Multicomponent degradable cationic polymers

Patent metadata

Field	Value
Publication number	US-12049530-B2
Application number	US-202117150796-A
Country	US
Kind code	B2
Filing date	Jan 15, 2021
Priority date	May 15, 2009
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000™, FUGENE®, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.

First claim

That which is claimed:

1. A compound of formula (I):

wherein:
n is an integer from 1 to 10,000;
R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are each hydrogen
R 1 is absent

wherein:
R is selected from the group consisting of:

R′ is selected from the group consisting of:

 and
pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , wherein n is an integer selected from the group consisting of from 1 to 1000, from 1 to 100, and from 5 to 20.

3. The compound of claim 1 , wherein the compound of formula (I) has a molecular weight selected from the group consisting of from 5 to 10 kDa, from 10 to 15 kDa, from 15 to 25 kDa, and from 25 to 50 kDa.

4. A nanoparticle or microparticle comprising the compound of claim 1 and a nucleic acid.

5. The nanoparticle or microparticle according to claim 4 , wherein the nucleic acid is selected from the group consisting of a gene, DNA, RNA, siRNA, miRNA, isRNA, agRNA, saRNA, and combinations thereof.

6. A pharmaceutical composition comprising a compound of claim 1 .

7. A method for delivering a nucleic acid to a cell, a specific cell line, a tissue, or an organism, the method comprising associating a nucleic acid with a compound of claim 1 to form one or more particles comprising the nucleic acid and compound of formula (I), and administering the one or more particles or contacting the one or more particles with the cell, specific cell line, tissue or organism.

8. A pharmaceutical composition comprising a nanoparticle or microparticle according to claim 4 .

Assignees

• Univ Johns Hopkins
• The Johns Hopkins Univeristy

Inventors

• Green Jordan J
• Sunshine Joel C
• Bhise Nupura S
• Shmueli Ron B
• Tzeng Stephany Y

Classifications

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61K38/02

  Peptides of undefined number of amino acids; Derivatives thereof · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title