# US 11,897,939 B2 · Compositions and methods for inhibiting pathogen infection

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- Number: US 11,897,939 B2
- Document ID: US11897939B2
- Status: Granted
- Kind: B2
- Application number: 17/066,874
- Filed: 2020-10-09
- Published: 2021-03-04
- Granted: 2024-02-13
- Earliest claimed: 2012-10-29
- Assignees: The University of North Carolina at Chapel Hill; The Johns Hopkins University
- Applicants: The University of North Carolina at Chapel Hill; The Johns Hopkins University
- Inventors: Samuel Lai; Ying-Ying Wang; Arthi Kannan; Kenetta Nunn; Durai Babu Subramani; Richard Cone; Bing Yang; Justin Mccallen
- Web page: https://patentgrep.com/patent/US11897939B2

## CPC

- C07K 16/087: Herpes simplex virus
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/22: for herpes viruses
- C07K 16/10: RNA viruses
- C07K 16/11: Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
- C07K 16/1214: Pseudomonadaceae (F)
- A61K 2039/505: {comprising antibodies}
- A61K 2039/544: {to the airways}
- C07K 2317/13: isolated from plants
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/54: F(ab')2
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 1

A method for immobilizing or inhibiting a sexually transmitted infection by a pathogen, or reducing pathogen load in a subject in need thereof, the method comprising administering to a mucosal surface of the subject a recombinant antibody with a specific affinity for the pathogen, 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 GOF glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with a fucose residue and a terminal N-acetylglucosamine, wherein the terminal N-acetylglucosamine is on each branch, that enhances the trapping potency of the recombinant antibody in mucus, so that the recombinant antibody binds to the pathogen to form an antibody/pathogen complex that is trapped in the subject's mucus.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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 the fucose and with the terminal N-acetylglucosamine on each branch.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

The method of claim 1, wherein the recombinant antibody is formulated as a topical composition.

### Claim 10 (depends on 1)

The method of claim 1, wherein the pathogen is selected from: Neisseria gonorrhoeae (gonorrhea); Chlamydia trachomatis (chlamydia, lymphogranuloma venereum); Treponema pallidum (syphilis); Haemophilus ducreyi (chancroid); Klebsiella granulomatis or Calymmatobacterium granulomatis (donovanosis), Mycoplasma genitalium, Ureaplasma urealyticum (mycoplasmas); human immunodeficiency virus HIV-1 and HIV-2 (HIV, AIDS); HTLV-1 (T-lymphotrophic virus type 1); herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2); Epstein-Barr virus; cytomegalovirus; human herpesvirus 6; varicella-zoster virus; human papillomaviruses (genital warts); hepatitis A virus, hepatitis B virus, hepatitis C virus (viral hepatitis); molluscum contagiosum virus (MCV); Trichomona vaginalis (trichomoniasis); and Candida albicans (vulvovaginal candidiasis).

### Claim 11 (depends on 1)

The method of claim 1, wherein the pathogen is herpes simplex virus type 1 or type 2.

### Claim 12

A method of immobilizing a sexually transmitted pathogen in mucus of a subject's reproductive tract, the method comprising administering to the subject, via a topical route, a population of recombinant antibodies with a specific affinity for the pathogen, the recombinant antibodies comprising a human or humanized Fc region, wherein at least 40% 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 a fucose and a terminal N-acetylglucosamine, wherein the terminal N-acetylglucosamine is on each branch to enhance the trapping potency of the recombinant antibody in mucus, so that the recombinant antibodies bind to the pathogen to form an antibody/pathogen complex that is trapped in the subject's mucus.

### Claim 13 (depends on 12)

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

### Claim 14 (depends on 12)

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

### Claim 15 (depends on 12)

The method of claim 12, wherein the recombinant antibodies comprise N-linked glycosylation sites on the Fc region of the antibodies to which the oligosaccharide is attached.

### Claim 16 (depends on 12)

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

### Claim 17 (depends on 12)

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

### Claim 18 (depends on 12)

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

### Claim 19 (depends on 12)

The method of claim 12, wherein the recombinant antibody is formulated as a gel, lotion, cream, or ointment.

### Claim 20 (depends on 12)

The method of claim 12, wherein at least 50% 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.

### Claim 21 (depends on 12)

The method of claim 12, wherein the pathogen is selected from: Neisseria gonorrhoeae (gonorrhea); Chlamydia trachomatis (chlamydia, lymphogranuloma venereum); Treponema pallidum (syphilis); Haemophilus ducreyi (chancroid); Klebsiella granulomatis or Calymmatobacterium granulomatis (donovanosis), Mycoplasma genitalium, Ureaplasma urealyticum (mycoplasmas); human immunodeficiency virus HIV-1 and HIV-2 (HIV, AIDS); HTLV-1 (T-lymphotrophic virus type 1); herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2); Epstein-Barr virus; cytomegalovirus; human herpesvirus 6; varicella-zoster virus; human papillomaviruses (genital warts); hepatitis A virus, hepatitis B virus, hepatitis C virus (viral hepatitis); molluscum contagiosum virus (MCV); Trichomona vaginalis (trichomoniasis); and Candida albicans (vulvovaginal candidiasis).

### Claim 22 (depends on 12)

The method of claim 12, wherein the pathogen is herpes simplex virus type 1 or type 2.

### Claim 23

A method for inhibiting a sexually transmitted pathogen in mucus of a subject's reproductive tract, the method comprising immobilizing the pathogen by administering to the subject a population of recombinant antibody in which at least 40% comprise an oligosaccharide having a GOF glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-→GlcNAcβ1-4GlcNAcβ1 with a fucose reside and a terminal N-acetylglucosamine, wherein the terminal N-acetylglucosamine is on each branch, wherein the recombinant antibody has a specific affinity for the pathogen 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.