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US 11,299,515 B2Granted
Optimized peptides for targeting human nerves and their use in image guided surgery, diagnostics and therapeutic
AssigneeThe Regents of the University of California
InventorsQuyen T. Nguyen, Mike Whitney, Dina Hingorani, Roger Y. Tsien, Stephen Adams
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Abstract
The present invention provides methods for guiding preservation of human neurons or human nerves during surgery by administering a fluorescently-labeled peptide that specifically binds to the human neurons or human nerves. The invention further provides human neuron or nerve targeting molecules comprising fluorescently-labeled peptides that specifically bind to human neurons or human nerves and compositions thereof.
Claims28
A targeting molecule comprising a peptide selected from the group consisting of:
- SGQVPWEEPYYVVKKSS (HNP 401;
- SEQ ID NO:1), WEYHYVDLNWTSQHPQ (HNP 402;
- SEQ ID NO:2), DLPDIIWDFNWETA (HNP 403;
- SEQ ID NO:3), DTHAHAKPRVPAFKSV (HNP 404;
- SEQ ID NO:16), Ac-SGQVPWEEPYYVVKKSSGGC (HNP401 with GGC linker;
- SEQ ID NO:4), Ac-WEYHYVDLNWTSQHPQGGC (HNP402 with GGC linker;
- SEQ ID NO:5), Ac-DLPDIIWDFNWETAGGC (HNP403;
- SEQ ID NO:6), Ac-QVPWEEPYYVVKKSSGGC (HNP401-N-2 with GGC linker;
- SEQ ID NO:7), Ac-PWEEPYYVVKKSSGGC (HNP401-N-4 with GGC linker;
- SEQ ID NO:8), Ac-EEPYYVVKKSSGGC (HNP401-N-6 with GGC linker;
- SEQ ID NO:9), Ac-PYYVVKKSSGGC (HNP401-N-8 with GGC linker;
- SEQ ID NO:10), Ac-SGQVPWEEPYYVVKKGGC (HNP401-C-2 with GGC linker;
- SEQ ID NO:11), Ac-SGQVPWEEPYYVVGGC (HNP401-C-4 with GGC linker;
- SEQ ID NO:12), Ac-SGQVPWEEPYYGGC (HNP401-C-6 with GGC linker;
- SEQ ID NO:13), Ac-SGQVPWEEPGGC (HNP401-C-8 with GGC linker;
- SEQ ID NO:14), QVPWEEPYYVVKKSS (HNP401-N-2;
- SEQ ID NO:20);
- QVPWEEPYYVVKKSSGG (HNP401-N-2 with GG linker;
- SEQ ID NO:21), PWEEPYYVVKKSS (HNP401-N-4;
- SEQ ID NO:22);
- EEPYYVVKKSS (HNP401-N-6;
- SEQ ID NO:23), PYYVVKKSS (HNP401-N-8;
- SEQ ID NO:24), SGQVPWEEPYYVVKK (HNP401-C-2;
- SEQ ID NO:25), SGQVPWEEPYYVV (HNP401-C-4;
- SEQ ID NO:26), SGQVPWEEPYY (HNP401-C-6;
- SEQ ID NO:27), SGQVPWEEP (HNP401-C-8;
- SEQ ID NO:28), PWEEPYYVVKKSSGG (HNP401-N-4 with GG linker;
- SEQ ID NO:118), EEPYYVVKKSSGG (HNP401-N-6 with GG linker;
- SEQ ID NO:119), PYYVVKKSSGG (HNP401-N-8 with GG linker;
- SEQ ID NO:120), SGQVPWEEPYYVVKKGG (HNP401-C-2;
- with GG linker;
- SEQ ID NO:121), SGQVPWEEPYYVVGG (HNP401-C-4 with GG linker;
- SEQ ID NO:122), SGQVPWEEPYYGG, (HNP401-C-6 with GG linker;
- SEQ ID NO:123), and SGQVPWEEPGG (HNP401-C-8 with GG linker;
- SEQ ID NO:124);
- or
- a targeting molecule comprising a peptide having at least 80% identity to a peptide selected from the group consisting of:
- SGOVPWEEPYYVVKKSS (HNP 401:
- SEQ ID NO:1) WEYHYVDLNWTSQHPQ (HNP 402;
- SEQ ID NO:2) DLPDIIWDFNWETA (HNP 403;
- SEQ ID NO:3), DTHAHAKPRVPAFKSV (HNP 404:
- SEQ ID NO:16), Ac-SGQVPWEEPYYVVKKSSGGC (HNP401 with GGC linker;
- SEQ ID NO:4), Ac-WEYHYVDLNWTSQHPQGGC (HNP402 with GGC linker;
- SEQ ID NO:5), Ac-DLPDIIWDFNWETAGGC (HNP403;
- SEQ ID NO:6), Ac-QVPWEEPYYVVKKSSGGC (HNP401-N-2 with GGC linker;
- SEQ ID NO:7), Ac-PWEEPYYVVKKSSGGC (HNP401-N-4 with GGC linker;
- SEQ ID NO:8), Ac-EEPYYVVKKSSGGC (HNP401-N-6 with GGC linker;
- SEQ ID NO:9), Ac-PYYVVKKSSGGC (HNP401-N-8 with GGC linker;
- SEQ ID NO:10), Ac-SGQVPWEEPYYVVKKGGC (HNP401-C-2 with GGC linker:
- SEQ ID NO:
- 11), Ac-SGQVPWEEPYYVVGGC (HNP401-C-4 with GGC linker SEQ ID NO:12), Ac-SGQVPWEEPYYGGC (HNP401-C-6 with GGC linker;
- SEQ ID NO:13), Ac-SGQVPWEEPGGC (HNP401-C-8 with GGC linker;
- SEQ ID NO:
- 14), QVPWEEPYYVVKKSS (HNP401-N-2:
- SEQ ID NO:20):
- QVPWEEPYYVVKKSSGG (HNP401-N-2 with GG linker:
- SEQ ID NO:21), PWEEPYYVVKKSS (HNP401-N-4;
- SEQ ID NO:22);
- EEPYYVVKKSS (HNP401-N-6;
- SEQ ID NO:23), PYYVVKKSS (HNP401-N-8, SEQ ID NO:24), SGQVPWEEPYYVVKK (HNP401-C-2;
- SEQ ID NO:25), SGQVPWEEPYYVV (HNP401-C-4 SEQ ID NO:26), SGQVPWEEPYY (HNP401-C-6;
- SEQ ID NO:27), SGQVPWEEP (HNP401-C-8:
- SEQ ID NO:28), PWEEPYYVVKKSSGG (HNP401-N-4 with GG linker;
- SEQ ID NO:118), EEPYYVVKKSSGG (HNP401-N-6 with GG linker:
- SEQ ID NO:119), PYYVVKKSSGG (HNP401-N-8 with GG linker;
- SEQ ID NO:120), SGQVPWEEPYYVVKKGG (HNP401-C-2;
- with GG linker:
- SEQ ID NO:121), SGQVPWEEPYYVVGG (HNP401-C-4 with G linker, SEQ ID NO:122), SGQVPWEEPYYGG, (HNP401-C-6 with GG linker:
- SEQ ID NO:
- 123), and SGQVPWEEPGG (HNP401-C-8 with GG linker;
- SEQ ID NO:124).
68 more elements
A multidomain targeting molecule comprising two or more peptides, wherein the first peptide, second peptide, or both the first peptide and second peptide are selected from the group consisting of:
- SGQVPWEEPYYVVKKSS (HNP 401;
- SEQ ID NO:1), WEYHYVDLNWTSQHPQ (HNP 402;
- SEQ ID NO:2), DLPDIIWDFNWETA (HNP 403;
- SEQ ID NO:3), DTHAHAKPRVPAFKSV (HNP 404;
- SEQ ID NO:16), Ac-SGQVPWEEPYYVVKKSSGGC (HNP401 with GGC linker;
- SEQ ID NO:4), Ac-WEYHYVDLNWTSQHPQGGC (HNP402 with GGC linker;
- SEQ ID NO:5), Ac-DLPDIIWDFNWETAGGC (HNP403 with GGC linker;
- SEQ ID NO:6), Ac-QVPWEEPYYVVKKSSGGC (HNP401-N-2 with GGC linker;
- SEQ ID NO:7), Ac-PWEEPYYVVKKSSGGC (HNP401-N-4 with GGC linker;
- SEQ ID NO:8), Ac-EEPYYVVKKSSGGC (HNP401-N-6 with GGC linker;
- SEQ ID NO:9), Ac-PYYVVKKSSGGC (HNP401-N-8 with GGC linker;
- SEQ ID NO:10), Ac-SGQVPWEEPYYVVKKGGC (HNP401-C-2 with GGC linker;
- SEQ ID NO:11), Ac-SGQVPWEEPYYVVGGC (HNP401-C-4 with GGC linker;
- SEQ ID NO:12), Ac-SGQVPWEEPYYGGC (HNP401-C-6 with GGC linker;
- SEQ ID NO:13), Ac-SGQVPWEEPGGC (HNP401-C-8 with GGC linker;
- SEQ ID NO:14), QVPWEEPYYVVKKSS (HNP401-N-2;
- SEQ ID NO:20);
- QVPWEEPYYVVKKSSGG (HNP401-N-2 with GG linker;
- SEQ ID NO:21);
- PWEEPYYVVKKSS (HNP401-N-4;
- SEQ ID NO:22);
- EEPYYVVKKSS (HNP401-N-6;
- SEQ ID NO:23);
- PYYVVKKSS (HNP401-N-8;
- SEQ ID NO:24);
- SGQVPWEEPYYVVKK (HNP401-C-2;
- SEQ ID NO:25), SGQVPWEEPYYVV (HNP401-C-4;
- SEQ ID NO:26), SGQVPWEEPYY (HNP401-C-6;
- SEQ ID NO:27), SGQVPWEEP (HNP401-C-8;
- SEQ ID NO:28), PWEEPYYVVKKSSGG (HNP401-N-4 with GG linker;
- SEQ ID NO:118), EEPYYVVKKSSGG (HNP401-N-6 with GG linker;
- SEQ ID NO:119), PYYVVKKSSGG (HNP401-N-8 with GG linker;
- SEQ ID NO:120), SGQVPWEEPYYVVKKGG (HNP401-C-2;
- with GG linker;
- SEQ ID NO:121), SGQVPWEEPYYVVGG (HNP401-C-4 with GG linker;
- SEQ ID NO:122), SGQVPWEEPYYGG, (HNP401-C-6 with GG linker;
- SEQ ID NO:123), and SGQVPWEEPGG (HNP401-C-8 with GG linker;
- SEQ ID NO:124).
35 more elements
Dependencies are inferred from the claim text.