USRE50230EActiveUtility

Method of treatment of hypoxia inducible factor (HIF)-related conditions

69
Assignee: GRIFOLS WORLDWIDE OPERATIONS LTDPriority: Jul 11, 2014Filed: May 25, 2022Granted: Dec 10, 2024
Est. expiryJul 11, 2034(~8 yrs left)· nominal 20-yr term from priority
Inventors:David RossRalph Christian Crumine
A61P 9/10A61P 39/04A61P 25/28A61K 31/472A61K 31/426A61K 31/223A61K 31/4412A61K 31/4196A61K 31/198A61K 31/16A61K 45/06A61K 31/4704A61K 31/164A61K 38/40A61P 43/00A61K 38/39A61K 38/26A61K 2300/00
69
PatentIndex Score
0
Cited by
78
References
38
Claims

Abstract

The present invention relates to methods of treatment of Hypoxia Inducible Factor (HIF)-related conditions, and in particular to methods of treatment of HIF-related conditions comprising the administration of a composition comprising transferrins.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A method of treating a Hypoxia Inducible Factor (HIF)-related pathological condition in a patient in need thereof, wherein the HIF-related pathological condition is Middle Cerebral Artery occlusion (MCAo), comprising administering to the patient a composition comprising a therapeutically effective amount of transferrin, and wherein the transferrin is a mixture of apo-transferrin and holo-transferrin in a ratio from 99% Apo-Tf:1% Holo-Tf to 30% Apo-Tf:70% Holo-Tf. 
     
     
       2. The method of  claim 1 , wherein the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor. 
     
     
       3. The method of  claim 2 , wherein the iron chelator is selected from the group consisting of M30, deferoxamine (DFO), Deferasirox, deferiprone, deferitrin, L1NAll, CP363, CP502 and Ethylenediaminetetraacetic acid (EDTA). 
     
     
       4. The method of  claim 2 , wherein the PHD2 enzyme inhibitor is selected from the group consisting of IOX2, IOX3 and dimethyloxallylglycine. 
     
     
       5. The method of  claim 1 , wherein the patient is a transplant recipient of an organ. 
     
     
       6. The method of  claim 5 , wherein the organ has been treated with the composition in preparation for the transplantation into the recipient. 
     
     
       7. The method of  claim 6 , where the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor. 
     
     
       8. The method of  claim 1 , wherein the condition is associated with ischemia or oxygen deprivation in the patient prior to surgery. 
     
     
       9. The method of  claim 8 , wherein the ischemia is due to cardiac arrest, thrombotic clots, traumatic injury or stroke. 
     
     
       10. The method of  claim 1 , wherein the condition is associated with interruption of blood flow during a surgical intervention in the patient. 
     
     
       11. The method of  claim 1 , wherein the transferrin is recombinant. 
     
     
       12. The method of  claim 1 , wherein the transferrin is modified by pegylation, glycosylation or polysialylation to extend its plasma half-life. 
     
     
       13. The method of  claim 1 , wherein the composition further comprises an iron chelator. 
     
     
       14. The method of  claim 1 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
       15. The method of  claim 1 , wherein the neurodegenerative disease is Alzheimer's disease. 
     
     
       16. The method of  claim 1 , wherein the neurodegenerative disease is Amvlotrophic Lateral Sclerosis. 
     
     
       17. The method of  claim 1 , wherein the transferrin is recombinant. 
     
     
       18. The method of  claim 1 , wherein the transferrin is modified by pegylation, glvcosvlation or polvsialvlation to extend its plasma half-life. 
     
     
       19. The method of  claim 1 , wherein the transferrin comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 1. 
     
     
       20. The method of  claim 1 , wherein the transferrin comprises an amino acid sequence with at least 90% identity to SEQ ID NO: 1. 
     
     
       21. A method of treating a Hypoxia Inducible Factor (HIF)-related pathological condition in a patient in need thereof, wherein the HIF-related pathological condition is a neurodegenerative disease selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amylotrophic Lateral Sclerosis, comprising administering to the patient a composition comprising a therapeutically effective amount of transferrin, wherein the transferrin comprises an amino acid sequence with at least 70% identity to SEQ ID NO: 1 and wherein the transferrin is a mixture of apo-transferrin and holo-transferrin in a ratio from 99% Apo-Tf:1% Holo-Tf to 30% Apo-Tf:70% Holo-Tf. 
     
     
       22. The method of  claim 21 , wherein the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor. 
     
     
       23. The method of  claim 22 , wherein the iron chelator is selected from the group consisting of M30, deferoxamine (DFO), Deferasirox, deferiprone, deferitrin, L1NAll, CP363, CP502 and Ethylenediaminetetraacetic acid (EDTA). 
     
     
       24. The method of  claim 22 , wherein the PHD2 enzyme inhibitor is selected from the group consisting of IOX2, IOX3 and dimethyloxallylglycine. 
     
     
       25. The method of  claim 21 , wherein the patient is a transplant recipient of an organ. 
     
     
       26. The method of  claim 25 , wherein the organ has been treated with the composition in preparation for the transplantation into the recipient. 
     
     
       27. The method of  claim 26 , where the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor. 
     
     
       28. The method of  claim 21 , wherein the condition is associated with ischemia or oxygen deprivation in the patient prior to surgery. 
     
     
       29. The method of  claim 28 , wherein the ischemia is due to cardiac arrest, thrombotic clots, traumatic injury or stroke. 
     
     
       30. The method of  claim 21 , wherein the condition is associated with interruption of blood flow during a surgical intervention in the patient. 
     
     
       31. The method of  claim 21 , wherein the transferrin is recombinant. 
     
     
       32. The method of  claim 21 , wherein the transferrin is modified by pegylation, glycosylation or polysialylation to extend its plasma half-life. 
     
     
       33. The method of  claim 21 , wherein the composition further comprises an iron chelator. 
     
     
       34. The method of  claim 21 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
       35. The method of  claim 21 , wherein the neurodegenerative disease is Alzheimer's disease. 
     
     
       36. The method of  claim 21 , wherein the neurodegenerative disease is Amylotrophic Lateral Sclerosis. 
     
     
       37. The method of  claim 21 , wherein the transferrin comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 1. 
     
     
       38. The method of  claim 21 , wherein the transferrin comprises an amino acid sequence with at least 90% identity to SEQ ID NO: 1.

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