Human antibodies to Ebola virus glycoprotein
The present invention provides monoclonal antibodies, or antigen-binding fragments thereof, that bind to Ebola virus glycoproteins, pharmaceutical compositions comprising the antibodies and methods of use. The antibodies of the invention are useful for inhibiting or neutralizing Ebola virus activity, thus providing a means of treating or preventing Ebola virus infection in humans. In some embodiments, the invention provides for use of one or more antibodies that bind to the Ebola virus for preventing viral attachment and/or entry into host cells. The antibodies of the invention may be used prophylactically or therapeutically and may be used alone or in combination with one or more other anti-viral agents or vaccines.
1. A method of treating or ameliorating at least one symptom of EBOV infection, or of decreasing the frequency or severity of at least one symptom of EBOV infection, the method comprising administering to a subject in need thereof at least one antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within any one of the heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pairs selected from the group consisting of SEQ ID NOs: 18/26, 66/74, and 146/154, or a pharmaceutically acceptable composition comprising the at least one antibody or antigen-binding fragment thereof.
2. The method of claim 1 , comprising administering an antibody cocktail comprising a mixture of at least two anti-EBOV antibodies.
3. The method of claim 1 , comprising administering an antibody cocktail comprising a mixture of three anti-EBOV antibodies, wherein the three anti-EBOV antibodies comprise HCVR/LCVR amino acid sequence pairs as set forth in SEQ ID NOs: 18/26, 66/74 and 146/154.
4. The method of claim 3 , wherein the at least one symptom is selected from the group consisting of fever, headache, fatigue, loss of appetite, myalgia, diarrhea, vomiting, abdominal pain, dehydration and unexplained bleeding.
5. The method of claim 3 , wherein the pharmaceutical composition is administered prophylactically or therapeutically to the subject in need thereof.
6. The method of claim 3 , wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition comprising the antibody or antigen-binding fragment thereof is administered in combination with a second therapeutic agent.
7. The method of claim 6 , wherein the second therapeutic agent is selected from the group consisting of an anti-viral drug, an anti-inflammatory drug, a different antibody to EBOV, a vaccine for EBOV, small interfering RNAs that target viral RNA polymerase, brincidofovir, favipiravir, BCX-4430, antisense phosphorodiamidate morpholino oligomers that target Ebola virus VP24 gene, and interferons.
8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition comprising the antibody or antigen-binding fragment thereof is administered subcutaneously, intravenously, intradermally, intramuscularly, intranasally, or orally.
9. The method of claim 1 , wherein the composition comprises an antibody having the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID Nos: 20/22/24/28/30/32, respectively.
10. The method of claim 1 , where the composition comprises an antibody having the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 68/70/72/76/78/80, respectively.
11. The method of claim 1 , wherein the composition comprises an antibody having the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 148/150/152/156/158/160, respectively.
12. The method of claim 1 , wherein the composition comprises at least three antibodies, and wherein the antibodies comprise the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 20/22/24/28/30/32, 68/70/72/76/78/80, and 148/150/152/156/158/160, respectively.
13. The method of claim 7 , wherein the second therapeutic agent is an anti-inflammatory selected from corticosteroids and non-steroidal anti-inflammatory drugs.