OX40-Binding Polypeptides and Uses Thereof
Provided herein are VHH-containing polypeptides that bind OX40. In some embodiments, VHH-containing polypeptides that bind and agonize OX40 are provided. Uses of the VHH-containing polypeptides are also provided.
1 - 74 . (canceled)
75 . A method of producing a polypeptide comprising at least one VHH domain that binds OX40, wherein the VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, comprising incubating a host cell that comprises a nucleic acid encoding the polypeptide under conditions suitable for expression of the polypeptide.
76 . The method of claim 75 , wherein the host cell comprises an isolated nucleic acid encoding the polypeptide.
77 . The method of claim 75 , further comprising isolating the polypeptide.
78 . The method of claim 75 , wherein the VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.
79 . The method of claim 75 , wherein the VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.
80 . The method of claim 75 , wherein the VHH domain is humanized.
81 . The method of claim 75 , wherein the VHH domain comprises the amino acid sequence of SEQ ID NO: 9.
82 . The method of claim 75 , wherein the polypeptide comprises two, three, or four VHH domains.
83 . The method of claim 75 , wherein each VHH domain of the polypeptide binds OX40.
84 . The method of any claim 83 , wherein each VHH domain of the polypeptide comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12.
85 . The method of claim 84 , wherein each VHH domain comprises a and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22
86 . The method of claim 84 , wherein each VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.
87 . The method of claim 84 , wherein each VHH domain comprises the amino acid sequence of SEQ ID NO: 9.
88 . The method of claim 75 , wherein the polypeptide comprises at least one binding domain that binds a second antigen other than OX40.
89 . The method of claim 75 , wherein the polypeptide comprises an Fc domain.
90 . The method of claim 89 , wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.
91 . The method of claim 82 , wherein the polypeptide comprises an Fc domain.
92 . The method of claim 91 , wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.
93 . The method of claim 75 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 14.
94 . The method of claim 84 , wherein the polypeptide comprises an Fc domain.
95 . The method of claim 75 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 15.
96 . A method of producing a polypeptide comprising at least one VHH domain that binds OX40 comprising incubating a host cell that comprises a nucleic acid encoding the polypeptide consisting of the amino acid sequence of SEQ ID NO: 15 under conditions suitable for expression of the polypeptide.