HUMAN ANTIBODIES THAT BIND THE P40 SUBUNIT OF HUMAN IL-12/IL-23 AND USES THEREFOR
The invention provides human antibodies that bind to the p40 subunit of human IL-12 and/or IL-23. The invention further provides a method of treating psoriasis in a subject by administering to a subject an antibody that binds to the p40 subunit of IL-12 and/or IL-23.
1 . An isolated antibody, or antigen-binding portion thereof, which is capable of binding to an epitope of the p40 subunit of IL-12 and/or IL-23, wherein the antibody, or antigen binding portion thereof, when administered subcutaneously or intravenously to a subject at a dose of about 100 mg or about 200 mg, is capable of exhibiting one or more pharmacokinetic properties selected from the group consisting of:
a) a rate of clearance (C L ) of about 0.5 to about 1.0 L/day;
b) an absorption constant (k a ) of about 0.4 to about 0.8 L/day;
c) a volume of central compartment volume (V c ) of about 3.5 to about 8.5 L;
d) a second (peripheral compartment) volume (V 2 ) of about 2.2 to about 4.2 L;
e) a rate of clearance from the central compartment to the second compartment (Q) of about 0.6 to about 1.1 L/day; and
f) a bioavailability (F1) of about 0.29 to about 0.50.
2 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen binding portion thereof, has 1, 2, 3, 4, 5, or 6 of the pharmacokinetic properties of claim 1 .
3 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits a rate of clearance (C L ) of about 0.5 to about 1.0 L/day.
4 . The isolated antibody, or antigen-binding portion thereof, of claim 3 , wherein the antibody, or antigen-binding portion thereof, exhibits a rate of clearance (C L ) of about 0.8 L/day.
5 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits an absorption constant (k a ) of about 0.4 to about 0.8 L/day.
6 . The isolated antibody, or antigen-binding portion thereof, of claim 5 , wherein the antibody, or antigen-binding portion thereof, exhibits an absorption constant (k a ) of about 0.6 L/day.
7 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits a volume of central compartment volume (V c ) of about 3.5 to about 8.5 L.
8 . The isolated antibody, or antigen-binding portion thereof, of claim 7 , wherein the antibody, or antigen-binding portion thereof, exhibits a volume of central compartment volume (V c ) of about 6.0 L.
9 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits a second (peripheral compartment) volume (V 2 ) of about 2.2 to about 4.2 L.
10 . The isolated antibody, or antigen-binding portion thereof, of claim 9 , wherein the antibody, or antigen-binding portion thereof, exhibits a second (peripheral compartment) volume (V 2 ) of about 3.2 L.
11 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits a rate of clearance from the central compartment to the second compartment (Q) of about 0.6 to about 1.1 L/day.
12 . The isolated antibody, or antigen-binding portion thereof, of claim 11 , wherein the antibody, or antigen-binding portion thereof, exhibits a rate of clearance from the central compartment to the second compartment (Q) of about 0.8 L/day.
13 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, exhibits a bioavailability (F1) of about 0.29 to about 0.50.
14 . The isolated antibody, or antigen-binding portion thereof, of claim 13 , wherein the antibody, or antigen-binding portion thereof, exhibits a bioavailability (F1) of about 0.4.
15 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody is administered intravenously.
16 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody is administered subcutaneously.
17 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody has been administered once.
18 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody has been administered more than once.
19 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 100 mg.
20 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody, or antigen-binding portion thereof, is administered at a dose of about 200 mg.
21 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein said pharmacokinetic properties are determined using a two compartment model.
22 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the subject is suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental.
23 . The isolated antibody, or antigen-binding portion thereof, of claim 1 , wherein the antibody is J695.
24 . A method for inhibiting the activity of the p40 subunit of IL-12 and/or IL-23 in a subject suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental, comprising administering to the subject the isolated antibody, or antibody binding portion thereof, of claim 1 , such that the activity of the p40 subunit of IL-12 and/or IL-23 in the subject is inhibited.
25 . A method for treating a subject suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental, comprising administering to the subject an antibody, or antigen-binding portion thereof, of claim 1 , thereby treating the subject.
26 . The method of claim 24 or 25 , wherein the disorder in which the activity of the p40 subunit IL-12 and/or IL-23 is detrimental is psoriasis.
27 . The method of claim 26 , wherein the psoriasis is moderate to severe plaque psoriasis.
28 . The method of claim 24 or 25 , further comprising the administration of an additional agent.
29 . A pharmaceutical composition comprising an antibody, or antigen-binding portion thereof, which is capable of binding to an epitope of the p40 subunit of IL-12 and/or IL-23, wherein the pharmaceutical composition, when administered subcutaneously or intravenously to a subject at a dose of about 100 mg or about 200 mg, allows said antibody, or antigen-binding portion thereof, to exhibit one or more pharmacokinetic properties selected from the group consisting of:
a) a rate of clearance (C L ) of about 0.5 to about 1.0 L/day;
b) an absorption constant (k a ) of about 0.4 to about 0.8 L/day;
c) a volume of central compartment volume (V c ) of about 3.5 to about 8.5 L;
d) a second (peripheral compartment) volume (V 2 ) of about 2.2 to about 4.2 L;
e) a rate of clearance from the central compartment to the second compartment (Q) of about 0.6 to about 1.1 L/day; and
f) a bioavailability (F1) of about 0.29 to about 0.50.
30 . The pharmaceutical composition of claim 29 , wherein the antibody, or antigen binding portion thereof, has 1, 2, 3, 4, 5, or 6 of the pharmacokinetic properties of claim 29 .
31 . The pharmaceutical composition of claim 29 , wherein the composition is administered intravenously.
32 . The pharmaceutical composition of claim 29 , wherein the composition is administered subcutaneously.
33 . The pharmaceutical composition of claim 29 , wherein the composition is administered once.
34 . The pharmaceutical composition of claim 29 , wherein the composition is administered more than once.
35 . The pharmaceutical composition of claim 29 , wherein the composition is administered at a dose of about 100 mg.
36 . The pharmaceutical composition of claim 29 , wherein the composition is administered at a dose of about 200 mg.
37 . The pharmaceutical composition of claim 29 , wherein said pharmacokinetic properties are determined using a two compartment model.
38 . The pharmaceutical composition of claim 29 , wherein the subject is suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental.
39 . A method for inhibiting the activity of the p40 subunit of IL-12 and/or IL-23 in a subject suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental, comprising administering to the subject the pharmaceutical composition of claim 29 , such that the activity of the p40 subunit of IL-12 and/or IL-23 in the subject is inhibited.
40 . A method for treating a subject suffering from a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental, comprising administering to the subject the pharmaceutical composition of claim 29 , thereby treating the subject.
41 . The method of claim 39 or 40 , wherein the disorder in which the activity of the p40 subunit IL-12 and/or IL-23 is detrimental is psoriasis.
42 . The method of claim 41 , wherein the psoriasis is moderate to severe plaque psoriasis.
43 . The method of claim 39 or 40 , further comprising the administration of an additional agent.