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US 2025/0026820 A1Published application
ANTI-TGFbeta ANTIBODY AND PREPARATION METHOD AND APPLICATION THEREOF
AssigneeWuhan YZY Biopharma Co., Ltd.
InventorsJian SHI, Lijuan FANG, Yongxiang YAN, Jing ZHANG, Shan HUA, Pengfei ZHOU
Life of this patent
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Abstract
The present invention relates to an anti-TGFβ antibody, such as B2G8, comprising CDR1, CDR2 and CDR3 contained in a sequence shown in SEQ ID NO: 7, preferably according to the Kabat and IMGT numbering system, comprising CDR1 as shown in SEQ ID NO: 49, CDR2 as shown in SEQ ID NO: 50 and CDR3 as shown in SEQ ID NO: 51, and an application of said anti-TGFβ antibody.
Claims12
An anti-TGFβ antibody, comprising or consisting of a sequence selected from the group consisting of:
- (1) B2G8, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 7, preferably comprising a CDR1 set forth in SEQ ID NO:
- 49, a CDR2 set forth in SEQ ID NO:
- 50, and a CDR3 set forth in SEQ ID NO:
- 51, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 49, the CDR2 set forth in SEQ ID NO:
- 50, and/or the CDR3 set forth in SEQ ID NO:
- 51 and retaining the binding affinity to TGFβ, preferably comprising the CDR1 set forth in SEQ ID NO:
- 49, a variant of the CDR2 set forth in SEQ ID NO:
- 50, and the CDR3 set forth in SEQ ID NO:
- 51, wherein the variant of the CDR2 set forth in SEQ ID NO:
- 50 is that the 13th amino acid of an amino acid sequence set forth in SEQ ID NO:
- 50 is replaced with alanine, or
- comprising a CDR1 set forth in SEQ ID NO:
- 49, a CDR2 set forth in SEQ ID NO:
- 50, and a CDR3 set forth in SEQ ID NO:
- 51, wherein amino acids 5-8 in the CDR1 set forth in SEQ ID NO:
- 49, amino acids 1-5 and amino acids 7-9 in the CDR2 set forth in SEQ ID NO:
- 50, and amino acid 1 and amino acids 4-9 in the CDR3 set forth in SEQ ID NO:
- 51 are selected from amino acid X, wherein the amino acid X is selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val,
- (2) B1B8, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 4, preferably comprising a CDR1 set forth in SEQ ID NO:
- 40, a CDR2 set forth in SEQ ID NO:
- 41, and a CDR3 set forth in SEQ ID NO:
- 42, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 40, the CDR2 set forth in SEQ ID NO:
- 41, and/or the CDR3 set forth in SEQ ID NO:
- 42 and retaining the binding affinity to TGFβ, or
- comprising a CDR1 set forth in SEQ ID NO:
- 40, a CDR2 set forth in SEQ ID NO:
- 41, and a CDR3 set forth in SEQ ID NO:
- 42, wherein amino acid 3 and amino acids 5-8 in the CDR1 set forth in SEQ ID NO:
- 40, amino acids 1, 3, and 5-10 in the CDR2 set forth in SEQ ID NO:
- 41, and amino acids 4-9 and 11 in the CDR3 set forth in SEQ ID NO:
- 42 are selected from amino acid X, wherein the amino acid X is selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val,
- (3) B3F3, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 16, preferably comprising a CDR1 set forth in SEQ ID NO:
- 76, a CDR2 set forth in SEQ ID NO:
- 77, and a CDR3 set forth in SEQ ID NO:
- 78, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 76, the CDR2 set forth in SEQ ID NO:
- 77, and/or the CDR3 set forth in SEQ ID NO:
- 78 and retaining the binding affinity to TGFβ;
- or
- comprising a CDR1 set forth in SEQ ID NO:
- 76, a CDR2 set forth in SEQ ID NO:
- 77, and a CDR3 set forth in SEQ ID NO:
- 78, wherein amino acids 2-3 and amino acids 5-8 in the CDR1 set forth in SEQ ID NO:
- 76, amino acids 2-4 and amino acid 6 in the CDR2 set forth in SEQ ID NO:
- 77, and amino acid 1 and amino acids 3-8 in the CDR3 set forth in SEQ ID NO:
- 78 are selected from amino acid X, wherein the amino acid X is selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val,
- (4) B2A1, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 1, preferably comprising a CDR1 set forth in SEQ ID NO:
- 31, a CDR2 set forth in SEQ ID NO:
- 32, and a CDR3 set forth in SEQ ID NO:
- 33, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 31, the CDR2 set forth in SEQ ID NO:
- 32, and/or the CDR3 set forth in SEQ ID NO:
- 33 and retaining the binding affinity to TGFβ;
- (5) B1F8, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 5, preferably comprising a CDR1 set forth in SEQ ID NO:
- 43, a CDR2 set forth in SEQ ID NO:
- 44, and a CDR3 set forth in SEQ ID NO:
- 45, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 43, the CDR2 set forth in SEQ ID NO:
- 44, and/or the CDR3 set forth in SEQ ID NO:
- 45 and retaining the binding affinity to TGFβ;
- (6) B3D6, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 6, preferably comprising a CDR1 set forth in SEQ ID NO:
- 46, a CDR2 set forth in SEQ ID NO:
- 47, and a CDR3 set forth in SEQ ID NO:
- 48, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 46, the CDR2 set forth in SEQ ID NO:
- 47, and/or the CDR3 set forth in SEQ ID NO:
- 48 and retaining the binding affinity to TGFβ;
- (7) B2A9, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 2, preferably comprising a CDR1 set forth in SEQ ID NO:
- 34, a CDR2 set forth in SEQ ID NO:
- 35, and a CDR3 set forth in SEQ ID NO:
- 36, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 34, the CDR2 set forth in SEQ ID NO:
- 35, and/or the CDR3 set forth in SEQ ID NO:
- 36 and retaining the binding affinity to TGFβ;
- (8) B2C2, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 8, preferably comprising a CDR1 set forth in SEQ ID NO:
- 52, a CDR2 set forth in SEQ ID NO:
- 53, and a CDR3 set forth in SEQ ID NO:
- 54, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 52, the CDR2 set forth in SEQ ID NO:
- 53, and/or the CDR3 set forth in SEQ ID NO:
- 54 and retaining the binding affinity to TGFβ;
- (9) B1B7, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 9, preferably comprising a CDR1 set forth in SEQ ID NO:
- 55, a CDR2 set forth in SEQ ID NO:
- 56, and a CDR3 set forth in SEQ ID NO:
- 57, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 55, the CDR2 set forth in SEQ ID NO:
- 56, and/or the CDR3 set forth in SEQ ID NO:
- 57 and retaining the binding affinity to TGFβ;
- (10) B1C5, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 10, preferably comprising a CDR1 set forth in SEQ ID NO:
- 58, a CDR2 set forth in SEQ ID NO:
- 59, and a CDR3 set forth in SEQ ID NO:
- 60, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 58, the CDR2 set forth in SEQ ID NO:
- 59, and/or the CDR3 set forth in SEQ ID NO:
- 60 and retaining the binding affinity to TGFβ;
- (11) B2F6, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 11, preferably comprising a CDR1 set forth in SEQ ID NO:
- 61, a CDR2 set forth in SEQ ID NO:
- 62, and a CDR3 set forth in SEQ ID NO:
- 63, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 61, the CDR2 set forth in SEQ ID NO:
- 62, and/or the CDR3 set forth in SEQ ID NO:
- 63 and retaining the binding affinity to TGFβ;
- (12) B2H1, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 12, preferably comprising a CDR1 set forth in SEQ ID NO:
- 64, a CDR2 set forth in SEQ ID NO:
- 65, and a CDR3 set forth in SEQ ID NO:
- 66, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 64, the CDR2 set forth in SEQ ID NO:
- 65, and/or the CDR3 set forth in SEQ ID NO:
- 66 and retaining the binding affinity to TGFβ;
- (13) B2A2, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 13, preferably comprising a CDR1 set forth in SEQ ID NO:
- 67, a CDR2 set forth in SEQ ID NO:
- 68, and a CDR3 set forth in SEQ ID NO:
- 69, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 67, the CDR2 set forth in SEQ ID NO:
- 68, and/or the CDR3 set forth in SEQ ID NO:
- 69 and retaining the binding affinity to TGFβ;
- (14) B3D2, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 14, preferably comprising a CDR1 set forth in SEQ ID NO:
- 70, a CDR2 set forth in SEQ ID NO:
- 71, and a CDR3 set forth in SEQ ID NO:
- 72, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 70, the CDR2 set forth in SEQ ID NO:
- 71, and/or the CDR3 set forth in SEQ ID NO:
- 72 and retaining the binding affinity to TGFβ;
- (15) B3C5, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 15, preferably comprising a CDR1 set forth in SEQ ID NO:
- 73, a CDR2 set forth in SEQ ID NO:
- 74, and a CDR3 set forth in SEQ ID NO:
- 75, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 73, the CDR2 set forth in SEQ ID NO:
- 74, and/or the CDR3 set forth in SEQ ID NO:
- 75 and retaining the binding affinity to TGFβ;
- (16) B2C9, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 3, preferably comprising a CDR1 set forth in SEQ ID NO:
- 37, a CDR2 set forth in SEQ ID NO:
- 38, and a CDR3 set forth in SEQ ID NO:
- 39, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 37, the CDR2 set forth in SEQ ID NO:
- 38, and/or the CDR3 set forth in SEQ ID NO:
- 39 and retaining the binding affinity to TGFβ, and
- (17) B3F1, comprising a CDR1, a CDR2, and a CDR3 comprised in a sequence set forth in SEQ ID NO:
- 17, preferably comprising a CDR1 set forth in SEQ ID NO:
- 79, a CDR2 set forth in SEQ ID NO:
- 80, and a CDR3 set forth in SEQ ID NO:
- 81, or a variant thereof according to the Kabat numbering system and the IMGT numbering system, wherein the variant is an amino acid sequence having one or more (preferably 1, 2 or 3) conservative amino acid mutations (preferably substitutions, insertions or deletions) as compared to the CDR1 set forth in SEQ ID NO:
- 79, the CDR2 set forth in SEQ ID NO:
- 80, and/or the CDR3 set forth in SEQ ID NO:
- 81 and retaining the binding affinity to TGFβ.
160 more elements
(canceled)
Dependencies are inferred from the claim text.