Optimized crosslinkers for trapping a target on a substrate

Patent metadata

Field	Value
Publication number	US-12110320-B2
Application number	US-202217698645-A
Country	US
Kind code	B2
Filing date	Mar 18, 2022
Priority date	Nov 13, 2015
Publication date	Oct 8, 2024
Grant date	Oct 8, 2024

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.

First claim

We 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 1×10 4 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.

2. 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.

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

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

5. 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.

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

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 1×10 4 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.

8. 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.

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

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

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

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Lai Samuel
• Forest M Gregory
• Henry Christine
• Wessler Timothy
• Chen Alexander
• Schiller Jennifer
• Newby Jay

Classifications

• C07K16/114

  Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV] · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K16/087

  Herpes simplex virus · CPC title

• A61K38/00

  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) · CPC title

• A61P31/00 Primary

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