# US 9,040,060 B2 · Hydrolytically degradable alkylene oxide based polymers

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- Number: US 9,040,060 B2
- Document ID: US9040060B2
- Status: Granted
- Kind: B2
- Application number: 13/108,616
- Filed: 2011-05-16
- Published: 2011-09-08
- Granted: 2015-05-26
- Earliest claimed: 2002-02-15
- Assignees: Nektar Therapeutics
- Applicants: Michael D. Bentley; J. Milton Harris; Xuan Zhao; William Dudley Battle, III; Xiaoming Shen
- Inventors: Michael D. Bentley; J. Milton Harris; Xuan Zhao; William Dudley Battle, III; Xiaoming Shen
- Web page: https://patentgrep.com/patent/US9040060B2

## CPC

- C08G 65/04: from cyclic ethers only
- A61K 9/00: Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- C08G 64/183: {containing polyether sequences}
- C08G 65/329: with organic compounds
- C08G 65/333: containing nitrogen
- C08G 65/33337: {cyclic}
- C08G 65/33344: {containing carbamate group}
- C08G 65/33396: {having oxygen in addition to nitrogen}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- C08L 2203/02: for biomedical use
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- 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)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present invention provides a water soluble, non-peptidic polymer comprising two or more alkylene oxide-based oligomers linked together by hydrolytically degradable linkages such as carbonates. Typically, the oligomer portion of the polymer is an amphiphilic triblock copolymer having a central propylene oxide block or butylene oxide block positioned between two ethylene oxide blocks. The polymer can be hydrolytically degraded into oligomers under physiological conditions. In aqueous media, the polymer preferably forms thermally reversible, hydrolytically degradable hydrogels that can be used, for example, for drug delivery and related biomedical applications.

## Claims

### Claim 1

An in-vivo gel-forming composition comprising:
(i) a polymer having the formula:
X—O—[(—CH2CH2—O—)n—(CHR1CHR2—O—)q—(CH2CH2—O)r—CO2—]m—(CH2CH2O)n—(CHR3CHR4—O—)q—(CH2CH2—O)r—Y,
wherein:
n is an integer of from about 5 to about 500,
q and r are integers each independently ranging from about 2 to about 2,000,
m is an integer ranging from 1 to about 5,
R1, R2, R3, and R4 are independently selected from alkyl or H, where
R1 is H when R2 is alkyl or R1 is alkyl when R2 is H,
R3 is H when R4 is alkyl or R3 is alkyl when R4 is H, and
X and Y are each independently selected from the group consisting of H, alkyl, alkenyl and aryl, and
(ii) a PEGylated antibody,
in aqueous solution, wherein the polymer is not covalently crosslinked and is present at a concentration of from about 5% by weight to about 8% by weight, and the composition (i) is a liquid at ambient temperatures and (ii) forms a hydrolytically degradable gel at body temperature (37° C.).

### Claim 2 (depends on 1)

The composition of claim 1, wherein X and Y are independently selected from H and alkyl.

### Claim 3 (depends on 1)

The composition of claim 1, wherein n is an integer of from about 80 to about 120.

### Claim 4 (depends on 1)

The composition of claim 1, wherein q is an integer of from about 40 to about 70.

### Claim 5 (depends on 1)

The composition of claim 1, wherein r is an integer of from about 5 to about 100.

### Claim 6 (depends on 1)

The composition of claim 1, wherein:
R1 is H when R2 is methyl or ethyl, or R1 is methyl or ethyl when R2 is H; and
R3 is H when R4 is methyl or ethyl, or R3 is methyl or ethyl when R4 is H.

### Claim 7 (depends on 1)

The composition of claim 1, wherein n is an integer of from about 80 to about 120, q is an integer of from about 40 to about 70, r is an integer of from about 10 to about 50, and m is an integer of from 1 to about 5.

### Claim 8 (depends on 1)

The composition of claim 1, wherein R1 is H, R2 is methyl, R3 is H, and R4 is methyl.

### Claim 9 (depends on 1)

The composition of claim 1, wherein R1 is H, R2 is methyl, R3 is H and R4 is methyl.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the PEGylated antibody is a PEGylated Fab.

### Claim 11 (depends on 1)

The composition of claim 1 in a form suitable for injection.

### Claim 12 (depends on 1)

The composition of claim 1, in the form of a hydrogel.