Cd33 binding agents

Abstract

The present invention relates to immunotherapies that are based on myeloid cell depletion. In particular, the present invention relates to CD33 binding agents for use in such therapies, e.g. in the treatment of myeloid cell malignancies and myelodysplastic syndrome (MDS).

1 . A CD33 binding agent binding to human CD33, the CD33 binding agent being defined by
 a) having a heavy chain variable region comprising CDR1, CDR2 and CDR3, and a light chain variable region comprising CDR4, CDR5 and CDR6, wherein CDR1 has an amino acid sequence selected from SeqID No:1-14, CDR2 has an amino acid sequence selected from SeqID No:15-28, CDR3 has an amino acid sequence selected from SeqID No:29-42, CDR4 has an amino acid sequence selected from SeqID No: 43-56, CDR5 has an amino acid sequence selected from SeqID No: 57-70, CDR6 has an amino acid sequence selected from SeqID No: 71-84, or   b) recognizing an epitope within the amino acid sequence FFHPIPYYDKNSPVHGYW (SeqID No: 141) of human CD33.   
     
     
         2 . The CD33 binding agent according to  claim 1 , wherein the epitope is determined by Hydrogen Exchange Mass Spectroscopy. 
     
     
         3 . The CD33 binding agent according to  claim 1 , wherein the internalization kinetics of the CD33 binding agent are such that at least 30% of the initial amount of the CD33 binding agent remains on the cell surface of HL60 cells at a time of 4 hours after incubation. 
     
     
         4 . The CD33 binding agent according to  claim 3 , wherein the internalization kinetics of the CD33 binding agents are such that at least 40% of the initial amount of the CD33 binding agents remain on the cell surface at a time of 4 hours after incubation. 
     
     
         5 . The CD33 binding agent according to  claim 1 , wherein the heavy chain variable region comprises an amino acid sequence selected from SeqID No:85-98 and the light chain variable region comprises an amino acid sequence selected from SeqID No:99-112. 
     
     
         6 . The CD33 binding agent according to  claim 1 , wherein the CD33 binding agent has a heavy chain having an amino acid sequence selected from SeqID No: 113-126 and a light chain having an amino acid sequence selected from SeqID No: 127-140. 
     
     
         7 . The CD33 binding agent according to  claim 1 , wherein the CD33 binding agent has an affinity to both human CD33 and cynomolgus CD33 with a KD of equal to or less than 10 nM. 
     
     
         8 . The CD33 binding agent according to  claim 1 , wherein the CD33 binding agent is humanized 
     
     
         9 . The CD33 binding agent according to  claim 1 , wherein the CD33 binding agent is fully human. 
     
     
         10 . The CD33 binding agent according to  claim 1 , wherein the CD33 binding agent further comprises an effector function. 
     
     
         11 . The CD33 binding agent according to  claim 10 , wherein the effector function is mediated by an F c  domain. 
     
     
         12 . The CD33 binding agent according to  claim 10 , wherein the CD33 binding agent comprises one or more mutations in the F c  domain that modulate the function of the F c  domain. 
     
     
         13 . The CD33 binding agent according to  claim 12 , wherein the modulation of the function of the Fc domain is an increase of ADCC by at least 10%, by at least 50% or by at least 100%. 
     
     
         14 . The CD33 binding agent according to  claim 12 , wherein the one or more mutations in the F c  domain are located at one or more positions selected from amino acids at positions 332 and/or 239 and/or 236 according to the Kabat EU numbering index. 
     
     
         15 . The CD33 binding agent according to  claim 12 , wherein the one or more mutations in the F c  domain are a combination of substitutions at positions 239 and 332, preferably S239D/I332E. 
     
     
         16 . The CD33 binding agent according to  claim 15 , wherein the mutations in the F c  domain are a combination of substitutions at S239D/I332E. 
     
     
         17 . A CD33 binding agent selected from
 an antibody comprising a CDR1 of SeqID No: 1, a CDR2 of SeqID No: 15, a CDR3 of SeqID No: 29, a CDR4 of SeqID No: 43, a CDR5 of SeqID No: 57 and a CDR6 of SeqID No: 71,   an antibody comprising a CDR1 of SeqID No: 2, a CDR2 of SeqID No: 16, a CDR3 of SeqID No: 30, a CDR4 of SeqID No: 44, a CDR5 of SeqID No: 58 and a CDR6 of SeqID No: 72,   an antibody comprising a CDR1 of SeqID No: 3, a CDR2 of SeqID No: 17, a CDR3 of SeqID No: 31, a CDR4 of SeqID No: 45, a CDR5 of SeqID No: 59 and a CDR6 of SeqID No: 73,   an antibody comprising a CDR1 of SeqID No: 4, a CDR2 of SeqID No: 18, a CDR3 of SeqID No: 32, a CDR4 of SeqID No: 46, a CDR5 of SeqID No: 60 and a CDR6 of SeqID No: 74,   an antibody comprising a CDR1 of SeqID No: 5, a CDR2 of SeqID No: 19, a CDR3 of SeqID No: 33, a CDR4 of SeqID No: 47, a CDR5 of SeqID No: 61 and a CDR6 of SeqID No: 75,   an antibody comprising a CDR1 of SeqID No: 6, a CDR2 of SeqID No: 20, a CDR3 of SeqID No: 34, a CDR4 of SeqID No: 48, a CDR5 of SeqID No: 62 and a CDR6 of SeqID No: 76,   an antibody comprising a CDR1 of SeqID No: 7, a CDR2 of SeqID No: 21, a CDR3 of SeqID No: 35, a CDR4 of SeqID No: 49, a CDR5 of SeqID No: 63 and a CDR6 of SeqID No: 77,   an antibody comprising a CDR1 of SeqID No: 8, a CDR2 of SeqID No: 22, a CDR3 of SeqID No: 36, a CDR4 of SeqID No: 50, a CDR5 of SeqID No: 64 and a CDR6 of SeqID No: 78,   an antibody comprising a CDR1 of SeqID No: 9, a CDR2 of SeqID No: 23, a CDR3 of SeqID No: 37, a CDR4 of SeqID No: 51, a CDR5 of SeqID No: 65 and a CDR6 of SeqID No: 79,   an antibody comprising a CDR1 of SeqID No: 10, a CDR2 of SeqID No: 24, a CDR3 of SeqID No: 38, a CDR4 of SeqID No: 52, a CDR5 of SeqID No: 66 and a CDR6 of SeqID No: 80,   an antibody comprising a CDR1 of SeqID No: 11, a CDR2 of SeqID No: 25, a CDR3 of SeqID No: 39, a CDR4 of SeqID No: 53, a CDR5 of SeqID No: 67 and a CDR6 of SeqID No: 81,   an antibody comprising a CDR1 of SeqID No: 12, a CDR2 of SeqID No: 26, a CDR3 of SeqID No: 40, a CDR4 of SeqID No: 54, a CDR5 of SeqID No: 68 and a CDR6 of SeqID No: 82,   an antibody comprising a CDR1 of SeqID No: 13, a CDR2 of SeqID No: 27, a CDR3 of SeqID No: 41, a CDR4 of SeqID No: 55, a CDR5 of SeqID No: 69 and a CDR6 of SeqID No: 83, or   an antibody comprising a CDR1 of SeqID No: 14, a CDR2 of SeqID No: 28, a CDR3 of SeqID No: 42, a CDR4 of SeqID No: 56, a CDR5 of SeqID No: 70 and a CDR6 of SeqID No: 84.   
     
     
         18 . A CD33 binding agent selected from
 an antibody comprising a heavy chain variable region of SeqID No: 85 and a light chain variable region of SeqID No: 99,   an antibody comprising a heavy chain variable region of SeqID No: 86 and a light chain variable region of SeqID No: 100,   an antibody comprising a heavy chain variable region of SeqID No: 87 and a light chain variable region of SeqID No: 101,   an antibody comprising a heavy chain variable region of SeqID No: 88 and a light chain variable region of SeqID No: 102,   an antibody comprising a heavy chain variable region of SeqID No: 89 and a light chain variable region of SeqID No: 103,   an antibody comprising a heavy chain variable region of SeqID No: 90 and a light chain variable region of SeqID No: 104,   an antibody comprising a heavy chain variable region of SeqID No: 91 and a light chain variable region of SeqID No: 105,   an antibody comprising a heavy chain variable region of SeqID No: 92 and a light chain variable region of SeqID No: 106,   an antibody comprising a heavy chain variable region of SeqID No: 93 and a light chain variable region of SeqID No: 107,   an antibody comprising a heavy chain variable region of SeqID No: 94 and a light chain variable region of SeqID No: 108,   an antibody comprising a heavy chain variable region of SeqID No: 95 and a light chain variable region of SeqID No: 109,   an antibody comprising a heavy chain variable region of SeqID No: 96 and a light chain variable region of SeqID No: 110,   an antibody comprising a heavy chain variable region of SeqID No: 97 and a light chain variable region of SeqID No: 111, or   an antibody comprising a heavy chain variable region of SeqID No: 98 and a light chain variable region of SeqID No: 113.   
     
     
         19 . A CD33 binding agent selected from
 an antibody comprising a heavy chain of SeqID No: 113 and a light chain of SeqID No: 127,   an antibody comprising a heavy chain of SeqID No: 114 and a light chain of SeqID No: 128,   an antibody comprising a heavy chain of SeqID No: 115 and a light chain of SeqID No: 129,   an antibody comprising a heavy chain of SeqID No: 116 and a light chain of SeqID No: 130,   an antibody comprising a heavy chain of SeqID No: 117 and a light chain of SeqID No: 131,   an antibody comprising a heavy chain of SeqID No: 118 and a light chain of SeqID No: 132,   an antibody comprising a heavy chain of SeqID No: 119 and a light chain of SeqID No: 133,   an antibody comprising a heavy chain of SeqID No: 120 and a light chain of SeqID No: 134,   an antibody comprising a heavy chain of SeqID No: 121 and a light chain of SeqID No: 135,   an antibody comprising a heavy chain of SeqID No: 122 and a light chain of SeqID No: 136,   an antibody comprising a heavy chain of SeqID No: 123 and a light chain of SeqID No: 137,   an antibody comprising a heavy chain of SeqID No: 124 and a light chain of SeqID No: 138,   an antibody comprising a heavy chain of SeqID No: 125 and a light chain of SeqID No: 139, or   an antibody comprising a heavy chain of SeqID No: 126 and a light chain of SeqID No: 140.   
     
     
         20 . A DNA molecule comprising a region encoding the heavy chain variable region or a light chain variable region of a CD33 binding agent according to  claim 1 . 
     
     
         21 - 30 . (canceled)