US 12,291,564 B2
Binding protein of NS1 protein
Peng Cui, Dongguan (CN); Zhiqiang He, Dongguan (CN); Yuan Meng, Dongguan (CN); and Dongmei Zhong, Dongguan (CN)
Assigned to FAPON BIOTECH INC., Guangdong (CN)
Appl. No. 17/270,341
Filed by FAPON BIOTECH INC., Shenzhen (CN)
PCT Filed Aug. 26, 2019, PCT No. PCT/CN2019/102630
§ 371(c)(1), (2) Date Apr. 8, 2024,
PCT Pub. No. WO2020/043067, PCT Pub. Date Mar. 5, 2020.
Claims priority of application No. 201811001557.1 (CN), filed on Aug. 28, 2018.
Prior Publication US 2021/0324054 A1, Oct. 21, 2021
Int. Cl. C07K 16/10 (2006.01); G01N 33/569 (2006.01)
CPC C07K 16/1081 (2013.01) [G01N 33/56983 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/92 (2013.01); G01N 2333/185 (2013.01)] 17 Claims
 
1. An isolated binding protein of dengue virus NS1 protein, the binding protein comprising a light chain and a heavy chain,
wherein an antigen-binding domain of the heavy chain comprises:
a complementary determining region CDR1-VH of G-Y-T-X1-T-S-X2-V-I-H as set forth in SEQ ID NO: 13 wherein the complementary determining region CDR1-VH corresponds to the amino acid sequence at position 26 to 35 on the heavy chain according to the Kabat numbering system;
a complementary determining region CDR2-VH of Y-M-N-X1-Y-N-D-G-X2-K-Y-N-X3-K-F-I-G as set forth in SEQ ID NO: 14 wherein the complementary determining region CDR2-VH corresponds to the amino acid sequence at position 50 to 65 on the heavy chain according to the Kabat numbering system;
a complementary determining region CDR3-VH of T-X1-E-G-L-F-Y-V-X2-D-Y as set forth in SEQ ID NO: 15 wherein the complementary determining region CDR3-VH corresponds to the amino acid sequence at position 93 to 102 on the heavy chain according to the Kabat numbering system,
wherein an antigen-binding domain of the heavy chain comprises:
a complementary determining region CDR1-VL of S-X1-T-S-S-X2-S-Y-M-H as set forth in SEQ ID NO: 16 wherein the complementary determining region CDR1-VL corresponds to the amino acid sequence at position 24 to 34 on the light chain according to the Kabat numbering system;
a complementary determining region CDR2-VL of D-X1-S-K-L-A-S-X2-V as set forth in SEQ ID NO: 17 wherein the complementary determining region CDR2-VL corresponds to the amino acid sequence at position 50 to 58 on the light chain according to the Kabat numbering system; and
a complementary determining region CDR3-VL of Q-X1-W-R-S-X2-L-P-T as set forth in SEQ ID NO: 18 wherein the complementary determining region CDR3-VL corresponds to the amino acid sequence at position 89 to 97 on the light chain according to the Kabat numbering system,
wherein an amino acid at a corresponding site of the complementary determining regions is as follows:
 
 
CDR1- CDR2- CDR3- CDR1- CDR2- CDR3-
Site VH X2 VH X2 VH X1/X2 VL X2 VL X1 VL X1
 
Mutation T L K/M I T Q
1
 
 
 
 
 
 
Mutation S I K/F L S W
1-1
 
 
 
 
 
 
Mutation Y L R/M V T Q
1-2
 
 
 
 
 
 
Mutation T I R/F I S Y
1-3
 
 
 
 
 
 
Mutation S L K/M L T W
1-4
 
 
 
 
 
 
Mutation Y I R/F V S Q
1-5
 
 
 
 
 
 
Mutation T I K/M I T Y
1-6
 
 
 
 
 
 
Mutation S L K/F L S W
1-7
 
 
 
 
 
 
Mutation Y I R/M V T Q
1-8
 
 
 
 
 
 
Mutation T L R/F I S Y
1-9
 
 
 
 
 
 
Mutation S I K/M L T W
1-10
 
 
 
 
 
 
Mutation Y L K/F V S Q
1-11
 
 
 
 
 
 
Mutation T I R/M I T Y
1-12
 
 
 
 
 
 
Mutation S L R/F L S W
1-13
 
 
 
 
 
 
Mutation Y I K/M V S Q
1-14
 
 
 
 
 
 
Mutation T I K/F I S Y
1-15
 
 
 
 
 
 
Mutation S L R/M L T W
1-16
 
 
 
 
 
 
Mutation Y I K/M V S W
1-17
 
 
 
 
 
 
Mutation T L K/F L S Y
1-18
 
 
 
 
 
 
Mutation S I R/M V T Q
1-19
 
 
 
 
 
 
Mutation Y L K/F I S Y
1-20
 
 
 
 
 
 
Mutation T I R/M L T W
1-21
 
 
 
 
 
 
Mutation S L R/F V S W
1-22
 
 
 
 
 
 
Mutation Y L K/F L S Q
1-23
 
 
 
 
 
 
Mutation T I R/M V T Y
1-24
 
 
 
 
 
 
Mutation S L R/F I S W
1-25
 
 
 
 
 
 
Mutation Y I R/M L T W
1-26
 
 
 
 
 
 
Mutation T L R/F V S Q
1-27
 
 
 
 
 
 
Mutation S I K/M V T Y
1-28
 
 
 
 
 
 
Mutation Y I R/F I S W
1-29
 
 
 
 
 
 
Mutation T L R/M L T Y
1-30
 
 
 
 
 
 
Mutation S I R/F V S W
1-31
 
 
 
 
 
 
Mutation Y I K/M V T Q
1-32
 
 
 
 
 
 
Mutation T L R/F I S W
1-33
 
 
 
 
 
 
Mutation S I R/F L T Y
1-34
 
 
 
 
 
 
Mutation Y L K/M V S W
1-35
 
 
 
 
 
 
Mutation T L R/F L S Q
1-36
 
 
 
 
 
 
Mutation S I R/F V T Y
1-37
 
 
 
 
 
 
Mutation Y L K/M I S W
1-38
 
 
 
 
 
 
Mutation T I R/F L S Q
1-39
 
 
 
 
 
 
Mutation S L K/F V T Y
1-40
 
 
 
 
 
 
Mutation Y I R/M I S W
1-41
 
 
 
 
 
 
Mutation T I R/F L T Q
1-42
 
 
 
 
 
 
Mutation S I K/M L T Y
1-43
 
 
 
 
 
 
Mutation Y L R/F V S Y
1-44
 
 
 
 
 
 
Mutation T I K/F L S W
1-45
 
 
 
 
 
 
Mutation S L R/M V T Q
1-46
 
 
 
 
 
 
Mutation Y I R/F I S Y
1-47
 
 
 
 
 
 
Mutation T L K/M L S W
1-48
 
 
 
 
 
 
Mutation S I R/F V T Q
1-49
 
 
 
 
 
 
Mutation Y L K/F I T Y
1-50
 
 
 
 
 
 
Mutation T L R/M I S W
1-51
 
 
 
 
 
 
Mutation S L K/F L S Q
1-52
 
 
 
 
 
 
Mutation Y I R/M V T  Y.
1-53