Anti-CD200R1 antibody and its applications

Abstract

The present invention relates to an anti-CD200R1 antibody or an antigen-binding fragment thereof, nucleic acids encoding them, an expression vector containing the nucleic acid, host cells into which the nucleic acid or expression vector has been introduced, a method for producing the antibody or the antigen-binding fragment, a bi- or multi-specific antibody containing the antibody or the antigen-binding fragment, a chimeric antigen receptor (CAR) containing the antibody or the antigen-binding fragment, immune cells expressing the antibody or the antigen-binding fragment or a chimeric antigen receptor containing the same, an immunosuppressive composition containing the antibody or the antigen-binding fragment, and pharmaceutical uses.

Claims

1. An antibody or antigen-binding fragment that specifically binds to CD200R1 containing the following: Heavy chain CDR1 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1 to 8, SEQ ID NOs: 100 to 103, and SEQ ID NO: 158; A heavy chain CDR2 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 9 to 21, SEQ ID NOs: 104 to 109, and SEQ ID NO: 159; A heavy chain CDR3 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs. 22 to 35, SEQ ID NOs. 110 to 115, SEQ ID NOs. 160, SEQ ID NOs. 172 and 173; Light chain CDR1 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 36 to 47, SEQ ID NOs: 116 to 122, SEQ ID NO: 161, SEQ ID NO: 192, and SEQ ID NO: 193; Light chain CDR2 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 48 to 58, SEQ ID NOs: 123 to 127, SEQ ID NOs: 162, and SEQ ID NOs: 194; and A light chain CDR3 comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs. 59 to 70, SEQ ID NOs. 128 to 134, SEQ ID NOs. 163, SEQ ID NOs. 174 to 183, SEQ ID NOs. 195, and SEQ ID NOs.

196.

2. The antibody or antigen-binding fragment according to claim 1, comprising a heavy chain variable region containing one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 71 to 85, SEQ ID NOs: 135 to 141, SEQ ID NOs: 149 to 153, SEQ ID NO: 184, and SEQ ID NO:

185.

3. The antibody or antigen-binding fragment according to claim 1, comprising a light chain variable region containing one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 86 to 99, SEQ ID NOs: 142 to 148, SEQ ID NOs: 154 to 157, SEQ ID NOs: 186 to 191, and SEQ ID NOs: 197 to 200.

4. The antibody or antigen-binding fragment according to claim 1, comprising a heavy chain variable region and a light chain variable region selected from the group consisting of the above: - The heavy chain variable region of Sequence ID No. 71 and the light chain variable region of Sequence ID No. 86; - The heavy chain variable region of Sequence ID No. 72 and the light chain variable region of Sequence ID No. 87; - The heavy chain variable region of Sequence ID No. 73 and the light chain variable region of Sequence ID No. 88; - Heavy chain variable region of Sequence ID No. 74 and light chain variable region of Sequence ID No. 89; - The heavy chain variable region of Sequence ID No. 75 and the light chain variable region of Sequence ID No. 90; - The heavy chain variable region of SEQ ID NO: 76 and the light chain variable region of SEQ ID NO: 91; - The heavy chain variable region of Sequence ID No. 77 and the light chain variable region of Sequence ID No. 92; - The heavy chain variable region of Sequence ID No. 78 and the light chain variable region of Sequence ID No. 93; - The heavy chain variable region of Sequence ID No. 79 and the light chain variable region of Sequence ID No. 94; - The heavy chain variable region of SEQ ID NO: 80 and the light chain variable region of SEQ ID NO: 95; - The heavy chain variable region of sequence number 81 and the light chain variable region of sequence number 96; - The heavy chain variable region of Sequence ID No. 82 and the light chain variable region of Sequence ID No. 97; - The heavy chain variable region of Sequence ID No. 83 and the light chain variable region of Sequence ID No. 98; - The heavy chain variable region of Sequence ID No. 84 and the light chain variable region of Sequence ID No. 94; - The heavy chain variable region of Sequence ID No. 85 and the light chain variable region of Sequence ID No. 99; - The heavy chain variable region of sequence number 135 and the light chain variable region of sequence number 142; - The heavy chain variable region of sequence number 136 and the light chain variable region of sequence number 143; - The heavy chain variable region of sequence number 137 and the light chain variable region of sequence number 144; - The heavy chain variable region of sequence number 138 and the light chain variable region of sequence number 145; - The heavy chain variable region of sequence number 139 and the light chain variable region of sequence number 146; - Heavy chain variable region of SEQ ID NO: 140 and light chain variable region of SEQ ID NO: 147; - The heavy chain variable region of sequence number 141 and the light chain variable region of sequence number 148; - Heavy chain variable region of Sequence ID No. 150 and light chain variable region of Sequence ID No. 155; - Heavy chain variable region of Sequence ID No. 151 and light chain variable region of Sequence ID No. 155; - The heavy chain variable region of Sequence ID No. 152 and the light chain variable region of Sequence ID No. 157; - Heavy chain variable region of Sequence ID No. 153 and light chain variable region of Sequence ID No. 157; - Heavy chain variable region of Sequence ID No. 151 and light chain variable region of Sequence ID No. 157; - The heavy chain variable region of sequence number 152 and the light chain variable region of sequence number 155; - Heavy chain variable region of Sequence ID No. 184 and light chain variable region of Sequence ID No. 155; - Heavy chain variable region of SEQ ID NO: 150 and light chain variable region of SEQ ID NO: 186; - The heavy chain variable region of Sequence ID No. 150 and the light chain variable region of Sequence ID No. 187; - Heavy chain variable region of SEQ ID NO: 150 and light chain variable region of SEQ ID NO: 188; - The heavy chain variable region of Sequence ID No. 150 and the light chain variable region of Sequence ID No. 189; - Heavy chain variable region of Sequence ID No. 185 and light chain variable region of Sequence ID No. 155; - The heavy chain variable region of sequence number 150 and the light chain variable region of sequence number 190; - The heavy chain variable region of sequence number 185 and the light chain variable region of sequence number 186; - Heavy chain variable region of Sequence ID No. 185 and light chain variable region of Sequence ID No. 187; - Heavy chain variable region of SEQ ID NO: 150 and light chain variable region of SEQ ID NO: 191; - The heavy chain variable region of Sequence ID No. 185 and the light chain variable region of Sequence ID No. 190; - The heavy chain variable region of sequence number 185 and the light chain variable region of sequence number 191; - The heavy chain variable region of Sequence ID No. 79 and the light chain variable region of Sequence ID No. 197; - The heavy chain variable region of Sequence ID No. 79 and the light chain variable region of Sequence ID No. 198; - The heavy chain variable region of Sequence ID No. 79 and the light chain variable region of Sequence ID No. 199; and - The heavy chain variable region of sequence number 79 and the light chain variable region of sequence number 200.

5. The antibody or antigen-binding fragment according to claim 1, comprising the single-chain Fvs(scFv), single-chain antibody, Fab, F(ab'), and disulfide-linked Fvs(sdFv).

6. The aforementioned scFv is a heavy chain variable region comprising one or more amino acid sequences selected from the group consisting of SEQ ID NOs. 71 to 85, SEQ ID NOs. 135 to 141, SEQ ID NOs. 149 to 153, SEQ ID NOs. 184, and SEQ ID NOs. 185; and The antibody or antigen-binding fragment according to claim 5, characterized in that a light chain variable region containing one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 86 to 99, SEQ ID NOs: 142 to 148, SEQ ID NOs: 154 to 157, SEQ ID NOs: 186 to 191, and SEQ ID NOs: 197 to 200 is linked via a linker.

7. A nucleic acid encoding the antibody or antigen-binding fragment according to any one of claims 1 to 6.

8. A recombinant expression vector comprising the nucleic acid described in claim 7.

9. Host cells transfected with the recombinant expression vector described in claim 8.

10. A method for producing an antibody that specifically binds to CD200R1 or an antigen-binding fragment thereof, comprising the steps of: culturing the host cells described in claim 9 to produce an antibody; and separating and purifying the produced antibody.

11. A bispecific or multiplespecific antibody comprising the antibody according to any one of claims 1 to 6 or the antigen-binding fragment thereof.

12. A chimeric antigen receptor (CAR) comprising an extracellular domain containing an antigen-binding site as described in any one of claims 1 to 6, a transmembrane domain, and an intracellular signaling domain.

13. Immune cells into which the chimeric antigen receptor (CAR) described in claim 12 has been introduced.

14. The immune cell according to claim 13, wherein the immune cell is a regulatory T cell.

15. A composition for the prevention or treatment of an immune disease or inflammatory disease, comprising the antibody according to any one of claims 1 to 6, a bispecific or multispecific antibody comprising the antibody or the antigen-binding fragment, a chimeric antigen receptor comprising the antibody or the antigen-binding fragment, or an immune cell comprising the chimeric antigen receptor.

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