IP Library › Granted Patent US 12,233,056
Granted Patent B2
US 12,233,056 · App. 18/131,183 · Granted Feb 25, 2025

Lysyl oxidase inhibitors for treating myeloid malignancies

Inventors: Wolf-Karsten Hofmann (Mannheim, DE); Daniel Nowak (Mannheim, DE); Vladimir Ryabov (Mannheim, DE); Qingyu Xu (Mannheim, DE); Eva Altrock (Vaihingen/Enz, DE)
Assignee: Syntara Limited
A61K31/47A61K31/706A61P35/00A61P35/02
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 12,233,056
App. No.
18/131,183
Granted
Feb 25, 2025
Kind
B2
Abstract

Lysyl oxidase (LOX) inhibitors, lysyl oxidase-like (LOXL) inhibitors, or pharmaceutically acceptable salts thereof and methods for the treatment of myeloid malignancies, comprising administering a therapeutically effective amount of those inhibitors alone or optionally in combination with a second therapeutic agent.

Claims (10)

1. A method for the treatment of a myeloid malignancy in a subject, the method comprising administering to the subject a therapeutically effective amount of a lysyl oxidase (LOX) inhibitor, a lysyl oxidase-like (LOXL) inhibitor, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the inhibitors or salts, wherein the LOX or LOXL inhibitor is

or a pharmaceutically acceptable salt thereof, the method further comprising administering to the subject one or more additional therapeutic agents or a pharmaceutical composition comprising one or more of the additional agents, wherein the additional therapeutic agent is a hypomethylating agent or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1 , wherein the myeloid malignancy is selected from the group consisting of myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPS overlap syndromes and acute myeloid leukemia (AML).

3. The method according to claim 2 , wherein the AML is acute promyelocytic leukemia (APL).

4. The method according to claim 2 , wherein the myeloid malignancy is MDS.

5. The method according to claim 1 , wherein the additional therapeutic agent is 5-azacytidine or a pharmaceutically acceptable salt thereof.

6. The method according to claim 5 , wherein the myeloid malignancy is MDS.

7. The method according to claim 1 , wherein the additional therapeutic agent is decitabine or a pharmaceutically acceptable salt thereof, or a combination of decitabine or a pharmaceutically acceptable salt thereof and a further additional therapeutic agent, the further agent being cedazuridine or a pharmaceutically acceptable salt thereof.

8. The method according to claim 7 , wherein the myeloid malignancy is MDS.

9. The method according to claim 7 , wherein the combination of the LOX or LOXL inhibitor, or a pharmaceutically acceptable salt thereof, decitabine, or a pharmaceutically acceptable salt thereof, and cedazuridine, or a pharmaceutically acceptable salt thereof, are formulated for oral administration.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2024
From: HEIDELBERG UNIVERSITY
To: PHARMAXIS LTD.
Reel/Frame 066058/0967 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 24, 2023
From: HOFMANN, WOLF-KARSTEN; NOWAK, DANIEL; RYABOV, VLADIMIR; XU, QINGYU; ALTROCK, EVA
To: HEIDELBERG UNIVERSITY
Reel/Frame 064354/0961 →
Priority Claims (1)
AU 2022900904 · Apr 6, 2022 · national
Continuity (1)
Related Publication 20230321075A1 · Oct 12, 2023
References Cited (61)
US 4454158A · Bey · 1984 [cited by applicant]
US 4699928A · McDonald · 1987 [cited by applicant]
US 4943593A · Palfreyman et al. · 1990 [cited by applicant]
US 4965288A · Palfreyman et al. · 1990 [cited by applicant]
US 5021456A · Palfreyman et al. · 1991 [cited by applicant]
US 5059714A · Palfreyman et al. · 1991 [cited by applicant]
US 5182297A · Palfreyman et al. · 1993 [cited by applicant]
US 5252608A · Palfreyman et al. · 1993 [cited by applicant]
US 20060004015A1 · Schohe et al. · 2006 [cited by applicant]
US 20080293936A1 · Burchardt · 2008 [cited by applicant]
US 20090053224A1 · Smith et al. · 2009 [cited by applicant]
US 20210353571A1 · Findlay · 2021 [cited by examiner]
US 20230349907A1 · Findlay et al. · 2023 [cited by applicant]
WO 2003097612A1 · 2003 [cited by applicant]
WO 2006053555A2 · 2006 [cited by applicant]
WO 2007120528A2 · 2007 [cited by applicant]
WO 2011090760A1 · 2011 [cited by applicant]
WO 2016144702A1 · 2016 [cited by applicant]
WO 2016144703A1 · 2016 [cited by applicant]
WO 2017003862A1 · 2017 [cited by applicant]
WO 2017015221A1 · 2017 [cited by applicant]
WO 2017136870A1 · 2017 [cited by applicant]
WO 2017136871A1 · 2017 [cited by applicant]
WO 2017139274A1 · 2017 [cited by applicant]
WO 2017141049A1 · 2017 [cited by applicant]
WO 2018048930A1 · 2018 [cited by applicant]
WO 2018157190A1 · 2018 [cited by applicant]
WO 2019073251A1 · 2019 [cited by applicant]
WO 2019234418A1 · 2019 [cited by applicant]
WO 2020024017A1 · 2020 [cited by applicant]
WO 2020099886A1 · 2020 [cited by applicant]
WO 2021012014A1 · 2021 [cited by applicant]
Duarte D, Vale N. Evaluation of synergism in drug combinations and reference models for future orientations in oncology. Curr Res Pharmacol Drug Discov. May 12, 2022;3:100110. doi: 10.1016/j.crphar.2022.100110 (Year: 20… [cited by examiner]
Talleirda et al.Quantitative Methods for Assessing Drug Synergism. Genes and Cancer. 2012, 2(11), 1003-1008 (Year: 2012). [cited by examiner]
Piasecki et al. Lysyl oxidase inhibition in primary myelofibrosis: A renewed strategy. Arch Stem Cell Ther. 2020, 1(1), 23-27 (Year: 2020). [cited by examiner]
Mokhtari et al., Combination therapy in combating cancer. Oncotarget, 2017, 8 (23), 38022-38043 (Year: 2017). [cited by examiner]
Ma et al.Comparison Between Decitabine and Azacitidine for Patients With Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndrome: A Systematic Review and Network Meta-Analysis. Front. Pharmacol. 2021, 12, 701690… [cited by examiner]
Ball et al. (Leuk Lymphoma. May 2017 ; 58(5): 1022-1036). (Year: 2017). [cited by examiner]
Appelbaum, F. et al., Allogeneic bone marrow transplantation for myelodysplastic syndrome: outcomes analysis according to IPSS score, Leukemia, 12(1):S25-29 (1998). [cited by applicant]
Bessler, M. et al., Dyskeratosis congenita, FEBS Lett, 584, 3831-3838 (2020). [cited by applicant]
Cazzola, M. et al., Myelodysplastic Syndromes, New England Journal of Medicine, 383, 1358-1374 (2020). [cited by applicant]
Chen, W. et al., Lysyl oxidase (LOX) family members: rationale and their potential as therapeutic targets for liver fibrosis, Hepatology, 72:729-741 (2020). [cited by applicant]
Cutler, C. S. et al., A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome, Blood, 104,… [cited by applicant]
Damaj, G., et al., Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francopho… [cited by applicant]
Fenaux, P. et al., Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study, The Lancet Oncology, 10: … [cited by applicant]
Gary Philips, Clinical stage novel, small molecule medicines focused on cancer and fibrotic disease, Investor Presentation, Apr. 2021, 30 pages. [cited by applicant]
Greenberg, P. et al., International scoring system for evaluating prognosis in myelodysplastic syndromes, Blood, 89(6):2079-88 (1997). [cited by applicant]
Gueller, S. et al., Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34( +) cells selected from patients with both low- and high-risk myelodysplastic syndrom… [cited by applicant]
Kee, Y. et al., Molecular pathogenesis and clinical management of Fanconi anemia, J. Clin. Invest., 122:3799-3806 (2012). [cited by applicant]
Ley, T. et al., Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, N. Engl. J. Med., 368(22):2059-74 (2013). [cited by applicant]
Ma, X, Epidemiology of myelodysplastic syndromes, Am. J. Med., 125 S2-5 (2012). [cited by applicant]
Martino, R. et al., Myelodysplastic Syndrome subcommittee of the Chronic Leukemia Working Party of the European, G. Marrow Transplantation, Retrospective comparison of reduced-intensity conditioning and conventional hig… [cited by applicant]
Medyouf, H. et al., Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit, Cell Stem Cell, 14:824-837 (2014). [cited by applicant]
Mossner, M. et al., Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure, Blood, 128:1246-1259 (2016). [cited by applicant]
Rissin, D. et al., Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations, Nat. Biotechnol., 28:595-599 (2010). [cited by applicant]
Schilter, H. et al., The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis, J. Cell Mol. Med., 23:1759-1770 (2018). [cited by applicant]
Sierra, J. et al., Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia, Blood, 100:1997-2004 (2002). [cited by applicant]
Sloand, E. M. et al., Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy, J. Clin. Oncol., 26:2505-2511 (2008). [cited by applicant]
Spivak, J.L., Myeloproliferative Neoplasms, N Engl J Med, 376:2168-2181 (2017). [cited by applicant]
Tanaka, T. et al., MDS overlap disorders and diagnostic boundaries, Blood, 133:1086-1095 (2019). [cited by applicant]
Witte, T. et al., Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS, Blood, 98:2326-2331 (2… [cited by applicant]