11-11-2021 дата публикации
Номер: US20210347902A1
Автор:
BHINDER Tejinder Kaur,
Ding Chong,
Feng Xu,
Jiang Wenqing,
Lewis Alan Peter,
MA Yingli,
NAGAPPAN Guhan,
Parmar Radha Shah,
QIU Yangsheng,
Yang Liuqing,
Zhang Qing,
ZHOU Yanjiao
Принадлежит:
The present invention relates to TrkB binding agonists, and to the use of such agonists in the treatment of neurological disorders and other disorders. The present invention also relates to specific TrkB binding agonists comprising CDRs, variable regions, heavy and light chains, and variant sequences thereof. 155-. (canceled)56. A TrkB binding agonist that either:a) interacts with one or more residues of human TrkB: Thr290, Glu293, Ser294, Asp358, Ser375, Lys372, Gln373 and Glu341;b) approaches to less than or equal to 4.5 Å one or more residues of human TrkB: T288, 1289, T290, F291, L292, E293, S294, K308, D358, E371, K372, Q373, I374, and S375;c) binds to human TrkB extracellular domain in which a residue from E210, F285, T288, T290, F291, E293, D370 and K372 (numbering according to full length human TrkB) is mutated with an altered affinity compared to human TrkB extracellular domain with no mutation;d) binds to human TrkB and results in peptides derived from human TrkB containing part or the whole of the sequence from residues 284-291 (numbering according to full length human TrkB) being more resistant to deuterium incorporation compared to corresponding peptides derived from uncomplexed human TrkB; ore) binds to a peptide having the amino acid sequence set forth in SEQ ID NO: 71.57. The TrkB binding agonist of claim 56 , wherein the TrkB binding agonist binds to human TrkB and results in peptides derived from human TrkB containing part or the whole of the sequence from residues 284-291 (numbering according to full length human TrkB) being more resistant to deuterium incorporation compared to corresponding peptides derived from uncomplexed human TrkB.58. The TrkB binding agonist of claim 56 , wherein the TrkB binding agonist binds to a peptide having the amino acid sequence set forth in SEQ ID NO: 71.59. The TrkB binding agonist of claim 56 , wherein the TrkB binding agonist does not compete with BDNF and/or NT-4 for binding to TrkB.60. The TrkB binding agonist ...
Подробнее