Enhanced delivery of drugs to the brain

Abstract

Compositions and methods related to antibodies or antibody fragments which are capable of crossing the blood brain barrier are provided.

1 .- 46 . (canceled) 
     
     
         47 . An antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain acceptor framework of SEQ ID NO: 1; and wherein the light chain comprises a light chain acceptor framework of SEQ ID NO: 2, wherein the light chain CDR1, CDR2 and CDR3 at amino acids 28-34, 50-56, and 91-97 of SEQ ID NO:2, respectively, are replaced with the CDR1, CDR2 and CDR3 of a desired antibody respectively; and wherein the heavy chain CDR1, CDR2 and CDR3 at amino acids 31-35, 50-59, and 101-109 of SEQ ID NO:1, respectively, are replaced with the CDR1, CDR2 and CDR3 of the desired antibody, respectively. 
     
     
         48 . The antibody of  claim 47 , wherein the desired antibody is selected from the group consisting of ibritumomab, tositumomab, ofatumumab, catumaxomab, gemtuzumab, alemtuzumab, eculizumab, cetuximab, pantiumumab, trastuzumab, certoluzimab, bevacizumab, ranibizumab, ipilimumab 
     
     
         49 . The antibody of  claim 47 , wherein the heavy chain CDRs from the desired antibody are from SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11 
     
     
         50 . The antibody of  claim 47 , wherein the light chain CDRs from the desired antibody are from SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11 
     
     
         51 . The antibody of  claim 47 , wherein the recombinant antigen binding protein has an isoelectric point of 8.0-9.0. 
     
     
         52 . The antibody of  claim 47 , wherein the recombinant antigen binding protein has an isoelectric point of about 8.7. 
     
     
         53 . The antibody of  claim 47 , wherein the recombinant antigen binding protein is capable of crossing the blood brain barrier. 
     
     
         54 . A composition comprising the antibody of  claim 47  and a pharmaceutically acceptable carrier. 
     
     
         55 . The composition of  claim 54 , wherein the composition is formulated for delivery to the brain. 
     
     
         56 . The composition of  claim 54 , wherein the composition is capable of crossing the blood brain barrier. 
     
     
         57 . The composition of  claim 54 , wherein the composition further comprises one or more agents. 
     
     
         58 . The composition of  claim 57 , wherein the agent is an imaging agent. 
     
     
         59 . The composition of  claim 57 , wherein the agent is a therapeutic agent. 
     
     
         60 . The composition of  claim 59 , wherein the therapeutic agent is a chemotherapeutic agent. 
     
     
         61 . The composition of  claim 57 , wherein the one or more agents are conjugated to the antibody.