Methods of treating central nervous system disorders via administration of nanoparticles of an mTOR inhibitor and an albumin

Patent metadata

Field	Value
Publication number	US-12324860-B2
Application number	US-202418441673-A
Country	US
Kind code	B2
Filing date	Feb 14, 2024
Priority date	Mar 20, 2018
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent).

First claim

The invention claimed is:

1. A method of treating epilepsy in an individual, comprising systemically administering to the individual an effective amount of a composition comprising nanoparticles comprising albumin-bound sirolimus, wherein the ratio of albumin to sirolimus in the nanoparticles is from about 1:1 to about 9:1.

2. The method of claim 1 , wherein the nanoparticle composition is administered once every week, twice every three weeks, or three times every four weeks.

3. The method of claim 1 , wherein the average diameter of the nanoparticles in the nanoparticle composition is no greater than about 200 nm.

4. The method of claim 1 , wherein the nanoparticle composition is administered to the individual at a dose of about 0.1 mg/m 2 to 25 mg/m 2 .

5. The method of claim 1 , wherein the nanoparticle composition is administered to the individual at a dose of about 1 mg/m 2 to 10 mg/m 2 , and wherein the nanoparticle composition is administered once every week, twice every three weeks, or three times every four weeks.

6. The method of claim 1 , wherein the nanoparticle composition is administered for at least about one to six cycles, wherein each cycle consists of 21 days or 28 days.

7. The method of claim 1 , wherein the individual is a human.

8. The method of claim 1 , wherein the nanoparticle composition is parenterally administered into the individual.

9. The method of claim 8 , wherein the nanoparticle composition is intravenously administered into the individual.

10. The method of claim 8 , wherein the nanoparticle composition is subcutaneously administered into the individual.

11. The method of claim 1 , wherein the epilepsy is associated with cortical dysplasia.

12. The method of claim 11 , wherein the epilepsy is associated with focal cortical dysplasia.

13. The method of claim 1 , wherein the epilepsy is associated with a lesion imaged by magnetic resonance imaging (MRI), or associated with tuberous sclerosis complex (TSC).

14. The method of claim 1 , wherein the epilepsy is associated with infantile spasms.

15. The method of claim 14 , wherein the epilepsy is surgically refractory epilepsy.

16. The method of claim 1 , wherein the epilepsy is metabolic epilepsy, immune epilepsy, or idiopathic localization-related epilepsy with a genetic basis.

17. The method of claim 1 , wherein the individual is selected for treatment on the basis of having an mTOR-activation aberration.

18. The method of claim 17 , wherein the mTOR-activating aberration comprises an aberration at one or more genes selected from the group consisting of PTEN, TSC1, TSC2, AKT1, MTOR, PI3K, PIK3CA, PIK3CG, RHEB, TP53, NF1, NF2, FGFR4, and BAP1.

19. The method of claim 18 , wherein the mTOR-activating aberration comprises a somatic mutation or germline mutation in the one or more genes.

20. The method of claim 18 , wherein the mTOR-activating aberration comprises a loss of function mutation or deletion of the one or more genes.

Assignees

• Abraxis Bioscience Llc

Inventors

• Desai Neil P
• Hou Shihe

Classifications

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K31/436

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P25/08 Primary

  Antiepileptics; Anticonvulsants · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title