	US 12,071,666 B2
	Human genetic markers associated with response to treatments that target clostridium difficile toxin B
Peter M. Shaw, Yardley, PA (US); Devan V. Mehrotra, Lansdale, PA (US); Rebecca L. Blanchard, Allentown, PA (US); Judong Shen, Westfield, NJ (US); Robin Mogg, Chalfont, PA (US); Mary Beth Dorr, Collegeville, PA (US); Junhua Li, Shenzhen (CN); and Xun Xu, Shenzhen (CN)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US); and Beijing Genomics Institute at Shenzhen, Shenzhen (CN)
Appl. No. 16/468,982
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US); and Beijing Genomics Institute at Shenzhen, Guangdong (CN)
PCT Filed Dec. 7, 2017, PCT No. PCT/US2017/064985 § 371(c)(1), (2) Date Jun. 12, 2019, PCT Pub. No. WO2018/111662, PCT Pub. Date Jun. 21, 2018.
Claims priority of provisional application 62/508,066, filed on May 18, 2017.
Claims priority of application No. PCT/CN2016/109900 (WO), filed on Dec. 14, 2016.
Prior Publication US 2020/0017909 A1, Jan. 16, 2020
Int. Cl. C12Q 1/6876 (2018.01); A61K 31/4164 (2006.01); A61K 31/7048 (2006.01); A61K 38/14 (2006.01); A61K 39/40 (2006.01); A61P 31/04 (2006.01); C07K 16/12 (2006.01)

CPC C12Q 1/6876 (2013.01) [A61K 31/4164 (2013.01); A61K 31/7048 (2013.01); A61K 38/14 (2013.01); A61K 39/40 (2013.01); A61P 31/04 (2018.01); C07K 16/1282 (2013.01); C07K 2317/565 (2013.01); C12Q 2600/106 (2013.01); C12Q 2600/156 (2013.01)]

30 Claims

1. A method of preventing the recurrence of a Clostridium difficile (C. difficile) infection comprising:

administering a therapeutically effective amount of bezlotoxumab that targets C. difficile toxin B (TcdB treatment) to a patient in need thereof,

wherein said patient, prior to the administration of the TcdB treatment, has tested positive for at least one copy of a better response allele from one or more TcdB treatment response markers, wherein the better response allele from one or more TcdB treatment response marker is selected from the group consisting of:

a) the T allele of the rs2516513 single nucleotide polymorphism (SNP);

b) the A allele of the rs113379306 SNP;

c) the A allele of the rs76166871 SNP;

d) the HLA-DRB1*07:01 allele of the HLA-DRB1 gene;

e) the HLA-DQB1*02:02 allele of the HLA-DQB1 gene;

f) the HLA-DQA1*02:01 allele of the HLA-DQA1 gene; and

g) a linked variant having a linkage disequilibrium r²value of at least 0.75 to one or more of the TcdB treatment response markers set forth in a)-f).