US 11,981,749 B2
Methods for treating conditions associated with MASP-2 dependent complement activation
Gregory A. Demopulos, Mercer Island, WA (US); Thomas A. Dudler, Bellevue, WA (US); and Hans-Wilhelm Schwaeble, Cambridge (GB)
Assigned to OMEROS CORPORATION, Seattle, WA (US); and UNIVERSITY OF LEICESTER, Leicester (GB)
Filed by Omeros Corporation, Seattle, WA (US); and University of Leicester, Leicestershire (GB)
Filed on Aug. 4, 2020, as Appl. No. 16/984,509.
Application 16/984,509 is a continuation of application No. 15/347,434, filed on Nov. 9, 2016, abandoned.
Claims priority of provisional application 62/406,726, filed on Oct. 11, 2016.
Claims priority of provisional application 62/252,814, filed on Nov. 9, 2015.
Prior Publication US 2021/0047433 A1, Feb. 18, 2021
Int. Cl. A61P 7/02 (2006.01); A61P 37/02 (2006.01); C07K 16/40 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/40 (2013.01) [A61P 7/02 (2018.01); A61P 37/02 (2018.01); C12Y 304/21104 (2013.01); A61K 2039/505 (2013.01); C07K 2317/20 (2013.01); C07K 2317/21 (2013.01); C07K 2317/33 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 8 Claims
 
1. A method of treating a human subject suffering from persistent TMA associated with hematopoietic stem cell transplant (HSCT-TMA) comprising
(i) identifying a human subject suffering from persistent HSCT-TMA wherein said subject has TMA that persists despite a reduction or discontinuation of an immunosuppressive agent, or wherein said subject has TMA that persists at least 30 days after transplant; and
(ii) administering to the subject a composition comprising a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, wherein the MASP-2 inhibitory monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable region set forth as SEQ ID NO:67 and a light chain variable region set forth as SEQ ID NO:70, wherein the composition is administered at a dosage of at least 4 mg/kg at least once a week for a time period of at least three weeks, wherein said administration is effective to improve at least one or more of the following clinical parameters associated with persistent TMA associated with hematopoietic stem cell transplant: (i) an increase in platelet count (e.g., at least double, at least triple, at least quadruple the platelet count prior to treatment)); (ii) an increase in haptoglobin; (iii) a decrease in lactate dehydrogenase (LDH); and/or (iv) a decrease in creatinine.