Patent ID: 11913945
Assignee: HOFFMANN-LA ROCHE, INC.
Field: Measurement (Instruments)
Classification: CPC G  C | IPC C  G

Claim 0:
1. A method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal, whereby the tissue has a barrier to the blood circulation of said animal and whereby the therapeutic antibody had been administered to said experimental animal, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, the method comprising the following steps of administering a therapeutic antibody and an inert reference antibody to the experimental animal,
i) determining the concentration of the therapeutic antibody in a blood sample of the experimental animal,
ii) determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal,
iii) determining the concentration of an inert reference antibody in the blood sample of the experimental animal,
iv) determining the concentration of the inert reference antibody in the tissue sample of the experimental animal,
v) determining the tissue concentration in the tissue sample,
and determining the concentration of the therapeutic antibody in the tissue of the experimental animal with the following formula:, C
    
      tmAb
      ,
      tissue
    
  
  =
  
    
      
        C
        
          tmAb
          ,
          tissue
          ,
          
            det
            .
          
        
      
      
        C
        
          tissue
          ,
          sample
        
      
    
    -
    
      
        
          
            C
            
              refmAb
              ,
              tissue
              ,
              
                det
                .
              
            
          
          
            C
            
              tissue
              ,
              sample
            
          
        
        
          C
          
            refmAb
            ,
            
              plasma
              .
              det
              .
            
          
        
      
      *
      
        C
        
          tmAb
          ,
          plasma
          ,
          
            det
            .
          
        
      
    
  

with
CtmAb,plasma,det.=concentration of the therapeutic antibody of i)
CtmAb,tissue,det.=concentration of the therapeutic antibody of ii)
CrefmAb,tissue,det.=concentration of the inert reference antibody of iii)
CrefmAb,plasma,det.=concentration of the inert reference antibody of iv)
Ctissue,sample=tissue concentration of v)

whereby the inert reference antibody does not cross said barrier between the tissue and the blood circulation,
whereby the inert reference antibody had been administered i) either together with the therapeutic antibody in case the sample is to be taken within 5 minutes after the administration of the therapeutic antibody, or ii) 2 to 10 minutes prior to taking the tissue sample,
whereby the blood sample is taken directly prior to the tissue sample, wherein the inert reference antibody is DP47GS, wherein the inert reference antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 67 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 68.