US 12,343,377 B2
Combination therapies comprising a hypomethylation agent for treating cancer
Jaume Pons, San Francisco, CA (US); Hong Wan, Foster City, CA (US); and Sophia Randolph, Chico, CA (US)
Assigned to ALX Oncology Inc., South San Francisco, CA (US)
Filed by ALX Oncology Inc., Burlingame, CA (US)
Filed on May 28, 2021, as Appl. No. 17/334,151.
Claims priority of provisional application 63/145,925, filed on Feb. 4, 2021.
Claims priority of provisional application 63/114,959, filed on Nov. 17, 2020.
Claims priority of provisional application 63/109,083, filed on Nov. 3, 2020.
Claims priority of provisional application 63/106,285, filed on Oct. 27, 2020.
Claims priority of provisional application 63/033,074, filed on Jun. 1, 2020.
Prior Publication US 2022/0401516 A1, Dec. 22, 2022
Int. Cl. A61K 38/17 (2006.01); A61K 31/122 (2006.01); A61K 31/352 (2006.01); A61K 31/405 (2006.01); A61K 31/513 (2006.01); A61K 31/635 (2006.01); A61K 31/706 (2006.01); A61K 31/7068 (2006.01); A61K 47/64 (2017.01); A61P 35/02 (2006.01)
CPC A61K 38/1774 (2013.01) [A61K 31/122 (2013.01); A61K 31/352 (2013.01); A61K 31/405 (2013.01); A61K 31/513 (2013.01); A61K 31/635 (2013.01); A61K 31/706 (2013.01); A61K 31/7068 (2013.01); A61K 47/6425 (2017.08); A61P 35/02 (2018.01)] 17 Claims
 
1. A method of treating a myeloid cancer in an individual having a myeloid cancer, comprising administering to the individual an effective amount of: (a) a fusion polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant, and (b) azacitidine;
wherein the SIRPα D1 domain variant of the fusion polypeptide comprises the amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 85;
wherein the Fc domain variant of the fusion polypeptide is
(i) a human IgG1 Fc region comprising L234A, L235A, G237A, and N297A mutations, wherein numbering is according to the EU index of Kabat;
(ii) a human IgG2 Fc region comprising A330S, P331S, and N297A mutations, wherein numbering is according to the EU index of Kabat;
(iii) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, and delG236 mutations, wherein numbering is according to the EU index of Kabat; or
(iv) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, delG236, and N297A mutations, wherein numbering is according to the EU index of Kabat; and
wherein the C-terminus of the SIRPα D1 domain variant of the fusion polypeptide is linked to the N-terminus of the Fc-domain variant.