US 11,912,775 B2
Anti-human CCR1 monoclonal antibody
Masayuki Kai, Tokyo (JP); Shinya Ogawa, Tokyo (JP); Makoto Taketo, Kyoto (JP); Kenji Kawada, Kyoto (JP); Hideyo Hirai, Kyoto (JP); Yoshiharu Sakai, Kyoto (JP); and Taira Maekawa, Kyoto (JP)
Assigned to KYOWA KIRIN CO., LTD., Tokyo (JP); and KYOTO UNIVERSITY, Kyoto (JP)
Appl. No. 16/631,655
Filed by KYOWA KIRIN CO., LTD., Tokyo (JP); and KYOTO UNIVERSITY, Kyoto (JP)
PCT Filed Jul. 18, 2018, PCT No. PCT/JP2018/026958
§ 371(c)(1), (2) Date Jan. 16, 2020,
PCT Pub. No. WO2019/017401, PCT Pub. Date Jan. 24, 2019.
Claims priority of application No. 2017-139157 (JP), filed on Jul. 18, 2017.
Prior Publication US 2020/0199240 A1, Jun. 25, 2020
Int. Cl. C07K 16/24 (2006.01); C07K 16/28 (2006.01); A61P 43/00 (2006.01); A61K 39/395 (2006.01); C12N 5/12 (2006.01); G01N 33/577 (2006.01)
CPC C07K 16/2866 (2013.01) [A61K 39/395 (2013.01); A61P 43/00 (2018.01); C12N 5/12 (2013.01); G01N 33/577 (2013.01)] 17 Claims
 
1. A monoclonal antibody or an antibody fragment thereof which binds to an extracellular region of a human CC chemokine receptor 1 (CCR1) and inhibits activation of the human CCR1 by a human CC chemokine ligand 15 (CCL15)
wherein the monoclonal antibody is any one antibody selected from the following (a) to (n);
(a) an antibody in which the CDRs 1 to 3 of VH comprise the amino acid sequences of SEQ ID NOs: 75, 76, and 77, respectively, and in which the CDRs 1 to 3 of VL comprise the amino acid sequences of SEQ ID NOs: 78, 79, and 80, respectively,
(b) an antibody in which the CDR1 of VH comprises the amino acid sequence of SEQ ID NO: 75, the CDR2 of VH comprises the amino acid sequence of SEQ ID NO: 76 or the amino acid sequence in which at least one modification selected from modifications of substituting Ile at a position 2 with Thr, Val at a position 9 with Ala, Phe at a position 14 with Ala, and Ile at a position 15 with Ala is introduced in the amino acid sequence of SEQ ID NO: 76, and the CDR3 of VH comprises the amino acid sequence of SEQ ID NO: 77 or the amino acid sequence in which at least one of modifications of substituting Tyr at a position 5 with Ala and Thr at a position 7 with Ala is introduced in the amino acid sequence of SEQ ID NO: 77, and in which the CDR1 of VL comprises the amino acid sequence of SEQ ID NO: 126 or the amino acid sequence in which a modification of substituting Phe at a position 15 with Ala is introduced in the amino acid sequence SEQ ID NO: 126, the CDR2 of VL comprises the amino acid sequence of SEQ ID NO: 127 or the amino acid sequence in which at least one of modifications of substituting Val at a position 2 with Ile, and Arg at a position 5 with Lys is introduced in the amino acid sequence of SEQ ID NO: 127, and the CDR3 of VL comprises the amino acid sequence of SEQ ID NO: 128,
(c) an antibody in which the CDRs 1 to 3 of VH comprise the amino acid sequences of SEQ ID NOs: 75, 131, and 77, respectively, and in which the CDRs 1 to 3 of VL comprise the amino acid sequences of SEQ ID NOs: 126, 134, and 128, respectively,
(d) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 53, and in which VL comprises the amino acid sequence of SEQ ID NO: 54,
(e) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 130, and in which VL comprises the amino acid sequence of SEQ ID NO: 133,
(f) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 136 or the amino acid sequence in which at least one of amino acid modifications of substituting Glu at a position 6 with Gln, Leu at a position 20 with Ile, Gly at a position 27 with Phe, Val at a position 29 with Leu, Ser at a position 30 with Asn, Ile at a position 37 with Val, Ile at a position 48 with Leu, Val at a position 67 with Leu, Val at a position 71 with Lys, Thr at a position 73 with Asp, Asn at a position 76 with Ser, Phe at a position 78 with Val, Leu at a position 80 with Phe, Leu at a position 82 with Met, Val at a position 85 with Leu, Val at a position 92 with Ile, and Arg at a position 97 with Lys is introduced in the amino acid sequence of SEQ ID NO: 136, and in which VL comprises the amino acid sequence of SEQ ID NO: 135 or the amino acid sequence in which at least one of amino acid modifications of substituting Ile at a position 2 with Val, Pro at a position 15 with Leu, Gln at a position 50 with Lys, Tyr at a position 92 with Phe, and Val at a position 109 with Leu is introduced in the amino acid sequence of SEQ ID NO: 135,
(g) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 135,
(h) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 137,
(i) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 138,
(j) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 139,
(k) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 140,
(l) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 141,
(m) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 144, and in which VL comprises the amino acid sequence of SEQ ID NO: 142,
(n) an antibody in which VH comprises the amino acid sequence of SEQ ID NO: 143, and in which VL comprises the amino acid sequence of SEQ ID NO: 142.