Compositions and methods for inhibiting pathogen infection

Patent metadata

Field	Value
Publication number	US-10100102-B2
Application number	US-201314438511-A
Country	US
Kind code	B2
Filing date	Oct 29, 2013
Priority date	Oct 29, 2012
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating pathogen infection and providing contraception. In particular, the presently-disclosed subject matter relates to inhibiting and treating pathogen infection and providing contraception in a subject using compositions and antibodies capable of trapping pathogens or sperm in mucus, thereby inhibiting transport of pathogens or sperm across mucus secretions. The subject matter further relates to methods for monitoring the effectiveness of vaccines by detecting antibodies capable of trapping pathogens in mucus.

First claim

We claim:

1. An aerosol composition comprising a population of a human or humanized IgG monoclonal antibody directed against a virus that causes a respiratory disease, each antibody in the population comprising an oligosaccharide at a glycosylation site, the population comprising glycosylation patterns that enhance trapping potency of the antibody in mucus, wherein the antibody specifically binds an epitope of the virus, and wherein at least 30% of the 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.

2. The aerosol composition of claim 1 , wherein the glycosylation site is in an N-linked glycosylation site in an Fe region of the antibodies.

3. The aerosol composition of claim 1 , wherein the epitope is a non-neutralizing epitope.

4. The aerosol composition of claim 1 , wherein the epitope is a neutralizing epitope.

5. The aerosol composition of claim 4 , wherein the antibody has trapping potency at a sub-neutralization dose.

6. The aerosol composition of claim 1 , wherein the epitope is a conserved epitope.

7. The aerosol composition of claim 1 , wherein the antibody comprises at least one Fc region.

8. The aerosol composition of claim 1 , further comprising a second population of a second IgG monoclonal antibody, each antibody in the second population comprising an oligosaccharide at a glycosylation site, the second population comprising glycosylation patterns that enhance trapping potency of the second antibody in mucus, wherein the second antibody specifically binds a second epitope of the virus, wherein said second epitope is distinct from the epitope to which the first antibody specifically binds, or wherein the second antibody specifically binds an epitope of a target pathogen, wherein said target pathogen is different from the virus, wherein at least 30% of the antibodies in the second 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.

9. A pharmaceutical composition comprising the aerosol composition of claim 1 and a pharmaceutically acceptable carrier.

10. A kit comprising the aerosol composition of claim 1 .

11. The aerosol composition of claim 1 , wherein the antibody reduces the mobility of at least 50% of the virus within mucus to at least one-tenth of its mobility in saline.

12. The aerosol composition of claim 1 , wherein the antibody has a sufficient binding rate to an epitope of the virus to accumulate on the surface of the virus at sufficient levels to trap the virus in mucus within one hour at an antibody concentration of less than 100 μg/ml.

13. An aerosol composition comprising a population of a human or humanized IgG monoclonal antibody directed against a virus that causes a respiratory disease, each antibody in the population comprising an oligosaccharide at a glycosylation site, the population comprising glycosylation patterns that enhance trapping potency of the antibody in mucus, wherein the antibody specifically binds an epitope of the virus, and wherein the population comprises a sufficient amount of antibody having a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch for the concentration of the antibody having a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch in mucus after administration to a subject to be at least about 1 μg/ml.

14. An aerosol composition comprising a population of a human or humanized IgG monoclonal antibody directed against a virus that causes a respiratory disease, each antibody in the population comprising an oligosaccharide at a glycosylation site, the population comprising glycosylation patterns that enhance trapping potency of the antibody in mucus, wherein the antibody specifically bind an epitope of the virus, and wherein the population comprises a sufficient amount of antibody 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 trap the virus in mucus after administration to a subject.

Assignees

• Univ North Carolina Chapel Hill
• Univ Johns Hopkins

Inventors

• Lai Samuel
• Wang Ying-Ying
• Kannan Arthi
• Nunn Kennetta
• Subramani Durai Babu
• Cone Richard

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• C07K16/087

  Herpes simplex virus · CPC title

• C07K16/1235 Primary

  Salmonella (G) · CPC title