# US 11,998,614 B2 · Compositions and methods for inducing scarring by peri-tumoral cells

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- Number: US 11,998,614 B2
- Document ID: US11998614B2
- Status: Granted
- Kind: B2
- Application number: 16/696,960
- Filed: 2019-11-26
- Published: 2020-06-04
- Granted: 2024-06-04
- Earliest claimed: 2018-11-26
- Assignees: Duke University
- Applicants: Duke University
- Inventors: Tarun Saxena; Ravi Bellamkonda; Nassir Mokarram-Dorri
- Web page: https://patentgrep.com/patent/US11998614B2

## CPC

- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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)
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Compositions are provided, the compositions comprising: (1) a nanoparticle; (2) optionally, a linker and/or masking agent; and (3) a ligand configured to activate peri-tumoral cells to induce scarring by the peri-tumoral cells. In some aspects, administration of the compositions to a subject may generate an environment capable of walling-off and containing invasive tumors.

## Claims

### Claim 1

A composition comprising a conjugate, the conjugate comprising: (1) a gold nanoparticle; (2) optionally, a linker or a masking agent; and (3) a ligand,
wherein the ligand comprises an isolated water-soluble mixture of zymosan polypeptides obtained by extracting zymosan with an extraction buffer comprising CHAPS detergent and applying the CHAPS detergent extract to a 10 kDa centrifugal spin column, and
wherein the conjugate has a diameter of about 50 nm to about 200 nm.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the linker or masking agent comprises PEG, a PEG derivative, or a hydrophilic polycarbonate.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the ligand further comprises one or more of peptidoglycan, LPS, zymosan, Pam3CSK4, amyloid-beta peptide, lipoteichoic acid, HMGB1, heat shock proteins, CSF-1R inhibitors, LPS+IFN-gamma, xyloside, IFN-gamma, TNF-alpha, IL-2, lipocalin 2, miRNA-155, or a combination thereof.

### Claim 4

A composition comprising: (1) a nanoparticle; and (2) a ligand, wherein the ligand comprises an isolated water-soluble mixture of zymosan polypeptides obtained by extracting zymosan with an extraction buffer comprising CHAPS detergent and applying the CHAPS detergent extract to a 10 kDa centrifugal spin column, wherein the nanoparticle forms a conjugate with the ligand or encapsulates the ligand, and wherein the conjugate or the nanoparticle encapsulating the ligand has a diameter of about 5 nm to about 200 nm and is capable of crossing the blood brain barrier.

### Claim 5 (depends on 4)

The composition of claim 4, further comprising PEG, a PEG derivative, a hydrophilic polycarbonate, or a derivative thereof.

### Claim 6 (depends on 4)

The composition of claim 4, wherein the nanoparticle comprises a gold nanoparticle.

### Claim 7 (depends on 4)

The composition of claim 4, wherein the conjugate or the nanoparticle encapsulating the ligand has a diameter of about 50 nm to about 200 nm.

### Claim 8 (depends on 4)

The composition of claim 4, wherein the ligand further comprises one or more of peptidoglycan, LPS, zymosan, Pam3CSK4, amyloid-beta peptide, lipoteichoic acid, HMGB1, heat shock proteins, CSF-1R inhibitors, LPS+IFN-gamma, xyloside, IFN-gamma, TNF-alpha, IL-2, lipocalin 2 miRNA-155, or a combination thereof.

### Claim 9 (depends on 1)

The composition of claim 1 wherein the isolated water-soluble mixture of zymosan polypeptides is formed by a process comprising:
snap freezing the zymosan;
crushing the snap frozen zymosan;
mixing the crushed zymosan and the extraction buffer comprising the CHAPS detergent to obtain the CHAPS detergent extract;
centrifuging the CHAPS detergent extract and collecting the supernatant; and
applying the supernatant to the 10 kDa centrifugal spin column to concentrate the isolated water-soluble mixture of zymosan polypeptides.

### Claim 10 (depends on 4)

The composition of claim 4 wherein the isolated water-soluble mixture of zymosan polypeptides is formed by a process comprising:
snap freezing the zymosan;
crushing the snap frozen zymosan;
mixing the crushed zymosan and the extraction buffer comprising the CHAPS detergent to obtain the CHAPS detergent extract;
centrifuging the CHAPS detergent extract and collecting the supernatant; and
applying the supernatant to the 10 kDa centrifugal spin column to concentrate the isolated water-soluble mixture of zymosan polypeptides.
