Transferrin receptor-binding molecules, conjugates thereof and their uses

A conjugate compound comprising:

• (i) one or more VHH molecule(s) of formula FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, and
• (ii) at least one therapeutic compound or a vehicle comprising such a therapeutic compound,
• wherein said VHH molecule binds TfR at the surface of a cell of the central nervous system (CNS), and
• wherein said VHH molecule comprises:
• a CDR1 comprising an amino acid sequence selected from SEQ ID NOs:
• 1, 5, 9, 17, 125, 175, 179, 182, 184, 186, 190, 194, 198, 201, 205, 392, 410, 413, 426, 434, 437, 607, 610, 671-674, 710 and 711, and
• a CDR2 comprising an amino acid sequence selected from SEQ ID Nos:
• 2, 6, 73, 113, 115, 128, 160, 162, 164, 166, 169, 171, 176, 187, 191, 195, 199, 202, 206, 416, 419, 431, 608, 611 and 712, and
• a CDR3 comprising an amino acid sequence selected from SEQ ID NOs:
• 3, 7, 11, 117, 119, 121, 123, 177, 180, 188, 192, 196, 200, 203, 207, 452, 455, 609, 612 and 713-715,
• with the proviso that:
• when the CDR1 comprises SEQ ID NOs:
• 1, 5, 9 or 17, then the CDR2 is not selected from SEQ ID NOs:
• 2, 6 and 73, and the CDR3 is not selected from SEQ ID NOs:
• 3, 7 and 11, simultaneously;
• when the CDR2 comprises SEQ ID NOs:
• 2, 6, or 73, then the CDR1 is not selected from SEQ ID NOs:
• 1, 5, 9 and 17, and the CDR3 is not selected from SEQ ID NOs:
• 3, 7 and 11, simultaneously;
• when the CDR3 comprises SEQ ID NOs:
• 3, 7 or 11, then the CDR1 is not selected from SEQ ID NOs:
• 1, 5, 9 and 17, and the CDR2 is not selected from SEQ ID NOs:
• 2, 6 and 73, simultaneously.