US 12,391,760 B2
Method of treating primary sclerosing cholangitis
Brihad Abhyankar, Watford (GB)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed on Feb. 24, 2021, as Appl. No. 17/184,116.
Application 17/184,116 is a continuation of application No. 15/556,186, abandoned, previously published as PCT/US2016/020819, filed on Mar. 4, 2016.
Claims priority of provisional application 62/129,698, filed on Mar. 6, 2015.
Prior Publication US 2021/0388092 A1, Dec. 16, 2021
Int. Cl. A61K 39/395 (2006.01); A61K 39/00 (2006.01); C07K 16/28 (2006.01)
CPC C07K 16/2839 (2013.01) [A61K 39/39533 (2013.01); A61K 2039/505 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); C07K 2317/24 (2013.01); C07K 2317/76 (2013.01)] 10 Claims
 
1. A method of preventing progression of primary sclerosing cholangitis (PSC) in a human patient in need thereof, said method comprising:
identifying a human patient who has a serum alkaline phosphatase (ALP) level at baseline of at least 1.6 times the upper limit of normal (ULN) and is being treated with up to 20 mg/kg ursodeoxycholic acid (UDCA), and
administering 300 mg of an anti-α4β7 antibody to the human patient at weeks 0, 2, and 6 and every 4 weeks thereafter, wherein the human patient has stopped UDCA treatment by the start of the antibody treatment,
such that the progression of PSC is prevented,
wherein the serum ALP level of the human patient is reduced by at least 20% from the baseline,
wherein the human patient has non-endstage PSC and inflammatory bowel disease (IBD),
wherein prevention of progression of PSC is defined as prevention of a PSC-related outcome selected from the group consisting of progression to cirrhosis, liver failure, and liver transplantation, and
wherein the anti-α4β7 antibody is a humanized antibody and has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs:
 
 Light chain: CDR1 SEQ ID NO: 11,
 
 
 CDR2 SEQ ID NO: 12,
 
 
 CDR3 SEQ ID NO: 13,
 
 
 
 Heavy chain: CDR1 SEQ ID NO: 8,
 
 
 CDR2 SEQ ID NO: 9, and
 
 
 CDR3 SEQ ID NO: 10.