IP Library Granted Patent US 11,213,594
Granted Patent B2
US 11,213,594 · App. 16/097,187 · Granted Jan 4, 2022

Poly(histidine)-based micelles for complexation and delivery of proteins and nucleic acids

Inventors: Paiman Peter Ghoroghchian (San Diego, CA); Gabriela Romero Uribe (San Diego, CA); Eric Ostertag (San Diego, CA)
Assignee: POSEIDA THERAPEUTICS, INC.
A61K48/0016A61K9/107A61K31/711A61K31/7105A61K47/34A61K47/50A61K47/6907A61K48/0066C12N15/88C12N15/90A61K38/00C12N15/86
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Quick Facts
Patent No.
US 11,213,594
App. No.
16/097,187
Granted
Jan 4, 2022
Kind
B2
Abstract

Disclosed are compositions for delivering gene editing molecules to a cell. Exemplary compositions comprise a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein: the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule.

Claims (38)

1. A composition for delivering at least one gene editing molecule to a cell, the composition comprising:

a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block,

wherein:

the at least one poly(L-histidine) block complexes with the at least one gene editing molecule;

the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule;

the at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid); and

wherein the at least one gene editing molecule comprises one or more of a nucleic acid encoding for a protein, wherein the protein is selected from the group consisting of a transposase, a nuclease and an integrase;

wherein the molar ratio of triblock copolymers to the at least one gene editing molecule is about 20:1.

2. The composition of claim 1 , wherein the nuclease is selected from the group comprising:

a CRISPR associated protein 9 (Cas9);

a type IIS restriction enzyme;

a transcription activator-like effector nuclease (TALEN); and

a zinc finger nuclease (ZFN).

3. The composition of claim 1 , wherein the at least one gene editing molecule further comprises one or more transposable elements.

4. The composition of claim 3 , wherein the one or more transposable elements comprise a piggyBac transposon, a Sleeping Beauty transposon or a LINE-1 (L1) transposon.

5. The composition of claim 1 , wherein the protein is a transposase.

6. A kit, comprising:

a pharmaceutical composition comprising the composition of claim 1 ; and

an implement for administering the pharmaceutical composition intravenously, via inhalation, topically, per rectum, per the vagina, transdermally, subcutaneously, intraperitoneally, intrathecally, intramuscularly or orally.

7. A composition for delivering at least one gene editing molecule to a cell, the composition comprising:

a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block,

wherein:

the at least one poly(L-histidine) block complexes with the at least one gene editing molecule;

the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule;

the at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid); and

wherein the at least one gene editing molecule comprises one or more of a protein, wherein the protein is selected from the group consisting of a transposase, a nuclease and an integrase;

wherein the molar ratio of triblock copolymers to the at least one gene editing molecule is about 2:3.

8. The composition of claim 7 , wherein the nuclease is selected from the group comprising:

a CRISPR associated protein 9 (Cas9);

a type IIS restriction enzyme;

a transcription activator-like effector nuclease (TALEN); and

a zinc finger nuclease (ZFN).

9. The composition of claim 7 , wherein the at least one gene editing molecule further comprises one or more transposable elements.

10. The composition of claim 9 , wherein the one or more transposable elements comprise a piggyBac transposon, a Sleeping Beauty transposon or a LINE- 1 (L 1 ) transposon.

11. The composition of claim 7 , wherein the protein is a transposase.

12. A kit, comprising:

a pharmaceutical composition comprising the composition of claim 7 ; and

an implement for administering the pharmaceutical composition intravenously, via inhalation, topically, per rectum, per the vagina, transdermally, subcutaneously, intraperitoneally, intrathecally, intramuscularly or orally.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2018
From: GHOROGHCHIAN, PAIMAN PETER; URIBE, GABRIELA ROMERO; OSTERTAG, ERIC
To: POSEIDA THERAPEUTICS, INC.
Reel/Frame 047706/0946 →
Continuity (4)
Provisional Application 62329892 · Apr 29, 2016
Provisional Application 62330775 · May 2, 2016
Provisional Application 62330784 · May 2, 2016
Related Publication 20190255191A1 · Aug 22, 2019