US 12,351,598 B2 · Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use

Abstract

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Claims44

Dependent claims

A compound of Formula (B):

Rx-LN-(Q)e (B)
or a stereoisomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers;
or a pharmaceutically acceptable salt, solvate, or hydrate thereof;
wherein:
Rx is —NH2;
LN is a linker comprising a polyethylene glycol (PEG);
Q is an oligonucleotide comprising a phosphotriester;
e is 1;
Q has the structure of Formula (D):
wherein
each XN is independently a nucleotide;
X3′ is a 3′ terminal nucleotide;
X5′ is a 5′ terminal nucleotide;
YP comprises an internucleoside phosphotriester;
and
b and c are each an integer ranging from about 0 to about 25;
with the proviso that their sum is no less than 5;
wherein the oligonucleotide comprises a nucleotide with a modified nucleobase.

15 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/461,797Filed 30 Aug 2021 · continuation

Priority

14 Apr 2017

Published

US 2022/0056069 A124 Feb 2022

Granted

8 Jul 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification53 codes

C07H 21/04
Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of…: with…
A61K 31/7125
Compounds having three or more nucleosides or nucleotides: nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other…
A61K 39/0011
Vertebrate antigens: cancer antigens
A61K 39/39
Medicinal preparations containing antigens or antibodies: characterised by the immunostimulating additives, e.g. chemical adjuvants

Family

Application62/485,748Us provisional application · filed 14 Apr 2017

Application62/537,925Us provisional application · filed 27 Jul 2017

Application15/953,290Parent of this continuation · filed 13 Apr 2018

US 2022/0056069 A1Pre-grant publication · published 24 Feb 2022

US 11,203,611 B2Parent of this continuation

US 2018/0312536 A1Published application

US 12,351,598 B2This patent

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

Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use

Life of this patent

Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use

Life of this patent

Abstract

Claims44