US 12,076,363 B2
Peptide epoxyketone proteasome inhibitors in combination with PIM kinase inhibitors for treatment of cancers
Shirin Kapur, Burlingame, CA (US); Alana Lerner, San Francisco, CA (US); Christopher J. Kirk, San Francisco, CA (US); Eric Lowe, Moraga Town, CA (US); and Tracey Lin, Union City, CA (US)
Assigned to ONYX PHARMACEUTICALS, INC., Thousand Oaks, CA (US)
Filed by ONYX PHARMACEUTICALS, INC., Thousand Oaks, CA (US)
Filed on Sep. 23, 2021, as Appl. No. 17/482,699.
Application 17/482,699 is a continuation of application No. 17/150,319, filed on Jan. 15, 2021, abandoned.
Application 17/150,319 is a continuation of application No. 16/895,328, filed on Jun. 8, 2020, abandoned.
Application 16/895,328 is a continuation of application No. 16/659,123, filed on Oct. 21, 2019, abandoned.
Application 16/659,123 is a continuation of application No. 16/289,255, filed on Feb. 28, 2019, abandoned.
Application 16/289,255 is a continuation of application No. 14/905,179, abandoned, previously published as PCT/US2014/046950, filed on Jul. 17, 2014.
Claims priority of provisional application 61/863,760, filed on Aug. 8, 2013.
Claims priority of provisional application 61/863,768, filed on Aug. 8, 2013.
Claims priority of provisional application 61/856,636, filed on Jul. 19, 2013.
Claims priority of provisional application 61/856,626, filed on Jul. 19, 2013.
Prior Publication US 2022/0265758 A1, Aug. 25, 2022
Int. Cl. A61K 38/07 (2006.01); A61K 31/426 (2006.01); A61K 31/427 (2006.01); A61K 31/454 (2006.01); A61K 31/4545 (2006.01); A61K 31/4745 (2006.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 38/04 (2006.01); A61K 38/06 (2006.01); A61K 38/08 (2019.01); A61K 45/06 (2006.01); C07K 5/083 (2006.01); C07K 5/107 (2006.01)
CPC A61K 38/07 (2013.01) [A61K 31/426 (2013.01); A61K 31/427 (2013.01); A61K 31/454 (2013.01); A61K 31/4545 (2013.01); A61K 31/4745 (2013.01); A61K 31/5025 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 38/04 (2013.01); A61K 38/06 (2013.01); A61K 38/08 (2013.01); A61K 45/06 (2013.01); C07K 5/081 (2013.01); C07K 5/1016 (2013.01)] 16 Claims
 
1. A method for the treatment of a multiple myeloma in a patient, the method comprising administering to the patient
(a) a therapeutically effective amount of a proteasome inhibitor carfilzomib having a structure of:

OG Complex Work Unit Chemistry
 or a pharmaceutically acceptable salt thereof, and
(b) a PIM kinase inhibitor, or a pharmaceutically acceptable salt thereof, wherein the ratio of carfilzomib to the PIM kinase inhibitor administered is between about 3:1 to about 1:3, or is 1:1, wherein the PIM kinase inhibitor comprises 5-[[2-[(3R)-3-aminopiperidin-1-yl]biphenyl-3-yl]methylidene]-1,3-thiazolidine-2,4-dione or ((Z)-5-(4-propxybenzylidene) thiazolidine-2,4-dione) or a pharmaceutically acceptable salt thereof.