# US 12,110,320 B2 · Optimized crosslinkers for trapping a target on a substrate

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- Number: US 12,110,320 B2
- Document ID: US12110320B2
- Status: Granted
- Kind: B2
- Application number: 17/698,645
- Filed: 2022-03-18
- Published: 2022-11-24
- Granted: 2024-10-08
- Earliest claimed: 2015-11-13
- Assignees: The University of North Carolina at Chapel Hill
- Applicants: The University of North Carolina at Chapel Hill
- Inventors: Samuel Lai; M. Gregory Forest; Christine Henry; Timothy Wessler; Alexander Chen; Jennifer Schiller; Jay Newby
- Web page: https://patentgrep.com/patent/US12110320B2

## CPC

- C07K 16/1235: Salmonella (G)
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C07K 16/087: Herpes simplex virus
- C07K 16/114: Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- G01N 33/54346: {Nanoparticles}
- G01N 33/557: using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
- G01N 33/56983: {Viruses}
- G01N 33/6854: {Immunoglobulins}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- G01N 2333/16: HIV-1, HIV-2
- G01N 2333/4725: Mucins, e.g. human intestinal mucin
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The presently-disclosed subject matter relates to crosslinkers, compositions, and methods for trapping a target of interest on a substrate of interest. The methods may be used to inhibit and treat pathogen infection and provide contraception. The methods may be used to trap or separate particles and other substances. The subject matter further relates to methods of identifying and preparing optimal crosslinkers and methods for manipulating targets of interest.

## Claims

### Claim 1

A method for preventing or treating an infection by a viral pathogen including either a human immunodeficiency virus or a herpes virus in a vaginal mucosal extracellular matrix substrate in a subject, said method comprising: altering a binding affinity of a crosslinker to the vaginal mucosal extracellular matrix substrate to form a pool of candidate crosslinkers that binds to both the vaginal mucosal extracellular matrix substrate and to the viral pathogen; selecting an altered crosslinker that associates with the vaginal mucosal extracellular matrix substrate between 20% to less than 95% of the time, has a rate of binding to the viral pathogen greater than about 1×104 M−1 s−1, and has a diffusion coefficient that is between 20% to 99% less than a diffusion coefficient of the altered crosslinker in water; and administering the altered crosslinker to the subject, wherein the crosslinker comprises an antibody or portion of an antibody that binds to the viral pathogen.

### Claim 2 (depends on 1)

The method of claim 1, wherein altering the binding affinity of the crosslinker to the vaginal mucosal extracellular matrix substrate comprises chemically modifying the crosslinkers by increasing the number of moieties on the crosslinkers that can interact with the vaginal mucosal extracellular matrix substrate.

### Claim 3 (depends on 2)

The method of claim 2, wherein chemically modifying the crosslinker further comprises biotinylating the crosslinker.

### Claim 4 (depends on 2)

The method of claim 2, wherein chemically modifying the crosslinker comprises covalently linking an N-glycan and Fc domain to the crosslinker.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody or portion of the antibody is selected from IgG, IgA, IgM, or a fragment or-derivative thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein at least one Fc region is preserved.

### Claim 7

A method for preventing or treating an infection by a viral pathogen including either a human immunodeficiency virus or a herpes virus in a vaginal mucosal extracellular matrix substrate in a subject, said method comprising: altering a binding affinity of crosslinkers to the vaginal mucosal extracellular matrix substrate, wherein the crosslinkers are antibodies or antibody fragments that bind to both the vaginal mucosal extracellular matrix substrate and to the viral pathogen to form a pool of candidate crosslinkers; selecting an altered crosslinker that associates with the vaginal mucosal extracellular matrix substrate between 20% to less than 95% of the time, has a rate of binding to the viral pathogen greater than about 1×104 M−1 s−1, and has a diffusion coefficient that is between 20% to 99% less than a diffusion coefficient of the altered crosslinker in water; and administering the altered crosslinker to the subject.

### Claim 8 (depends on 7)

The method of claim 7, wherein altering the binding affinity of the crosslinker to the vaginal mucosal extracellular matrix substrate comprises chemically modifying the crosslinker by increasing the number of moieties on the crosslinker that can interact with the vaginal mucosal extracellular matrix substrate.

### Claim 9 (depends on 8)

The method of claim 8, wherein chemically modifying the crosslinker further comprises biotinylating the crosslinker.

### Claim 10 (depends on 8)

The method of claim 8, wherein chemically modifying the crosslinker comprises covalently linking an N-glycan and Fc domain to the crosslinker.

### Claim 11 (depends on 7)

The method of claim 7, wherein the antibodies or antibody fragments are selected from IgG, IgA, IgM, or a fragment or-derivative thereof.