METHOD, COMPOSITION, AND ARTICLE OF MANUFACTURE FOR PROVIDING ALPHA-1 ANTITRYPSIN
The present invention provides a method for providing alpha-1 antitrypsin (α1-AT) to a subject, in particular a method for treating or preventing a disorder of disease associated with α1-AT deficiency in the subject, wherein the method comprises providing, subcutaneously, a therapeutically or prophylactically effective amount of α1-AT to the subject. Also provided is a composition and article of manufacture comprising α1-AT, in particular a formulation suitable for subcutaneous administration of α1-AT.
1 . A method for treating a disorder or disease associated with α1-AT deficiency in a subject, the method comprising:
administering subcutaneously to the subject in need thereof a dose of α1-AT, wherein the dose of α1-AT administered is about 120% of a dose of α1-AT administered to the subject by intravenous route; wherein the dose administered by intravenous route achieves a blood α1-AT trough level of at least about 80 mg/dL;
wherein the amount administered to the subject by intravenous route is therapeutically effective in preventing or treating a disorder or disease associated with α1-AT deficiency; and wherein the frequency of α1-AT subcutaneous administration is sufficient to maintain a trough level of at least about 80 mg/dL.
2 . The method of claim 1 , wherein the α1-AT is a plasma-derived α1-AT.
3 . The method of claim 1 , wherein the dose of α1-AT is administered in combination with one or more reagents comprising a hyaluronidase.
4 . The method of claim 3 , wherein the subcutaneous administration of α1-AT achieves at least about a 1.40-fold higher plasma C max relative to an identical subcutaneous administration of α1-AT without one or more reagents comprising hyaluronidase.
5 . The method of claim 4 , wherein the subcutaneous administration of α1-AT achieves at least about a 2-fold lower T max relative to an identical subcutaneous administration without one or more reagents comprising hyaluronidase.
6 . The method of claim 1 , wherein the subcutaneous administration of α1-AT does not result in a rapid blood serum concentration spike of α1-AT when compared to an identical dose of α1-AT administered intravenously.
7 . The method of claim 1 , wherein the subcutaneous administration of α1-AT achieves a C max ratio relative to an identical dose of α1-AT administered intravenously of about 1:3.
8 . The method of claim 1 , wherein the subcutaneous administration of α1-AT achieves a blood serum C max peak to C min trough ratio of about 1.5 after about 72 hours following initial administration of α1-AT.
9 . The method of claim 8 , wherein the C max peak to C min trough ratio of α1-AT is at least about 3-fold less than an identical dose of α1-AT administered intravenously after about 72 hours following initial administration of α1-AT.
10 . The method of claim 1 , wherein the blood serum concentration AUCO—+24 of α1-AT is at least about 20% less than an identical dose of α1-AT administered intravenously.
11 . The method of claim 1 , wherein the α1-AT deficiency is protease inhibitor type Z (PiZ) α1-AT deficiency.
12 . The method of claim 11 , wherein the disease or disorder associated with the α1-AT deficiency is pulmonary emphysema.
13 . A method for treating a disorder or disease associated with α1-AT deficiency in a subject, the method consisting of:
administering subcutaneously to the subject in need thereof a dose of α1-AT, wherein the dose of α1-AT administered is about 120% of a dose of α1-AT administered to the subject by intravenous route; wherein the dose administered by intravenous route achieves a blood α1-AT trough level of at least about 80 mg/dL;
wherein the amount administered to the subject by intravenous route is therapeutically effective in preventing or treating a disorder or disease associated with α1-AT deficiency; and
wherein the frequency of α1-AT subcutaneous administration is sufficient to
maintain a trough level of at least about 80 mg/dL.