US 12,371,522 B2Granted

Bioreducible poly (beta-amino ester)s for siRNA delivery

AssigneeThe Johns Hopkins University

InventorsJordan J Green, Kristen Kozielski, Stephany Yi Tzeng

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Abstract

Degradable polymers were synthesized that self-assemble with nucleic acids, proteins, hydrophobic drugs, and other small molecules to form particles that are effective for delivery into a cell, tissue and/or organism either in vitro or in vivo. The presently disclosed polymers demonstrate differential cell-type specificity, an ability to promote endosomal escape to protect the cargos from degradation and enhance delivery to the cytoplasm, and/or bioreducibility, which enables triggered intracellular drug release to be tuned to promote optimal delivery to the target cell type. The presently disclosed materials may be used to treat a wide variety of conditions or diseases, such as cancer, cardiovascular diseases, infectious diseases, and ophthalmic diseases.

Claims31

Dependent claims

A nanoparticle or microparticle comprising siRNA or miRNA and a compound of formula (I) or formula (II):

wherein:
n is an integer from 1 to 10,000;
X and Y are integers selected from 1 and 3;
Z is an integer from 1 to 10,000;
R1 and R2 can be the same or different and are each independently a C1-C30 alkyl chain;
each R3 is a C3-C8 linear or branched alkyl chain;
R′ is a side chain derived from:
the R″ end groups are the same or different and are derived from a compound selected from the group consisting of:
or R″ comprises a biomolecule selected from the group consisting of poly(ethyleneglycol) (PEG), a targeting ligand, and a labeling molecule, or R″ comprises a C1-C30 alkyl chain, wherein the C1-C30 alkyl chain is terminated with a functional group selected from the group consisting of —OH and —NH2;
and
pharmaceutically acceptable salts thereof.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/438,353Filed 25 Oct 2013 · continuation in part
Priority: 12 Oct 2011
Published: US 2015/0273071 A11 Oct 2015
Granted: 29 Jul 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C08F 222/14
Of phenols or saturated alcohols: esters having no free carboxylic acid groups , e.g. dialkyl maleates or fumarates
A61K 9/5153
Obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides:…
A61K 31/713
Compounds having three or more nucleosides or nucleotides: double-stranded nucleic acids or oligonucleotides
A61K 47/32
Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates: macromolecular compounds obtained by reactions only involving…

Family

Application13/272,042Parent of this continuation-in-part · filed 12 Oct 2011
Application61/718,536Us provisional application · filed 25 Oct 2012
Application61/860,638Us provisional application · filed 31 Jul 2013
Application61/883,376Us provisional application · filed 27 Sep 2013
US 2015/0273071 A1Pre-grant publication · published 1 Oct 2015
US 9,717,694 B2Parent of this continuation-in-part · filed 1 Aug 2017
US 2019/0209690 A9Pre-grant publication · published 11 Jul 2019
US 2012/0114759 A1Published application
US 2016/0374949 A9Published application
US 12,371,522 B2This patent

From the US filing history. Foreign family members aren’t listed.