US 12,246,064 B2
Method of treating Crohn's disease by administering a triple combination therapy of anti-integrin antibody, adalimumab and methotrexate
Trevor Warren Lissoos, Deerfield, IL (US); and Jean-Frederic Colombel, New York, NY (US)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by Millennium Pharmaceuticals, Inc., Cambridge, MA (US); and Icahn School of Medicine at Mount Sinai, New York, NY (US)
Filed on Jan. 19, 2021, as Appl. No. 17/152,585.
Application 17/152,585 is a continuation of application No. 16/098,572, granted, now 10,918,716, previously published as PCT/US2017/031089, filed on May 4, 2017.
Claims priority of provisional application 62/331,813, filed on May 4, 2016.
Prior Publication US 2021/0252141 A1, Aug. 19, 2021
Int. Cl. A61K 39/395 (2006.01); A61K 31/519 (2006.01); A61K 31/573 (2006.01); A61K 31/58 (2006.01); A61K 38/00 (2006.01); A61P 1/00 (2006.01); C07K 16/24 (2006.01); C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC A61K 39/3955 (2013.01) [A61K 31/519 (2013.01); A61K 31/573 (2013.01); A61K 31/58 (2013.01); A61K 38/00 (2013.01); A61K 39/395 (2013.01); A61P 1/00 (2018.01); C07K 16/241 (2013.01); C07K 16/2842 (2013.01); A61K 2039/505 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); A61K 2300/00 (2013.01); C07K 2317/24 (2013.01)] 15 Claims
 
1. A method of treating Crohn's Disease (CD) in a patient, wherein the method comprises the step of:
administering to a human patient identified as a high-risk CD patient, a triple combination therapy comprising a humanized anti-α4β7 antibody, adalimumab, and methotrexate,
wherein the triple combination therapy is administered to the patient according to the following dosing regimen:
a. an initial dose of 155 to 180 mg of humanized anti-α4β7 antibody as an intravenous infusion, followed by a second subsequent dose of 155 to 180 mg of humanized anti-α4β7 antibody as an intravenous infusion at about two weeks after the initial dose; followed by a third subsequent dose of 155 to 180 mg of the humanized anti-α4β7 antibody as an intravenous infusion at about six weeks after the initial dose;
b. an initial dose of 160 mg of adalimumab as a subcutaneous injection, followed by a second subsequent dose of 80 mg of adalimumab as a subcutaneous injection, followed by a third subsequent dose of 40 mg of adalimumab at about four weeks after the initial dose; and
c. an initial dose of 15 mg of methotrexate;
further wherein the anti-α4β7 antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs:
Light chain:
CDR1 SEQ ID NO:7
CDR2 SEQ ID NO:8 and
CDR3 SEQ ID NO:9; and
Heavy chain:
CDR1 SEQ ID NO:4
CDR2 SEQ ID NO:5 and
CDR3 SEQ ID NO:6.