Immune-stimulating monoclonal antibodies against human interleukin-2

Abstract

The invention relates to a human lnterieuldn-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hlL-2 inhibits binding of hlL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (KD)≤7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (Koff)≤1×10−4 s−1 and/or the antibody displays no measurable cross-reactivity to murine IL-2.

1 - 19 . (canceled) 
     
     
         20 . A fusion protein comprising:
 a) a VH domain fragment, wherein said VH domain fragment comprises amino acid sequences of SEQ ID NOs: 007, 008 and 009;   b) a VL domain fragment, wherein said VL domain fragment comprises amino acid sequences SEQ ID NOs: 010, 011, and 012; and   c) a human interleukin 2 (hIL-2) polypeptide comprising an amino acid sequence having at least 80% sequence identify to SEQ ID NO:001 or SEQ ID NO:002, wherein said hIL-2 polypeptide has hIL-2 activity.   
     
     
         21 . The fusion protein of  claim 20 , wherein said VH domain fragment is fused to the hIL-2 polypeptide to produce a single polypeptide chain. 
     
     
         22 . The fusion protein of  claim 21 , wherein the VH domain fragment is fused to the hIL-2 polypeptide by an amino acid linker, wherein said amino acid linker is 1 to 50 amino acids. 
     
     
         23 . The fusion protein of  claim 20 , wherein said VH domain fragment comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 019. 
     
     
         24 . The fusion protein of  claim 20 , wherein said VH domain fragment comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 005. 
     
     
         25 . The fusion protein of  claim 20 , wherein said fusion protein comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 023. 
     
     
         26 . The fusion protein of  claim 20 , wherein said VL domain fragment is fused to the hIL-2 polypeptide to produce a single polypeptide chain. 
     
     
         27 . The fusion protein of  claim 26 , wherein said VL domain fragment is fused to the hIL-2 polypeptide by an amino acid linker, wherein said amino acid linker is between 1 and 50 amino acids. 
     
     
         28 . The fusion protein of  claim 20 , wherein said VL domain fragment comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 020. 
     
     
         29 . The fusion protein of  claim 28 , wherein VL domain fragment is fused to the hIL-2 polypeptide by an amino acid linker to produce a single polypeptide chain. 
     
     
         30 . The fusion protein of  claim 29 , wherein said amino acid linker is between 1 and 50 amino acids. 
     
     
         31 . The fusion protein of  claim 20 , wherein said fusion protein comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 006. 
     
     
         32 . The fusion protein of  claim 31 , wherein said amino acid sequence is fused to the hIL-2 polypeptide by an amino acid linker to produce a single polypeptide chain. 
     
     
         33 . The fusion protein of  claim 32 , wherein said amino acid linker is between 1 and 50 amino acids. 
     
     
         34 . The fusion protein of  claim 20 , wherein said VH domain fragment comprises a first polypeptide at least 70% identical to SEQ ID NO: 19 and said VL domain fragment comprises second polypeptide at least 70% identity to SEQ ID NO:20. 
     
     
         35 . The fusion protein of  claim 34 , wherein said hIL-2 polypeptide is fused to the VL domain fragment to produce a single polypeptide chain. 
     
     
         36 . The fusion protein of  claim 35 , wherein said amino acid linker is between 1 and 50 amino acids. 
     
     
         37 . A pharmaceutical composition comprising the fusion protein of  claim 20 . 
     
     
         38 . A nucleic acid molecule encoding the fusion protein according to  claim 20 . 
     
     
         39 . A vector comprising the nucleic acid molecule of  claim 38 . 
     
     
         40 . A cell comprising the nucleic acid molecule of  claim 38  or expressing the nucleic acid molecule according of  claim 38   
     
     
         41 . The cell of  claim 40  expressing the fusion protein. 
     
     
         42 . The fusion protein expressed from the cell of  claim 41 . 
     
     
         43 . A method of treating cancer or viral infection by (1) selecting a patient having cancer or viral infection and (2) administering a therapeutically effective amount of the fusion protein of  claim 20 .