Epstein-barr virus antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2020055924-A1
Application number	US-201816609078-A
Country	US
Kind code	A1
Filing date	Apr 27, 2018
Priority date	Apr 28, 2017
Publication date	Feb 20, 2020
Grant date	—

Abstract

Disclosed herein are antibodies or immunogenic fragments thereof that specifically bind to Epstein-Barr virus (EBV) glycoprotein 350 (gp350) or 220 or one or more epitopes of EBV gp350 and neutralize EBV infection. Also disclosed are immunogenic peptides comprising one or more gp350 epitopes, EBV antibody-small molecule conjugates and pharmaceutical compositions comprising the antibody or an immunogenic fragment thereof, one or more epitopes of EBV gp350, one or more immunogenic peptides, or the EBV antibody-small molecule conjugate. The antibodies, epitopes, immunogenic peptides, conjugates, and pharmaceutical compositions can be used to treat or prevent EBV infections and EBV-associated conditions and diseases.

First claim

1 . An antibody or an immunogenic fragment thereof that specifically binds to Epstein-Barr virus (EBV) glycoprotein (gp) 350 or glycoprotein 220.

2 . The antibody or the immunogenic fragment thereof of claim 1 , wherein the antibody or the immunogenic fragment thereof specifically binds to a gp350 epitope comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

3 . The antibody or the immunogenic fragment thereof of claim 1 or claim 2 , comprising a VH region comprising CDR1, CDR2 and CDR3 having an amino acid sequence of SEQ ID NOs: 4-51.

4 . The antibody or the immunogenic fragment thereof of claim 1 or claim 2 , comprising a VL region comprising CDR1, CDR2 and CDR3 having an amino acid sequence of SEQ ID NOs: 52-99.

5 . The antibody of any one of claims 1 - 4 , wherein the antibody is a monoclonal antibody.

6 . The antibody of any one of claims 1 - 4 , wherein the antibody is a chimeric antibody, a humanized antibody or a human antibody.

7 . An immunogenic peptide comprising one or more gp350 epitopes, wherein each epitope has an amino acid sequence identical to or sharing at least 60% similarity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

8 . The immunogenic peptide of claim 7 , comprising a first domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO:1, a second domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 2, and a third domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 3.

9 . The immunogenic peptide of claim 7 , comprising a first domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, and a second domain comprising a known immunogenic peptide such as keyhole limpet hemocyanin (KLH) peptide.

10 . An antibody-small molecule conjugate comprising:
an antibody or an immunogenic fragment thereof that specifically binds to EBV gp350 or EBV gp220; and a small molecule having an anti-proliferative activity against EBV-transformed cells, wherein the small molecule is conjugated to the antibody.

11 . The conjugate of claim 10 , wherein the antibody is a monoclonal antibody.

12 . The conjugate of claim 10 , wherein the antibody is a chimeric antibody, a humanized antibody or a human antibody.

13 . The conjugate of any one of claims 10 - 12 , wherein the small molecule is a growth inhibitor of EBV infected B cells.

14 . The conjugate of any one of claims 10 - 13 , wherein the small molecule is L 2 P 4 , 2-butynediamide, or a derivative thereof.

15 . The conjugate of any one of claims 10 - 14 , wherein the small molecule is conjugated to the antibody via a linker or an adaptor.

16 . The conjugate of any one of claims 10 - 15 , wherein the small molecule is conjugated to the constant region of the heavy chain or the light chain of the antibody.

17 . A pharmaceutical composition comprising the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , or the conjugate of any one of claim 10 - 16 .

18 . A method of neutralizing EBV infection comprising administering to a subject infected with EBV a therapeutically effective amount of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , the conjugate of any one of claim 10 - 16 , or the pharmaceutical composition of claim 17 .

19 . A method of preventing EBV infection comprising administering to a subject at an elevated risk of EBV infection a therapeutically effective amount of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , the conjugate of any one of claim 10 - 16 , or the pharmaceutical composition of claim 17 .

20 . A method of preventing a post-transplant lymphoproliferative disease (PTLD) comprising administering to a subject who is a transplant recipient a therapeutically effective amount of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , the conjugate of any one of claim 10 - 16 , or the pharmaceutical composition of claim 17 .

21 . The method of claim 20 , wherein the subject is a pediatric transplant recipient who is EBV naïve or an adult transplant recipient.

22 . The method of claim 20 or claim 21 , wherein the administration is before, during, and/or after the transplant.

23 . A method of treating an EBV-associated cancer comprising administering to a subject suffering from an EBV-associated cancer a therapeutically effective amount of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , the conjugate of any one of claim 10 - 16 , or the pharmaceutical composition of claim 17 .

24 . The method of claim 23 , wherein the EBV-associated cancer is selected from the group consisting of Hodgkin lymphoma, Burkitt lymphoma, gastric cancer, and nasopharyngeal carcinoma.

25 . A method of immunizing or vaccinating a subject against EBV infection comprising administering to the subject a therapeutically effective amount of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 , or a pharmaceutical composition thereof.

26 . A method of inducing the production of neutralizing antibodies against a EBV in a subject, comprising administering an effective amount of a gp350 epitope represented by SEQ ID NO: 3 or an immunogenic peptide comprising SEQ ID NO: 3.

27 . The method of any one of claims 18 - 26 , wherein the subject is human.

28 . Use of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 for inducing the production of a neutralizing antibody against EBV in a subject.

29 . Use of the antibody or the immunogenic fragment thereof of any one of claims 1 - 6 , the immunogenic peptide of any one of claims 7 - 9 for the manufacture of a medicament for inducing the production of a neutralizing antibody against EBV in a subject.

Assignees

• Hope City
• California Inst Of Techn

Inventors

• Ogembo Javier Gordon
• Mutsvunguma Lorraine Zvichapera
• Ondrus Alison Evelynn

Classifications

• C07K2317/76

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

• A61K47/6839

  the antibody targeting material from viruses · CPC title

• A61K47/6811

  the drug being a protein or peptide, e.g. transferrin or bleomycin · CPC title

• C07K16/085 Primary

  Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus · 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