# US 2021/0330795 A1 · Compositions comprising tri- and penta-block synthetic copolypeptide hydrogels

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- Number: US 2021/0330795 A1
- Document ID: US20210330795A1
- Status: Published application
- Kind: A1
- Application number: 17/238,632
- Filed: 2021-04-23
- Published: 2021-10-28
- Earliest claimed: 2020-04-23
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Timothy J. Deming; Yintao Sun
- Web page: https://patentgrep.com/patent/US20210330795A1

## CPC

- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- 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)
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C08G 69/10: Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)}
- C08L 77/04: Polyamides derived from alpha-amino carboxylic acids (C08L77/10 takes precedence)
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

Disclosed herein are mixtures of triblock or pentablock copolypeptide hydrogels (DCH). These hydrogels possess improved mechanical properties, such as elasticity, that are synergistically increased over the individual component DCHs, to greater than would be expected for a linear combination of the components. Also disclosed herein are methods of making and using the triblock and pentablock copolypeptide hydrogels.

## Claims

### Claim 1

A composition comprising:
i) a first copolypeptide comprising Substructure I, and a second copolypeptide comprising Substructure II, and water, wherein
Substructure I is depicted as follows:
-A1n1-B1m1-A1n1- Substructure I;
Substructure II is depicted as follows:
—X1n2—Y1m2—X1n2— Substructure II;
each instance of A1 is an amino acid residue independently selected from a non-ionic hydrophilic amino acid, sarcosine, glycine, and alanine;
in at least 20% of the instances of B1, B1 is an amino acid residue independently selected from an anionic hydrophilic amino acid or a salt thereof;
each instance of X1 is an amino acid residue independently selected from a non-ionic hydrophilic amino acid, sarcosine, glycine, and alanine;
in at least 20% of the instances of Y1, Y1 is an amino acid residue independently selected from a cationic hydrophilic amino acid or a salt thereof;
each n1 and n2 is independently about 25 to about 600;
m1 and m2 are independently about 15 to about 600;
at least 75 mol % of the B1 amino acid residues are (D)-amino acid residues or at least 75 mol % of the B1 amino acid residues are (L)-amino acid residues;
at least 75 mol % of the Y1 amino acid residues are (D)-amino acid residues or at least 75 mol % of the Y1 amino acid residues are (L)-amino acid residues; and
the first copolypeptide and the second copolypeptide are not covalently linked; or
ii) Substructure III, and a second copolypeptide comprising Substructure IV, and water, wherein Substructure III is depicted as follows:
-A1n1-B1m1-A1n3-B1m1-A1n1- Substructure III:
Substructure IV is depicted as follows:
—X1n2—Y1m2—X1n4—Y1m2—X1n2— Substructure IV;
each instance of A1 is an amino acid residue independently selected from a non-ionic, hydrophilic amino acid, sarcosine, glycine, and alanine;
in at least 20% of the instances of B1, B1 is an amino acid residue independently selected from an anionic hydrophilic amino acid or a salt thereof;
each instance of X1 is an amino acid residue independently selected from a non-ionic hydrophilic amino acid, sarcosine, glycine, and alanine;
in at least 20% of the instances of Y1, Y1 is an amino acid residue independently selected from a cationic hydrophilic amino acid or a salt thereof;
each n1, n2, n3, and n4 is independently about 25 to about 600;
each m1 and m2 is independently about 15 to about 600;
at least 75 mol % of the B1 amino acid residues are (D)-amino acid residues or at least 75 mol % of the B1 amino acid residues are (L)-amino acid residues;
at least 75 mol % of the Y1 amino acid residues are (D)-amino acid residues or at least 75 mol % of the Y1 amino acid residues are (L)-amino acid residues; and
the first copolypeptide and the second copolypeptide are not covalently linked.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The composition of claim 1, wherein each instance of A1 is an amino acid residue independently selected from a non-ionic hydrophilic amino acid.

### Claim 4 (depends on 1)

The composition of claim 1, wherein each instance of A1 is an amino acid residue independently selected from sarcosine, glycine, alanine, methionine sulfoxide, S-alkyl-cysteine sulfoxide, S-alkyl cysteine sulfone, S-alkyl-homocysteine, S-alkyl-homocysteine sulfoxide, glycosylated cysteine, serine, homoserine, and homomethionine sulfoxide.

### Claim 5

(canceled)

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The composition of claim 1, wherein at least 85 mol % of the A1 amino acid residues are methionine sulfoxide.

### Claim 8

(canceled)

### Claim 9

(canceled)

### Claim 10 (depends on 1)

The composition of claim 1, wherein each instance of B1 is an amino acid residue independently selected from an anionic, hydrophilic amino acid.

### Claim 11

(canceled)

### Claim 12

(canceled)

### Claim 13 (depends on 1)

The composition of claim 1, wherein each instance of B1 is glutamic acid or aspartic acid.

### Claim 14

(canceled)

### Claim 15

(canceled)

### Claim 16 (depends on 1)

The composition of claim 1, wherein each instance of X1 is an amino acid residue independently selected from a non-ionic, hydrophilic amino acid.

### Claim 17 (depends on 1)

The composition of claim 1, wherein each instance of X1 is an amino acid residue independently selected from sarcosine, glycine, alanine, methionine sulfoxide, S-alkyl-cysteine sulfoxide, S-alkyl cysteine sulfone, S-alkyl-homocysteine, S-alkyl-homocysteine sulfoxide, glycosylated cysteine, serine, homoserine, and homomethionine sulfoxide.

### Claim 18

(canceled)

### Claim 19

(canceled)

### Claim 20 (depends on 1)

The composition of claim 1, wherein at least 85 mol % of the X1 amino acid residues are methionine sulfoxide.

### Claim 21

(canceled)

### Claim 22

(canceled)

### Claim 23 (depends on 1)

The composition of claim 1, wherein each instance of Y1 is an amino acid residue independently selected from a cationic, hydrophilic amino acid.

### Claim 24

(canceled)

### Claim 25

(canceled)

### Claim 26 (depends on 1)

The composition of claim 1, wherein each instance of Y1 is lysine, ornithine, or arginine.

### Claim 27

(canceled)

### Claim 28

(canceled)

### Claim 29 (depends on 1)

The composition of claim 1, wherein each n1 is independently about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, or about 100: each m1 is independently about 10, about 20, about 30, about 40, about 50, or about 60; each n2 is independently about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, or about 100; each m2 is independently about 10, about 20, about 30, about 40, about 50, or about 60; n3 is about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, or about 150; and n4 is about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, or about 150.

### Claim at position 30

30-42. (canceled)

### Claim 43 (depends on 1)

The composition of claim 1, wherein the polydispersity of the second copolypeptide is less than 1.5.

### Claim 44

(canceled)

### Claim 45 (depends on 1)

The composition of claim 1, wherein the number of amino acid residues in the first copolypeptide is from about 90% to about 110% of the number of amino acid residues in the second copolypeptide.

### Claim 46 (depends on 1)

The composition of claim 1, wherein the composition comprises (MOA)50E30(MOA)50, (MOA)50K30(MOA)50, (MOA)50E30(MOA)100E30(MOA)50, (MOA)50K30(MOA)100K30(MOA)50, (MOA)46E27(MOA)52, (MOA)46K29(MOA)49, (MOA)46E28(MOA)89E31(MOA)48, or (MOA)46K29(MOA)95K31(MOA)46.

### Claim 47 (depends on 1)

The composition of claim 1, wherein the total concentration of the first copolypeptide and the second copolypeptide in the composition is about 1% to about 15 wt. %.

### Claim at position 36

48-50. (canceled)

### Claim 51 (depends on 1)

The composition of claim 1, wherein the molar ratio of A1 to B1 is about 3:1 or about 4:1.

### Claim 52 (depends on 1)

The composition of claim 1, wherein the molar ratio of X1 to Y1 is about 3:1 or about 4:1.

### Claim at position 39

53-58. (canceled)

### Claim 59 (depends on 1)

A method of making a composition of claim 1 comprising either:
dissolving the first copolypeptide in an aqueous medium; and
mixing the aqueous medium with a solution of the second copolypeptide, thereby forming the composition; or
dissolving the second copolypeptide in an aqueous medium; and
mixing the aqueous medium with a solution of the first copolypeptide, thereby forming the composition.

### Claim at position 41

60-65. (canceled)

### Claim 66 (depends on 1)

A method of delivering a drug to a biological target using a composition of claim 1, the method comprising:
dissolving the drug in a first aqueous medium;
dissolving the first copolypeptide in the first aqueous medium, thereby forming a second aqueous medium;
mixing the second aqueous medium with a solution of the second copolypeptide, thereby forming a composition with the drug; and
contacting the biological target with the composition with the drug; or
dissolving the drug in a first aqueous medium;
dissolving the second copolypeptide in the first aqueous medium, thereby forming a second aqueous medium;
mixing the second aqueous medium with a solution of the first copolypeptide, thereby forming a composition with the drug; and
contacting the biological target with the composition with the drug.

### Claim at position 43

67-76. (canceled)