US 12,275,784 B2
Engineered anti-IL-2 antibodies
Inbar Amit, Modi'in (IL); Itay Levin, Herzeliya (IL); Guy Nimrod, Tel Aviv (IL); Sharon Fischman, Modi'in (IL); Reut Barak Fuchs, Rehovot (IL); Marek Strajbl, Jerusalem (IL); Timothy Wyant, Bellingham, MA (US); Michael Zhenin, Jerusalem (IL); Olga Bluvshtein Yermolaev, Rishon-LeZion (IL); Yehezkel Sasson, Tzur Yigal (IL); Noam Grossman, Mazkeret Batyia (IL); Natalia Levitin, Ashdod (IL); and Yanay Ofran, Tel Aviv (IL)
Assigned to AULOS BIOSCIENCE, INC., Larkspur, CA (US)
Filed by Aulos Bioscience, Inc., Larkspur, CA (US)
Filed on Oct. 23, 2023, as Appl. No. 18/492,028.
Application 18/492,028 is a continuation of application No. 18/055,975, filed on Nov. 16, 2022, granted, now 11,851,485.
Application 18/055,975 is a continuation of application No. 17/795,960, previously published as PCT/IB2021/051267, filed on Feb. 15, 2021.
Claims priority of provisional application 63/139,315, filed on Jan. 20, 2021.
Claims priority of provisional application 62/977,292, filed on Feb. 16, 2020.
Prior Publication US 2024/0092888 A1, Mar. 21, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/24 (2006.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/246 (2013.01) [A61K 39/395 (2013.01); A61P 35/00 (2018.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/74 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 21 Claims
 
1. A method of treating a disease or a condition in a subject comprising the step of administering to the subject a combination therapy comprising an anti-IL-2 antibody, an IL-2, and an immune checkpoint inhibitor, said anti-IL-2 antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HCDR2 and HCDR3, said VL comprises light chain complementarity determining regions (LCDRs) LCDR1, LCDR2 and LCDR3, wherein said CDRs have the amino acid sequences of
(a) the HCDR1 comprises the amino acid sequence of SEQ ID NO:62, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 63, the HCDR3 comprises the amino acid sequence of SEQ ID NO:64, the LCDR1 comprises the amino acid sequence of SEQ ID NO:65, the LCDR2 comprises the amino acid sequence DAS, the LCDR3 comprises the amino acid sequence of SEQ ID NO:67;
(b) the HCDR1 comprises the amino acid sequence of SEQ ID NO:38, the HCDR2 comprises the amino acid sequence of SEQ ID NO:39, the HCDR3 comprises the amino acid sequence of SEQ ID NO:40, the LCDR1 comprises the amino acid sequence of SEQ ID NO:41, the LCDR2 comprises the amino acid sequence YAS, the LCDR3 comprises the amino acid sequence of SEQ ID NO:43;
(c) the HCDR1 comprises the amino acid sequence of SEQ ID NO:44, the HCDR2 comprises the amino acid sequence of SEQ ID NO:45, the HCDR3 comprises the amino acid sequence of SEQ ID NO:46, the LCDR1 comprises the amino acid sequence of SEQ ID NO:47, the LCDR2 comprises the amino acid sequence YAS, the LCDR3 comprises the amino acid sequence of SEQ ID NO:49;
(d) the HCDR1 comprises the amino acid sequence of SEQ ID NO:50, the HCDR2 comprises the amino acid sequence of SEQ ID NO:51, the HCDR3 comprises the amino acid sequence of SEQ ID NO:52, the LCDR1 comprises the amino acid sequence of SEQ ID NO:53, the LCDR2 comprises the amino acid sequence YAS, the LCDR3 comprises the amino acid sequence of SEQ ID NO:55; or
(e) the HCDR1 comprises the amino acid sequence of SEQ ID NO:56, the HCDR2 comprises the amino acid sequence of SEQ ID NO:57, the HCDR3 comprises the amino acid sequence of SEQ ID NO:58, the LCDR1 comprises the amino acid sequence of SEQ ID NO:59, the LCDR2 comprises the amino acid sequence YAS, the LCDR3 comprises the amino acid sequence of SEQ ID NO:61;
wherein said antibody promotes differential growth of subsets of immune cells and decreases undesirable effects caused by IL-2, wherein said disease is cancer and said cancer is selected from melanoma and metastatic renal cell carcinoma, or wherein said disease is a viral infection and said virus is a SARS-COV-2 virus, and wherein said condition is selected from pulmonary edema or vascular leak syndrome, thereby treating said disease or condition in said subject.