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US 10,647,773 B2Granted
Trispecific antagonists
AssigneeGensun Biopharma Inc.
InventorsJackie Sheng, Bo Liu
Life of this patent
Estimating the term…
Abstract
Antitumor antagonists that bind specifically to immune checkpoint regulator and/or components of the angiogenesis pathways and/or components of the TGF pathway are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists.
Claims15
A trispecific antagonist, comprising:
- an immunoglobulin scaffold comprising a CH1 domain, a CH2 domain and a CH3 domain;
- a first targeting domain comprising one or more immunoglobulin variable domains selected from the group consisting of
- (1) an anti-PD-1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:48, 51, 54, 56 and 59, the HCDR2 is selected from the group consisting of SEQ ID NOS:49, 52, 57 and 60, HCDR3 is selected from the group consisting of SEQ ID NOS:50, 53, 55, 58 and 61, the LCDR1 is selected from the group consisting of SEQ ID NOS:62, 65, 68, 69, 70 and 73, the LCDR2 is selected from the group consisting of SEQ ID NOS:63, 66, 71 and 74, and the LCDR3 is selected from the group consisting of SEQ ID NOS:64, 67, 72 and 75,
- (2) an anti-PD-L1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:76, 79, 85 and 88, the HCDR2 is selected from the group consisting of SEQ ID NOS:77, 80, 82, 84, 86 and 89, the HCDR3 is selected from the group consisting of SEQ ID NOS:78, 81, 83, 87 and 90, the LCDR1 is selected from the group consisting of SEQ ID NOS:91, 94, 98, 101 and 104, the LCDR2 is selected from the group consisting of SEQ ID NOS:92, 95, 99, 102, 105, and the LCDR3 is selected from the group consisting of SEQ ID NOS:93, 96, 97, 100 and 106,
- (3) an anti-TIGIT variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:1, 6, 11, 15, 17, 20, 23, the HCDR2 is selected from the group consisting of SEQ ID NOS:2, 4, 7, 9, 12, 13, 16, 18, 21 and 24, the HCDR3 is selected from the group consisting of SEQ ID NOS:3, 5, 8, 10, 14, 19, 22, 25, the LCDR1 is selected from the group consisting of SEQ ID NOS:26, 29, 31, 33, 35, 39, 42 and 45, the LCDR2 is selected from the group consisting of SEQ ID NOS:27, 30, 36, 37, 40, 43, 46, and the LCDR3 is selected from the group consisting of SEQ ID NOS:28, 32, 34, 38, 41, 44 and 47, and
- (4) an anti-LAG-3 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:155-157, the HCDR2 is selected from the group consisting of SEQ ID NOS:158-160, the HCDR3 is selected from the group consisting of SEQ ID NOS:161-163, the LCDR1 is selected from the group consisting of SEQ ID NOS:164-166, the LCDR2 is selected from the group consisting of SEQ ID NOS:167 and 168, and the LCDR3 is selected from the group consisting of SEQ ID NOS:169 and 170,
- a second targeting domain that binds specifically to VEGF and comprises SEQ ID NO:185 or 207;
- and
- a third targeting domain comprising a peptide inhibitor of the angiopoietin/Tie-2 signaling pathway, wherein the peptide inhibitor comprises SEQ ID NO:194.
6 more elements
A trispecific antagonist, comprising:
- an immunoglobulin scaffold comprising a CH1 domain, a CH2 domain and a CH3 domain;
- a first targeting domain comprising
- (1) an anti-PD-1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:48, 51, 54, 56 and 59, the HCDR2 is selected from the group consisting of SEQ ID NOS:49, 52, 57 and 60, HCDR3 is selected from the group consisting of SEQ ID NOS:50, 53, 55, 58 and 61, the LCDR1 is selected from the group consisting of SEQ ID NOS:62, 65, 68, 69, 70 and 73, the LCDR2 is selected from the group consisting of SEQ ID NOS:63, 66, 71 and 74, and the LCDR3 is selected from the group consisting of SEQ ID NOS:64, 67, 72 and 75, or
- (2) an anti-PD-L1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:76, 79, 85 and 88, the HCDR2 is selected from the group consisting of SEQ ID NOS:77, 80, 82, 84, 86 and 89, the HCDR3 is selected from the group consisting of SEQ ID NOS:78, 81, 83, 87 and 90, the LCDR1 is selected from the group consisting of SEQ ID NOS:91, 94, 98, 101 and 104, the LCDR2 is selected from the group consisting of SEQ ID NOS:92, 95, 99, 102, 105, and the LCDR3 is selected from the group consisting of SEQ ID NOS:93, 96, 97, 100 and 106;
- a second targeting domain comprising a component of VEGFR comprising SEQ ID NO:185 or 207;
- and
- a third targeting domain comprising a TGF-β pathway inhibitor comprising SEQ ID NO:186 or 197.
4 more elements
Dependencies are inferred from the claim text.