FORMULATION FOR ANTI-ALPHA4BETA7 ANTIBODY
Antibody formulations are described comprising a mixture of an anti-α4β7 antibody, an antioxidant or chelator, and at least one free amino acid. The disclosed formulations may have improved stability, reduced aggregate formation, or both. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-α4β7 antibody in vivo.
1 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, an antioxidant or chelator, and at least one free amino acid, wherein the formulation is in liquid form.
2 . The stable liquid pharmaceutical formulation of claim 1 , wherein the molar ratio of die anti-α4β7 antibody to die antioxidant or chelator is about 1:4 to about 1:100.
3 - 4 . (canceled)
5 . The stable liquid pharmaceutical formulation of claim 1 , wherein said antioxidant or chelator is citrate.
6 . (canceled)
7 . The stable liquid pharmaceutical formulation of claim 1 , wherein said free amino acid is selected from die group consisting of histidine, alanine, arginine, glycine, glutamic acid and combinations thereof.
8 . The stable liquid pharmaceutical formulation of claim 1 , wherein said formulation further comprises a surfactant.
9 . The stable liquid pharmaceutical formulation of claim 8 , wherein the molar ratio of die antioxidant or chelator to die surfactant is about 3:1 to about 156:1.
10 - 14 . (canceled)
15 . A stable liquid pharmaceutical formulation comprising at least about 60 mg/ml to about 160 mg/ml anti-α4β7 antibody, a buffering agent and at least about 5 mM citrate, wherein said formulation is a liquid formulation.
16 - 18 . (canceled)
19 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, citrate, histidine, arginine, and polysorbate 80, wherein die formulation is in liquid form.
20 . The stable liquid pharmaceutical formulation of claim 19 , wherein said formulation is present in a container selected from the group consisting of a vial, cartridge, syringe and autoinjector.
21 . (canceled)
22 . The stable liquid pharmaceutical formulation of claim 1 , wherein said antibody is vedolizumab.
23 . (canceled)
24 . A method of treating inflammatory bowel disease, comprising administering to a patient in need thereof die pharmaceutical formulation of claim 1 .
25 . The method of claim 24 , wherein said administering is subcutaneous or intramuscular administering.
26 . The method of claim 24 , wherein said administering is self-administering.
27 .- 28 . (canceled)
29 . A method for treating a human patient suffering from inflammatory bowel disease, wherein the method comprises die step of:
administering to a patient suffering from inflammatory bowel disease, a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for human α4β7 integrin,
wherein the humanized immunoglobulin or antigen-binding fragment thereof is administered to die patient according to the following dosing regimen:
(a) initial doses of 165 mg of die humanized immunoglobulin or antigen-binding fragment thereof as a subcutaneous injection every other dry for six doses;
(b) followed by a seventh and subsequent doses of 165 mg of die humanized immunoglobulin or antigen-binding fragment thereof as a subcutaneous injection every two weeks or every four weeks as needed;
wherein the dosing regimen induces a clinical response and clinical remission in die inflammatory bowel disease of the patient;
further wherein the humanized immunoglobulin or antigen-binding fragment thereof comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized immunoglobulin or antigen-binding fragment thereof has binding specificity for die α4β7 complex, wherein die antigen-binding region comprises die CDRs:
Light chain: CDR1 SEQ ID NO: 11
CDR2 SEQ ID NO:12 and
CDR3 SEQ ID NO:13; and
Heavy chain: CDR1 SEQ ID NO:8
CDR2 SEQ ID NO:9 and
CDR3 SEQ ID NO:10.
30 . The method of claim 29 , wherein die patient had a lack of an adequate response with, loss response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist or combinations thereof.
31 . The method of claim 29 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
32 .- 33 . (canceled)
34 . The method of claim 29 , wherein die dosing regimen results in mucosal healing in patients suffering from moderate to severely active ulcerative colitis.
35 . The method of claim 29 , wherein die dosing regimen results in a reduction, elimination or reduction and elimination of corticosteroids use by the patient.
36 - 63 . (canceled)
64 . The stable liquid pharmaceutical formulation of claim 19 , wherein die anti-α4β7 antibody is vedolizumab.
65 . The method of claim 24 , wherein die anti-α4β7 antibody is vedolizumab.