DAC HYP compositions and methods
View Patent ↗The present disclosure relates to compositions of daclizumab suitable for subcutaneous administration and methods of manufacturing thereof.
1. A method of treating a patient suffering from multiple sclerosis, comprising administering to the patient an amount of a daclizumab composition sufficient to provide therapeutic benefit, wherein the daclizumab has two or more of the following:
(a) an N-terminal isoform with one pyroglutamate residue and one glutamine residue that comprises 3%-17% of the total daclizumab:
(b) an N-linked oligosaccharide profile comprising two main peaks and a minor peak, wherein one of the two main peaks is GO-GlcNAc glycoform present in about 5% to about 20% of the AUC, the other main peak is GO glycoform present in about 70% to about 99.2% of the AUC, and the minor peak is G1 glycoform present in 1% to 9% of the AUC when determined according to the method described in Section 7.6.14,
(c) <3% aggregates when formulated at a concentration of about 150 mg/mL.
2. The method of claim 1 in which the daclizumab composition is administered:
(a) subcutaneously;
(b) in an amount corresponding to about 1 mg/kg daclizumab, once every two weeks or in an amount corresponding to about 2 mg/kg daclizumab, once every month;
(c) for a total of about 24 weeks; or
(d) according to any combination of (a)-(c).
3. The method of claim 2 , in which the daclizumab composition is administered in an amount corresponding to 75 mg to 300 mg daclizumab, or 150 mg, or 300 mg.
4. The method of claim 3 wherein the daclizumab composition is administered subcutaneously in an amount corresponding to 150 mg daclizumab once every month.
5. The method of claim 3 in which the daclizumab is administered as monotherapy, in which the patient has either failed to respond to prior treatment with interferon-beta or has discontinued prior treatment with interferon-beta.
6. The method of claim 3 in which the daclizumab is administered adjunctively to interferon-beta.
7. The method of claim 1 in which the daclizumab has an N-linked glycosylation profile determined according to the method described in Section 7.6.14, in which the total AUC of the peaks in the profile corresponding to non-fucosylated mannose glycosyls is less than about 6% of the total AUC of all peaks in the profile.
8. The method of claim 4 which is administered for a total of at least 48 weeks.