Compositions and methods for inhibiting pathogen infection

Patent metadata

Field	Value
Publication number	US-10829543-B2
Application number	US-201816138643-A
Country	US
Kind code	B2
Filing date	Sep 21, 2018
Priority date	Oct 29, 2012
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating virus infection in the respiratory tract and virus transmission through the respiratory tract. In particular, the presently-disclosed subject matter relates to inhibiting and treating virus infection in a subject using compositions and antibodies that trap viruses in mucus of the respiratory tract, thereby inhibiting transport of virus across or through mucus secretions.

First claim

What is claimed is:

1. A method for treating, immobilizing or inhibiting a viral infection by a virion in a subject in need thereof, the method comprising administering to the subject, via an inhaled route, a recombinant antibody with a specific affinity for the virion, the recombinant antibody comprising a human or humanized Fc region, wherein the recombinant antibody comprises a population of antibodies in which at least 40% comprise an oligosaccharide having a G0 glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch that enhances the trapping potency of the recombinant antibody in mucus, so that the recombinant antibody binds to the virion to form an antibody/virion complex that is trapped in the subject's mucus.

2. The method of claim 1 , wherein the recombinant antibody comprises an N-linked glycosylation site on the Fc region of the antibodies to which the oligosaccharide is attached.

3. The method of claim 1 , wherein 50% or more of the recombinant antibodies in the population have a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch.

4. The method of claim 1 , wherein the recombinant antibody is configured to bind to a non-neutralizing epitope of the virion.

5. The method of claim 1 , wherein administering comprises administering a dose at a sub-neutralization dose level.

6. The method of claim 1 , further comprising reducing the mobility of the virion in the patient's mucus to no more than about 50% relative to its mobility in water.

7. The method of claim 1 , further comprising reducing the percentage of virion that can penetrate the patient's mucus by at least 10%.

8. The method of claim 1 , wherein the recombinant antibody is a human or humanized IgG or IgM monoclonal antibody, or a fragment or derivative thereof.

9. The method of claim 1 , wherein the recombinant antibody is formulated as an aerosol composition.

10. The method claim 1 , wherein the virion is selected from: respiratory syncytial virus (RSV), influenza virus, adenovirus, human rhinovirus, coronavirus, and parainfluenza virus.

11. The method claim 1 , wherein the virion is respiratory syncytial virus.

12. A method of immobilizing a respiratory virion in mucus of a subject's lung, the method comprising administering to the subject, via an inhaled route, a population of recombinant antibodies with a specific affinity for the virion, the recombinant antibodies comprising a human or humanized Fc region, wherein at least 50% of the recombinant antibodies comprise an oligosaccharide having a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch to enhance the trapping potency of the recombinant antibody in mucus, so that the recombinant antibodies bind to the virion to form an antibody/virion complex that is trapped in the subject's mucus.

13. The method of claim 12 , wherein the recombinant antibodies are configured to bind to a non-neutralizing epitope of the virion.

14. The method of claim 12 , wherein administering comprises administering a dose at a sub-neutralization dose level.

15. The method of claim 12 , wherein the recombinant antibodies comprise an N-linked glycosylation site on the Fe region of the antibodies to which the oligosaccharide is attached.

16. The method of claim 12 , further comprising reducing the mobility of the virion to no more than about 50% relative to its mobility in water.

17. The method of claim 12 , further comprising reducing the percentage of virion that can penetrate mucus by at least 10%.

18. The method of claim 12 , wherein the recombinant antibody is a human or humanized IgG or IgM monoclonal antibody, or a fragment or derivative thereof.

19. The method of claim 12 , wherein the recombinant antibody is formulated as an aerosol composition.

20. The method of claim 12 , wherein at least 60% of the recombinant antibodies in the population have a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch.

21. The method of claim 12 , wherein the virion is selected from: respiratory syncytial virus (RSV), influenza virus, adenovirus, human rhinovirus, coronavirus, and parainfluenza virus.

22. The method claim 12 , wherein the virion is respiratory syncytial virus.

23. A method for inhibiting a respiratory virion in mucus of a subject's lung, the method comprising immobilizing the virion by administering to the subject, via an inhaled route, a population of recombinant antibody in which at least 40% comprise an oligosaccharide having a G0 glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manα1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch, wherein the recombinant antibody has a specific affinity for the virion so that the recombinant antibody is trapped in the subject's mucus, the recombinant antibody comprising a human or humanized Fc region, wherein the recombinant antibody comprises an oligosaccharide having a glycosylation pattern that enhances the trapping potency of the recombinant antibody in mucus.

Assignees

• Univ North Carolina Chapel Hill
• Univ Johns Hopkins

Inventors

• Lai Samuel
• Wang Ying-Ying
• Kannan Arthi
• Nunn Kenetta
• Subramani Durai Babu
• Cone Richard
• Yang Bing
• Mccallen Justin

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C07K16/10

  RNA viruses · CPC title

• C07K16/1214

  Pseudomonadaceae (F) · CPC title

• C07K2317/54

  F(ab')2 · CPC title

• C07K2317/13

  isolated from plants · CPC title