Peptide ligands for hepatic stellate cells

Patent metadata

Field	Value
Publication number	US-10138273-B2
Application number	US-201615288837-A
Country	US
Kind code	B2
Filing date	Oct 7, 2016
Priority date	Oct 7, 2015
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

Methods and compositions for identifying and using polypeptides that target hepatic stellate cells are described. Embodiments include a targeting composition that may include one or more polypeptides including an amino acid sequence that binds to an insulin-like growth factor 2 receptor. Other embodiments relate to targeting systems that may include a one or more polypeptides including an amino acid sequence that binds to an insulin-like growth factor 2 receptor of hepatic stellate cells. Further embodiments relate to methods for treating health disorders in which the methods include the targeting composition or targeting systems as well as an agent capable of treating the disorder.

First claim

What is claimed is:

1. A composition comprising:
a polypeptide comprising an amino acid sequence having the amino acid sequence of SEQ ID NO: 6, wherein the polypeptide binds to at least a portion of an insulin-like growth factor 2 receptor (IGF2R) extracellular domain; and
at least one of an anti-fibrotic agent, an anti-cancer agent, or a proapoptotic agent.

2. The composition according to claim 1 , wherein the polypeptide comprises a dimer, wherein the dimer comprises a first and a second amino acid sequence, wherein each of the first and second amino acid sequences has the amino acid sequence of SEQ ID NO: 6.

3. The composition according to claim 2 , wherein the first and second amino acid sequences are linked to one another via a linking moiety.

4. The composition according to claim 3 , wherein the linking moiety comprises lysine.

5. The composition according to claim 1 , wherein the at least one of an anti-fibrotic agent, an anti-cancer agent, or a proapoptotic agent is covalently attached to the polypeptide.

6. A Hepatic stellate cell (HSC) targeting system comprising:
a targeting composition that comprises:
a dimeric polypeptide, wherein the dimeric polypeptide comprises a first and a second amino acid sequence, wherein each of the first and second amino acid sequences comprises the amino acid sequence of SEQ ID NO: 6, and wherein the first and second amino acid sequences are linked to one another via a linking moiety; and
at least one of an anti-fibrotic agent, an anti-cancer agent, or a proapoptotic agent, wherein at least a portion of the dimeric polypeptide binds to at least a portion of an insulin-like growth factor 2 receptor (IGF2R) extracellular domain associated with Hepatic Stellate Cells (HSCs).

7. The HSC targeting system according to claim 6 , wherein the targeting composition comprises an anti-fibrotic agent, and wherein the anti-fibrotic agent is covalently attached to at least a portion of the dimeric polypeptide via an attachment moiety.

8. The HSC targeting system according to claim 6 , wherein the linking moiety comprises a lysine residue.

9. A composition comprising:
a polypeptide comprising the amino acid sequence of SEQ ID NO:6; and
an anti-fibrotic agent covalently attached to at least a portion of the polypeptide.

10. The composition of claim 9 , wherein the anti-fibrotic agent comprises the amino acid sequence of SEQ ID NO: 13.

11. The composition of claim 9 , wherein the polypeptide comprises a dimer, wherein the dimer comprises a first and a second amino acid sequence, wherein each of the first and second amino acid sequences comprise the amino acid sequence of SEQ ID NO: 6.

12. The composition of claim 9 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 6, and wherein the polypeptide exhibits an apparent dissociation constant of about 6.19 μM for LX-2 human hepatic stellate cells.

13. The composition of claim 9 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 6, and wherein the polypeptide exhibits an apparent dissociation constant of about 12.35 μM for HSC-T6 rat hepatic stellate cells.

Assignees

• Cheng Kun
• Chen Zhijin
• Univ Missouri

Inventors

• Cheng Kun
• Chen Zhijin

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• C07K14/72

  for hormones {(for neuromediators C07K14/70571)} · CPC title

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title