NZ739132B2 - Anti-human transferrin receptor antibody permeating blood-brain barrier - Google Patents
Anti-human transferrin receptor antibody permeating blood-brain barrier Download PDFInfo
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- NZ739132B2 NZ739132B2 NZ739132A NZ73913216A NZ739132B2 NZ 739132 B2 NZ739132 B2 NZ 739132B2 NZ 739132 A NZ739132 A NZ 739132A NZ 73913216 A NZ73913216 A NZ 73913216A NZ 739132 B2 NZ739132 B2 NZ 739132B2
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- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
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Abstract
Disclosed is a means that can be used for modifying a biologically or pharmacologically active substance from a form incapable of permeating the blood-brain barrier to a form capable of permeating the blood-brain barrier. Also disclosed is a modified substance obtained by using the means. The means is anti-human transferrin receptor antibody and the modified substance is a molecular conjugate of a biologically active protein or a pharmacologically active low-molecular-weight compound and anti-human transferrin receptor antibody.
Claims (14)
1. An anti-human transferrin receptor antibody, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ 5 ID NO:16 or SEQ ID NO:17 as CDR1, the amino acid sequence set forth as SEQ ID NO:18 or SEQ ID NO:19 or the amino acid sequence Lys-Val- Ser as CDR2, and the amino acid sequence set forth as SEQ ID NO:20 as CDR3; and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:88 or SEQ ID NO:89 as CDR1, the 10 amino acid sequence set forth as SEQ ID NO:90 or SEQ ID NO:91 as CDR2, and the amino acid sequence set forth as SEQ ID NO:92 or SEQ ID NO:93 as CDR3.
2. The anti-human transferrin or antibody according to claim 15 1, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:16 as CDR1, the amino acid sequence set forth SEQ ID NO:18 as CDR2, and the amino acid sequence set forth as SEQ ID NO:20 as CDR3; and the heavy chain variable region ses the amino acid sequence set forth as SEQ ID NO:88 as CDR1, 20 the amino acid ce set forth as SEQ ID NO:90 as CDR2, and the amino acid sequence set forth as SEQ ID NO:92 as CDR3.
3. The anti-human transferrin receptor antibody according to claim 1 or claim 2, wherein the light chain variable region of the antibody 25 comprises an amino acid ce selected from the group consisting of the amino acid sequences set forth as SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, and SEQ ID NO:195, and n the heavy chain le region of the antibody ses an amino acid sequence selected from the group consisting of the amino acid sequences set forth as SEQ ID NO:204, SEQ ID , 5 SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, and SEQ ID NO:209.
4. The anti-human transferrin receptor antibody according to claim 1 or claim 2, selected from the group consisting of (1) to (4) below: 10 (1) an antibody, wherein the light chain variable region thereof comprises the amino acid sequence set forth as SEQ ID NO:191; and wherein the heavy chain variable region thereof comprises the amino acid sequence set forth as SEQ ID NO:205, (2) an antibody, wherein the light chain variable region thereof 15 ses the amino acid sequence set forth as SEQ ID NO:193; and wherein the heavy chain variable region thereof comprises the amino acid sequence set forth as SEQ ID NO:205, (3) an antibody, wherein the light chain variable region thereof comprises the amino acid sequence set forth as SEQ ID NO:194; and 20 wherein the heavy chain variable region thereof comprises the amino acid sequence set forth as SEQ ID NO:205, and (4) an antibody, n the light chain variable region thereof ses the amino acid sequence set forth as SEQ ID NO:195; and wherein the heavy chain variable region thereof comprises the amino acid 25 sequence set forth as SEQ ID NO:205.
5. The anti-human errin receptor antibody ing to claim 1 or claim 2, ed from the group consisting of (1) to (8) below: (1) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:196; and wherein the heavy 5 chain thereof comprises the amino acid ce set forth as SEQ ID NO:210, (2) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:198; and wherein the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID 10 NO:210, (3) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:200; and wherein the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID 15 (4) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:202; and wherein the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID NO:210, (5) an antibody, wherein the light chain thereof comprises the 20 amino acid sequence set forth as SEQ ID NO:196; and wherein the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID (6) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:198; and wherein the heavy 25 chain thereof comprises the amino acid sequence set forth as SEQ ID NO:212, (7) an antibody, wherein the light chain thereof comprises the amino acid sequence set forth as SEQ ID NO:200; and whereof the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID NO:212, and 5 (8) an antibody, wherein the light chain thereof ses the amino acid sequence set forth as SEQ ID NO:202; and wherein the heavy chain thereof comprises the amino acid sequence set forth as SEQ ID 10
6. The anti-human transferrin receptor antibody according to any one of claims 1 to 5, wherein the antibody has an ty to both the extracellular region of human transferrin receptor and the extracellular region of monkey transferrin receptor. 15
7. The anti-human transferrin receptor antibody according to claim 6, wherein the dissociation constant of its x with the extracellular region of human transferrin receptor is not greater than 1?10-8 M, and the dissociation constant of its complex with the extracellular region of monkey transferrin receptor is not greater than 5?10-8 M.
8. The anti-human transferrin receptor antibody according to any one of claims 1 to 7, wherein the antibody is Fab antibody, F(ab')2 antibody, or F(ab') antibody. 25
9. The anti-human transferrin receptor antibody ing to any one of claims 1 to 7, n the antibody is a single-chain antibody selected from the group consisting of scFab, scF(ab'), scF(ab')2 and scFv.
10. The anti-human transferrin or antibody according to claim 9, wherein the light chain and the heavy chain thereof are linked via a 5 linker sequence.
11. The anti-human transferrin receptor antibody according to claim 9, wherein the heavy chain is linked, via a linker sequence, to the light chain on the inal side of the light chain.
12. The anti-human transferrin receptor antibody according to claim 9, wherein the light chain is linked, via a linker sequence, to the heavy chain on the inal side of the heavy chain. 15
13. The anti-human transferrin receptor antibody according to any one of claims 10 to 12, wherein the linker sequence consists of 8 to 50 amino acid residues.
14. The anti-human transferrin receptor antibody according to any 20 one of claims 10 to 12, wherein the linker sequence is selected from the group consisting of the amino acid ce Gly-Ser, the amino acid sequence Gly-Gly-Ser, the amino acid sequence Gly-Gly-Gly, the amino acid sequences set forth as SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, and the amino acid sequence consisting of three consecutively 25 linked amino acid sequences each set forth as SEQ ID NO:3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015144379 | 2015-06-24 | ||
| PCT/JP2016/068738 WO2016208695A1 (en) | 2015-06-24 | 2016-06-24 | Anti-human transferrin receptor antibody permeating blood-brain barrier |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ739132A NZ739132A (en) | 2024-09-27 |
| NZ739132B2 true NZ739132B2 (en) | 2025-01-07 |
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