AN INHALED IL-1 BLOCKADE TREATMENT FOR RESPIRATORY TRACT IMMUNOPATHOLOGY
The invention is directed to a method for treating an inflammatory disorder of the lower airways in a human subject in need thereof, comprising administering an effective amount of a recombinant human IL-1 receptor antagonist (rhIL-IRa) directly to the lower airways in the human subject; wherein the inflammatory disorder is caused by a coronavirus infection.
1 . A method for treating an inflammatory disorder of the lower airways in a human subject in need thereof, comprising administering an effective amount of a recombinant human IL-1 receptor antagonist (rhIL-1Ra) directly to the lower airways in the human subject, wherein the inflammatory disorder is caused by a coronavirus infection.
2 . The method of claim 1 , wherein the rhIL-1Ra is anakinra.
3 . The method of claim 2 , wherein the anakinra is a component of a composition, and wherein the composition is an inhaled formulation.
4 . The method of claim 3 , wherein the inhaled formulation is ALTA-2530.
5 . The method of claim 1 , wherein the coronavirus infection is caused by a coronavirus selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, 229E, NL63, OC43, and HKU1.
6 . The method of claim 1 , wherein the coronavirus infection is caused by a coronavirus selected from the group consisting of SARS-CoV-2 and a mutant thereof.
7 . The method of claim 6 , wherein the SARS-CoV-2 mutant is a variant selected from the group consisting of B.1.526, B.1.526.1, B.1.525, B.1.617, B.1.617.1, B.1.617.2, B.1.617.3, B.1.1.7, B.1.351, B.1.427, B.1.429, P.1, and P.2.
8 . The method of claim 1 , wherein the human subject is diagnosed with COVID-19.
9 . The method of claim 1 , wherein the inflammatory disorder of the lower airways is acute respiratory distress syndrome or cytokine storm syndrome.
10 . The method of claim 1 , wherein the rhIL-1Ra is nebulized.
11 . The method of claim 10 , wherein the nebulized rhIL-1Ra has a mass median aerodynamic diameter (MMAD) of about 1 μm to 15 μm.
12 . The method of claim 11 , wherein the nebulized rhIL-1Ra has a mass median aerodynamic diameter (MMAD) of about 3 μm.
13 . The method of claim 10 , wherein the nebulized rhIL-1Ra is delivered using a nebulizer.
14 . The method of claim 13 , wherein the nebulizer is selected from the group consisting of PARI eFlow nebulizer, PARI VELOX nebulizer, Philips iNeb Advanced nebulizer, Philips InnoSpire Go nebulizer, a Vectura nebulizer, and AeroEclipse II nebulizer.
15 . The method of claim 14 , wherein the nebulizer is a PARI nebulizer or a Vectura nebulizer.
16 . The method of claim 1 , wherein the rhIL-1Ra inhibits at least one pro-inflammatory cytokine selected from the group consisting of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and interleukin 18 (IL-18).
17 . A method for treating an inflammatory disorder of the lower airways in a human subject in need thereof, comprising administering an effective amount of a recombinant human IL-1 receptor antagonist (rhIL-1Ra) directly to the lower airways in the human subject, wherein the rhIL-1Ra causes blockade of interleukin 1 to about the same degree as caused by the upregulation of endogenous IL-1Ra during a restoration of physiologic immune regulation.
18 . The method of claim 17 , wherein the rhIL-1Ra is anakinra.
19 . The method of claim 17 , wherein the anakinra is a component of a composition, and wherein the composition is an inhaled formulation.
20 . The method of claim 19 , wherein the inhaled formulation is ALTA-2530.
21 . The method of claim 17 , wherein the inflammatory disorder is caused by a coronavirus infection.
22 . The method of claim 17 , wherein the human subject is diagnosed with a coronavirus infection.
23 . The method of claim 22 , wherein the coronavirus infection is COVID-19.
24 . The method of claim 21 , wherein the coronavirus infection is caused by a coronavirus selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, 229E, NL63, OC43, and HKU1.
25 . The method of claim 24 , wherein the coronavirus infection is caused by a coronavirus selected from the group consisting of SARS-CoV-2 and a mutant thereof.
26 . The method of claim 25 , wherein the SARS-CoV-2 mutant is a variant selected from the group consisting of B.1.526, B.1.526.1, B.1.525, B.1.617, B.1.617.1, B.1.617.2, B.1.617.3, B.1.1.7, B.1.351, B.1.427, B.1.429, P.1, and P.2.
27 . The method of claim 17 , wherein the inflammatory disorder of the lower airways is acute respiratory distress syndrome or cytokine storm syndrome.
28 . The method of claim 17 , wherein the rhIL-1Ra is nebulized.
29 . The method of claim 28 , wherein the nebulized rhIL-1Ra has a mass median aerodynamic diameter (MMAD) of about 1 μm to 15 μm.
30 . The method of claim 29 , wherein the nebulized rhIL-1Ra has a mass median aerodynamic diameter (MMAD) of about 3 μm.
31 . The method of claim 28 , wherein the nebulized rhIL-1Ra is delivered using a nebulizer.
32 . The method of claim 31 , wherein the nebulizer is selected from the group consisting of PARI eFlow nebulizer, PARI VELOX nebulizer, Philips iNeb Advanced nebulizer, Philips InnoSpire Go nebulizer, a Vectura nebulizer, and AeroEclipse II.
33 . The method of claim 32 , wherein the nebulizer is a PARI nebulizer or a Vectura nebulizer.
34 . The method of claim 17 , wherein the rhIL-1Ra inhibits at least one pro-inflammatory cytokine selected from the group consisting of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and interleukin 18 (IL-18).