Method for comparing botulinum neurotoxins

Abstract

Skin topographical methods for quantifying pharmacodynamic parameters of a paralytic effect of a Clostridial toxin, such as a botulinum toxin upon a muscle, such as a frontalis muscle. The methods are effective in determining the potency of a Clostridial toxin, and in comparing toxins. For example, wrinkle reduction effects caused by one or more neurotoxins may be monitored, and differences in effects correspond to differences of neurotoxins.

1 .- 18 . (canceled)  
   
   
       19 . A method for comparing botulinum neurotoxins, comprising the steps of: 
 (a) making a first impression of a skin surface region of an individual in proximity to a first muscle and a second muscle into or in the vicinity of which a first botulinum neurotoxin and a second botulinum neurotoxin, respectively are to be administered, the impression being made while the first and second muscles are at a first maximum voluntary contraction;    (b) administering the first and second botulinum toxins to the first and second muscles, respectively;    (c) making a second impression of the skin surface region in proximity to the first and second muscles, the impression being made while the first and second muscles are at a second maximum voluntary contraction;    (d) examining the first and second impressions;    (e) obtaining from the impressions mean depth of a skin wrinkle, and;    (f) comparing the mean depth of the skin wrinkle for the first and second botulinum neurotoxins.    
   
   
       20 . The method of  claim 19 , wherein the obtaining step further comprises obtaining from the impressions a mean length of a skin wrinkle.  
   
   
       21 . The method of  claim 19 , wherein the obtaining step further comprises obtaining from the impressions a total length of a skin wrinkle.  
   
   
       22 . The method of  claim 19 , wherein the obtaining step further comprises obtaining from the impressions a total number of skin wrinkles.  
   
   
       23 . The method of  claim 19 , wherein the obtaining step further comprises obtaining from the impressions a surface area of a skin wrinkle.  
   
   
       24 . The method of  claim 19 , wherein the obtaining step further comprises obtaining from the impressions a form factor skin surface characteristic.  
   
   
       25 . The method of  claim 19 , wherein the comparing step comprises determining a paralytic effect of the first and second botulinum neurotoxins upon the muscles.  
   
   
       26 . The method of  claim 19 , wherein the first botulinum neurotoxin and the second botulinum neurotoxin are different.  
   
   
       27 . The method of  claim 19 , wherein the first botulinum neurotoxin is selected from the group consisting of botulinum neurotoxin types A, B, C, D, E, F and G, and the second botulinum neurotoxin is of a serotype other than the first botulinum neurotoxin.  
   
   
       28 . The method of  claim 19 , wherein the first botulinum neurotoxin is a botulinum neurotoxin produced by a first strain of a Clostridial bacteria, and wherein the second botulinum neurotoxin is a botulinum neurotoxin produced by a strain of Clostridial bacterial other than the first strain.  
   
   
       29 . The method of  claim 19 , wherein the first botulinum neurotoxin is botulinum toxin type A, and the second botulinum neurotoxin is botulinum toxin type B.  
   
   
       30 . The method of  claim 19 , wherein the first botulinum neurotoxin is a native botulinum neurotoxin obtained from Clostridial bacteria, and wherein the second botulinum neurotoxin is a modified botulinum neurotoxin.  
   
   
       31 . The method of  claim 19 , wherein the first botulinum neurotoxin is provided in a composition which comprises a polysaccharide in an amount effective to stabilize the botulinum neurotoxin, and wherein the second botulinum neurotoxin is provided in a composition which is substantially free of the polysaccharide.  
   
   
       32 . The method of  claim 19 , wherein the first botulinum neurotoxin is provided in a composition which comprises a recombinant albumin in an amount effective to stabilize the botulinum neurotoxin, and wherein the second botulinum neurotoxin is provided in a composition which is substantially free of recombinant albumin.  
   
   
       33 . The method of  claim 19 , wherein the first botulinum neurotoxin is provided in a composition which comprises gelatin in an amount effective in stabilizing the botulinum neurotoxin, and wherein the second botulinum neurotoxin is provided in a composition which is substantially free of gelatin.  
   
   
       34 . The method of  claim 19 , wherein the first botulinum toxin is provided in a composition which comprises human serum albumin in an amount effective in stabilizing the botulinum neurotoxin, and wherein the second botulinum neurotoxin is provided in a composition which comprises a stabilizer other than human serum albumin.  
   
   
       35 . The method of  claim 19 , wherein the comparing step comprises comparing the mean depth of a skin wrinkle in proximity to the first muscle before administration of the first botulinum neurotoxin, and the mean depth of the skin wrinkle after administration of the first botulinum neurotoxin to determine an effect of the first botulinum neurotoxin on the depth of the skin wrinkle; comparing the mean depth of a skin wrinkle in proximity to the second muscle before administration of the second botulinum neurotoxin, and the mean depth of the skin wrinkle after administration of the second botulinum neurotoxin to determine an effect of the second botulinum neurotoxin on the skin wrinkle; and comparing the effects of the first botulinum neurotoxin and the second botulinum neurotoxin.  
   
   
       36 .- 42 . (canceled)