Antibodies that bind Ebola glycoprotein and uses thereof

An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Ebola virus glycoprotein, comprising:

• (a) a heavy chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 83, 84, and 85, respectively, and variable region framework residues selected from the group consisting of 44H, 48H, 70H, 72H, or a combination thereof (Kabat numbering convention) from the heavy chain variable region set forth in SEQ ID NO:
• 96, wherein the remainder of the heavy chain is from a human immunoglobulin;
• and
• (b) a light chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 87, 88, and 89 respectively, wherein the remainder of the light chain is from a human immunoglobulin;
• or
• (a) a heavy chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 74, 75, and 76, respectively, and variable region framework residues selected from the group consisting of 49H, 50H, or a combination thereof (Kabat numbering convention) from the heavy chain variable region set forth in SEQ ID NO:
• 94, wherein the remainder of the heavy chain is from a human immunoglobulin;
• and
• (b) a light chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 80, 81, and 82, respectively, and variable region framework residues selected from the group consisting of 3 L, 43 L, 45 L, 70 L, 71 L, 100 L, or a combination thereof (Kabat numbering convention) from the light chain variable region set forth in SEQ ID NO:
• 95, wherein the remainder of the light chain is from a human immunoglobulin;
• or
• (a) a heavy chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 45, 46, and 47, respectively, wherein the remainder of the heavy chain is from a human immunoglobulin;
• and
• (b) a light chain comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 48, 50, and 51, respectively, wherein the remainder of the light chain is from a human immunoglobulin.

An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Ebola virus glycoprotein, and comprises a heavy chain variable region and light chain variable region comprising an amino acid sequence at least 90% identical to the amino acid sequences selected from the group consisting of:

• (a) SEQ ID NOs:
• 15 and 17, respectively;
• (b) SEQ ID NOs:
• 32 and 37, respectively;
• and
• (c) SEQ IS NOs:
• 39 and 14, respectively;
• wherein the monoclonal antibody is a neutralizing antibody and specifically binds to Ebola virus glycoprotein with an EC50 of 200 pM or less, as measured by ELISA.

An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Ebola virus glycoprotein, comprising:

• (a) a heavy chain and a light chain, wherein:
• (i) the heavy chain comprises CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 83, 84, and 85, respectively, and variable region framework residues selected from the group consisting of 44H, 48H, 70H, 72H, or a combination thereof (Kabat numbering convention) from the heavy chain variable region set forth in SEQ ID NO:
• 96, wherein the remainder of the heavy chain is from a human immunoglobulin;
• and
• (ii) the light chain comprises CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 87, 88, and 89 respectively, wherein the remainder of the light chain is from a human immunoglobulin;
• or
• (b) a heavy chain and light chain, wherein:
• (i) the heavy chain comprises CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 74, 75, and 76, respectively, and variable region framework residues selected from the group consisting of 49H, 50H, or a combination thereof (Kabat numbering convention) from the heavy chain variable region set forth in SEQ ID NO:
• 94, wherein the remainder of the heavy chain is from a human immunoglobulin;
• and
• (ii) the light chain comprises CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs:
• 80, 81, and 82, respectively, and variable region framework residues selected from the group consisting of 3 L, 43 L, 45 L, 70 L, 71 L, 100 L, or a combination thereof (Kabat numbering convention) from the light chain variable region set forth in SEQ ID NO:
• 95, wherein the remainder of the light chain is from a human immunoglobulin;
• and wherein the monoclonal antibody binds to a conformational epitope on Ebola virus glycoprotein (SEQ ID NO:
• 91) comprising an amino acid sequence that spans V505-C511 and N550-E564.