US 11,813,308 B2
Treatment of cardiovascular disease using ActRII ligand traps
Keith Hruska, Creve Coeur, MO (US); Yifu Fang, St. Louis, MO (US); William Smith, Woodstock, NY (US); and Nianhang Chen, Basking Ridge, NJ (US)
Assigned to Celgene Corporation, Missouri (MO); and Washington University, St. Louis, MO (US)
Appl. No. 15/517,782
Filed by CELGENE CORPORATION, Summit, NJ (US); and WASHINGTON UNIVERSITY, St. Louis, MO (US)
PCT Filed Oct. 8, 2015, PCT No. PCT/US2015/054674
§ 371(c)(1), (2) Date Apr. 7, 2017,
PCT Pub. No. WO2016/069234, PCT Pub. Date May 6, 2016.
Claims priority of provisional application 62/062,021, filed on Oct. 9, 2014.
Claims priority of provisional application 62/078,321, filed on Nov. 11, 2014.
Claims priority of provisional application 62/103,515, filed on Jan. 14, 2015.
Claims priority of provisional application 62/167,052, filed on May 27, 2015.
Claims priority of provisional application 62/170,015, filed on Jun. 2, 2015.
Prior Publication US 2017/0304397 A1, Oct. 26, 2017
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/17 (2006.01); A61K 38/00 (2006.01); C07K 14/71 (2006.01); A61P 9/10 (2006.01); A61P 9/00 (2006.01); A61P 19/10 (2006.01)
CPC A61K 38/179 (2013.01) [A61P 9/00 (2018.01); A61P 9/10 (2018.01); A61P 19/10 (2018.01); C07K 14/71 (2013.01); A61K 38/00 (2013.01); C07K 2319/30 (2013.01)] 26 Claims
 
1. A method for treating a disease in a subject, comprising administering to the subject a pharmaceutically effective dose of an activin receptor type II (ActRII) signaling inhibitor, wherein the subject has:
(a) elevated levels of snail homolog 1 (Snai1) as compared to levels of Snai1 in a reference population;
(b) decreased levels of alpha smooth muscle actin (alpha-SMA) as compared to levels of alpha-SMA in a reference population;
(c) elevated levels of urinary protein as compared to levels of urinary protein in a reference population; and/or
(d) decreased levels of Axin2 as compared to levels of Axin2 in a reference population,
wherein the disease is:
(a) cardiovascular disease;
(b) vascular calcification;
(c) cardiovascular disease associated with and/or resulting from vascular calcification;
(d) arterial stiffness;
(e) cardiovascular disease associated with and/or resulting from arterial stiffness;
(f) left ventricular hypertrophy (LVH);
(g) cardiovascular disease associated with and/or resulting from left ventricular hypertrophy;
(h) cardiovascular disease associated with and/or resulting from renal disease; or
(i) bone resorption associated with chronic kidney disease-mineral and bone disease (CKD-MBD), and
wherein said ActRII signaling inhibitor comprises an amino acid sequence that is
(a) at least 98% identical to SEQ ID NO:2;
(b) at least 98% identical to SEQ ID NO:3;
(c) at least 98% identical to SEQ ID NO:6;
(d) at least 98% identical to SEQ ID NO:7; or
(e) at least 98% identical to SEQ ID NO:12.