Methods and compositions relating to lung repair

Patent metadata

Field	Value
Publication number	US-12337027-B2
Application number	US-201916977854-A
Country	US
Kind code	B2
Filing date	Jan 24, 2019
Priority date	Mar 22, 2018
Publication date	Jun 24, 2025
Grant date	Jun 24, 2025

Abstract

Described herein are methods of inducing and/or enhancing lung growth and/or repair by administering an agonist of sFlt1-Hif signaling to a subject or contacting lung tissue with an agonist of sFlt1-Hif signaling.

First claim

What is claimed is:

1. A method of inducing growth and/or repair of lung tissue in a subject in need thereof, the method comprising administering a therapeutically effective amount of an agonist of soluble Feline McDonough Sarcoma (FMS) like tyrosine kinase 1 (sFlt1)-hypoxia inducible factor 1 (Hif) signalling to the subject,
wherein the agonist of sFlt1-Hif signalling is a Hif prolyl hydroxylase antagonist selected from JTZ-951, FG-4592, GSK1278863, and MK-8617:
wherein the subject has severe pulmonary hypoplasia, hypoplastic lung disease, congenital diaphragmatic hernia, a disease with deficient alveolar count, alveolar capillary dysplasia, or has undergone a pneumonectomy, and
wherein the subject is not diagnosed with or in need of treatment for an inflammatory condition.

2. The method of claim 1 , wherein the growth and/or repair of lung tissue is compensatory lung growth.

3. The method of claim 1 , wherein the agonist of sFlt1-Hif signalling is administered to the airway.

4. The method of claim 1 , wherein the agonist of sFlt1-Hif signalling is administered intravenously.

5. The method of claim 1 , wherein the agonist of sFlt1-Hif signalling is administered topically.

6. The method of claim 1 , wherein the agonist of sFlt1-Hif signalling is administered at a dose of from 5 mcg/kg to 50 mcg/kg.

7. The method of claim 6 , wherein the agonist of sFlt1-Hif signalling is administered at a dose of 20 mcg/kg.

8. The method of claim 1 , whereby endogenous vascular endothelial growth factor (VEGF) levels increase in the lung tissue of the subject.

9. The method of claim 1 , wherein the method results in a higher lung volume, an increase in inspiratory capacity, an increase in exercise capacity, and/or an increase in pulmonary compliance.

10. A method of inducing growth and/or repair of lung tissue in a subject in need thereof, the method comprising administering a therapeutically effective amount of FG-4592, wherein the subject is not diagnosed with or in need of treatment for an inflammatory condition.

11. The method of claim 10 , wherein the subject has severe pulmonary hypoplasia, hypoplastic lung disease, congenital diaphragmatic hernia, a disease with deficient alveolar count, alveolar capillary dysplasia, or has undergone a pneumonectomy.

12. The method of claim 10 , wherein the FG-4592 is administered to the airway.

13. The method of claim 10 , wherein the FG-4592 is administered intravenously.

14. The method of claim 10 , wherein the FG-4592 is administered topically.

15. The method of claim 10 , whereby endogenous vascular endothelial growth factor (VEGF) levels increase in the lung tissue of the subject.

16. The method of claim 10 , wherein the method results in a higher lung volume, an increase in inspiratory capacity, an increase in exercise capacity, and/or an increase in pulmonary compliance.

17. A method of inducing compensatory lung growth in a subject in need thereof, the method comprising administering a therapeutically effective amount of an agonist of soluble Feline McDonough Sarcoma (FMS) like tyrosine kinase 1 (sFlt1)-hypoxia inducible factor 1 (Hif) signalling to the subject,
wherein the agonist of sFlt1-Hif signalling is a Hif prolyl hydroxylase antagonist selected from JTZ-951, FG-4592, GSK1278863, and MK-8617.

18. The method of claim 17 , wherein the subject has severe pulmonary hypoplasia, hypoplastic lung disease, congenital diaphragmatic hernia, emphysema, a disease with deficient alveolar count, alveolar capillary dysplasia, or has undergone a pneumonectomy.

19. The method of claim 17 , wherein the agonist of sFlt1-Hif signalling is administered to the airway.

20. The method of claim 17 , wherein the agonist of sFlt1-Hif signalling is administered intravenously.

21. The method of claim 17 , wherein the agonist of sFlt1-Hif signalling is administered topically.

22. The method of claim 17 , wherein the agonist of sFlt1-Hif signalling is administered at a dose of from 5 mcg/kg to 50 mcg/kg.

23. The method of claim 22 , wherein the agonist of sFlt1-Hif signalling is administered at a dose of 20 mcg/kg.

24. The method of claim 17 , whereby endogenous vascular endothelial growth factor (VEGF) levels increase in the lung tissue of the subject.

25. The method of claim 17 , wherein the method results in a higher lung volume, an increase in inspiratory capacity, an increase in exercise capacity, and/or an increase in pulmonary compliance.

26. A method of inducing compensatory lung growth in a subject in need thereof, the method comprising administering a therapeutically effective amount of FG-4592.

27. The method of claim 26 , wherein the subject has severe pulmonary hypoplasia, hypoplastic lung disease, congenital diaphragmatic hernia, emphysema, a disease with deficient alveolar count, alveolar capillary dysplasia, or has undergone a pneumonectomy.

28. The method of claim 26 , wherein the FG-4592 is administered to the airway.

29. The method of claim 26 , wherein the FG-4592 is administered intravenously.

30. The method of claim 26 , wherein the FG-4592 is administered topically.

31. The method of claim 26 , whereby endogenous vascular endothelial growth factor (VEGF) levels increase in the lung tissue of the subject.

32. The method of claim 26 , wherein the method results in a higher lung volume, an increase in inspiratory capacity, an increase in exercise capacity, and/or an increase in pulmonary compliance.

Assignees

• Childrens Medical Ct Corp

Inventors

• Puder Mark
• Dao Duy T

Classifications

• A61K38/177

  Receptors; Cell surface antigens; Cell surface determinants · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/472

  Non-condensed isoquinolines, e.g. papaverine · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title