IP Library › Granted Patent US 12,377,060
Granted Patent B2
US 12,377,060 · App. 18/215,989 · Granted Aug 5, 2025

Methods and compositions for preventing or treating tissue calcification

Inventors: James A. Tumlin (Lawrenceville, GA); Paul L. Darke (Hingham, MA); John M. Rudey (New York, NY)
Assignee: Epizon Pharma, Inc.
A61K31/122A61K9/0053A61K31/05A61K31/22A61K31/366A61P3/10A61P3/14A61P13/12A61P43/00A61K45/06A61K2300/00
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Quick Facts
Patent No.
US 12,377,060
App. No.
18/215,989
Granted
Aug 5, 2025
Kind
B2
Abstract

The invention provides methods and compositions for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) tissue calcification in a subject in need thereof and, more particularly, the invention relates to methods of using menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7) for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) tissue calcification in a subject with diabetes, chronic kidney disease, end stage renal failure, or a subject undergoing hemodialysis and/or receiving anticoagulant therapy. The invention further provides methods and compositions for reducing one or more symptoms of chronic obstructive pulmonary disorder (COPD), including using menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7), for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) one or more symptoms of COPD.

Claims (30)

1. A method of treating tissue calcification in a pre-diabetic subject or a subject with diabetes, chronic kidney disease or a combination thereof, and in need thereof, the method comprising administering to the subject at least 2 mg of menaquinol-7 (MKH2-7) per day, wherein the MKH2-7 is a compound of the formula:

whereupon the administration of the MKH2-7: (i) increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration; or (ii) decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration.

2. The method of claim 1 , wherein the subject has diabetes, type II diabetes, or has been diagnosed as pre-diabetic.

3. The method of claim 1 , wherein the subject has chronic kidney disease.

4. The method of claim 1 , wherein the subject has stage 4 or 5 chronic kidney disease/end stage renal disease.

5. The method of claim 1 , wherein the subject is receiving non-warfarin-based anti-coagulant therapy.

6. The method of claim 5 , wherein the anti-coagulation therapy comprises an inhibitor of Factor Xa activity or Factor IIa activity.

7. A method of treating tissue calcification in a subject with stage 5 chronic kidney disease and undergoing oral, non-warfarin-based anticoagulant therapy, and in need thereof, the method comprising administering to the subject a composition comprising menaquinol-7 (MKH2-7) per-day, thereby to treat tissue calcification in the subject, wherein the MKH2-7 is administered in a pharmaceutical composition; and whereupon the administration of the MKH2-7:

(i) increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration; or

(ii) decreases a plasma level of Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of hs-CRP prior to administration; and where the MKH2-7 is:

8. The method of claim 7 , wherein the subject is diabetic or has been diagnosed as pre-diabetic.

9. The method of claim 7 , wherein the subject has end stage renal disease.

10. The method of claim 7 , whereupon administration of the MKH2-7 to the subject increases the subject's serum T50 value relative to the subject's serum T50 value prior to administration of the MKH2-7.

11. The method of claim 7 , wherein administration of the MKH2-7:

(a) increases a ratio of a carboxylated to a non-carboxylated of a Vitamin K dependent protein; or

(b) decreases an amount of a non-carboxylated Vitamin K dependent protein in plasma of the subject relative to the ratio or amount present prior to administration of the MKH2-7.

12. The method of claim 7 , wherein the Vitamin K-dependent protein is selected from Matrix Gla Protein, Growth Arrest Specific Gene 6 (Gas-6) protein, PIVKA-II protein, osteocalcin, activated Protein C, or activated Protein S.

13. The method of claim 4 , wherein, when the subject has a dermal lesion and/or a vascular lesion, the administration of the MKH2-7 reduces the size of the dermal and/or vascular lesion.

14. A method of treating tissue calcification in a subject in need thereof, the method comprising administering to the subject menaquinol-7 (MKH2-7) daily, wherein the MKH2-7 is administered in a pharmaceutical composition, so as to cause at least one of the following:

(i) increase the subject's serum T50 value relative to the subject's serum T50 value prior to administration of the MKH2-7;

(ii) increase a ratio of a carboxylated to a non-carboxylated form of a Vitamin K-dependent protein in the subject's plasma relative to the ratio prior to administration of the MKH2-7;

(iii) increase the plasma level of Fetuin A relative to the plasma concentration of Fetuin A prior to administration of the MKH2-7; or

(iv) decrease the plasma level of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma concentration of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) prior to administration of the MKH2-7, thereby to treat tissue calcification in the subject; and where the MKH2-7 is:

15. The method of claim 14 , wherein the subject:

(i) has diabetes or has been diagnosed as pre-diabetic;

(ii) has chronic kidney disease; or

(iii) is undergoing hemodialysis.

16. The method of claim 14 , wherein the composition is administered orally.

17. The method of claim 14 , wherein the composition is administered in liquid form.

18. The method of claim 14 , wherein the composition is administered in a capsule or soft gel formulation.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2023
From: TUMLIN, JAMES A.; DARKE, PAUL L.; RUDEY, JOHN M.
To: EPIZON PHARMA, INC.
Reel/Frame 065003/0695 →
Continuity (6)
Continuation 17317488 · May 11, 2021
Continuation 17100256 · Nov 20, 2020
Continuation 16817347 · Mar 12, 2020
Continuation 16435241 · Jun 7, 2019
Provisional Application 62682796 · Jun 8, 2018
Related Publication 20240009144A1 · Jan 11, 2024
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