# US 2014/0194370 A1 · Silk-elastin like protein polymers for embolization and chemoembolization to treat cancer

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- Number: US 2014/0194370 A1
- Document ID: US20140194370A1
- Status: Published application
- Kind: A1
- Application number: 14/150,652
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2013-01-08
- Applicants: University of Utah Research Foundation
- Inventors: Joseph Cappello; Hamidreza Ghandehari; Azadeh E. Poursaid
- Web page: https://patentgrep.com/patent/US20140194370A1

## CPC

- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- 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 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 38/1767: {from invertebrates}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- C07K 14/43586: {from silkworms}
- 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)
- 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)

## Abstract

A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.

## Claims

### Claim 1

An injectable embolic agent comprising at least one silk-elastin like protein copolymer.

### Claim 2 (depends on 1)

An embolic agent according to claim 1, wherein the agent is a liquid at 18-23° C. and wherein the agent transforms to a cross-linked hydrogel at 37° C.

### Claim 3 (depends on 1)

An embolic agent according to claim 1, wherein the at least one silk-elastin like protein copolymer is produced using recombinant methods.

### Claim 4 (depends on 1)

An embolic agent according to claim 1, wherein the at least one silk-elastin like protein copolymer comprises one or more of
(SEQ ID NO: 3)
MDPVVLQRRDWENPGVTQLVRLAAHPPFASDPMGAGSGAG
AGS[(GVGVP)4GKGVP(GVGVP)3(GAGAGS)4]12(GVGVP)4GKG
VP(GVGVP)2(GAGAGS)2GAMDPGRYQDLRSHHHHHH
and
(SEQ ID NO: 4)
MDPVVLQRRDWENPGVTQLNRLAAHPPFASDPM[GAGS(GA
GAGS)2(GVGVP)4GKGVP(GVGVP)11(GAGAGS)5GA]6GAMDP
GRYQDLRSHHHHHH.

### Claim 5 (depends on 1)

An embolic agent according to claim 1, wherein the at least one silk-elastin like protein copolymer comprises one or more matrix metalloprotease cleavage sites.

### Claim 6 (depends on 2)

An embolic agent according to claim 2, wherein the agent has a viscosity of equal to or less than 1000 cP at 18-23° C.

### Claim 7 (depends on 2)

An embolic agent according to claim 2, wherein the agent has a viscosity of equal to or less than 150 cP at 18-23° C.

### Claim 8 (depends on 2)

An embolic agent according to claim 2, wherein the stiffness of the cross-linked hydrogel is approximately at least approximately 1×105 Pa.

### Claim 9 (depends on 1)

An embolic agent according to claim 1, wherein the agent contains a contrast-agent.

### Claim 10

An injectable chemoembolic agent comprising at least one silk-elastin like protein copolymer and at least one chemotherapeutic agent.

### Claim 11 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein at least one chemotherapeutic agent comprises a biologic compound.

### Claim 12 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the agent is a liquid at 18-23° C. and wherein the agent transforms to a cross-linked hydrogel at 37° C.

### Claim 13 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the at least one silk-elastin-like protein copolymer is produced using recombinant methods.

### Claim 14 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the at least one silk-elastin-like protein copolymer comprises one or more of
(SEQ ID NO: 3)
MDPVVLQRRDWENPGVTQLVRLAAHPPFASDPMGAGSGAG
AGS[(GVGVP)4GKGVP(GVGVP)3(GAGAGS)4]12(GVGVP)4GKG
VP(GVGVP)2(GAGAGS)2GAMDPGRYQDLRSHHHHHH
and
(SEQ ID NO: 4)
MDPVVLQRRDWENPGVTQLNRLAAHPPFASDPM[GAGS(GA
GAGS)2(GVGVP)4GKGVP(GVGVP)11(GAGAGS)5GA]6GAMDP
GRYQDLRSHHHHHH.

### Claim 15 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the at least one silk-elastin-like protein copolymer comprises one or more matrix metalloprotease cleavage sites.

### Claim 16 (depends on 12)

An injectable chemoembolic agent according to claim 12, wherein the agent has a viscosity of equal to or less than 1000 cP at 18-23° C.

### Claim 17 (depends on 12)

An injectable chemoembolic agent according to claim 12, wherein the agent has a viscosity of equal to or less than 150 cP at 18-23° C.

### Claim 18 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the stiffness of the cross-linked hydrogel is at least approximately 1×105 Pa.

### Claim 19 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the at least one chemotherapeutic agent is effective in treating hepatocellular carcinoma.

### Claim 20 (depends on 10)

An injectable chemoembolic agent according to claim 10, wherein the at least one chemotherapeutic agent comprises one or more of a drug targeting vascular endothelial growth factor and vascular endothelial growth factor receptor.