US 12,437,836 B2
Quantitation and modeling of quality attributes of therapeutic monoclonal antibodies
Xiaobin Xu, White Plains, NY (US); and Yu Huang, Ossining, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on May 25, 2022, as Appl. No. 17/824,098.
Application 17/824,098 is a continuation of application No. 16/264,044, filed on Jan. 31, 2019, granted, now 11,355,217.
Claims priority of provisional application 62/625,219, filed on Feb. 1, 2018.
Prior Publication US 2022/0367001 A1, Nov. 17, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/48 (2006.01); G01N 33/50 (2006.01); G01N 33/68 (2006.01); G06F 17/11 (2006.01); G16B 5/20 (2019.01); C07K 16/00 (2006.01); G16B 20/20 (2019.01)
CPC G16B 5/20 (2019.02) [G01N 33/6842 (2013.01); G01N 33/6854 (2013.01); G06F 17/11 (2013.01); C07K 16/00 (2013.01); C07K 2317/00 (2013.01); G01N 2440/00 (2013.01); G16B 20/20 (2019.02)] 11 Claims
OG exemplary drawing
 
1. A method for providing a subject with an effective dosing regimen of an antibody drug, the method comprising:
(a) determining the subject's exposure to a range of a product quality attribute (PQA) of the antibody drug, wherein determining the subject's exposure comprises:
(i) predicting an in vivo serum concentration of the antibody drug with a PQA after a single administration of the antibody drug to the subject by:
(ii) predicting a percentage of the antibody drug with the PQA using an in vivo rate constant determined for the PQA, wherein the in vivo rate constant for the PQA is determined by quantitating a percentage of the PQA as a function of time, thereby producing a quantified percentage, and fitting the quantitated percentage of the PQA to the equation PPQA(t)=1−(1−P0)·e−kPQAt, where PPQA(t) is the proportion of the PQA as a function of time; P0 is an initial percentage of the PQA; and kPQA is the PQA rate constant; and
(iii) multiplying the predicted percentage of the antibody drug with the PQA by a total in vivo concentration of the antibody drug to determine the concentration of the antibody drug with the PQA and thereby producing a single-administration model;
(b) repeating step (a) at least once and thereby producing one or more additional single-administration models;
(c) superimposing the single-administration models of steps (a) and (b) and thereby producing a multiple-administration model;
(d) using the multiple-administration model to determine a relationship between an initial PQA level and a PQA level after multiple administrations of the antibody,
(e) using the relationship to determine the range of the PQA of the antibody, wherein the range of the PQA comprises a maximum and a minimum PQA level observed in a multiple-dose regimen, and
(f) using the maximum and minimum PQA levels to provide the subject with an effective dosing regimen of the antibody drug.