Targeted lipid particles for systemic delivery of nucleic acid molecules to leukocytes

Patent metadata

Field	Value
Publication number	US-10920246-B2
Application number	US-201615571535-A
Country	US
Kind code	B2
Filing date	May 25, 2016
Priority date	May 26, 2015
Publication date	Feb 16, 2021
Grant date	Feb 16, 2021

Abstract

Disclosed are targeted lipid based particles for delivery of nucleic acid molecules (such as siRNA) to leukocytes (such as T-Cells and B-cells). Further disclosed are uses of the targeted lipid based particles for treating Leukocytes-associated diseases, such as, cancer.

First claim

The invention claimed is:

1. A particle for targeted delivery of a nucleic acid to a leukocyte cell, the particle comprising: a lipid membrane suitable for encapsulating a nucleic acid, wherein the lipid membrane comprises Dlin-MC3-DMA, cholesterol, DSPC, DMG-PEG, and DSPE-PEG-maleimide conjugated to a targeting moiety and wherein the targeting moiety is an antibody selected from the group consisting of an anti-CD38 antibody, an anti-CD4 antibody, an anti-CD8 antibody, and an anti-CD3 antibody, or an antigen binding fragment thereof.

2. The particle of claim 1 , further comprising a nucleic acid encapsulated within the particle.

3. The particle of claim 1 , wherein the leukocyte cells are primary lymphocytes.

4. The particle of claim 3 , wherein the lymphocytes are selected from B-cells and T-cells.

5. The particle of claim 1 , which is internalized by the leukocyte cell.

6. The particle of claim 1 , wherein the targeting moiety is a single antibody configured to specifically recognize an antigen expressed by said leukocyte.

7. The particle of claim 1 , wherein the targeting moiety is an anti-CD38 antibody.

8. The particle of claim 1 , wherein the targeting moiety is an antibody selected from an anti-CD4 antibody, an anti-CD8 antibody, and an anti-CD3 antibody.

9. The particle of claim 2 , wherein the nucleic acid is the only molecule having a biological effect on the target site.

10. The particle of claim 2 , wherein the percentage of encapsulation of the nucleic acid is over about 90%.

11. The particle of claim 2 , wherein the nucleic acid comprises an interfering RNA selected from the group consisting of siRNA, miRNA, shRNA, and antisense RNA, modified forms thereof or combinations thereof.

12. The particle of claim 11 , wherein the nucleic acid is an siRNA.

13. The particle of claim 12 , wherein the targeting moiety is an anti-CD38 antibody.

14. The particle of claim 2 , wherein the nucleic acid comprises an siRNA against a cell cycle regulator selected from the group consisting of: Polo-like Kinase 1 (PLK), Cyclin D1, CHK1, Notch pathway genes, PDGFRA, EGFRvIII, PD-L1, RelB, STAT1, STAT3, MCL1, CKAP5, RRM1, SF3A1 and CDK11B, or any combinations thereof.

15. The particle of claim 14 , wherein the cell cycle regulator is Cyclin D1.

16. A composition comprising a plurality of particles according to claim 1 .

17. A composition comprising a plurality of particles according to claim 2 .

Assignees

• Univ Ramot

Inventors

• Peer Dan
• Weinstein Shiri
• Toker Itai Antoine
• Ramishetti Srinivas

Classifications

• C07K16/2812

  against CD4 · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title