Granted Patent
B2
US 12,698,346 · App. 18/463,087 · Granted Aug 4, 2026
Parathyroid hormone receptor 1(PTH1R) antibodies and uses thereof
Inventors:
Raphael D. Levy (Redwood City, CA); Hassan Issafras (Kensington, CA); Agnes Choppin Holmes (Mountain View, CA); Kirk W. Johnson (Moraga, CA); Amer M. Mirza (San Francisco, CA); Daniel H. Bedinger (Pleasant Hill, CA); Rachel A. Hunt (Emeryville, CA); Toshihiko Takeuchi (Oakland, CA); Kiranjit Kaur Ahluwalia (Fremont, CA); Robyn Cotter (Oakland, CA)
Assignee:
XOMA (US) LLC
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Abstract
The present disclosure relates, in general, human antibodies against human parathyroid hormone receptor 1 (PTH1R) and methods of use of such antibodies in the treatment of cancer, Humoral Hypercalcemia of Malignancy (HHM), or Primary Hyperparathyroidism (PHPT) and Secondary Hyperparathyroidism (SHPT) and cachexia.
Claims (18)
1 . An antibody that binds parathyroid hormone receptor 1 (PTH1R) with an affinity K d of 2×10 −8 M or less, wherein the antibody comprises:
(a) a heavy chain CDR1 amino acid sequence set forth in SQ ID No: 45;
(b) a heavy chain CDR2 amino acid sequence set forth in SQ ID No: 46;
(c) a heavy chain CDR3 amino acid sequence set forth in SQ ID No: 47;
(d) a light chain CDR1 amino acid sequence set forth in SQ ID No: 149;
(e) a light chain CDR2 amino acid sequence set forth in SQ ID No: 150; and
(f) a light chain CDR3 amino acid sequence set forth in SQ ID No: 151;
wherein the antibody is an IgG1 antibody.
2 . The antibody of claim 1 wherein the antibody binds the N-terminal portion of PTH1R and/or the antibody does not bind parathyroid hormone receptor 2 (PTH2R).
3 . The antibody of claim 1 , wherein the antibody binds allosterically to PTH1R.
4 . The antibody of claim 1 , wherein the antibody is a negative modulator antibody, optionally wherein the antibody is capable of weakening the binding affinity between PTH or PTHrP and with PTH1R by at least about 2-fold, optionally up to 1000-fold.
5 . The antibody of claim 1 , wherein the antibody i) inhibits calcium flux in a cell in response to stimulation of the receptor with parathyroid hormone (PTH) or parathyroid hormone related protein (PTHrP), and/or ii) inhibits PTH- or PTHrP-mediated cyclic adenosine mono-phosphate (cAMP) accumulation.
6 . The antibody of claim 1 that is a monoclonal antibody.
7 . The antibody of claim 1 , in which one or more light chain framework amino acids have been replaced with corresponding amino acid(s) from another human antibody amino acid sequence, optionally wherein the framework comprises one or more of the changes set out in SEQ ID NOs: 105-130.
8 . The antibody of claim 1 , further comprising a human light chain constant region.
9 . The antibody of claim 8 , wherein the light chain constant region is a modified or unmodified lambda light chain constant region, a kappa light chain constant region, a fragment thereof, or combinations thereof.
10 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes antibody of claim 1 .
11 . A sterile pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 8, 2023
From: LEVY, RAPHAEL D.; ISSAFRAS, HASSAN; HOLMES, AGNES CHOPPIN; JOHNSON, KIRK W.; MIRZA, AMER M.; BEDINGER, DANIEL H.; HUNT, RACHEL A.; TAKEUCHI, TOSHIHIKO; AHLUWALIA, KIRANJIT KAUR; COTTER, ROBYN
To: XOMA (US) LLC
Reel/Frame 064838/0014 →
Continuity (6)
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