable domain nucleic acid sequence and/or a heavy chain variable domain nucleic acid sequence of  FIG. 1 . 
     
     
         15 . A plasmid comprising said isolated polynucleotide of  claim 13 . 
     
     
         16 . The plasmid of  claim 15 , wherein said plasmid is an expression vector. 
     
     
         17 . An isolated cell comprising said isolated polynucleotide of  claim 13 . 
     
     
         18 . The isolated cell of  claim 17 , wherein a chromosome of said cell comprises said polynucleotide. 
     
     
         19 . The isolated cell of  claim 17 , wherein said cell is a hybridoma. 
     
     
         20 . The isolated cell of  claim 17 , wherein an expression vector comprises said polynucleotide. 
     
     
         21 . The isolated cell of  claim 17 , wherein said cell is a CHO cell. 
     
     
         22 . The isolated cell of  claim 17 , wherein said cell is a bacterial cell. 
     
     
         23 . The isolated cell of  claim 17 , wherein said cell is an  E. coli  cell. 
     
     
         24 . The isolated cell of  claim 17 , wherein said cell is a yeast cell. 
     
     
         25 . The isolated cell of  claim 17 , wherein said cell is an animal cell. 
     
     
         26 . The isolated cell of  claim 17 , wherein said cell is a human cell. 
     
     
         27 . A method of making a CCR7 antigen binding protein, comprising incubating said isolated cell of  claim 17  under conditions that allow it to express said antigen binding protein. 
     
     
         28 . A pharmaceutical composition comprising the CCR7 antigen binding protein of  claim 1  or the anti-CCR7 antibody of  claim 8 .