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US 2022/0064312 A1Published application
Novel Anti-CCR8 Antibody
AssigneesShionogi & Co., Ltd., Osaka University
InventorsMai Yoshikawa, Tatsuya Takahashi, Junji Onoda, Sunao Imai, Etsuo Nakamura, Kentaro Furukawa, Tsuguo Miyauchi, Tetsuya Yoshida, Morio Nagira, Naganari Ohkura, Atsushi Tanaka, Shimon Sakaguchi, Hisashi Wada, Atsunari Kawashima
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Abstract
Disclosed is a novel anti-CCR8 antibody. The antibody can be used for treating or preventing cancers or the like.
Claims36
1:
- A monoclonal antibody or an antibody fragment thereof that binds to CCR8, which recognizes tyrosine at position 17 in the amino acid sequence set forth in SEQ ID NO:
- 1.
2:
- The antibody or an antibody fragment thereof according to claim 1, which is a neutralizing antibody.
3:
- The antibody or an antibody fragment thereof according to claim 1, which further recognizes one or more of amino acids at positions 94 to 107 in the amino acid sequence set forth in SEQ ID NO:
- 1.
4:
- The antibody or an antibody fragment thereof according to claim 1, which further recognizes one or more of amino acids at positions 172 to 202 in the amino acid sequence set forth in SEQ ID NO:
- 1.
5:
- The antibody or an antibody fragment thereof according to claim 1, which recognizes one or more amino acids of isoleucine at position 20, serine at position 22, lysine at position 35, leucine at position 181, cysteine at position 183, and asparagine at position 188 in the amino acid sequence set forth in SEQ ID NO:
- 1.
6:
- The antibody or an antibody fragment thereof according to claim 1, which is a humanized monoclonal antibody or an antibody fragment thereof.
7:
- The monoclonal antibody or an antibody fragment thereof that binds to CCR8, having:
- 1) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 4 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 5 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 7 optionally having deletion, substitution, insertion and/or addition of one or two amino acids;
- 2) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 4 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 8 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 7 optionally having deletion, substitution, insertion and/or addition of one or two amino acids;
- 3) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 9 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 10 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 8 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 11 optionally having deletion, substitution, insertion and/or addition of one or two amino acids;
- 4) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 10 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 12 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 13 optionally having deletion, substitution, insertion and/or addition of one or two amino acids;
- 5) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 14 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 15 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 16 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 17 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 18 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 19 optionally having deletion, substitution, insertion and/or addition of one or two amino acids;
- or
- 6) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 20 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 21 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 22 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 23 optionally having deletion, substitution, insertion and/or addition of one or two amino acids,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 24 optionally having deletion, substitution, insertion and/or addition of one or two amino acids, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 25 optionally having deletion, substitution, insertion and/or addition of one or two amino acids.
83 more elements
8:
- The antibody or an antibody fragment thereof according to claim 7, having:
- 1) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 4, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 5,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 7,
- wherein one or more of the following substitutions are optionally present:
- A) substitution of asparagine with lysine at position 10 in the amino acid sequence of SEQ ID NO:
- 2,
- B) substitution of glycine with glutamine, threonine, alanine, lysine, leucine or arginine at position 11 in the amino acid sequence of SEQ ID NO:
- 2,
- C) substitution of asparagine with glutamine at position 4 in the amino acid sequence of SEQ ID NO:
- 3,
- D) substitution of leucine with isoleucine at position 5 in the amino acid sequence of SEQ ID NO:
- 3,
- E) substitution of leucine with isoleucine at position 4 in the amino acid sequence of SEQ ID NO:
- 4,
- F) substitution of tyrosine with phenylalanine at position 6 in the amino acid sequence of SEQ ID NO:
- 4,
- G) substitution of serine with threonine at position 16 in the amino acid sequence of SEQ ID NO:
- 6, and
- H) substitution of aspartic acid with glutamic acid at position 19 in the amino acid sequence of SEQ ID NO:
- 6;
- 2) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 4, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 8,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 7;
- 3) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 9, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 10, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 8,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 11,
- wherein one or more of the following substitutions are optionally present:
- A) substitution of serine with threonine at position 2 in the amino acid sequence of SEQ ID NO:
- 2,
- B) substitution of serine with threonine at position 3 in the amino acid sequence of SEQ ID NO:
- 2,
- C) substitution of serine with threonine at position 5 in the amino acid sequence of SEQ ID NO:
- 2,
- D) substitution of glutamine with asparagine at position 2 in the amino acid sequence of SEQ ID NO:
- 10,
- E) substitution of threonine with serine at position 1 in the amino acid sequence of SEQ ID NO:
- 8,
- F) substitution of alanine with valine at position 14 in the amino acid sequence of SEQ ID NO:
- 6,
- G) substitution of lysine with arginine at position 18 in the amino acid sequence of SEQ ID NO:
- 6,
- H) substitution of aspartic acid with glutamic acid at position 19 in the amino acid sequence of SEQ ID NO:
- 6,
- I) substitution of asparagine with glutamine at position 5 in the amino acid sequence of SEQ ID NO:
- 11, and
- J) substitution of tyrosine with phenylalanine at position 12 in the amino acid sequence of SEQ ID NO:
- 11;
- 4) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 10, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 12,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 13;
- 5) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 14,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 15, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 16, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 17,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 18, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 19;
- or
- 6) a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 20,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 21, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 22, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 23,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 24, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 25.
121 more elements
9:
- The antibody or an antibody fragment thereof according to claim 8, having:
- a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 3, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 4, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 5,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 7,
- wherein one or more of the following substitutions are present:
- A) substitution of asparagine with lysine at position 10 in the amino acid sequence of SEQ ID NO:
- 2;
- B) substitution of glycine with glutamine, threonine, alanine, lysine, leucine or arginine at position 11 in the amino acid sequence of SEQ ID NO:
- 2;
- C) substitution of asparagine with glutamine at position 4 in the amino acid sequence of SEQ ID NO:
- 3;
- D) substitution of leucine with isoleucine at position 5 in the amino acid sequence of SEQ ID NO:
- 3;
- E) substitution of leucine with isoleucine at position 4 in the amino acid sequence of SEQ ID NO:
- 4;
- F) substitution of tyrosine with phenylalanine at position 6 in the amino acid sequence of SEQ ID NO:
- 4;
- G) substitution of serine with threonine at position 16 in the amino acid sequence of SEQ ID NO:
- 6;
- and
- H) substitution of aspartic acid with glutamic acid at position 19 in the amino acid sequence of SEQ ID NO:
- 6.
30 more elements
10:
- The antibody or an antibody fragment thereof according to claim 9, wherein one or more of the following substitutions are present:
- A) substitution of asparagine with lysine at position 10 in the amino acid sequence of SEQ ID NO:
- 2;
- B) substitution of glycine with leucine or arginine at position 11 in the amino acid sequence of SEQ ID NO:
- 2;
- and
- C) substitution of asparagine with glutamine at position 4 in the amino acid sequence of SEQ ID NO:
- 3.
5 more elements
11:
- The antibody or an antibody fragment thereof according to claim 9, wherein
- asparagine at position 4 in the amino acid sequence of SEQ ID NO:
- 3 is substituted with glutamine;
- and
- further, any one of the following substitutions are optionally present:
- A) substitution of asparagine with lysine at position 10 in the amino acid sequence of SEQ ID NO:
- 2;
- and
- B) substitution of glycine with leucine or arginine at position 11 in the amino acid sequence of SEQ ID NO:
- 2.
7 more elements
12:
- The antibody or an antibody fragment thereof according to claim 11, wherein asparagine at position 4 in the amino acid sequence of SEQ ID NO:
- 3 is substituted with glutamine;
- and glycine at position 11 in the amino acid sequence of SEQ ID NO:
- 2 is substituted with arginine.
1 more element
13:
- The antibody or an antibody fragment thereof according to claim 8, having:
- a light chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 2,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 9, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 10, and
- a heavy chain variable region including
- a CDR1 having the amino acid sequence of SEQ ID NO:
- 8,
- a CDR2 having the amino acid sequence of SEQ ID NO:
- 6, and
- a CDR3 having the amino acid sequence of SEQ ID NO:
- 11,
- wherein one or more of the following substitutions are present:
- A) substitution of serine with threonine at position 2 in the amino acid sequence of SEQ ID NO:
- 2;
- B) substitution of serine with threonine at position 3 in the amino acid sequence of SEQ ID NO:
- 2;
- C) substitution of serine with threonine at position 5 in the amino acid sequence of SEQ ID NO:
- 2;
- D) substitution of glutamine with asparagine at position 2 in the amino acid sequence of SEQ ID NO:
- 10;
- E) substitution of threonine with serine at position 1 in the amino acid sequence of SEQ ID NO:
- 8;
- F) substitution of alanine with valine at position 14 in the amino acid sequence of SEQ ID NO:
- 6;
- G) substitution of lysine with arginine at position 18 in the amino acid sequence of SEQ ID NO:
- 6;
- H) substitution of aspartic acid with glutamic acid at position 19 in the amino acid sequence of SEQ ID NO:
- 6;
- I) substitution of asparagine with glutamine at position 5 in the amino acid sequence of SEQ ID NO:
- 11;
- and
- J) substitution of tyrosine with phenylalanine at position 12 in the amino acid sequence of SEQ ID NO:
- 11.
34 more elements
14:
- The antibody or an antibody fragment thereof according to claim 7, which is a humanized monoclonal antibody or an antibody fragment thereof.
15:
- The antibody or an antibody fragment thereof according to claim 14, having:
- a light chain variable region having
- the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45, or 47, or
- an amino acid sequence having 95% or more identity to the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45, or 47;
- and
- a heavy chain variable region having
- the amino acid sequence of SEQ ID NO:
- 41 or 46, or
- an amino acid sequence having 95% or more identity to the amino acid sequence of SEQ ID NO:
- 41 or 46.
9 more elements
16:
- The antibody or an antibody fragment thereof according to claim 14, having:
- 1) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 40, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 2) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 3) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 43, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 4) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 44, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 5) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 45, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 6) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 47, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41;
- 7) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 40, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46;
- 8) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46;
- 9) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 43, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46;
- 10) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 44, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46;
- 11) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 45, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46;
- or
- 12) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 47, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 46,
- wherein one or more of the following substitutions are optionally present:
- A) substitution of asparagine with lysine at position 33 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- B) substitution of glycine with glutamine, threonine, alanine, lysine, leucine or arginine at position 34 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- C) substitution of asparagine with glutamine at position 58 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- D) substitution of leucine with isoleucine at position 59 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- E) substitution of leucine with isoleucine at position 97 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- F) substitution of tyrosine with phenylalanine at position 99 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- G) substitution of serine with threonine at position 65 in the amino acid sequence of SEQ ID NO:
- 41 or 46;
- and
- H) substitution of aspartic acid with glutamic acid at position 68 in the amino acid sequence of SEQ ID NO:
- 41 or 46.
65 more elements
17:
- The antibody or an antibody fragment thereof according to claim 16, wherein one or more of the following substitutions are present:
- A) substitution of asparagine with lysine at position 33 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- B) substitution of glycine with glutamine, threonine, alanine, lysine, leucine or arginine at position 34 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- C) substitution of asparagine with glutamine at position 58 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- D) substitution of leucine with isoleucine at position 59 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- E) substitution of leucine with isoleucine at position 97 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- F) substitution of tyrosine with phenylalanine at position 99 in the amino acid sequence of SEQ ID NO:
- 40, 42, 43, 44, 45 or 47;
- G) substitution of serine with threonine at position 65 in the amino acid sequence of SEQ ID NO:
- 41 or 46;
- and
- H) substitution of aspartic acid with glutamic acid at position 68 in the amino acid sequence of SEQ ID NO:
- 41 or 46.
15 more elements
18:
- The antibody or an antibody fragment thereof according to claim 17, having
- a light chain variable region having the amino acid sequence of SEQ ID NO:
- 40 or 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41,
- wherein one or more of the following substitutions are present:
- A) substitution of asparagine with lysine at position 33 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- B) substitution of glycine with glutamine, threonine, alanine, lysine, leucine or arginine at position 34 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- C) substitution of asparagine with glutamine at position 58 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- D) substitution of leucine with isoleucine at position 59 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- E) substitution of leucine with isoleucine at position 97 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- F) substitution of tyrosine with phenylalanine at position 99 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- G) substitution of serine with threonine at position 65 in the amino acid sequence of SEQ ID NO:
- 41;
- and
- H) substitution of aspartic acid with glutamic acid at position 68 in the amino acid sequence of SEQ ID NO:
- 41.
20 more elements
19:
- The antibody or an antibody fragment thereof according to claim 17, having
- a light chain variable region having the amino acid sequence of SEQ ID NO:
- 40 or 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41,
- wherein one or more of the following substitutions are present:
- A) substitution of asparagine with lysine at position 33 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- B) substitution of glycine with leucine or arginine at position 34 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- and
- C) substitution of asparagine with glutamine at position 58 in the amino acid sequence of SEQ ID NO:
- 40 or 42.
10 more elements
20:
- The antibody or an antibody fragment thereof according to claim 17, having:
- a light chain variable region having the amino acid sequence of SEQ ID NO:
- 40 or 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41,
- wherein asparagine at position 58 in the amino acid sequence of SEQ ID NO:
- 40 or 42 is substituted with glutamine, and
- further, any one of the following substitutions are optionally present:
- A) substitution of asparagine with lysine at position 33 in the amino acid sequence of SEQ ID NO:
- 40 or 42;
- and
- B) substitution of glycine with leucine or arginine at position 34 in the amino acid sequence of SEQ ID NO:
- 40 or 42.
10 more elements
21:
- The antibody or an antibody fragment thereof according to claim 20, having
- a light chain variable region having the amino acid sequence of SEQ ID NO:
- 42, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41,
- wherein asparagine at position 58 in the amino acid sequence of SEQ ID NO:
- 42 is substituted with glutamine, and glycine at position 34 in the amino acid sequence of SEQ ID NO:
- 42 is substituted with arginine.
5 more elements
22:
- The antibody or an antibody fragment thereof according to claim 20, having
- a light chain variable region having the amino acid sequence of SEQ ID NO:
- 59, and a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 41.
1 more element
23:
- The antibody or an antibody fragment thereof according to claim 14, having:
- a light chain variable region having
- the amino acid sequence of SEQ ID NO:
- 54, 55, or, 56, or
- an amino acid sequence having 95% or more identity to the amino acid sequence of SEQ ID NO:
- 54, 55, or, 56;
- and
- a heavy chain variable region having
- the amino acid sequence of SEQ ID NO:
- 57 or 58, or
- an amino acid sequence having 95% or more identity to the amino acid sequence of SEQ ID NO:
- 57 or 58.
9 more elements
24:
- The antibody or an antibody fragment thereof according to claim 14, having
- 1) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 54, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 57;
- 2) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 55, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 57;
- 3) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 56, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 57;
- 4) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 54, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 58;
- 5) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 55, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 58;
- 6) a light chain variable region having the amino acid sequence of SEQ ID NO:
- 56, and
- a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 58,
- wherein one or more of the following substitutions are optionally present:
- A) substitution of serine with threonine at position 25 in the amino acid sequence of SEQ ID NO:
- 54, 55 or 56;
- B) substitution of serine with threonine at position 26 in the amino acid sequence of SEQ ID NO:
- 54, 55 or 56;
- C) substitution of serine with threonine at position 28 in the amino acid sequence of SEQ ID NO:
- 54, 55 or 56;
- D) substitution of glutamine with asparagine at position 95 in the amino acid sequence of SEQ ID NO:
- 54, 55 or 56;
- E) substitution of threonine with serine at position 31 in the amino acid sequence of SEQ ID NO:
- 57 or 58;
- F) substitution of alanine with valine at position 63 in the amino acid sequence of SEQ ID NO:
- 57 or 58;
- G) substitution of lysine with arginine at position 67 in the amino acid sequence of SEQ ID NO:
- 57 or 58;
- H) substitution of aspartic acid with glutamic acid at position 68 in the amino acid sequence of SEQ ID NO:
- 57 or 58;
- I) substitution of asparagine with glutamine at position 99 in the amino acid sequence of SEQ ID NO:
- 57 or 58;
- and
- J) substitution of tyrosine with phenylalanine at position 105 in the amino acid sequence of SEQ ID NO:
- 57 or 58.
44 more elements
25:
- The antibody or an antibody fragment thereof according to claim 24, having a light chain variable region having the amino acid sequence of SEQ ID NO:
- 56, and a heavy chain variable region having the amino acid sequence of SEQ ID NO:
- 57, wherein one or more of the following substitutions are optionally present:
- A) substitution of serine with threonine at position 25 in the amino acid sequence of SEQ ID NO:
- 56;
- B) substitution of serine with threonine at position 26 in the amino acid sequence of SEQ ID NO:
- 56;
- C) substitution of serine with threonine at position 28 in the amino acid sequence of SEQ ID NO:
- 56;
- D) substitution of glutamine with asparagine at position 95 in the amino acid sequence of SEQ ID NO:
- 56;
- E) substitution of threonine with serine at position 31 in the amino acid sequence of SEQ ID NO:
- 57;
- F) substitution of alanine with valine at position 63 in the amino acid sequence of SEQ ID NO:
- 57;
- G) substitution of lysine with arginine at position 67 in the amino acid sequence of SEQ ID NO:
- 57;
- H) substitution of aspartic acid with glutamic acid at position 68 in the amino acid sequence of SEQ ID NO:
- 57;
- I) substitution of asparagine with glutamine at position 99 in the amino acid sequence of SEQ ID NO:
- 57;
- and
- J) substitution of tyrosine with phenylalanine at position 105 in the amino acid sequence of SEQ ID NO:
- 57.
21 more elements
26:
- The antibody or an antibody fragment thereof according to claim 14, further having:
- a light chain constant region having the amino acid sequence of SEQ ID NO:
- 52, and
- a heavy chain constant region having the amino acid sequence of SEQ ID NO:
- 53,
- wherein lysine is optionally added to the C-terminal end of SEQ ID NO:
- 53.
4 more elements
27:
- A pharmaceutical composition comprising the antibody or an antibody fragment thereof according to claim 1.
28:
- A method of inhibiting a binding of CCR8 to a CCR8 ligand in a subject, comprising administering an effect amount of the antibody or an antibody fragment thereof according to claim 1 to the subject.
29:
- A pharmaceutical composition comprising the antibody or an antibody fragment thereof according to claim 1, wherein the antibody or an antibody fragment thereof is a neutralizing antibody.
30:
- A pharmaceutical composition comprising the monoclonal antibody or an antibody fragment thereof according to claim 1 that binds to CCR8 and recognizes tyrosine at position 17 in the amino acid sequence set forth in SEQ ID NO:
- 1.
31:
- A method of inhibiting a binding of CCR8 to a CCR8 ligand in a subject, comprising administering an effect amount of the pharmaceutical composition according to claim 30 to the subject.
32:
- The pharmaceutical composition according to claim 27, wherein the antibody has ADCC activity.
33:
- The pharmaceutical composition according to claim 27, wherein the antibody is an IgG antibody.
34:
- A method of treating cancer in a subject in need thereof, comprising administering an effect amount of the pharmaceutical composition according to claim 33 to the subject.
35:
- A polynucleotide encoding a light chain variable region or a heavy chain variable region of the antibody according to claim 7.
36:
- An expression vector comprising the polynucleotide according to claim 35.