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 method for treating ulcerative colitis in a human patient in need thereof, the method comprising:
an induction phase comprising,
intravenously administering an initial dose of 300 mg of a humanized anti-α4β7 antibody to the human patient, and
intravenously administering a second dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 2 weeks after the initial dose, and
a maintenance phase comprising,
subcutaneously administering a dose of 108 mg of the humanized anti-α4β7 antibody to the human patient via a prefilled syringe every two weeks starting at 6 weeks after the initial dose,
wherein the human patient has a mean steady state trough serum concentration of 30 μg/mL to 45 μg/mL of the humanized anti-α4β7 antibody during the maintenance phase,
wherein the humanized anti-α4β7 antibody is an IgG1 isotype, and
wherein the humanized anti-α4β7 antibody comprises a light chain comprising SEQ ID NO: 11 (LCDR1), SEQ ID NO: 12 (LCDR2), and SEQ ID NO: 13 (LCDR3), and a heavy chain comprising SEQ ID NO: 8 (HCDR1), SEQ ID NO: 9 (HCDR2), and SEQ ID NO: 10 (HCDR3).
2 . The method of claim 1 , wherein the method induces clinical remission in the ulcerative colitis of the human patient.
3 . The method of claim 1 , wherein the human patient had a lack of an adequate response with, loss of response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist, or combinations thereof.
4 . The method of claim 1 , wherein the dose of 108 mg is self-administered.
5 . The method of claim 1 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region that is at least 95% identical to amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region that is at least 95% identical to amino acids 20 to 131 of SEQ ID NO:4.
6 . The method of claim 1 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids to 20 to 131 of SEQ ID NO:4.
7 . The method of claim 1 , wherein the humanized anti-α4β7 antibody is vedolizumab.
8 . A method for treating ulcerative colitis in a human patient in need thereof, the method comprising:
an induction phase comprising,
intravenously administering an initial dose of 300 mg of a humanized anti-α4β7 antibody to the human patient,
intravenously administering a second dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 2 weeks after the initial dose,
intravenously administering a third dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 6 weeks after the initial dose, and
a maintenance phase comprising,
subcutaneously administering a dose of 108 mg of the humanized anti-α4β7 antibody to the human patient via a prefilled syringe every two weeks starting at 14 weeks after the initial dose,
wherein the human patient has a mean steady state trough serum concentration of 30 μg/mL to 45 μg/mL of the humanized anti-α4β7 antibody during the maintenance phase,
wherein the humanized anti-α4β7 antibody is an IgG1 isotype, and
wherein the humanized anti-α4β7 antibody comprises a light chain comprising SEQ ID NO: 11 (LCDR1), SEQ ID NO: 12 (LCDR2), and SEQ ID NO: 13 (LCDR3), and a heavy chain comprising SEQ ID NO: 8 (HCDR1), SEQ ID NO: 9 (HCDR2), and SEQ ID NO: 10 (HCDR3).
9 . The method of claim 8 , wherein the method induces clinical remission in the ulcerative colitis of the human patient.
10 . The method of claim 8 , wherein the human patient had a lack of an adequate response with, loss of response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist, or combinations thereof.
11 . The method of claim 8 , wherein the dose of 108 mg is self-administered.
12 . The method of claim 8 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region that is at least 95% identical to amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region that is at least 95% identical to amino acids 20 to 131 of SEQ ID NO:4.
13 . The method of claim 8 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids to 20 to 131 of SEQ ID NO:4.
14 . The method of claim 8 , wherein the humanized anti-α4β7 antibody is vedolizumab.
15 . A method for treating ulcerative colitis in a human patient in need thereof, the method comprising:
an induction phase comprising,
intravenously administering an initial dose of 300 mg of a humanized anti-α4β7 antibody to the human patient, and
intravenously administering a second dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 2 weeks after the initial dose, and a maintenance phase comprising,
subcutaneously administering a dose of 108 mg of the humanized anti-α4β7 antibody to the human patient via an autoinjector every two weeks starting at 6 weeks after the initial dose,
wherein the human patient has a mean steady state trough serum concentration of 30 μg/mL to 45 μg/mL of the humanized anti-α4β7 antibody during the maintenance phase,
wherein the humanized anti-α4β7 antibody is an IgG1 isotype, and
wherein the humanized anti-α4β7 antibody comprises a light chain comprising SEQ ID NO: 11 (LCDR1), SEQ ID NO: 12 (LCDR2), and SEQ ID NO: 13 (LCDR3), and a heavy chain comprising SEQ ID NO: 8 (HCDR1), SEQ ID NO: 9 (HCDR2), and SEQ ID NO: 10 (HCDR3).
16 . The method of claim 15 , wherein the method induces clinical remission in the ulcerative colitis of the human patient.
17 . The method of claim 15 , wherein the human patient had a lack of an adequate response with, loss of response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist, or combinations thereof.
18 . The method of claim 15 , wherein the dose of 108 mg is self-administered.
19 . The method of claim 15 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region that is at least 95% identical to amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region that is at least 95% identical to amino acids 20 to 131 of SEQ ID NO:4.
20 . The method of claim 15 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids to 20 to 131 of SEQ ID NO:4.
21 . The method of claim 15 , wherein the humanized anti-α4β7 antibody is vedolizumab.
22 . A method for treating ulcerative colitis in a human patient in need thereof, the method comprising:
an induction phase comprising,
intravenously administering an initial dose of 300 mg of a humanized anti-α4β7 antibody to the human patient,
intravenously administering a second dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 2 weeks after the initial dose,
intravenously administering a third dose of 300 mg of the humanized anti-α4β7 antibody to the human patient 6 weeks after the initial dose, and
a maintenance phase comprising,
subcutaneously administering a dose of 108 mg of the humanized anti-α4β7 antibody to the human patient via an autoinjector every two weeks starting at 14 weeks after the initial dose,
wherein the human patient has a mean steady state trough serum concentration of 30 μg/mL to 45 μg/mL of the humanized anti-α4β7 antibody during the maintenance phase,
wherein the humanized anti-α4β7 antibody is an IgG1 isotype, and
wherein the humanized anti-α4β7 antibody comprises a light chain comprising SEQ ID NO: 11 (LCDR1), SEQ ID NO: 12 (LCDR2), and SEQ ID NO: 13 (LCDR3), and a heavy chain comprising SEQ ID NO: 8 (HCDR1), SEQ ID NO: 9 (HCDR2), and SEQ ID NO: 10 (HCDR3).
23 . The method of claim 22 , wherein the method induces clinical remission in the ulcerative colitis of the human patient.
24 . The method of claim 22 , wherein the human patient had a lack of an adequate response with, loss of response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist, or combinations thereof.
25 . The method of claim 22 , wherein the dose of 108 mg is self-administered.
26 . The method of claim 22 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region that is at least 95% identical to amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region that is at least 95% identical to amino acids 20 to 131 of SEQ ID NO:4.
27 . The method of claim 22 , wherein the humanized anti-α4β7 antibody comprises a heavy chain variable region comprising amino acids 20 to 140 of SEQ ID NO:2, and a light chain variable region comprising amino acids to 20 to 131 of SEQ ID NO:4.
28 . The method of claim 22 , wherein the humanized anti-α4β7 antibody is vedolizumab.