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Table 1 Most common potential chemical liability motifs among variable regions of commercial mAbs

From: Utilizing cross-product prior knowledge to rapidly de-risk chemical liabilities in therapeutic antibody candidates

Potential Chemical Liability

AHo#

Position

Motif

Domain

% Commercial mAbs (n = 94)

Tryptophan Oxidation

43

H_FR2

W

HC

100

Tryptophan Oxidation

139

H_FR4

W

HC

100

Tryptophan Oxidation

43

L_FR2

W

LC

98.94

Tryptophan Oxidation

54

H_FR2

W

HC

98.94

Isomerization

100

H_FR3

DT

HC

89.36

O-Xylosylation

81

L_FR3

GSG

LC

89.36

O-Xylosylation

83

L_FR3

GSG

LC

85.11

Glycation

47

L_FR2

KPG

LC

80.85

Glycation

148

L_FR4

KRT

LC

79.79

Methionine Oxidation

41

H_CDR1

M

HC

63.83

Lysine Hydroxylation

75

H_CDR2

KG

HC

58.51

Methionine Oxidation

4

L_FR1

M

LC

57.45

Lysine Hydroxylation

50

H_FR2

KG

HC

56.38

Glycation

50

H_FR2

KGL

HC

55.32

Glycation

144

L_FR4

KVE

LC

52.13

Methionine Oxidation

93

H_FR3

M

HC

51.06

Glycation

75

H_CDR2

KGR

HC

48.94

Pyroglutamic Acid

1

H_FR1

Q

HC

48.94

Deamidation

94

H_FR3

NS

HC

47.87

Pyroglutamic Acid

1

H_FR1

E

HC

47.87

Glycation

53

L_FR2

KLL

LC

46.81

Isomerization

17

L_FR1

DR

LC

46.81

Glycation

50

L_FR2

KAP

LC

43.62

Isomerization

137

H_CDR3

DY

HC

42.55

O-Sulfation

138

H_CDR3

DY

HC

42.55

Glycation

14

H_FR1

KPG

HC

39.36

Isomerization

83

H_FR3

DN

HC

38.3

Methionine Oxidation

91

H_FR3

M

HC

37.23

Deamidation

87

H_FR3

NT

HC

36.17

Non-Consensus N-linked Glycosylation

87

H_FR3

SKN

HC

36.17

Glycation

24

H_FR1

KAS

HC

34.04

Glycation

86

H_FR3

KNT

HC

30.85

Glycation

144

L_FR4

KLE

LC

30.85

Isomerization

72

H_CDR2

DS

HC

28.72

Glycation

13

H_FR1

KKP

HC

27.66

Isomerization

76

L_FR3

DR

LC

27.66

Isomerization

83

H_FR3

DT

HC

27.66

Glycation

20

H_FR1

KVS

HC

25.53

Deamidation

42

L_CDR1

NW

LC

24.47

Deamidation

84

H_FR3

NS

HC

24.47