# US 2024/0197643 A1 · Oral delivery of nanoparticles for kidney disease

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2024/0197643 A1
- Document ID: US20240197643A1
- Status: Published application
- Kind: A1
- Application number: 17/998,618
- Filed: 2021-05-11
- Published: 2024-06-20
- Earliest claimed: 2020-05-11
- Assignees: University of Southern California
- Applicants: University of Southern California
- Inventors: Eun Ji Paige CHUNG YOO; Jonathan WANG; Yi HUANG; Alysia COX
- Web page: https://patentgrep.com/patent/US20240197643A1

## CPC

- A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin}
- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/66: the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
- A61K 47/6909: {Micelles formed by phospholipids}
- A61P 13/12: of the kidneys
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/141: MicroRNAs, miRNAs
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A drug delivery system for oral administration is provided. The drug delivery system includes an oral delivery carrier and a plurality of micelles attached to or dispersed in the oral delivery carrier. Each of the micelles includes a hydrophobic core and a hydrophilic corona targeted to a subject's kidney. A pharmaceutical payload is carried by the plurality of micelles. Another drug delivery system includes a plurality of micelles and a payload within each micelle. Each micelle has a kidney targeting peptide conjugated thereto with a polyethylene glycol linking group having a molecular weight less than 1800 Daltons.

## Claims

### Claim 1

A drug delivery system for oral administration comprising a plurality of nanoparticles, each drug delivery system including:
an oral delivery carrier; and
a plurality of micelles attached to or dispersed in the oral delivery carrier, each micelle including a hydrophobic core and a hydrophilic corona targeted to a subject's kidney; and
a pharmaceutical payload carried by the plurality of micelles.

### Claim 2 (depends on 1)

The drug delivery system of claim 1 wherein the hydrophilic corona includes a kidney targeting peptide conjugated to the hydrophobic core with a linking compound.

### Claim 3 (depends on 2)

The drug delivery system of claim 2 wherein the kidney targeting peptide includes a sequence selected from the group consisting of KKEEE (SEQ ID NO: 1), KKEEEK (SEQ ID NO: 2), KKEEEKKEEE (SEQ ID NO: 3), KKEEEKKEEEK (SEQ ID NO: 4), KKEEEKKEEEKKEEE (SEQ ID NO: 5), and KKEEEKKEEEKKEEEK (SEQ ID NO: 6).

### Claim 4 (depends on 2)

The drug delivery system of claim 2 wherein the kidney targeting peptide includes a sequence selected from the group consisting of EEKKK (SEQ ID NO: 7), EEKKKE (SEQ ID NO: 8), EEKKKEEKKK (SEQ ID NO: 9), EEKKKEEKKKE (SEQ ID NO: 10), and EEKKKEEKKKEEE (SEQ ID NO: 11), and EEKKKEEKKKEEEK (SEQ ID NO: 12).

### Claim 5 (depends on 2)

The drug delivery system of claim 2 wherein the kidney targeting peptide includes a sequence selected from the group consisting of EEEEE (SEQ ID NO: 13), KKKKK (SEQ ID NO: 14), MGSHIEPGG (SEQ ID NO: 15), KMGGTNHPE (SEQ ID NO: 16), GRGDSP (SEQ ID NO: 17), ELRGDRAKL (SEQ ID NO: 18), and CKDSPKSSKSIRFIPVST (SEQ ID NO: 19).

### Claim 6 (depends on 2)

The drug delivery system of claim 2 including one or more targeting peptides.

### Claim 7 (depends on 2)

The drug delivery system of claim 2 wherein the kidney targeting peptide is selected from the group consisting of SEQ ID Nos: 1-19 with a cysteine added to the N-terminus or C-terminus thereof.

### Claim 8 (depends on 2)

The drug delivery system of claim 2 wherein the kidney targeting peptide is connected to the micelles by reaction with a functional group attached to an end of a polyethylene glycol linking group.

### Claim 9 (depends on 8)

The drug delivery system of claim 8 wherein the functional group that can be used for linking includes amines, carboxylic acids, NHS esters, acid anhydrides, or unsaturated imides (e.g., maleimide).

### Claim 10 (depends on 2)

The drug delivery system of claim 2 wherein the linking compound is polyethylene glycol having a weight average molecular weight from about 500 Daltons to 10000 Daltons.

### Claim 11 (depends on 2)

The drug delivery system of claim 2 wherein the linking compound is polyethylene glycol having a weight average molecular weight less than or equal to 1800 Daltons.

### Claim 12 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload is located in a micelle surface and/or a micelle middle and/or a micelle core.

### Claim 13 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload includes one or more pharmaceutical compounds.

### Claim 14 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload is an mTOR inhibitor.

### Claim 15 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload is selected from the group consisting of pioglitazone, niacinamide, rapamycin, everolimus, tesevatinib, tolvaptan, metformin, somatostatin, octreotide, pasireotide, lixivaptan, venglustat, bardoxolone methyl, salsalate, curcumin, and combinations thereof.

### Claim 16 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload is selected from the group consisting of epigenetic modifying drugs including DNA methyltransferase inhibitors (especially Acytidine, Decitabine, RG108) and histone deacetylase inhibitors (especially Trichostatin A).

### Claim 17 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload is a pravastatin, another statin, or combinations thereof.

### Claim 18 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload includes nucleic acids such as microRNA, messenger RNA (mRNA), aptamers, antibodies, and/or lectins.

### Claim 19 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload includes a microRNA-17 inhibitor.

### Claim 20 (depends on 1)

The drug delivery system of claim 1 wherein the pharmaceutical payload includes mRNA encoding PKD1, PKD2, and/or PKHD1.

### Claim 21 (depends on 1)

The drug delivery system of claim 1 wherein the oral delivery carrier includes an enteric coating and/or gelatin.

### Claim 22 (depends on 21)

The drug delivery system of claim 21 wherein the oral delivery carrier is an enteric coating that includes a component selected from the group consisting of cellulose acetate, hydroxypropyl methyl cellulose, methyl acrylate, and combinations thereof.

### Claim 23 (depends on 1)

The drug delivery system of claim 1 wherein the oral delivery carrier includes chitosan.

### Claim 24 (depends on 23)

The drug delivery system of claim 23 wherein the chitosan includes crosslinked chitosan.

### Claim 25 (depends on 24)

The drug delivery system of claim 24 wherein crosslinked chitosan includes chitosan crosslinked with poly-glutamic acid or tripolyphosphate.

### Claim 26 (depends on 24)

The drug delivery system of claim 24 wherein crosslinked chitosan includes acetylated chitosan having a degree of acetylation from about 70 to 98 mole percent.

### Claim 27 (depends on 1)

The drug delivery system of claim 1 wherein each micelle includes a plurality of targeting peptide-conjugated amphiphiles and a plurality of non-targeted amphiphiles, the plurality of targeting peptide-conjugated amphiphiles including amphiphiles having a targeting peptide selected from the group consisting of SEQ ID NOs 1-19 conjugated to a base amphiphile and SEQ ID NOs 1-19 with a cysteine added to the N-terminus or C-terminus thereof.

### Claim 28 (depends on 27)

The drug delivery system of claim 27 wherein the plurality of targeting peptide-conjugated amphiphiles include amphiphiles having a phospholipid conjugated to the targeting peptide with a linking group.

### Claim 29 (depends on 28)

The drug delivery system of claim 28 wherein the phospholipid is selected from the group consisting of phosphatidic acids, phosphatidyl inositols, phosphatidyl cholines, phosphatidyl ethanolamines, phosphatidyl serines, phosphatidyl glycerols, and any combinations thereof.

### Claim 30 (depends on 28)

The drug delivery system of claim 28 wherein the phospholipid is selected from the group consisting of phosphatidylglycerol, lecithin, sphingomyelin, phosphatidylserine, phosphatidic acid, N-(2,3-di(9-(Z)-octadecenyloxy))-prop-1-yl-N,N,N-trimethylammonium chloride, phosphatidylethanolamine, lysolecithin, lysophosphatidylethanolamine, phosphatidylinositol, cephalin, cardiolipin, cerebrosides, dicetylphosphate, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylglycerol, palmitoyl-oleoyl-phosphatidylcholine, di-stearoyl-phosphatidylcholine, stearoyl-palmitoyl-phosphatidylcholine, di-palmitoyl-phosphatidylethanolamine, di-stearoyl-phosphatidylethanolamine, di-myrstoyl-phosphatidylserine, di-oleyl-phosphatidylcholine, dimyristoyl phosphatidyl choline (DMPC), dioleoylphosphatidylethanolamine, palmitoyloleoylphosphatidylcholine, di stearoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dioleoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, -phosphatidylethanolamine, dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), 1-stearoyl-2-oleoyl phosphatidylcholine, 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine, and combinations thereof.

### Claim 31 (depends on 27)

The drug delivery system of claim 27 wherein the plurality of non-targeted amphiphiles includes amphiphiles having formula:

### Claim 32 (depends on 1)

A method for treating kidney disease in a subject, the method including a step of administering a therapeutically effective amount of the drug delivery system of claim 1 to the subject.

### Claim 33 (depends on 32)

The method of claim 32 wherein the kidney disease is a chronic or acute kidney disease.

### Claim 34 (depends on 32)

The method of claim 32 wherein the kidney disease is diabetic kidney disease, a tubulointerstitial disease, glomerulonephritis, Alport Syndrome, or polycystic kidney disease.

### Claim 35 (depends on 32)

The method of claim 32 wherein the kidney disease is polycystic kidney disease.

### Claim 36

A drug delivery system comprising:
a plurality of micelles, each micelle having a kidney targeting peptide conjugated thereto with a polyethylene glycol linking group having a molecular weight less than 1800 Daltons, and
a payload conjugated to or encapsulated by each micelle.

### Claim 37 (depends on 36)

The drug delivery system of claim 36 wherein the kidney targeting peptide includes a sequence selected from the group consisting of KKEEE (SEQ ID NO: 1), KKEEEK (SEQ ID NO: 2), KKEEEKKEEE (SEQ ID NO: 3), KKEEEKKEEEK (SEQ ID NO: 4), KKEEEKKEEEKKEEE (SEQ ID NO: 5), and KKEEEKKEEEKKEEEK (SEQ ID NO: 6).

### Claim 38 (depends on 36)

The drug delivery system of claim 36 wherein the kidney targeting peptide includes a sequence selected from the group consisting of EEKKK (SEQ ID NO: 7), EEKKKE (SEQ ID NO: 8), EEKKKEEKKK (SEQ ID NO: 9), EEKKKEEKKKE (SEQ ID NO: 10), and EEKKKEEKKKEEE (SEQ ID NO: 11), and EEKKKEEKKKEEEK (SEQ ID NO: 12).

### Claim 39 (depends on 36)

The drug delivery system of claim 36 wherein the kidney targeting peptide includes a sequence selected from the group consisting of EEEEE (SEQ ID NO: 11), KKKKK (SEQ ID NO: 12), MGSHIEPGG (SEQ ID NO: 15), KMGGTNHPE (SEQ ID NO: 16), GRGDSP (SEQ ID NO: 17), ELRGDRAKL (SEQ ID NO: 18), and CKDSPKSSKSIRFIPVST (SEQ ID NO: 19).

### Claim 40 (depends on 36)

The drug delivery system of claim 36 wherein the kidney targeting peptide is selected from the group consisting of SEQ ID Nos: 1-19 with a cysteine added to the N-terminus or C-terminus thereof.

### Claim at position 41

41-59. (canceled)