Targeted sensitization of non-del(5q) malignant cells

Patent metadata

Field	Value
Publication number	US-9956294-B2
Application number	US-201414761641-A
Country	US
Kind code	B2
Filing date	Jan 21, 2014
Priority date	Jan 18, 2013
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Acα, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

First claim

What is claimed is:

1. A molecule comprising
a nucleic acid inhibitor comprising SEQ ID NO: 1, a nucleic acid inhibitor comprising SEQ ID NO: 2, or a nucleic acid inhibitor comprising a combination of SEQ ID NOS 1 and 2;
a toll like receptor-9 (TLR9) targeting ligand; and
lenalidomide.

2. The molecule of claim 1 , wherein the nucleic acid inhibitor comprising a combination of SEQ ID NOS: 1 and 2 are combined via a bivalent linker.

3. The molecule of claim 1 , wherein the TLR9 targeting ligand is coupled to the nucleic acid inhibitor of Cdc25C or the nucleic acid inhibitor of PP2 Acα by a bivalent linker.

4. The molecule of claim 1 , wherein the lenalidomide is coupled to the nucleic acid inhibitor comprising SEQ ID NO: 1 or the nucleic acid inhibitor comprising SEQ ID NO: 2, or the nucleic acid inhibitor comprising a combination of SEQ ID NOS: 1 and 2 by a bivalent linker.

5. The molecule of claim 1 , wherein the molecule is defined by the formula:
TTL-IC-IP-LEN, or
TTL-IP-IC-LEN,
wherein “TTL” represents the TLR9 targeting ligand,
wherein “IC” represents the inhibitor comprising SEQ ID NO: 1,
wherein “IP” represents the inhibitor comprising SEQ ID NO: 2,
wherein “LEN” represents lenalidomide, and
wherein “-” represents a bivalent linker.

6. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide, or an analogue or derivative thereof that binds TLR9.

7. A composition comprising the molecule of claim 1 in a pharmaceutically acceptable carrier.

Assignees

• H Lee Moffitt Cancer Ct & Res

Inventors

• List Alan
• Wei Sheng

Classifications

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K38/00 Primary

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K47/48092 Primary

  Human Necessities · mapped topic