IP Library › Granted Patent US 12,310,964
Granted Patent B2
US 12,310,964 · App. 18/389,574 · Granted May 27, 2025

Compositions and methods for the treatment of Lowe Syndrome

Inventor: Ruben Claudio Aguilar (West Lafayette, IN)
A61K31/505A61K31/436A61P3/00
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Quick Facts
Patent No.
US 12,310,964
App. No.
18/389,574
Granted
May 27, 2025
Kind
B2
Abstract

A combination of active agents for the treatment of Lowe Syndrome (LS) comprising a RhoA inhibitor and a mTOR inhibitor; a pharmaceutical composition comprising the combination and a pharmaceutically acceptable carrier; a combination of pharmaceutical compositions in which one composition comprises a RhoA inhibitor and the other composition comprises a mTOR inhibitor; and a method of treating a patient for LS.

Claims (20)

1. A combination of active agents for the treatment of Lowe Syndrome, which combination comprises rosuvastatin and a mTOR inhibitor in amounts sufficient to treat Lowe Syndrome therapeutically, wherein the mTOR inhibitor is selected from WYE132 and INK128.

2. A pharmaceutical composition comprising the combination of claim 1 and a pharmaceutically acceptable carrier.

3. A combination of pharmaceutical compositions comprising a first pharmaceutical composition comprising rosuvastatin in an amount sufficient to treat Lowe Syndrome (LS) therapeutically and a pharmaceutically acceptable carrier and a second pharmaceutical composition comprising a mTOR inhibitor selected from WYE132 and INK128 in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier.

4. The combination of pharmaceutical compositions of claim 3 , in which the first and second pharmaceutical compositions are formulated to be administered by the same or different routes.

5. A method of treating a patient for Lowe Syndrome (LS), which method comprises administering to the patient:

(i) a combination of claim 1 ;

(ii) a pharmaceutical composition comprising the combination of claim 1 and a pharmaceutically acceptable carrier; or

(iii) a combination of pharmaceutical compositions comprising:

(a) a first pharmaceutical composition comprising rosuvastatin in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier, and

(b) a second pharmaceutical composition comprising a mTOR inhibitor selected from WYE132 and INK128 in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier.

6. A combination of active agents for the treatment of Lowe Syndrome, which combination comprises a Ras homolog family member A (RhoA) inhibitor and rapamycin in amounts sufficient to treat Lowe Syndrome therapeutically, wherein the RhoA inhibitor is selected from a statin selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and simvastatin and a geranylgeranyl transferase 1 (GGTase-1) inhibitor (GGTI) selected from P61A6 and GGTI-2418.

7. A pharmaceutical composition comprising the combination of claim 6 and a pharmaceutically acceptable carrier.

8. A combination of pharmaceutical compositions comprising a first pharmaceutical composition comprising a Ras homolog family member A (RhoA) inhibitor selected from a statin selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and simvastatin and a geranylgeranyl transferase 1 (GGTase-1) inhibitor (GGTI) selected from P61A6 and GGTI-2418 in an amount sufficient to treat Lowe Syndrome (LS) therapeutically and a pharmaceutically acceptable carrier and a second pharmaceutical composition comprising rapamycin in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier.

9. The combination of pharmaceutical compositions of claim 8 , in which the first and second pharmaceutical compositions are formulated to be administered by the same or different routes.

10. A method of treating a patient for Lowe Syndrome (LS), which method comprises administering to the patient:

(i) a combination of claim 6 ;

(ii) a pharmaceutical composition comprising the combination of claim 6 and a pharmaceutically acceptable carrier; or

(iii) a combination of pharmaceutical compositions comprising:

(a) a first pharmaceutical composition comprising a Ras homolog family member A (RhoA) inhibitor selected from a statin selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and simvastatin and a geranylgeranyl transferase 1 (GGTase-1) inhibitor (GGTI) selected from P61A6 and GGTI-2418 in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier, and

(b) a second pharmaceutical composition comprising rapamycin in an amount sufficient to treat LS therapeutically and a pharmaceutically acceptable carrier.

Assignments (1)
CONFIRMATORY LICENSE Recorded Feb 1, 2024
From: PURDUE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066407/0134 →
Continuity (3)
Continuation 17370676 · Jul 8, 2021
Provisional Application 63079536 · Sep 17, 2020
Related Publication 20240082246A1 · Mar 14, 2024
References Cited (12)
Choudhury, R. et al., Lowe Syndrome Protein OCRL1 Interacts with Clathrin and Regulates Protein Trafficking between Endosomes and the Trans-Golgi Network, Molecular Biology of the Cell, 16, pp. 3467-3479, 2005. [cited by applicant]
Coon, B. et al., Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase, Human Molecular Genetics, 18, pp. 4478-4491, 2009. [cited by applicant]
Coon, B. et al., The Lowe syndrome protein OCRL1 is involved in primary cilia assembly, Human Molecular Genetics, 21, pp. 1835-1847, 2012. [cited by applicant]
Lasne, D. et al., Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders, British Journal of Haematology, 150, pp. 685-688, 2010. [cited by applicant]
Madhivanan, K. et al., Lowe syndrome. Between primary cilia assembly and Rac1-mediated membrane remodeling, Communicative & Integrative Biology, 5, pp. 641-644, 2012. [cited by applicant]
Madhivanan, K. et al., Role of Ocrl1 in Primary Cilia Assembly, International review of cell and molecular biology, 317, pp. 331-347, 2015. [cited by applicant]
Madhivanan, K. et al., Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins, Human Molecular Genetics, vol. 00, pp. 1-16, 2020. [cited by applicant]
Mehta, Z. et al., The Cellular and Physiological Functions of the Lowe Syndrome Protein OCRL1, Traffic, 15, pp. 471-487, 2014. [cited by applicant]
Oltrabella, F. et al., The Lowe Syndrome Protein OCRL1 Is Required for Endocytosis in the Zebrafish Pronephric Tubule, PLOS Genetics, 10.1371, pp. 1-24, 2015. [cited by applicant]
Pirruccello, M. et al., Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL, Trends in Biochemical Sciences, 37, pp. 134-143, 2012. [cited by applicant]
Suchy, S. et al., The Deficiency of PIP2 5-Phosphatase in Lowe Syndrome Affects Actin Polymerization, Am. J. Hum. Genet., 71, pp. 1420-1427, 2002. [cited by applicant]
Van Rahden, V. et al., The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module, Human Molecular Genetics, 21, pp. 5019-5038, 2012. [cited by applicant]