# US 11,896,800 B2 · Enhanced cancer immunotherapy by microneedle patch-assisted delivery

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- Number: US 11,896,800 B2
- Document ID: US11896800B2
- Status: Granted
- Kind: B2
- Application number: 16/081,188
- Filed: 2017-03-01
- Published: 2019-03-21
- Granted: 2024-02-13
- Earliest claimed: 2016-03-01
- Assignees: North Carolina State University
- Applicants: North Carolina State University
- Inventors: Zhen Gu; Chao Wang; Yanqi Ye
- Web page: https://patentgrep.com/patent/US11896800B2

## CPC

- A61M 5/158: Needles {for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body}
- A61B 5/1486: using enzyme electrodes, e.g. with immobilised oxidase
- A61B 5/150022: {for capillary blood or interstitial fluid}
- A61B 5/150984: {Microneedles or microblades}
- A61B 5/41: {Detecting, measuring or recording for evaluating the immune or lymphatic systems}
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- A61K 31/728: Hyaluronic acid
- A61K 31/734: Alginic acid
- A61M 5/168: Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61B 5/150969: {Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing}
- A61M 2037/0046: {Solid microneedles}
- A61M 2037/0061: {Methods for using microneedles}
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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)

## Abstract

Disclosed herein are self-degradable microneedle devices for the controlled-release of an immunotherapeutic agent. Also disclosed are methods for treating a disease (for example, cancer) using a self-degradable microneedle patch for the sustained delivery of an immunotherapeutic agent (for example, a PD1 antibody).

## Claims

### Claim 1

A method for treating a skin cancer in a subject in need thereof, comprising:
providing a microneedle patch to a subject, wherein the microneedle patch comprises:
a plurality of microneedles each having a base end and a tip;
a substrate to which the base ends of the microneedles are attached or integrated;
acid-degradable nanoparticles, wherein the nanoparticles encapsulate an immunotherapeutic agent and a pH altering agent;
inserting the microneedles into a biological barrier, wherein the pH altering agent decreases the pH within the acid-degradable nanoparticles, and wherein the decrease in the pH degrades the nanoparticle and releases the immunotherapeutic agent into the subject in a controlled-release manner;
wherein the immunotherapeutic agent comprises an anti-PD1 antibody and an anti-CTLA4 antibody.

### Claim 2 (depends on 1)

The method of claim 1, wherein the skin cancer is melanoma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the pH altering agent is glucose oxidase.

### Claim 4 (depends on 1)

The method of claim 1, wherein the acid-degradable nanoparticles comprise modified dextran.

### Claim 5 (depends on 1)

The method of claim 1, wherein the microneedles comprise hyaluronic acid.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-PD1 antibody is nivolumab.

### Claim 7 (depends on 1)

The method of claim 1, wherein the anti-PD1 antibody is pembrolizumab.

### Claim 8 (depends on 1)

The method of claim 1, wherein the anti-CTLA4 antibody is ipilimumab.

### Claim 9 (depends on 1)

The method of claim 1, wherein the acid-degradable nanoparticles further comprise a surfactant.

### Claim 10 (depends on 9)

The method of claim 9, wherein the surfactant is alginate.