Process for the measurement of the potency of glatiramer acetate

Abstract

The subject invention provides a process for measuring the relative potency of a test batch of glatiramer acetate. In addition, the subject invention provides a process for preparing a batch of glatiramer acetate as acceptable for pharmaceutical use.

1 - 17 . (canceled) 
     
     
         18 . A pharmaceutical composition containing glatiramer acetate whose potency is between 80% and 125% of the potency of a reference batch of glatiramer acetate and is other than the potency of the reference batch, and which is prepared by:
 a) obtaining a batch of glatiramer acetate, wherein the batch of glatiramer acetate is other than the reference batch of glatiramer acetate;   b) measuring the potency of the batch of glatiramer acetate relative to the potency of the reference batch of glatiramer acetate by:
 i) immunizing a test mammal with a predetermined amount of glatiramer acetate from the reference batch; 
 ii) preparing a primary culture of T-cells from the test mammal of step (i) at a predetermined time after immunization; 
 iii) separately incubating at least two reference samples, each of which contains a predetermined number of cells from the primary culture of step (ii) and a predetermined amount of glatiramer acetate from the reference batch; 
 iv) incubating at least two samples, each of which contains a predetermined number of cells from the primary culture of step (ii) and a predetermined amount of glatiramer acetate from the batch of glatiramer acetate; 
 v) determining for each sample in steps (iii) and (iv), the amount of a cytokine secreted by the cells in each sample after a predetermined time period of incubation of such sample; 
 vi) correlating the amounts of the cytokine secreted by the samples incubated with the batch of glatiramer acetate with the amounts of the cytokine secreted by the samples incubated with the reference batch of glatiramer acetate so as to determine the potency of the batch of glatiramer acetate relative to the reference batch of glatiramer acetate, 
    wherein in each sample in steps (iii) and (iv) the predetermined number of cells is substantially identical, and wherein for each sample containing a predetermined amount of glatiramer acetate from the batch of glatiramer acetate there is a corresponding reference sample containing a substantially identical predetermined amount of glatiramer acetate from the reference batch; and   c) preparing the drug product using the batch of glatiramer acetate if the relative potency of the batch of the glatiramer acetate is between 80% and 125% of the potency of the reference batch and is other than the potency of the reference batch.   
     
     
         19 . The method of  claim 18 , wherein the cytokine is interleukin-2. 
     
     
         20 . The method of  claim 18 , wherein the cytokine is interleukin-6. 
     
     
         21 . The method of  claim 18 , wherein the cytokine is interleukin-10. 
     
     
         22 . The method of  claim 18 , wherein the cytokine is interferon-gamma. 
     
     
         23 . The method of  claim 18 , wherein the test mammal is a rodent. 
     
     
         24 . The method of  claim 23 , wherein the rodent is a mouse. 
     
     
         25 . The method of  claim 24 , wherein the mouse is a female (SJL×BALB/C)F1 mouse. 
     
     
         26 . The method of  claim 25 , wherein the cells are lymph node cells. 
     
     
         27 . The method of  claim 25 , wherein the cells are spleen cells. 
     
     
         28 . The method of  claim 18 , wherein the test mammal is about 8 to about 12 weeks old. 
     
     
         29 . A pharmaceutical composition containing glatiramer acetate whose potency is between 80% and 125% of the potency of a reference batch of glatiramer acetate and is other than the potency of the reference batch, and which is prepared by:
 a) obtaining a batch of glatiramer acetate, wherein the batch of glatiramer acetate is other than the reference batch of glatiramer acetate;   b) measuring the potency of the batch of glatiramer acetate relative to the potency of the reference batch of glatiramer acetate by:
 i) immunizing a female (SJL×BALB/C)F1 mouse with a predetermined amount of glatiramer acetate from the reference batch; 
 ii) preparing a primary culture of T-cells from the female (SJL×BALB/C)F1 mouse of step (i) at a predetermined time after immunization; 
 iii) separately incubating at least two reference samples, each of which contains a predetermined number of cells from the primary culture of step (ii) and a predetermined amount of glatiramer acetate from the reference batch; 
 iv) incubating at least two samples, each of which contains a predetermined number of cells from the primary culture of step (ii) and a predetermined amount of glatiramer acetate from the batch of glatiramer acetate; 
 v) determining for each sample in steps (iii) and (iv), the amount of a cytokine secreted by the cells in each sample after a predetermined time period of incubation of such sample; 
 vi) correlating the amounts of the cytokine secreted by the samples incubated with the batch of glatiramer acetate with the amounts of the cytokine secreted by the samples incubated with the reference batch of glatiramer acetate so as to determine the potency of the batch of glatiramer acetate relative to the reference batch of glatiramer acetate, 
    wherein in each sample in steps (iii) and (iv) the predetermined number of cells is substantially identical, and wherein for each sample containing a predetermined amount of glatiramer acetate from the batch of glatiramer acetate there is a corresponding reference sample containing a substantially identical predetermined amount of glatiramer acetate from the reference batch; and   c) preparing the drug product using the batch of glatiramer acetate if the relative potency of the batch of the glatiramer acetate is between 80% and 125% of the potency of the reference batch and is other than the potency of the reference batch.   
     
     
         30 . The method of  claim 29 , wherein the cytokine is interleukin-2. 
     
     
         31 . The method of  claim 29 , wherein the cytokine is interleukin-6. 
     
     
         32 . The method of  claim 29 , wherein the cytokine is interleukin-10. 
     
     
         33 . The method of  claim 29 , wherein the cytokine is interferon-gamma. 
     
     
         34 . The method of  claim 29 , wherein the cells are lymph node cells. 
     
     
         35 . The method of  claim 29 , wherein the cells are spleen cells. 
     
     
         36 . The method of  claim 29 , wherein the female (SJL×BALB/C)F1 mouse is about 8 to about 12 weeks old.