US 12,239,688 B2
IL-15/IL-15RA heterodimeric Fc fusion proteins and uses thereof
Matthew Bernett, Monrovia, CA (US); John Desjarlais, Pasadena, CA (US); Rumana Rashid, Temple City, CA (US); Rajat Varma, Monrovia, CA (US); and Christine Bonzon, Los Angeles, CA (US)
Assigned to Xencor, Inc., Pasadena, CA (US)
Filed by Xencor, Inc., Monrovia, CA (US)
Filed on Mar. 22, 2021, as Appl. No. 17/209,047.
Application 17/209,047 is a continuation of application No. 16/388,174, filed on Apr. 18, 2019, abandoned.
Claims priority of provisional application 62/756,800, filed on Nov. 7, 2018.
Claims priority of provisional application 62/724,396, filed on Aug. 29, 2018.
Claims priority of provisional application 62/684,143, filed on Jun. 12, 2018.
Claims priority of provisional application 62/659,563, filed on Apr. 18, 2018.
Prior Publication US 2022/0040264 A1, Feb. 10, 2022
Int. Cl. A61K 38/20 (2006.01); A61K 38/17 (2006.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01); C07K 14/54 (2006.01); C07K 14/715 (2006.01); C07K 16/28 (2006.01)
CPC A61K 38/2086 (2013.01) [A61K 38/1793 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07K 14/5443 (2013.01); C07K 14/7155 (2013.01); C07K 16/2818 (2013.01); C07K 16/28 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2319/30 (2013.01)] 20 Claims
 
1. A method of inducing T cell expansion in a patient comprising administering:
a therapeutically effective amount of an IL-15/IL-15Rα heterodimeric Fc fusion protein comprising:
a) a first monomer comprising, from N- to C-terminal:
i) an IL-15 receptor alpha (IL-15Rα) sushi domain;
ii) a first domain linker; and
iii) a first variant Fc domain comprising CH2-CH3; and
b) a second monomer comprising from N- to C-terminal:
i) a variant IL-15 domain comprising the amino acid sequence of SEQ ID NO:2 and any one of the amino acid substitutions selected from the group consisting of N4D/N65D, D30N/N65D, and D30N/E64Q/N65D;
ii) a second domain linker; and
iii) a second variant Fc domain comprising CH2-CH3;
wherein the first and second variant Fc domains are variants of a human IgG1 Fc domain and have a set of amino acid substitutions selected from the group consisting of S267K/L368D/K370S:S267K/S364K/E357Q; S364K/E357Q:L368D/K370S; L368D/K370S:S364K; L368E/K370S:S364K; T411E/K360E/Q362E:D401K; L368D/K370S:S364K/E357L and K370S:S364K/E357Q, according to EU numbering; and
a therapeutically effective amount of an anti-PD-L1 antibody.