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Resumen

The present invention refers to the treatment of fungal infections or diseases by using specific affinity reagents, such as nanobodies, which specifically bind the fungal β-1,3-glucanosyltransferase gel4.

Reivindicaciones

1. Affinity reagents such as nanobodies which specifically bind the fungal β-1,3-glucanosyltransferase gel4, or orthologs thereof, for use in the treatment of fungal infections or diseases. 2. Nanobody for use, according to claim 1, characterized in that it specifically binds the catalytic-domain of fungal β-1,3-glucanosyltransferase gel4 which is placed between the residues 1 and 365 of SEQ ID NO: 1. 3. Nanobody for use, according to claim 2, characterized in that it specifically binds the residues E49, N59, D61, R125, N158, E159, D200, D202, Y230, E231, E261, D266, Y293, E298, N300 and Y302 of the catalytic-domain of fungal β-1,3-glucanosyltransferase gel4 of SEQ ID NO: 1. 4. Nanobody for use, according to claim 3, characterized in that it further binds the residues N124, 1123, S122, S120, N162, D163, H204, A203, D201, R206, R246, Y90 and K240 of the catalytic-domain of fungal β-1,3-glucanosyltransferase gel4 of SEQ ID NO: 1. 5. Nanobody for use, according to claim 1, characterized in that it specifically binds the CBM43 domain of fungal β-1,3-glucanosyltransferase gel4 which is placed between the residues 366 and 532 of SEQ ID NO: 1. 6. Nanobody for use, according to claim 5, characterized in that it specifically binds the residues D127, D392, F394, D395, Y396, A399, N407, K426, Y434, K437, N438 and D448 of the CBM43 domain of fungal β-1,3-glucanosyltransferase gel4 of SEQ ID NO: 1. 7. Nanobody for use, according to claim 6, characterized in that it further binds the residues F447, A400, 1406, L393, A129 and S408 of the CBM43 domain of fungal β-1,3-glucanosyltransferase gel4 of SEQ ID NO: 1. 8. Nanobody for use, according to any of the previous claims, in the treatment of aspergillosis and/or cryptococcosis. 9. Nanobody for use, according to claims 2 to 4, characterized in that it comprises complementary determining regions (CDR) consisting of CDR1 of SEQ ID NO: 2, CDR2 of SEQ ID NO: 3 and CDR3 of SEQ ID NO: 4. 10. Nanobody for use, according to claim 9, characterized in that CDR1, CDR2 and CDR3 are separated by frame regions FR1 of SEQ ID NO: 5, FR2 of SEQ ID NO: 6, FR3 of SEQ ID NO: 7 and FR4 of SEQ ID NO: 8. 11. Nanobody for use, according to claims 5 to 7, characterized in that it comprises complementary determining regions (CDR) consisting of CDR1 of SEQ ID NO: 9, CDR2 of SEQ ID NO: 10 and CDR3 of SEQ ID NO: 11. 12. Nanobody for use, according to claim 11, characterized in that CDR1, CDR2 and CDR3 are separated by frame regions FR1 of SEQ ID NO: 12, FR2 of SEQ ID NO: 13, FR3 of SEQ ID NO: 14 and FR4 of SEQ ID NO: 15. 13. Nanobody characterized in that it comprises complementary determining regions (CDR) consisting of CDR1 of SEQ ID NO: 2, CDR2 of SEQ ID NO: 3 and CDR3 of SEQ ID NO: 4; or consisting of CDR1 of SEQ ID NO: 9, CDR2 of SEQ ID NO: 10 and CDR3 of SEQ ID NO: 11. 14. Nanobody, according to claim 13, wherein the CDR1 of SEQ ID NO: 2, CDR2 of SEQ ID NO: 3 and CDR3 of SEQ ID NO: 4 are separated by frame regions FR1 of SEQ ID NO: 5, FR2 of SEQ ID NO: 6, FR3 of SEQ ID NO: 7 and FR4 of SEQ ID NO: 8; or wherein the CDR1 of SEQ ID NO: 9, CDR2 of SEQ ID NO: 10 and CDR3 of SEQ ID NO: 11 are separated by frame regions FR1 of SEQ ID NO: 12, FR2 of SEQ ID NO: 13, FR3 of SEQ ID NO: 14 and FR4 of SEQ ID NO: 15. 15. Pharmaceutical composition comprising the nanobodies of claims 13 or 14 and, optionally, pharmaceutically acceptable carriers or excipients.

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