# US 12,109,307 B2 · Compositions and methods for controlled release of target agent

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

- Number: US 12,109,307 B2
- Document ID: US12109307B2
- Status: Granted
- Kind: B2
- Application number: 17/261,411
- Filed: 2019-07-19
- Published: 2021-07-22
- Granted: 2024-10-08
- Earliest claimed: 2018-07-20
- Assignees: The Hong Kong University of Science and Technology
- Applicants: The Hong Kong University Of Science and Technology
- Inventors: Ying Chau; Chi Ming Laurence Lau; Yu Yu
- Web page: https://patentgrep.com/patent/US12109307B2

## CPC

- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- C07K 16/22: against growth factors {; against growth regulators}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- C08L 5/02: Dextran; Derivatives thereof
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- 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)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present disclosure provides compositions and methods for controlled release of macromolecules (such as proteins and polypeptides). The present disclosure also provides method for preparing and using the same.

## Claims

### Claim 1

A composition comprising one or more hydrogel forming polymers, said hydrogel enables sustained release of a target agent, at least one of said one or more hydrogel forming polymers comprises a degradable backbone, and wherein said degradable backbone comprises precursor polymers linked by a degradable linker,
wherein said hydrogel forming polymer is selected from the group consisting of a polysaccharide, a polyethylene glycol, a derivative thereof, and any combinations thereof;
comprising at least a first hydrogel forming polymer derivative and a second hydrogel forming polymer derivative, wherein said first hydrogel forming polymer derivative comprises a first modification and said second hydrogel forming polymer derivative comprises a second modification, said first modification is different from said second modification, and said first polymer derivative is capable of reacting with said second polymer derivative to form said hydrogel;
wherein a mass ratio between said first hydrogel forming polymer derivative and said second hydrogel forming polymer derivative in said composition is from about 3:1 to about 1:3; or
wherein a molar ratio between said first hydrogel forming polymer derivative and said second hydrogel forming polymer derivative in said composition is from about 10:1 to about 1:10; or
wherein a volume ratio between said first hydrogel forming polymer derivative and said second hydrogel forming polymer derivative in said composition is from about 3:1 to about 1:3; or
wherein said first hydrogel forming polymer derivative has a first DM, said second hydrogel forming polymer derivative has a second DM, and a ratio between said first DM and said second DM is from about 3:1 to about 1:3.

### Claim 2 (depends on 1)

The composition according to claim 1,
wherein said hydrogel forming polymer comprising the degradable backbone is formed by cross linking said precursor polymers with said degradable linker, wherein said degradable linker enables formation of degradable linkage between said precursor polymers and
wherein said degradable linker comprises two or more modifications, and a degree of modification of said degradable linker is less than about 30%; wherein said modification of said degradable linker is selected from the group consisting of an acrylate, a methacrylate, a maleimide, a vinylsulfone, a thiol, an amine, and any combinations thereof.

### Claim 3 (depends on 1)

The composition according to claim 1, wherein said degradable linker is selected from the following groups:

### Claim 4 (depends on 1)

A hydrogel for sustained release of a target agent, wherein said hydrogel is formed with the composition according to claim 1.

### Claim 5 (depends on 4)

The hydrogel according to claim 4, wherein about less than 30% of said target agent is cumulatively released within an initial 24 hours from said hydrogel, and the remaining portion of said target agent is cumulatively released from said hydrogel in about 3 to about 36 months.

### Claim 6 (depends on 1)

A method for producing a composition according to claim 1, comprising:
a) crosslinking the precursor polymer with the degradable linker to obtain the hydrogel forming polymer comprising the degradable backbone; and
b) mixing said hydrogel forming polymer comprising the degradable backbone with an additional polymer, wherein said additional polymer is capable of reacting with said hydrogel forming polymer comprising the degradable backbone under a condition enabling formation of the hydrogel.