Antibodies against bace1 and use thereof for neural disease immunotherapy
AssigneesGenentech, Inc., Adimab, LLC
InventorsYichin Liu, Jasvinder Atwal, Cecilia Pui Chi Chiu, Ryan J. Watts, Yan WU, Eric Krauland, Michael Feldhaus
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Abstract
The invention provides antagonistic antibodies to BACE1 and methods of using the same for the treatment of neurological disease and disorders.
Claims46
An isolated antibody that binds to BACE1, wherein the antibody comprises:
- a) an HVR-H1 sequence selected from SEQ ID NOs:
- 1 to 6;
- an HVR-H2 sequence selected from SEQ ID NOs:
- 22 to 25;
- an HVR-H3 sequence selected from SEQ ID NOs:
- 50 and 51;
- an HVR-L1 sequence selected from SEQ ID NOs:
- 62 and 63;
- an HVR-L2 sequence selected from SEQ ID NOs:
- 69 and 70;
- and an HVR-L3 sequence selected from SEQ ID NOs:
- 75 to 78 and 98;
- or
- b) an HVR-H1 sequence selected from SEQ ID NOs:
- 7 to 21, 218, and 222 to 224;
- an HVR-H2 sequence selected from SEQ ID NOs:
- 26 to 49, 232, 219, and 225;
- an HVR-H3 sequence selected from SEQ ID NOs:
- 52 to 61, 220, 221, 226, and 227;
- an HVR-L1 sequence selected from SEQ ID NOs:
- 64 to 68;
- an HVR-L2 sequence selected from SEQ ID NOs:
- 69 to 74 and 217;
- and an HVR-L3 sequence selected from SEQ ID NOs:
- 79 to 97.
The isolated antibody of any one of the preceding claims, wherein the antibody modulates the activity of BACE1.
The isolated antibody of any one of the preceding claims, wherein the antibody is an allosteric inhibitor of BACE1 activity.
The isolated antibody of any one of the preceding claims, wherein the antibody binds BACE1 with an affinity (KD) of between 0.1 nM and 10 nM, or between 0.1 nM and 8 nM, or between 0.1 nM and 7 nM, or between 0.1 nM and 5 nM, or between 0.5 nM and 5 nM, or between 0.1 nM and 3 nM, or between 0.5 nM and 3 nM, as measured by surface plasmon resonance (SPR).
The isolated antibody of any one of the preceding claims, wherein the antibody achieves a maximum inhibition of BACE1 activity of greater than 60%, greater than 70%, greater than 75%, or greater than 80%, as measured, for example, using the dissociated cortical neuron culture assay.
The isolated antibody of any one of the preceding claims, wherein the antibody is a monoclonal antibody.
The isolated antibody of any one of the preceding claims, wherein the antibody is a human antibody or a chimeric antibody.
The isolated antibody of any one of the preceding claims, wherein the antibody is an antibody fragment.
Dependencies are inferred from the claim text.