US 12,274,736 B2
Hematopoietic growth factor proteins and analogs thereof and angiotensin converting enzyme inhibitors for treatment of radiation exposure
George N. Cox, Louisville, CO (US); Christie M. Orschell, Indianapolis, IN (US); Meetha Manek Medhora, Brookfield, WI (US); and Brian Fish, Waukesha, WI (US)
Assigned to Bolder Biotechnology, Inc., Boulder, CO (US); Indiana University Research and Technology Corporation, Indianapolis, IN (US); and The Medical College of Wisconsin, Inc., Milwaukee, WI (US)
Filed by Bolder BioTechnology, Inc., Boulder, CO (US); Indiana University Research and Technology Corporation, Indianapolis, IN (US); and The Medical College of Wisconsin, Inc., Milwaukee, WI (US)
Filed on Dec. 13, 2021, as Appl. No. 17/548,929.
Application 17/548,929 is a continuation of application No. 15/269,746, filed on Sep. 19, 2016, granted, now 11,229,683.
Claims priority of provisional application 62/220,819, filed on Sep. 18, 2015.
Prior Publication US 2022/0202903 A1, Jun. 30, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/20 (2006.01); A61K 38/05 (2006.01); A61K 38/19 (2006.01)
CPC A61K 38/2073 (2013.01) [A61K 38/05 (2013.01); A61K 38/193 (2013.01)] 20 Claims
 
1. A method of improving 90 day to 12 month survival from hematopoietic acute radiation syndrome (H-ARS) in a subject who has been exposed to radiation and has delayed effects of acute radiation exposure (DEARE), comprising administering to the subject a combination therapy comprising an effective dose of an angiotensin-converting enzyme inhibitor (ACEI) and an effective dose of at least one hematopoietic growth factor (HGF) or protein analog thereof or combinations thereof;
wherein the ACEI is selected from the group consisting of lisinopril, perindopril, captopril, enalapril, and ramipril; and
wherein the HGF or protein analog thereof is selected from the group consisting of:
a granulocyte colony-stimulating factor (G-CSF) analog comprising a methionine at the N-terminus of SEQ ID NO:1;
a G-CSF analog comprising a cysteine residue substituted for A141 of G-CSF having SEQ ID NO:1 and a serine residue substituted for C17 of G-CSF having SEQ ID NO:1;
a granulocyte-macrophage colony-stimulating factor (GM-CSF) analog (SEQ ID NO:2);
a GM-CSF analog comprising a cysteine substitution at amino acid position 3 of SEQ ID NO: 2;
an interleukin-11 (IL-11) analog comprising a cysteine residue added following the C-terminus of the protein having SEQ ID NO:3 or SEQ ID NO:7, wherein the P1 amino acid is deleted; and
combinations thereof; and
wherein the survival obtained by treatment with the combination of at least one HGF or protein analog thereof and the ACEI is greater than the survival obtained by treatment with at least one HGF or protein analog thereof alone or treatment with the ACEI alone.