Calreticulin nanobodies
Provided are nanobodies that bind human calreticulin, fusion proteins including the nanobodies, pharmaceutical compositions including the nanobodies or fusion proteins, and radioconjugates of the nanobodies or fusion proteins.
1 . A protein comprising a human-calreticulin binding nanobody amino acid sequence comprising the CDR1, CDR2, and CDR3 sequences:
(i) SEQ ID NO:18, SEQ ID NO: 41, and SEQ ID NO:60, respectively;
(ii) SEQ ID NO:21, SEQ ID NO: 44, and SEQ ID NO:63, respectively;
(iii) SEQ ID NO:26, SEQ ID NO:49, and SEQ ID NO:68, respectively;
(iv) SEQ ID NO:22, SEQ ID NO:45, and SEQ ID NO:64, respectively;
(v) SEQ ID NO:14, SEQ ID NO:39, and SEQ ID NO:58, respectively;
(vi) SEQ ID NO:20, SEQ ID NO:43, and SEQ ID NO:62, respectively; or
(vii) SEQ ID NO:19, SEQ ID NO: 42, and SEQ ID NO:61, respectively.
2 . A protein comprising one or more of the human-calreticulin binding nanobody amino acid sequences set forth in SEQ ID NOS: 120, 126, 131, 127, 115, 111, 125 or 123.
3 . The protein of claim 2 , comprising the human-calreticulin binding nanobody amino acid sequence set forth in SEQ ID NO: 120.
4 . The protein of claim 1 , consisting of a single VHH domain.
5 . The protein of claim 1 , wherein the protein is a nanobody Fc fusion protein.
6 . A pharmaceutical composition comprising the protein of claim 1 and at least one pharmaceutically acceptable excipient.
7 . A radiopharmaceutical composition comprising the protein of claim 1 linked to a radionuclide.
8 . The radiopharmaceutical composition of claim 7 , further comprising at least one pharmaceutically acceptable excipient.
9 . The radiopharmaceutical composition of claim 8 , wherein the radionuclide is an alpha particle emitter.
10 . The radiopharmaceutical composition of claim 8 , wherein the radionuclide is a beta particle emitter.
11 . The radiopharmaceutical composition of claim 8 , wherein the radionuclide comprises 131 I.
12 . The radiopharmaceutical composition of claim 8 , wherein the radionuclide comprises 225 Ac, 177 Lu or 90 Y.
13 . A composition comprising the protein of claim 1 , chemically conjugated to a chelator.
14 . The composition of claim 13 , wherein the chelator comprises DOTA or a DOTA derivative.
15 . The composition of claim 13 , further comprising a radionuclide chelated by the chelator.
16 . The protein of claim 2 , consisting of a single VHH domain.
17 . The protein of claim 2 , wherein the protein is a nanobody Fc fusion protein.
18 . A pharmaceutical composition comprising the protein of claim 2 and at least one pharmaceutically acceptable excipient.
19 . A radiopharmaceutical composition comprising the protein of claim 2 linked to a radionuclide.
20 . A radiopharmaceutical composition comprising the protein of claim 3 linked to a radionuclide.
21 . The protein of claim 1 , comprising a human-calreticulin binding nanobody amino acid sequence comprising the CDR1, CDR2, and CDR3 sequences:
SEQ ID NO:18, SEQ ID NO: 41, and SEQ ID NO:60, respectively.