Prolactin receptor binding proteins and uses thereof

Abstract

The present invention encompasses PRLR binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hPRLR and neutralize hPRLR activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hPRLR and for inhibiting hPRLR activity, e.g., in a human subject suffering from a disorder in which hPRLR activity is detrimental. Also included in the invention are anti-PRLR antibody drug conjugates (ADCs).

1 - 18 . (canceled) 
     
     
         19 . A nucleic acid encoding a monoclonal antibody capable of binding prolactin receptor (PRLR), said antibody comprising:
 (i) a heavy chain variable domain CDR set comprising SEQ ID NOs: 40, 41, 42; and   (ii) a light chain variable domain CDR set comprising SEQ ID NOs: 49, 50, and 51.   
     
     
         20 . A vector comprising the nucleic acid according to  claim 19 . 
     
     
         21 . A host cell comprising the vector according to  claim 20 . 
     
     
         22 . The host cell according to  claim 21 , wherein said host cell is a eukaryotic cell. 
     
     
         23 . The host cell according to  claim 22 , wherein
 said host cell is selected from the group consisting of a CHO cell, a COS cell, a yeast cell, an insect Sf9 cell, and a HEK 293 cell.   
     
     
         24 . A method of producing a monoclonal antibody capable of binding PRLR, comprising culturing a host cell of  claim 21  in culture medium under conditions sufficient to produce said monoclonal antibody capable of binding PRLR. 
     
     
         25 .- 36 . (canceled) 
     
     
         37 . The vector of  claim 20 , wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pVJ, and pBJ. 
     
     
         38 . A nucleic acid encoding a monoclonal antibody capable of binding prolactin receptor (PRLR), said antibody comprising:
 (i) a heavy chain variable domain comprising SEQ ID NO: 44; and   (ii) a light chain variable domain comprising SEQ ID NO: 52.   
     
     
         39 . A vector comprising the nucleic acid according to  claim 38 . 
     
     
         40 . The vector of  claim 39 , wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pVJ, and pBJ. 
     
     
         41 . A host cell comprising the vector according to  claim 39 . 
     
     
         42 . The host cell according to  claim 41 , wherein said host cell is a eukaryotic cell. 
     
     
         43 . The host cell according to  claim 42 , wherein cell is selected from the group consisting of a CHO cell, a COS cell, a yeast cell, an insect Sf9 cell, and a HEK 293 cell. 
     
     
         44 . A method of producing a monoclonal antibody capable of binding PRLR, comprising culturing a host cell of  claim 41  in culture medium under conditions sufficient to produce said monoclonal antibody capable of binding PRLR. 
     
     
         45 . A nucleic acid encoding a monoclonal antibody capable of binding prolactin receptor (PRLR), said antibody comprising:
 (i) a heavy chain comprising SEQ ID NO: 129; and   (ii) a light chain variable domain comprising SEQ ID NO: 126.   
     
     
         46 . A vector comprising the nucleic acid according to  claim 45 . 
     
     
         47 . The vector of  claim 46 , wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pVJ, and pBJ. 
     
     
         48 . A host cell comprising the vector according to  claim 46 . 
     
     
         49 . The host cell according to  claim 48 , wherein said host cell is a eukaryotic cell. 
     
     
         50 . The host cell according to  claim 49 , wherein cell is selected from the group consisting of a CHO cell, a COS cell, a yeast cell, an insect Sf9 cell, and a HEK 293 cell. 
     
     
         51 . A method of producing a monoclonal antibody capable of binding PRLR, comprising culturing a host cell of  claim 48  in culture medium under conditions sufficient to produce said monoclonal antibody capable of binding PRLR.