Monoclonal antibodies and cocktails for treatment of ebola infections

Patent metadata

Field	Value
Publication number	US-2020354438-A1
Application number	US-202016896991-A
Country	US
Kind code	A1
Filing date	Jun 9, 2020
Priority date	Feb 17, 2017
Publication date	Nov 12, 2020
Grant date	—

Abstract

Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.

First claim

We claim:

1 . A composition for the treatment of Ebola, the composition comprising:
a therapeutically effective combination of
i. a first monoclonal antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 21, and affinity matured variants thereof; and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 23, and affinity matured variants thereof, wherein said first monoclonal antibody or antigen binding fragment thereof has a heavy chain CDR1 comprising SEQ ID NO: 47, a heavy chain CDR2 comprising SEQ ID NO: 48, a heavy chain CDR3 comprising SEQ ID NO: 49, a light chain CDR1 comprising SEQ ID NO: 50, a light chain CDR2 comprising SEQ ID NO: 51, and a light chain CDR3 comprising SEQ ID NO: 52 and amino acid sequences 90% identical thereto, and wherein the antigen to which the antigen binding fragment binds comprises Ebola glycoprotein; and
ii. a pharmaceutically acceptable excipient or carrier.

2 . The composition of claim 1 , wherein said first monoclonal antibody or antigen binding fragment thereof binds at least two species of Filovirus glycoprotein.

3 . The composition of claim 1 , wherein the first monoclonal antibody or antigen binding fragment that binds to the Ebola glycoprotein antigen thereof comprises predominantly a single glycoform.

4 . The composition of claim 3 , wherein the predominantly single glycoform is one of GnGn, G1/G2, and NaNa.

5 . The composition of claim 3 , wherein the predominantly single glycoform substantially lacks at least one of fucose and xylose.

6 . The composition of claim 2 further comprising a second monoclonal antibody or antigen binding fragment thereof, wherein said second monoclonal antibody or antigen binding fragment thereof binds Ebola glycoprotein.

7 . A composition for the treatment of Ebola, the composition comprising:
a therapeutically effective combination of
i. a first monoclonal antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 21, and affinity matured variants thereof; and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 23, and affinity matured variants thereof, wherein said first monoclonal antibody or antigen binding fragment thereof binds at least two species of Filovirus, and wherein the antigen to which the antigen binding fragment binds comprises Ebola glycoprotein; and
ii. a pharmaceutically acceptable excipient or carrier.

8 . The composition of claim 7 , wherein said first monoclonal antibody or antigen binding fragment thereof has a heavy chain CDR1 comprising SEQ ID NO: 47, a heavy chain CDR2 comprising SEQ ID NO: 48, a heavy chain CDR3 comprising SEQ ID NO: 49, a light chain CDR1 comprising SEQ ID NO: 50, a light chain CDR2 comprising SEQ ID NO: 51, and a light chain CDR3 comprising SEQ ID NO: 52 and amino acid sequences 90% identical thereto.

9 . The composition of claim 7 , wherein the first monoclonal antibody or antigen binding fragment that binds to the Ebola glycoprotein antigen thereof comprises predominantly a single glycoform.

10 . The composition of claim 9 , wherein the predominantly single glycoform is one of GnGn, G1/G2, and NaNa.

11 . The composition of claim 9 , wherein the predominantly single glycoform substantially lacks at least one of fucose and xylose.

12 . The composition of claim 7 further comprising a second monoclonal antibody or antigen binding fragment thereof, wherein said second monoclonal antibody or antigen binding fragment thereof binds the Ebola glycoprotein.

13 . A monoclonal antibody or antigen binding fragment thereof effective to treat Ebola comprising a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 21, and affinity matured variants thereof; and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 23, and affinity matured variants thereof, wherein said first monoclonal antibody or antigen binding fragment thereof comprises predominantly a single glycoform that binds at least two species of Filovirus, and wherein the antigen to which the antigen binding fragment binds comprises Ebola glycoprotein.

14 . The monoclonal antibody or antigen binding fragment thereof of claim 13 , wherein said first monoclonal antibody or antigen binding fragment thereof has a heavy chain CDR1 comprising SEQ ID NO: 47, a heavy chain CDR2 comprising SEQ ID NO: 48, a heavy chain CDR3 comprising SEQ ID NO: 49, a light chain CDR1 comprising SEQ ID NO: 50, a light chain CDR2 comprising SEQ ID NO: 51, and a light chain CDR3 comprising SEQ ID NO: 52 and amino acid sequences 90% identical thereto.

15 . The monoclonal antibody or antigen binding fragment thereof of claim 13 , wherein the predominantly single glycoform is one of GnGn, G1/G2, and NaNa.

16 . The monoclonal antibody or antigen binding fragment thereof of claim 13 , wherein the predominantly single glycoform substantially lacks at least one of fucose and xylose.

Assignees

• Mapp Biopharmaceutical Inc
• Albert Einstein College Medicine Inc
• Adimab Llc

Inventors

• Bornholdt Zachary A
• Zeitlin Larry
• Chandran Kartik
• Wec Anna
• Walker Laura

Classifications

• C07K16/10 Primary

  RNA viruses · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K2039/62

  characterised by the link between antigen and carrier · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title