USES OF PDL1-BINDING PROTEINS
This invention relates generally to molecules that specifically engage 41BB, a member of the TNF receptor superfamily (TNFRSF). More specifically, this invention relates to multivalent and multispecific molecules that bind at least 41BB.
1 - 47 . (canceled)
48 . A method of treating cancer comprising administering to a human subject with cancer a polypeptide comprising at least one VHH domain that binds human programmed death ligand 1 (PDL1), wherein at least one VHH domain that binds PDL1 comprises:
(i) a CDR1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 102, and a CDR3 comprising an amino acid sequence of SEQ ID NO: 103;
(ii) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 105, a CDR2 comprising an amino acid sequence of SEQ ID NO: 106, and a CDR comprising an amino acid sequence of SEQ ID NO: 107;
(iii) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 109, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 111;
(iv) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 113;
(v) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 115; or
(vi) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 117, and a CDR comprising an amino acid sequence of SEQ ID NO: 118.
49 . The method of claim 48 , wherein at least one VHH domain that binds PDL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 107.
50 . The method of claim 48 , wherein each VHH domain that binds PDL1 is humanized.
51 . The method of claim 48 , wherein the polypeptide is monospecific.
52 . The method of claim 48 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
54 . The method of claim 48 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
55 . The method of claim 48 , wherein at least one VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
56 . The method of claim 48 , wherein each VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
57 . The method of claim 48 , wherein the isolated polypeptide comprises an Fc region.
58 . The method of claim 57 , wherein the Fc region comprises an amino acid sequence that is at least 97% or 100% identical to an amino acid sequence selected from SEQ ID NOs: 1-6.
59 . The method of claim 48 , wherein the cancer is selected from carcinoma, sarcoma, lymphoma, and leukemia.
60 . A method of increasing T cell activation and/or proliferation comprising contacting T cells with a polypeptide of claim comprising at least one VHH domain that binds human programmed death ligand 1 (PDL1), wherein at least one VHH domain that binds PDL1 comprises:
(i) a CDR1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 102, and a CDR3 comprising an amino acid sequence of SEQ ID NO: 103;
(ii) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 105, a CDR2 comprising an amino acid sequence of SEQ ID NO: 106, and a CDR comprising an amino acid sequence of SEQ ID NO: 107;
(iii) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 109, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 111;
(iv) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 113;
(v) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 110, and a CDR comprising an amino acid sequence of SEQ ID NO: 115; or
(vi) a CDR 1 comprising an amino acid sequence of SEQ ID NO: 101, a CDR2 comprising an amino acid sequence of SEQ ID NO: 117, and a CDR comprising an amino acid sequence of SEQ ID NO: 118.
61 . The method of claim 60 , wherein the T cells are CD4 + T cells and/or CD8 + T cells.
62 . The method of claim 60 , wherein at least one VHH domain that binds PDL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 107.
63 . The method of claim 60 , wherein each VHH domain that binds PDL1 is humanized.
64 . The method of claim 60 , wherein the polypeptide is monospecific.
65 . The method of claim 60 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
66 . The method of claim 60 , wherein at least one VHH domain that binds PDL1 comprises an amino acid sequence selected from SEQ ID NOs: 100, 104, 108, 112, 114, 116, and 119-124.
67 . The method of claim 60 , wherein at least one VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
68 . The method of claim 60 , wherein each VHH domain that binds PDL1 comprises the amino acid sequence of SEQ ID NO: 124.
69 . The method of claim 60 , wherein the isolated polypeptide comprises an Fc region.
70 . The method of claim 69 , wherein the Fc region comprises an amino acid sequence that is at least 97% or 100% identical to an amino acid sequence selected from SEQ ID NOs: 1-6.