Multimeric elastin-like polypeptides

Patent metadata

Field	Value
Publication number	US-12458704-B2
Application number	US-202217963037-A
Country	US
Kind code	B2
Filing date	Oct 10, 2022
Priority date	Feb 13, 2018
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

This disclosure provides a novel compositions and methods to deliver cyclosporine A using genetically engineered protein polymers.

First claim

What is claimed is:

1 . An agent comprising an elastin-like peptide (ELP) that comprises the amino acid sequence set forth in SEQ ID NO: 11 fused to an intracellular adhesion molecule 1 (ICAM-1) targeting peptide selected from an ICAM-1 targeting peptide that comprises EWCEYLGGYLRCYA (SEQ ID NO: 29) or FEGFSFLAFEDFVSSI (SEQ ID NO:28).

2 . The agent of claim 1 , further comprising a therapeutic agent.

3 . The agent of claim 1 , further comprising an FK506 binding protein (FKBP).

4 . The agent of claim 1 , further comprising a drug binding domain selected from the group consisting of a knob ligand comprising the amino acid sequence set forth in SEQ ID NO: 26, an mIgA ligand comprising the amino acid sequence set forth in SEQ ID NO: 27, and a peptidyl-prolyl cis/trans isomerase (PIN1) comprising the amino acid sequence set forth in SEQ ID NO: 31.

5 . The agent of claim 4 , wherein the drug binding domain comprises a peptidyl-prolyl cis/trans isomerase (PIN1) comprising the amino acid sequence set forth in SEQ ID NO: 31.

6 . The agent of claim 2 , wherein the therapeutic agent is a cyclosporin A comprising the amino acid sequence set forth in SEQ ID NO:22 or SEQ ID NO: 23, a prodrug thereof, or a pharmaceutically acceptable salt thereof.

7 . The agent of claim 2 , wherein the therapeutic agent is bound or trapped by the ELP or coacervate formed by the ELP.

8 . The agent of claim 1 , further comprising a detectable label.

9 . The agent of claim 1 , further comprising a rapamycin or an analog thereof selected from the group consisting of Everolimus, Temsirolimus, Ridaforolimus, and Tacrolimus.

10 . The agent of claim 3 , wherein the FK506 binding protein (FKBP) comprises the amino acid sequence set forth in SEQ ID NO: 12.

11 . The agent of claim 2 , further comprising a rapamycin or an analog thereof selected from the group consisting of Everolimus, Temsirolimus, Ridaforolimus, and Tacrolimus.

12 . The agent of claim 3 , further comprising a rapamycin or an analog thereof selected from the group consisting of Everolimus, Temsirolimus, Ridaforolimus, and Tacrolimus.

13 . An isolated polynucleotide that encodes the agent of claim 1 .

14 . A method for delivering a therapeutic agent in vitro comprising contacting a tissue with the agent of claim 2 .

15 . A method for delivering a therapeutic agent in vivo comprising administering an effective amount of the agent of claim 2 to a subject.

16 . A method for delivering a therapeutic agent in vivo comprising administering an effective amount of the agent of claim 1 to a subject.

17 . A method for delivering a therapeutic agent in vivo comprising administering an effective amount of the agent of claim 3 to a subject.

18 . A method for delivering a therapeutic agent in vivo comprising administering an effective amount of the agent of claim 12 to a subject.

Assignees

• Univ Southern California

Inventors

• Mackay John Andrew
• Shah Mihir
• Hamm-Alvarez Sarah F
• Guo Hao
• Peddi Santosh

Classifications

• C12N15/62

  DNA sequences coding for fusion proteins · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• C07K16/2887

  against CD20 · CPC title

• A61K38/13

  Cyclosporins · CPC title

• A61K31/436

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title