METHOD FOR THE TREATMENT OF A VIRAL INFECTION WITH HUMAN ALPHA-1 ANTITRYPSIN

Abstract

A method is for the treatment of a viral infection with human alpha-1 antitrypsin (A1AT). Methods and compositions for the treatment of coronavirus disease 2019 (COVID-19) in a patient, include administering to the patient a therapeutically effective amount of human alpha-1 antitrypsin. The A1AT is administered in an amount between 60 mg/kg and 200 mg/kg. Methods and compositions for the treatment of Cytokine Release Syndrome (CRS) in a patient, include administering to the patient a therapeutically effective amount of an inhibitor of interleukin-6 in combination with a therapeutically effective amount of A1AT.

Claims

1. A method for the treatment of coronavirus disease 2019 (COVID-19) in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of human alpha-1 antitrypsin (A1AT), wherein A1AT is administered in an amount between 60 mg/kg and 200 mg/kg.

2. The method according to claim 1, wherein the patient is also subjected to standard medical treatment (SMT) for COVID-19.

3. The method according to claim 1, wherein the COVID-19 is mild, moderate or severe.

4. The method according to claim 1, wherein the composition comprising A1AT is administered intravenously.

5. The method according to claim 1, wherein the composition comprising A1AT is administered in an amount between 80 mg/kg and 160 mg/kg.

6. The method according to claim 5, wherein the composition comprising A1AT is administered in an amount of 120 mg/kg.

7. The method according to claim 1, wherein the composition comprising A1AT is administrated at least every 6 hours, or at least every 8 hours, or at least every 12 hours, or at least every 24h, or at least every 48 hours, or at least every 72 hours, or at least once a week, or at least once every two weeks.

8. The method according to claim 1, wherein the composition comprising A1AT is administered as a single dose.

9. The method according to claim 1, wherein the patient in need thereof is a hospitalized male or female subject ≥ 18 years of age at time of screening who is being treated for COVID-19.

10. The method according to claim 1, wherein the patient in need thereof has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by any nucleic acid technology (NAT) or any other commercial or public health assay.

11. The method according to claim 1, wherein the patient in need thereof has COVID-19 illness (symptoms) of any duration.

12-54. (canceled)

55. A method for the treatment of Acute Respiratory Distress Syndrome (ARDS) resulting from CRS, the method comprises administering to the patient a composition according to claim 57.

56. A method for the treatment of Septic Shock, the method comprises administering to the patient a compostion according to claim 58.

57. A composition comprising a therapeutically effective amount of an inhibitor of interleukin-6 (IL-6) in combination with a therapeutically effective amount of human alpha-1 antitrypsin (A1AT) for use in the treatment of Acute respiratory Distress Syndrome (ARDS).

58. A composition comprising a therapeutically effective amount of an inhibitor of interleukin-6 (IL-6) in combination with a therapeutically effective amount of human alpha-1 antitrypsin (A1AT) for use in the treatment of Septic Shock.

59. The method according to claim 55, wherein said composition is administered intravenously.

60. The method according to claim 55, wherein the inhibitor of interleukin-6 (IL-6) is administered to the patient in an amount of about 4 mg/kg to about 8 mg/kg.

61. The composition according to claim 57, wherein A1AT is administered to a subject in an amount between 60 mg/kg and 200 mg/kg.

62. The composition according to claim 57, wherein a subject the A1AT is administered is also subjected to a standard medical treatment (SMT) for COVID-19.

63. The composition according to claim 57, wherein the composition is administered intravenously.

Description

EXAMPLE

Example 1. Simulation of the Predicted Effect of the Method of the Present Invention on CRS

[0072] To identify new indications of A1AT in combination with other drugs a prediction technology was used. This technology, which is known to the skilled person, creates mathematical models that integrate biochemical, pharmaceutical, and clinical data with the aim of simulating human physiology. The analysis of these models provides mechanistic insight into biological processes and has the potential to uncover non-obvious patterns and molecular explanations.

[0073] In this case, a repositioning screening was performed, where the efficacy of combinations of A1AT with other approved drugs (aprox 3000 drugs; source Drugbank database) were computationally predicted by calculating their molecular impact on a set of mathematical models simulating different indications.

[0074] A1AT was molecularly characterized: the main proteins, including known A1AT targets and off-targets mediating the known downstream effect of the A1AT.

[0075] Once the mathematical models were generated, a drug repositioning analysis was performed on them in order to calculate the efficacy of each combination of A1AT with an existing approved drug for treating each disease. Approximately, 3000 drug combinations were tested on each indication. They were ranked according to the degree of predicted modulation of the indication (100 - 0 %). From all the 3000 combinations made, the higher effect (95 %) on the treatment of CRS was obtained with A1AT in combination with tocilizumab, which is higher than the predicted effect for each of these drugs separately, i.e. 67 % and 47 %, respectively.

[0076] The following table shows the predicted effect on Cytokyne Release Syndrome of each drug separately and in combination.

TABLE-US-00001 Drug A Drug B Predicted effect of Drug A Predicted effect of Drug B Predicted effect of Drug A + Drug B Tocilizumab A1AT 47 % 67 % 95 % Esmolol A1AT 76 % 67 % 78 % Lutropin α A1AT 78 % 67 % 79 % Cimetidine A1AT 74 % 67 % 79 %