IP Library › Granted Patent US 12,433,885
Granted Patent B2
US 12,433,885 · App. 18/516,174 · Granted Oct 7, 2025

Procaspase combination therapy for glioblastoma

Inventors: Paul J. Hergenrother (Champaign, IL); Rachel C Botham (Champaign, IL); Timothy M. Fan (Mahomet, IL); Mark J. Gilbert (Seattle, WA); Michael K. Handley (Windsor, CO); Avadhut Joshi (Towson, MD); Gregory J. Riggins (White Hall, MD); Theodore M. Tarasow (San Ramon, CA)
Assignees: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS; VANQUISH ONCOLOGY, INC.; THE JOHNS HOPKINS UNIVERSITY
A61K31/495A61K9/0019A61K9/008A61K9/2018A61K9/2054A61K9/4858A61K31/4188A61K31/53A61K47/10
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Quick Facts
Patent No.
US 12,433,885
App. No.
18/516,174
Granted
Oct 7, 2025
Kind
B2
Abstract

Compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other cancer therapies that achieve the same or similar therapeutic effect.

Claims (18)

1. A method of treating a brain cancer in a human subject in need thereof comprising administering to a human subject, concurrently or sequentially, a therapeutically effective amount of each of the compounds temozolomide (TMZ) and first procaspase activating compound (PAC-1):

wherein the therapeutically effective amount of each of the compounds TMZ and PAC-1 is about 8.1 mg/kg, or about 300 mg/m 2 , wherein the TMZ and PAC-1 form a synergistic anticancer combination that is about 56% to about 316% more effective than an additive anticancer effect of TMZ and PAC-1, the brain cancer is glioblastoma multiform or meningioma, and the glioblastoma multiform or meningioma is thereby treated.

2. The method of claim 1 wherein the synergistic anticancer combination is more effective than an additive anticancer effect of TMZ and PAC-1, by about 63%, about 66%, about 70%, about 75%, about 79%, about 93%, about 95%, about 100%, about 128%, about 158%, about 182%, about 225%, about 226%, or about 315%.

3. The method of claim 1 wherein the synergistic anticancer combination is more effective than an additive anticancer effect of TMZ and PAC-1, by about 100%, about 128%, about 158%, about 182%, about 225%, about 226%, or about 315%.

4. The method of claim 1 wherein the brain cancer is glioblastoma multiforme (GBM).

5. The method of claim 1 wherein the brain cancer is meningioma.

6. The method of claim 1 wherein the brain cancer is meningioma, and the synergistic anticancer combination is about 100% to about 316% more effective than an additive anticancer effect of TMZ and PAC-1.

7. The method of claim 1 wherein the brain cancer is glioblastoma multiforme (GBM), and the synergistic anticancer combination is about 100% to about 316% more effective than an additive anticancer effect of TMZ and PAC-1.

8. The method of claim 1 wherein the synergistic anticancer combination induces apoptosis in cancer cells of the brain cancer.

9. The method of claim 1 wherein the synergistic anticancer combination inhibits the growth or proliferation of cancer cells of the brain cancer.

10. The method of claim 1 wherein TMZ and PAC-1 are administered orally, intravenously, or a combination thereof.

11. The method of claim 1 wherein the synergistic anticancer combination is formed in vivo.

12. The method of claim 1 wherein TMZ and PAC-1 are administered concurrently.

13. The method of claim 1 wherein TMZ and PAC-1 are administered sequentially.

14. The method of claim 13 wherein TMZ is administered before PAC-1.

15. The method of claim 13 wherein TMZ is administered after PAC-1.

16. A method of treating a brain cancer in a human subject in need thereof comprising administering to a human subject, sequentially, about 300 mg/m 2 of temozolomide (TMZ) and about 300 mg/m 2 of PAC-1:

wherein the brain cancer is glioblastoma multiform or meningioma, and the glioblastoma multiform or meningioma is thereby treated.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2023
From: HERGENROTHER, PAUL J.; BOTHAM, RACHEL C.; FAN, TIMOTHY M.
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Reel/Frame 065732/0517 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2023
From: GILBERT, MARK J.; HANDLEY, MICHAEL K.; TARASOW, THEODORE M.
To: VANQUISH ONCOLOGY, INC.
Reel/Frame 065732/0545 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2023
From: JOSHI, AVADHUT; RIGGINS, GREGORY J.
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 065732/0574 →
Continuity (6)
Continuation 17130387 · Dec 22, 2020
Continuation 16148344 · Oct 1, 2018
Continuation 15243860 · Aug 22, 2016
Continuation 14383460
Provisional Application 61607103 · Mar 6, 2012
Related Publication 20240082241A1 · Mar 14, 2024
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