USE OF ANTIBODIES TO TNF OR FRAGMENTS DERIVED THEREOF AND XANTHINE DERIVATIVES FOR COMBINATION THERAPY AND COMPOSITIONS THEREFOR

摘要

2094154 9207585 PCTABS00013 A combined preparation for simultaneous combined, simultaneous separate, or sequential use in the therapy or prophylaxis of disorders associated with undesirably high levels of TNF, e.g. septic or endotoxic shock and immunoregulatory and inflammatory disorders, which comprises an antibody to TNF or a TNF binding fragment thereof and a xanthine derivative. Particular preferred xanthine derivatives are 3,7-dimethyl-1-(5-oxo-hexyl)xanthine (known as Pentoxifylline or Trental) and 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine and similar compounds. The anti-TNF antibody or fragment is preferably monospecific especially a humanised recombinant antibody or fragment. The ratio of xanthine derivative to anti-TNF antibody component used may be in the range between 450:1 and 1:10 and doses of anti-TNF component in the range 0.001-30mg/kg/day and doses of xanthine derivative in the range 0.5 to 100mg/kg/day may be administered during treatment of human or animal subjects. It has been found that when an anti-TNF antibody and a xanthine derivative are used together in some experimental models of septic shock, a surprising combination effect is observed.