Bi-Specific Monovalent Diabodies That are Capable of Binding CD123 and CD3, and Uses Thereof

Abstract

The present invention is directed to sequence-optimized CD123×CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

1 - 20 . (canceled) 
     
     
         21 . A method of treating a disease or condition associated with or characterized by the expression of CD123, wherein said disease or condition is cancer or an inflammatory condition, comprising administering to a subject in need thereof a bi-specific diabody capable of specific binding to an epitope of CD123 and to an epitope of CD3, wherein:
 I. said bi-specific diabody comprises a first polypeptide chain and a second polypeptide chain, covalently bonded to one another, and wherein:
 (A) said first polypeptide chain comprises the amino acid sequence of SEQ ID NO:1; and 
 (B) said second polypeptide chain comprises the amino acid sequence of SEQ ID NO:3; and 
   II. said bi-specific diabody is administered at a dose of between about 0.3 ng/kg per day and about 1,000 ng/kg per day.   
     
     
         22 . The method of  claim 21 , wherein the administered dose escalates over the first quarter of the treatment regimen. 
     
     
         23 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of between about 30 ng/kg per day and about 90 ng/kg per day. 
     
     
         24 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of between about 100 ng/kg per day and about 300 ng/kg per day. 
     
     
         25 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of between about 200 ng/kg per day and about 600 ng/kg per day. 
     
     
         26 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of 100 ng/kg per day. 
     
     
         27 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of 300 ng/kg per day. 
     
     
         28 . The method of  claim 21 , wherein said bi-specific diabody is administered at a dose of 500 ng/kg per day. 
     
     
         29 . The method of  claim 21 , wherein said bi-specific diabody is administered on day 1, day 2, day 3, and day 4 of a given week, and is not administered on day 5, day 6 and day 7 of the given week. 
     
     
         30 . The method of  claim 21 , wherein said disease or condition is cancer, and wherein said cancer is selected from the group consisting of: acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), blastic crisis of CML, Abelson oncogene associated with CML (Bcr-ABL translocation), myelodysplasia syndrome (MDS), acute B lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), Richter's syndrome, Richter's transformation of CLL, hairy cell leukemia (HCL), blastic plasmacytoid dendritic cell neoplasm (BPDCN), non-Hodgkin's lymphoma (NHL), mantel cell leukemia (MCL), small lymphocytic lymphoma (SLL), Hodgkin lymphoma, systemic mastocytosis, and Burkitt's lymphoma. 
     
     
         31 . The method of  claim 30 , wherein said cancer is AML. 
     
     
         32 . The method of  claim 21 , wherein said disease or condition is an inflammatory condition, and wherein said inflammatory condition is selected from the group consisting of: Autoimmune Lupus (SLE), allergy, asthma, and rheumatoid arthritis.