IL-2R-BETA-GAMMA BINDING COMPOUNDS AND USES THEREOF
IL-2Rβγc binding compounds, and pharmaceutical compositions comprising the IL-2Rβγc binding compounds are disclosed. IL-2Rβγc binding compounds can act as IL-2R agonists and are useful in treating cancer, an autoimmune disease, and an inflammatory disease.
1 - 65 . (canceled)
66 . An IL-2Rβγc ligand comprising:
the IL-2Rβ ligand having greater than 60% amino acid sequence similarity to the IL-2Rβ ligand having any one of SEQ ID NOS: 2859, 2934, 3100-3128, 3130-3151, 3160-3166, 3170-3186, and 3200-3207; and
an IL-2Rγc ligand having greater than 60% sequence similarity to any one of SEQ ID NOS: 944-1028, 1032-1060, and 1601-1613.
67 . The IL-2Rβ ligand of claim 66 , wherein the IL-2Rβ ligand comprises an amino acid sequence of any one of SEQ ID NOS: 2859, 2934, 3100-3128, 3130-3151, 3160-3166, 3170-3186, and 3200-3207.
68 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rβ ligand has an amino acid sequence selected from SEQ ID NO: 2858 and SEQ ID NO: 2859.
69 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rβ ligand has an amino acid sequence having greater than 60% sequence similarity to an amino acid sequence selected from SEQ ID NO: 2858 and SEQ ID NO: 2859.
70 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rβ ligand independently comprises from 1 to 4 flanking glycines on the C-terminus, on the N-terminus, or on both the C-terminus and the N terminus.
71 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rγc ligand comprises an amino acid sequence of any one of any one of SEQ ID NOS: 944-1028, 1032-1060, and 1601-1613.
72 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rγc ligand comprises an amino acid sequence of any one of SEQ ID NOS: 944-1028, 1032-1060, and 1601-1613 having from 1 to 4 amino acid substitutions.
73 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rγc ligand comprises an amino acid sequence of any one of SEQ ID NOS: 944-1028, 1032-1060, and 1601-1613 having from 1 to 4 flanking glycines.
74 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rγc ligand comprises:
an amino acid sequence of SEQ ID NO: 965;
a truncated amino acid sequence of SEQ ID NO: 965;
an amino acid sequence of SEQ ID NO: 965 having from 1 to 4 amino acid substitutions;
an amino acid sequence of SEQ ID NO: 965 having from 1 to 4 flanking glycines;
an amino acid sequence having greater than 60% sequence similarity to SEQ ID NO: 965; or
a combination of any of the foregoing.
75 . The IL-2Rβγc ligand of claim 66 , wherein,
the IL-2Rβ ligand comprises amino acid sequence selected from SEQ ID NO: 2858 and SEQ ID NO: 2859; and
the IL-2Rγc ligand comprises the amino acid sequence of SEQ ID NO: 965.
76 . The IL-2Rβγc ligand of claim 66 , wherein, the IL-2Rβγc ligand comprises the amino acid sequence of any one of SEQ ID NOS: 4100-4137, 4160-4168, and 4170-4185.
77 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rβγc ligand has greater than 60% sequence similarity to an amino acid sequence selected from any one of SEQ ID NOS: 4100-4137, 4160-4168, and 4170-4185.
78 . The IL-2Rβγc ligand of claim 66 , wherein the IL-2Rβ ligand is bound to the IL-2Rγc ligand through a rigid ligand linker.
79 . The IL-2Rβγc ligand of claim 78 , wherein the rigid ligand linker comprises (P)n where n is an integer from 1 to 50 (SEQ ID NO: 9419) or (PA)n where n is an integer from 1 to 50 (SEQ ID NO: 9418).
80 . An IL-2Rβγc binding compound comprising the IL-2Rβγc ligand of claim 66 .
81 . The IL-2Rβγc binding compound of claim 80 , wherein the IL-2Rβγc ligand is bound to a construct partner.
82 . The IL-2Rβγc binding compound of claim 81 , wherein the construct partner is selected from an IgG Fc fragment, a ZW1_A fragment, a Cys-Hole fragment, a Cys-Knob fragment, an antibody, and a protein.
83 . The IL-2Rβγc binding compound of claim 80 , wherein the IL-2Rβγc binding compound binds to hu-IL-2R with an IC50 less than 100 μM as determined using a phage ELISA competition assay.
84 . The IL-2Rβγc binding compound of claim 80 , wherein the IL-2Rβγc binding compound binds to cyno-IL-2R with an IC50 less than 100 μM as determined using a phage ELISA competition assay.
85 . The IL-2Rβγc binding compound of claim 80 , wherein the IL-2Rβγc binding compound is a hu-IL-2R agonist.
86 . The IL-2Rβγc binding compound of claim 80 , wherein the IL-2Rβγc binding compound is a cyno-IL-2R agonist.
87 . An IL-2Rβγc binding compound, wherein the IL-2Rβγc binding compound comprises an amino acid sequence having greater than 60% sequence similarity to any one of SEQ ID NOS: 8100-8136.
88 . An IL-2Rβγc binding compound, wherein the IL-2Rβγc binding compound comprises an amino acid sequence of any one of SEQ ID NOS: 8100-8136.
89 . A pharmaceutical composition comprising the IL-2Rβγc ligand of claim 66 .
90 . A pharmaceutical composition comprising the IL-2Rβγc binding compound of claim 80 .
91 . A pharmaceutical composition comprising the IL-2Rβγc binding compound of claim 87 .
92 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the IL-2Rβγc ligand of claim 66 , wherein the disease is selected from cancer, an autoimmune disease, an inflammatory disease, an infectious disease, and a viral disease.
93 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the IL-Wye binding compound of claim 80 , wherein the disease is selected from cancer, an autoimmune disease, an inflammatory disease, an infectious disease, and a viral disease.
94 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the IL-Wye binding compound of claim 87 , wherein the disease is selected from cancer, an autoimmune disease, an inflammatory disease, an infectious disease, and a viral disease.