Antagonist anti-NPR1 antibodies and methods of use thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsMichael E. Dunn, Lori C. Morton
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Abstract
The present disclosure provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the disclosure, the antibodies are fully human antagonist antibodies that bind to NPR1. In some embodiments, the antibodies of the disclosure are useful for blocking NPR1 signaling and/or activity, thus providing a means of treating or preventing a disease, disorder, or condition associated with NPR1, including hypotension, in humans.
Claims31
An isolated antibody or antigen-binding fragment thereof that binds specifically to natriuretic peptide receptor 1 (NPR1) protein, wherein the antibody or antigen-binding fragment thereof binds to NPR1 and blocks NPR1, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs), HCDR1, HCDR2, and HCDR3, contained within a heavy chain variable region (HCVR);
- and three light chain CDRs, LCDR1, LCDR2, and LCDR3, contained within a light chain variable region (LCVR), wherein the HCVR and LCVR pair comprises amino acid sequences, the amino acid sequences selected from the group consisting of SEQ ID NOs:
- 2 and 10, SEQ ID NOs:
- 22 and 30, SEQ ID NOs:
- 38 and 46, and SEQ ID NOs:
- 55 and 63, wherein the heavy chain region CDRs and light chain region CDRs are identified by Kabat, Chothia, or AbM.
An isolated antibody or antigen-binding fragment thereof that binds specifically to natriuretic peptide receptor 1 (NPR1) protein, wherein the antibody or antigen-binding fragment thereof binds to NPR1 and blocks NPR1, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs), HCDR1, HCDR2, and HCDR3 contained within a heavy chain variable region (HCVR);
- and three light chain CDRs, LCDR1, LCDR2, and LCDR3 contained within a light chain variable region (LCVR), wherein,
- (a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 domains contained within a HCVR and LCVR pair comprise SEQ ID NOs:
- 4, 6, 8, 12, AAS, and SEQ ID NO:
- 16, respectively, wherein the HCVR and LCVR pair comprises SEQ ID NOs:
- 2 and 10;
- (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 domains contained within a HCVR and LCVR pair comprise SEQ ID NOs:
- 24, 26, 28, 12, AAS, and SEQ ID NO:
- 32, respectively, wherein the HCVR and LCVR pair comprises SEQ ID Nos:
- 22 and 30;
- (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 domains contained within a HCVR and LCVR pair comprise SEQ ID NOs:
- 40, 42, 44, 48, AAS, and SEQ ID NO:
- 16, respectively, wherein the HCVR and LCVR pair comprises SEQ ID Nos:
- 38 and 46;
- and
- (d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 domains contained within a HCVR and LCVR pair comprise SEQ ID NOs:
- 57, 59, 61, 65, GAS, and SEQ ID NO:
- 69, respectively, wherein the HCVR and LCVR pair comprises SEQ ID Nos:
- 55 and 63.
Dependencies are inferred from the claim text.