Methods of treating inflammatory and autoimmune diseases with natalizumab
First Claim
1. A method of treating a patient with an inflammatory or autoimmune disease with natalizumab comprising:
- (a) administering a dose of natalizumab for a first dosage period;
(b) monitoring the amount of bivalent natalizumab in the patient'"'"'s plasma or serum during the first dosage period;
(c) determining a second dose of natalizumab based on the level of bivalent natalizumab observed; and
(d) administering a second dose of natalizumab for a second dosage period;
wherein the second dose improves the safety and/or efficacy of the treatment during the second dosage period.
3 Assignments
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Accused Products
Abstract
Natalizumab is a safe and efficacious treatment for inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn'"'"'s Disease, and rheumatoid arthritis. Chain swapping between natalizumab and IgG4 molecules acts to reduce the level of bivalent natalizumab present following administration of natalizumab, and thus to lower the activity of natalizumab in the patient. Differences in IgG4 levels across patients or within a single patient across time may change the pharmacokinetic profile of natalizumab. Patients with lower levels of IgG4 may experience higher nadir levels of natalizumab during a dosing period. Monitoring IgG4 and/or bivalent natalizumab levels, and determining a dose or dosage period based on the monitoring may improve the safety and/or efficacy of natalizumab therapy.
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Citations
63 Claims
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1. A method of treating a patient with an inflammatory or autoimmune disease with natalizumab comprising:
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(a) administering a dose of natalizumab for a first dosage period;
(b) monitoring the amount of bivalent natalizumab in the patient'"'"'s plasma or serum during the first dosage period;
(c) determining a second dose of natalizumab based on the level of bivalent natalizumab observed; and
(d) administering a second dose of natalizumab for a second dosage period;
wherein the second dose improves the safety and/or efficacy of the treatment during the second dosage period. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of treating a patient with an inflammatory or autoimmune disease with natalizumab comprising:
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(a) determining the amount of IgG4 in the patient'"'"'s plasma or serum;
(b) determining a dose and dosage period of natalizumab based on the amount of IgG4 in the patient'"'"'s plasma or serum; and
(c) administering the dose of natalizumab to the patient over the dosage period;
wherein the dose and dosage period improve the safety and/or efficacy of the treatment compared to the safety and/or efficacy provided by the standard dose and dosage period of natalizumab. - View Dependent Claims (20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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23. The method of 20, wherein the amount of IgG4 in the patient'"'"'s blood is below 200 μ
- g/ml, the determined dose of natalizumab is below 300 mg by IV infusion, and the determined dosage period is longer than four weeks.
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35. A method of using natalizumab to treat a patient with an inflammatory or autoimmune disease comprising:
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(a) determining the amount of IgG4 in the patient'"'"'s plasma or serum;
(b) administering a dose of natalizumab for a first dosage period;
(c) monitoring the level of bivalent natalizumab in the patient'"'"'s plasma or serum during the first dosage period;
(d) determining a second dose and dosage period of natalizumab based on the amount of IgG4 in the patient'"'"'s plasma or serum and on the level of bivalent natalizumab in the patient'"'"'s plasma or serum; and
(e) administering the second dose of natalizumab for the second dosage period;
wherein the second dose and dosage period improve the safety and/or efficacy of the treatment. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53)
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54. A method of using natalizumab to treat a patient with an inflammatory or autoimmune disease comprising:
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(a) determining the amount of IgG4 in the patient'"'"'s plasma or serum prior to initiating treatment;
(b) initiating treatment of the patient with natalizumab in the event the amount of IgG4 in the patients plasma or serum is above a predefined threshold; and
(c) initiating treatment of the patient with natalizumab with increased monitoring for indicators of progressive multifocal leukoencephalopathy and/or opportunistic infections in the event the amount of IgG4 in the patients plasma or serum is at or below a predefined threshold;
wherein determining of the amount of IgG4 in the patient'"'"'s plasma or serum improves the safety and/or efficacy of the treatment. - View Dependent Claims (55, 56, 57, 58, 59, 60)
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61. A method of treating a patient with an inflammatory or autoimmune disease with natalizumab comprising:
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(a) administering a dose of natalizumab for a first dosage period;
(b) monitoring the amount of bivalent natalizumab in the patient'"'"'s plasma or serum during the first dosage period;
(c) determining a second dose of natalizumab based on the level of bivalent natalizumab observed;
(d) administering a second dose of natalizumab for a second dosage period; and
(e) administering the second dose of natalizumab for one or more subsequent second dosage periods;
wherein the second dose improves the safety and/or efficacy of the treatment during the second dosage period.
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62. A method of treating a patient with an inflammatory or autoimmune disease with natalizumab comprising:
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(a) determining the amount of IgG4 in the patient'"'"'s plasma or serum;
(b) determining a dose and dosage period of natalizumab based on the amount of IgG4 in the patient'"'"'s plasma or serum;
(c) administering the dose of natalizumab to the patient over the dosage period; and
(d) administering the dose of natalizumab to the patient over one or more subsequent dosage periods;
wherein the dose and dosage period improve the safety and/or efficacy of the treatment compared to the safety and/or efficacy provided by the standard dose and dosage period of natalizumab.
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63. A method of using natalizumab to treat a patient with an inflammatory or autoimmune disease comprising:
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(a) determining the amount of IgG4 in the patient'"'"'s plasma or serum;
(b) administering a dose of natalizumab for a first dosage period;
(c) monitoring the level of bivalent natalizumab in the patient'"'"'s plasma or serum during the first dosage period;
(d) determining a second dose and dosage period of natalizumab based on the amount of IgG4 in the patient'"'"'s plasma or serum and on the level of bivalent natalizumab in the patient'"'"'s plasma or serum;
(e) administering the second dose of natalizumab for the second dosage period; and
(f) administering the second dose of natalizumab for one or more subsequent second dosage periods;
wherein the second dose and dosage period improve the safety and/or efficacy of the treatment.
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Specification