Identification of novel broadly cross-reactive neutralizing human monoclonal antibodies using sequential antigen panning of phage display libraries

Abstract

The present invention provides a method of identifying novel broadly crossreactive neutralizing monoclonal antibodies using sequential antigen panning of phage display libraries, antibodies obtained in accordance with such a method, as well as fusion proteins and conjugates comprising same, and related isolated or purified nucleic acid molecules, vectors, host cells, compositions, and methods of use to inhibit an infection, reduce the severity of an infection, treat an infection, and inhibit cancer.

1 .- 68 . (canceled) 
     
     
         69 . An isolated antibody or antibody fragment to HIV envelope glycoprotein that can recognize one or more strains of HIV, wherein the antibody or antibody fragment comprises the sequence of SEQ ID NO: 4 or a variant thereof, wherein the variant comprises the sequence of SEQ ID NO: 19 as complementarity determining region 3 (CDR3) and retains the ability to bind to the same epitope on HIV envelope glycoprotein as that of the sequence of SEQ ID NO: 4. 
     
     
         70 - 131 . (canceled) 
     
     
         132 . The antibody or antibody fragment of  claim 69 , wherein the antibody or antibody fragment is a scFv. 
     
     
         133 . The antibody or antibody fragment of  claim 69 , wherein the antibody or antibody fragment is a Fab. 
     
     
         134 . The antibody or antibody fragment of  claim 69 , wherein the antibody or antibody fragment further comprises the sequence of SEQ ID NO: 7 or a variant thereof comprising the sequence of SEQ ID NO: 22 as CDR3. 
     
     
         135 . The antibody or antibody fragment of  claim 134 , wherein the variant of SEQ ID NO: 4 further comprises the sequence of SEQ ID NO: 18 as the CDR2. 
     
     
         136 . The antibody or antibody fragment of  claim 135 , wherein the variant of SEQ ID NO: 4 further comprises the sequence of SEQ ID NO: 17 as the CDR1. 
     
     
         137 . The antibody or antibody fragment of  claim 136 , wherein the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 21 as the CDR2. 
     
     
         138 . The antibody or antibody fragment of  claim 137 , wherein the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 20 as the CDR1. 
     
     
         139 . The antibody or antibody fragment of  claim 134 , wherein the variant of SEQ ID NO: 4 further comprises the sequence of SEQ ID NO: 18 as the CDR2, and the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 21 as the CDR2. 
     
     
         140 . The antibody or antibody fragment of  claim 139 , wherein the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 20 as the CDR1. 
     
     
         141 . The antibody or antibody fragment of  claim 69 , wherein the variant of SEQ ID NO: 4 further comprises the sequence of SEQ ID NO: 18 as complementarity determining region 2 (CDR2). 
     
     
         142 . The antibody or antibody fragment of  claim 141 , wherein the variant of SEQ ID NO: 4 further comprises the sequence of SEQ ID NO: 17 as complementarity determining region 1 (CDR1). 
     
     
         143 . The antibody or antibody fragment of  claim 134 , wherein the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 21 as complementarity determining region 2 (CDR2). 
     
     
         144 . The antibody or antibody fragment of  claim 143 , wherein the variant of SEQ ID NO: 7 further comprises the sequence of SEQ ID NO: 20 as complementarity determining region 1 (CDR1). 
     
     
         145 . An isolated antibody or antibody fragment to HIV envelope glycoprotein that can recognize one or more strains of HIV, wherein the antibody or antibody fragment comprises the sequence of SEQ ID NO: 4, the sequence of SEQ ID NO: 7, or both the sequence of SEQ ID NO: 4 and the sequence of SEQ ID NO: 7. 
     
     
         146 . The antibody or antibody fragment of  claim 145 , wherein the antibody or antibody fragment comprises the sequence of SEQ ID NO: 4. 
     
     
         147 . The antibody or antibody fragment of  claim 145 , wherein the antibody or antibody fragment comprises the sequence of SEQ ID NO: 7. 
     
     
         148 . The antibody or antibody fragment of  claim 145 , wherein the antibody or antibody fragment comprises both the sequence of SEQ ID NO: 4 and the sequence of SEQ ID NO: 7. 
     
     
         149 . The antibody or antibody fragment of  claim 145 , wherein the antibody or antibody fragment is a scFv. 
     
     
         150 . The antibody or antibody fragment of  claim 145 , wherein the antibody or antibody fragment is a Fab.