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US 12,180,287 B2Granted
Anti-c-Met antibody showing enhanced stability or antigen-binding fragments thereof
AssigneeHelixmith Co., Ltd
InventorsJae-Gyun Jeong, Junghun Lee, Sang Ho Kwon
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Abstract
The present invention relates to an anti-c-Met antibody showing enhanced stability or antigen-binding fragments thereof, and the use thereof. Compared to 1E4 which is a parent antibody, the anti-c-Met antibody showing enhanced stability or antigen-binding reduced immunogenicity. Therefore, the anti-c-Met antibody or antigen-binding fragments thereof according to the present invention exhibits, in anti-c-Met antibody development, excellent properties such as reduced production cost, inhibition of reduced efficacy, reduced side effects and the like.
Claims5
An anti-c-Met antibody or an antigen-binding fragment comprising:
- (a) an immunoglobulin heavy chain variable domain comprising the structure of FRH1-CDRH1-FRH2-CDRH2-FRH3-CDRH3-FRH4;
- and
- (b) an immunoglobulin light chain variable domain comprising the structure of FRL1-CDRL1-FRL2-CDRL2-FRL3-CDRL3-FRL4:
- wherein the CDRH1, the CDRH2, and the CDRH3 comprise the amino acid sequences of SEQ ID NOS:
- 1, 2, and 3, respectively, and the CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOS:
- 4, 5, and 6, respectively,
- wherein (a) and (b) are selected from the following group:
- i) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 11 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- ii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 12 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- iii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 12 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- iv) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- v) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18
- vi) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 21;
- vii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 15 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- viii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 15 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- ix) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 16 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- and
- x) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 16 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18.
35 more elements
An anti-c-Met antibody or antigen-binding fragment, comprising:
- (a) a heavy chain variable domain comprising CDRH1 (complementarity determining region 1 of heavy chain) of SEQ ID NO:
- 1, CDRH2 of SEQ ID NO:
- 2, and CDRH3 of SEQ ID NO:
- 3;
- (b) an immunoglobulin heavy chain constant domain comprising CH1 (constant domain 1 of heavy chain) of SEQ ID NO:
- 7;
- (c) an immunoglobulin light chain variable domain comprising CDRL1 (complementarity determining region 1 of light chain) of SEQ ID NO:
- 4, CDRL2 of SEQ ID NO:
- 5, and CDRL3 of SEQ ID NO:
- 6;
- and
- (d) an immunoglobulin light chain constant domain comprising Ck (kappa-constant domain) of SEQ ID NO:
- 8,
- wherein at least one of the amino acid residue at position 97 in CH1 of SEQ ID NO:
- 7 and the amino acid residue at position 2 in Ck of SEQ ID NO:
- 8 is mutated by substitution with arginine or threonine,
- wherein (a) and (b) are selected from the following group:
- i) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 11 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- ii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 12 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- iii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 12 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- iv) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- v) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18 vi) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 14 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 21;
- vii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 15 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- viii) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 15 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18;
- ix) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 16 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 17;
- and
- x) immunoglobulin heavy chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 16 and immunoglobulin light chain variable domain comprising an amino acid sequence of SEQ ID NO:
- 18.
44 more elements
Dependencies are inferred from the claim text.