Anti-cd3 antibody dosing in autoimmune disease
OwnerCharlotte McKee, Paul Ponath +3inventors
InventorsCharlotte McKee, Paul Ponath, Douglas Ringler, Michael Rosenzweig, Lou Vaickus
Life of this patent
Estimating the term…
Abstract
Provided herein are methods of administering anti-CD3 antibodies or antigen-binding fragments thereof to an animal. In certain embodiments, the anti-CD3 antibody or fragment thereof does not bind or has reduced binding to at least one class of Fc (gamma) receptors. In certain embodiments, the animal has an immune-related disease.
Claims22
A method of treating a human with an anti-CD3 antibody or an antigen binding fragment thereof, the method comprising:
- administering the antibody or the fragment to the human in a regimen such that:
- (a) in a therapy window of at least 2 days and no more than 6 days, for at least 48 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 10 percent and less than 40 percent of the mean baseline level;
- (b) in a therapy window of 7 days or more, for at least 48 hours of the first 6 days of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 10 percent and less than 40 percent of the mean baseline level;
- (c) in a therapy window of at least 8 days, for at least 48 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 10 percent and less than 40 percent of the mean baseline level and at least 30 of the 48 hours occur after the first 6 days of the window;
- or
- (d) in a therapy window of at least 4 days, for at least 90 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 10 percent and less than 40 percent of the mean baseline level,
- wherein the antibody or fragment does not bind, or has reduced binding, to at least one class of Fc (gamma) receptor as compared to the OKT3 antibody.
A method of treating a human with an anti-CD3 antibody or an antigen binding fragment thereof, the method comprising:
- administering the antibody or the fragment to the human in a regimen such that:
- (a) in a therapy window of at least two days and no more than 6 days, for at least 12 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 20 percent and less than 30 percent of the mean baseline level;
- (b) in a therapy window of 7 days or more, for at least 18 hours of the first 6 days of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 20 percent and less than 30 percent of the mean baseline level;
- (c) in a therapy window of at least 7 days, for at least 24 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 20 percent and less than 30 percent of the mean baseline level and at least 15 of the at least 24 hours occur after the first 6 days of the window;
- or
- (d) in a therapy window of at least 7 days, for at least 40 hours of the window, the mean level of free CD3/TCR complexes on CD4+ and on CD8+ T cells is at least 20 percent and less than 30 percent of the mean baseline level and at least half of the at least 40 hours in the window occur after the first 6 days of the window,
- wherein the antibody or fragment does not bind, or has reduced binding, to at least one class of Fc (gamma) receptor as compared to the OKT3 antibody.
A method of treating a human with an anti-CD3 antibody or an antigen binding fragment thereof, the method comprising:
- administering the antibody or the fragment to the human in a regimen such that:
- (a) in a regimen of 3 days or more, the daily dose administered is at least 1 mg and no greater than 3 mg in any 24 hour period and on each of at least 3 days of the regimen;
- (b) in a regimen of 3 days or more, the daily dose administered is at least 1 mg and no greater than 1.75 mg in any 24 hour period and on each of at least 3 days of the regimen;
- (c) in a regimen of 3 days or more, the daily dose administered is at least 14 μg/kg and no greater than 42 μg/kg in any 24 hour period and on each of at least 3 days of the regimen;
- (d) in a regimen of 3 days or more, the total dose administered is 2.5 mg to 9 mg and no greater than 3 mg on any single day of the regimen;
- (e) in a regimen of 3 days or more, the total dose administered is 2.5 mg to 6.6 mg and no greater than 2.2 mg on any single day of the regimen;
- (f) in a regimen of 3 days or more, the total dose administered is 35 μg/kg to 126 μg/kg and no greater than 42 μg/kg on any single day of the regimen;
- (g) in a regimen of 3 days or more, the total dose administered is 35 μg/kg to 93 μg/kg and no greater than 31 μg/kg on any single day of the regimen;
- (h) in a therapy window of at least three days, where a dose is administered over a period of 24 hours or more, the total dose administered to the human is at least 2.5 mg;
- or
- (i) in a therapy window of at least three days, where a dose is administered over a period of 24 hours or more, the total dose administered to the human is at least 35 μg/kg,
- wherein the antibody or fragment does not bind, or has reduced binding, to at least one class of Fc (gamma) receptor as compared to the OKT3 antibody and, optionally, the three days are not continuous.
A method of treating a human with an anti-CD3 antibody, or an antigen binding fragment thereof, the method comprising administering the antibody or fragment to the human in a regimen that comprises a dosing ramp of at least four days, wherein the antibody or fragment does not bind or has reduced binding to at least one class of the Fc (gamma) receptor as compared to the OKT3 antibody.
-37. (canceled)
Dependencies are inferred from the claim text.