# US 11,998,616 B2 · Nanoparticles for crossing the blood brain barrier and methods of treatment using the same

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- Number: US 11,998,616 B2
- Document ID: US11998616B2
- Status: Granted
- Kind: B2
- Application number: 17/215,443
- Filed: 2021-03-29
- Published: 2021-07-22
- Granted: 2024-06-04
- Earliest claimed: 2018-06-13
- Assignees: California Institute of Technology
- Applicants: California Institute of Technology
- Inventors: Mark E. Davis; Emily A. Wyent
- Web page: https://patentgrep.com/patent/US11998616B2

## CPC

- A61K 47/6935: {the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol}
- A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers}
- A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61P 35/00: Antineoplastic agents
- C07K 16/32: against translation products of oncogenes
- A61K 2039/505: {comprising antibodies}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/906: 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present application discloses nanoparticles carrying therapeutic agents, including chemotherapeutic agents, and targeting ligands suitable for delivering these therapeutic agents through the blood brain barrier and methods of using these patients on those patients in need of such treatment.

## Claims

### Claim 1

A method for slowing growth of a brain tumor by 82%-94%, the method comprising systemically administering, to a subject having the brain tumor, a nanoparticle comprising:
(a) a nanoparticle core comprising a mucic acid-containing polymer;
(b) transferrin joined to the nanoparticle core by a nitrophenyl boronic ester linkage to vicinal diols of the mucic acid-containing polymer;
(c) trastuzumab; and
(d) camptothecin.

### Claim 2 (depends on 1)

The method of claim 1, wherein the brain tumor is metastasized from a HER2-positive breast cancer.

### Claim 3 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 4 (depends on 1)

The method of claim 1, wherein the nanoparticle core comprises a polymer containing units having the structure:
wherein n is from 1-20.

### Claim 5 (depends on 1)

The method of claim 1, wherein the nanoparticle core comprises the structure:
wherein:
x is from 15-100;
y is from 10-25; and
R is an amino acid, or salt thereof, coupled to one or more of transferrin, trastuzumab and/or camptothecin.

### Claim 6 (depends on 1)

The method of claim 1, wherein the nanoparticle core comprises a polymer containing units having the structure:
wherein:
n is from 1-20; and
p is from 20-200.

### Claim 7 (depends on 1)

The method of claim 1, wherein the structure of (b) is:
wherein:
s is from 2-2,000;
L is an amide, a carbonate, an ester or a disulfide group; and
X5 is C1-6 alkyl, optionally substituted with —OH, —COOH, —B(OH)2, —C(═O)—O— alkyl, C(═O)—O-aryl, —NH2, —NH(alkyl), —N(alkyl)2 or —SH; with transferrin coupled thereto.

### Claim 8 (depends on 1)

The method of claim 1, wherein the camptothecin is joined to the nanoparticle core by an amino acid.

### Claim 9 (depends on 1)

The method of claim 1, wherein the nanoparticle comprises a unit structure:
wherein:
x is from 15-100; and
n is from 1-20.