Anti-transferrin receptor / anti-BACE1 multispecific antibodies and methods of use
AssigneesGenentech, Inc., Adimab, LLC
InventorsYichin Liu, Jasvinder Atwal, Cecilia Pui Chi Chiu, Ryan J. Watts, Yan Wu, Eric Krauland, Michael Feldhaus, Yin Zhang, Joy Yu Zuchero, Jessica Couch, Mark S Dennis, James A Ernst, Gregory A Lazar
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Abstract
The present invention relates to bispecific antibodies that bind to transferrin receptor and BACE1 and methods of using the same.
Claims25
A multispecific antibody comprising a first half antibody comprising a first antigen binding site that binds to human transferrin receptor (TfR) and primate TfR, wherein the antibody does not inhibit the binding of transferrin to TfR;
- and a second half antibody comprising a second antigen binding site that binds BACE1, wherein the second antigen binding site comprises:
- (i) HVR-H1, HVR-H2, and HVR-H3, respectively comprising the amino acid sequences of:
- (a) SEQ ID NOs:
- 165, 179, and 202;
- (b) 376, 377, and 202;
- (c) 376, 377, and 378;
- (d) 376, 377, and 379;
- (e) 380, 179, and 384;
- (f) 381, 179, and 202;
- (g) 382, 179, and 202;
- (h) 165, 383, and 385;
- or (i) 165, 179, and 379 and (ii) HVR-L1, HVR-L2, and HVR-L3, respectively comprising the amino acid sequences of:
- (a) SEQ ID NO:
- 215, 221, and 230;
- (b) 215, 223, and 230;
- or
- (c) 215, 375, and 230;
- and wherein the first antigen binding site comprises (iii) HVR-H1, HVR-H2, and HVR-H3, respectively comprising the amino acid sequences of:
- (a) SEQ ID NOs:
- 53, 54 and 55;
- (b) SEQ ID NOs:
- 53, 406 and 55;
- or
- (c) SEQ ID NOs:
- 53, 407 and 55;
- and (iv) HVR-L1, HVR-L2, and HVR-L3, respectively comprising the amino acid sequences of:
- (a) SEQ ID NOs:
- 50, 51 and 52 or
- (b) SEQ ID NOs:
- 50, 51 and 408.
A multispecific antibody comprising a first half antibody comprising a first antigen binding site that binds to human transferrin receptor (TfR) and primate TfR, and a second half antibody comprising a second antigen binding site that binds BACE1, wherein:
- a) the first half antibody comprises a first heavy chain having the sequence of SEQ ID NO:
- 394 and a first light chain having the sequence of SEQ ID NO:
- 342, and the second half antibody comprises a second heavy chain having the sequence of SEQ ID NO:
- 343 and a second light chain having the sequence of SEQ ID NO:
- 344;
- or
- b) the first half antibody comprises a first heavy chain variable region comprising the sequence of SEQ ID NO:
- 396 and a first light chain variable region comprising the sequence of SEQ ID NO:
- 398, and the second half antibody comprises a second heavy chain variable region comprising the sequence of SEQ ID NO:
- 399 and a second light chain variable region comprising the sequence of SEQ ID NO:
- 400.
Dependencies are inferred from the claim text.