Mesothelin-specific binding constructs and their use in radiotherapy

Abstract

The present invention relates to MSLN-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for MSLN and a chelator capable of bonding to a radionuclide, as well as to such MSLN-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled MSLN-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

Description

[0001] New PCT Patent Application

[0002] Molecular Partners AG; Orano Med Theranostics

[0003] Vossius Ref.: AJ4272 PCT S3

[0004] MESOTHELIN-SPECIFIC BINDING CONSTRUCTS AND THEIR USE IN RADIOTHERAPY

[0005] FIELD

[0006] The present invention relates to mesothelin-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for mesothelin and a chelator capable of bonding to a radionuclide, such as Pb-212, as well as to such mesothelin-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled mesothelin-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

[0007] BACKGROUND

[0008] Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in serosal tissues, such as pleura, pericardium and peritoneum, but not in the parenchyma of any vital organs. Mesothelin is overexpressed in a variety of cancers, and hence it is commonly expressed on the surface of tumor cells, e.g. in ovarian cancer, mesothelioma, pancreatic adenocarcinoma, gastric cancer, and other malignancies. Due to its strong differential expression between normal and tumor tissues and its presence on the cell surface, mesothelin is considered a promising target for cancer therapy and diagnosis (Hagerty and Takabe, World J Oncol. 2023;14(5):340-349).

[0009] The mesothelin gene encodes a precursor protein, known as pre-pro mesothelin, which is 622 amino acids long (69 kDa). Upon expression, this precursor protein is processed, among others by cleavage by the endoprotease furin, yielding a mature GPI-anchored, membrane-bound fragment of about 40 kDa (the membrane-bound mesothelin (MSLN)) and an about 31 kDa secreted fragment, also referred to as “megakaryocyte-potentiating factor” (MPF).

[0010] Similar to other GPI-anchored proteins, the membrane-bound mesothelin undergoes shedding in the extracellular environment, which is rich in proteases. Shedding can occur through proteolytic cleavage at one of several cleavage sites in the membrane-proximal region of mesothelin, resulting in truncated mesothelin protein that remains on the cell surface (tMSLN) as well as soluble mesothelin (sMSLN). The specific biological function of mesothelin in normal tissue is still poorly understood. However, various studies have suggested that mesothelin plays a role in regulating tumor cell proliferation, dissemination, metastasis, and chemotherapy resistance (Chen et al., Discover Oncology 15:289 (2024); Hagerty and Takabe, World J Oncol. 2023;14(5):340-349). Furthermore, the expression of mesothelin has also been linked to the prognosis of cancer patients. In many cases, higher levels of mesothelin expression correlate with more aggressive disease and poorer clinical outcomes.

[0011] Various different therapeutic approaches targeting mesothelin have been developed and explored in clinical trials for cancer treatment, including monoclonal antibodies, bispecific antibodies, immunotoxins, chimeric antigen receptor-T (CAR-T) cells, vaccines, and antibody-drug conjugates (ADCs) (Chen et al., Discover Oncology 15:289 (2024); Hagerty and Takabe, World J Oncol. 2023;14(5):340-349; Hagerty et al.,Biomolecules 2020, 10, 973; Chu, Curr Oncol Rep 2023 Apr;25(4):309-323). However, in many cases, the therapeutic benefit has been modest and / or the administration has been limited by on-target, off-tumor toxicities. Some of these clinical programs were discontinued, mainly due to adverse effects or lack of efficacy. Taken together, there remains a need for new mesothelin-specific therapeutic and / or diagnostic agents and their use in treating and / or diagnosing diseases, such as cancer.

[0012] SUMMARY OF THE INVENTION

[0013] Designing targeted radioisotope delivering platforms, including for alpha-particle emitting, beta-particle emitting or Auger electron emitting radioisotopes, and / or related drug candidates, requires simultaneous optimization of multiple aspects of such platforms ordrug candidates. These aspects include, e.g., stability, target specificity, serum half-life, biodistribution, tissue penetration, pharmacodynamic properties, ease of manufacturing, acceptable therapeutic window and / or immunogenicity.

[0014] As an example, despite the excellent specificity of antibodies, such as IgGs, to their antigens, which makes antibodies an outstanding targeting platform for therapeutics, the typical serum half-life of an IgG of at least three weeks is disadvantageous for the delivery of radioisotopes, including alpha-emitting isotopes such as actinium-225 (225Ac or Ac-225) or lead-212 (212Pb or Pb-212) and beta-emitting isotopes such as lutetium-177 (177Lu or Lu-177) and yttrium-90 (90Y or Y-90), in particular due to prolonged exposure and chronic off-target toxicities. Smaller antibody formats (e.g. monomeric scFv’s, heavy-chain only antibodies, or single-domain antibody fragments) with a molecular weight of, e.g., 15 to 30 kDa have been engineered, which provide similarly good specificity as a full-size antibody, such as an IgG (about 150 kDa), but have a much shorter serum half-life (e.g., 30 minutes to 2 hours). However, such short half-lives do not provide sufficient time for efficacious target binding due to poor retention and tumor uptake, and furthermore plasma clearance of such small antibody formats by the renal system can lead to isotope accumulation in renal tissues and problematic off target toxicities.

[0015] Thus, despite the general potential of targeted radioisotope delivering therapy, further elucidation of biochemical, immunological, pharmacological, and molecular aspects of targeted radioisotope delivering platforms must be pursued to better design and develop effective targeted radioisotope delivering drug candidates. In this pursuit, various aspects may play a role, including the choice of the target antigen, of the target-specific delivery system, of the radionuclide payload, of the chelator used to bind the radionuclide payload, of the chemistry used to connect the chelator to the delivery system, and / or of the molecular mechanism or entity used to modulate pharmacokinetic properties.

[0016] Applicant has found that designed ankyrin repeat proteins (DARPins) with binding specificity for MSLN can be formatted into targeted radioisotope delivering conjugates with beneficial properties. Such DARPin-based radioisotope delivering conjugates targeting MSLN, and methods of using such conjugates, are disclosed herein.

[0017] Based on the disclosure provided herein, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following embodiments (E).E1. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide.

[0018] E2. The conjugate or pharmaceutically acceptable salt thereof of E1 , wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator.

[0019] E3. The conjugate or pharmaceutically acceptable salt thereof of E1 or E2, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134.

[0020] E4. The conjugate or pharmaceutically acceptable salt thereof of any one of E1 to E3, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0021] E5. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Ac-225.

[0022] E6. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Lu-177.

[0023] E7. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is ln-111.

[0024] E8. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212 or Pb-203.

[0025] E9. The conjugate or pharmaceutically acceptable salt of any one of E1 to E8, wherein said conjugate has the formula: M-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide.

[0026] E10. The conjugate or pharmaceutically acceptable salt of any one of E1 to E9, wherein said conjugate further comprises a connector, wherein said connector is covalently connected to said ankyrin repeat domain and to said chelator.

[0027] E11. The conjugate or pharmaceutically acceptable salt of E10, wherein said conjugate has the formula: M-Co-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0028] E12. The conjugate or pharmaceutically acceptable salt of any one of E1 to E11 , wherein said ankyrin repeat domain with binding specificity for MSLN binds human MSLN with a KD value of or below 100 nM,of or below 10 nM, of or below 1 nM, of or below 350 pM, of or below 100 pM, of or below 35 pM, or of or below 10 pM.

[0029] E13. The conjugate or pharmaceutically acceptable salt of any one of E1 to E12, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

[0030] E14. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 1.

[0031] E15. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 2.

[0032] E16. The conjugate or salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 3.

[0033] E17. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 4.

[0034] E18. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 42.

[0035] E19. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%,at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 43.

[0036] E20. The conjugate or pharmaceutically acceptable salt of any one of E1 to E13, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 44.

[0037] E21. The conjugate or pharmaceutically acceptable salt of any one E1 to E20, wherein said chelator is diethylenetriaminepentaacetic acid (DTPA), 1 ,4,7-triazacyclononane-1 ,4,7-triacetic acid (NOTA), 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA), 1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide (TCMC), or a derivative thereof.

[0038] E22. The conjugate or pharmaceutically acceptable salt of any one E1 to E21 , wherein said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid) or TCMC (1,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof.

[0039] E23. The conjugate or pharmaceutically acceptable salt of any one of E1 to E22, wherein said chelator has a structure of Formula (I):

[0040]

[0041] Formula (I)

[0042] wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or said connector.

[0043] E24. The conjugate or pharmaceutically acceptable salt of any one of E1 to E23, wherein said chelator has a structure of Formula (II):

[0044]

[0045] Formula (II)

[0046] wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or said connector.

[0047] E25. The conjugate or pharmaceutically acceptable salt of any one E1 to E22, wherein said chelator has a structure of Formula (III):

[0048]

[0049] Formula (III)

[0050] wherein R1 , R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or said connector. E26. The conjugate or pharmaceutically acceptable salt of any one of E1 to E22 and E25, wherein said chelator has a structure of Formula (IV):

[0051]

[0052] Formula (IV)

[0053] wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or said connector.

[0054] E27. The conjugate or pharmaceutically acceptable salt of any one of E1 to E26, further comprising a tag, wherein said tag comprises a Cysteine.

[0055] E28. The conjugate or pharmaceutically acceptable salt of E27, wherein said tag is located at the C-terminal side of said ankyrin repeat domain with binding specificity for MSLN.

[0056] E29. The conjugate or pharmaceutically acceptable salt of any one of E27 to E28, wherein said conjugate has the formula: M-T-Co-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0057] E30. The conjugate or pharmaceutically acceptable salt of any one of E27 to E29, wherein said tag comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof.

[0058] E31. The conjugate or pharmaceutically acceptable salt of any one of E27 to E30, wherein said connector is covalently bound to said tag via a thioether bond.

[0059] E32. The conjugate or pharmaceutically acceptable salt of any one of E10 to E31 , wherein said connector comprises a maleimide or a derivative thereof.

[0060] E33. The conjugate or pharmaceutically acceptable salt of any one of E10 to E31 , wherein said connector has a structure of Formula (V):

[0061]

[0062] wherein the dotted line originating from N represents the covalent connection to said chelator, and wherein the dotted line originating from a carbon atom represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or said tag.

[0063] E34. The conjugate or pharmaceutically acceptable salt of any one of E1 to E33, further comprising a halflife extending moiety.

[0064] E35. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: H-M-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide.

[0065] E36. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: M-H-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide.

[0066] E37. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: H-M-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0067] E38. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: H-M-T-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. E39. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: M-H-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0068] E40. The conjugate or pharmaceutically acceptable salt of E34, wherein said conjugate has the formula: M-H-T-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. E41. The conjugate or pharmaceutically acceptable salt of any one of E34 to E40, wherein said half-life extending moiety has binding specificity for human serum albumin.

[0069] E42. The conjugate or pharmaceutically acceptable salt of any one of E34 to E41 , wherein said half-life extending moiety is an ankyrin repeat domain with binding specificity for human serum albumin.

[0070] E43. The conjugate or pharmaceutically acceptable salt of E42, wherein said ankyrin repeat domain with binding specificity for human serum albumin is covalently connected to said ankyrin repeat domain with binding specificity for MSLN at the C-terminal side of said ankyrin repeat domain with binding specificity for MSLN.

[0071] E44. The conjugate or pharmaceutically acceptable salt of any one of E42 to E43, wherein said ankyrin repeat domain with binding specificity for human serum albumin binds human serum albumin with a KD value of or below 500 nM, of or below 250 nM, or of or below 100 nM.E45. The conjugate or pharmaceutically acceptable salt of any one of E42 to E44, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 5 to 7 or 45.

[0072] E46. The conjugate or pharmaceutically acceptable salt of any one of E42 to E45, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 5. E47. The conjugate or pharmaceutically acceptable salt of any one of E42 to E45, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 6. E48. The conjugate or pharmaceutically acceptable salt of any one of E42 to E46, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 7. E49. The conjugate or pharmaceutically acceptable salt of any one of E42 to E46, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 45. E50. The conjugate or pharmaceutically acceptable salt of any one of E42 to E49, wherein said tag is located at the C-terminal side of said ankyrin repeat domain with binding specificity for human serum albumin.

[0073] E51. The conjugate or pharmaceutically acceptable salt of any one of E42 to E50, wherein said ankyrin repeat domain with binding specificity for human serum albumin is covalently connected to said ankyrin repeat domain with binding specificity for MSLN by a peptide linker.

[0074] E52. The conjugate or pharmaceutically acceptable salt of E51 , wherein said peptide linker comprises the amino acid sequence of any one of SEQ ID NOs: 9 to 15 or a variant thereof.

[0075] E53. The conjugate or pharmaceutically acceptable salt of any one of E51 to E52, wherein said peptide linker comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof.E54. The conjugate or pharmaceutically acceptable salt of any one of E51 to E52, wherein said peptide linker comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof.

[0076] E55. The conjugate or pharmaceutically acceptable salt of any one of E51 to E54, wherein said peptide linker has a length of 1 to 24 amino acids, of 1 to 22 amino acids, of 1 to 20 amino acids, of 1 to 19 amino acids, of 1 to 18 amino acids, of 1 to 17 amino acids, of 1 to 16 amino acids, of 1 to 15 amino acids, of 1 to 14 amino acids, of 1 to 13 amino acids, of 1 to 12 amino acids, of 1 to 11 amino acids, of 1 to 10 amino acids, of 1 to 9 amino acids, of 1 to 8 amino acids, of 1 to 7 amino acids, of 1 to 6 amino acids, of 1 to 5 amino acids, of 1 to 4 amino acids, of 1 to 3 amino acids, of 1 to 2 amino acids, or of 1 amino acid or about 2 to 20 amino acids, of about 2 to 15 amino acids, of about 2 to 11 amino acids, of about 2 to 10 amino acids, of about 2 to 9 amino acids, of about 2 to 8 amino acids, of about 3 to 11 amino acids, of about 3 to 10 amino acids, of about 3 to 9 amino acids, or of about 3 to 8 amino acids.

[0077] E56. The conjugate or pharmaceutically acceptable salt of any one of E51 to E55, wherein said conjugate has the formula: H-L-M-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0078] E57. The conjugate or pharmaceutically acceptable salt of any of E51 to E55, wherein said conjugate has the formula: H-L-M-T-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0079] E58. The conjugate or pharmaceutically acceptable salt of any one of E51 to E55, wherein said conjugate has the formula: M-L-H-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0080] E59. The conjugate or pharmaceutically acceptable salt of any one of E51 to E55, wherein said conjugate has the formula: M-L-H-T-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0081] E60. The conjugate or pharmaceutically acceptable salt of any one of E1 to E59, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50.

[0082] E61. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 17.E62. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 18.

[0083] E63. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 19.

[0084] E64. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 20.

[0085] E65. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 21.

[0086] E66. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 22.

[0087] E67. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 23.

[0088] E68. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 24.

[0089] E69. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, atleast 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 25.

[0090] E70. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 26.

[0091] E71. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 46.

[0092] E72. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 47.

[0093] E73. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 48.

[0094] E74. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 49.

[0095] E75. The conjugate or pharmaceutically acceptable salt of any one of E1 to E60, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 50.

[0096] E76. The conjugate or pharmaceutically acceptable salt of any one of E60 to E75, wherein said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, atleast 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50 is covalently bound at its N-terminal end to Glycine-Serine (GS). E77. The conjugate or pharmaceutically acceptable salt of any one of E60 to E76, wherein said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50 is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0097] E78. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said connector is covalently connected to said ankyrin repeat protein, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0098] E79. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said connector is covalently connected to said ankyrin repeat protein, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212 or Pb-203, or wherein said radionuclide is Lu-177 or Ac-225.

[0099] E80. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 29.

[0100] E81. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 30.E82. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 31.

[0101] E83. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 32.

[0102] E84. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 33.

[0103] E85. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 34.

[0104] E86. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 38.

[0105] E87. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 51.

[0106] E88. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 52.

[0107] E89. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 53.

[0108] E90. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 54.

[0109] E91. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 55.

[0110] E92. The conjugate or pharmaceutically acceptable salt of E78 or E79, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 56.

[0111] E93. The conjugate or pharmaceutically acceptable salt of any one of E78 to E92, wherein said ankyrin repeat protein comprises a Cysteine, wherein said connector comprises maleimide or a derivative thereof, and wherein said Cysteine is covalently bound to said connector via a thioether bond.

[0112] E94. The conjugate or pharmaceutically acceptable salt of E93, wherein said Cysteine is located at the C-terminal end of said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56.

[0113] E95. The conjugate or pharmaceutically acceptable salt of any one of E78 to E94, wherein said chelator is diethylenetriaminepentaacetic acid (DTPA), 1 ,4,7-triazacyclononane-1 ,4,7-triacetic acid (NOTA), 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA), 1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide (TCMC), or a derivative thereof.

[0114] E96. The conjugate or pharmaceutically acceptable salt of any one of E78 to E95, wherein said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid) or TCMC (1,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof.

[0115] E97. The conjugate or pharmaceutically acceptable salt of any one of E78 to E96, wherein said chelator has a structure of Formula (I):

[0116]

[0117] Formula (I)

[0118] wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector.

[0119] E98. The conjugate or pharmaceutically acceptable salt of any one of E78 to E97, wherein said chelator has a structure of Formula (II):

[0120]

[0121] Formula (II)

[0122] wherein the dotted line represents the covalent connection to said connector.

[0123] E99. The conjugate or pharmaceutically acceptable salt of any one of E78 to E96, wherein said chelator has a structure of Formula (III):

[0124]

[0125] Formula (III)

[0126] wherein R1, R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector.

[0127] E100. The conjugate or pharmaceutically acceptable salt of any one of E78 to E96 and E99, wherein said chelator has a structure of Formula (IV):

[0128]

[0129] Formula (IV)

[0130] wherein the dotted line represents the covalent connection to said connector.

[0131] E101. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VI):

[0132]

[0133] Formula (VI)

[0134] wherein R1 , R2, and R3 are independently NH2 or OH;

[0135] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0136] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine, and wherein R5 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0137] E102. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VI):

[0138]

[0139] Formula (VI)

[0140] wherein R1 , R2, and R3 are independently NH2 or OH;

[0141] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0142] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine;

[0143] and wherein R5 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203.

[0144] E103. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VI):

[0145]

[0146] Formula (VI)

[0147] wherein R1 , R2, and R3 are independently NH2 or OH;

[0148] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0149] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine, and wherein R5 is a chelated radionuclide, wherein said radionuclide is Ac-225 or Lu-177.

[0150] E104. The conjugate or pharmaceutically acceptable salt of any one of E101 to E103, wherein said Cysteine is connected to a heterocyclic ring structure by a thioether bond, wherein said heterocyclic ring structure connects A and R4.

[0151] E105. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VII):

[0152]

[0153] Formula (VII)

[0154] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0155] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0156] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine, and wherein R6 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0157] E106. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VII):

[0158]

[0159] Formula (VII)wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0160] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0161] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, 51 to 56 wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine;

[0162] and wherein R6 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203.

[0163] E107. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VII):

[0164]

[0165] Formula (VII)

[0166] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0167] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0168] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine, and wherein R6 is a chelated radionuclide, wherein said radionuclide is Ac-225 or Lu-177.

[0169] E108. The conjugate or pharmaceutically acceptable salt of any one of E105 to E107, wherein said Cysteine is connected to a heterocyclic ring structure by a thioether bond, wherein said heterocyclic ring structure connects A and R5.

[0170] E109. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, atleast 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 29.

[0171] E110. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 30.

[0172] E111. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 31.

[0173] E112. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 32.

[0174] E113. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 33.

[0175] E114. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 34.

[0176] E115. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 38.

[0177] E116. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%,at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 51.

[0178] E117. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 52.

[0179] E118. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 53.

[0180] E119. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 54.

[0181] E120. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 55.

[0182] E121. The conjugate or pharmaceutically acceptable salt of any one of E101 to E108, wherein said conjugate or salt comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 56.

[0183] E122. The conjugate or pharmaceutically acceptable salt of any one of E101 to E121 , wherein said Cysteine is located at the C-terminal end of said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56.

[0184] E123. The conjugate or pharmaceutically acceptable salt of any one of E78 to E122, wherein said ankyrin repeat protein binds human MSLN with a KD value of or below 100 nM, of or below 10 nM, of or below 1 nM, of or below 350 pM, of or below 100 pM, of or below 35 pM, or of or below 10 pM.

[0185] E124. The conjugate or salt of any one of E78 to E123, wherein said ankyrin repeat protein binds human serum albumin with a KD value of or below 500 nM, of or below 250 nM, or of or below 100 nM.E125. The conjugate or pharmaceutically acceptable salt of any one of E1 to E124, wherein said conjugate binds to cells expressing human MSLN on their surface.

[0186] E126. The conjugate or pharmaceutically acceptable salt of any one of E1 to E125, wherein said conjugate does not specifically bind to human soluble MSLN (sMSLN).

[0187] E127. The conjugate or pharmaceutically acceptable salt of any one of E1 to E126, wherein said conjugate binds to cells expressing human MSLN on their surface, and wherein said cells are OVCAR-3 cells or OVCAR-8 cells.

[0188] E128. The conjugate or pharmaceutically acceptable salt of E127, wherein said conjugate binds said OVCAR-3 cells with an EC50 of about or below 5 x 10-7M, of about or below 1.5 x 10-7M, of about or below 5 x 10-8M, of about or below 1.5 x 10-8M, of about or below 5 x 10-9M, of about or below 2 x 10-9M, of about or below 10-9M, or of about or below 5 x 10'1°M.

[0189] E129. The conjugate or pharmaceutically acceptable salt of any one of E1 to E128, wherein said conjugate binds to cells expressing human MSLN on their surface, and wherein said binding to cells expressing human MSLN on their surface is not inhibited by the presence of human soluble MSLN (sMSLN).

[0190] E130. The conjugate or pharmaceutically acceptable salt of any one of E1 to E129, wherein said conjugate has a terminal half-life in a mouse model of at least about 5 hours, at least about 7.5 hours, at least about 10 hours, at least about 12.5 hours, at least about 15 hours, at least about 17.5 hours, at least about 20 hours, at least about 22.5 hours, at least about 25 hours, at least about 27.5 hours, at least about 30 hours, or at least about 32.5 hours.

[0191] E131. The conjugate or pharmaceutically acceptable salt of any one of E1 to E130, wherein said conjugate has a terminal half-life in a mouse model of about 5 to 45 hours, about 5 to 40 hours, about 5 to 35 hours, about 10 to 30 hours, or about 13 to 27 hours.

[0192] E132. The conjugate or pharmaceutically acceptable salt of any one of E130 and E131 , wherein said mouse model is a BALB / c mouse model.

[0193] E133. The conjugate or pharmaceutically acceptable salt of any one of E1 to E132, wherein said radionuclide is Pb-212 or Ac-225, and wherein said conjugate is capable of inhibiting tumor growth in a human MSLN-expressing mouse tumor model.

[0194] E134. The conjugate or pharmaceutically acceptable salt of E133, wherein said human MSLN-expressing mouse tumor model comprises tumors formed by human MSLN-expressing MC38 colon carcinoma cells, by Capan-2 pancreatic carcinoma cells, by OVCAR-3 ovarian carcinoma cells, or by OVCAR-8 ovarian carcinoma cells.

[0195] E135. A pharmaceutical composition comprising the conjugate or pharmaceutically acceptable salt of any one of E1 to E134, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent. E136. A kit comprising (i) a first container containing the conjugate or pharmaceutically acceptable salt of any one of E1 to E134 or the pharmaceutical composition of E135; and (ii) a second container containing a buffered solution.E137. The conjugate or pharmaceutically acceptable salt of any of E1 to E134 or the pharmaceutical composition of E135 for use in a method of imaging, diagnosing and / or treating a medical condition, the method comprising the step of administering to a subject in need thereof an amount of said conjugate or salt or said pharmaceutical composition effective for imaging, diagnosing and / or treating said medical condition.

[0196] E138. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of E137, wherein said medical condition is cancer.

[0197] E139. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of E138, wherein said cancer comprises cells that express MSLN on their surface.

[0198] EMO. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E138 to E139, wherein said cancer is ovarian cancer, mesothelioma, pancreatic cancer, gastric cancer, or breast cancer.

[0199] E141. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E138 to £140, wherein said cancer is epithelial ovarian cancer, epithelioid mesothelioma, pancreatic adenocarcinoma, gastric adenocarcinoma, or triple negative breast cancer.

[0200] E142. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E138 to E141 , wherein said cancer is ovarian cancer.

[0201] E143. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E138 to E141 , wherein said cancer is pancreatic cancer.

[0202] E144. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E143, wherein said subject is a mammal, preferably a human.

[0203] E145. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E144, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0204] E146. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Pb-212.E147. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Pb-203.

[0205] E148. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Ac-225.

[0206] E149. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Lu-177.

[0207] E150. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is In-111.

[0208] E151. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Tb-161.

[0209] E152. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Cu-64.

[0210] E153. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Cu-67.

[0211] E154. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Zr-89.

[0212] E155. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Y-86.

[0213] E156. The conjugate or pharmaceutically acceptable salt or the pharmaceutical composition for use in a method of imaging, diagnosing and / or treating a medical condition of any one of E137 to E145, wherein said radionuclide is Ce-134.

[0214] E157. A method of treating a medical condition, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of the conjugate or pharmaceutically acceptable salt of any one of E1 to E134 or the pharmaceutical composition of E135.

[0215] E158. The method of E157, wherein said radionuclide is Ac-225, Lu-177, Tb-161, Pb-212 or Cu-67. E159. The method of E157, wherein said radionuclide is Pb-212.E160. The method of E157, wherein said radionuclide is Ac-225.

[0216] E161. The method of E157, wherein said radionuclide is Lu-177.

[0217] E162. The method of E157, wherein said radionuclide is Tb-161.

[0218] E163. The method of E157, wherein said radionuclide is Cu-67.

[0219] E164. A method of imaging and / or diagnosing a medical condition, the method comprising the steps of: (i) administering to a subject an amount of the conjugate or pharmaceutically acceptable salt of any one of E1 to E134, or of the pharmaceutical composition of E135, effective for binding of the conjugate or salt to cells expressing MSLN on their surface, and (ii) detecting cells bound by the conjugate or salt thereof or tissues comprising cells bound by the conjugate or salt thereof.

[0220] E165. The method of E164, wherein said detecting in step (ii) is performed by in vivo imaging.

[0221] E166. The method of E165, wherein said in vivo imaging uses single photon emission computed tomography (SPECT).

[0222] E167. The method of any one of E164 to E166, wherein said radionuclide is ln-111 , Cu-64, Zr-89, Y-86, Lu-177, Tb-161 , Pb-203 or Ce-134.

[0223] E168. The method of any one of E164 to E167, wherein said radionuclide is Pb-203.

[0224] E169. The method of any one of E164 to E167, wherein said radionuclide is Lu-177.

[0225] E170. The method of any one of E157 to E169, wherein said medical condition is cancer.

[0226] E171. The method of E170, wherein said cancer comprises cells that express MSLN on their surface. E172. The method of any one of E170 to E171 , wherein said cancer is ovarian cancer, mesothelioma, pancreatic cancer, gastric cancer, or breast cancer.

[0227] E173. The method of any one of E170 to E172, wherein said cancer is epithelial ovarian cancer, epithelioid mesothelioma, pancreatic adenocarcinoma, gastric adenocarcinoma, or triple negative breast cancer. E174. The method of any one of E170 to E173, wherein said cancer is ovarian cancer.

[0228] E175. The method of any one of E170 to E173, wherein said cancer is pancreatic cancer.

[0229] E176. The method of any one of E157 to E175, wherein said subject is a mammal, preferably a human. E177. Use of the conjugate or pharmaceutically acceptable salt thereof of any of E1 to E134 or the pharmaceutical composition of E135 in the manufacture of a medicament.

[0230] E178. Use of the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition of E177, wherein said medicament is for treatment of cancer, optionally for treatment of ovarian cancer, mesothelioma, pancreatic cancer, gastric cancer, or breast cancer.E179. A method of manufacturing a medicament for the treatment of a medical condition, wherein the conjugate or pharmaceutically acceptable salt of any one of E1 to E134 or the pharmaceutical composition of E135 is an active ingredient of said medicament.

[0231] E180. The method of manufacturing a medicament for the treatment of a medical condition of E179, wherein said medical condition is cancer, optionally ovarian cancer, mesothelioma, pancreatic cancer, gastric cancer, or breast cancer.

[0232] BRIEF DESCRIPTION OF THE DRAWINGS FIGURES 1A and 1B: Illustration of the structures of exemplary embodiments of the MSLN-specific conjugates disclosed herein. Figure 1A: R1 , R2, and R3 are independently NH2 or OH; A is CaHbNcOd, wherein a, b, c, and d are integers; R4 is an ankyrin repeat protein comprising the amino acid sequence of any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 or a variant thereof; R5 is a chelated radionuclide, either Pb-212 or Pb-203. Figure 1B: R1 , R2, R3 and R4 are independently NH2 or OH; A is CaHbNcOd, wherein a, b, c, and d are integers; R5 is an ankyrin repeat protein comprising the amino acid sequence of any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 or a variant thereof; R6 is a chelated radionuclide, either Pb-212 or Pb-203.

[0233] FIGURES 2A to 2H: Binding of different concentrations of selected single domain (1D) and two domain (2D) DARPins to Ovcar-3 cells and MC38 cells expressing human MSLN (hMSLN-MC38), in absence and presence of 10 pM human serum albumin. Anetumab was used as a positive control, and a non-binding DARPin (SEQ ID NO: 41) as a negative control. DARPin #1 , DARPin #11 and DARPin #13 on Ovcar-3 cells, with HSA (Figure 2A) and without HSA (Figure 2C), and on hMSLN-MC38 cells, with HSA (Figure 2E) and without HSA (Figure 2G). DARPin #4, DARPin #16 and DARPin #18 on Ovcar-3 cells, with HSA (Figure 2B) and without HSA (Figure 2D), and on hMSLN-MC38 cells, with HSA (Figure 2F) and without HSA (Figure 2H).

[0234] FIGURE 3: Binding of different concentrations of selected two domain (2D) DARPins (DARPin #25 and DARPin #26), which have a different positioning of the two ankyrin repeat domains within the proteins, to Ovcar-3 cells, in absence and presence of 10 pM human serum albumin.

[0235] FIGURES 4A to 4D: Binding of different concentrations of selected two domain (2D) DARPins, which comprise different linkers connecting the two ankyrin repeat domains, to Ovcar-3 cells and hMSLN-MC38 cells, in absence of human serum albumin. DARPin #10, DARPin #11 , DARPin #12, and DARPin #13 on hMSLN-MC38 cells (Figure 4A) and Ovcar-3 cells (Figure 4B); DARPin #14, DARPin #16, DARPin #17, and DARPin #18 on hMSLN-MC38 cells (Figure 4C) and Ovcar-3 cells (Figure 4D).

[0236] FIGURES 5A and 5B: In vivo biodistribution of Pb-212 labelled DARPin conjugates. Radio-labelled DARPin (DARPin #21 , DARPin #24) conjugate was injected i.v. at 0.01mg / kg (10pCi) into athymic nude mice xenografted subcutaneously with hMSLN-MC38 cells. Blood, small intestine, colon, kidneys, liver, lung, heart, tail and tumor were collected and weighed 4h and 24h post injection and radioactivity of each sample was measured using a y-counter instrument (Wizard22470, Perkin Elmer). Figure 5A: DARPin #21 conjugate; Figure 5B: DARPin #24 conjugate.FIGURE 6: Pharmacokinetic analysis of natural lead-labelled DARPin conjugates in WT mice. Natural lead-labeled DARPin conjugates (DARPin #21 , DARPin #24, DARPin #27) were injected i.v. at 0.01mg / kg or 1mg / kg into the tail vein of WT Athymic nude mice. Serum was collected 5 min, 4 h, 24 h, 48 h, 72 h, 96h and 168h post injection. DARPin was detected and measured by ELISA. LLOQ: Lower Limit of Quantification.

[0237] FIGURE 7: Pharmacokinetic analysis of natural lead-labelled DARPin conjugates in tumor-bearing mice. Athymic nude mice were subcutaneously engrafted with hMSLN-MC38 cells, and once tumor volumes reached the predetermined volume (~300-500 mm3), animals were randomized and injected with DARPins. Natural lead-labeled DARPin conjugates (DARPin #21, DARPin #27) were injected i.v. at 0.01mg / kg or 1mg / kg into the tail vein of the tumor-bearing mice. Serum was collected 4 h, 24 h, 72 h and 96h post injection. DARPin was detected and measured by ELISA. LLOQ: Lower Limit of Quantification.

[0238] FIGURES 8A to 8C: Binding of different concentrations of selected two domain (2D) DARPins to MC38 cells expressing human MSLN (hMSLN-MC38) (Fig. 8A) and OVCAR-3 cells (Fig. 8B, 8C) in absence and presence of 10 pM human serum albumin. DARPin #33, DARPin #34, DARPin #35, and DARPin #11 with and without HSA binding to hMSLN-MC38 cells (FIGURE 8A) and to OVCAR-3 cells (Figure 8B). His-tagged or DOTAM-conjugated DARPin #33 (His-tagged), DARPin #38 (DOTAM-conjugated), DARPin #35 (His-tagged), DARPin #40 (DOTAM-conjugated), and DARPin #19 (His-tagged) binding to OVCAR-3 cells in the presence of 10 pM human serum albumin (HSA). Anetumab and 15B6 were used as a positive control. MFI: mean fluorescence intensity.

[0239] DETAILED DESCRIPTION OF THE INVENTION

[0240] Designed ankyrin repeat domains are structural units of designed ankyrin repeat proteins. Designed repeat protein libraries, including designed ankyrin repeat protein libraries (W02002020565; Binz et al., Nat. Biotechnol. 22, 575-582, 2004; Stumpp et al., Drug Discov. Today 13, 695-701 , 2008), can be used for the selection of target-specific designed repeat domains that bind to their target with high affinity. Such targetspecific designed repeat domains in turn can be used as valuable components of recombinant binding proteins for the treatment and / or diagnosis of diseases.

[0241] Designed ankyrin repeat proteins are a class of binding molecules which have the potential to overcome limitations of monoclonal antibodies, hence allowing novel therapeutic and / or diagnostic approaches. Such ankyrin repeat proteins may comprise a single designed ankyrin repeat domain, or may comprise a combination of two, three, four, five or more designed ankyrin repeat domains with the same or different target specificities (Stumpp et al., Drug Discov. Today 13, 695-701 , 2008; U.S. Patent No. 9,458,211). Ankyrin repeat proteins comprising only a single designed ankyrin repeat domain are small proteins (14 kDa) which can be selected to bind a given target protein with high affinity and specificity. These characteristics, and the possibility of combining two, three, four, five or more designed ankyrin repeat domains in one protein, make designed ankyrin repeat proteins ideal agonistic, antagonistic and / or inhibitory drug candidates. Furthermore, such ankyrin repeat proteins can be engineered to carry various effector functions, e.g. cytotoxic agents or half-life extending agents, enabling completely new drug formats. Taken together, designed ankyrin repeat proteins are an example of the next generation of protein therapeutics with the potential to surpass existing antibody drugs.Various approaches have been explored to harness the potential of mesothelin as a therapeutic target, including antibody-drug conjugates (ADCs), immunotherapies including chimeric antigen receptor (CAR) T-cell therapy, and targeted drug delivery systems. However, soluble mesothelin (sMSLN) can act as a significant antigen sink and thereby reduce the efficacy of therapeutic agents targeting mesothelin. At the same time, targeting membrane-proximal epitopes of mesothelin, which are part of the truncated mesothelin protein (tMSLN) that remains on the cell surface after shedding and / or which are not part of soluble mesothelin (sMSLN), is not amenable to all therapeutic approaches.

[0242] The inventors of the present invention have found that designed ankyrin repeat domains with binding specificity for MSLN can be covalently combined with other moieties to form MSLN-specific binding constructs that can be loaded with various radionuclides, including actinium-225 (225Ac, Ac-225, ti / 2= 9.92 days), lutetium-177 (177Lu or Lu-177, ti / 2= 6.647 days), and the theranostic pair of lead-203 (203Pb or Pb-203, ti / 2= 51.9 h) and lead-212 (212Pb or Pb-212, ti / 2= 10.6 h). These radio-labelled MSLN-specific DARPin conjugates have beneficial properties that make them useful for applications in imaging, diagnosing and / or treating medical conditions characterized by MSLN expression on the surface of cells, such as certain cancers. Actinium-225 is an alpha emitter with a short range (a few cell diameters) of alpha particles in tissue and high energy, making it effective in targeting and killing cancer cells. The approximately 10-day half-life of 225Ac is long enough to facilitate treatment, but short enough that little remains in the body months after treatment. Lutetium-177 (Lu177) is a medium-energy p-emitter (Emax of 498.3 keV) and low-energy gamma emitter (Ey max of 208 keV) with maximaltissue penetration of <3 mm of diameter, enabling localized cytotoxic radiation in relatively small tumors as well as metastatic lesions. Additionally, Lu177’s relatively long half-life, allows delivery to sites distant from the reactor production facility with minimal decay loss. Lead-212 serves as an in vivo generator of alpha-particle emitters through its daughter nuclides (212Bi and212Po), which undergo a-decay The higher linear-energy transfer of alpha-particles (compared to beta-particles) may result in increased incidence of double-strand DNA breaks and improved localized cancer cell damage, while Pb-203 provides imaging capabilities for the theranostic pair. Moreover, the inventors were able to design MSLN-specific DARPin conjugates with binding specificity to membrane-proximal epitopes of mesothelin, which are part of the truncated mesothelin protein (tMSLN) that remains on the cell surface after shedding and / or which are not part of soluble mesothelin (sMSLN). These MSLN-specific DARPin conjugates of the invention bind to membrane-bound mesothelin (full length or truncated forms) on the cell surface, but do not specifically bind to soluble mesothelin (sMSLN) and hence are not affected by a sMSLN antigen sink.

[0243] Conjugates or pharmaceutically acceptable salts thereof

[0244] In one aspect, provided is a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide. In one embodiment, said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator. Said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.Accordingly, provided is a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Ac-225.

[0245] Also provided is a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Lu-177.

[0246] Also provided is a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is In-111.

[0247] In one main aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212 or Pb-203. In one embodiment, said radionuclide is Pb-212. In another embodiment, said radionuclide is Pb-203.

[0248] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has the formula: M-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide. Different methods of covalently connecting a polypeptide to a chelator have been described (see, e.g., in Morais and Ma, Drug Discovery Today: Technologies, Antibody - Drug Conjugates (ADC), Vol. 30, pp. 91-104, 2018; Tsuchikama and An, Protein Cell 2018, 9(1):33-46; Kang et al., Chem. Sci., 2021 , 12, 13613).

[0249] In another aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212 or Pb-203. In one embodiment, said radionuclide is Pb-212. In another embodiment, said radionuclide is Pb-203.

[0250] In another aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Ac-225, Lu-177, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134. In one embodiment, said radionuclide is Ac-225. In another embodiment, said radionuclide is Lu-177. In another embodiment, said radionuclide is In-111.In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has the formula: M-Co-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0251] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN binds human MSLN (hMSLN) with a KD value of or below 100 nM, of or below 30 nM, of or below 10 nM, of or below 3 nM, or of or below 1 nM, or of or below 350 pM, of or below 300 pM, of or below 100 pM, of or below 35 pM, of or below 30 pM, or of or below 10 pM. Thus, in one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 100 nM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 30 nM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 10 nM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 3 nM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value or of or below 1 nM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 350 pM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 300 pM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 100 pM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 35 pM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 30 pM. In one embodiment, said ankyrin repeat domain binds hMSLN with a KD value of or below 10 pM. Furthermore, in one embodiment, said ankyrin repeat domain binds to the extracellular domain of hMSLN. In one embodiment, said ankyrin repeat domain binds to a membrane-proximal epitope of mesothelin, which is part of truncated mesothelin protein (tMSLN) that remains on the cell surface after shedding and / or is not part of soluble mesothelin (sMSLN).

[0252] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91 % identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acidsequence that is at least 95% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and said any one of SEQ ID NOs: 1 to 4, or 42 to 44 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

[0253] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 1. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 1. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 1. In one embodiment,said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 1. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 1 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 1.

[0254] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 2. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 2. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 2. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 2 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 2.

[0255] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 3. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91%identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 3. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 3. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 3 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 3.

[0256] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 4. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 4. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 4. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 4 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 4.In one embodiment, said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 42. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 42. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 42. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 42 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 42.

[0257] In one embodiment, said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 43. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprisesan amino acid sequence that is at least 96% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 43. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 43. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 43 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 43.

[0258] In one embodiment, said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 44. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 44. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 44. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain and SEQ ID NO: 44 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence that is 100% identical to SEQ ID NO: 44.

[0259] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 25, or up to 24, or up to 23, or up to 22, or up to 21 , or up to 20, or up to 19, or up to 18, or up to 17, or up to 16, or up to 15, or up to 14, or up to 13, or up to 12, or up to 11 , or up to 10, or up to 9, or up to 8, or up to 7, or up to 6, or up to 5, or up to 4, or up to 3, or up to 2, or up to 1 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. Thus, in one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) anyone of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 25 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 20 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 15 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 10 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 5 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 4 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 3 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 2 amino acids in any one of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 1 amino acid in any one of SEQ ID NOs: 1 to 4, or 42 to 44 is substituted by another amino acid. In one embodiment, all of said 25, 24, 23, 22, 21 , 20, 19, 18, 17, 16, 15, 14, 13, 12, 11 , 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid substitutions occur in framework positions. In one embodiment, said ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 4, or 42 to 44.

[0260] In any of the conjugates, or pharmaceutically acceptable salts thereof, of the invention described herein, said ankyrin repeat domain with binding specificity for MSLN may optionally further comprise a “G,” an “S,” or a “GS” sequence at its N-terminus. Accordingly, in some embodiments, said ankyrin repeat domain with binding specificity for MSLN (i) comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (ii) further comprises at its N-terminus, a G, an S, or a GS. In some embodiments, said ankyrin repeat domain with binding specificity for MSLN (i) comprises an amino acid sequence selected from the group consisting of (1) any one of SEQ ID NOs: 1 to 4, or 42 to 44 and (2) sequences in which up to 25, or up to 24, or up to 23, or up to 22, or up to 21 , or up to 20, or up to 19, or up to 18, or up to 17, or up to 16, or up to 15, or up to 14, or up to 13, or up to 12, or up to 11 , or up to 10, or up to 9, or up to 8, or up to 7, or up to 6, or upto 5, or up to 4, or up to 3, or up to 2, or up to 1 amino acids in any of SEQ ID NOs: 1 to 4, or 42 to 44 are substituted by other amino acids, and (ii) further comprises at its N-terminus, a G, an S, or a GS. Thus, in an exemplary embodiment, said ankyrin repeat domain with binding specificity for MSLN (i) comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 1 and (ii) further comprises a GS at its N-terminus. In another exemplary embodiment, said ankyrin repeat domain with binding specificity for MSLN (i) comprises an amino acid sequence selected from the group consisting of (1) SEQ ID NO: 1 and (2) sequences in which up to 25, or up to 24, or up to 23, or up to 22, or up to 21 , or up to 20, or up to 19, or up to 18, or up to 17, or up to 16, or up to 15, or up to 14, or up to 13, or up to 12, or up to 11 , or up to 10, or up to 9, or up to 8, or up to 7, or up to 6, or up to 5, or up to 4, or up to 3, or up to 2, or up to 1 amino acids in SEQ ID NO: 1 are substituted by other amino acids, and (ii) further comprises a GS at its N-terminus.

[0261] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator comprises a 1 ,4,7,10-tetraazacyclododecane ring (PubChem CID 64963), or a derivative thereof. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises one or more side chains. In one embodiment, said one or more side chains are connected to one or more of the nitrogen atoms of said 1 ,4,7,10-tetraazacyclododecane ring. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises one, two, three or four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring. In one embodiment, at least one of said one or more side chains comprises a carboxyl group (-COOH) or an amide group (-CONH2). In one embodiment, at least one of said one or more side chains comprises a -CH2-COOH group or a -CH2-CONH2 group. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein each of said side chains comprises a carboxyl group (-COOH) or an amide group (-CONH2). In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein each of said side chains comprises a -CH2-COOH group or a -CH2-CONH2 group. In one embodiment, said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid) or TCMC (1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof. In one embodiment, said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid), or a derivative thereof. In one embodiment, said chelator is TCMC (1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof. TCMC is also called DOTAM or DOTA-amide. Derivatives of TCMC include, for example, monoacid forms of TCMC. Thus, in one exemplary embodiment, said chelator comprises a 1 ,4,7,10-tetraazacyclododecane ring, wherein said 1 ,4,7,10-tetraazacyclododecane ring comprises four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein one of said side chains comprises a -CH2-COOH group and at least one of said side chains comprises a -CH2-CONH2 group.

[0262] In one embodiment, the chelator is diethylenetriaminepentaacetic acid (DTPA), 1 ,4,7-triazacyclononane-1 ,4,7-triacetic acid (NOTA), 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA), 1 ,4, 7, IQ-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide (TCMC), or a derivative thereof. In one embodiment, the chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid), or a derivative thereof. In another embodiment, the chelator is TCMC (1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof.

[0263] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator comprises a 1 ,4,7,10-tetraazacyclododecane ring, wherein said 1,4,7,10-tetraazacyclododecane ring comprises one or more side chains, wherein said one or more side chains are connected to one or more of the nitrogen atoms of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein said chelator is covalently connected to said connector via one of said side chains. In one embodiment, said chelator has a structure of Formula (I):

[0264]

[0265] Formula (I)

[0266] wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN. In one embodiment, said chelator has a structure of Formula (II):

[0267]

[0268] Formula (II)

[0269] wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN.In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator comprises a 1 ,4,7,10-tetraazacyclododecane ring, and wherein said chelator is covalently connected to said connector via one ofthe carbon atoms of said 1 ,4,7,10-tetraazacyclododecane ring. In one embodiment, said chelator has a structure of Formula (III):

[0270]

[0271] wherein R1, R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN. In one embodiment, said chelator has a structure of Formula (IV):

[0272]

[0273] wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN.

[0274] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate further comprises a tag, wherein said tag comprises a Cysteine. In one embodiment, said tag is a peptide tag. In one embodiment, said tag is on one side covalently connected to said ankyrin repeat domain with binding specificity for MSLN and is on another side covalently connected to said chelator. In one embodiment, said tag is on one side covalently connected to said ankyrin repeat domain with binding specificity for MSLN and is on another side covalently connected to said connector. In one embodiment, said tag is located at the C-terminal side of said ankyrin repeat domain with binding specificityfor MSLN. In one embodiment, said tag is covalently connected by a peptide bond to the C-terminal end of said ankyrin repeat domain with binding specificity for MSLN. In one embodiment, said conjugate has the formula: M-T-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: M-T-Co-Ch-R, wherein M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. In one embodiment, said tag comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof.

[0275] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said connector is covalently connected to said tag via a thioether bond. In one embodiment, said connector comprises a maleimide or a derivative thereof. In one embodiment, said thioether bond covalently connecting said tag and said connector is formed between said Cysteine comprised in said tag and said maleimide comprised in said connector. In one embodiment, said connector has a structure of Formula (V):

[0276]

[0277] Formula (V)

[0278] wherein the dotted line originating from N represents the covalent connection to said chelator, and wherein the dotted line originating from a carbon atom represents the covalent connection to said tag or to said ankyrin repeat domain with binding specificity for MSLN.

[0279] In any of the aspects or embodiments described herein, the pharmaceutically acceptable salt may be a trifluoroacetate salt. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate further comprises a half-life extending moiety. In one embodiment, said conjugate has the formula: H-M-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: M-H-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: H-M-T-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: M-H-T-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: H-M-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: H-M-T-Co-Ch-R, wherein H is said half-life extendingmoiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: M-H-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: M-H-T-Co-Ch-R, wherein H is said half-life extending moiety, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. In one embodiment, said half-life extending moiety comprises an immunoglobulin domain. In one embodiment, the immunoglobulin domain comprises an Fc domain, or a variant thereof. In one embodiment, the Fc domain is derived from any one of the known heavy chain isotypes: IgG (y), IgM (p), IgD (6), IgE (s), or IgA (a). In another embodiment, the Fc domain is derived from any one of the known heavy chain isotypes or subtypes: IgGi (y1), lgG2 (y2), lgG3 (y3), lgG4 (y4), IgAi (a1), or lgA2 (a2). In one embodiment, the Fc domain is the Fc domain of human IgGi, or a variant thereof. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate further comprises a half-life extending moiety, and wherein said half-life extending moiety has binding specificity for human serum albumin. In one embodiment, said half-life extending moiety is an ankyrin repeat domain with binding specificity for human serum albumin. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin binds human serum albumin with a KD value of or below 500 nM, of or below 250 nM, or of or below 100 nM. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin binds human serum albumin with a KD value of or below 500 nM. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin binds human serum albumin with a KD value of or below 250 nM. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin binds human serum albumin with a KD value of or below 100 nM.

[0280] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 5 to 7, or 45. Thus, in one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 88% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 91% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 92% identical toany one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 93% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 94% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 96% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 98% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 5 to 7, or 45. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain with binding specificity for human serum albumin and any one of SEQ ID NOs: 5 to 7, or 45 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is 100% identical to any one of SEQ ID NOs: 5 to 7, or 45.

[0281] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 5. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain with binding specificity for human serum albumin and SEQ ID NO: 5 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is 100% identical to SEQ ID NO: 5.

[0282] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 6. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain with binding specificity for human serum albumin and SEQ ID NO: 6 represent amino acid substitutions in framework positions. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is 100% identical to SEQ ID NO: 6.

[0283] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat domain with binding specificity for human serum albumin comprises an aminoacid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 7. Thus, in one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 93% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 7. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is 100% identical to SEQ ID NO: 7. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain with binding specificity for human serum albumin and SEQ ID NO: 7 represent amino acid substitutions in framework positions.

[0284] In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 45. Thus, in one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 45. In one embodiment, said ankyrinrepeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 93% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 45. In one embodiment, said ankyrin repeat domain with binding specificity for human serum albumin comprises an amino acid sequence that is 100% identical to SEQ ID NO: 45. In one embodiment, any amino acid sequence differences between said ankyrin repeat domain with binding specificity for human serum albumin and SEQ ID NO: 45 represent amino acid substitutions in framework positions. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate further comprises a peptide linker, and wherein said ankyrin repeat domain with binding specificity for human serum albumin is covalently connected to said ankyrin repeat domain with binding specificity for MSLN by said peptide linker. Different peptide linkers are known in the art. Examples of peptide linkers include PT-rich linkers, PAS-rich linkers and GS-rich linkers. Peptide linkers can have different lengths. Thus, in one embodiment, said peptide linker comprises the amino acid sequence of any one of SEQ ID NOs: 9 to 15, or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 10 ora variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof. In one embodiment, said peptide linker comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof. Said peptide linker may have a length of 1 to 24 amino acids, of 1 to 22 amino acids, of I to 20 amino acids, of 1 to 19 amino acids, of 1 to 18 amino acids, of 1 to 17 amino acids, of 1 to 16 amino acids, of 1 to 15 amino acids, of 1 to 14 amino acids, of 1 to 13 amino acids, of 1 to 12 amino acids, of 1 to I I amino acids, of 1 to 10 amino acids, of 1 to 9 amino acids, of 1 to 8 amino acids, of 1 to 7 amino acids, of 1 to 6 amino acids, of 1 to 5 amino acids, of 1 to 4 amino acids, of 1 to 3 amino acids, of 1 to 2 aminoacids, or of 1 amino acid or about 2 to 20 amino acids, of about 2 to 15 amino acids, of about 2 to 11 amino acids, of about 2 to 10 amino acids, of about 2 to 9 amino acids, of about 2 to 8 amino acids, of about 3 to 11 amino acids, of about 3 to 10 amino acids, of about 3 to 9 amino acids, or of about 3 to 8 amino acids In one embodiment, said conjugate has the formula: H-L-M-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: M-L-H-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Ch is said chelator, and R is said radionuclide. In one embodiment, said conjugate has the formula: H-L-M-T-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: M-L-H-T-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: H-L-M-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: H-L-M-T-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: M-L-H-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, Co is said connector, Ch is said chelator, and R is said radionuclide. In another embodiment, said conjugate has the formula: M-L-H-T-Co-Ch-R, wherein H is said half-life extending moiety, L is said peptide linker, M is said ankyrin repeat domain with binding specificity for MSLN, T is said tag, Co is said connector, Ch is said chelator, and R is said radionuclide.

[0285] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. Said amino acid sequence comprised in said conjugate comprises an ankyrin repeat domain with binding specificity for human MSLN at the N-terminal side and an ankyrin repeat domain with binding specificity for human serum albumin at the C-terminal side, and a peptide linker that connects said two ankyrin repeat domains. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92%identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and said any one of SEQ ID NOs: 17 to 26, or 46 to 50 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16. In one embodiment, said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50 is covalently bound at its N-terminal end to Glycine-Serine (GS). In another embodiment, said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50 is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0286] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 18. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequencethat is at least 85% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 18. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 18 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 18. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0287] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 23. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 23. In one embodiment,said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 23. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 23 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 23. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0288] In one embodiment, said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 47. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 47. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 47 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 47. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.In one embodiment, said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 48. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 48. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 48 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 48. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0289] In one embodiment, said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 49. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 49. In oneembodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 49. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 49 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 49. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0290] In one embodiment, said conjugate comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 50. Thus, in one embodiment, said conjugate comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 50. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said conjugate and SEQ ID NO: 50 represent amino acid substitutions in framework positions of said two ankyrin repeat domains and / or in said peptide linker. In one embodiment, said conjugate comprises an amino acid sequence that is 100% identical to SEQ ID NO: 50. In one embodiment, said conjugate comprises said amino acid sequence described in any of the above embodiments, wherein said amino acid sequence is covalently bound at its N-terminal end to Glycine-Serine (GS). In one embodiment, said conjugate comprises said amino acid sequencedescribed in any of the above embodiments, wherein said amino acid sequence is covalently bound at its C-terminal end to the amino acid sequence of SEQ ID NO: 16.

[0291] In one aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said ankyrin repeat protein has binding specificity for human MSLN and for human serum albumin, wherein said connector is covalently connected to said ankyrin repeat protein, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0292] In another main aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said ankyrin repeat protein has binding specificity for human MSLN and for human serum albumin, wherein said connector is covalently connected to said ankyrin repeat protein, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212, Pb-203, Lu-177, Ac-225, or ln-111. An amino acid sequence of any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 comprises an ankyrin repeat domain with binding specificity for human serum albumin and an ankyrin repeat domain with binding specificity for human MSLN, wherein said ankyrin repeat domains are connected by a peptide linker, wherein said amino acid sequence comprises a Glycine-Serine (GS) at its N-terminus, and wherein said amino acid sequence comprises a Cysteine-containing tag at its C-terminus. In one embodiment, said radionuclide is Pb-212. In one embodiment, said radionuclide is Pb-203. In one embodiment, said radionuclide is Lu-177. In one embodiment, said radionuclide is Ac-225. In one embodiment, said radionuclide is In-111. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least at least 80% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identicalto any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and said any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and said any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of said any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56.

[0293] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 29. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence thatis at least 91% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 29. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 29. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 29 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 29 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 29 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 29.

[0294] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 30. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises anamino acid sequence that is at least 92% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 30. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 30. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 30 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 30 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 30 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 30.

[0295] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 31. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 31. In one embodiment, said ankyrinrepeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 31. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 31. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 31 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 31 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 31 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 31.

[0296] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 32. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 32. In oneembodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 32. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 32. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 32 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 32 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 32 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 32.

[0297] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 33. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 33. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 33. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 33 represent amino acid substitutions in positions other than positions of potential targetinteraction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 33 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 33 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 33.

[0298] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 34. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 34. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 34. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 34 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acidsequence comprised in said ankyrin repeat protein and SEQ ID NO: 34 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 34 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 34.

[0299] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 38. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 81% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 82% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 83% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 84% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 86% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 87% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 89% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 38. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 38. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 38 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 38 represent amino acid substitutionsin (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 38 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 38.

[0300] In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 51. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 51. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 51. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 51 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 51 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 51 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 51.

[0301] In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 52. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 52. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 52. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 52 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 52 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 52 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 52.

[0302] In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 53. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97%identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 53. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 53. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 53 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 53 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 53 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 53.

[0303] In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 54. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 54. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 54. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 54 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 54 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 54 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 54.In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 55. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 55. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 55. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 55 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 55 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 55 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 55.

[0304] In one embodiment, said ankyrin repeat protein with binding specificity for MSLN and for human serum albumin comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 56. Thus, in one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 91% identical to SEQ ID NO: 56. In one embodiment,said ankyrin repeat protein comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 93% identical SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 56. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 56. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 56 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein and SEQ ID NO: 56 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 56 is not substituted with another amino acid. In one embodiment, said ankyrin repeat protein comprises an amino acid sequence that is 100% identical to SEQ ID NO: 56.

[0305] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein comprises a Cysteine, wherein said connector comprises maleimide or a derivative thereof, and wherein said Cysteine is covalently bound to said connector via a thioether bond. In one embodiment, said Cysteine is located at the C-terminal end of said amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56.

[0306] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator comprises a 1 ,4,7,10-tetraazacyclododecane ring (PubChem CID 64963), or a derivative thereof. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises one or more side chains. In one embodiment, said one or more side chains are connected to one or more of the nitrogen atoms of said 1 ,4,7,10-tetraazacyclododecane ring. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises one, two, three or four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring. In one embodiment, at least one of said one or more side chains comprises a carboxyl group (-COOH) or an amide group (-CONH2). In one embodiment, at least one of said one or more side chains comprises a -CH2-COOH group or a -CH2-CONH2 group. In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein each of said side chains comprises a carboxyl group (-COOH) or an amide group (-CONH2). In one embodiment, said 1 ,4,7,10-tetraazacyclododecane ring comprises four side chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecanering, and wherein each of said side chains comprises a -CH2-COOH group or a -CH2-CONH2 group. In one embodiment, said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid) or TCMC (1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof. In one embodiment, said chelator is DOTA (1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid), or a derivative thereof. In one embodiment, said chelator is TCMC (1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide), or a derivative thereof. TCMC is also called DOTAM or DOTA-amide. Derivatives of TCMC include, for example, monoacid forms of TCMC. Thus, in one embodiment, said chelator comprises a 1,4,7,10-tetraazacyclododecane ring, wherein said 1 ,4,7,10-tetraazacyclododecane ring comprises fourside chains, wherein each of said side chains is connected to a nitrogen atom of said 1 ,4,7,10-tetraazacyclododecane ring, and wherein one of said side chains comprises a -CH2-COOH group and at least one of said side chains comprises a -CH2-CONH2 group.

[0307] In one embodiment, the chelator is diethylenetriaminepentaacetic acid (DTPA), 1 ,4,7-triazacyclononane-1 ,4,7-triacetic acid (NOTA), 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA), 1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide (TCMC), or a derivative thereof. In one embodiment, the chelator is 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA), or a derivative thereof. In another embodiment, the chelator is 1 ,4,7,10-Tetraazacyclododecane-1 ,4,7,10-tetraacetamide (TCMC), or a derivative thereof.

[0308] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator has a structure of Formula (I):

[0309]

[0310] Formula (I)

[0311] wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN; or of Formula (III):

[0312]

[0313] Formula (III)

[0314] wherein R1, R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator has a structure of Formula (I):

[0315]

[0316] Formula (I)

[0317] wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN. In one embodiment, said chelator has a structure of Formula (II):

[0318]

[0319] Formula (II)

[0320] wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN.

[0321] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said chelator has a structure of Formula (III):

[0322]

[0323] Formula (III)

[0324] wherein R1, R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN. In one embodiment, said chelator has a structure of Formula (IV):

[0325]

[0326] Formula (IV)

[0327] wherein the dotted line represents the covalent connection to said connector or to said ankyrin repeat domain with binding specificity for MSLN.

[0328] In another aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VI):

[0329]

[0330] Formula (VI)

[0331] wherein R1 , R2, and R3 are independently NH2 or OH;

[0332] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0333] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin,wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0334] and wherein R5 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111 ;

[0335] or the conjugate having a structure of Formula (VII):

[0336]

[0337] Formula (VII)

[0338] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0339] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0340] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0341] and wherein R6 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111.

[0342] Thus, in one aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VI):

[0343]

[0344] Formula (VI)

[0345] wherein R1 , R2, and R3 are independently NH2 or OH;

[0346] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0347] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0348] and wherein R5 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111. In one embodiment, said R5 in Formula (VI) is a chelated radionuclide, wherein said radionuclide is Ac-225. In one embodiment, said R5 in Formula (VI) is a chelated radionuclide, wherein said radionuclide is Lu-177. In one embodiment, said R5 in Formula (VI) is a chelated radionuclide, wherein said radionuclide is ln-111.

[0349] Thus, in one aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VII):

[0350]

[0351] Formula (VII)

[0352] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0353] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0354] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0355] and wherein R6 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111. In one embodiment, said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is Ac-225. In one embodiment, said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is Lu-177. In one embodiment, said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is ln-111.

[0356] In another main aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VI):

[0357]

[0358] Formula (VI)

[0359] wherein R1 , R2, and R3 are independently NH2 or OH;

[0360] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0361] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0362] and wherein R5 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203;

[0363] or the conjugate having a structure of Formula (VII):

[0364]

[0365] Formula (VII)

[0366] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0367] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0368] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0369] and wherein R6 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203.

[0370] In one embodiment, said R5 in Formula (VI) or said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is Pb-212. In one embodiment, said R5 in Formula (VI) or said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is Pb-203.

[0371] Thus, in one aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VI):

[0372]

[0373] Formula (VI)

[0374] wherein R1 , R2, and R3 are independently NH2 or OH;

[0375] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0376] wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0377] and wherein R5 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203. In one embodiment, said R5 in Formula (VI) is a chelated radionuclide, wherein said radionuclide is Pb-212. In one embodiment, said R5 in Formula (VI) is a chelated radionuclide, wherein said radionuclide is Pb-203. Thus, in one aspect, the invention relates to a conjugate or pharmaceutically acceptable salt thereof, the conjugate having a structure of Formula (VII):

[0378]

[0379] Formula (VII)

[0380] wherein R1 , R2, R3 and R4 are independently NH2 or OH;

[0381] wherein A is CaHbNcOd, wherein a, b, c, and d are integers;

[0382] wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, wherein said ankyrin repeat protein comprises a Cysteine, and wherein said Cysteine forms a thioether bond connecting said ankyrin repeat protein with a maleimide ring;

[0383] and wherein R6 is a chelated radionuclide, wherein said radionuclide is Pb-212 or Pb-203. In one embodiment, said R6 in Formula (VII) is a chelated radionuclide, wherein said radionuclide is Pb-212. In one embodiment, said R6 in Formula (VI I) is a chelated radionuclide, wherein said radionuclide is Pb-203. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 29 to 34, 38,and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in Formula (VI) or in said ankyrin repeat protein (R5) in Formula (VII) and said any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in Formula (VI) or in said ankyrin repeat protein (R5) in Formula (VII) and said any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of said any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56 is not substituted with another amino acid. In one embodiment, said amino acid sequence comprised in said ankyrin repeat protein (R4) in Formula (VI) or in said ankyrin repeat protein (R5) in Formula (VII) has a Cysteine at the C-terminal end. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to any one of SEQ ID NOs: 29 to 34, 38, and 51 to 56. In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 30. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat proteincomprising an amino acid sequence that is at least 81% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 82% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 83% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 84% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 86% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 87% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 89% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 30. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 30. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 30 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 30 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 30 is not substituted with another amino acid. In one embodiment, said amino acid sequencecomprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) has a Cysteine at the C-terminal end. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 30.

[0384] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 33. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 33. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 33. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 33 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 33 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 33is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 33.

[0385] In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 51. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 51. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 51. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 51 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 51 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 51 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 inFormula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 51.

[0386] In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 52. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 52. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 52. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 52 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 52 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 52 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 52.In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 53. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 53. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 53. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 53 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 53 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 53 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 53.

[0387] In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 54. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 54. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 54. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 54 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 54 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 54 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 54.

[0388] In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%,or 100% identical to SEQ ID NO: 55. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 55. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 55. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 55 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 55 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 55 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 55.

[0389] In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 56. Thus, in one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identicalto SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 88% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 91% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 93% identical SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 94% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VI I) is an ankyrin repeat protein comprising an amino acid sequence that is at least 96% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 56. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is at least 99% identical to SEQ ID NO: 56. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 56 represent amino acid substitutions in positions other than positions of potential target interaction residues of ankyrin repeat domains. In one embodiment, any amino acid sequence differences between said amino acid sequence comprised in said ankyrin repeat protein (R4) in structure (I) or in said ankyrin repeat protein (R5) in structure (II) and SEQ ID NO: 56 represent amino acid substitutions in (i) framework positions of ankyrin repeat domain(s), (ii) a peptide linker, (iii) a Glycine-Serine (GS), and / or (iv) a Cysteine-containing tag. In one embodiment, the C-terminal Cysteine of SEQ ID NO: 56 is not substituted with another amino acid. In one embodiment, said R4 in Formula (VI) or said R5 in Formula (VII) is an ankyrin repeat protein comprising an amino acid sequence that is 100% identical to SEQ ID NO: 56.

[0390] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein binds human MSLN (hMSLN) with a KD value of or below 100 nM, of or below 30 nM, of or below 10 nM, of or below 3 nM, or of or below 1 nM, of or below 300 pM, of or below 100 pM, of or below 30 pM, or of or below 10 pM. Thus, in one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 100 nM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 30 nM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 10 nM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 3 nM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value or ofor below 1 nM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 400 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 350 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 300 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 200 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 100 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 35 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 30 pM. In one embodiment, said ankyrin repeat protein binds hMSLN with a KD value of or below 10 pM. Furthermore, in one embodiment, said ankyrin repeat protein binds to the extracellular domain of hMSLN. In one embodiment, said conjugate does not specifically bind to human soluble MSLN (sMSLN). In another embodiment, said conjugate binds to cells expressing human MSLN on their surface, wherein said binding to cells expressing human MSLN on their surface is not inhibited by the presence of human soluble MSLN (sMSLN).

[0391] In another aspect, the invention relates to such a conjugate or pharmaceutically acceptable salt thereof, wherein said ankyrin repeat protein binds human serum albumin with a KD value of or below 500 nM, of or below 250 nM, or of or below 100 nM. In one embodiment, said ankyrin repeat protein binds human serum albumin with a KD value of or below 500 nM. In one embodiment, said ankyrin repeat protein binds human serum albumin with a KD value of or below 250 nM. In one embodiment, said ankyrin repeat protein binds human serum albumin with a KD value of or below 100 nM.

[0392] In another aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the disclosed aspects and embodiments, wherein said conjugate binds to cells expressing human MSLN on their surface. In one embodiment, said cells are hMSLN-MC38 cells, wherein hMSLN-MC38 cells are MC38 cells engineered to express human MSLN on their surface. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 below 10_7M, or about or below 5 x 10-8M, or about or below 2 x 10-8M, or about or below 10-8M, or about or below 5 x 10-9M, or about or below 10-9M, or about or below 5 x 10'1°M, or about or below 2 x 10'1°M, or about or below 10'1°M. Thus, in one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 below 10-7M, and in another embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 5 x 10-8M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 2 x 10-8M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 10-8M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 5 x 10-9M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 10-9M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 5 x 10'1°M. In one embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 2 x 10'1°M. In another embodiment, said conjugate binds human MSLN-expressing hMSLN-MC38 cells with an EC50 about or below 10'1°M.In another aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the disclosed aspects and embodiments, wherein said conjugate binds to cells expressing human MSLN on their surface, and wherein said cells are OVCAR-3 cells. In another embodiment, said conjugate binds to cells expressing human MSLN on their surface, and wherein said cells are OVCAR-8 cells. OVCAR-3 / OVCAR-8 ovarian carcinoma cells naturally (endogenously) express human MSLN on their cell surface. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 below 10-7M, or about or below 3 x 10-8M, or about or below 10-8M, or about or below 6 x 10-9M, or about or below 3 x 10-9M, or about or below 10-9M, or about or below 6 x 10'1°M, or about or below 3 x 10'1°M, or about or below 10'1°M. Thus, in one embodiment, said conjugate binds OVCAR-3 cells with an EC50 below 10-7M, and in another embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 3 x 10-8M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 5 x 10-7M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 1.5 x 10-7M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 5 x 10-8M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 1.5 x 10-8M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 10-8M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 6 x 10-9M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 5 x 10-9M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 3 x 10-9M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 about or below 2 x 10-9M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 10-9M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 6 x 10'1°M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 5 x 10'1°M. In one embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 3 x 10'1°M. In another embodiment, said conjugate binds OVCAR-3 cells with an EC50 or about or below 10'1°M.

[0393] In another aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the disclosed aspects and embodiments, wherein said conjugate has a terminal half-life in a mouse model of at least about 5 hours, at least about 7.5 hours, at least about 10 hours, at least about 12.5 hours, at least about 15 hours, at least about 17.5 hours, at least about 20 hours, at least about 22.5 hours, at least about 25 hours, at least about 27.5 hours, at least about 30 hours, at least about 32.5 hours, at least about 35 hours, or at least about 40 hours. In one embodiment, said conjugate has a terminal half-life in a mouse model of about 5 to 45 hours, about 5 to 40 hours, about 5 to 35 hours, about 10 to 35 hours, about 10 to 30 hours, about 15 to 35 hours, about 15 to 30 hours, or about 13 to 27 hours. In one embodiment, said conjugate has a terminal half-life in a mouse model of at least about 12.5 hours. In another embodiment, said conjugate has a terminal half-life in a mouse model of about 13 to 27 hours. In one embodiment, said terminal half-life of said conjugate is measured in a BALB / c mouse model. In one embodiment, said terminal half-life of said conjugate is measured after intravenous injection of 1 mg / kg of conjugate into said mouse model.

[0394] In another aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the disclosed aspects and embodiments, wherein said radionuclide is Pb-212 or Ac-225, and wherein said conjugate is capable of inhibiting tumor growth in a human MSLN-expressing mouse tumor model. In one embodiment, said human MSLN-expressing mouse tumor model is an hMSLN-expressing MC38 (hMSLN-MC38) colon carcinoma mouse model, an OVCAR-3 ovarian carcinoma mouse model, a Capan-2 pancreatic carcinoma mouse model, or an OVCAR-8 ovarian carcinoma mouse model. In one embodiment, said human MSLN-expressing mouse tumor model is an hMSLN-expressing MC38 (hMSLN-MC38) colon carcinoma mouse model. To generate the hMSLN-MC38 mouse tumor model, MC38 cells are engineered to express human MSLN on their surface. In one embodiment, said conjugate is capable of inhibiting tumor growth in a hMSLN-expressing MC38 (hMSLN-MC38) colon carcinoma mouse model. In another embodiment, said human MSLN-expressing mouse tumor model is an OVCAR-3 ovarian carcinoma mouse model. OVCAR-3 ovarian carcinoma cells naturally (endogenously) express human MSLN on their cell surface. In one embodiment, said conjugate is capable of inhibiting tumor growth in an OVCAR-3 ovarian carcinoma mouse model.

[0395] Pharmaceutical compositions and kits

[0396] In another aspect, the invention relates to a pharmaceutical composition comprising any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the aforementioned aspects and embodiments, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent. In one exemplary embodiment, the invention relates to a pharmaceutical composition comprising a conjugate or pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or ln-111 , and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In another exemplary embodiment, the invention relates to a pharmaceutical composition comprising a conjugate or pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or ln-111 , and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.In another aspect, the invention relates to a pharmaceutical composition comprising any one of said conjugates or pharmaceutically acceptable salts thereof described herein in any of the aforementioned aspects and embodiments, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent. In one exemplary embodiment, the invention relates to a pharmaceutical composition comprising a conjugate or pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Pb-212 or Ac-225, and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In another exemplary embodiment, the invention relates to a pharmaceutical composition comprising a conjugate or pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Pb-212 or Ac-225, and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

[0397] Pharmaceutically acceptable carriers, excipients, stabilizers and / or diluents are known to the person skilled in the art and are explained in more detail below.

[0398] In one embodiment, a pharmaceutical composition comprises a conjugate or pharmaceutically acceptable salt thereof according to the present invention, and a pharmaceutically acceptable carrier, excipient, stabilizer and / or diluent, for example as described in Remington, The Science and Practice of Pharmacy; 23rd edition; Adeboye A. Ed., 2020.

[0399] Pharmaceutically acceptable carriers, excipients, stabilizers and / or diluents known to one of skill in the art include, for example, saline, Ringer's solution, dextrose solution, Hank's solution, fixed oils, ethyl oleate, 5% dextrose in saline, substances that enhance isotonicity and chemical stability, buffers and preservatives. Other potentially suitable carriers include any carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids and amino acid copolymers. A pharmaceutical composition may also comprise an antioxidant and / or a scavenger. A pharmaceutical composition may further be a combination formulation, comprising an additional active agent, such as an anti-cancer agent or an anti-angiogenic agent, or an additional bioactive compound.In one embodiment, a pharmaceutical composition comprises a conjugate or pharmaceutically acceptable salt thereof according to the present invention, and a detergent such as nonionic detergent, a buffer such as phosphate buffer, and / or a sugar such as sucrose. In one embodiment, a pharmaceutical composition comprises a conjugate or pharmaceutically acceptable salt thereof according to the present invention, and PBS.

[0400] The formulations to be used for in vivo administration must be aseptic or sterile. This can be readily accomplished, e.g., by filtration through sterile filtration membranes.

[0401] In one embodiment, provided is the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, for manufacturing a pharmaceutical composition. In one embodiment, the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, is for manufacturing a pharmaceutical composition, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, orCe-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or ln-111 , and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In another embodiment, the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, is for manufacturing a pharmaceutical composition, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, orCe-134, preferably Ac-225, Lu-177, Pb-203, Pb-212, or In-111 , and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

[0402] In one embodiment, the present invention relates to the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, for manufacturing a pharmaceutical composition. In one exemplary embodiment, the present invention relates to the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, for manufacturing a pharmaceutical composition, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Pb-212, and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acidsequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44. In another exemplary embodiment, the present invention relates to the use of a conjugate or pharmaceutically acceptable salt thereof, as described herein, for manufacturing a pharmaceutical composition, wherein said conjugate comprises (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a connector, (iii) a chelator, and (iv) a radionuclide, wherein said connector is covalently connected to said ankyrin repeat domain with binding specificity for MSLN, wherein said chelator is covalently connected to said connector, wherein said radionuclide is bound to said chelator, wherein said radionuclide is Pb-212, and wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

[0403] In another aspect, the invention relates to a kit comprising (i) a first container containing any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical compositions described herein in any of the aforementioned aspects and embodiments; and (ii) a second container containing a buffered solution.

[0404] Methods of imaging, diagnosing and / or treating medical conditions

[0405] In another aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical composition, described herein in any of the aforementioned aspects and embodiments, for use in a method of imaging, diagnosing and / or treating a medical condition, the method comprising the step of administering to a subject in need thereof an amount of said conjugate or salt or of said pharmaceutical composition effective for imaging, diagnosing and / or treating said medical condition. In a more particular aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical composition, described herein in any of the aforementioned aspects and embodiments, for use in a method of treating a medical condition, the method comprising the step of administering to a subject in need thereof an amount of said conjugate or salt or of said pharmaceutical composition effective for treating said medical condition. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Pb-212. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Ac-225. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Lu-177. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Th-227. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Tb-149. In oneembodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Tb-161. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of treating a medical condition is Y-90.

[0406] In another more particular aspect, the invention relates to any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical compositions, described herein in any of the aforementioned aspects and embodiments, for use in a method of imaging and / or diagnosing a medical condition, the method comprising the step of administering to a subject an amount of said conjugate or salt or of said pharmaceutical composition effective for imaging and / or diagnosing said medical condition. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Pb-203. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Lu-177. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Tc-99m. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is In-111. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Ga-68. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Cu-64. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Zr-89. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Y-86. In one embodiment, said radionuclide comprised in said conjugates or pharmaceutically acceptable salts thereof or in said pharmaceutical compositions for use in a method of imaging and / or diagnosing a medical condition is Ce-134.

[0407] In another aspect, the invention relates to a method of treating a medical condition, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical compositions described herein in any of the aforementioned aspects and embodiments. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Pb-212. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Ac-225. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Lu-177. In one embodiment, said radionuclide comprised in said conjugate or pharmaceuticallyacceptable salt thereof or in said pharmaceutical composition administered to said subject is Th-227. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Tb-149. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Tb-161. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Y-90. . In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Cu-67.

[0408] In another aspect, the invention relates to a method of imaging and / or diagnosing a medical condition, the method comprising the step of administering to a subject an amount of any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical compositions described herein in any of the aforementioned aspects and embodiments, effective for imaging and / or diagnosing said medical condition. In one embodiment, said method of imaging and / or diagnosing a medical condition comprises the steps of (i) administering to a subject an amount of any one of said conjugates or pharmaceutically acceptable salts thereof or said pharmaceutical compositions, effective for binding of conjugate or salt thereof to cells expressing MSLN on their surface, and (ii) detecting cells bound by conjugate or salt thereof and / or tissues comprising cells bound by conjugate or salt thereof. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is ln-111 , Cu-64, Zr-89, Y-86, Lu-177, Tb-161 , Pb-203 or Ce-134. In one embodiment, said detecting in step (ii) is performed by in vivo imaging. In one embodiment, said detecting in step (ii) is performed by in vivo imaging, wherein said in vivo imaging uses single photon emission computed tomography (SPECT). In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Pb-203. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Lu-177. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is Tc-99m. In one embodiment, said radionuclide comprised in said conjugate or pharmaceutically acceptable salt thereof or in said pharmaceutical composition administered to said subject is ln-111.

[0409] In o...

Claims

New PCT Patent ApplicationMolecular Partners AG; Orano Med TheranosticsVossius Ref.: AJ4272 PCT S3CLAIMS1. A conjugate or pharmaceutically acceptable salt thereof, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide.

2. The conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator.

3. The conjugate or pharmaceutically acceptable salt thereof of claim 1 or claim 2, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, ln-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134.

4. The conjugate or pharmaceutically acceptable salt thereof of any one of the preceding claims, the conjugate comprising (i) an ankyrin repeat domain with binding specificity for MSLN, (ii) a chelator, and (iii) a radionuclide, wherein said chelator is covalently connected to said ankyrin repeat domain, wherein said radionuclide is bound to said chelator, and wherein said radionuclide is Pb-212 or Pb-203.

5. The conjugate or pharmaceutically acceptable salt thereof of any one of the preceding claims, wherein said ankyrin repeat domain with binding specificity for MSLN comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 1 to 4, or 42 to 44.

6. The conjugate or pharmaceutically acceptable salt thereof of any one of the preceding claims, wherein said chelator has a structure of Formula (I):Formula (I)wherein R1 , R2 and R3 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or to a connector; or wherein said chelator has a structure of Formula (III):Formula (III)wherein R1 , R2, R3 and R4 are independently NH2 or OH, and wherein the dotted line represents the covalent connection to said ankyrin repeat domain with binding specificity for MSLN or to a connector.

7. The conjugate or pharmaceutically acceptable salt of claim 6, wherein said connector comprises a maleimide or a derivative thereof.

8. The conjugate or pharmaceutically acceptable salt thereof of any one of the preceding claims, further comprising a tag, wherein said tag comprises a Cysteine and / or further comprising a half-life extending moiety.

9. The conjugate or pharmaceutically acceptable salt thereof of claim 8, wherein said half-life extending moiety is an ankyrin repeat domain with binding specificity for human serum albumin.

10. The conjugate or pharmaceutically acceptable salt thereof any one of the preceding claims, wherein said conjugate comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 17 to 26, or 46 to 50.

11. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VI):Formula (VI)wherein R1 , R2, and R3 are independently NH2 or OH;wherein A is CaHbNcOd, wherein a, b, c, and d are integers;wherein R4 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine;and wherein R5 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134.

12. A conjugate or pharmaceutically acceptable salt thereof, wherein said conjugate has a structure of Formula (VII):Formula (VII)wherein R1 , R2, R3 and R4 are independently NH2 or OH;wherein A is CaHbNcOd, wherein a, b, c, and d are integers;wherein R5 is an ankyrin repeat protein comprising an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 29 to 34, 38, or 51 to 56, wherein said ankyrin repeat protein has binding specificity for MSLN and for human serum albumin, and wherein said ankyrin repeat protein comprises a Cysteine;and wherein R6 is a chelated radionuclide, wherein said radionuclide is Ac-225, Lu-177, Pb-203, Pb-212, In-111 , Tb-161 , Cu-64, Cu-67, Zr-89, Y-86, or Ce-134.

13. A pharmaceutical composition comprising the conjugate or salt of any one of claims 1 to 12, and optionally a pharmaceutically acceptable carrier or excipient.

14. A method of treating cancer, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of the conjugate or pharmaceutically acceptable salt thereof of any one of claims 1 to 12 or the pharmaceutical composition of claim 13.

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