US 12,213,979 B2
Biomarkers of methotrexate-induced immune tolerance
Alexandra Joseph, Lexington, MA (US); Johnson Tran, Sacramento, CA (US); and Susan M. Richards, Sudbury, MA (US)
Assigned to Genzyme Corporation, Cambridge, MA (US)
Appl. No. 16/955,391
Filed by Genzyme Corporation, Cambridge, MA (US)
PCT Filed Dec. 21, 2018, PCT No. PCT/US2018/067098
§ 371(c)(1), (2) Date Jun. 18, 2020,
PCT Pub. No. WO2019/126647, PCT Pub. Date Jun. 27, 2019.
Claims priority of provisional application 62/609,986, filed on Dec. 22, 2017.
Prior Publication US 2021/0008074 A1, Jan. 14, 2021
Int. Cl. A61K 31/519 (2006.01); A61K 9/00 (2006.01); A61K 31/365 (2006.01); A61K 31/52 (2006.01); A61K 31/675 (2006.01); A61K 31/69 (2006.01); A61K 38/13 (2006.01); A61K 38/47 (2006.01); A61K 39/395 (2006.01); A61P 3/00 (2006.01); C12Q 1/6883 (2018.01); G01N 33/68 (2006.01); A61K 39/00 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 9/0019 (2013.01); A61K 31/365 (2013.01); A61K 31/52 (2013.01); A61K 31/675 (2013.01); A61K 31/69 (2013.01); A61K 38/13 (2013.01); A61K 38/47 (2013.01); A61K 39/395 (2013.01); A61K 39/3955 (2013.01); A61P 3/00 (2018.01); C12Q 1/6883 (2013.01); C12Y 302/0102 (2013.01); C12Y 302/01022 (2013.01); G01N 33/6893 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/38 (2013.01); G01N 2800/52 (2013.01)] 18 Claims
 
1. A method for treating Pompe disease in a subject in need of treatment with human acid α-glucosidase, comprising:
(a) administering to the subject an effective amount of methotrexate;
(b) administering to the subject an effective amount of human acid α-glucosidase;
(c) detecting an erythropoiesis biomarker in a sample obtained from the subject between at least one day and about 30 days after administration of methotrexate, wherein the detecting the erythropoiesis biomarker is detecting the expression of a gene encoding transferrin receptor; and
(d) continuing further treatment with human acid α-glucosidase with or without administering rituximab based on a level of the erythropoiesis biomarker compared to that of a control.