Treatment and Diagnosis of Macrophage Mediated Disease

Abstract

The invention relates to a method of treating or monitoring/diagnosing a disease state mediated by activated macrophages. The method comprises the step of administering to a patient suffering from a macrophage mediated disease state an effective amount of a composition comprising a conjugate or complex of the general formula A b -X where the group A b comprises a ligand capable of binding to activated macrophages, and when the conjugate is being used for treatment of the disease state, the group X comprises an immunogen, a cytotoxin, or a compound capable of altering macrophage function, and when the conjugate is being used for monitoring/diagnosing the disease state, X comprises an imaging agent. The method is useful for treating a patient suffering from a disease selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, inflammation, infections, osteomyelitis, atherosclerosis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, and systemic sclerosis.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating arthritis, said method comprising the step of administering to a patient suffering from arthritis an effective amount of a composition comprising a conjugate of the general formula
   A b -X   
       wherein the group A b  comprises folate, wherein folate binds to the folate receptor and is capable of binding to the activated macrophages, and wherein the group X comprises a cytotoxin that is an antifolate or a corticoid, wherein folate is conjugated to the cytotoxin through a γ-carboxy moiety of a glutamic acid of folate. 
     
     
         21 . The method of  claim 20  wherein Ab comprises an antifolate. 
     
     
         22 . The method of  claim 21  wherein the group X further comprises a liposome. 
     
     
         23 . The method of  claim 21  wherein the antifolate is methotrexate. 
     
     
         24 . The method of  claim 21  wherein the conjugate is administered in combination with a pharmaceutically acceptable carrier. 
     
     
         25 . The method of  claim 24  wherein the conjugate is administered to the patient using a route selected from the group consisting of intradermally, subcutaneously, intramuscularly, intraperitoneally, and intravenously. 
     
     
         26 . The method of  claim 25  wherein the route of administration is intraperitoneal administration. 
     
     
         27 . The method of  claim 25  wherein the route of administration is subcutaneous administration. 
     
     
         28 . The method of  claim 25  wherein the route of administration is intravenous administration. 
     
     
         29 . The method of  claim 21  wherein the conjugate is administered as a single dose. 
     
     
         30 . The method of  claim 21  wherein the conjugate is administered in one or more doses. 
     
     
         31 . The method of  claim 24  wherein the conjugate is administered in a multiple-dose daily regimen. 
     
     
         32 . The method of  claim 24  wherein the carrier comprises an aqueous solution. 
     
     
         33 . The method of  claim 32  wherein the aqueous solution is selected from the group consisting of isotonic saline or a glucose solution. 
     
     
         34 . The method of  claim 24  wherein the carrier comprises an alcohol, a glycol, an ester, or an amide. 
     
     
         35 . The method of  claim 24  wherein the effective amount ranges from about to 1 ng/kg to about 1 mg/kg of patient body weight. 
     
     
         36 . The method of  claim 35  wherein the effective amount ranges from about 1 μg/kg to about 500 μg/kg of patient body weight. 
     
     
         37 . The method of  claim 36  wherein the effective amount ranges from about 1 μg/kg to about 100 μg/kg of patient body weight.