Granted Patent B2

US 10,912,790 · App. 15/568,139 · Granted Feb 9, 2021

Inventors: Andreas Wagner (Vienna, AT); Robert Habib (London, GB); Hans E. Huber (Lansdale, PA); Pål Sætrom (Trondheim, NO); Endre Bakken Stovner (Trondheim, NO); Markus Hossbach (Kulmbach, DE); Monika Krampert (Bamberg, DE); Hans-Peter Vornlocher (Bayreuth, DE)

Assignee: MiNA THERAPEUTICS LIMITED

A61K31/7105A61K9/127A61P1/16A61P3/08A61P35/00C12N15/113C12N2310/113C12N2310/14C12N2310/315C12N2310/351

Abstract

Claims (23)

1. A pharmaceutical composition comprising a synthetic isolated saRNA encapsulated in a liposome, wherein the saRNA up-regulates expression of C/EBPα gene, wherein the saRNA is double-stranded and comprises a sense strand and an antisense strand comprising SEQ ID No. 109 (CEBPA51) or SEQ ID No. 93 (AW51), wherein the liposome comprises 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), cholesteryl-hemi succinate (CHEMS), and 4-(2-aminoethyl)-morpholino-cholesterol hemisuccinate (MOCHOL), and wherein the saRNA has a concentration of about 2 mg/mL to about 5 mg/mL.

2. The pharmaceutical composition of claim 1 , wherein the molar ratio of POPC:DOPE:CHEMS:MOCHOL is around 6:24:23:47.

3. The pharmaceutical composition of claim 1 , wherein the size of the liposome is between about 50 nm to about 150 nm.

4. The pharmaceutical composition of claim 3 , wherein the size of the liposome is between 100 nm to about 120 nm.

5. The pharmaceutical composition of claim 1 , wherein the antisense strand and/or the sense strand of the saRNA comprises a 3′ overhang.

6. The pharmaceutical composition of claim 1 , wherein the sense strand of the saRNA comprises at least one chemical modification.

7. The pharmaceutical composition of claim 6 , wherein the sense strand of the saRNA comprises at least 2 modifications.

8. The pharmaceutical composition of claim 6 , wherein the modification comprises any of 2′-F, 2′-OMe, inverted deoxyribose, or phosphorothioate linkage between nucleotides.

9. The pharmaceutical composition of claim 1 , wherein the sense strand of the saRNA comprises SEQ ID No. 110 (CEBPA51) or SEQ ID No. 94 (AW51).

10. The pharmaceutical composition of claim 1 , wherein the saRNA has an antisense strand of SEQ ID No. 109 and a sense strand of SEQ ID No. 110.

11. The pharmaceutical composition of claim 1 , wherein the saRNA has a concentration of about 2.5 mg/mL.

12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH between about 7.2 to about 7.8.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition has a pH of about 7.5.

14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a phosphate buffer.

15. The pharmaceutical composition of claim 14 , wherein the phosphate buffer comprises disodium hydrogen phosphate, dihydrate and potassium dihydrogen phosphate.

16. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises a cryoprotectant.

17. The pharmaceutical composition of claim 16 , wherein the cryoprotectant is sucrose.

18. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises an ionic strength adjuster.

19. The pharmaceutical composition of claim 18 , wherein the ionic strength adjuster is potassium chloride.

20. A method of treating hepatocellular carcinoma (HCC) of a subject comprising administering the pharmaceutical composition in claim 1 to the subject.

21. The method of claim 20 , wherein the HCC is advanced HCC.

22. The method of claim 20 , wherein the dose of the pharmaceutical composition is between about 20 to about 160 mg/m 2 .

23. The method of claim 20 , wherein the pharmaceutical composition is administered once a week for 3 weeks on Day 1, Day 8 and Day 15 by intravenous infusion.

Assignments (8)

Continuity (4)