Claims for Patent: 11,255,842

Summary for Patent: 11,255,842

Title:	Methods for detecting neutralizing antibodies to parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP) analog
Abstract:	The present disclosure is directed to methods (e.g., in vitro methods) for detecting the presence of neutralizing antibodies to PTH or PTHrP analog in a sample. The in vitro method comprises the steps of obtaining a sample from a subject; contacting the sample with a cell; measuring cyclic adenosine monophosphate (cAMP) levels; and detecting the presence of neutralizing antibodies when cAMP levels are reduced relative to a negative control sample without neutralizing antibodies. An in vitro method of detecting the presence of neutralizing antibodies in a sample from a subject treated with Abaloparatide, is also provided. Further provided herein is a kit for carrying out the methods described herein comprising components required to carry out the obtaining, contacting, measuring and detecting steps and instructions for use.
Inventor(s):	Chandler; Heidi K. (Boxborough, MA)
Assignee:	Radius Health, Inc. (Boston, MA)
Application Number:	17/369,163
Patent Claims:	1. An in vitro method for detecting the presence of neutralizing antibodies to abaloparatide in a sample from a subject treated with abaloparatide, the method comprising: obtaining the sample from a subject; contacting the sample with a population of cells or a cell, wherein the cell or cells comprise a receptor for abaloparatide; measuring cyclic adenosine monophosphate (cAMP) levels; and detecting the presence of neutralizing antibodies indicated by reduced cAMP levels. 2. The method of claim 1, wherein the measuring cAMP levels is performed by a competitive immunoassay. 3. The method of claim 2, wherein the competitive immunoassay is an electrochemiluminescent detection method. 4. The method of claim 1, wherein the contacting step comprises incubating the cell or cells with the serum sample. 5. The method of claim 1, wherein the method further comprises preincubation of the serum sample with a predetermined amount of abaloparatide PH prior to the contacting step. 6. The method of claim 5, wherein the preincubation is for a period of at least 30 minutes. 7. The method of claim 1, wherein the cell or cells are lysed prior to the measuring step. 8. The method of claim 1, further comprising incubation of the cell or cells with a cell permeable cAMP-specific phosphodiesterase inhibitor prior to the contacting step. 9. The method of claim 8, wherein the cAMP-specific phosphodiesterase inhibitor is 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone. 10. The method of claim 1, wherein the measuring cAMP levels is performed using a Mesoscale Discovery Multi-Array 96-well cAMP Plate. 11. The method of claim 1, wherein the predetermined amount of abaloparatide is at least 100, 200, 300, 400, or 500 pg/mL. 12. The method of claim 1, wherein the predetermined amount of abaloparatide is about 600 pg/mL. 13. The method of claim 1, wherein the cell or cells are rat epithelial cell line UMR-106. 14. The method of claim 13, further comprising serum-starving the UMR-106 cell or cells for a period of time prior to the contacting step. 15. The method of claim 14, wherein the period of time ranges from about 4 hours to about 48 hours, about 4 hours to about 24 hours, about 4 hours to about 16 hours, about 4 hours to about 12 hours, or about 6 hours to about 12 hours. 16. The method of claim 1, wherein the sample is a human sample. 17. The method of claim 16, wherein the human sample is a human serum sample. 18. The method of claim 1, further comprising discontinuing treatment when neutralizing antibodies are detected in the serum sample. 19. A kit for carrying out the method of claim 1, comprising components required to carry out the obtaining, contacting, measuring and detecting steps and instructions for use. 20. The method of claim 1, further comprising increasing or decreasing a dosage of abaloparatide when neutralizing antibodies are detected in the sample.