IP Library › Granted Patent US 12,673,033
Granted Patent B2
US 12,673,033 · App. 18/754,044 · Granted Jul 7, 2026

Multiple myeloma treatment

Inventors: Mihael H. Polymeropoulos (Potomac, MD); Louis William Licamele (Potomac, MD); Christian Lavedan (Potomac, MD)
Assignee: Vanda Pharmaceuticals Inc.
A61K31/165A61K9/0019A61K9/0053A61P35/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,673,033
App. No.
18/754,044
Filed
Jun 25, 2024
Granted
Jul 7, 2026
Kind
B2
Art Unit
1621
USPC
514/575
Abstract

The invention relates generally to the treatment of multiple myeloma. One embodiment of the invention provides a method of treating multiple myeloma (MM) in an individual, the method comprising: administering to the individual an effective amount of trichostatin A (TSA).

Claims (21)

1 . A method of treating a patient suffering from multiple myeloma (MM), the method consisting essentially of:

administering to the patient an amount of trichostatin A (TSA) effective to decrease expression of at least one gene in the patient, the at least one gene being selected from a group consisting of: CCNB1, AURKB, CDC2, KIF11, KIF2C, TOP2A, ASPM, CKS1B, and WEE1.

2 . The method of claim 1 , wherein the amount of TSA is effective to decrease expression of either or both of CCNB1 and AURKB in the patient.

3 . The method of claim 1 , wherein the amount of TSA is effective to decrease expression of either or both of CKS1B and WEE1.

4 . The method of claim 1 , wherein the amount of TSA is effective to decrease expression of each of CCNB1, AURKB, CDC2, KIF11, KIF2C, TOP2A, ASPM, CKS1B, and WEE1.

5 . The method of claim 1 , wherein the amount of TSA is between about 0.01 mg/kg/day and about 100 mg/kg/day.

6 . The method of claim 1 , wherein the amount of TSA is between about 0.1 mg/kg/day and about 10 mg/kg/day.

7 . The method of claim 6 , wherein the amount of TSA is between about 0.5 mg/kg/day and about 5 mg/kg/day.

8 . The method of claim 1 , wherein administering includes orally administering.

9 . The method of claim 1 , wherein administering includes intravenously administering.

10 . A method of treating a patient suffering from multiple myeloma (MM), the method consisting essentially of:

determining, from a biological sample obtained from the spatient's body, a level of expression of one or more gene in the patient, the one or more gene selected from a group consisting of: CCNB1, AURKB, CDC2, KIF11, KIF2C, TOP2A, ASPM, CKS1B, and WEE1; and

in the case that the level of expression of the one or more gene is indicative of overexpression, as compared to an individual not suffering from MM, administering to the patient an amount of trichostatin A (TSA) effective to decrease expression of the one or more gene.

11 . The method of claim 10 , wherein the effective amount is an amount sufficient to decrease expression of either or both of CCNB1 and AURKB in the patient.

12 . The method of claim 10 , wherein the effective amount is an amount sufficient to decrease expression of either or both of CKS1B and WEE1.

13 . The method of claim 10 , wherein the effective amount is an amount sufficient to decrease expression of each of CCNB1, AURKB, CDC2, KIF11, KIF2C, TOP2A, ASPM, CKS1B, and WEE1.

14 . The method of claim 10 , wherein the amount of TSA is between about 0.01 mg/kg/day and about 100 mg/kg/day.

15 . The method of claim 14 , wherein the amount of TSA is between about 0.1 mg/kg/day and about 10 mg/kg/day.

16 . The method of claim 15 , wherein the amount of TSA is between about 0.5 mg/kg/day and about 5 mg/kg/day.

17 . The method of claim 10 , wherein administering includes orally administering.

18 . The method of claim 10 , wherein administering includes intravenously administering.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 26, 2024
From: POLYMEROPOULOS, MIHAEL H.; LICAMELE, LOUIS WILLIAM; LAVEDAN, CHRISTIAN
To: VANDA PHARMACEUTICALS INC.
Reel/Frame 067844/0526 →
Continuity (7)
Continuation 18350914 · Jul 12, 2023
Continuation 16550936 · Aug 26, 2019
Continuation 15979287 · May 14, 2018
Continuation 14912078 · Aug 22, 2014
Provisional Application 61870747 · Aug 27, 2013
Provisional Application 61869039 · Aug 22, 2013
Related Publication 20240342120A1 · Oct 17, 2024
References Cited (54)
US 4218478A · Omura et al. · 1980 [cited by applicant]
US 4690918A · Beppu · 1987 [cited by applicant]
US 9296753B2 · Smyth · 2016 [cited by applicant]
US 9670549B2 · Mock · 2017 [cited by applicant]
US 10265282B2 · Polymeropoulos · 2019 [cited by examiner]
US 11078289B2 · Polymeropoulos · 2021 [cited by examiner]
US 11667718B2 · Polymeropoulos · 2023 [cited by examiner]
US 11737993B2 · Polymeropoulos · 2023 [cited by examiner]
US 20020183388A1 · Gudas · 2002 [cited by applicant]
US 20050260664A1 · Shaughnessy · 2005 [cited by examiner]
US 20090123925A1 · Collie-Duguid et al. · 2009 [cited by applicant]
EP 0196415A2 · 1986 [cited by applicant]
EP 3026006 · 2016 [cited by applicant]
JP S61176523 · 1986 [cited by applicant]
JP 2007521259 · 2007 [cited by applicant]
JP 2010516628 · 2010 [cited by applicant]
JP 2020073508 · 2020 [cited by applicant]
WO 02060430A1 · 2002 [cited by applicant]
WO 2007067516A2 · 2007 [cited by applicant]
WO WO2007139939A2 · 2007 [cited by examiner]
WO WO2010064016A2 · 2010 [cited by examiner]
WO 2011134898A1 · 2011 [cited by applicant]
WO 2013083098A2 · 2013 [cited by applicant]
WO 2015027125A1 · 2015 [cited by applicant]
Ahn (Oncology Reports vol. 27 p. 455-460 published 2012) (Year: 2012). [cited by examiner]
Hsu (Biochimica et Biophysica Acta vol. 1820 pp. 104-115 Published 2012) (Year: 2012). [cited by examiner]
Reagan-Shaw et al (FASEBJ vol. 22 pp. 659-661. Published 2007) (Year: 2007). [cited by examiner]
Ahn (Oncology Reports vol. 27 pp. 455-460 published 2012) (Year: 2012). [cited by examiner]
Ahn et al., “The histone deacetylase inhibitor, Trichostatin A, induces G2/M phase arrest and apoptosis in YD-10B oral squamous carcinoma cells,” Oncology Reports, 2012, vol. 27, pp. 455-460. [cited by applicant]
Chang et al., “Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation,” British Journal of Haemotology, vol. 135, pp. 486-491. [cited by applicant]
Gorgun et al., “A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma,” Blood, Jun. 24, 2010, vol. 115, No. 25, pp. 5202-5213. [cited by applicant]
Heller et al., “Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells,” Cancer Research, Jan. 1, 2008, vol. 68, No. 1, pp. 44-54. [cited by applicant]
International Search Report and Written Opinion in PCT/US2014/052216, mailed Nov. 3, 2014, 10 pages. [cited by applicant]
Legartova et al., “Expression of RAN, ZHX-2, and CHC1L genes in multiple myeloma patients and in myeloma cell lines treated with HDAC and Dnmts inhibitors,” Neoplasma, 2010, vol. 57, No. 5, pp. 482-487. [cited by applicant]
Ling et al., “Mechanisms of Proteaseome Inhibitor PS-341-induced G2-M-Phase Arrest and Apoptosis in Human Non-Small Cell Lung Cancer Cell Lines,” Clinical Cancer Research, Mar. 2003, vol. 9, pp. 1145-1154. [cited by applicant]
Liu et al., “Trichostatin A affects breast cancer cell viability by modulating Fhit and Survivin expression,” 2012 International Conference on Biomedical Engineering and Biotechnology, 2012, pp. 1133-1135. [cited by applicant]
Moreaux et al., “Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors,” British Journal of Cancer, 2013, vol. 109, No. 3, pp. 676-685. [cited by applicant]
Nair et al., “Paradoxical effects of trichostatin A: inhibition of NF-Y-associated histone acetyltransferase activity, phosphorylation of hGCN5 and downregulation of cyclin A and B1 mRNA,” Cancer Letters, 2001, vol. 166… [cited by applicant]
Nara et al., “Bortezomib Reduces the Tumorigenicity of Multiple Myeloma via Downregulation of Upregulated Targets in Clonogenic Side Population Cells,” Plos One, Mar. 2013, vol. 8, No. 3, pp. 1-13. [cited by applicant]
Office Action in EA201690446, mailed Nov. 28, 2016, 4 pages. [cited by applicant]
Office Action in U.S. Appl. No. 14/912,078, mailed Nov. 14, 2017, 23 pages. [cited by applicant]
Park et al., “Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase,” Journal of Molecular Medicine, 2008, vol. 86, pp. 117-128. [cited by applicant]
Reagan-Shaw et al., “Dose translation from animal to human studies revisited,” The FASEB Journal, Mar. 2007, vol. 22, pp. 659-661. [cited by applicant]
Shaughnessy et al., “Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27kip1 and an aggressive clinical course in multiple myeloma,” Hematology, 2005, vol. 10, Supp… [cited by applicant]
Shaughnessy Jr. et al., “A validated gene expression model of high-risk multiple myeloma is defined by deregulated expressions of genes mapping to chromosome 1,” Blood, Mar. 15, 2007, vol. 109, No. 6, pp. 2276-2284. [cited by applicant]
Vigushin et al., “Trichostatin A Is a Histone Deacetylase Inhibitor with Potent Antitumor Activity against Breast Cancer in Vivo,” Clinical Cancer Research, Apr. 2001, vol. 7, pp. 971-976. [cited by applicant]
Zhang et al., “Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer,” Cancer Biology & Therapy, Sep. 2008, vol. 7, No. 9, pp. 13… [cited by applicant]
Notice of Reasons for Rejection for Japanese Application No. P2021-42699, dated Dec. 17, 2024, 9 pages. [cited by applicant]
Chinese Second Office Action and Search Report for Application No. 201480046624.5, dated Oct. 19, 2018. [cited by applicant]
Chen, New Ideas and New Targets in Pharmacological Research, 2012, pp. 85-86. [cited by applicant]
International Search Report and Written Opinion for PCT/US2014/052209, mailed Mar. 30, 2015, 18 pages. [cited by applicant]
Xu et al., J Am Soc Nephrol 21: 2041-2046. (Year: 2010). [cited by applicant]
Nadler et al., Clin Cancer Res 2008;4455 14(14) Jul. 15, 2008 (Year: 2008). [cited by applicant]
X Wang, Y-X Zhou, W Qiao, Y Tominaga, M Ouchi, T Ouchi, C-X Deng, “Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation”, Oncogene, Scientific & Med… [cited by applicant]