Antibodies that bind Notum Pectinacetylesterase
Inventors
Brommage, JR., Robert Joseph • Feng, Xiao • Hong, Seokjoo • Landes, Gregory • Liu, Jeff • Potter, David George • Powell, David Reed
Assignees
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Publication Number
US-11059907-B2
Publication Date
2021-07-13
Expiration Date
Abstract
Antibodies that neutralize Notum Pectinacetylesterase are described, as well as compositions comprising them, and methods of their use to treat diseases and disorders affecting the bone.
Core Innovation
NOTUM inhibitory monoclonal antibodies are disclosed that bind human notum pectinacetylesterase (NOTUM) and neutralize at least one activity of NOTUM. The antibodies are characterized by binding to a region of NOTUM from amino acids 47 to 177 of SEQ ID NO: 1 and by reducing NOTUM activity in vitro in a trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS) assay and in a Wnt signaling assay in vitro.
The disclosed antibodies comprise defined heavy chain variable regions and light chain variable regions, including heavy chain variable region CDR1, CDR2, and CDR3 sequence assignments and light chain variable region CDR1, CDR2, and CDR3 sequence assignments using specified SEQ ID numbers. The disclosure further includes alternative heavy chain and light chain variable region sequence options corresponding to multiple SEQ ID numbers.
A related therapeutic approach is disclosed for patients in need of increased endocortical bone formation and for patients with bone loss disorders. A pharmaceutical composition comprising a monoclonal antibody that binds NOTUM and neutralizes at least one activity of NOTUM is administered to stimulate endocortical bone formation. Treatment and management include disease or disorder prevention, including osteoporosis as a specified example.
Claims Coverage
The partial content includes two independent claims. Each independent claim centers on administering a NOTUM-binding, NOTUM-neutralizing monoclonal antibody with a defined NOTUM binding epitope and specified in vitro activity readouts, together with defined antibody variable-region structures via specified CDR sequence options.
Stimulating endocortical bone formation with a NOTUM-neutralizing monoclonal antibody
A method of stimulating endocortical bone formation in a patient by administering an effective amount of a pharmaceutical composition comprising a monoclonal antibody that binds human NOTUM and neutralizes at least one activity of NOTUM, where the antibody binds a NOTUM region from amino acids 47 to 177 of SEQ ID NO: 1 and reduces NOTUM activity in a trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS) assay in vitro and reduces NOTUM activity in a Wnt signaling assay in vitro, and where the antibody comprises a heavy chain variable region and a light chain variable region with specified CDR1, CDR2, and CDR3 sequence identities.
Treating bone loss with a NOTUM-neutralizing monoclonal antibody
A method of treating, managing, or preventing a disease or disorder characterized by bone loss in a patient by administering an effective amount of a pharmaceutical composition comprising a monoclonal antibody that binds human NOTUM and neutralizes at least one activity of NOTUM, where the antibody binds a NOTUM region from amino acids 47 to 177 of SEQ ID NO: 1 and reduces NOTUM activity in a trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS) assay in vitro and reduces NOTUM activity in a Wnt signaling assay in vitro, and where the antibody comprises a heavy chain variable region and a light chain variable region with specified CDR1, CDR2, and CDR3 sequence identities.
Across the independent claims, the coverage is directed to patient methods that use a NOTUM-binding and NOTUM-neutralizing monoclonal antibody with a defined NOTUM binding region (amino acids 47 to 177 of SEQ ID NO: 1) and in vitro functional reduction in both OPTS and Wnt signaling assays, coupled to defined antibody variable-region structure via specified heavy/light CDR sequence options.
Stated Advantages
Stimulates endocortical bone formation in a patient.
Reduces NOTUM activity as measured in vitro by an OPTS assay and a Wnt signaling assay.
Treats, manages, or prevents a disease or disorder characterized by bone loss, including osteoporosis.
Documented Applications
Stimulating endocortical bone formation in a patient in need thereof.
Treating, managing, or preventing a disease or disorder characterized by bone loss in a patient, including osteoporosis.
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