09-06-2022 дата публикации
Номер: US20220177576A1
Принадлежит:
In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody decreases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody enhances TREM2 activity. 188-. (canceled)89. A method of treating a neurodegenerative disease in a subject , comprising administering to the subject an isolated antibody that specifically binds to a human triggering receptor expressed on myeloid cells 2 (TREM2) , wherein the antibody comprises: [{'sub': 6', '6, 'i. a CDR-H1 sequence comprising the sequence of G-F-T-F-T-α-F-Y-M-S (SEQ ID NO:28), wherein αis D or N;'}, {'sub': 5', '6', '8', '11', '12', '5', '6', '8', '11', '12, 'ii. a CDR-H2 sequence comprising the sequence of V-I-R-N-β-β-N-β-Y-T-β-β-Y-N-P-S-V-K-G (SEQ ID NO:29), wherein βis K or R; βis A or P; βis G or A; βis A or T; and βis G or D;'}, {'sub': 1', '4', '1', '4, 'iii. a CDR-H3 sequence comprising the sequence of γ-R-L-γ-Y-G-F-D-Y (SEQ ID NO:30), wherein γis A or T; and γis T or S;'}, {'sub': 10', '10, 'iv. a CDR-L1 sequence comprising the sequence of Q-S-S-K-S-L-L-H-S-δ-G-K-T-Y-L-N (SEQ ID NO:31), wherein δis N or T;'}, 'v. a CDR-L2 sequence comprising the sequence WMSTRAS (SEQ ID NO:8); and', {'sub': 6', '6, 'vi. a CDR-L3 sequence comprising the sequence of Q-Q-F-L-E-ϕ-P-F-T (SEQ ID NO:32), wherein ϕis Y or F], '(a) a variable region comprising(b) a first Fc polypeptide that specifically binds to human transferrin receptor 1 and comprises a sequence having at least 90% sequence identity to SEQ ID NO:49; and(c) a second Fc polypeptide.90. The method of claim 89 , wherein the neurodegenerative disease is selected from the group consisting of: Alzheimer's disease claim 89 , primary age-related tauopathy claim 89 , progressive supranuclear palsy (PSP) claim 89 , frontotemporal dementia claim 89 , frontotemporal dementia with parkinsonism linked to chromosome 17 claim 89 , argyrophilic grain dementia claim 89 ...
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