polypeptide containing a single variable immunoglobulin domain that targets glypican-3 and T cell receptors
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- ABLYNX NV
- Filing Date
- 2026-02-10
- Publication Date
- 2026-06-24
AI Technical Summary
【0014】 3 本発明の要約 本発明者らは、GPC3およびTCRを同時に特異的に標的とするポリペプチドが、インビトロでGPC3発現細胞の効率的なT細胞媒介性死滅をもたらすことを見出した。前記ポリペプチドは、効率的に生産することができた(例えば微生物宿主で)。さらに、このようなポリペプチドは、処置しようとする対象において、既存の抗体(すなわち、抗体構築物での第1の処置の前に対象に存在する抗体)には限定的な反応性を呈することを示すことができた。好ましい実施形態において、このようなポリペプチドは、処置しようとする対象において、連続する処置間にうまく間隔をあけることができるように十分長い半減期を呈示する。さらに、このようなポリペプチドは、GPC3を全く発現しないかまたは低レベルのそれを発現する細胞に対しては限定的な活性のみを示した。このことは、GPC3陽性がん標的細胞に対して高度に特異的なT細胞媒介性細胞傷害性応答を誘導できる可能性を示唆するが、一方、良好な安全性プロファイルを呈する。
Smart Images
Figure 2026103881000041 
Figure 2026103881000042 
Figure 2026103881000043
Abstract
Claims
1. A polypeptide comprising or consisting of at least three immunoglobulin single variable domains (ISVDs), Each of the ISVDs includes three complementarity determination regions (CDR1 to CDR3, respectively), At least three ISVDs are linked, in some cases, via one or more peptidic linkers: a) The first ISVD specifically binds to the constant domain of the TCR on T cells. i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 6 or has a difference of two or one amino acid from SEQ ID NO: 6; ii. CDR2 is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that differs from SEQ ID NO: 10 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 14 or has two or one amino acid differences from sequence number 14. Includes, b) The second ISVD specifically binds to GPC3, iv. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has two or one amino acid differences from SEQ ID NO: 7; v. CDR2 is the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 15 or has a difference of two or one amino acid from SEQ ID NO:
15. Including; c) The third ISVD specifically binds to GPC3, vii. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 8 or has two or one amino acid differences from SEQ ID NO: 8; viiii. CDR2 is the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and ix. CDR3 is an amino acid sequence that is the amino acid sequence of SEQ ID NO: 16 or an amino acid sequence that differs from SEQ ID NO: 16 by two or one amino acid. Includes, The order of the ISVDs indicates their relative positions relative to each other in the direction from the N-terminus to the C-terminus of the polypeptide, where the first ISVD is optionally located at the N-terminus of the polypeptide. Polypeptide.
2. a) The first ISVD comprises CDR1, which is the amino acid sequence of SEQ ID NO: 6; CDR2, which is the amino acid sequence of SEQ ID NO: 10; and CDR3, which is the amino acid sequence of SEQ ID NO: 14; b) The second ISVD comprises CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO: 15; c) The polypeptide according to claim 1, wherein the third ISVD comprises CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO:
16.
3. a) The amino acid sequence of the first ISVD exhibits more than 90% sequence identity with SEQ ID NO: 2; b) The amino acid sequence of the second ISVD has more than 90% sequence identity with SEQ ID NO:
3. Present; c) The amino acid sequence of the third ISVD exhibits more than 90% sequence identity with SEQ ID NO:
4. The polypeptide according to claim 1 or 2.
4. a) The first ISVD consists of the amino acid sequence of SEQ ID NO: 2; b) The second ISVD consists of the amino acid sequence of SEQ ID NO: 3; c) The third ISVD consists of the amino acid sequence of SEQ ID NO: 4, The polypeptide according to any one of claims 1 to 3.
5. The first ISVD and the second ISVD are linked to each other via a linker consisting of fewer than 10 amino acids, preferably fewer than 6 amino acids, the linker being most preferably a 5GS linker. The polypeptide according to any one of claims 1 to 4.
6. The polypeptide according to any one of claims 1 to 5, wherein the polypeptide further comprises one or more other groups, residues, parts or binding units optionally linked via one or more peptide linkers, the one or more other groups, residues, parts or binding units providing a polypeptide having an increased half-life compared to a corresponding polypeptide without the one or more other groups, residues, parts or binding units.
7. The polypeptide according to claim 6, wherein the one or more other groups, residues, moieties or binding units that provide a polypeptide having an increased half-life are selected from the group consisting of polyethylene glycol molecules, serum proteins or fragments thereof, binding units that can bind to serum proteins, Fc moieties, and small proteins or peptides that can bind to serum proteins.
8. The polypeptide according to claim 6 or 7, wherein the one or more other binding units that provide the polypeptide having an increased half-life are selected from the group consisting of binding units that can bind to serum albumin (such as human serum albumin) or serum immunoglobulin (such as IgG).
9. The polypeptide according to claim 8, wherein the binding unit that provides the polypeptide having an increased half-life is an ISVD that binds to human serum albumin.
10. ISVD, which binds to human serum albumin, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 9 or has a difference of two or one amino acid from SEQ ID NO: 9; ii. CDR2 which is the amino acid sequence of SEQ ID NO: 13 or an amino acid sequence which differs from SEQ ID NO: 13 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 17 or has two or one amino acid differences from sequence number 17. The polypeptide according to claim 9, comprising:
11. The polypeptide according to claim 9 or 10, wherein the ISVD that binds to human serum albumin comprises CDR1, which is the amino acid sequence of SEQ ID NO: 9; CDR2, which is the amino acid sequence of SEQ ID NO: 13; and CDR3, which is the amino acid sequence of SEQ ID NO:
17.
12. The amino acid sequence of ISVD that binds to human serum albumin is 90% of SEQ ID NO.
5. A polypeptide according to any one of claims 9 to 11, exhibiting superior sequence identity.
13. The polypeptide according to any one of claims 9 to 12, wherein the ISVD that binds to human serum albumin consists of the amino acid sequence of SEQ ID NO:
5.
14. The polypeptide according to any one of claims 1 to 13, comprising or consisting of an amino acid sequence exhibiting more than 90% sequence identity with SEQ ID NO:
1.
15. The polypeptide according to any one of claims 1 to 14, wherein the polypeptide comprises or consists of the amino acid sequence of SEQ ID NO:
1.
16. A polypeptide comprising or comprising at least one immunoglobulin single variable domain (ISVD) that specifically binds to GPC3, The ISVD includes three complementarity determination regions (CDR1 to CDR3, respectively), and at least one of the ISVDs is: a) CDR1 is an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 7 or has an amino acid sequence that differs from SEQ ID NO: 7 by two or one amino acid; CDR2 is an amino acid sequence that is the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and CDR3 is an amino acid sequence that is the amino acid sequence of SEQ ID NO: 15 or an amino acid sequence that differs from SEQ ID NO: 15 by two or one amino acid, or b) CDR1 is the amino acid sequence of SEQ ID NO: 8 or an amino acid sequence that differs from SEQ ID NO: 8 by two or one amino acid; CDR2 is the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and CDR3 is an amino acid sequence that is either the amino acid sequence of SEQ ID NO: 16 or an amino acid sequence that differs from SEQ ID NO: 16 by two or one amino acid. polypeptides, including
17. At least one ISVD: a) CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO: 15, or b) CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO:
16. The polypeptide according to claim 16, comprising:
18. The amino acid sequence of at least one ISVD is: a) An amino acid sequence having more than 90% sequence identity with Sequence ID No. 3, or b) Amino acid sequences having more than 90% sequence identity with Sequence ID No. 4 including or consisting of The polypeptide according to claim 16 or 17.
19. The aforementioned at least one ISVD is: a) The amino acid sequence of Sequence ID No. 3, or b) Amino acid sequence of SEQ ID NO: 4 including or consisting of The polypeptide according to any one of claims 16 to 18.
20. A polypeptide comprising or consisting of at least two ISVDs, Each of the ISVDs includes three complementarity determination regions (CDR1 to CDR3, respectively). fruit, At least two ISVDs are linked, in some cases, via one or more peptidic linkers: a) The first and second ISVDs specifically bind to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has a difference of two or one amino acid from SEQ ID NO: 7; ii. CDR2 is the amino acid sequence of SEQ ID NO: 11 or has an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 15 or has two or one amino acid differences from sequence number 15. Includes, b) The first and second ISVDs bind specifically to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 8 or has an amino acid sequence that differs from SEQ ID NO: 8 by two or one amino acid; ii. CDR2 is the amino acid sequence of SEQ ID NO: 12 or has an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 16 or has two or one amino acid differences from sequence number 16. Includes, c) The first ISVD specifically binds to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has a difference of two or one amino acid from SEQ ID NO: 7; ii. CDR2 is the amino acid sequence of SEQ ID NO: 11 or has an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 15 or has two or one amino acid differences from sequence number 15. Includes, The second ISVD specifically binds to GPC3, iv. CDR1 is an amino acid sequence that is the same as sequence number 8 or has two or one amino acid differences from sequence number 8; v. CDR2 is the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 16 or has a difference of two or one amino acid from SEQ ID NO:
16. Includes, d) The first ISVD specifically binds to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 8 or has an amino acid sequence that differs from SEQ ID NO: 8 by two or one amino acid; ii. CDR2 is the amino acid sequence of SEQ ID NO: 12 or has an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 16 or has two or one amino acid differences from sequence number 16. Includes, The second ISVD specifically binds to GPC3, iv. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has two or one amino acid differences from SEQ ID NO: 7; v. CDR2 is the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 15 or has a difference of 2 or 1 amino acid from SEQ ID NO:
15. Includes, e) The first ISVD specifically binds to the constant domain of the T cell receptor (TCR) on T cells. i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 6 or has an amino acid sequence that differs from SEQ ID NO: 6 by two or one amino acid; ii. CDR2 which is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence which differs from SEQ ID NO: 10 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 14 or has two or one amino acid differences from sequence number 14. Includes, The second ISVD specifically binds to GPC3, iv. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has two or one amino acid differences from SEQ ID NO: 7; v. CDR2 is the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 15 or has a difference of 2 or 1 amino acid from SEQ ID NO:
15. Includes, f) The first ISVD specifically binds to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 7 or has a difference of two or one amino acid from SEQ ID NO: 7; ii. CDR2 is the amino acid sequence of SEQ ID NO: 11 or has an amino acid sequence that differs from SEQ ID NO: 11 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 15 or has two or one amino acid differences from sequence number 15. Includes, The second ISVD specifically binds to the constant domain of the TCR on T cells. iv. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 6 or has two or one amino acid differences from SEQ ID NO: 6; v. CDR2 is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that differs from SEQ ID NO: 10 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 14 or has a difference of two or one amino acid from SEQ ID NO:
14. Includes, g) The first ISVD specifically binds to the constant domain of the TCR on T cells, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 6 or has an amino acid sequence that differs from SEQ ID NO: 6 by two or one amino acid; ii. CDR2 which is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence which differs from SEQ ID NO: 10 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 14 or has two or one amino acid differences from sequence number 14. Includes, The second ISVD specifically binds to GPC3, iv. CDR1 is an amino acid sequence that is the same as sequence number 8 or has two or one amino acid differences from sequence number 8; v. CDR2 is the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 16 or has a difference of two or one amino acid from SEQ ID NO:
16. Includes, or h) The first ISVD specifically binds to GPC3, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 8 or has an amino acid sequence that differs from SEQ ID NO: 8 by two or one amino acid; ii. CDR2 is the amino acid sequence of SEQ ID NO: 12 or has an amino acid sequence that differs from SEQ ID NO: 12 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 16 or has two or one amino acid differences from sequence number 16. Includes, The second ISVD specifically binds to the constant domain of the TCR on T cells. iv. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 6 or has two or one amino acid differences from SEQ ID NO: 6; v. CDR2 is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that differs from SEQ ID NO: 10 by two or one amino acid; and vi. CDR3 is an amino acid sequence that is the same as SEQ ID NO: 14 or has a difference of two or one amino acid from SEQ ID NO:
14. Includes, The order of ISVD indicates the relative positions of the polypeptides in the direction from the N-terminus to the C-terminus. Polypeptide.
21. a) The first and second ISVDs specifically bind to GPC3 and include CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO:
15. b) The first and second ISVDs specifically bind to GPC3 and include CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO:
16. c) The first ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO:
15. The second ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO:
16. d) The first ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO:
16. The second ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO:
15. e) The first ISVD specifically binds to the constant domain of the TCR on T cells and includes CDR1, the amino acid sequence of SEQ ID NO: 6, CDR2, the amino acid sequence of SEQ ID NO: 10, and CDR3, the amino acid sequence of SEQ ID NO: 14; the second ISVD specifically binds to GPC3 and includes CDR1, the amino acid sequence of SEQ ID NO: 7, CDR2, the amino acid sequence of SEQ ID NO: 11, and CDR3, the amino acid sequence of SEQ ID NO:
15. f) The first ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 7; CDR2, which is the amino acid sequence of SEQ ID NO: 11; and CDR3, which is the amino acid sequence of SEQ ID NO: 15; the second ISVD specifically binds to the constant domain of the TCR on T cells and includes CDR1, which is the amino acid sequence of SEQ ID NO: 6; CDR2, which is the amino acid sequence of SEQ ID NO: 10; and CDR3, which is the amino acid sequence of SEQ ID NO:
14. g) The first ISVD specifically binds to the constant domain of the TCR on T cells and contains CDR1, the amino acid sequence of SEQ ID NO: 6, CDR2, the amino acid sequence of SEQ ID NO: 10, and CDR3, the amino acid sequence of SEQ ID NO: 14, and the second ISVD specifically binds to GPC3 and contains CDR1, the amino acid sequence of SEQ ID NO: 8, and the amino acid sequence of SEQ ID NO:
12. It contains a CDR2 and a CDR3 which is the amino acid sequence of SEQ ID NO: 16, or h) The first ISVD specifically binds to GPC3 and includes CDR1, which is the amino acid sequence of SEQ ID NO: 8; CDR2, which is the amino acid sequence of SEQ ID NO: 12; and CDR3, which is the amino acid sequence of SEQ ID NO: 16; the second ISVD specifically binds to the constant domain of the TCR on T cells and includes CDR1, which is the amino acid sequence of SEQ ID NO: 6; CDR2, which is the amino acid sequence of SEQ ID NO: 10; and CDR3, which is the amino acid sequence of SEQ ID NO:
14. The polypeptide according to claim 20.
22. a) The amino acid sequences of the first and second ISVDs that specifically bind to GPC3 exhibit more than 90% sequence identity with SEQ ID NO:
3. b) The amino acid sequences of the first and second ISVDs that specifically bind to GPC3 exhibit more than 90% sequence identity with SEQ ID NO:
4. c) The amino acid sequence of the first ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO: 3, and the second ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO:
4. d) The amino acid sequence of the first ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO: 4, and the second ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO:
3. e) The amino acid sequence of the first ISVD that specifically binds to the constant domain of the TCR on T cells exhibits more than 90% sequence identity with SEQ ID NO: 2, and the second ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO:
3. f) The amino acid sequence of the first ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO: 3, and the second ISVD that specifically binds to the constant domain of the TCR on T cells exhibits more than 90% sequence identity with SEQ ID NO:
2. g) The amino acid sequence of the first ISVD that specifically binds to the constant domain of the TCR on T cells exhibits more than 90% sequence identity with SEQ ID NO: 2, and the second ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO: 4, or h) The amino acid sequence of the first ISVD that specifically binds to GPC3 exhibits more than 90% sequence identity with SEQ ID NO: 4, and the second ISVD that specifically binds to the constant domain of the TCR on T cells exhibits more than 90% sequence identity with SEQ ID NO:
2. The polypeptide according to claim 20 or 21.
23. a) The first and second ISVDs that specifically bind to GPC3 consist of the amino acid sequence of SEQ ID NO: 3, b) The first and second ISVDs that specifically bind to GPC3 consist of the amino acid sequence of SEQ ID NO: 4, c) The first ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO: 3, and the second ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO:
4. d) The first ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO: 4, and the second ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO:
3. e) The first ISVD that specifically binds to the constant domain of the TCR on T cells consists of the amino acid sequence of SEQ ID NO: 2, and the second ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO:
3. f) The first ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO: 3, and the second ISVD that specifically binds to the constant domain of the TCR on T cells consists of the amino acid sequence of SEQ ID NO:
2. g) The first ISVD that specifically binds to the constant domain of the TCR on T cells consists of the amino acid sequence of SEQ ID NO: 2, and the second ISVD that specifically binds to GPC3 consists of SEQ ID NO: 4 It consists of the amino acid sequence, or h) The first ISVD that specifically binds to GPC3 consists of the amino acid sequence of SEQ ID NO: 4, and the second ISVD that specifically binds to the constant domain of the TCR on T cells consists of the amino acid sequence of SEQ ID NO:
2. The polypeptide according to any one of claims 20 to 22.
24. The polypeptide according to any one of claims 20 to 23, comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 1, 49 to 72, and 78 to 81.
25. The polypeptide according to any one of claims 16 to 24, further comprising one or more other groups, residues, parts or binding units optionally linked via one or more peptide linkers, wherein the one or more other groups, residues, parts or binding units provide a polypeptide having an increased half-life compared to a corresponding polypeptide without the one or more other groups, residues, parts or binding units.
26. The polypeptide according to claim 25, wherein the one or more other groups, residues, moieties or binding units that provide a polypeptide having an increased half-life are selected from the group consisting of polyethylene glycol molecules, serum proteins or fragments thereof, binding units that can bind to serum proteins, Fc moieties, and low molecular weight proteins or peptides that can bind to serum proteins.
27. The polypeptide according to claim 25 or 26, wherein the one or more other binding units that provide the polypeptide having an increased half-life are selected from the group consisting of binding units that can bind to serum albumin (such as human serum albumin) or serum immunoglobulin (such as IgG).
28. The polypeptide according to claim 27, wherein the binding unit that provides the polypeptide having an increased half-life is an ISVD that binds to human serum albumin.
29. ISVD, which binds to human serum albumin, i. CDR1 is an amino acid sequence that is the same as SEQ ID NO: 9 or has a difference of two or one amino acid from SEQ ID NO: 9; ii. CDR2 which is the amino acid sequence of SEQ ID NO: 13 or an amino acid sequence which differs from SEQ ID NO: 13 by two or one amino acid; and iii. CDR3 is an amino acid sequence that is the same as sequence number 17 or has two or one amino acid differences from sequence number 17. The polypeptide according to claim 28, comprising:
30. The polypeptide according to claim 28 or 29, wherein the ISVD that binds to human serum albumin comprises CDR1, which is the amino acid sequence of SEQ ID NO: 9; CDR2, which is the amino acid sequence of SEQ ID NO: 13; and CDR3, which is the amino acid sequence of SEQ ID NO:
17.
31. The polypeptide according to any one of claims 28 to 30, wherein the amino acid sequence of ISVD that binds to human serum albumin exhibits more than 90% sequence identity with SEQ ID NO:
5.
32. The polypeptide according to any one of claims 28 to 31, wherein the ISVD that binds to human serum albumin consists of the amino acid sequence of SEQ ID NO:
5.
33. A nucleic acid comprising a nucleotide sequence encoding a polypeptide according to any one of claims 1 to 32, preferably according to any one of claims 1 to 15.
34. A host or host cell comprising the nucleic acid described in claim 33.
35. A method for producing a polypeptide according to any one of claims 1 to 32, preferably one of claims 1 to 15, comprising at least: a) expressing the nucleic acid according to claim 33 in a suitable host cell or host organism, or in another suitable expression system; optionally thereafter: b) A step of isolating and / or purifying a polypeptide according to any one of claims 1 to 32, preferably any one of claims 1 to 15. Methods that include...
36. A composition comprising at least one polypeptide according to any one of claims 1 to 32, preferably at least one polypeptide according to any one of claims 1 to 15, or a nucleic acid according to claim 33.
37. The composition according to claim 36, further comprising at least one pharmaceutically acceptable carrier, diluent or excipient and / or adjuvant, and optionally one or more further pharmaceutically active polypeptides and / or compounds.
38. A polypeptide according to any one of claims 1 to 32, preferably one of claims 1 to 15, or a composition according to claim 36 or 37, for use as a pharmaceutical.
39. A polypeptide according to any one of claims 1 to 32, preferably one of claims 1 to 15, or a composition according to claim 36 or 37, for use in the treatment of cancer, preferably liver cancer or lung cancer.
40. The polypeptide or composition for use according to claim 39, wherein the liver cancer is hepatocellular carcinoma.
41. A method for treating cancer, preferably liver cancer or lung cancer, A method comprising administering a pharmaceutically active amount of a polypeptide according to any one of claims 1 to 32, preferably one of claims 1 to 15, or a composition according to claim 36 or 37, to a subject requiring it.
42. The method according to claim 41, wherein the liver cancer is hepatocellular carcinoma.
43. Use in the preparation of pharmaceuticals of a polypeptide according to any one of claims 1 to 32, preferably the polypeptide according to any one of claims 1 to 15, or the composition according to claim 36 or 37.
44. Use of a polypeptide according to any one of claims 1 to 32, preferably one of claims 1 to 15, or the composition according to claim 36 or 37, in the preparation of a pharmaceutical composition for treating cancer, preferably liver cancer or lung cancer.
45. The use of the polypeptide or composition according to claim 44, wherein the liver cancer is hepatocellular carcinoma.