Trans-cyclooctene with enhanced T-ligand

Abstract

Disclosed herein include trans-cyclooctenes (TCOs) that may have improved properties, for example in clinical use. In certain embodiments, the TCOs may have improved in vitro and in vivo properties as compared to other TCOs. The disclosure also pertains to in vivo and in vitro methods of using said trans-cyclooctenes, as well as medical uses thereof, methods for making said TCOs, and compositions and / or combinations comprising said TCOs.

Description

Trans-cyclooctene with enhanced T-ligand Technological field

[001] The disclosure disclosed here refers to transcyclooctenes (TCOs) with improved properties. The compositions and combinations comprising the TCOs of the disclosure, as well as methods for their use, are also provided. Background

[002] In the field of bioorthogonal chemistry, the linkage between TCOs and dienes, particularly tetrazines, has been studied in depth. Although the linkage works well both in vitro and in vivo, the identification of ideal compounds for clinical use remains a focus of research.

[003] In this sense, the aim is to identify new TCOs with good general in vitro and in vivo properties, for example one or more of: rapid blood clearance rate, high uptake at the target site (e.g. a tumor), low uptake off the target, a good metabolism profile, good stability, good reactivity with tetrazines, and / or high payload release (especially in vivo).

[004] There is therefore a need for new TCOs that address one or more of the problems and / or desires mentioned above. Summary

[005] The disclosure refers to at least the following modalities:

[006] Modality 1. A compound or a salt, hydrate, or solvate thereof; wherein said compound has a structure in accordance with Formula (1): Petition 870250092139, dated 08 / 10 / 2025, p. 9 / 254 2 / 246 T—L—L—L—L—T3 Formula (1); wherein L1 is selected from the group consisting of alkylene C4-C12linear or branched, (hetero)C3-C8 cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene; L2a, L2b, and L2d are each independently a ligand; L2 is selected from the group consisting of (hetero)C1-C8 alkanetriyl, (hetero)C5-C6 arenotriyl, C3-C7 cycloalkanethriyl, and C2-C7 heterocycloalkanethriyl; T1 is selected from the group consisting of OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5-C12 alkyl (hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, -N(T1A)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1A-C(O)N(T1a)2, -N(T1a)2-CO-T1a, and -Si(T1A)3; Each T1A is independently selected from the group consisting of hydrogen, (hetero) alkyl, (hetero) alkenyl, (hetero) alkynyl, (hetero) aryl, and an amino acid residue; T2 is a bioconjugation moiety or group -L3-CB; wherein L3 is a residue of a bioconjugation moiety, and CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, Petition 870250092139, dated 08 / 10 / 2025, p. 10 / 254 3 / 246 gels, cells and combinations thereof; T3 is a polymer; and R48 is selected from the group consisting of OH, -O-acetyl, -O-C1-4alkyl, halogen, active carbonate, and a releasable group; and preferably L1 is linear or branched C4-C12 alkylene, more preferably L1 is linear or branched C4-C10 alkylene, and most preferably L1 is linear C5-C6 alkylene; Preferably, L2a, L2b, and L2d are each independently a ligand containing at most twenty atoms; more preferably, L2a, L2b, and L2d are each independently selected from the group consisting of C(O)NL2t-, -NL2tC(O)-, -O-, -S-, -NL2t-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl, preferably L2T is hydrogen; preferably L2 is (hetero) C1C8 alkanetriyl, more preferably L2 is C1-C8 alkanetriyl, and most preferably L2 is C4-C6 alkanetriyl; preferably T1 is -OT1a; and most preferably T1 is -OH; preferably T1A is hydrogen or methyl, more preferably T1A is hydrogen; preferably T2 is maleimidyl, N-hydroxysuccinimidyl, or -L3-CB; preferably L3 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety; preferably CB is a protein, more preferably CB is an antibody or a diabody, even more preferably CB is a diabody, and most preferably CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably T3 is a polymer comprising a polyethylene glycol moiety; Petition 870250092139, dated 08 / 10 / 2025, p. 11 / 254 4 / 246 and preferably R48 is a releasable group.

[007] Modality 2. The compound according to Modality 1, or a salt, hydrate, or solvate thereof; wherein said compound is according to Formula (2): where y is an integer in a range from 1 to 50; preferably y is an integer in a range from 2 to 45; more preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, even more preferably in a range from 20 to 30, and most preferably in a range from 23 to 25.

[008] Modality 3. The compound according to any of the preceding Modalities, or a salt, hydrate, or solvate thereof; wherein said compound is according to Formula (3): x Formula (3); Petition 870250092139, dated 08 / 10 / 2025, p. 12 / 254 5 / 246 where y is as defined in Modality 2; x is an integer in a range from 4 to 12; preferably x is an integer in a range from 4 to 8, more preferably x is an integer in a range from 4 to 6.

[009] Embodiment 4. The compound according to any of the preceding Embodiments, or a salt, hydrate, or solvate thereof; where R48 is a releasable group, and said releasable group is -O-CO-CA; where CA is a drug; preferably the drug is linked to the -O-CO- moiety by means of a secondary or tertiary nitrogen atom that is part of the drug, forming a carbamate; preferably the drug is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative, more preferably the drug is MMAE.

[010] Modality 5. The compound according to any of the preceding Modalities, or a salt, hydrate, or solvate thereof; wherein T2 is selected from the group consisting of is a protein; preferably CB is an antibody or a diabody, more preferably a diabody, and most preferably AVP0458 which consists of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the remainder of T2 by means of S or N which is part of CB, more preferably S.

[011] Modality 6. The compound according to any Petition 870250092139, dated 08 / 10 / 2025, p. 13 / 254 6 / 246 one of the preceding modalities, or a salt, hydrate, or solvate thereof; wherein the said compound is:

[012] Modality 7. The compound according to any of the preceding Modalities, or a salt, hydrate, or solvate thereof; wherein the said compound is: or

[013] Modality 8. The compound according to any of Modalities 1 to 5, or a salt, hydrate, or solvate thereof; wherein said compound is: Petition 870250092139, dated 08 / 10 / 2025, p. 14 / 254 7 / 246 wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the maleimidyl group by means of a sulfur atom that is part of CB, preferably the sulfur atom is part of a cysteine.

[014] Modality 9. The compound according to the Modality 8, or a salt, hydrate, or solvate thereof; wherein the said compound is: or HO'h <o CB THE Of,. the

[015] Modality 10. A compound or a salt, hydrate, or Petition 870250092139, dated 08 / 10 / 2025, p. 15 / 254 8 / 246 solvate thereof; wherein said compound comprises an eight-membered non-aromatic cyclic monoalkenylene moiety, wherein said moiety comprises a non-vinyl carbon atom, wherein said non-vinyl carbon atom is substituted by at least one structure according to Formula (A): L1 t3 Formula (A); in which L1 and L2 are each independently a ligand; and T2 and T3 are organic moieties.

[016] Embodiment 11. A conjugate, or a salt, hydrate, or solvate thereof, wherein the conjugate comprises a protein conjugated to at least one compound according to Formula (1) as defined in any of Embodiments 1 to 9, wherein L1, L2a, L2b, L2c, L2d, T1, T3, and R48 are as defined in any of Embodiments 1 to 9, and wherein T2 is a residue of a bioconjugation moiety, and said protein and said compound are conjugated by means of T2; preferably the protein is a diabody or an antibody; more preferably the protein is a diabody; and most preferably the protein is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably the protein is conjugated to at most 12 of said compounds;Most preferably, the protein is conjugated to a maximum of 8 of said compounds; or most preferably, the protein is conjugated to a maximum of 4 of said compounds; preferably, said protein and said compound are conjugated via T2e-1; Petition 870250092139, dated 08 / 10 / 2025, p. 16 / 254 9 / 246 a sulfhydryl residue of said protein, a hydroxyl residue of said protein, or an amine residue of said protein; more preferably said protein and said compound are conjugated by means of T2 and a sulfhydryl residue of said protein; preferably T2 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety; more preferably T2 is a residue of a maleimidyl moiety.

[017] Modality 12. The conjugate according to Modality 11, or a salt, hydrate, or solvate thereof, wherein the conjugate is: CJ where CJ is in a range of 1 to 12; where CB is AVP0458 which consists of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CJ is from 2 to 10, more preferably from 2.5 to 8, even more preferably from 3 to 6, even more preferably still from 3.5 to 4, and most preferably about 4; preferably CB is linked to each maleimidyl group by means of a sulfur atom, preferably the sulfur atom is part of a cysteine.

[018] Modality 13. The conjugate according to Modality 12, or a salt, hydrate, or solvate thereof, wherein the conjugate is: Petition 870250092139, dated 08 / 10 / 2025, p. 17 / 254 10 / 246 CJ or CJ

[019] Modality 14. A composition comprising: (a) a compound according to any one of Embodiments 1 to 10, or the salt, hydrate, or solvate thereof; and / or (b) the conjugate according to any one of Embodiments 11 to 13, or the salt, hydrate, or solvate thereof; preferably the composition is a pharmaceutical composition.

[020] Modality 15. A composition in accordance with Modality 14, in which said composition comprises: (a) a compound according to any one of Embodiments 1 to 10, or the salt, hydrate, or solvate thereof; and (b) the enantiomer of said compound, or the salt, hydrate, or solvate thereof; preferably said composition is a racemic mixture of (a) and (b). Petition 870250092139, dated 08 / 10 / 2025, p. 18 / 254 11 / 246

[021] Modality 16. A combination of: (Al) a compound according to any of the Embodiments 1 to 10, or the salt, hydrate, or solvate thereof; (A2) a conjugate according to any of Embodiments 11 to 13, or the salt, hydrate, or solvate thereof; and / or (A3) a composition according to Embodiment 14 or 15; with (B) a diene or salt, solvate, or hydrate thereof; preferably the diene is a tetrazine.

[022] Modality 17. The combination according to Modality 16, in which the diene is selected from the group consisting of: Petition 870250092139, dated 08 / 10 / 2025, p. 19 / 254 12 / 246 or a salt, hydrate, and / or solvate thereof.

[023] Modality 18. The compound according to any of Modalities 1 to 10, or the salt, hydrate, or solvate thereof; the conjugate according to any of Modalities 11 to 13, or the salt, hydrate, or solvate thereof; the composition according to any of Modalities 14 to 15; or the combination according to any of Modalities 16 to 17; for use as a medicament.

[024] Modality 19. The compound according to any of Modalities 1 to 10, or the salt, hydrate, or solvate thereof; the conjugate according to any of Modalities 11 to 13, or the salt, hydrate, or solvate thereof; the composition according to any of Modalities 14 to 15; or the combination according to any of Modalities 16 to 17; for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[025] Modality 20. A method of treating a disease in an individual, wherein the method comprises the step of administering to the individual:

[026] (a) the compound according to any of the Embodiments 1 to 10, or the salt, hydrate, or solvate thereof;

[027] (b) the conjugate according to any of the Petition 870250092139, dated 08 / 10 / 2025, p. 20 / 254 13 / 246 Modalities 11 to 13, or the salt, hydrate, or solvate thereof;

[028] (c) the composition in accordance with any of the Modalities 14 to 15; and / or

[029] (d) the combination according to any of the Modalities 16 to 17; preferably the individual is a human; preferably the disease is cancer.

[030] Modality 21. A non-therapeutic method for reacting:

[031] (ia) the compound according to any of the Modalities 1 to 10, or the salt, hydrate, or solvate thereof;

[032] (iia) the conjugate according to any of Modalities 11 to 13, or the salt, hydrate, or solvate thereof; and / or

[033] (iiia) the composition in accordance with any of the Modalities 14 to 15;

[034] with a diene or salt, solvate, or hydrate thereof,

[035] wherein the said method comprises the step of contacting (ia), (iia), or (iiia) the said diene or salt, solvate, or hydrate thereof, preferably the said non-therapeutic method is an in vitro method; and preferably the said diene is a tetrazine.

[036] Modality 22. A non-therapeutic use of:

[037] (a) the compound according to any of the Embodiments 1 to 10, or the salt, hydrate, or solvate thereof;

[038] (b) the conjugate according to any of the Modalities 11 to 13, or the salt, hydrate, or solvate thereof;

[039] (c) the composition in accordance with any of the Modalities 14 to 15; and / or

[040] (d) the combination in accordance with any of the Modalities 16 to 17; in a click reaction.

[041] Modality 23. A method for the synthesis of a Petition 870250092139, dated 08 / 10 / 2025, p. 21 / 254 14 / 246 compound according to any of the Modalities 1 to 10, or a salt, hydrate, or solvate thereof; wherein the said method comprises:

[042] a compound of Formula (R) to a compound of (A) couple hey R48, T1, where they are as defined in any of the Modalities 10; T2 S10xFormula (S); where T2, e.g., are as defined in any of the Modalities 1 to 10, and S10e-COOH or an active ester, preferably S10e-COOH; or (B) couple a compound of Formula (T) to a compound of Formula (U): S1 T1, R48 Formula (T); where R48, T1s are as defined in any of the Modalities 10; and S11 is -COOH or an active ester preferably S11 is an active ester; Petition 870250092139, dated 08 / 10 / 2025, p. 22 / 254 15 / 246 THE NH x THE NH2 y Formula (U); where T2, x, are as defined in any of the Modalities

[043] Embodiment 24. A method for the synthesis of a conjugate according to any one of Embodiments 11 to 13, or a salt, hydrate, or solvate thereof; wherein said method comprises the step of coupling a protein to a compound according to any one of Embodiments 1 to 10, or a salt, hydrate, or solvate thereof; wherein, in said compound, T2 is a bioconjugation moiety; wherein, preferably in said protein, the disulfide bonds have been reduced. Detailed description

[044] As an example from the field of bioorthogonal chemistry, WO 2022 / 197182 describes AVP0458-22-PEG24, referred to here as compound 1. Compound 1 is a modified AVP0458 diabody with four TCO-containing moieties, and has the following structure: the AVP0458

[045] However, the inventors HO / HN^ identified, for the first time, that certain properties of compound 1 can be improved.

[046] First, it was discovered that, although the Petition 870250092139, dated 08 / 10 / 2025, p. 23 / 254 16 / 246 Compound 1 has good blood clearance, further improvements are desired. Compound 1 has a half-life in the blood of healthy mice of 4.22 hours, and 48 hours after injection into healthy mice, 1.14% ID / g of Compound 1 in the blood of said mice was observed. Based on this, it is desirable that new TCOs be provided that show faster clearance rates compared to Compound 1.

[047] Secondly, it was found that while compound 1 demonstrates good tumor uptake of 18.42% ID / g in mice bearing LS174T xenografts, further improvements are needed. Therefore, it is also desirable that TCOs with higher tumor uptake be provided.

[048] Third, it was observed that compound 1 shows uptake from off-target sites, for example non-tumor sites, such as the heart, lung, etc. It is also desirable that TCOs have less off-target uptake.

[049] Fourth, it was observed that compound 1 shows a metabolism profile that can be improved. Therefore, it is also desirable that TCOs with a better metabolism profile be provided.

[050] Some aspects and modalities of disclosure are therefore, in a broad sense, based on the judicious perception that disclosure TCOs may satisfy one or more of the aforementioned desires. In particular, it has been surprisingly discovered that substituting the PEG4 moiety of compound 1 can result in a higher clearance rate, greater tumor uptake, less off-target uptake, a better metabolism profile, and / or in vitro properties. Petition 870250092139, dated 08 / 10 / 2025, p. 24 / 254 17 / 246 and even more improved in vivo.

[051] In particular, the combination of a faster clearance rate and greater tumor uptake is surprising, as this means that the faster elimination from the blood is not due to, for example, excretion from the body. Instead, the dissemination compounds can be rapidly absorbed by the tumor. Even more advantageously, the uptake of dissemination compounds in non-target tissues can be much lower compared to uptake in the tumor. This means that a higher percentage of payload can be released at the desired target site and that the trigger to activate this payload release (usually a diene, for example a tetrazine) can be administered at an earlier point in time, shortening the entire procedure. Therefore, dissemination compounds can also result in greater convenience for patients, as fewer and / or less severe side effects can be expected, as well as a shorter treatment time.

[052] The preferred forms of disclosure are described in more detail below, also in relation to a List of Clauses below. All such forms, regardless of whether said forms are disclosed in the general part of the description or as part of the List of Clauses, may be combined provided that said forms are not mutually exclusive. Dissemination compounds

[053] The compounds of the disclosure are in accordance with Clause 1 as defined below, and preferably in accordance with Formula (1) as defined above. It is understood that any compounds as provided herein may be in a form, formulation or solution in which the compound is Petition 870250092139, dated 08 / 10 / 2025, p. 25 / 254 18 / 246 present as a salt, solvate, or hydrate of the compound. Similarly, wherever a compound or genus of compounds is provided herein, or reference is made to the “disclosure compound” or “disclosure compounds,” it shall be understood that the salt, hydrate, or solvate of said compound(s) are also included by said disclosure, even if the terms salt, hydrate, or solvate are not specifically mentioned in each case. In certain embodiments, a disclosure compound is purified or in a form or state in which it is not present as a salt, or as a hydrate, or as a solvate of the compound; however, unless specifically indicated as such, it is intended to be presumed that any compound may be present herein in the form of a salt, hydrate, or solvate.

[054] Preferred forms of disclosure compounds are further described below in relation to various Formulas and variables. Formulas

[055] Preferably, the disclosure compound is in accordance with a Formula selected from the group consisting of: Formula (1), Formula (2), Formula (3), Formula (B), Formula (C), Formula (D), Formula (E), Formula (F), Formula (G), Formula (H), Formula (I), Formula (J), Formula (K), Formula (L), Formula (M), Formula (N), Formula (O), Formula (P) and Formula (Q).

[056] Preferably, the disclosure compound is in accordance with Formula (B). More preferably, the disclosure compound is in accordance with Formula (C). Even more preferably, the disclosure compound is in accordance with Formula (1). Even more preferably, the disclosure compound is in accordance with Formula (D). Even more Petition 870250092139, dated 08 / 10 / 2025, p. 26 / 254 19 / 246 preferably, the disclosure compound is according to Formula (E). Even more preferably, the disclosure compound is according to Formula (F). Even more preferably, the disclosure compound is according to Formula (G). Even more preferably, the disclosure compound is according to Formula (2). Even more preferably, the disclosure compound is according to Formula (H). Even more preferably, the disclosure compound is according to Formula (I). Even more preferably, the disclosure compound is according to Formula (J). Even more preferably, the disclosure compound is according to Formula (K). Even more preferably, the disclosure compound is according to Formula (L). Even more preferably, the disclosure compound is according to Formula (M). Even more preferably, the disclosure compound is according to Formula (N).Even more preferably, the disclosure compound is according to Formula (O). Even more preferably, the disclosure compound is according to Formula (3). Even more preferably, the disclosure compound is according to Formula (P). Even more preferably, the disclosure compound is according to Formula (Q).

[057] Formula (1) is: Petition 870250092139, dated 08 / 10 / 2025, p. 27 / 254 20 / 246

[058] Formula (2)

[059] Formula (3)

[060] Formula (B)

[061] The Formula (C) Petition 870250092139, dated 08 / 10 / 2025, p. 28 / 254 21 / 246

[062] Formula (D) is:

[063] The Formula (E)

[064] The Formula (F)

[065] The Formula (G)

[066] The Formula (H) T—LLL—L—T3 and: and: and: R48 T—L— T1|2a LL—L—T3 Petition 870250092139, dated 08 / 10 / 2025, p. 29 / 254 22 / 246

[067] Formula (I)

[068] Formula (J)

[069] Formula (K)

[070] Formula (L)

[071] Formula (M)

[072] Formula (N) χ—γ' R48 T1^ is…..Q> L2 .ΊΊ-τΊ··2 / L.-' : . z—T' R48 Tt P'X 1 H L2a -2 l'A / L2·'- ·3 : . R48 TÍ-ft-.H L2a τΊ'.2ΐ2Ί / 1τ' : . R48 tl / < LT is. T—LLL—L—T3 : . X R48 T1-P>.oH LT is. T—LLL—L—T3 : . R48 t^T>h Lf is. T—LLL—L—T3 : . Petition 870250092139, dated 08 / 10 / 2025, p. 30 / 254 23 / 246

[073] Formula (O) is:

[075] The Formula (Q) is: L1

[074] The Formula (P) is:

[076] L1 is a binder. Preferably, L1 agrees with Root Group 2 as here defined.

[077] Preferably, L1 contains from 1 to 100 atoms, preferably from 2 to 75 atoms, more preferably from 3 to 60 atoms, even more preferably from 4 to 50 atoms, even more preferably from 5 to 40 atoms, still Petition 870250092139, dated 08 / 10 / 2025, p. 31 / 254 24 / 246 more preferably from 6 to 35 atoms, even more preferably from 7 to 30 atoms, even more preferably from 8 to 25 atoms, even more preferably from 9 to 22 atoms, and most preferably from 10 to 20 atoms. Preferably, L1 contains about 15 atoms.

[078] More preferably, L1 is selected from the group consisting of linear or branched C1-C12 (hetero)alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[079] More preferably than the foregoing, L1 is selected from the group consisting of linear or branched C1C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene. More preferably than the foregoing, L1 is selected from the group consisting of linear or branched C2-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene. More preferably than the foregoing, L1 is selected from the group consisting of linear or branched C3-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene. More preferably than the previous one, L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene. More preferably than the previous one, L1 is a linear or branched C1-C12 alkylene.More preferably than the previous one, L1 is a linear or branched C2-C12 alkylene, namely linear or branched C2-C12 alkylene, linear or branched C3 alkylene, linear or branched C4 alkylene, linear or branched C5 alkylene, linear or branched C6 alkylene, linear or branched C7 alkylene, linear or branched C8 alkylene, linear or branched C9 alkylene, linear or branched C10 alkylene. Petition 870250092139, dated 08 / 10 / 2025, page 32 / 254 25 / 246 branched, linear or branched Cn alkylene, or linear or branched C12 alkylene. More preferably than the above, L1 is a linear or branched C3-C12 alkylene. More preferably than the above, L1 is a linear or branched C4-C12 alkylene. More preferably than the above, L1 is a linear or branched C4-C11 alkylene. More preferably than the above, L1 is a linear or branched C4-C10 alkylene. More preferably than the above, L1 is a linear or branched C4-C9 alkylene. More preferably than the above, L1 is a linear or branched C4-C8 alkylene. More preferably than the above, L1 is a linear or branched C4-C7 alkylene. More preferably than the above, L1 is a linear or branched C4-C6 alkylene. More preferably than the previous one, L1 is a linear or branched C5 alkylene. More preferably than the previous one, L1 is a linear C1-C12 alkylene.More preferably than above, L1 is a linear C2-C12 alkylene, namely linear C2 alkylene, linear C3 alkylene, linear C4 alkylene, linear C5 alkylene, linear C6 alkylene, linear C7 alkylene, linear C8 alkylene, linear C9 alkylene, linear C10 alkylene, linear C11 alkylene, or linear C12 alkylene. More preferably than above, L1 is a linear C3-C12 alkylene. More preferably than above, L1 is a linear C4-C12 alkylene. More preferably than above, L1 is a linear C4-C11 alkylene. More preferably than above, L1 is a linear C4-C10 alkylene. More preferably than above, L1 is a linear C4-C9 alkylene. More preferably than the previous one, L1 is a linear C4-C8 alkylene. More preferably than the previous one, L1 is a linear C4-C7 alkylene. More. Petition 870250092139, dated 08 / 10 / 2025, page 33 / 254 26 / 246 more preferably than the previous one, L1 is a linear C4-C6 alkylene. More preferably, L1 is a linear C5 alkylene.

[080] L1 may be substituted or unsubstituted. Preferably, L1 is unsubstituted. Most preferably, L1 is an unsubstituted linear C5 alkylene.

[081] Without wanting to get bogged down in theory, the inventors believe that the L1 ligand of the compounds of Formula (1) of the present disclosure can provide a faster blood clearance rate while maintaining a high uptake of the compound of Formula (1) at the target site. Still without wanting to get bogged down in theory, an advantage of L1 ligands with a length such as defined in claim 1, in particular linear C4-C12 alkylene, may be that sufficient distance between the CB moiety and a trans-cyclooctene can be achieved, so that the double bond of the trans-cyclooctene can readily react with a diene. Still without wanting to get bogged down in theory, an advantage of L1 ligands with a length such as defined in claim 1, in particular linear C4-C12 alkylene, may be that they are not too long, so that they can still be protected by the CB moiety, which may prevent, for example, deactivation.One advantage of relatively short alkylene ligands, such as C4-C6 alkylene, may be that their solubility is also greater than that of relatively long alkylene ligands. L2

[082] L2 is a ligand. Preferably, L2 conforms to Radical Group 2 as defined herein.

[083] Preferably, L2 contains from 1 to 200 atoms, preferably from 2 to 150 atoms, more preferably Petition 870250092139, dated 08 / 10 / 2025, p. 34 / 254 27 / 246 from 3 to 100 atoms, even more preferably from 4 to 90 atoms, even more preferably from 5 to 80 atoms, even more preferably from 6 to 70 atoms, even more preferably from 7 to 60 atoms, even more preferably from 8 to 50 atoms, even more preferably from 9 to 45 atoms, and most preferably from 10 to 35 atoms.

[084] Preferably, L2 is selected from the group consisting of linear or branched C1-C12 (hetero)alkanetriyl, C3-C8 (hetero)cycloalkanetriyl, C6C12 arenetriyl, and C4-C11 heteroarenetriyl. More preferably than the foregoing, L2 is a linear or branched C1-C12 (hetero)alkanetriyl. More preferably than the foregoing, L2 is a linear or branched C1-C12 heteroalkanetriyl. More preferably than the foregoing, L2 is a branched C1-C12 (hetero)alkanetriyl. More preferably than the foregoing, L2 is a branched C1-C12 heteroalkanetriyl. More preferably than the foregoing, L2 is a branched C3-C11 heteroalkanetriyl. More preferably than the foregoing, L2 is a branched C6-C10 heteroalkanetriyl. More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl. More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl substituted with up to five =O groups.More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl substituted with three =O groups. More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl containing up to five -NH- groups. More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl containing three -NH- groups. More preferably than the previous one, L2 is a branched C8 heteroalkanetriyl containing three -NH- groups, and in which the C8 heteroalkanetriyl is... Petition 870250092139, dated 08 / 10 / 2025, p. 35 / 254 28 / 246 replaced with three =O groups.

[085] More preferably, L2 is:

[086] Even more preferably, L

[087] Even more preferably, L

[088] Most preferably, L2 is:

[089] In preferred embodiments, L2 structure: ^T2a S 2b 12c 2d PH l—l—l^ •

[090] Here, L2a, L2b, L2c, and L2d N o O < Â 1 NH ? NH YO • hnA> Nh' NH hnA 0 ( u A Á NH ç 2 é 0' * hnXo 0 í u Λ Λ „NH P VNH Ύ Ύ 0 • has the following 1 are each one Petition 870250092139, dated 08 / 10 / 2025, p. 36 / 254 29 / 246 independently a ligand. Preferably, L2a, L2b, L2c, and L2d are each independently according to Radical Group 2 as defined herein. L2a

[091] L2a is a ligand. Preferably, L2a conforms to Radical Group 2 as defined herein. More preferably, L2a is a ligand containing at most twenty atoms. More preferably than the previous one, L2a is a ligand containing at most fifteen atoms. More preferably than the previous one, L2a is a ligand containing at most ten atoms. More preferably than the previous one, L2a is a ligand containing at most five atoms. More preferably than the previous one, L2a is selected from the group consisting of -C(O)NL2T-, -NL2TC(O)-, O-, -S-, -NL2T-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl. More preferably than the previous one, L2a is selected from the group consisting of -C(O)NL2T-, and -NL2TC(O)-. More preferably than the previous one, L2a is selected from the group consisting of -C(O)NH- and NHC(O)-. Most preferably, L2a is -NHC(O)-. L2b

[092] L2 is a ligand. Preferably, L2 is in accordance with Radical Group 2 as defined herein. More preferably, L2 is a ligand containing at most twenty atoms. More preferably than the previous one, L2 is a ligand containing at most fifteen atoms. More preferably than the previous one, L2 is a ligand containing at most ten atoms. More preferably than the previous one, L2 is a ligand containing at most five atoms. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NL2T-, -NL2TC(O)-, Petition 870250092139, dated 08 / 10 / 2025, p. 37 / 254 30 / 246 O-, -S-, -NL2t-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NL2t- and -NL2tC(O)-. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NH- and NHC(O)-. Most preferably, L2 is -NHC(O)-. L2c

[093] L2 is a ligand. Preferably, L2 is in accordance with Radical Group 2 as defined herein. More preferably than the foregoing, L2 is a ligand comprising at most 50 atoms. More preferably than the foregoing, L2 is a ligand comprising at most 40 atoms. More preferably than the foregoing, L2 is a ligand comprising at most 30 atoms. More preferably than the foregoing, L2 is a ligand comprising at most 20 atoms. More preferably than the foregoing, L2 is a ligand comprising at most 15 atoms. More preferably than the foregoing, L2 is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenotriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl. More preferably than the previous one, L2ε (hetero) alkanetriyl C1-C8. More preferably than the previous one, L2ε alkanetriyl C1-C8. More preferably than the previous one, L2ε alkanetriyl C2-C7.More preferably than the previous one, L2 is C3-C6 alkanetriyl. More preferably than the previous one, L2 is C4-C5 alkanetriyl. More preferably than the previous one, L2 is C5 alkanetriyl. Most preferably, L2 is >CH-CH2-CH2-CH2-CH2-. L2d

[094] L2 is a ligand. Preferably, L2 is of Petition 870250092139, dated 08 / 10 / 2025, page 38 / 254 31 / 246 according to Radical Group 2 as defined herein. More preferably than the previous one, L2 is a ligand containing at most twenty atoms. More preferably than the previous one, L2 is a ligand containing at most fifteen atoms. More preferably than the previous one, L2 is a ligand containing at most ten atoms. More preferably than the previous one, L2 is a ligand containing at most five atoms. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NL2T-, -NL2TC(O)-, -O-, -S-, -NL2T-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NL2T-, and -NL2TC(O)-. More preferably than the previous one, L2 is selected from the group consisting of -C(O)NH- and -NHC(O)-. Most preferably, L2 is -C(O)NH-. T1

[095] T1 is in accordance with Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein. Preferably, each T1 is independently in accordance with Radical Group 1 as defined herein.

[096] More preferably, each T1 is selected independently from the group consisting of -OT1A, hydrogen, C1-C12 (hetero)alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 (hetero)cycloalkyl, C5-C12 (hetero)aryl alkyl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, -N(T1A)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1A-C(O)N(T1A)2, N(T1A)2-CO-T1A, and -Si(T1A)3. Even more preferably, each T1 is selected independently from the group consisting of -OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5 alkyl (hetero)aryl. Petition 870250092139, dated 08 / 10 / 2025, page 39 / 254 32 / 246 C12, (hetero)aryl C5-C12 alkyl, C4-C12 alkylcycloalkyl, N(T1a)2, -ST1a, -SO3H, -C(O)T1a, -C(O)Ot1A, -OC(O)T1aC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Sí(T1A)3. Even more preferably, each T1 is selected independently from the group consisting of -OT1A, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5-C12 alkyl (hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, N(T1A)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1AC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3. More preferably still, T1 is -OT1A.

[097] Most preferably, T1 is -OH.

[098] As used herein, each T1A is independently selected from the group consisting of hydrogen, (hetero)alkyl, (hetero)alkenyl, (hetero)alkynyl, (hetero)aryl, and an amino acid residue. More preferably, each T1A is independently selected from the group consisting of hydrogen, C1-C6 (hetero)alkyl, C1-C6 (hetero)alkenyl, C1-C6 (hetero)alkynyl, C2-C5 heteroaryl, phenyl, and an amino acid residue. Even more preferably, each T1A is independently selected from the group consisting of hydrogen, C1-C4 (hetero)alkyl, C1-C4 (hetero)alkenyl, C1-C4 (hetero)alkynyl, C3-C5 heteroaryl, phenyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue. Even more preferably, each T1A is independently selected from the group consisting of hydrogen, a C1-C3 alkyl group, an aspartic acid residue, a glutamic acid residue, and a glycine residue.Most preferably, T1A is hydrogen.

[099] Preferably, T1 is in an axial position. Without wanting to get bogged down in theory, the inventors believe that Petition 870250092139, dated 08 / 10 / 2025, page 40 / 254 33 / 246 in this case and when R48 is a releasable group, when the releasing compound reacts with a diene, T1 assists in the release of the payload. This results in ideal release yields and / or release kinetics. T2

[100] T2 is an organic fraction. Preferably, T2 is in accordance with any one of Radical Group 1, Radical Group 3, or Radical Group 5, as defined herein, or wherein T2 is an -L3-CB group. More preferably, T2 is a bioconjugation moiety, a residue of a bioconjugation moiety, or an -L3-CB group. More preferably, T2 is a bioconjugation moiety, or an -L3-CB group. (a) In preferred embodiments, T2 is a bioconjugation moiety. These embodiments typically refer to compounds that can be coupled to, for example, a protein. More preferably, T2 is according to the 1f Radical Group as defined herein. Residues of these bioconjugation moieties are known in the art. More preferably, T2 is N-maleimidyl. In these embodiments, it is most preferred that T2 be: THE

[101] In other preferred embodiments, T2 is a residue of a bioconjugation moiety. These embodiments typically refer to dissemination conjugates, where T2 binds to, for example, a protein. The aforementioned residues are well known to those skilled in the art. In these embodiments, it is more preferred that T2 be: Petition 870250092139, dated 08 / 10 / 2025, p. 41 / 254 34 / 246 where the asterisk indicates a protein binding, and the wavy line denotes a binding to the rest of the disclosure compound.

[102] In other preferred embodiments, T2 is an L3-CB group. These embodiments refer to when T2 alone comprises a B construct (CB), which is normally a protein. CB is as defined herein. L3 corresponds to Radical Group 2. Preferably, L3 is a residue of a bioconjugation moiety. More preferably, L3 is a residue of an N-maleimidyl moiety or a residue of an N-hydroxy-succinimidyl moiety. In these embodiments, it is preferred that T2 be selected from the group consisting of

[103] In these modalities, it is more preferable that T2 be:

[104] For the -L3-CB moiety, it is preferred that L3 be a sulfur atom, a secondary nitrogen atom, or a tertiary nitrogen atom, preferably a sulfur atom, and CB together form any of the following Petition 870250092139, dated 08 / 10 / 2025, p. 42 / 254 35 / 246 structures -L3-CB: where CB1 indicates S, secondary N, or tertiary N that is part of CB, preferably S; wavy lines indicate a connection to the L1 portion, and the asterisk indicates a connection to the remainder of CB, preferably AVP0458. CB

[105] CB is in accordance with Radical Group 4 or Radical Group 5, as defined herein. Preferably, CB is a targeting agent as defined herein. Preferably, CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptides, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells and combinations thereof. More preferably, CB is a protein. Even more preferably, CB is an antibody or a diabody. Even more preferably, CB is a diabody.

[106] An antibody is a protein generated by the immune system that is capable of recognizing and binding to a specific antigen. Although antibodies or immunoglobulins derived from IgG antibodies are particularly suitable for use in this disclosure, immunoglobulins of any of the classes or subclasses may be selected, for example, IgG, IgA, IgM, IgD, and IgE. Properly speaking, immunoglobulin is of the IgG class, including, but not limited to, IgA, IgM, IgD, and IgE. Petition 870250092139, dated 08 / 10 / 2025, p. 43 / 254 36 / 246 limiting to the IgG subclasses (IgG1, 2, 3 and 4) or to the IgM class which is capable of specifically binding to a specific epitope on an antigen. Antibodies can be intact immunoglobulins derived from natural sources or recombinant sources and can be immunoreactive portions of intact immunoglobulins. Antibodies can exist in a variety of forms, including, for example, polyclonal antibodies, monoclonal antibodies, single-domain camelid antibodies, recombinant antibodies, anti-idiotype antibodies, multispecific antibodies, antibody fragments such as Fv, VHH, Fab, F(ab)2, Fab', Fab'-SH, F(ab')2, single-chain variable fragment antibodies (scFv), tandem / bis-scFv, Fc, pFc', scFv-Fc, Fv disulfide (dsFv), bispecific antibodies (bc-scFv) such as BiTE antibodies, trispecific antibody derivatives such as tribobodies, camelid antibodies, minibodies, nanobodies, resurgent antibodies, humanized antibodies,Fully human antibodies, single-domain antibodies (sdAb, also known as Nanobody™), chimeric antibodies, chimeric antibodies comprising at least one human constant region, dual-affinity antibodies such as dual-affinity redirecting proteins (DART™) and multimers and their derivatives, such as divalent or multivalent single-chain variable fragments (e.g., di-scFvs, tri-scFvs) including, but not limited to, minibodies, diabodies, triabodies, tribobodies, tetrabodies and the like, multivalent antibodies. Reference is made to [Trends in Biotechnology 2015, 33, 2, 65], [Trends Biotechnol. 2012, 30, 575-582], and [Canc. Gen. Prot. [2013 10, 1 - 18], and [BioDrugs 2014, 28, 331 - 343], the content of which is incorporated here by reference. “Fragment of, Petition 870250092139, dated 08 / 10 / 2025, page 44 / 254 37 / 246 antibody” refers to at least a portion of the variable region of the immunoglobulin that binds to its target, that is, the antigen-binding region. Other embodiments utilize antibody mimetics such as drug-targeting DDs or TT targeting agents, such as, but not limited to, Afimers, Antichalins, Avimers, Alphabodies, Affibodies, DARPins, and multimers and derivatives thereof; reference is made to [Trends in Biotechnology 2015, 33, 2, 65], the contents of which are incorporated herein by reference. For the avoidance of doubt, in the context of this disclosure, the term “antibody” is intended to encompass all variations, fragments, derivatives, fusions, analogs, and antibody mimetics described in this paragraph, unless otherwise specified.

[107] Preferably, an antibody is selected from the group consisting of AVP0458, CC49, 3F8, AVP0458, Abcixima, Accumulate, Ambrace, Ablite, Actoxuma, Adalimumab, Adecatum, AfeseMovima, AfeseMovima pegol, alemtuzumabe, alirocumabe, altumomabe pentetato, amatuximabe, amivantamabe, anatumomabe mafenatox, andecaliximabe, anetumabe ravtansine, anifrolumabe, ansuvimabe, anrukinzumabe, apolizumabe, aprutumabe, asecrimovazumabe, arcitumabe, arcitumabe atezolizumabe, atidortoxumabe, atinumabe, atolvimabe, atolvimabe, mafvimabe, odevimabe, atorolimumabe, avelumabe, and vedotina, gamlanivimabe, bapineuzumabe, basilimabe, bavitumovimabe, BCD-100be, bedintelo, bebdinovimabe becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, becomes, Petition 870250092139, dated 08 / 10 / 2025, p. 45 / 254 38 / 246 bimagrumabe, bimekizumabe, birtamimabe, bivatuzumabe, bleselumabe, blinatumomabe, blontuvetmabe, blosozumabe, bococizumabe, brazikumabe, brentuximabe vedotin, briakinumabe, brodalumabe, brolucizumabe, brontictuzumabe, burosumabe, cabiralizumabe, camidanlumabe tesirina, camrelizumabe, canakinumabe, cantuzumabe mertansina, cantuzumabe ravtansina, caplacizumabe, casirivimabe, capromabe, carlumabe, carotuximabe, catumaxomabe, immunoconjugado cBR96-doxorubicin, cedelizumabe, cemiplimabe, cergutuzumabe amunaleucina, certolizumabe pegol, cetrelimabe, cetuximabe, cibisatamabe, cilgavimabe, cirmtuzumabe, citatuzumabe bogatox, cixutumumabe, clazakizumab, clenoliximab, clivatuzumabe tetraxetano, codrituzumabe, cofetuzumabe pelidotina, coltuximab ravtansina, conatumumabe, concizumabe, cosfroviximabe, crenezumabe, crizanlizumabe, crotedumabe, CR6261, cusatuzumabe, dacetuzumabe, daclizumabe, dalotuzumabe, dapirolizumab pegol, daratumumabe, dectrekumabe, demcizumabe,denintuzumab mafodotina, denosumab, depatuxizumab mafodotina, derlotuximab biotin, detumomab, dezamizumab, dinutumab, dinutumab beta, diredavuma, divozilima, domagrozuma, donanema, dorlimomab-dostar8 aritox0, duligotuzumabe, duligotuzumabe, duligotuzumabe, durvalumabe, dusigizumabe, duvorduzumabe, ecromeximabe, eculizumabe, eculizumabe, eculizumabe, eculizumabe, eculizumabe, eculizumabe, ecumenical, elezumabe, eculizumabe, eluzumabe, elezumabe, elezanomabe, elezumabe, elozumabe, elezumabe, elezumabe, elezumabe emicizumabe, enapotamabe vedotina, enavatuzumabe, enfortumabe vedotina, enlimomabe pegol, enoblituzumabe, enokizumabe, enoticumabe, ensituximabe, epcoritamabe, epitumomab cituxetan, epratuzumabe, Petition 870250092139, dated 08 / 10 / 2025, p. 46 / 254 39 / 246 eptinezumab, erenumab, erlizumab, ertumaxomab, etaracizumab, etesevimab, etigilimabe, etrolizumab, evinacumab, evolocumabe, exbiviromab, phenolesoma, pharamoma, fashioma, farizuma, FTA, far felvizumab, fezakinumab, fibatuzumab, ficlatuzumab, figitumab, fibrizumab, flanvotum, fleticuma, flotetuzumab, fontolizumab, foralumab, foravizumab, fremanezumab, fresolimumab, frovocima, gall, caca, frunefulanbet galixima, gancotama, ganitum, gantenerumabe, gatipotuzuma, gavilimoma, gedivuma, gemtuzuma ozogamycina, gevokizuma, gilvetma, gimiluma, girentuximab, glembatum vedotina, gloximabe, gosellimobe, gosuramabe ianalumabe, ibalizumabe, sintilimabe, ibritumomabe tiuxetano, icrucumabe, idarucizumabe, ifabotzumabe, igovomabe, iladatuzumabe vedotina, imalumabe, imaprelimabe, imciromabe, imdevimabe, imgatanlatuximabe, ravcindusatumabe vedotina, inebilizumabe, infliximab, intetumumabe, inolimomabe, inotuzumabe ozogamycin, ipilimumabe, iomab-B, iratumumabe, isatuximabe, iscalimabe, istratumabe, itolizumabe, ixekizumabe, kelizumabe, labedotinatube, labediratumabe lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, lightning, starlight, lightning; vedotina, gegelzumabe, loncastuxumabe tesirine, losatuxizumabe vedotin, lilotumabe satetraxetane, lintuzumabe, lirolumabe, lodelcizumabe, lokivetmabe, lorvotuzumabe mertansine, Petition 870250092139, dated 08 / 10 / 2025, p. 47 / 254 40 / 246 lucatumumabe, lulizumabe pegol, lumiliximabe, lucatuzumabe, lupartumabe, lupartumabe amadotina, lutizumabe, maftivimabe, matumumabe, margetuximabe, marstacimabe, muslimomabe, mavrilimumabe, matuzumabe, melathumazumabe, metelimuzumabe minretumomabe, mirikizumabe, mirvetuximabe soravtansine, mitumomabe, modetuximabe, mogamulizumabe, monalizumabe, morolimumabe, mosunetuzumabe, motavizumabe, moxetumomabe pasudotox, muromonab-CD3, naximabetumabe naramabetu, tafenatox emtansina, sent, sent, sent, received, sent, received, sent, received, received, sent, received, received, received, received, received, received, received, received, received, obinutuzumabe, ocratuzumabe, ocratuzumabe, odesivimabe, odulimomabe, ofatumumabe, olaratumabe, oleclumabe, olendalizumabe, olokizumabe, omalizumabe, omburtamabe, OMS721, onartuzumabe, ontuxizumabe, opicinumabe, onvacinumabeoportuzumabe monatox, oregovoma, orticumabe, otelixizumabe, otilimabe, otlertuzumabe, oxelumabe, ozanezumabe, ozoralizumabe, pagibaximabe, palivizumabe, pamrevlumabe, panitumumabe, pankomabe, pascobacumabe, parsacotuzumabe, pasotuxizumab, pateclizumab, patritumab, PDR001, pembrolizumab, pemtumoma, perachizumab, pertuzumab, phenlizumab, pidylizumab, pinatuzumab vedotina, pintumoma, placuluma, pozelizumab,polzulizumab,pol pregalizumab, vedotina, ponezumab, porgavixima, prasinezumab, prezalizumab, prilixima, pritoxaxima, prituma, PRO 140, chilizumab, racetuma, raretuma, rafivima, rhinovima, ranibima, ranivizuma, ranibima Petition 870250092139, dated 08 / 10 / 2025, p. 48 / 254 41 / 246 raxibacumabe, ravagalimabe, ravulizumabe, refanezumabe, regavirumabe, regdanvimabe, relatlimabe, remtolumabe, reslizumabe, retifanlimabe, rilotumumabe, rinucumabe, risankizumabe, Rma pegol, rizuwa,rotumabe, rituximabe roledumabe, romilkima, romosozuma, rontalizuma, rosmantuzuma, rovalpituzuma tesirina, rovelizuma, rozanolixizuma, ruplizuma, SA237, sactuzuma, govitecano, samalizuma, samrotama, vedolizuma, satradalizuma, saridalumabe secukinumab, selecreluma, seribaumab, setoxaxima, setruzumab, seviroma, cybrotuzumab, SGN-CD19A, SHP647, sifalimumab, siltuximab, simtuzumab, siplizumab, sirtrauma vedotina, solucumabe, sofituzumab, sofituzumab sonepcizuma, sontuzuma, sotrovima, spartalizuma, spesolima, stamuluma, sulesoma, suptavuma, sutimlima, suvizuma, suvratoxuma, tabaluma, tacatuzuma, tetraxetano, tadocizuma, thalizuma, thalacozuma, talacozumatalquetamabe, tamtuvetmabe, tanezumabe, taplitumomabe paptox, tarexumabe, tavolimabe, teclistamabe, tefibazumabe, telemomabe aritox, telisotuzumabe, telesotuzumabe vedotina, tenatumomabe, teneliximabe, teplizumabe, tetulomabe, tesidoprotumabe, tepoditamabe tezepelumabe, TGN1412, tibulizozumabe, tildrakizumabe, tigatuzumabe, temigutuzumabe, thymolumabe, tragol, umabe, tragozumabe, tixagevima, tisomabe vedotina, tixagevimabe, TNX-650, tocilizozumabe, tomulizozumabe, tomulizozumabe, tomulizozumabe, tomolizozumabe tositumobe, tovetuma, tralokinumabe, trastuzumab, trastuzumab duocarmazine, trastuzumabe emtansine, TRBS07, tregalizumabe, tremelimumabe, trevogrumabe, tucotuzumabe celmoleucine, tuvirumabe, ublituximabe, uluelumabe, uluelumabe Petition 870250092139, dated 08 / 10 / 2025, p. 49 / 254 42 / 246 urtoxazumabe, ustekinumabe, utomilumabe, vadastuximabe talirina, vanalimabe, vandortuzumabe vedotina, vantictumabe, vanucizumabe, vapalizumabe, varisacumabe, varlilumabe, vatelizumabe, vedolizumabe, velpatulizumabe,, velpalizumabe vilobelizumabe, visilizumabe, voparilizumabe, volociximabe, vonlerolizumabe, vopratelimabe, vorsetuzumabe mafodotina, votumabe, votumabe, xentuzumabe, XMAB-5574, zalutumabe, zanolimumabe, zatuximabe, zeno zolimomab aritox.

[108] Preferably, CB is selected from the group consisting of AVP0458, CC49, insulin, transferrin, fibrinogen fragment-gamma, thrombospondin, claudin, apolipoprotein E, Affibody molecules, such as for example ABY-025, ankyrin repeat proteins, ankyrin-like repeat proteins, interferons, for example interferon alpha, beta and gamma, interleukins, lymphokines, colony-stimulating factors and protein growth factor, such as tumor growth factor, for example tumor growth factor alpha, beta, platelet-derived growth factor (PDGF), uPAR-targeted proteins, apolipoprotein, LDL, annexin V, endostatin and angiostatin. Examples of peptides as targeting agents include LHRH receptor targeting peptides, EC-1 peptide, RGD peptides, HER2 targeting peptides, PSMA targeting peptides, somatostatin-targeted peptides, and bombesin.Other examples of targeting agents include lipocalins, such as anticalins. One particular embodiment uses Affibodies™ and multimers and derivatives.

[109] More preferably, CBé AVP0458 or CC49. Most preferably, CBé AVP0458 which consists of two Petition 870250092139, dated 08 / 10 / 2025, p. 50 / 254 43 / 246 monomers, where each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[110] Preferably, CB is linked to the rest of the disclosure compound or the disclosure conjugate by way of S or N which is part of CB. More preferably, CB is linked to the rest of the disclosure compound or the disclosure conjugate by way of S which is part of CB. AVP0458

[111] As used herein, AVP0458 refers to a TAG72-binding diabody derived from the CC49 antibody. AVP0458 is a diabody consisting of two monomers, each monomer having an amino acid sequence according to SEQ ID NO: 1:

[112] SEQ ID NO: 1 (amino acid sequence of diabody monomer AVP0458): 113 GQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLSISSSVETEDLAVYYCQQYYSYPLTFG AGTKLVLKR

[114] Here, the underline indicates cysteines that are preferentially modified with or linked to a disclosure compound or to the remainder thereof if AVP0458 is itself part of the disclosure compound.

[115] So, in SEQ ID NO: 1 it is preferred that at least one of the underlined cysteines, more preferably both underlined cysteines, be modified with or linked to a compound as disclosed. In other words: it is preferred that the sulfur atom of the underlined cysteines be coupled to a T2 moiety as defined herein, preferably T2 being the residue of an N-maleimidyl group. Petition 870250092139, dated 08 / 10 / 2025, p. 51 / 254 44 / 246 Targeting agent

[116] A targeting agent, TT, binds to a primary target. A “primary target” as used in this disclosure may be any molecule present in an organism, tissue or cell. Preferably, a “primary target” refers to a target for a targeting agent for therapy, imaging, theranostics, diagnostics or in vitro studies.

[117] In order to allow specific targeting of the primary targets listed above, the TT targeting agent may comprise compounds including, but not limited to, antibodies, antibody derivatives, antibody fragments, antibody fusions (fragments) (e.g., fragments or derivatives of bi-specific and tri-specific mAbs), proteins, peptides, e.g., octreotide and VIP derivatives, MSH, LHRH, chemotactic peptides, cell-penetrating peptide, membrane translocation fraction, bombesin, elastin, peptide mimetics, organic compounds, inorganic compounds, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, oligonucleotides, aptamers, viruses, whole cells, phages, drugs, polymers, liposomes, chemotherapeutic agents, receptor agonists and antagonists, cytokines, hormones, steroids, toxins.Examples of organic compounds mentioned in the context of this disclosure are, or derived from, dyes, compounds that target CAIX and PSMA, estrogens, for example estradiol, androgens, progestins, corticosteroids, methotrexate, folic acid, and cholesterol. Examples of targeting agents of a protein nature include insulin, transferrin, and fibrinogen fragments. Petition 870250092139, dated 08 / 10 / 2025, page 52 / 254 45 / 246 gamma, thrombospondin, claudin, apolipoprotein E, Affibody molecules such as ABY-025, ankyrin repeat proteins, ankyrin-like repeat proteins, interferons, for example interferon alpha, beta and gamma, interleukins, lymphokines, colony-stimulating factors and protein growth factors, such as tumor growth factor, for example tumor growth factor alpha, beta, platelet-derived growth factor (PDGF), uPAR targeting protein, apolipoprotein, LDL, annexin V, endostatin, and angiostatin. Examples of peptides as targeting agents include LHRH receptor targeting peptides, EC-1 peptide, RGD peptides, HER2 targeting peptides, PSMA targeting peptides, somatostatin targeting peptides, bombesin. Other examples of targeting agents include lipocalins, such as anticalins.One specific modality uses Affibodies™ and multimers and derivatives.

[118] In one embodiment, antibodies are used as TT. Although antibodies or immunoglobulins derived from IgG antibodies are particularly suitable for use in this disclosure, immunoglobulins of any of the classes or subclasses may be selected, for example, IgG, IgA, IgM, IgD, and IgE. Properly, the immunoglobulin is of the IgG class, including but not limited to the IgG subclasses (IgG1, 2, 3, and 4), or the IgM class, which is capable of specifically binding to a specific epitope on an antigen. Antibodies may be intact immunoglobulins derived from natural or recombinant sources and may be immunoreactive portions of intact immunoglobulins. Antibodies may exist in a variety of forms, including, by Petition 870250092139, dated 08 / 10 / 2025, p. 53 / 254 46 / 246 example, polyclonal antibodies, monoclonal antibodies, single-domain camelid antibodies, recombinant antibodies, anti-idiotype antibodies, multispecific antibodies, antibody fragments, such as Fv, VHH, Fab, F(ab)2, Fab', Fab'-SH, F(ab')2, single-chain variable fragment antibodies (scFv), tandem / bisscFv, Fc, pFc', scFv-Fc, Fv disulfide (dsFv), bispecific antibodies (bc-scFv) such as BiTE antibodies, trispecific antibody derivatives such as tribodies, camelid antibodies, minibodies, nanobodies, resurfaced antibodies, humanized antibodies, fully human antibodies, single-domain antibodies (sdAb, also known as Nanobody™), chimeric antibodies, chimeric antibodies comprising at least one human constant region, dual-affinity antibodies such as dual-affinity redirecting proteins (DART™), and multimers and their derivatives,such as bivalent or multivalent single-chain variable fragments (e.g., di-scFvs, tri-scFvs) including, but not limited to, minibodies, diabodies, triabodies, tribobodies, tetrabodies, and the like, and multivalent antibodies. Reference is made to [Trends in Biotechnology 2015, 33, 2, 65], [Trends Biotechnol. 2012, 30, 575–582], and [Canc. Gen. Prot. 2013 10, 1–18], and [BioFármacos 2014, 28, 331–343], the contents of which are incorporated herein by reference. “Antibody fragment” refers to at least a portion of the variable region of the immunoglobulin that binds to its target, i.e., the antigen-binding region. Other modalities utilize antibody mimetics such as TT, including, but not limited to, Afimers, Antichalins, Avimers, Alphabodies, Affibodies, DARPins, and multimers and derivatives thereof; this is done, Petition 870250092139, dated 08 / 10 / 2025, page 54 / 254 47 / 246 reference to [Trends in Biotechnology 2015, 33, 2, 65], the content of which is incorporated herein by reference. For the avoidance of doubt, in the context of this disclosure, the term “antibody” shall encompass all variations, fragments, derivatives, fusions, analogs and mimetics of antibodies described in this paragraph, unless otherwise specified.

[119] Preferably, the TT is selected from antibodies and antibody derivatives such as antibody fragments, fragment fusions, proteins, peptides, peptide mimetics, organic molecules, dyes, fluorescent molecules, enzymatic substrates.

[120] Preferably, TT being an organic molecule has a molecular weight less than 2000 Da, more preferably less than 1500 Da, more preferably less than 1000 Da, even more preferably less than 500 Da.

[121] In another preferred embodiment, TT is selected from antibody fragments, fragment fusions and other antibody derivatives that do not contain an Fc domain.

[122] In another embodiment, TT is a polymer and accumulates on the primary target by virtue of the EPR effect. Typical polymers used in this embodiment include, but are not limited to, polyethylene glycol (PEG), poly(N-(2-hydroxypropyl) methacrylamide) (HPMA), polylactic acid (PLA), polylactic-glycolic acid (PLGA), polyglutamic acid (PG), polyvinylpyrrolidone (PVP), poly(1-hydroxymethylethylene hydroxymethyl-formula (PHF). Other examples are copolymers of a polyacetal / polyketal and a hydrophilic polymer selected from the group consisting of polyacrylates, polyvinyl polymers, polyesters, polyorthoesters, polyamides, oligopeptides, Petition 870250092139, dated 08 / 10 / 2025, page 55 / 254 48 / 246 polypeptides and their derivatives. Other examples are oligopeptides, polypeptides, glycopolysaccharides, and polysaccharides such as dextran and hyaluronan. In addition, reference is made to [G. Pasut, FM Veronese, Prog. Polym. Sci. 2007, 32, 933-961]. In some embodiments, TT may be a cell-penetrating moiety, such as a cell-penetrating peptide. In other embodiments, TT is a polymer, particle, gel, biomolecule, or other TT moiety listed above and is injected locally to create a prodrug depot, which can subsequently be activated by the activator. In another embodiment, the targeting agent TT is a solid material such as, but not limited to, polymer, metal, ceramic, wherein this solid material is or consists of a cartridge, reservoir, or depot, wherein said cartridge, reservoir, or depot is preferably used for the in vivo release of drugs.In some embodiments, the targeting agent TT also acts as a drug, which may be denoted as DD. T3

[123] T3 is an organic fraction. Preferably, T3 is according to any one of Radical Group 1, Radical Group 3, or Radical Group 5, as defined herein. More preferably, T3 is according to Radical Group 3, as defined herein. Even more preferably, T3 is a polymer. Even more preferably, T3 is a polymer comprising a polyethylene glycol moiety.

[124] More preferably, T3 comprises a portion -(CH2CH2-O-)y-T4. Here, y is an integer in a range from 1 to 50, preferably y is an integer in a range from 2 to 45, more preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, still Petition 870250092139, dated 08 / 10 / 2025, p. 56 / 254 49 / 246 more preferably in a range of 15 to 35, more preferably still in a range of 20 to 30, even more preferably in a range of 23 to 25, and most preferably y is 24. This definition and these preferences also apply to compounds of Formula (2), Formula (3), Formula (G), Formula (O), Formula (P), and Formula (Q), wherein y is also used.

[125] T4 is in accordance with Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5 as defined herein. Preferably, T4 is in accordance with Radical Group 1. More preferably, T4 is in accordance with Radical Group 1a. More preferably, T4 is in accordance with Radical Group 1b. More preferably, T4 is in accordance with Radical Group 1c. More preferably, T4 is in accordance with Radical Group 1d. Even more preferably, T4 is in accordance with Radical Group 1e. Most preferably, T4 is methyl.

[126] Even more preferably, T3 is a (CH2CH2-O-)y-T4 moiety. Most preferably, T3 is a (CH2CH2-O-)24-CH3 moiety. Formula Variables (B)

[127] In Formula (B), R48 and T1 are as defined herein. In Formula (B), TL is a structure according to Formula (A) as defined in any of Clauses 1 - 128, and preferably TL is as defined in any of Clauses 216 - 227.

[128] In Formula (B), y1 is an integer from 0 to 4, preferably an integer from 1 to 2, most preferably y1 is 1.

[129] In Formula (B), y2 is an integer from 0 to 5, preferably an integer from 1 to 4, more preferably Petition 870250092139, dated 08 / 10 / 2025, p. 57 / 254 50 / 246 is an integer from 1 to 3, even more preferably an integer from 1 to 2, and most preferably y2 is 1.

[130] In Formula (B), y3 is an integer from 1 to 5, preferably an integer from 1 to 4, more preferably an integer from 1 to 3, even more preferably an integer from 1 to 2, and most preferably y3 is 1.

[131] In Formula (B), each of X1, X2, X3, X4, X5, and X6 is independently selected from the group consisting of a substituted or unsubstituted carbon atom, a nitrogen atom, or an oxygen atom, provided that if one of X1, X2, X3, X4, X5, and X6 is a nitrogen atom or an oxygen atom, an adjacent X1, X2, X3, X4, X5, and X6 is not a nitrogen atom or an oxygen atom.

[132] Preferably, each of X1, X2, X3, X4, X5, and X6 is independently a substituted or unsubstituted carbon atom. More preferably, X1 and / or X6 are independently a carbon atom substituted with R48. Even more preferably, X1 is a carbon atom substituted with R48, and most preferably, X1 is -CHR48-. Even more preferably, X1 is -CHR48-, and X4 is -CT1TL-. Preferably, X2, X3, X5, and X6 are unsubstituted carbon atoms, most preferably -CH2-. Variable x in Formulas (3), (O), (P), and (Q)

[133] In Formula (3), Formula (O), Formula (P), and Formula (Q), x is an integer in a range from 4 to 12; preferably x is an integer in a range from 4 to 8, most preferably x is an integer in a range from 4 to 6, and most preferably x is 5. R48

[134] R48 is selected from the group consisting Petition 870250092139, dated 08 / 10 / 2025, p. 58 / 254 51 / 246 in -OH, -O-acetyl, -O-C1_4alkyl, halogen, active carbonate, and a releasable group.

[135] Preferably, R48 is a substituent on an allylic carbon of a disclosure compound.

[136] Preferably, R48 is in the axial position. This preference is especially valid when R48 is a releasable group. Having the releasable group in an axial position results in better payload release compared to having the releasable group in an equatorial position.

[137] Preferably, the R48 group is a releasable group. These releasable groups are well known and have a clear meaning in the art. Especially in the context of click-to-release reactions, such as in the present disclosure, the person skilled in the art would immediately recognize that a releasable group on the allylic carbon of a transcyclooctene (namely R48 in Formula (1)) refers to a group that can be released from the transcyclooctene by contacting the transcyclooctene with an activator such as a diene.

[138] In preferred embodiments, the releasable group is (Y1-C(=Y2))i-(SP)j-CA. Here, each of Y1 and Y2 are independently selected from O, and S; preferably Y1 and Y2 are O.

[139] For the releasable group, j is 0 or 1; preferably j is 0; and i is 0 or 1; preferably i is 1. If i is 0, -(SP)j-CA is connected to the rest of the compound through O or S, which is part of -(SP)j-CA. On the other hand, if i is 1, -(SP)j-CA is connected to -C(=Y2)- through O, S, a secondary N, or a tertiary N, which is part of -(SP)j-CA. Preferably, if i is 1, -(SP)j-CA is connected to -C(=Y2)- through a secondary N, or a tertiary N, which is part of -(SP)j-CA. Petition 870250092139, dated 08 / 10 / 2025, p. 59 / 254 52 / 246

[140] More preferably, the releasable group is -(OC(=Y2))i-(SP)j-CA. More preferably, the releasable group is -(Y1-C(=O))i-(SP)j-CA. More preferably, the releasable group is -(OC(=O))i-(SP)j-CA. More preferably, the releasable group is -OC(=O)-(SP)j-CA.

[141] Most preferably, the releasable group is OC(=O)-CA.

[142] CA is Construct A, which is a payload. Preferably, CA is an organic molecule or an inorganic molecule. More preferably, CA is a drug. Preferably, CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative. Most preferably, CA is monomethyl auristatin E (MMAE).

[143] Preferably, CA is linked to the -(Y1C(=Y2))i- moiety, preferably -OC(=O)-, via a secondary or tertiary nitrogen atom that is part of CA, forming a carbamate. Preferably, CA is monomethyl auristatin E (MMAE) linked to the -(Y1-C(=Y2))i- moiety, preferably -OC(=O)-, via a secondary or tertiary nitrogen atom that is part of MMAE, forming a carbamate; or CA is exatecane or an exatecane derivative linked to the -(Y1-C(=Y2))i- moiety, preferably -OC(=O)-, via a primary or secondary nitrogen atom that is part of exatecane, forming a carbamate. More preferably, CA is monomethyl auristatin E (MMAE) linked to the -(Y1-C(=Y2))i- moiety, preferably -OC(=O)-, via a secondary or tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[144] Preferably, group R48 is: Petition 870250092139, dated 08 / 10 / 2025, page 60 / 254 53 / 246 or where E1 is -H or -CH3, preferably E1 is -H.

[145] Most preferably, the R48 group is:

[146] SP is a spacer, of which preferred embodiments are defined below. Preferably, when SP is part of a releasable group, SP is a self-immolating ligand, which is also referred to here as LC. Said self-immolating ligands are well known in the art, and preferred embodiments of self-immolating ligands are defined below. If the spacer in the releasable group is a self-immolating ligand, after the reaction of a disclosure compound with a diene, initially a -LC-CA construct is released. After that, the self-immolating ligand self-immolates and releases the CA payload. Petition 870250092139, dated 08 / 10 / 2025, p. 61 / 254 54 / 246 Pharmaceuticals

[147] The drugs that can be used in a compound of Formula (1) are pharmaceutically active compounds. Preferably, the pharmaceutically active compound is selected from the group consisting of cytotoxins, antiproliferative / antitumor agents, antiviral agents, antibiotics, anti-inflammatory agents, chemosensitizing agents, radiosensitizing agents, immunomodulators, immunosuppressants, immunostimulants, antiangiogenic factors and enzyme inhibitors. Preferably, these pharmaceutically active compounds are selected from the group consisting of antibodies, antibody derivatives, antibody fragments, proteins, aptamers, oligopeptides, oligonucleotides, oligosaccharides, carbohydrates, as well as peptides, peptoids, steroids, toxins, hormones, cytokines, and chemokines.Most preferably, the drug is a protein, a toxin, a chelating moiety, monomethyl auristatin E, or doxorubicin; wherein preferably the chelating moiety comprises a radionuclide. Preferably, these drugs are low to medium molecular weight compounds, preferably organic compounds (e.g., about 200 to about 2500 Da, preferably about 300 to about 1750 Da, more preferably about 300 to about 1000 Da). Exemplary types of cytotoxic drugs for use as conjugates to the Trigger and to be released after the reaction of IEDDA with the activator, for example for use in cancer therapy, including, but not limited to, DNA-damaging agents, DNA crosslinkers, DNA ligands, DNA alkylating agents, DNA intercalators, DNA cleavers, etc. Petition 870250092139, dated 08 / 10 / 2025, page 62 / 254 55 / 246 Microtubule stabilizing and destabilizing agents, topoisomerase inhibitors, radiation sensitizers, antimetabolites, natural products and analogues thereof, peptides, oligonucleotides, enzyme inhibitors such as dihydrofolate reductase inhibitors and thymidylate synthase inhibitors.Examples include, but are not limited to, colquinine, vinca alkaloids, anthracyclines (e.g., doxorubicin, epirubicin, idarubicin, daunorubicin), camptothecines, taxanes, taxols, vinblastine, vincristine, vindesine, calicheamicins, tubulisins, tubulisin M, cryptophycines, methotrexate, metopterine, aminopterin, dichlormethotrexate, irinotecans, enediines, amanitins, debouganine, dactinomycins, CC1065 and analogues thereof, duocarmycins, maitansines, maitansinoids, dolastatins, auristatins, pyrrolobenzodiazepines and dimers (PBDs), indolinobenzodiazepines and dimers, pyridinobenzodiazepines and dimers, mitomycins (e.g. mitomycin C, mitomycin A, caminomycin), melphalan, leurosin, leurosidein, actinomycin, talisomycin, lexitropsins, bleomycins, podophyllotoxins, etoposide, etoposide phosphate, staurosporine, esperamycin, the pteridine family of drugs, SN-38 and analogues thereof, platinum-based drugs, cytotoxic nucleosides.Other exemplary drug classes include angiogenesis inhibitors, cell cycle progression inhibitors, P13K / m-TOR / AKT pathway inhibitors, MAPK signaling pathway inhibitors, kinase inhibitors, protein chaperone inhibitors, HDAC inhibitors, PARP inhibitors, Wnt / Hedgehog signaling pathway inhibitors, and RNA polymerase inhibitors. In some embodiments, the drug is an auristatin. Examples of auristatins include dolastatin 10. Petition 870250092139, dated 08 / 10 / 2025, page 63 / 254 56 / 246 monomethyl auristatin E (MMAE), auristatin F, monomethyl auristatin F (MMAF), auristatin F hydroxypropylamide (AF HPA), auristatin F phenylenediamine (AFP), monomethyl auristatin D (MMAD), auristatin PE, auristatin EB, auristatin EFP, auristatin TP, and auristatins AQ. MMAE is a preferred auristatin. Suitable auristatins are also described in US publications nos. 2003 / 0083263, 2011 / 0020343, and 2011 / 0070248; PCT application publications nos. WO09 / 117531, WO2005 / 081711, WO04 / 010957; WO02 / 088172 and WO01 / 24763, and U.S. Patents Nos. 7,498,298; 6,884,869; 6,323,315; 6,239,104; 6,124,431; 6,034,065; 5,780,588; 5,767,237; 5,665,860; 5,663,149; 5,635,483; 5,599,902; 5,554,725; 5,530,097; 5,521,284; 5,504,191; 5,410,024; 5,138,036; 5,076,973; 4,986,988; 4,978,744; 4,879,278; 4,879,278; 4,816,444; and 4,486,414, disclosures of which are incorporated herein by reference in their entirety. Examples of drugs include dolastatins and analogues thereof, including: dolastatin A (U.S. Patent No. 4,486,414), dolastatin B (U.S. Patent No. 4,486,414), dolastatin 10 (U.S. Patents Nos. 4,486,444, 5,410,024, 5,504,191, 5,521,284, 5,530,097, 5,599,902, 5,635,483, 5,663,149, 5,665,860, 5,780,588, 6,034,065, 6,323,315), dolastatin 13 (U.S. Patent No. 4,986,988), dolastatin 14 (U.S. Patent No. 5,138,036), dolastatin 15 (U.S. Patent No. 4,879,278), dolastatin 16 (U.S. Patent No. 6,239,104), dolastatin 17 (U.S. Patent No. 6,239,104), and dolastatin 18 (U.S. Patent No. 6,239,104), each patent incorporated herein by reference in its entirety. Examples of maytansines, maytansinoids, such as DM-1 and DM-4, ​​or Petition 870250092139, dated 08 / 10 / 2025, p. 64 / 254 57 / 246 Maitansinoid analogs, including maitansinol and maitansinol analogs, are described in U.S. Patents Nos. 4,424,219; 4,256,746; 4,294,757; 4,307,016; 4,313,946; 4,315,929; 4,331,598; 4,361,650; 4,362,663; 4,364,866; 4,450,254; 4,322,348; 4,371,533; 5,208,020; 5,416,064; 5,475,092; 5,585,499; 5,846,545; 6,333,410; 6,441,163; 6,716,821 and 7,276,497. Other examples include mertansine and ansamycocin. Pyrrolobenzodiazepines (PBDs), which expressly include dimers and analogues, include, but are not limited to, those described in [Denny, Exp. Opin. Ther. Patents, 10(4): 459 - 474 (2000)], [Hartley et al., Expert Opin Investig Drugs. 2011, 20(6): 733 - 44], Antonow et al., Chem Rev. 2011, 111(4), 2815 - 64]. Calicheamycins include, for example, enediines, esperamycin, and those described in U.S. patents nos. 5,714,586 and 5,739,116.Examples of duocarmycin analogs include CC1065, duocarmycin SA, duocarmycin A, duocarmycin B1, duocarmycin B2, duocarmycin C1, duocarmycin C2, duocarmycin D, DU-86, KW-2189, adozelesin, bizelesin, carzelesin, seco-adozelesin, CPI, CBI. Other examples include those described, for example, in U.S. patents nos. 5,070,092; 5,101,092; 5,187,186; 5,475,092; 5,595,499; 5,846,545; 6,534,660; 6,548,530; 6,586,618; 6,660,742; 6,756,397; 7,049,316; 7,553,816; 8,815,226; US20150104407; 61 / 988,011 filed May 2, 2014 and 62 / 010,972 filed June 11, 2014; the disclosure of each of which is incorporated herein in its entirety. Examples of vinca alkaloids include vincristine, vinblastine, vindesine, and navelbine, and those disclosed in U.S. Publications Nos. 2002 / 0103136 and 2010 / 0305149, and in U.S. Patent No. 7,303,749a. Petition 870250092139, dated 08 / 10 / 2025, page 65 / 254 58 / 246 disclosure of which is incorporated herein in its entirety. Examples of epothilone compounds include epothilone A, B, C, D, E, and F, and derivatives thereof. Suitable epothilone compounds and derivatives thereof are described, for example, in U.S. Patents Nos. 6,956,036; 6,989,450; 6,121,029; 6,117,659; 6,096,757; 6,043,372; 5,969,145; and 5,886,026; and WO97 / 19086; WO98 / 08849; WO98 / 22461; WO98 / 25929; WO98 / 38192; WO99 / 01124; WO99 / 02514; WO99 / 03848; WO99 / 07692; WO99 / 27890; and WO99 / 28324; the disclosure of which is incorporated herein in its entirety. Examples of cryptophycin compounds are described in U.S. Patents Nos. 6,680,311 and 6,747,021; the disclosure of which is incorporated herein in its entirety. Examples of platinum compounds include cisplatin, carboplatin, oxaliplatin, iproplatin, ormaplatin, tetraplatin. Examples of DNA-binding or alkylating drugs include CC-1065 and its analogues, anthracyclines, calicheamicins, dactinomycins, mithromycins, pyrrolobenzodiazepines, indolinobenzodiazepines, pyridinobenzodiazepines, and the like.Examples of microtubule stabilizing and destabilizing agents include taxane compounds such as paclitaxel, docetaxel, tesetaxel, and carbazitaxel; maytansinoids, auristatins and their analogues, vinca alkaloid derivatives, epothilones, and cryptophycins. Examples of topoisomerase inhibitors include camptothecin and its derivatives, camptothecin analogues, and non-natural camptothecins, such as, for example, CPT-11, SN-38, topotecan, 9-aminocamptothecin, rubitecan, gimatecan, karenitecin, silatecan, lurtotecan, exatecan, diflomethotecan, belotecan, lurtotecan, and S39625. Other camptothecin compounds that... Petition 870250092139, dated 08 / 10 / 2025, page 66 / 254 59 / 246 that may be used in this disclosure include those described in, for example, J. Med. Chem., 29: 2358-2363 (1986); J. Med. Chem., 23: 554 (1980); J. Med Chem., 30: 1774 (1987). Angiogenesis inhibitors include, but are not limited to, MetAP2 inhibitors, VEGF inhibitors, PIGF inhibitors, VGFR inhibitors, PDGFR inhibitors, and MetAP2 inhibitors. Examples of VGFR and PDGFR inhibitors include sorafenib, sunitinib, and vatalanib. Examples of MetAP2 inhibitors include fumagillol analogs, i.e., compounds that include the fumarylin core structure.Examples of cell cycle progression inhibitors include CDK inhibitors such as, for example, BMS-387032 and PD0332991; Rho-kinase inhibitors such as, for example, AZD7762; aurora kinase inhibitors such as, for example, AZD1152, MLN8054 and MLN8237; PLK inhibitors such as, for example, BI 2536, BI6727, GSK461364, ON-01910; and KSP inhibitors such as, for example, SB 743921, SB 715992, MK0731, AZD8477, AZ3146 and ARRY-520. Examples of inhibitors of the P13K / m-TOR / AKT signaling pathway include phosphoinositide 3-kinase (P13K) inhibitors, GSK-3 inhibitors, ATM inhibitors, DNA-PK inhibitors, and PDK-1 inhibitors. Examples of P13 kinases are disclosed in U.S. Patent No. 6,608,053, and include BEZ235, BGT226, BKM120, CAL263, demethoxyviridine, GDC-0941, GSK615, IC87114. LY294002, Palomid 529, Perifosine, PF-04691502, PX-866, SAR245408, SAR245409, SF1126, Wortmannin, XL147, and XL765. Examples of AKT inhibitors include, but are not limited to, AT7867. Examples of MAPK signaling pathway inhibitors include MEK, Ras, JNK, B-Raf, and p38 MAPK inhibitors. Examples of MEK inhibitors are disclosed in U.S. Patent No. 7,517,944 and include GDC-0973, GSK1120212, Petition 870250092139, dated 08 / 10 / 2025, page 67 / 254 60 / 246 MSC1936369B, AS703026, RO5126766 and RO4987655, PD0325901, AZD6244, AZD8330 and GDC-0973. Examples of B-raf inhibitors include CDC-0879, PLX-4032, and SB590885. Examples of B p38 MAPK inhibitors include BIRB 796, LY2228820, and SB 202190. Examples of tyrosine kinase receptor inhibitors include, but are not limited to, AEE788 (NVP-AEE 788), BIBW2992 (Afatinib), Lapatinib, Erlotinib (Tarceva), Gefitinib (Iressa), AP24534 (Ponatinib), ABT-869 (linifanib), AZD2171, CHR-258 (Dovitinib), Sunitinib (Sutent), Sorafenib (Nexavar), and Vatalinib. Examples of protein chaperone inhibitors include HSP90 inhibitors. Examples of inhibitors include 17AAG derivatives, BIIB021, BIIB028, SNX-5422, NVP-AUY-922, and KW-2478.Examples of HDAC inhibitors include Belinostat (PR48101), CUDC-101, Droxinostat, ITF2357 (Givinostat, Gavinostat), JNJ-26481585, LAQ824 (NVPLAQ824, Dacinostat), LBH-589 (Panobinostat), MC1568, MGCD0103 (Mocetinostat), MS-275 (Entinostat), PCI-24781, Pyroxamide (NSC 696085), SB939, Trichostatin A and Vorinostat (SAHA). Examples of PARP inhibitors include iniparib (BSI 201), olaparib (AZD-2281), ABT-888 (Veliparib), AG014699, CEP9722, MK 4827, KU-0059436 (AZD2281), LT-673, 3-aminobenzamide, A-966492, and AZD2461. Examples of Wnt / Hedgehog signaling pathway inhibitors include vismodegib, cyclopamine, and XAV-939. Examples of RNA polymerase inhibitors include amatoxins. Examples of amatoxins include alpha amanitins, beta amanitins, gamma amanitins, eta amanitins, amanulin, amanulic acid, amanisamide, amanon, and proamanulin.Examples of immunomodulators are APRIL, cytokines including IL-2, IL-7, IL-10, IL12, IL-15, IL-21, TNF, interferon gamma, GMCSF, NDV-GMCSF, and STING agonists and antagonists, TLR agonists and antagonists. Petition 870250092139, dated 08 / 10 / 2025, p. 68 / 254 61 / 246 including TLR1 / 2, TLR3, TLR4, TLR7 / 8, TLR9, TLR12, GITR agonists and antagonists, CD3, CD28, CD40, CD74, CTLA4, OX40, PD1, PDL1, RIG, MDA-5, NLRP1, NLRP3, AIM2, IDO, MEK, cGAS, and CD25, NKG2A. Other examples of drugs include puromycins, topetecan, rhizoxine, echinomycin, combretastatin, netopsin, estramustine, cemadotine, discodermolide, eleutherobine, mitoxantrone, pyrrolobenzimidazoles (PBI), gamma-interferon, thialanostatin (A) analogs, CDK11, immunotoxins, including for example ricin A, diphtheria toxin, cholera toxin.In exemplary embodiments of the disclosure, the drug portion is a mitomycin compound, a vinca alkaloid compound, taxol or an analogue, an anthracycline compound, a calicheamicin compound, a maytansinoid compound, an auristatin compound, a duocarmycin compound, SN38 or an analogue, a pyrrolobenzodiazepine compound, an indolinobenzodiazepine compound, a pyridinobenzodiazepine compound, a tubulisin compound, a non-natural camptothecin compound, a DNA-binding drug, a kinase inhibitor, a MEK inhibitor, a KSP inhibitor, a P13 kinase inhibitor, a topoisomerase inhibitor, or analogues thereof.In a preferred embodiment, the drug is a non-natural compound of camptothecin, vinca alkaloid, kinase inhibitor (e.g., P13 kinase inhibitor: GDC-0941 and PI-103), MEK inhibitor, KSP inhibitor, RNA polymerase inhibitor, PARP inhibitor, docetaxel, paclitaxel, doxorubicin, dolastatin, calicheamicins, SN38, pyrrolobenzodiazepines, pyridinobenzodiazepines, indolinobenzodiazepines, DNA-binding drugs, maytansinoids DM1 and DM4, auristatin MMAE, CC1065 and its analogues, camptothecin and its analogues. Petition 870250092139, dated 08 / 10 / 2025, page 69 / 254 62 / 246 SN-38 and its analogues. In another preferred embodiment, the drug is selected from DNA-binding drugs and microtubule agents, including pyrrolobenzodiazepines, indolinobenzodiazepines, pyridinobenzodiazepines, maytansinoids, maytansines, auristatins, tubulisines, duocarmycins, anthracyclines, taxanes. In another preferred embodiment, the drug is selected from colchicine, vinca alkaloids, tubulisines, irinotecans, an inhibitory peptide, amanitin, and bougainine. In another preferred embodiment, the drug is a radioactive moiety, said moiety comprising a radioactive isotope for radiotherapy.A radionuclide used for therapy is preferably an isotope selected from the group consisting of 24Na, 32P, 33P, 47Sc, 59Fe, 67Cu, 76As, 77As, 80Br, 82Br, 89Sr, 90Nb, 90Y, 103Ru, 105Rh, 109Pd, 111Ag, 111In, 121Sn, 127Te, 131I, 140La, 141Ce, 142Pr, 143Pr, 144Pr, 149Pm, 149Tb, 151Pm, 153Sm, 159Gd, 161Tb, 165Dy, 166Dy, 166Ho, 169Er, 172Tm, 175Yb, 177Lu, 186Re, 188Re, 198Au, 199Au, 211At, 211Bi, 212Bi, 212Pb, 213Bi, 214Bi, 223Ra, 224Ra, 225Ac, and 227Th. When the radioactive portion is intended to comprise a metal, such as 177Lu, said radiometal is preferably provided in the form of a chelate. In this case, the radioactive portion preferably comprises a structural portion capable of forming a coordination complex with said metal. A good example of this are macrocyclic lanthanide(III) chelates derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (H4dota). Preferably, the structural portion capable of forming a coordination complex with the aforementioned metal is a chelating portion as defined herein. In other embodiments, the radioactive portion comprises a prosthetic group (i.e., a Petition 870250092139, dated 08 / 10 / 2025, p. 70 / 254 63 / 246 phenol) that is linked by a non-metallic radionuclide, such as 131I. Drugs optionally include a (portion of a) membrane translocation moiety (e.g., adamantine, polylysine / arginine, TAT, human lactoferrin) and / or a targeting agent (against, for example, a tumor cell receptor) optionally linked via a stable or labile ligand. Examples of references include: Trends in Biochemical Sciences, 2015, 40, 12, 749; J. Am. Chem. Soc. 2015, 137, 12153-12160; Pharmaceutical Research, 2007, 24, 11, 1977. It will also be understood that, in addition to one or more targeting agents (or CBs) that may be linked to the Trigger or Ligand LC, a targeting agent TT may optionally be linked to a drug, optionally via a spacer SP.Alternatively, it will be further understood that the targeting agent (or CB) may comprise one or more additional drugs that are linked to the targeting agent by other types of ligands, for example, cleavable by proteases, pH, thiols, or by catabolism. It will be understood that chemical modifications may also be made to the desired compound to make the reactions of that compound more convenient for the purpose of preparing the disclosure conjugates. Drugs containing an amine functional group for coupling to the Trigger include mitomycin-C, mitomycin-A, daunorubicin, doxorubicin, aminopterin, actinomycin, bleomycin, 9-aminocamptothecin, N8-acetylspermidine, 1-(2-chloroethyl)1,2-dimethanesulfonylhydrazide, thalisomycin, cytarabine, dolastatins (including auristatins) and derivatives thereof.Drugs containing a hydroxyl functional group for trigger coupling include etoposide, camptothecin, taxol, esperamycin, 1,8-dihydroxyPetition 870250092139, dated 08 / 10 / 2025, page 71 / 254. 64 / 246 bicyclo[7.3.1]trideca-4-9-dieno-2,6-diino-13-one (U.S. Patent No. 5,198,560), podophyllotoxin, anguidin, vincristine, vinblastine, morpholine-doxorubicin, n-(5,5-diacetoxypentyl)doxorubicin, and derivatives thereof. Drugs containing a sulfhydryl functional group for trigger coupling include esperamycin and 6-mecaptopurine, and their derivatives. Log P

[148] In preferred embodiments the Log P of the compounds of Formula (1) have a value in the range of 2.0 and 2.0, more preferably in the range of 1.0 and -1.0.

[149] In embodiments where it is required that a compound as disclosed herein, in particular a diene, has an extracellular volume of distribution, it is preferred that the Log P of said compound be at most 2, preferably at most 1, more preferably at most 0, even more preferably at most -1. In embodiments where it is required that a compound as disclosed herein, in particular a diene, has an intracellular volume of distribution, it is preferred that the Log P of the activator be at least -1, preferably at least 0, more preferably at least 1, even more preferably at least 2. Molecular weight

[150] For a compound of Formula (1) wherein T2 is a bioconjugation moiety, it is preferred that the molecular weight of said compound be at most 5 kDa, more preferably at most 4 kDa, even more preferably at most 3.5 kDa, even more preferably at most 3 kDa, and most preferably at most 2.5 kDa. For a compound of Formula (1) where T2 is a group Petition 870250092139, dated 08 / 10 / 2025, p. 72 / 254 65 / 246 -L3-Cb, it is preferred that the molecular weight of said compound be at most 100 kDa, more preferably at most 85 kDa, even more preferably at most 75 kDa, even more preferably at most 65 kDa, and most preferably at most 62.5 kDa. SP Spacers

[151] All ligands as used herein may independently be an SP spacer. As one skilled in the art knows, the specific structure of a spacer used in a dienophile or diene, as described herein, does not normally influence whether the payload is released. However, in some cases specific spacers are preferred. For example, if a payload is released, the spacer between, for example, the allylic carbon of the eight-membered non-aromatic cyclic monoalkenylene and the payload is preferably a self-immolating ligand. Said ligand, which is normally referred to as Lcc, ensures that, after the release of the end of the ligand connected to said allylic carbon, a new rearrangement reaction occurs, after which the payload is decoupled from the Lc ligand. Spacers in general are discussed below, and subsequently, more specific self-immolating ligands.

[152] In general, an SPtal spacer as used herein is a portion according to RG2, more preferably any of the preferred and / or specific embodiments thereof.

[153] Preferably, an SP spacer consists of one or more linearly and / or branched Spacer Units (SU) and can be connected to one or more CBe fractions and / or to one or more Lcou Tr fractions. The spacer can be used to connect CBa to Tr (Example A) Petition 870250092139, dated 08 / 10 / 2025, p. 73 / 254 66 / 246 below; with reference to Formula 5a and 5b: f, e, a = 1) or more TR (Example B below; with reference to Formula 5a and 5b: f, e = 1, ab 1), but it can also be used to modulate properties, for example pharmacokinetic properties of the CB-TR-CA conjugate (Example D below; with reference to Formula 5a and 5b: one or more of c, e, g, hb 1). Thus, a spacer unit does not necessarily connect two entities, it can also be linked to only one component, for example the TR or LC. Alternatively, the spacer may comprise a spacer unit that connects the CBa to the TR, in addition, it may comprise another spacer unit that is connected only to the spacer and serves to modulate the properties of the conjugate (Example F below; with reference to Formula 5a and 5b: eb 1).The spacer can also consist of two different types of SU constructs, for example a PEG linked to the peptide, or a PEG linked to an alkylene moiety (Example E below; with reference to Formula 5a and 5b: eb 1). For clarity, Example B describes a branched SU using a multivalent branched SU. Example C describes a branched SU using a linear SU polymer, such as a peptide, whose side chain residues serve as conjugation groups. Petition 870250092139, dated 08 / 10 / 2025, p. 74 / 254 67 / 246 ** indicates connection to IR or LC or (to the remainder of) ΞP - - - indicates connection to the [remaining of] CB

[154] The spacer can be connected to the activator in similar designs, such as those described in examples A - F above.

[155] Each individual spacer unit (SU) can be independently selected from the radical group according to RG2. Spacer units include but are not limited to amino acids, nucleosides, nucleotides, and biopolymer fragments, such as oligo- or polypeptides, oligo- or polypeptides, or oligo- or polylactides, or oligo- or polycarbohydrates, ranging from 2 to 200, particularly 2 to 113, preferably 2 to 50, more preferably 2 to 24 and most preferably 2 to 12 repeating units. Preferred biopolymer SUs are peptides. Preferably each SU comprises a maximum of 50 carbon atoms, more preferably a maximum of 25 carbon atoms, most preferably a maximum of 10 carbon atoms.In some embodiments, SU is independently selected from the group consisting of (CH2)r, (C3-C8 carbocycle), O-(CH2)r, arylene, (CH2)rarylene, arylene-(CH2)r, (CH2)r-(C3-C8 carbocycle), (C3-C8 carbocycle) - (CH2)r, (C3-C8 heterocycle), (CH2)r-. Petition 870250092139, dated 08 / 10 / 2025, page 75 / 254 68 / 246 (C3-C8 heterocycle), (C3-C8 heterocycle)-(CH2)r, (CH2)rC(O)NR'(CH2)r, (CH2CH2O)r, (CH2CH2O)rCH2,(CH2)rC(O)NR'(CH2CH2O)r, (CH2)rC(O)NR'(CH2CH2O)rCH2, (CH2CH2O)rC(O)NR'(CH2CH2O)r, (CH2CH2O)rC(O)NR'(CH2CH2O)rCH2, (CH2CH2O)rC(O)NR'CH2; wherein r is independently an integer from 1 to 10. As used herein, each R' is independently selected from the group consisting of radicals according to RG1. Preferably, R' is hydrogen. Other examples of SU spacer units are linear or branched polyalkylene glycols such as polyethylene glycol (PEG) or polypropylene glycol (PPG) chains ranging from 2 to 200, particularly from 2 to 113, preferably 2 to 50, more preferably 2 to 24 and most preferably 2 to 12 repeating units. It is preferred that when the polyalkylene glycol such as PEG and PPG polymers are only linked by means of one end of the polymer chain, that the other end is terminated with -OCH3, -OCH2CH3, OCH2CH2CO2H.Other polymeric spacer units are polymers and copolymers such as poly-(2-oxazoline), poly(N-(2-hydroxypropyl) methacrylamide) (HPMA), polylactic acid (PLA), polylactic-glycolic acid (PLGA), polyglutamic acid (PG), dextran, polyvinylpyrrolidone (PVP), poly(1-hydroxymethylethylene hydroxymethylformin (PHF)). Other examples of polymers are polysaccharides, glycopolysaccharides, glycolipids, polyglycosides, polyacetals, polyketals, polyamides, polyethers, and polyesters. Examples of natural polysaccharides that can be used as SU are cellulose, amylose, dextran, dextrin, levan, fucoidan, carrageenan, inulin, pectin, amylopectin, glycogen, lixenan, agarose, hyaluronan, chondroitin sulfate, dermatan sulfate, sulfate of. Petition 870250092139, dated 08 / 10 / 2025, page 76 / 254 69 / 246 keratan, alginic acid, and heparin. In further examples of embodiments, the polymeric SU comprises a copolymer of a polyacetal / polyketal and a hydrophilic polymer selected from the group consisting of polyacrylates, polyvinyl polymers, polyesters, polyorthoesters, polyamides, oligopeptides, polypeptides, and derivatives thereof. Preferred polymeric SUs are PEG, HPMA, PLA, PLGA, PVP, PHF, dextran, oligopeptides, and polypeptides. In some embodiments, the polymers used in a SU have a molecular weight ranging from 2 to 200 kDa, 2 to 100 kDa, 2 to 80 kDa, 2 to 60 kDa, 2 to 40 kDa, 2 to 20 kDa, 3 to 15 kDa, 5 to 10 kDa, and from 500 daltons to 5 kDa. Other examples of SUs are dendrimers, such as poly(propylene imine) (PPI) dendrimers, PAMAM dendrimers, and glycol-based dendrimers.The SU of the disclosure expressly includes, but is not limited to, conjugates prepared with commercially available crosslinking reagents such as BMPEO, BMPS, EMCS, GMBS, HBVS, LCSMCC, MBS, MPBH, SBAP, SIA, SIAB, SMCC, SMPB, SMPH, sulfoEMCS, sulfo-GMBS, sulfo-KMUS, sulfo-MBS, sulfo-SIAB, sulfoSMCC, sulfo-SMPB, and SVSB, DTME, BMB, BMDB, BMH, BMOE, BM(PEO)3 and BM(PEO)4. To construct a branched spacer, a SU based on one or more natural or non-natural amino acids, amino alcohols, amino aldehydes or polyamine residues, or combinations thereof, which collectively provide the functionality necessary for branching, may be used. For example, serine has three functional groups, namely acid, amino, and hydroxyl groups, and can be viewed as a combined amino acid, an amino alcohol residue with the purpose of acting as a branched SU. Other examples of amino acids are lysine and tyrosine. In some embodiments, Petition 870250092139, dated 08 / 10 / 2025, p. 77 / 254 70 / 246 the spacer consists of one spacer unit, therefore in these cases SP is equal to SU. Preferably, the spacer consists of two, three, or four spacer units. In some embodiments, SP has a molecular weight ranging from 2 to 200 kDa, from 2 to 100 kDa, from 2 to 80 kDa, from 2 to 60 kDa, from 2 to 40 kDa, from 2 to 20 kDa, from 3 to 15 kDa, from 5 to 10 kDa, or from 500 daltons to 5 kDa. In some cases, SP has a mass of no more than 5,000 daltons, no more than 4,000 daltons, no more than 3,000 daltons, no more than 2,000 daltons, no more than 1,000 daltons, no more than 800 daltons, no more than 500 daltons, no more than 300 daltons, no more than 200 daltons. In some aspects, SP has a mass of 100 daltons, 200 daltons, 300 daltons to 5000 daltons. In some aspects, SP has a mass of 30, 50, or 100 daltons to 1000 daltons, about 30, 50, or 100 daltons to 500 daltons.

[156] Preferably, SP comprises a portion of RG2a, RG2b, RG2c, or a residue of RG1f, as described herein. Preferably, said RG2a, RG2b, RG2c, or a residue of RG1f connects the SP to the CB, LC, or TR. Self-immolating ligands LC

[157] LC is an optional self-immolating ligand, which may consist of multiple linearly and / or branched arranged units. The possible structures of LC, its use, position and linkage forms of the LC, CA and TR ligands (the Trigger, i.e. the trans-cyclooctene moiety) are known to those skilled in the art, see for example [Papot et al., Anticancer Agents Med. Chem., 2008, 8, 618-637]. However, preferred, but not limiting, examples of self-immolating LC ligands are benzyl derivatives, such as those drawn below. There are two main mechanisms of Petition 870250092139, dated 08 / 10 / 2025, p. 78 / 254 71 / 246 Self-immolation: Electron cascade elimination and cyclization-mediated elimination. The preferred example below on the left works via the cascade mechanism, where the bond between the allylic carbon of the trigger and the -O- or -S- attached to said carbon is cleaved, and an electron pair from YC1, for example an electron pair from NR6, shifts to the benzyl portion resulting in an electron cascade and the formation of 4-hydroxybenzyl alcohol, CO2, and the released payload. The preferred example in the middle works via the cyclization mechanism, where the cleavage of the bond to NR6 on the trigger side leads to nucleophilic attack of the amine on the carbonyl, forming a 5-ring 1,3-dimethylimidazolidin-2-one and releasing the payload. The preferred example on the right combines both mechanisms. This ligand will degrade not only into CO2 and a 4-hydroxybenzyl alcohol unit (when YC1 is 0), but also into a 1,3-dimethylimidazolidine-2-one unit. where the wavy line indicates a linkage to -O- or -S on the allylic position of trans-cyclooctene, and the double dashed line indicates a linkage to CA.

[158] By replacing the benzyl groups of the aforementioned Lcacima self-immolating ligands, it is possible to adjust the payload release rate, caused by spherical and / or electronic effects in cyclization and / or cascade release. The synthetic procedures for preparing said substituted benzyl derivatives are known. Petition 870250092139, dated 08 / 10 / 2025, p. 79 / 254 72 / 246 by the expert in the field (see for example [Greenwald et al, J. Med. Chem., 1999, 42, 3657 - 3667] and [Thornthwaite et al, Polym. Chem., 2011, 2, 773 - 790]. Some preferred substituted benzylic derivatives with different release rates are shown below.

[159] Self-immolating ligands that undergo cyclization include, but are not limited to, substituted and unsubstituted aminobutyric acid amides, appropriately substituted bicyclic [2.2.1] and bicyclic [2.2.2] ring systems, 2-aminophenylpropionic acid amides and trimethyl lock-based ligands, see for example [Chem. Biol. 1995, 2, 223], [J. Am. Chem. Soc. 1972, 94, 5815], [J. Org. Chem. 1990, 55, 5867], the contents of which are incorporated herein by reference. Other preferred examples of LCs can be found in WO2009017394(A1), US7375078, WO2015038426A1, WO2004043493, Angew. Chem. International Edition 2015, 54, 7492 - 7509, the contents of which are incorporated herein by reference.

[160] Preferably, the LC has a mass of not more than 1,000 daltons, not more than 500 daltons, not more than 400 daltons, not more than 300 daltons, or from 10, 50 or 100 to 1000 daltons, from 10, 50, 100 to 400 daltons, from 10, 50, 100 to 300 daltons, from 10, 50, 100 to 200 daltons, for example, 10 - 1000 daltons, as well as 50 - 500 daltons, as well as 100 to 400 daltons.

[161] A person skilled in the art will know that an LC may be connected to another LC that is connected to the CA, wherein after the activator reaction with the TR trigger, Lc-Lc-Ca is released from the TR, leading to the autoimmune release of both LC portions and the payload. In relation to the LC formulas disclosed here, the connection of LC to TR and to another LC does not release the payload, but rather an LC that is connected via YC1 and still is Petition 870250092139, dated 08 / 10 / 2025, p. 80 / 254 73 / 246 connects to CA. A technician in the field will recognize that this principle also applies to other Lc-connected Lc ligands, for example Lc-Lc-Lc-Lc-CA.

[162] Preferably, if the releasable group contains a self-immolating ligand, the releasable group conforms to any of Group I, Group II, Group III, and Group IV as shown below. In the structures represented for the said Groups, only construct A bonded to an atom (typically oxygen) in the allylic position of the eight-membered non-aromatic cyclic monoalkenylene (preferably a trans-cyclooctene ring) is shown for clarity, but said construct A and said atom are part of the releasable group.

[163] The releasable groups according to Group I are indicates the linkage to -O- in the allylic position of the trans-cyclooctene ring; = _ indicates the linkage to CA where the wavy line may also indicate a linkage to -S- in the allylic position of trans-cyclooctene, where U, V, W, Z are each selected independently from the group consisting of -CR7-, and -N-, where e is 0 or 1, where X is selected from the group consisting of -O-, -S- and -NR6-, where preferably each R8 and R9 are selected independently from the group consisting of hydrogen, (hetero)alkyl C1-C4, (hetero)alkenyl C2-C4, and (hetero)aryl C4-C6; wherein R8 and R9, (hetero)alkyl, (hetero)alkenyl, and (hetero)aryl are optionally substituted with a selected portion of the group consisting of -Cl, -F, -Br, -I, -OH, -NH2, -OH, -SH, -SO3H, -PO3H, -PO4H2 and -NO2, preferably Petition 870250092139, dated 08 / 10 / 2025, p. 81 / 254 74 / 246 contains at most two heteroatoms selected from the group consisting of -O-, -S-, -NH-, -P-, and -Si-, wherein the N, S, and P atoms are optionally oxidized. Preferably, for releasable groups from Group I, both R8 and R9 are hydrogen.

[164] 0 releasable group according to Group II is indicates the linkage to -O- in the allylic position of the trans-cyclooctene ring; indicates the linkage to CA where the wavy line may also indicate a linkage to -S- in the allylic position of trans-cyclooctene, where m is an integer between 0 and 2, preferably m is 0, where e is 0 or 1. Preferably, for the releasable groups of Group II, both R8 and R9 are hydrogen. Preferably, for the releasable groups of Group II, R7 is methyl or isopropyl. Optionally, R6, R7, R8, R9, comprised in said Group I and II, are -(Sp)i-CB.

[165] For all releasable groups according to Group I and Group II, YC1 is selected from the group consisting of -0-, -S-, and -NR6-, preferably -NR6-. For all linkers according to Group I, and Group II, YC2 is selected from the group consisting of 0 and S, preferably 0.

[166] The releasable groups according to Group III are Petition 870250092139, dated 08 / 10 / 2025, p. 82 / 254 75 / 246 ™ indicates attachment to -O- at the allylic position of the trans-cyclooctene ring. --- indicates optional linkage to -{SP)i-CB indicates linkage to CA in which the wavy line may also indicate a linkage to -S- in the allylic position of trans-cyclooctene.

[167] The releasable groups according to Group IV are = = = indicates the linkage to CA where the wavy line can also indicate a linkage to -S- at the allylic position of trans-cyclooctene.

[168] Preferably, R6, R7, R8, R9 are in accordance with RG1 or any preferred embodiment thereof. Preferably, R6, R7, R8, R9 as used herein are not substituted. More preferably, R6, R7, R8, R9 Petition 870250092139, dated 08 / 10 / 2025, p. 83 / 254 76 / 246 as used here are hydrogen. Combined disclosure

[169] The disclosure also refers to a conjugate, or a salt, hydrate, or solvate thereof, wherein the conjugate comprises a protein conjugated to at least one compound according to the disclosure wherein T2 is a residue of a bioconjugation moiety, and said protein and said compound are conjugated via T2. Then, the conjugate of the disclosure should be understood as a compound of the disclosure (wherein T2 was originally a bioconjugation moiety) linked to a protein via T2, wherein due to the coupling of said compound and said protein, T2 in the conjugate of the disclosure is the residue of a bioconjugation moiety, preferably the residue of an N-maleimidyl group, namely: where the asterisk indicates a protein binding, and the wavy line denotes a binding to the rest of the disclosure compound.

[170] In the disclosure conjugate, the protein is preferably a diabody or an antibody, more preferably a diabody, and most preferably the protein is AVP0458 which consists of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[171] Preferably, in the disclosure conjugate the protein and the disclosure compound are conjugated by means of a T2e sulfhydryl residue of said protein, a hydroxyl residue of said protein, or a residue Petition 870250092139, dated 08 / 10 / 2025, page 84 / 254 77 / 246 of an amine of said protein; more preferably by means of T2e a sulfhydryl residue of said protein. Preferably, the sulfhydryl group residue of said protein is part of a cysteine ​​residue of said protein.

[172] Preferably, the conjugate of disclosure is CJ where E1 is -H or -CH3, preferably E1 is -H.

[173] More preferably, the combined disclosure Petition 870250092139, dated 08 / 10 / 2025, p. 85 / 254 78 / 246 CJ

[174] With respect to the conjugates of the disclosure, CJ is in a range of 1 to 12, preferably CJ is from 2 to 10, more preferably from 2.5 to 8, even more preferably from 3 to 6, and most preferably from 3.5 to 4. It will be understood that, for individual conjugates, CJ is normally an integer, and is most preferably about 4. When measuring CJ for multiple conjugates, however, an average number can be obtained, which is not necessarily an integer. As CJ is commonly determined for multiple conjugates, CJ with respect to a disclosure normally refers to an average number.

[175] More preferably, the conjugate is: Petition 870250092139, dated 08 / 10 / 2025, p. 86 / 254 79 / 246 preferably E1 is -H. where E1 is -H or -CH3, where E1 is -H or -CH3, preferably E1 is -H. — CJ in

[177] More preferably, the conjugate is: Petition 870250092139, dated 08 / 10 / 2025, p. 87 / 254 80 / 246 CJ

[178] More preferably, the conjugate is: CJ Compositions for dissemination

[179] The disclosure also refers to a composition comprising a compound according to the disclosure, or the salt, hydrate, or solvate thereof. Preferably, the composition is a pharmaceutical composition. Preferably, the disclosure composition further comprises a pharmaceutically acceptable carrier. It is also preferable that if a salt of a disclosure compound is included in the disclosure composition, a pharmaceutically acceptable salt is used. Disclosure combinations

[180] The disclosure also refers to a combination of (A1) a compound according to the disclosure, or the salt, hydrate, or solvate thereof; (A2) a conjugate according to the disclosure, or the salt, hydrate, or solvate thereof; and / or (A3) a composition according to the disclosure; with (B) a diene or salt, solvate, or hydrate thereof. It will be here Petition 870250092139, dated 08 / 10 / 2025, p. 88 / 254 81 / 246 understood that, a compound according to the disclosure is a dienophile and / or comprises a dienophilic moiety, and may be referred to as a Trigger. The diene may be referred to herein as an Activator.

[181] Preferably, the combination is (A1) and (B). Preferably, the combination is (A2) and (B). Preferably, the combination is (A3) and (B). Preferably, the combination is (A1), (A2), and (B). Preferably, the combination is (A1), (A3), and (B). Preferably, the combination is (A2), (A3), and (B). Preferably, the combination is (A1), (A2), (A3), and (B) .

[182] Preferably, the disclosure combination is a kit. More preferably, the disclosure combination is a kit in which (A1), (A2), and / or (A3) is / are physically separated from (B).

[183] ​​Preferably the diene is a tetrazine. More preferably, the diene is selected from the group consisting of: Petition 870250092139, dated 08 / 10 / 2025, page 89 / 254 82 / 246 or a salt, hydrate, and / or solvate thereof.

[184] Preferably, the diene is (TZ1) or a salt, hydrate, and / or solvate thereof. More preferably, the diene is (TZ2) or a salt, hydrate, and / or solvate thereof. More preferably, the diene is (TZ3) or a salt, hydrate, and / or solvate thereof. More preferably, the diene is (TZ4) or a salt, hydrate, and / or solvate thereof. Most preferably, the diene is (TZ5) or a salt, hydrate, and / or solvate thereof.

[185] (TZ1) is the most well-studied tetrazine for in vivo use in the literature, and the most promising candidate for clinical use. Reference is made to, inter alia, Rossin et al., Angew. Chem. Int. Ed. 2010, volume 49, pages 3375-3378; Rossin et al., J. Nucl. Med. 2013, volume 54; pages 1989-1995; Rossin et al., Bioconjugado Chem. 2013, volume 24, pages 1210-1217; Rossin et al., Mol. Pharm. 2014, volume 11, pages 3090-3096; Van Duijnhoven et al., J. Nucl. Med. 2015, volume 56, pages 1422-1428; Edem et al. Molecules 2020, volume 25, page 463; Rossin et al., Bioconjugate Chem. 2016, volume 27, pages 1697 - 1706; Rossin et al. , Nature Commun. 2018, volume 9, article 1484; WO 2020 / 256546 (in particular Example 5 on pages 294 - Petition 870250092139, dated 08 / 10 / 2025, page 90 / 254 83 / 246 296).

[186] However, the inventors identified several previously unknown disadvantages (TZ1). These problems arise mainly when (TZ1) is used in vivo as an activator for the release of the payload of an eight-membered non-aromatic cyclic monoalkenylene moiety (such as a trans-cyclooctene), which requires higher doses than when (TZ1) is used for radioimaging and / or radiotherapy.

[187] First, it was discovered that the compound (TZ1) strongly inhibits the physiologically relevant enzymes cyclooxygenase (COX-1), acetylcholinesterase (ACES), monoamine oxidase (MAO-B), L-type calcium channel, dihydropyridine. Each of these proteins is important for maintaining the health of the individual, and the unwanted inhibition of these enzymes and / or transporter can lead to side effects.

[188] Secondly, (TZ1) was found to have a relatively low tolerated maximum dose (TMD) in mice of about 39 pmol / kg.

[189] Furthermore, the synthesis of (TZ1) involves many steps, whereas it is preferred that tetrazines that can be synthesized in fewer steps be used.

[190] Finally, it is desirable that tetrazines with good general properties in vitro and in vivo be provided, i.e. one or more of: good stability, good reactivity with and / or high payload release of trans-cyclooctenes (especially in vivo), low membrane permeability, low cellular toxicity, and low genotoxicity.

[191] It has been found that (TZ2), (TZ3), (TZ4), and in particular (TZ5) overcome one or more of these disadvantages of Petition 870250092139, dated 08 / 10 / 2025, p. 91 / 254 84 / 246 (TZ1). Thus, combinations with at least one of (TZ2), (TZ3), (TZ4), and (TZ5) are preferred over combinations comprising (TZ1), and combinations with (TZ5) are most preferred. Non-therapeutic methods that use and uses for the use of compounds in the disclosure

[192] In some embodiments, the disclosure refers to non-therapeutic methods and non-therapeutic uses. Preferably, the dienophile used is as described in relation to the disclosure combination.

[193] For the non-therapeutic method of disclosure, it is preferred that the disclosure compound (namely (ia)), the disclosure conjugate (namely (iia)), and / or the disclosure composition (namely (iiia)), and the diene are further brought into contact with a solvent. The person skilled in the art has knowledge of suitable solvents for a reaction between a trans-cyclooctene (TCO) and a tetrazine. Preferably, the solvent comprises water, and more preferably the solvent is water.

[194] For non-therapeutic use, the click reaction is preferably a bioorthogonal click reaction. Preferably, the click reaction is performed in vitro, although non-therapeutic in vivo reactions can also be performed. Medical use

[195] The disclosure also refers to a compound of the disclosure, or the salt, hydrate, or solvate thereof; the conjugate of the disclosure, or the salt, hydrate, or solvate thereof; the composition of the disclosure; or the combination of the disclosure; for use in the treatment of a disease in an individual. Petition 870250092139, dated 08 / 10 / 2025, p. 92 / 254 85 / 246

[196] Disclosure also refers to a method of treating a disease in an individual, wherein the said method comprises the step of administering to said individual:

[197] (a) the compound according to the disclosure, or the salt, hydrate, or solvate thereof;

[198] (b) the conjugate according to the disclosure, or the salt, hydrate, or solvate thereof;

[199] (c) the composition in accordance with the disclosure; and / or

[200] (d) the combination according to the disclosure.

[201] Use of:

[202] (a) a compound according to disclosure, or the salt, hydrate, or solvate thereof;

[203] (b) a conjugate according to the disclosure, or the salt, hydrate, or solvate thereof;

[204] (c) a composition in accordance with the disclosure; and / or

[205] (d) a combination in accordance with disclosure; for the manufacture of a medicine for the treatment of a disease in an individual.

[206] In relation to medical use, preferably the individual is a human. Preferably, the disease is cancer. Synthesis methods for the compounds of the dissemination

[207] The disclosure also refers to a method for the synthesis of a compound of the disclosure, wherein said method comprises coupling a compound of Formula (R) to a compound of Formula (S): Petition 870250092139, dated 08 / 10 / 2025, p. 93 / 254 86 / 246 where R48, T1, and ey are as defined here; t^.s10 xFormula (S); where T2, e.g., are as defined herein, and S10 is COOH or an active ester, preferably S10 is -COOH. Preferably, in Formula (S) x is an integer from 4 to 6, and most preferably x is 5.

[208] In the method for the synthesis of a disclosure compound, where S10 is -COOH, it is preferred that the compound of Formula (S) be brought into contact with at least one coupling reagent, preferably in the presence of a base, preferably a non-nucleophilic base. Preferred non-nucleophilic bases are N,N-diisopropylethylamine (DIPEA), 1,8-diazabicycloundec-7-ene (DBU), and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN). Preferably, the at least one coupling reagent is as defined in Clause 583.

[209] A person skilled in the art has knowledge of the appropriate conditions for carrying out a coupling reaction between a compound of Formula (R) and a compound of Formula (S).

[210] Preferably, the coupling is carried out at a temperature of -20 °C to 80 °C, more preferably from 0 °C to 60 °C, even more preferably from 4 °C to 50 °C, Petition 870250092139, dated 08 / 10 / 2025, page 94 / 254 87 / 246 more preferably still from 10 °C to 40 °C, and most preferably from 15 °C to °C.

[211] Preferably, the coupling is carried out in the presence of a solvent, where preferably the solvent is an organic solvent.

[212] The disclosure also refers to an alternative method for the synthesis of a compound of the disclosure, wherein said method comprises coupling a compound of Formula (T) to a compound of Formula (U): s1 T1, R48 Formula in which T1e R48 are as defined here; and S11e-COOH or an active ester, preferably S11 is an active ester, more preferably S11 is selected from the group consisting of -C(O)ON-succinimidyl, -C(O)Opentafluorophenyl, -C(O)O-tetrafluorophenyl, -C(O)O-4nitrophenyl, and -C(O)Cl; even more preferably, S11 is C(O)ON-succinimidyl, or -C(O)O-pentafluorophenyl; and most preferably, S11 -C(O)O-pentafluorophenyl. nh2 O y Formula (U); where T2, x, and y are as defined here.

[213] Preferably, in Formula (U) x is an integer from 4 to 6, and most preferably x is 5.

[214] In the alternative method for the synthesis of a disclosure compound, when S11 is -COOH, it is preferred that Petition 870250092139, dated 08 / 10 / 2025, p. 95 / 254 88 / 246 the compound of Formula (S) is brought into contact with at least one coupling reagent, preferably in the presence of a base, preferably a non-nucleophilic base. Preferred non-nucleophilic bases are N,N-diisopropylethylamine (DIPEA), 1,8-diazabicycloundec-7-ene (DBU), and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN). Preferably, the at least one coupling reagent is as defined in Clause 583.

[215] A person skilled in the art has knowledge of the appropriate conditions for carrying out a coupling reaction between a compound of Formula (T) and a compound of Formula (U). Preferably, the coupling is carried out at a temperature of -20 °C to 80 °C, more preferably from 0 °C to 60 °C, even more preferably from 4 °C to 50 °C, even more preferably from 10 °C to 40 °C, and most preferably from 15 °C to 30 °C. Preferably, the coupling is carried out in the presence of a solvent, wherein the solvent is preferably an organic solvent. Methods for synthesizing conjugates from the dissemination process.

[216] The disclosure also refers to a method for the synthesis of a disclosure conjugate, wherein said method comprises the step of coupling a protein to a disclosure compound, or a salt, hydrate, or solvate thereof; wherein said compound, T2 is a bioconjugation moiety; wherein said protein preferably the disulfide bonds have been reduced.

[217] As T2no disclosure compound is preferably a bioconjugation moiety that can react with a sulfhydryl group, such as an N-maleimidyl group, it is preferred that the protein contain free sulfhydryl groups. Typically, said sulfhydryl groups can be obtained Petition 870250092139, dated 08 / 10 / 2025, p. 96 / 254 89 / 246 by reducing the disulfide bonds present in the protein. For this, it is preferred that the protein has been placed in contact with a reducing agent before coupling. Preferably, the reducing agent is selected from the group consisting of dithiothreitol (DTT) and tris-2-carboxyethylphosphine hydrochloride (TCEP).

[218] If the protein is brought into contact with a reducing agent before coupling, the reducing agent is preferably DTT. Additionally or alternatively, the formation of free sulfhydryl groups in the protein can also be carried out in situ. For this, coupling is preferably carried out in the presence of a reducing agent. In this case, it is preferable to use a reducing agent that does not contain free sulfhydryl groups. Then, if coupling is carried out in the presence of a reducing agent, it is preferred that the reducing agent be TCEP.

[219] The person skilled in the art has knowledge of suitable conditions for carrying out the method of synthesizing a conjugate of the disclosure.

[220] Preferably, the coupling is carried out at a temperature of 0 °C to 40 °C, more preferably from 1 °C to 30 °C, even more preferably from 2 °C to 20 °C, even more preferably from 4 °C to 10 °C, and most preferably at about 4 °C.

[221] Preferably, the coupling is carried out in an aqueous solution, preferably the aqueous solution is an aqueous buffer solution.

[222] Preferably, coupling is carried out at a pH of 6.0 to 8.5, preferably 6.2 to 8.0, more preferably 6.4 to 7.8, even more preferably 6.5 to 7.4, and even more preferably 6.6 to 7.0, and Petition 870250092139, dated 08 / 10 / 2025, p. 97 / 254 90 / 246, most preferably at a pH of around 6.8.

[223] The present disclosure is described here in relation to a particular embodiment, but the disclosure is not limited to that, but only to the claims. When an indefinite or definite article is used in referring to a singular noun, for example, “a” or “an”, “the”, this includes the plural of that noun, unless something different is specifically stated.

[224] The verb “to include, and its conjugations, as used in this descriptive report and claims, is used in its non-limiting sense to mean that the items that follow the word are included, but items not specifically mentioned are not excluded.

[225] Furthermore, the reference to an element by the indefinite article “a” or “an” does not exclude the possibility that more than one element is present, unless the context clearly requires that there be only one of the elements. The indefinite article “a” or “an” therefore generally means “at least one.”

[226] So the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. This means that, in relation to the present disclosure, the only relevant components of the device are A and B.

[227] The compounds herein may occur in different tautomeric forms. The compounds according to the disclosure are intended to include all tautomeric forms unless otherwise indicated. When the structure of a compound is depicted as a specific tautomer, it should be understood that the disclosure of this application is not limited to that specific tautomer unless otherwise indicated. Petition 870250092139, dated 08 / 10 / 2025, p. 98 / 254 91 / 246

[228] The compounds herein may occur in different enantiomeric forms. The compounds according to the disclosure are intended to include all enantiomeric forms, unless otherwise indicated. When the structure of a compound is represented as a specific enantiomer, it should be understood that the disclosure of the present application is not limited to that specific enantiomer, unless otherwise indicated.

[229] Unless otherwise indicated, the disclosure compounds and / or groups thereof may be protonated or deprotonated. It will be understood that it is possible for a compound to bear multiple charges which may be of opposite signs. For example, in a compound containing an amine and a carboxylic acid, the amine may be protonated while simultaneously the carboxylic acid is deprotonated.

[230] Unless otherwise indicated, if reference is made in this disclosure to a molecular structure such as “compound”, “diene”, “tetrazine”, and the like, it shall be understood that said molecular structure may also be in its salt, hydrate, and / or solvate form.

[231] In several Formulas, groups or substituents are indicated with reference to letters such as “A”, “B”, “X”, “Y”, and various “R” groups (numbered). In addition, the number of repeating units may be referred to with a letter, for example n in -(CH2)n-. The definitions of these letters should be read with reference to each Formula, i.e., in different Formulas these letters, each independently, may have different meanings, unless otherwise indicated.

[232] Here, reference is made to “alkyl”, and similar groups. The number of carbon atoms that these groups have, excluding the carbon atoms comprised in any Petition 870250092139, dated 08 / 10 / 2025, p. 99 / 254 92 / 246 optional substituents according to Radical Group 1, may be indicated by a designation preceding the said terms (for example, “C1-C8 alkyl” means that said alkyl may have from 1 to 8 carbon atoms). For avoidance of doubt, a butyl group substituted by an -OCH3 group is designated as a C4 alkyl, because the carbon atom in the substituent is not included in the carbon count.

[233] A cycloalkyl group is a cyclic alkyl group. Unsubstituted cycloalkyl groups comprise at least three carbon atoms and have the general formula CnH2n-1. Optionally, cycloalkyl groups are substituted by one or more substituents specified in this document. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[234] An alkenyl group comprises one or more carbon-carbon double bonds, and may be linear or branched. Unsubstituted alkenyl groups comprising one C-C double bond have the general formula CnH2n-1. Unsubstituted alkenyl groups comprising two C-C double bonds have the general formula CnH2n-3. An alkenyl group may comprise a terminal carbon-carbon double bond and / or an internal carbon-carbon double bond. A terminal alkenyl group is an alkenyl group in which a carbon-carbon double bond is located at a terminal position of a carbon chain. An alkenyl group may also comprise two or more carbon-carbon double bonds. Examples of an alkenyl group include ethenyl, propenyl, isopropenyl, t-butenyl, 1,3-butadienyl, 1,3-pentadienyl, etc. Unless otherwise indicated, an alkenyl group may optionally be replaced by one or more substituents according to Radical Group 1. Petition 870250092139, dated 08 / 10 / 2025, p. 100 / 254 93 / 246 selected independently.

[235] A cycloalkenyl group is a cyclic alkenyl group. An unsubstituted cycloalkenyl group comprising a double bond has the general formula CnH2n-3. Optionally, a cycloalkenyl group is substituted by one or more substituents specified in this document. An example of a cycloalkenyl group is cyclopentenyl.

[236] An alkynyl group comprises one or more carbon-carbon triple bonds, and may be linear or branched. Unsubstituted alkynyl groups comprising a C-C triple bond have the general formula CnH2n-3. An alkynyl group may comprise a terminal carbon-carbon triple bond and / or an internal carbon-carbon triple bond. A terminal alkynyl group is an alkynyl group in which a carbon-carbon triple bond is located at a terminal position of a carbon chain. An alkynyl group may also comprise two or more carbon-carbon triple bonds. Unless otherwise indicated, an alkynyl group may optionally be substituted by one or more substituents according to the Radical Group 1 selected independently. Examples of an alkynyl group include ethynyl, propynyl, isopropynyl, t-butynyl, etc.

[237] A cycloalkynyl group is a cyclic alkynyl group. An unsubstituted cycloalkynyl group comprising a triple bond has the general formula CnH2n-5. Optionally, a cycloalkynyl group is replaced by one or more substituents specified further in this document. An example of a cycloalkynyl group is cyclooctinyl.

[238] An aryl group refers to an aromatic hydrocarbon ring system comprising six to twenty-four carbon atoms, more preferably six to twelve atoms Petition 870250092139, dated 08 / 10 / 2025, p. 101 / 254 94 / 246 carbon, and may include monocyclic and polycyclic structures. When the aryl group is a polycyclic structure, it is preferably a bicyclic structure. Optionally, the aryl group may be replaced by one or more substituents specified in this document. Examples of aryl groups are phenyl and naphthyl. Preferably, an aryl group is phenyl.

[239] Arylalkyl and alkylaryl groups comprise at least seven carbon atoms and may include monocyclic and bicyclic structures. Optionally, arylalkyl and alkylaryl groups may be replaced by one or more substituents specified in this document. An arylalkyl group is, for example, benzyl. An alkylaryl group is, for example, 4-tert-butylphenyl.

[240] Preferably, heteroaryl groups comprise from five to sixteen carbon atoms and contain from one to five heteroatoms. Heteroaryl groups comprise at least two carbon atoms (i.e., at least C2) and one or more N, O, P, or S heteroatoms. A heteroaryl group may have a monocyclic or bicyclic structure. Optionally, the heteroaryl group may be replaced by one or more substituents specified in this document. Examples of suitable heteroaryl groups include pyridinyl, quinolinyl, pyrimidinyl, pyrazinyl, pyrazolyl, imidazolyl, thiazolyl, pyrrolyl, furanyl, triazolyl, benzofuranyl, indolyl, purinyl, benzoxazolyl, thienyl, phospholyl, and oxazolyl.

[241] Heteroarylalkyl groups and alkylheteroaryl groups comprise at least three carbon atoms (i.e., at least C3) and may include monocyclic and bicyclic structures. Optionally, heteroaryl groups may be substituted by one or more specified substituents. Petition 870250092139, dated 08 / 10 / 2025, p. 102 / 254 95 / 246 in this document.

[242] When an aryl group is denoted as a (hetero)aryl group, the notation is intended to include an aryl group and a heteroaryl group. Similarly, an alkyl (hetero)aryl group is intended to include an alkylaryl group and an alkylheteroaryl group, and a (hetero)arylalkyl group is intended to include an arylalkyl group and a heteroarylalkyl group. A C2-C24 (hetero)aryl group should therefore be interpreted as including a C2-C24 heteroaryl group and a C6-C24 aryl group. Similarly, a C3-C24 alkyl (hetero)aryl group is intended to include a C7-C24 alkylaryl group and a C3-C24 alkylheteroaryl group, and a C3-C24 (hetero)arylalkyl group is intended to include a C7-C24 arylalkyl group and a C3-C24 heteroarylalkyl group.

[243] In general, when (hetero) is placed before a group, it refers both to the variant of the group without the hetero- prefix and to the group with the hetero- prefix. Here, the hetero- prefix denotes that the group contains one or more heteroatoms selected from the group consisting of O, N, S, P, and Si. Preferably, the one or more heteroatoms are selected from the group consisting of O, N, S, and P. It will be understood that for any compound containing a heteroatom, the N, S, and P atoms are optionally oxidized and the N atoms are optionally quaternized. Preferably, up to two heteroatoms are consecutive, such as in, for example, -CH2-NH-OCH3 and -CH2O-Si(CH3)3. More preferably, however, the heteroatoms are not directly bonded to each other.

[244] Examples of heteroalkyl include -CH2CH2-O-CH3, CH2CH2-NH-CH3, -CH2CH2-S(O)-CH3, -ch=ch-o-ch3, ch2ch2-nh2, CH2CH2-SH, -CH2CH2-OH, -CH2CH2-COOH, -CH2C(O)H, -C(O)HCH3, and - Petition 870250092139, dated 08 / 10 / 2025, p. 103 / 254 96 / 246 Si(CH3)3 • Preferably, a C1-C4 heteroalkyl contains at most 2 heteroatoms

[245] Here, it will be understood that when the prefix hetero is used for group combinations, the prefix hetero- refers only to the group before it is directly placed. For example, heteroarylalkyl denotes the combination of a heteroaryl group and an alkyl group, not the combination of a heteroaryl group and a heteroalkyl group.

[246] Here, the prefix cyclo- denotes that the groups are cyclic. It will be understood that when the prefix cyclo- is used for combinations of groups, the prefix cyclo- refers only to the group before which it is placed directly. For example, cycloalkylalkenylene denotes the combination of a cycloalkylene group (see the definition of the suffix -ene below) and an alkenylene group, not a combination of a cycloalkylene group and a cycloalkenylene group. In general, when (cyclo) is positioned before a group, it refers both to the variant of the group without the cyclo- prefix and to the group with the cyclo- prefix.

[247] Here, the suffix -ene denotes divalent groups, that is, the group is attached to at least two other moieties. An example of an alkylene is propylene (-CH2-CH2CH2-), which is attached to another moiety at both ends. It is understood that if a group with the suffix -ene is substituted in one position with -H, then this group is identical to a group without the suffix. For example, an alkylene attached to an -H is identical to an alkyl group. That is, propylene, -CH2-CH2-CH2-, attached to an -H at one end, -CH2-CH2CH2-H, is logically identical to propyl, -CH2-CH2-CH3.

[248] Here, when group combinations are listed with the suffix -ene, this refers to a divalent group, this Petition 870250092139, dated 08 / 10 / 2025, p. 104 / 254 97 / 246 means that the group is linked to at least two other portions, where each group in the combination is linked to one of these two portions. As such, for example, alkylarylene is understood as a combination of an arylene group and an alkylene group. An example of an alkylarylene group is -phenylCH2-, and an example of an arylalkylene group is -CH2-phenyl-.

[249] Here, the suffix -triyl denotes trivalent groups, that is, the group is attached to at least three other moieties. An example of an arenotriyl is shown below: I where the wavy lines denote connections to different groups of the main compound.

[250] It is understood that if a group with the suffix -triyl is replaced in one position by -H, then this group is identical to a divalent group with the suffix -ene. For example, an arenotriyl replaced with -H is identical to an arylene group. Similarly, it is understood that if a group with the suffix -triyl is replaced in two positions by -H, then this group is identical to a monovalent group. For example, an arenotriyl replaced with two -H is identical to an aryl group.

[251] Unless otherwise indicated, a hetero group may contain a heteroatom in a non-terminal position or in one or more terminal positions. In this case, “terminal” refers to the terminal position within the group, and not necessarily to the terminal position of the entire compound. For example, C2 heteroalkylene may refer to -NH-CH2-CH2-, -CH2-NH-CH2-, and -CH2-CH2-NH-. For example, C2 heteroalkyl Petition 870250092139, dated 08 / 10 / 2025, p. 105 / 254 98 / 246 can refer to -NH-CH2-CH3, -CH2-NH-CH3, and -CH2-CH2-NH2.

[252] Here, cyclic compounds (i.e., aryl, cycloalkyl, cycloalkenyl, etc.) are understood to be monocyclic, polycyclic, or branched. It is understood that the number of carbon atoms for cyclic compounds does not refer only to the number of carbon atoms in one ring, but that carbon atoms may be contained in multiple rings. These rings may be fused to the main ring or substituted into the main ring. For example, C10 aryl optionally containing heteroatoms may refer inter alia to a naphthyl group (fused rings) or to, for example, a bipyridyl group (substituted rings, both containing an N atom).

[253] Unless otherwise indicated, any group disclosed herein that is not cyclic is understood to be linear or branched. In particular, (hetero) alkyl groups, (hetero) alkenyl groups, (hetero) alkynyl groups, (hetero) alkylene groups, (hetero) alkenylene groups, (hetero) alkynylene groups, and the like are linear or branched, unless otherwise indicated.

[254] As used herein, unless otherwise indicated, all of the following groups: (hetero) alkyl, (hetero) alkenyl, (hetero) alkynyl, (hetero) cycloalkyl, (hetero) cycloalkenyl, (hetero) cycloalkynyl, (hetero) aryl, (hetero) alkylene, (hetero) alkenylene, (hetero) alkynylene, (hetero) cycloalkylene, (hetero) cycloalkenylene, (hetero) cycloalkynylene, (hetero) arylene, (hetero) alkanetriyl, (hetero) cycloalkanetriyl, arenetriyl, heteroarenetriyl, and the like, may be substituted or unsubstituted; preferably these groups are unsubstituted. If the Petition 870250092139, dated 08 / 10 / 2025, p. 106 / 254 99 / 246 of the aforementioned groups are replaced, the aforementioned groups preferably contain up to 4, more preferably up to 3, even more preferably up to 2, and most preferably 1 substituent according to Radical Group 1 as defined herein.

[255] The general term “sugar” is used here to indicate a monosaccharide, for example glucose (Glc), galactose (Gal), mannose (Man) and fucose (Fuc). The term “sugar derivative” is used here to indicate a derivative of a monosaccharide sugar, i.e. a monosaccharide sugar comprising substituents and / or functional groups. Examples of a sugar derivative include amino acids and sugar acids, for example glucosamine (GlcNH2), galactosamine (GalNH2), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), sialic acid (Sia) which is also known as N-acetylneuraminic acid (NeuNAc), and N-acetylmuramic acid (MurNAc), glucuronic acid (GlcA) and iduronic acid (IdoA). A sugar may be without further substitution, and then it is understood to be a monosaccharide. A sugar can be replaced by at least one or more of its hydroxyl groups, and is then understood to be either a disaccharide or an oligosaccharide.A disaccharide contains two monosaccharide moieties linked together. An oligosaccharide chain can be linear or branched, and can contain from 3 to 10 monosaccharide moieties.

[256] The term “amino acid” is used here in its normal scientific meaning. In particular, the amino acids in relation to the disclosure comprise both natural and non-natural amino acids. Preferably, the amino acids as used here are selected from the group consisting of alanine, arginine, asparagine, and hydroxylase. Petition 870250092139, dated 08 / 10 / 2025, p. 107 / 254 100 / 246 aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, azidolysine, beta-alanine (bAla), 4-aminomethylphenylalanine (Amf), 4-guanidinephenylalanine (Gnf), 4-aminomethyl-N-isopropylphenylalanine (Iaf), 3-pyridylalanine (Pya), 4-piperidylalanine (Ppa), 4-aminomethylcyclohexylalanine (Ama), 4-aminocyclohexylalanine (Aca), ornithine (Orn), citrulline, hydroxylysine (Hyl), allohydroxylysine (aHyl), 6-N-methyllysine (MeLys), desmosine (Des) 2-aminopimelic acid (Apm), 2,4-diaminobutyric acid (Dbu), 2,2,-diaminopimelic acid (Dpm), 2-3diaminopropionic acid (Dpr), N-ethylglycine (EtGly),Netilasparagine (EtAsn), 3-hydroxyproline (3Hyp), 4-hydroxyproline (4Hyp), alloisoleucine (AIle), sarcosine (MeGly), N-methylisoleucine (MeIle), N-methylvaline (MeVal), norvaline (Nva), and norleucine (Nle).

[257] The term “protein” is used here in its usual scientific meaning. Here, polypeptides comprising about 10 or more amino acids are considered proteins. A protein may comprise natural amino acids, but also non-natural amino acids. The term “protein” here is understood as comprising antibodies and antibody fragments.

[258] The term “peptide” is used here in its normal scientific meaning. Here, peptides are Petition 870250092139, dated 08 / 10 / 2025, page 108 / 254 101 / 246 considered, comprising a number of amino acids in a range of 2 to 9.

[259] The term peptoid is used here in its normal scientific meaning.

[260] A spacer is defined here as a portion that connects two or more elements of a compound. The terms “spacer” and “linker” are used interchangeably here. Typically, a spacer is denoted here as SP, and the more specific self-linking ligands as LC. It will be understood that, where it is indicated here that each individual SP is linked at all ends to the rest of the structure, this refers to the fact that the SP spacer connects multiple portions within a structure, therefore the spacer has multiple ends by definition. The SP spacer may be linked to each individual portion by means of different or identical portions that may each be individually selected. Typically, these linking portions are seen as part of the SP spacer itself. If the SP spacer links two portions within a structure, “all ends” should be interpreted as “both ends”.As an example, if a spacer connects a trans-cyclooctene moiety to a Construct B, then the remainder of the molecule refers to the trans-cyclooctene moiety and Construct B, while the connecting portions between the spacer and the trans-cyclooctene moiety and Construct B (i.e., at both ends) can be selected individually.

[261] As used herein, an organic molecule is defined as a molecule comprising a CH linkage. Organic compound and organic molecule are used synonymously. Petition 870250092139, dated 08 / 10 / 2025, p. 109 / 254 102 / 246

[262] As used herein, an inorganic molecule is defined as any molecule that is not an organic molecule, i.e. not comprising a CH bond. It will be understood that “inorganic molecule” normally also comprises hydrogen, -COOH, etc.

[263] As used herein, a “small molecule” is preferably a small organic molecule. In general, a small molecule has a molecular weight of at most 2 kDa, more preferably at most 1 kDa, more preferably at most 750 Da, more preferably at most 500 Da, and most preferably at most 300 Da. Preferably, a small molecule has a molecular weight of at least 15 Da, more preferably at least 50 Da, more preferably at least 75 Da, and most preferably at least 100 Da.

[264] As used here, “particle” is preferably defined as a microparticle or a nanoparticle.

[265] The term “salt of the same” means a compound formed when an acidic proton, usually a proton of an acid, is replaced by a cation, such as a metallic cation or an organic cation and the like. The term “salt of the same” also means a compound formed when an amine is protonated. Where applicable, the salt is a pharmaceutically acceptable salt, although this is not required for salts not intended for administration to a patient. For example, in a salt of a compound, the compound may be protonated by an inorganic or organic acid to form a cation, with a conjugate base of the inorganic or organic acid as the anionic component of the salt.

[266] The term “pharmaceutically acceptable salt” Petition 870250092139, dated 08 / 10 / 2025, page 110 / 254 103 / 246 means a salt acceptable for administration to a patient, such as a mammal (salts with counter-ions of acceptable safety for mammals for a given dosage regimen). Such salts may be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

[267] “Pharmaceutically acceptable salt” refers to pharmaceutically acceptable salts of a compound, which salts are derived from a variety of organic and inorganic counter-ions known in the art and include, for example, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, etc., and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, formate, tartrate, besylate, mesylate, acetate, maleate, oxalate, etc.

[268] As used herein, the term “solvate” refers to a compound which, in addition to a principal molecule (for example, a diffusion compound, a diene, and the like), also includes a stoichiometric or non-stoichiometric amount of solvent bound to said principal molecule by non-covalent intermolecular forces. In particular, the term “solvate” may refer to a crystalline compound whose crystal structure contains one or more solvent molecules.

[269] As used herein, the term “hydrate” refers to a compound which, in addition to a main molecule (for example, a disclosure compound, a diene, and the like), also includes a stoichiometric or non-stoichiometric amount of water bound to said main molecule by non-covalent intermolecular forces. In particular, the term “hydrate” may refer to a crystalline compound, Petition 870250092139, dated 08 / 10 / 2025, p. 111 / 254 104 / 246 whose crystalline structure contains one or more water molecules.

[270] The logarithm of the partition coefficient, that is, Log P, is used here as a measure of the hydrophobicity of a compound. Typically, Log P is defined as: Log ([solute] non-ionized octanol / [solute] non-ionized water)

[271] A person skilled in the art has knowledge of methods for determining the partition coefficient of compounds without undue experimentation. Alternatively, a person skilled in the art knows that software is available to reliably estimate the value of Log P, for example as a function within the ChemDraw® software or tools available online.

[272] The unified atomic mass unit or Dalton is here abbreviated to Da. Those skilled in the art know that Dalton is a regular unit for molecular weight and that 1 Da is equivalent to 1 g / mol (grams per mole).

[273] It will be understood here that the terms portion and group are used interchangeably when referring to a part of a molecule.

[274] It will be understood that when a heteroatom is denoted as -X(R')2-, where X is the heteroatom and R' is a given portion, then this denotes that two R' portions are attached to the heteroatom.

[275] It will be understood that when a group is denoted as, for example, -((R51)2-R52)2- or a similar notation, in which R51 and R52 are certain portions, then this denotes that first, it must be written as -R51-R51-R52-R51-R51-R52- before the individual portions R51 and R52 are selected, instead of first selecting the portions R51 and R52 and then writing Petition 870250092139, dated 08 / 10 / 2025, p. 112 / 254 105 / 246 Formula.

[276] As used herein, “activated carboxylic acid” and “active ester” may be used interchangeably. As one skilled in the art knows, an “activated carboxylic acid” or an “active ester” is a derivative of a carboxylic acid (-C(O)OH) whose -OH portion has been replaced by a better leaving group. Preferred activated carboxylic acids or active esters are selected from the group consisting of -C(O)ON-succinimidyl, -C(O)opentafluorophenyl, -C(O)O-tetrafluorophenyl, -C(O)O-4-nitrophenyl, and -C(O)Cl. More preferably, the activated carboxylic acid or active ester is -C(O)ON-succinimidyl, or -C(O)O-pentafluorophenyl.

[277] As those skilled in the art are aware, an “active carbonate” is a derivative of a carbonate (-OC(O)-OH) whose -OH portion has been replaced by a better leaving group. Preferred active carbonates are -OC(O)ON-succinimidyl, OC(O)O-pentafluorophenyl, -OC(O)O-tetrafluorophenyl, -OC(O)O4-nitrophenyl, and -OC(O)Cl. More preferably, the active carbonate is -OC(O)ON-succinimidyl, or -OC(O)opentafluorophenyl.

[278] As used herein, a “drug” refers to a pharmaceutical agent. As such, “drug”, “pharmaceutical agent”, “therapeutic agent”, and “medicine” can usually be used interchangeably. Preferred drugs for disclosure are monomethyl auristatin E (MMAE), exatecan, and exatecan derivatives. Preferably, exatecan and exatecan derivatives have the following structure: Petition 870250092139, dated 08 / 10 / 2025, page 113 / 254 106 / 246 where E1 is -H, or an optionally substituted C1-C4 alkyl group. It will be understood that when E1 is -H, the said structure is exatecane. Preferably, E1 is -H, -CH3, or -C(O)-CH2-OH. If E1 is -H or -CH3, then the exatecane or exatecane derivative is preferably linked to the remainder of R48 through the nitrogen atom to which E1 is attached. If E1 is C(O)-CH2-OH, then the exatecane derivative is preferably linked to the remainder of R48 through the oxygen atom that is part of the hydroxyl group of E1. More preferably, E1 is -H or -CH3. Most preferably, E1 is -H.

[279] Most preferably, the drug is monomethyl auristatin E (MMAE). Radical Group (RG) Radical Group 1: terminal groups

[280] For Radical Group 1 (RG1), the radical is selected from the group consisting of -H, -Cl, -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -CN, -N3, -NCS, -SCN, SO3H, -PO3H, -po4h2, -no2, -cf3, -cf2h, -CFH2, =O, =NH, -SH, SO2H, -(SP)i-CB, (hetero)alkyl, (hetero)alkenyl, (hetero)alkynyl, (hetero)cycloalkyl, (hetero)cycloalkenyl, (hetero)cycloalkynyl, (hetero)aryl, and combinations thereof. Here, SP is a spacer as defined here, CB is the B construct as defined here, and ei is an integer in Petition 870250092139, dated 08 / 10 / 2025, p. 114 / 254 107 / 246 a range from 0 to 4, preferably i is 0 or 1.

[281] For RG1, “combinações dos mesmos” em particular refers to (hetero) alkylcycloalkyl, (hetero) alkylcycloalkenyl, (hetero) alkylcycloalkynyl, (hetero) cycloalkylalkyl, (hetero) cycloalkenylalkyl, (hetero) cycloalkynylalkyl, (hetero) alkenylcycloalkyl, (hetero) alkenylcycloalkenyl, (hetero) alkenylcycloalkynyl, (hetero) cycloalkylalkenyl, (hetero) cycloalkenylalkenyl, (hetero) cycloalkynylalkenyl, (hetero) alkynylcycloalkyl, (hetero) alkynylcycloalkenyl, (hetero) alkynylcycloalkynyl, (hetero) cycloalkylalkynyl, (hetero) cycloalkenylalkynyl, (hetero) cycloalkynylalkynyl, (hetero) arylalkyl, (hetero) arylalkenyl, (hetero) arylalkynyl, alkyl (hetero) aryl, alkenyl (hetero) aryl, alkynyl (hetero) aryl, cycloalkyl (hetero) aryl, cycloalkenyl (hetero) aryl, cycloalkynyl (hetero) aryl, (hetero) arylcycloalkyl, (hetero) arylcycloalkenyl, and (hetero) arylcycloalkynyl.Furthermore, “combinations thereof” in relation to RG1 also refers to, for example, a substituted alkyl group such as one or more -Cl and / or -OH groups. As such, RG1 also includes radicals such as -NHCH2-COOH (a glycine residue), which is a combination of a heteroalkyl and -COOH.

[282] Preferably, for RG1 the radical is selected from the RG1a group which consists of -H, -Cl, -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -SO3H, -PO3H, -PO4H2, -NO2, -CF3, =O, =NH, -SH, -(SP)i-CB, (hetero)alkyl C1-C24, (hetero)alkenyl C2-C24, (hetero)alkynyl C2-C24, cycloalkyl C3-C24, heterocycloalkyl C2-C24, cycloalkenyl C5-C24, heterocycloalkenyl C3-C24, cycloalkynyl C7-C24, Petition 870250092139, dated 08 / 10 / 2025, p. 115 / 254 108 / 246 (hetero)cycloalkynyl C5-C24, aryl C6-C24, heteroaryl C2-C24, and combinations thereof.

[283] More preferably, for RG1o the radical is selected from the RG1b group which consists of -H, -Cl, -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -SO3H, -PO3H, -PO4H2, -NO2, -CF3, =O, =NH, -SH, -(SP)i-CB, (hetero)alkyl C1-C12, (hetero)alkenyl C2-C12, (hetero)alkynyl C2-C12, cycloalkyl C3-C12, heterocycloalkyl C2-C12, cycloalkenyl C5-C12, heterocycloalkenyl C3-C12, cycloalkynyl C7-C12, (hetero)cycloalkynyl C5-C12, aryl C6-C12, heteroaryl C2-C12, and combinations thereof.

[284] Even more preferably, for RG1 the radical is selected from the RG1c group consisting of -H, Cl, -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -SO3H, -PO3H, PO4H2, -NO2, -CF3, =O, =NH, -SH, -(SP)i-CB, (hetero) alkyl C1-C8, (hetero) alkenyl C2-C8, (hetero) alkynyl C2-C8, cycloalkyl C3-C8, heterocycloalkyl C2-C8, cycloalkenyl C5-C8, heterocycloalkenyl C3-C8, cycloalkynyl C7-C8, (hetero) cycloalkynyl C5-C8, aryl C6-C8, heteroaryl C2-C8, and combinations thereof.

[285] More preferably still, for RG1o the radical is selected from the RG1d group which consists of -H, Cl, -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -SO3H, -PO3H, PO4H2, -NO2, -CF3, =O, =NH, -SH, -(SP)i-CB, (hetero) alkyl C1-C6, (hetero) alkenyl C2-C6, (hetero) alkynyl C2-C6, cycloalkyl C3-C6, heterocycloalkyl C2-C6, cycloalkenyl C5C7, heterocycloalkenyl C3-C5, cycloalkynyl C8, (hetero) cycloalkynyl C6-C7, phenyl, heteroaryl C3-C5, and combinations thereof.

[286] Most preferably, for RG1o the radical is selected from the RG1e group which consists of -H, -Cl, Petition 870250092139, dated 08 / 10 / 2025, p. 116 / 254 109 / 246 -F, -Br, -I, -OH, -NH2, -COOH, -CONH2, -SO3H, -PO3H, -PO4H2, -NO2, -CF3, =O, =NH, -SH, -(SP)i-CB, C1-C3 (hetero)alkyl, C3-C6 cycloalkyl, C2-C5 heterocycloalkyl, phenyl, C4-C5 heteroaryl, and combinations thereof.

[287] In some embodiments, for RG1o the radical is a conjugation moiety, which is a chemical group that can be used for linking, conjugation or coupling of a construct, such as construct B, or a spacer, or another molecule or construct of interest. The person skilled in the art is aware of the myriad of strategies that are available for chemoselective or nonselective or enzymatic coupling or conjugation of one molecule or construct to another.

[288] In some embodiments, RG1 is a moiety that allows conjugation to a protein comprising natural and / or non-natural amino acids. The moieties suitable for conjugation are known to those skilled in the art. Conjugation strategies are for example found in [O. Boutureira, GJL Bernardes, Chem. Rev., 2015, 115, 2174 - 2195].

[289] If RG1 is a conjugation moiety, it is preferably selected from the RG1f group consisting of N-maleimidyl, halogenated N-alkylamido, sulfonyloxy N-alkylamido, vinyl sulfone, carboxylic acids (activated), active ester, benzenesulfonyl halides, ester, carbonate, sulfonyl halide, thiol or derivatives thereof, C2-C6 alkenyl, C2-C6 alkynyl, C7-C18 cycloalkynyl, C5-C18 heterocycloalkynyl, bicyclo[6.1.0]non-4-yn-9-yl], C3-C12 cycloalkenyl, azido, phosphine, nitrile oxide, nitrone, nitrile imine, isonitrile, diazo, ketone, (O-alkyl)hydroxylamino, hydrazine, N-maleimidyl Petition 870250092139, dated 08 / 10 / 2025, p. 117 / 254 110 / 246 halogenated, aryloxymaleimides, dithiophenolmaleimides, bromopyridazinediones, 2,5-dibromohexanediamide, alcinone, 3-arylpropiolonitrile, 1,1-bis(sulfonylmethyl)methylcarbonyl or elimination derivatives thereof, carbonyl halide, alenamide, 1,2-quinone, isothiocyanate, isocyanate, aldehyde, triazine, squaric acids, 2-imino-2-methoxyethyl, (oxa)norbornene, (oxa)norbornadiene, (imino)sidnones, methylsulfonylphenyloxadiazole, aminooxy, 2-aminobenzamidoxime, ethinylphosphonamidates, reactives at Pictet-Spengler linkage and hydrazine-Pictet-Spengler linkage (HIPS), DNA intercalators, tetrazine, trans-cyclooctene, and photo-crosslinking agents. More preferably, RG1fNmaleimidyl.

[290] In other embodiments, RG1 is selected from the group consisting of hydroxyl, amine, halogens, vinyl pyridine, disulfide, pyridyl disulfide, sulfonyloxy, mercaptoacetamide, anhydride, hydroxyacetamide sulfonylated, sulfonyl chlorides, thiosemicarbazone, hydrazine carboxylate and aryl hydrazide. In other words, RG1 is a group that can be connected to another group by means of an enzyme, for example sortase or tubulin tyrosine ligase. Radical Group 2: connector groups

[291] For Radical Group 2 (RG2), the radical is selected from the group consisting of (hetero) alkylene, (hetero) alkenylene, (hetero) alkynylene, (hetero) cycloalkylene, (hetero) cycloalkenylene, (hetero) cycloalkynylene, (hetero) arylene, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[292] Radicals of RG2 are optionally linked to one or more radicals according to RG1. So, RG2 also covers Petition 870250092139, dated 08 / 10 / 2025, p. 118 / 254 111 / 246 for example -NH-CH(CH2OH)-C(O)- (this is a serine residue), which is a heteroalkylene bonded to -OH and =O.

[293] For RG2, “combinations thereof in particular, but not exclusively, refers to alkyl (hetero)arylene, (hetero)arylalkylene, (hetero)arylkenylene, (hetero)arylkynylene, alkenyl (hetero)arylene, and alkynyl (hetero)arylene.

[294] Preferably, for RG2o the radical is selected from the group consisting of (hetero) C1-C24 alkylene, (hetero) C2-C24 alkylene, (hetero) C2-C24 alkylene, (hetero) C3-C24 cycloalkylene, heterocycloalkylene, C5-C24 cycloalkenylene, heterocycloalkenylene, C3-C24 cycloalkynylene, C7-C24 cycloalkynylene, (hetero) C5-C24 cycloalkynylene, arylene C6-C24, heteroarylene C2-C24, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[295] More preferably, for RG2o the radical is selected from the group consisting of (hetero) C1-C12 alkylene, (hetero) C2-C12 alkylene, (hetero) C2-C12 alkylene, (hetero) C3-C12 cycloalkylene, heterocycloalkylene C2-C12, cycloalkenylene C5-C12, heterocycloalkenylene C3-C12, cycloalkenylene C7-C12, (hetero) C5-C12 cycloalkenylene, arylene C6-C12, heteroarylene C2-C12, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[296] Even more preferably, for RG2 the radical is selected from the group consisting of C1-C8 (hetero)alkylene, C2-C8 (hetero)alkenylene, C2-C8 (hetero)alkynylene, C3-C8 cycloalkylene, heterocycloalkylene Petition 870250092139, dated 08 / 10 / 2025, page 119 / 254 112 / 246 C2-C8, cycloalkenylene C5-C8, heterocycloalkenylene C3-C8, cycloalkynylene C7-C8, (hetero)cycloalkynylene C5-C8, arylene C6-C8, heteroarylene C2-C8, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[297] More preferably still, for RG2o the radical is selected from the group consisting of (hetero) C1-C6 alkylene, (hetero) C2-C6 alkylene, (hetero) C2-C6 alkylene, (hetero) C1-C3 cycloalkylene, heterocycloalkylene C2-C6 cycloalkenylene, cycloalkenylene C5-C7 cycloalkenylene, heterocycloalkenylene C3-C5 cycloalkynylene, cycloalkynylene C8, (hetero) C6-C7 cycloalkynylene, phenylene, heteroarylene C3-C5, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[298] Even more preferably still, for RG2o radical is selected from the group consisting of (hetero) C1-C3 alkylene, C3-C6 cycloalkylene, C2-C5 heterocycloalkylene, phenylene, C4-C5 heteroarylene, amino acid, peptide, protein, polymer, oligonucleotide, nucleotide, carbohydrate, RG2a, RG2b, RG2c, and combinations thereof.

[299] RG2a is selected from the group consisting of -O-, -S-, -SS-, -NR4-, -N=N-, -C(O)-, -C(O)NR4-, -OC(O)-, -C(O)O-, -OC(O)O-, -OC(O)NR4-, -NR4C(O)-, -NR4C(O)O-, NR4C(O)NR4-, -SC(O)-, -C(O)S-, -SC(O)O-, -OC(O)S-, -SC(O)NR4, -NR4C(O)S-, -S(O)-, -S(O)2-, -OS(O)2-, -S(O2)O-, -OS(O)2O-, -OS(O)2NR4-, -NR4S(O)2O-, -C(O)NR4S(O)2NR4-, -OC(O)NR4S(O)2NR4, -OS(O)-, -OS(O)O-, -OS(O)NR4-, -ONR4C(O)-, -ONR4C(O)O-, ONR4C(O)NR4-, -NR4OC(O)-, -NR4OC(O)O-, -NR4OC(O)NR4-, - ONR4C(S)-, -ONR4C(S)O-, -ONR4C(S)NR4-, -NR4OC(S)-, -NR4OC(S)O, -NR4OC(S)NR4-, -OC(S)-, -C(S)O-, -OC(S)O-, -OC(S)NR4-, Petition 870250092139, dated 08 / 10 / 2025, pp. 120 / 254 113 / 246 NR4C(S)-, -NR4C(S)O-, -SS(O)2-, -S(O)2S-, -OS(O2)S-, -SS(O)2O, -NR4OS(O)-, -NR4OS(O)O-, -NR4OS(O)NR4-, -NR4OS(O)2-, NR4OS(O)2O-, -NR4OS(O)2NR4-, -ONR4S(O)-, -ONR4S(O)O-, ONR4S(O)NR4-, -ONR4S(O)2O-, -ONR4S(O)2NR4-, -ONR4S(O)2-, OP(O)(R4)2-, -SP(O)(R4)2-, and -NR4P(O)(R4)2-.

[300] Here, R4 is in accordance with RG1, preferably R4 is hydrogen or methyl, more preferably R4 is hydrogen.

[301] Preferably, RG2a is selected from the group consisting of -O-, -S-, -SS-, -NR4-, -N=N-, -C(O)-, -C(O)NR4-, -OC(O)-, -C(O)O-, -OC(O)NR4-, -NR4C(O)-, - NR4C(O)O-, -NR4C(O)NR4-, -SC(O)-, -C(O)S-, -SC(O)O-, -OC(O)S, -SC(O)NR4-, -NR4C(O)S-, -S(O)-, -S(O)2-, -C(O)NR4S(O)2NR4-, -OC(O)NR4S(O)2NR4-, -OC(S)-, -C(S)O-, -OC(S)O-, -OC(S)NR4-, NR4C(S)-, -NR4C(S)O-, and -SS(O)2-.

[302] More preferably, for RG2o radical is RG2bou RG2c, the most preferably RG2b.

[303] RG2bé selected from the group consisting of Petition 870250092139, dated 08 / 10 / 2025, pp. 121 / 254 114 / 246 Petition 870250092139, dated 08 / 10 / 2025, pp. 122 / 254 115 / 246

[304] Here, R' is a radical according to RG1, preferably R' is hydrogen or C1-C3 alkyl. The dashed and wavy lines denote bonds with other parts of the molecule.

[305] RG2 is selected from the group consisting

[306] Here, R' is a radical according to RG1, preferably R' is hydrogen or C1-C3 alkyl. The dashed and wavy lines denote bonds with other parts of the molecule. Radical Group 3: organic molecule

[307] For Radical Group 3 (RG3) the radical is an organic molecule selected from the group consisting of a nucleic acid, a peptide, a protein, a carbohydrate, an aptamer, a hormone, a toxin, a steroid, a cytokine, a lipid, a small organic molecule as defined herein, a polymer, LNA, PNA, an amino acid, a peptide, a chelating moiety, a molecule Petition 870250092139, dated 08 / 10 / 2025, pp. 123 / 254 116 / 246 comprising a radionuclide, a fluorescent dye, a phosphorescent dye, a drug, a resin, a sphere, an organic particle, a gel, an organic surface, an organometallic compound, a cell, and combinations thereof.

[308] Preferably, for RG3o the radical is a nucleic acid, a peptide, a protein, a carbohydrate, a lipid, a polymer, an amino acid, a chelating moiety, a drug, or a gel.

[309] As used herein, a nucleic acid is preferably selected from the group consisting of an oligonucleotide, a polynucleotide, DNA, and RNA.

[310] As used herein, a protein is preferably an antibody or a diabody. A preferred antibody is CC49, and a preferred diabody is AVP0458.

[311] As used herein, a carbohydrate is preferably selected from the group consisting of a monosaccharide, an oligosaccharide, and a polysaccharide.

[312] As used herein, a polymer is normally selected from the group consisting of polyethylene glycol (PEG), poly(N-(2-hydroxypropyl)methacrylamide) (HPMA), polylactic acid (PLA), polylactic-glycolic acid (PLGA), polyglutamic acid (PG), polyvinylpyrrolidone (PVP), poly(1-hydroxymethylethylene hydroxymethylformal (PHF), copolymers of a polyacetal / polyketal and a hydrophilic polymer selected from the group consisting of polyacrylates, polyvinyl polymers, polyesters, polyorthoesters, polyamides, oligopeptides, polypeptides and derivatives thereof, oligopeptides, polypeptides, Petition 870250092139, dated 08 / 10 / 2025, pp. 124 / 254 117 / 246 glycopolysaccharides, and polysaccharides such as dextran and hyaluronan. Preferably, a polymer such as is used here is polyethylene glycol (PEG).

[313] As used herein, a resin is preferably a polystyrene resin or an agarose resin.

[314] As used herein, an organic particle is preferably a liposome or a polymer.

[315] As used herein, a chelating moiety is preferably selected from the group consisting of DTPA (diethylenetriaminepentaacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-N,N',N,N-tetraacetic acid), NOTA (1,4,7-triazacyclononane-N,N',N-triacetic acid), TETA (1,4,8,11-tetraazacyclotetradecane-N,N',N,N'tetraacetic acid), OTTA (N1-(p-isothiocyanatobenzyl)diethylenetriamine-N1,N2,N3,N3-tetraacetic acid), deferoxamine or DEA (N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]1,4-dioxobutyl]hydroxyamino]pentyl]-N-(5-aminopentyl)-N-hydroxybutane diamide) or HYNIC (hydrazinonicotinamide), EDTA (ethylenediaminetetraacetic acid), OTAM, TACN, sarcophagin, and 3,4-HOPO-based aqueous agents.

[316] More preferably, here a chelating moiety is selected from the group consisting of CO2h O A γνr~c°2Hí1I Η II \ ^^P'N^.COZH —X — —|ψ—\ ——N—\ \ Z* v ( co2h ( co2h * ( co2h co2h co2h co2h co2hZ Petition 870250092139, dated 08 / 10 / 2025, pp. 125 / 254 118 / 246 wherein the sinuous line denotes a linkage to the remaining part of the molecule, optionally linked by means of C(O)NHem, wherein the chelating moieties according to said chelating group are optionally a metal, wherein the metal is preferably selected from the group consisting of 44Sc, 62Cu, 64Cu, 66Ga, 67Ga, 67Cu, 68Ga, 86Y, 89Zr, 90Y, mTc, inIn, 166Ho, 177Lu, 186Re, i88Re, 211Bi, 212Bi, 212Pb, 213Bi, 214Bi, and 225Ac. Radical Group 4: inorganic molecule

[317] For Radical Group 4 (RG4), the radical is an inorganic molecule selected from the group consisting of an inorganic surface, an inorganic particle, a carbon allotrope, an inorganic drug, a radionuclide, and combinations thereof. Petition 870250092139, dated 08 / 10 / 2025, pp. 126 / 254 119 / 246

[318] As used herein, an inorganic surface is preferably selected from the group consisting of chips, wafers, metals such as gold and silica-based surfaces such as glass.

[319] As used herein, an inorganic particle is preferably selected from the group consisting of spheres, silica-based particles, polymer-based materials, iron oxide particles. Preferably, a sphere is a magnetic sphere or a gold sphere.

[320] As used herein, a carbon allotrope is preferably selected from the group consisting of fullerenes such as Buckminster fullerene; graphite, graphene, diamond, lonsdaleite, Q-carbon, linear acetylenic carbon, amorphous carbon and carbon nanotubes.

[321] As used herein, an inorganic drug is preferably cisplatin. Radical Group 5: additional terminal groups

[322] For RG5o radical it is: where the dashed line indicates a connection to the remaining part of the dienophile or diene.

[323] For RG5, each R10 is independently selected from RG2, preferably from RG2a.

[324] For RG5, each R11 is independently selected from RG2, preferably not being RG2a, RG2b, or RG2c.

[325] For RG5, R12 is selected from RG1 or RG3, preferably RG3, more preferably a protein, polymer, or chelating moiety. Petition 870250092139, dated 08 / 10 / 2025, pp. 127 / 254 120 / 246

[326] Preferably, z is an integer in a range from 0 to 12, preferably from 0 to 10, more preferably from 0 to 8, even more preferably from 1 to 6, most preferably from 2 to 4. Preferably, z is 0. In the case of the composite according to the disclosure comprising more than one RG5 portion, each z is independently selected.

[327] Preferably, h is 0 or 1. If the composite according to the disclosure comprises more than one RG5 portion, each h, z, en is independently selected. Preferably, each n belonging to RG5 is an integer independently selected from a range of 0 to 24, preferably from 1 to 12, more preferably from 1 to 6, even more preferably from 1 to 3. Preferably, n is 1. In other preferred embodiments, n is an integer in a range of 12 to 24.

[328] Preferably, z is 0, en is 1. In other embodiments, z is 1, en is 1. Preferably, the RG5 portion has a molecular weight in the range of 100 Da to 3000 Da, preferably in the range of 100 Da to 2000 Da, more preferably in the range of 100 Da to 1500 Da, even more preferably in the range of 150 Da to 1500 Da. Even more preferably, the RG5 portion has a molecular weight in the range of 150 Da to 1000 Da, most preferably in the range of 200 Da to 1000 Da.

[329] Preferably, RG5 is selected from the RG5a group which consists of: Petition 870250092139, dated 08 / 10 / 2025, pp. 128 / 254 121 / 246 Petition 870250092139, dated 08 / 10 / 2025, pp. 129 / 254 122 / 246 m= 1-24, pref max 12 n= 1-8, pref max 4 where the wavy line denotes a bond to the rest of the molecule.

[330] It is understood that when n is greater than 1, -((R10)hR11)n-(R10)h-R12 can be preceded by a group -(R10)h-R11- to form a group -(R10)h-R11-((R10)h-R11)n-(R10)h-R12. It is understood that this follows from the definition of how to write the repeating units, i.e. -((R10)h-R11)2- would first be written as -(R10)h-R11-(R10)h-R11- before R10, h, and R11 are independently selected. List of Clauses

[331] Disclosure refers to any of the following clauses.

[332] Clause 1. A compound or a salt, hydrate, or solvate thereof; wherein said compound comprises an eight-membered non-aromatic cyclic monoalkenylene moiety, Petition 870250092139, dated 08 / 10 / 2025, pp. 130 / 254 123 / 246 wherein said portion comprises a non-vinyl carbon atom, wherein said non-vinyl carbon atom is replaced by at least one structure according to Formula (A): 'VVV' L1t3 Formula (A); in which L1 and L2 are each independently a ligand; and T2 and T3 are organic moieties.

[333] Clause 2. A compound of Clause 1 or a salt, hydrate, or solvate thereof; wherein L1 is in accordance with Radical Group 2 as defined herein.

[334] Clause 3. A compound according to any of Clauses 1 - 2 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C1-C12 (hetero)alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[335] Clause 4. A compound according to any of Clauses 1-3 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C1-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[336] Clause 5. A compound according to any of Clauses 1 - 4 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C2-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[337] Clause 6. A compound according to any of Clauses 1 - 5 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting Petition 870250092139, dated 08 / 10 / 2025, pp. 131 / 254 124 / 246 in linear or branched C3-C12 alkylene, (hetero) C3-C8 cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[338] Clause 7. A compound according to any of Clauses 1 - 6 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[339] Clause 8. A compound according to any of Clauses 1 - 7 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C1-C12 alkylene.

[340] Clause 9. A compound according to any of Clauses 1 - 8 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C2-C12 alkylene.

[341] Clause 10. A compound according to any of Clauses 1 - 9 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C3-C12 alkylene.

[342] Clause 11. A compound according to any of Clauses 1 - 10 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C12 alkylene.

[343] Clause 12. A compound according to any of Clauses 1 - 11 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C11 alkylene.

[344] Clause 13. A compound according to any of Clauses 1 - 12 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C10 alkylene.

[345] Clause 14. A compound according to any of Clauses 1 - 13 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C9 alkylene.

[346] Clause 15. A compound according to any of Clauses 1 - 14 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C8 alkylene. Petition 870250092139, dated 08 / 10 / 2025, pp. 132 / 254 125 / 246

[347] Clause 16. A compound according to any of Clauses 1 - 15 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C7 alkylene.

[348] Clause 17. A compound according to any of Clauses 1 - 16 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C4-C6 alkylene.

[349] Clause 18. A compound according to any of Clauses 1 - 17 or a salt, hydrate, or solvate thereof; wherein L1 is linear or branched C5 alkylene.

[350] Clause 19. A compound according to any of Clauses 1 - 8 or a salt, hydrate, or solvate thereof; wherein L1 is linear C1-C12 alkylene.

[351] Clause 20. A compound according to any of Clauses 1 - 9 or a salt, hydrate, or solvate thereof; wherein L1 is linear C2-C12 alkylene.

[352] Clause 21. A compound according to any of Clauses 1 - 10 or a salt, hydrate, or solvate thereof; wherein L1 is linear C3-C12 alkylene.

[353] Clause 22. A compound according to any of Clauses 1 - 11 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C12 alkylene.

[354] Clause 23. A compound according to any of Clauses 1 - 12 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C11 alkylene.

[355] Clause 24. A compound according to any of Clauses 1 - 13 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C10 alkylene.

[356] Clause 25. A compound according to any of Clauses 1 - 14 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C9 alkylene.

[357] Clause 26. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 133 / 254 126 / 246 one of Clauses 1 - 15 or a salt, hydrate, or solvate thereof; wherein L1 is a C4-C8 linear alkylene.

[358] Clause 27. A compound according to any of Clauses 1 - 16 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C7 alkylene.

[359] Clause 28. A compound according to any of Clauses 1 - 17 or a salt, hydrate, or solvate thereof; wherein L1 is linear C4-C6 alkylene.

[360] Clause 29. A compound according to any of Clauses 1 - 28 or a salt, hydrate, or solvate thereof; wherein L1 is linear C5 alkylene.

[361] Clause 30. A compound according to any of Clauses 1 - 29 or a salt, hydrate, or solvate thereof; where L2 is according to Radical Group 2 as defined herein.

[362] Clause 31. A compound according to any of Clauses 1 - 30 or a salt, hydrate, or solvate thereof; wherein L2 contains from 1 to 200 atoms, preferably from 2 to 150 atoms, more preferably from 3 to 100 atoms, even more preferably from 4 to 90 atoms, even more preferably from 5 to 80 atoms, even more preferably from 6 to 70 atoms, even more preferably from 7 to 60 atoms, even more preferably from 8 to 50 atoms, even more preferably from 9 to 45 atoms, and most preferably from 10 to 35 atoms.

[363] Clause 32. A compound according to any of Clauses 1 - 31 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of linear or branched C1-C12 (hetero)alkanetriyl, C3-C8 (hetero)cycloalkanetriyl, C6-C12 arenotriyl, and C4-C11 heteroarenotriyl. Petition 870250092139, dated 08 / 10 / 2025, pp. 134 / 254 127 / 246

[364] Clause 33. A compound according to any of Clauses 1 - 32 or a salt, hydrate, or solvate thereof; where L2 is a linear or branched C1-C12 (hetero) alkanetriyl.

[365] Clause 34. A compound according to any of Clauses 1 - 33 or a salt, hydrate, or solvate thereof; where L2 is a linear or branched C1-C12 heteroalkanetriyl.

[366] Clause 35. A compound according to any of Clauses 1 - 33 or a salt, hydrate, or solvate thereof; where L2 is a branched C1-C12 (hetero) alkanetriyl.

[367] Clause 36. A compound according to any of Clauses 1 - 35 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C1-C12 heteroalkanetriyl.

[368] Clause 37. A compound according to any of Clauses 1 - 36 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C3-C11 heteroalkanetriyl.

[369] Clause 38. A compound according to any of Clauses 1 - 37 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C6-C10 heteroalkanetriyl.

[370] Clause 39. A compound according to any of Clauses 1 - 38 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C8 heteroalkanetriyl.

[371] Clause 40. A compound according to any of Clauses 1 - 39 or a salt, hydrate, or solvate thereof; where L2 is a branched C8 heteroalkanetriyl substituted with up to five =O groups.

[372] Clause 41. A compound according to any of Clauses 1 - 40 or a salt, hydrate, or solvate thereof; where L2 is a branched C8 heteroalkanetriyl substituted with three =O groups. Petition 870250092139, dated 08 / 10 / 2025, pp. 135 / 254 128 / 246

[373] Clause 42. A compound according to any of Clauses 1-41 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C8 heteroalkanetriyl containing up to five -NH- groups.

[374] Clause 43. A compound according to any of Clauses 1 - 42 or a salt, hydrate, or solvate thereof; where L2 is a branched C8 heteroalkanetriyl containing three -NH- groups.

[375] Clause 44. A compound according to any of Clauses 1 - 43 or a salt, hydrate, or solvate thereof; wherein L2 is a branched C8 heteroalkanetriyl containing three -NH- groups, and where the substituted with three =O groups.

[376] Clause 45. A compound of one of Clauses 1 - 44 or a salt, even; where L2 is: 'Wo' HN^ O < s  NH 7 \ NH | O

[377] Clause 46. A compound of one of Clauses 1 - 45 or a salt, even; where L2 is: HNC; 0 NHVHy heteroalkanetriyl C8 is according to any hydrate, or solvate of . according to any hydrate, or solvate of Petition 870250092139, of 08 / 10 / 2025, page 136 / 254 129 / 246

[378] Clause 47. A compound according to any of Clauses 1 even; where L2 is: either a salt, hydrate, or solvate of NH HN NH O

[379] Clause 48. A compound according to any of Clauses 1 itself; where L2 is: either a salt, hydrate, or solvate of NH HN NH O

[380] Clause 49.A compound according to any of Clauses 1 - 48 or a salt, hydrate, or solvate thereof; wherein T2 is according to any of Radical Group 1, Radical Group 3, or Radical Group 5, as defined herein, or wherein T2 is a -L3-CB group; wherein L3 is according to Radical Group 2, and CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells, and combinations thereof.

[381] Clause 50. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, p. 137 / 254 130 / 246 one of Clauses 1 - 49 or a salt, hydrate, or solvate thereof; where T2 is in accordance with Radical Group 1 as defined herein.

[382] Clause 51.A compound according to any of Clauses 1 - 50 or a salt, hydrate, or solvate thereof; where T2 is according to Radical Group 1a as defined herein.

[383] Clause 52. A compound according to any of Clauses 1 - 51 or a salt, hydrate, or solvate thereof; where T2 is according to Radical Group 1b as defined herein.

[384] Clause 53. A compound according to any of Clauses 1 - 52 or a salt, hydrate, or solvate thereof; where T2 is according to Radical Group 1c as defined herein.

[385] Clause 54. A compound according to any of Clauses 1 - 53 or a salt, hydrate, or solvate thereof; where T2 is according to Radical Group 1d as defined herein.

[386] Clause 55. A compound according to any of Clauses 1 - 54 or a salt, hydrate, or solvate thereof; where T2 is according to Radical Group 1e as defined herein.

[387] Clause 56.A compound according to any of Clauses 1 - 55 or a salt, hydrate, or solvate thereof; wherein T2 is according to Radical Group 1f as defined herein.

[388] Clause 57. A compound according to any of Clauses 1 - 56 or a salt, hydrate, or solvate thereof; wherein T2 is N-maleimidyl.

[389] Clause 58. A compound according to any of Clauses 1 or a salt, hydrate, or solvate thereof; Petition 870250092139, dated 08 / 10 / 2025, p. 138 / 254 131 / 246 where T2 is:

[390] Clause 59. A compound according to any of Clauses 1 - 49 or a salt, hydrate, or solvate thereof; where T2 is an -L3-CB group.

[391] Clause 60. A compound according to any of Clauses 1 - 49, and 59, or a salt, hydrate, or solvate thereof; where L3 is a residue of a bioconjugation moiety.

[392] Clause 61.A compound according to any of Clauses 1-49 and 59-60, or a salt, hydrate, or solvate thereof; wherein L3 is a residue of an Nmaleimidyl moiety or a residue of an Nhydroxysuccinimidyl moiety.

[393] Clause 62. A compound according to any of Clauses 1-49 and 59-61, or a salt, hydrate, or solvate thereof; wherein T2 is selected from the group consisting of

[394] Clause 63. A compound according to any of Clauses 1-49 and 59-62, or a salt, hydrate, or solvate thereof; wherein T2 is: Petition 870250092139, dated 08 / 10 / 2025, p. 139 / 254 132 / 246

[395] Clause 64. A compound according to any one of Clauses 1 - 49, and 59 - 63, or a salt, hydrate, or solvate thereof; wherein CB is a protein.

[396] Clause 65. A compound according to any one of Clauses 1 - 49, and 59 - 64, or a salt, hydrate, or solvate thereof; wherein CB is an antibody or a diabody.

[397] Clause 66.A compound according to any of Clauses 1-49, and 59-65, or a salt, hydrate, or solvate thereof; wherein CB is a diabody.

[398] Clause 67. A compound according to any of Clauses 1-49, and 59-66, or a salt, hydrate, or solvate thereof; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[399] Clause 68. A compound according to any of Clauses 1-49, and 59-67, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of S or N which is part of CB.

[400] Clause 69. A compound according to any of Clauses 1 - 49, and 59 - 68, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of S which is part of CB.

[401] Clause 70.A compound according to any of Clauses 1 - 69, or a salt, hydrate, or solvate thereof; wherein T3 is according to any of Radical Group 1, Radical Group 3, or Radical Group 5, as defined herein. Petition 870250092139, dated 08 / 10 / 2025, p. 140 / 254 133 / 246

[402] Clause 71. A compound according to any of Clauses 1 - 70 or a salt, hydrate, or solvate thereof; wherein T3 is according to Radical Group 3, as defined herein.

[403] Clause 72. A compound according to any of Clauses 1 - 71 or a salt, hydrate, or solvate thereof; wherein T3 is a polymer.

[404] Clause 73. A compound according to any of Clauses 1 - 72 or a salt, hydrate, or solvate thereof; wherein T3 is a polymer comprising a polyethylene glycol moiety.

[405] Clause 74.A compound according to any of Clauses 1 - 73 or a salt, hydrate, or solvate thereof; wherein T3 comprises a portion -(CH2CH2-O-)y-T4, wherein y is an integer in a range from 1 to 50, and T4 is according to Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5 as defined herein; preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, even more preferably in a range from 20 to 30, even more preferably in a range from 23 to 25, and most preferably y is 24.

[406] Clause 75. A compound of Clause 74 or a salt, hydrate, or solvate thereof; where T3 is a (CH2CH2-O-)y-T4 portion.

[407] Clause 76. A compound according to any of Clauses 74 - 75 or a salt, hydrate, or solvate thereof; where y is an integer in a range from 10 to 40.

[408] Clause 77.A compound according to any of Clauses 74 - 76 or a salt, hydrate, or solvate thereof; wherein y is an integer in a range from 12 to 37. Petition 870250092139, 08 / 10 / 2025, p. 141 / 254 134 / 246

[409] Clause 78. A compound according to any of Clauses 74 - 77 or a salt, hydrate, or solvate thereof; wherein y is an integer in a range from 15 to 35.

[410] Clause 79. A compound according to any of Clauses 74 - 78 or a salt, hydrate, or solvate thereof; wherein y is an integer in a range from 20 to 30.

[411] Clause 80. A compound according to any of Clauses 74 - 79 or a salt, hydrate, or solvate thereof; wherein y is an integer in a range from 23 to 25.

[412] Clause 81. A compound according to any of Clauses 74 - 80 or a salt, hydrate, or solvate thereof; wherein y is 24.

[413] Clause 82.A compound according to any of Clauses 74 - 81 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1.

[414] Clause 83. A compound according to any of Clauses 74 - 82 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1a.

[415] Clause 84. A compound according to any of Clauses 74 - 83 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1b.

[416] Clause 85. A compound according to any of Clauses 74 - 84 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1c.

[417] Clause 86. A compound according to any of Clauses 74 - 85 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1d.

[418] Clause 87. A compound according to any of Clauses 74 - 86 or a salt, hydrate, or solvate thereof; where T4 is according to Radical Group 1e.

[419] Clause 88.A compound according to any Petition 870250092139, dated 08 / 10 / 2025, p. 142 / 254 135 / 246 one of Clauses 74 - 87 or a salt, hydrate, or solvate thereof; wherein T4 is methyl.

[420] Clause 89. A compound according to any of Clauses 1 - 81 or a salt, hydrate, or solvate thereof; wherein T3 is a -(CH2CH2-O-)24-CH3 moiety.

[421] Clause 90. A compound according to any of Clauses 1 - 29, and 49 - 89 or a salt, hydrate, or solvate thereof; where Formula (A) is in accordance with Formula (A1): 2aThL_L2b_L2AL^T3 Formula (A1);

[422] where L1 is in accordance with any of Clauses 1 - 29;

[423] where T2 is in accordance with any of Clauses 1, and 49 - 69;

[424] where T3 is in accordance with any of Clauses 1, and 70 - 89;

[425] and L2a, L2b, L2c, and L2d are each independently a linker.

[426] Clause 91.A compound of Clause 90 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, L2c, and L2d are each independently in accordance with Radical Group 2 as defined herein.

[427] Clause 92. A compound according to any of Clauses 90 - 91 or a salt, hydrate, or solvate thereof; wherein L2a is a ligand containing at most twenty atoms.

[428] Clause 93. A compound according to any of Clauses 90 - 92 or a salt, hydrate, or solvate of the same; wherein L2a is a ligand containing at most fifteen atoms.

[429] Clause 94. A compound according to any of Clauses 90 - 93 or a salt, hydrate, or solvate thereof; wherein L2a is a ligand containing at most ten atoms.

[430] Clause 95. A compound according to any of Clauses 90 - 94 or a salt, hydrate, or solvate thereof; wherein L2a is a ligand containing at most five atoms.

[431] Clause 96.A compound according to any of Clauses 90 - 95 or a salt, hydrate, or solvate thereof; wherein L2a is selected from the group consisting of -C(O)NL2t-, -NL2tC(O)-, -O-, -S-, -NL2T-, -N=N-, and C(O)-; wherein L2T is hydrogen or methyl.

[432] Clause 97. A compound of Clause 96 or a salt, hydrate, or solvate thereof; wherein L2a is selected from the group consisting of -C(O)NL2T-, and -NL2TC(O)-.

[433] Clause 98. A compound according to any of Clauses 90 - 97 or a salt, hydrate, or solvate thereof; wherein L2a is selected from the group consisting of -C(O)NH-, and -NHC(O)-.

[434] Clause 99. A compound according to any of Clauses 90 - 98 or a salt, hydrate, or solvate thereof; where L2a is -NHC(O)-.

[435] Clause 100. A compound according to any of Clauses 90 - 99 or a salt, hydrate, or solvate thereof; wherein L2b is a ligand containing at most twenty atoms.

[436] Clause 101.A compound according to any of Clauses 90 - 100 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand containing at most fifteen atoms.

[437] Clause 102. A compound according to any of Clauses 90 - 101 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand containing at most ten atoms.

[438] Clause 103. A compound according to any of Clauses 90 - 102 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand containing at most five atoms.

[439] Clause 104. A compound according to any of Clauses 90 - 103 or a salt, hydrate, or solvate thereof; where L2b is selected from the group consisting of -C(O)NL2t-, -NL2tC(O)-, -O-, -S-, -NL2T-, -N=N-, and C(O)-; wherein L2T is hydrogen or methyl.

[440] Clause 105.A compound of Clause 104 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of -C(O)NL2T-, and -NL2TC(O)-.

[441] Clause 106. A compound according to any of Clauses 90 - 105 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of -C(O)NH-, and -NHC(O)-.

[442] Clause 107. A compound according to any of Clauses 90 - 106 or a salt, hydrate, or solvate thereof; wherein L2 is -NHC(O)-.

[443] Clause 108. A compound according to any of Clauses 90 - 107 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand containing at most twenty atoms.

[444] Clause 109. A compound according to any of Clauses 90 - 108 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand containing at most fifteen atoms.

[445] Clause 110.A compound according to any of Clauses 90 - 109 or a salt, hydrate, or solvate thereof; wherein L2d is a ligand containing at most ten atoms.

[446] Clause 111. A compound according to any of Clauses 90 - 110 or a salt, hydrate, or solvate thereof; wherein L2d is a ligand containing at most five atoms.

[447] Clause 112. A compound according to any of Clauses 90 - 111 or a salt, hydrate, or solvate thereof; where L2 is selected from the group consisting of -C(O)NL2t-, -NL2tC(O)-, -O-, -S-, -NL2T-, -N=N-, and C(O)-; wherein L2T is hydrogen or methyl.

[448] Clause 113. A compound of Clause 112 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of -C(O)NL2t-, and -NL2tC(O)-.

[449] Clause 114.A compound according to any of Clauses 90 - 113 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of -C(O)NH-, and -NHC(O)-.

[450] Clause 115. A compound according to any of Clauses 90 - 114 or a salt, hydrate, or solvate thereof; wherein L2 is -C(O)NH-.

[451] Clause 116. A compound according to any of Clauses 90 - 115 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand comprising at most 50 atoms.

[452] Clause 117. A compound according to any of Clauses 90 - 116 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand comprising at most 40 atoms.

[453] Clause 118. A compound according to any of Clauses 90 - 117 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand comprising at most 30 atoms.

[454] Clause 119. A compound according to any of Petition 870250092139, dated 08 / 10 / 2025, p.146 / 254 139 / 246 one of Clauses 90 - 118 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand comprising at most 20 atoms.

[455] Clause 120. A compound according to any of Clauses 90 - 119 or a salt, hydrate, or solvate thereof; wherein L2 is a ligand comprising at most 15 atoms.

[456] Clause 121. A compound according to any of Clauses 90 - 120 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenotriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl.

[457] Clause 122. A compound according to any of Clauses 90 - 121 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 (hetero) alkanetriyl.

[458] Clause 123. A compound according to any of Clauses 90 - 122 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 alkanetriyl.

[459] Clause 124.A compound according to any of Clauses 90-123 or a salt, hydrate, or solvate thereof; wherein L2 is a C2-C7 alkanetriyl.

[460] Clause 125. A compound according to any of Clauses 90-124 or a salt, hydrate, or solvate thereof; wherein L2 is a C3-C6 alkanetriyl.

[461] Clause 126. A compound according to any of Clauses 90-125 or a salt, hydrate, or solvate thereof; wherein L2 is a C4-C5 alkanetriyl.

[462] Clause 127. A compound according to any of Clauses 90-126 or a salt, hydrate, or solvate thereof; wherein L2 is a C5 alkanetriyl.

[463] Clause 128. A compound in accordance with any Petition 870250092139, dated 08 / 10 / 2025, p. 147 / 254 140 / 246 one of Clauses 90 - 127 or a salt, hydrate, or solvate thereof; where L2cé >CH-CH2-CH2-CH2-CH2-.

[464] Clause 129. A compound according to any of Clauses 1 - 128 or a salt, hydrate, or solvate thereof; wherein said non-vinyl carbon atom is replaced with at most one structure according to Formula (A).

[465] Clause 130. A compound according to any of Clauses 1 - 129 or a salt, hydrate, or solvate thereof; wherein said non-vinyl carbon atom is a non-allylic carbon atom.

[466] Clause 131. A compound according to any of Clauses 1 - 130 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is replaced with at most three structures according to Formula (A).

[467] Clause 132. A compound according to any of Clauses 1 - 131 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is replaced with at most two structures according to Formula (A).

[468] Clause 133. A compound according to any of Clauses 1 - 132 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is replaced with at most one structure according to Formula (A).

[469] Clause 134. A compound according to any of Clauses 1 - 133 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at most two heteroatoms. Petition 870250092139, dated 08 / 10 / 2025, pp. 148 / 254 141 / 246

[470] Clause 135. A compound according to any of Clauses 1 - 134 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic monoalkenylene moiety comprises at most two heteroatoms, wherein the heteroatoms are N or O.

[471] Clause 136. A compound according to any of Clauses 1 - 135 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at most one heteroatom, wherein the heteroatom is N or O.

[472] Clause 137. A compound according to any of Clauses 1 - 136 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at most one heteroatom, wherein the heteroatom is N.

[473] Clause 138. A compound according to any of Clauses 1 - 137 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least five carbon atoms.

[474] Clause 139. A compound according to any of Clauses 1 - 138 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least six carbon atoms.

[475] Clause 140. A compound according to any of Clauses 1 - 139 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least seven carbon atoms.

[476] Clause 141. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 149 / 254 142 / 246 one of Clauses 1 - 140 or a salt, hydrate, or solvate thereof; wherein the said eight-membered non-aromatic cyclic mono-alkenylene portion is an all-carbon ring.

[477] Clause 142. A compound according to any of Clauses 1 - 141 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is further substituted with a moiety according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein.

[478] Clause 143. A compound according to any of Clauses 1 - 142 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is further substituted with a maximum of 5 moieties according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein.

[479] Clause 144. A compound according to any of Clauses 1 - 143 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is further substituted with at most 4 moieties according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein.

[480] Clause 145. A compound according to any of Clauses 1 - 144 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is further substituted with at most 3 moieties according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein. Petition 870250092139, dated 08 / 10 / 2025, pp. 150 / 254 143 / 246

[481] Clause 146. A compound according to any of Clauses 1 - 145 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is further substituted with at most 2 moieties according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein.

[482] Clause 147. A compound according to any of Clauses 1 - 146 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with an R48 group, wherein R48 is selected from the group consisting of -OH, -O-acetyl, -O-C1-4 alkyl, halogen, active carbonate, and a releasable group.

[483] Clause 148. A compound of Clause 147 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least one allylic carbon, and said at least one allylic carbon is substituted with said R4 8 group.

[484] Clause 149. A compound according to any of Clauses 147 - 148 or a salt, hydrate, or solvate thereof; wherein said group R48 is in the axial position.

[485] Clause 150. A compound according to any of Clauses 147 - 149 or a salt, hydrate, or solvate thereof; wherein said group R48 is a releasable group.

[486] Clause 151. A compound according to any of Clauses 147 - 150 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at most one releasable group. Petition 870250092139, dated 08 / 10 / 2025, pp. 151 / 254 144 / 246

[487] Clause 152. A compound according to any of Clauses 147 - 151 or a salt, hydrate, or solvate thereof; wherein said releasable group is -(Y1-C(=Y2))i(SP)j-CA; wherein each of Y1 and Y2 are selected independently of O and S; CA is the construct A, which is a payload; SP is a ligand; j is 0 or 1; i is 0 or 1; if i is 0, -(SP)j-CA is linked to the rest of the compound by means of O or S, which is part of -(SP)j-CA; if i is 1, -(SP)j-CA is linked to -C(=Y2)- by means of O, S, a secondary N, or a tertiary N, which is part of -(SP)j-CA.

[488] Clause 153. A compound according to any of Clauses 147 - 152 or a salt, hydrate, or solvate thereof; wherein said releasable group is -(OC(=Y2))i(SP)j-CA.

[489] Clause 154. A compound according to any of Clauses 147 - 152 or a salt, hydrate, or solvate thereof; wherein the said releasable group is -(Y1-C(=O))i(SP)j-CA.

[490] Clause 155. A compound according to any of Clauses 147 - 154 or a salt, hydrate, or solvate thereof; wherein the said releasable group is -(OC(=O))i(SP)j-CA.

[491] Clause 156. A compound according to any of Clauses 147 - 155 or a salt, hydrate, or solvate thereof; wherein the said releasable group is -OC(=O)-(SP)jCA.

[492] Clause 157. A compound according to any of Clauses 147 - 156 or a salt, hydrate, or solvate thereof; where SP is according to Radical Group 2.

[493] Clause 158. A compound according to any of Clauses 147 - 157 or a salt, hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 152 / 254 145 / 246 of the same; wherein SP is a self-immolating ligand.

[494] Clause 159. A compound according to any of Clauses 147 - 158 or a salt, hydrate, or solvate thereof; wherein the said releasable group is —O—C(=O)—CA.

[495] Clause 160. A compound of Clause 159 or a salt, hydrate, or solvate thereof; wherein CA is linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of CA, forming a carbamate.

[496] Clause 161. A compound according to any of Clauses 147 - 160 or a salt, hydrate, or solvate thereof; wherein CA is a drug, preferably monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[497] Clause 162. A compound according to any of Clauses 147 - 161 or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE).

[498] Clause 163. A compound according to any of Clauses 1 - 162 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least one allylic carbon, and said at least one allylic carbon is substituted with an R48 group, wherein said R48 group is in the axial position, and wherein said R48 group is -OC(=O)CA; wherein CA is a drug.

[499] Clause 164. A compound of Clause 163 or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE) linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[500] Clause 165. A compound of Clause 164 or a salt, hydrate, or solvate thereof; wherein CA is monomethyl Petition 870250092139, dated 08 / 10 / 2025, pp. 153 / 254 146 / 246 auristatin E (MMAE) linked to the -OC(=O)- portion via a tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[501] Clause 166. A compound according to any of Clauses 147 - 165 or a salt, hydrate, or solvate

[502] Clause 167. A compound according to any of Clauses 1 - 166 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at least one T1 group, wherein T1 is according to Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5, as defined herein.

[503] Clause 168. A compound of Clause 167 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most 5 T1 groups.

[504] Clause 169. A compound according to any of Clauses 167 - 168 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most 4 T1 groups.

[505] Clause 170. A compound according to any of Clauses 167 - 169 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most 3 T1 groups. Petition 870250092139, dated 08 / 10 / 2025, pp. 154 / 254 147 / 246

[506] Clause 171. A compound according to any of Clauses 167 - 170 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most 2 T1 groups.

[507] Clause 172. A compound according to any of Clauses 167 - 171 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most 1 T1 group.

[508] Clause 173. A compound according to any of Clauses 167 - 172 or a salt, hydrate, or solvate thereof; wherein each T1 is independently according to Radical Group 1 as defined herein.

[509] Clause 174. A compound according to any of Clauses 167 - 173 or a salt, hydrate, or solvate thereof; wherein each T1 is selected independently from the group consisting of -OT1A, hydrogen, C1-C12 (hetero)alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 (hetero)cycloalkyl, C5-C12 (hetero)aryl alkyl, C5C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, -N(T1A)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1A-C(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3;

[510] each T1A is selected independently from the group consisting of hydrogen, (hetero) alkyl, (hetero) alkenyl, (hetero) alkynyl, (hetero) aryl, and an amino acid residue;

[511] preferably each T1A is independently selected from the group consisting of hydrogen, C1-C6 (hetero)alkyl, C1-C6 (hetero)alkenyl, C1-C6 (hetero)alkynyl, C5-C5 heteroaryl, phenyl, and an amino acid residue; even more preferably each T1A is Petition 870250092139, dated 08 / 10 / 2025, pp. 155 / 254 148 / 246 independently selected from the group consisting of hydrogen, C1-C4 (hetero)alkyl, C1C4 (hetero)alkenyl, C1-C4 (hetero)alkynyl, C3-C5 heteroaryl, phenyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; even more preferably each T1A is independently selected from the group consisting of hydrogen, C1-C3 alkyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; and most preferably T1A is hydrogen.

[512] Clause 175. A compound of Clause 174 or a salt, hydrate, or solvate thereof; wherein each T1 is selected independently from the group consisting of -OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5C12 alkyl (hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, N(T1a)2, -ST1a, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1AC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3.

[513] Clause 176. A compound according to any of Clauses 167 - 175 or a salt, hydrate, or solvate thereof; where T1 is -OT1A.

[514] Clause 177. A compound according to any of Clauses 167 - 176 or a salt, hydrate, or solvate thereof; where T1 is -OH.

[515] Clause 178. A compound according to any of Clauses 167 - 177 or a salt, hydrate, or solvate thereof; where T1 is in an axial position.

[516] Clause 179. A compound according to any of Clauses 167 - 178 or a salt, hydrate, or solvate thereof; wherein T1 is not a substituent on a vinylic carbon or an allylic atom of said eight-membered non-aromatic cyclic monoalkenylene moiety. Petition 870250092139, dated 08 / 10 / 2025, pp. 156 / 254 149 / 246

[517] Clause 180. A compound according to any of Clauses 1 - 179 or a salt, hydrate, or solvate thereof; wherein said eight-membered non-aromatic cyclic monoalkenylene moiety comprises at least one allylic carbon, and said at least one allylic carbon is substituted with an R48 group, wherein said R48 group is in the axial position, and wherein said R48 group is -OC(=O)CA; wherein CA is a drug; and

[518] wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety is substituted with at most one T1 group, wherein T1 is -OH, and wherein T1 is not a substituent on a vinylic carbon or an allylic atom of said eight-membered non-aromatic cyclic mono-alkenylene moiety.

[519] Clause 181. A compound of Clause 1-180 or a salt, hydrate, or solvate thereof; wherein the said group

[520] Clause 182. A compound according to any of Clauses 1 - 180 or a salt, hydrate, or solvate thereof; wherein said compound is according to Formula (B): Petition 870250092139, dated 08 / 10 / 2025, pp. 157 / 254 150 / 246 (R48)y1 X-Zχ1X 'X y2'4XX x'(T )y3 Formula (B); where R48 is as defined in any of Clauses 147 - 166; T1 is as defined in any of Clauses 167-179; TL is a structure in accordance with Formula (A) as defined in any of Clauses 1 - 128; y1 is an integer from 0 to 4; y2 is an integer from 0 to 5; y3 is an integer from 1 to 5; and each X1, X2, X3, X4, X5, and X6 is independently selected from the group consisting of a substituted or unsubstituted carbon atom, a nitrogen atom, or an oxygen atom, provided that if one of the X1, X2, X3, X4, X5, and X6 is a nitrogen atom or an oxygen atom, an adjacent X1, X2, X3, X4, X5, and X6 is not a nitrogen atom or an oxygen atom.

[521] Clause 183. A compound of Clause 182 or a salt, hydrate, or solvate thereof; where y1 is an integer from 1 to 2.

[522] Clause 184. A compound according to any of Clauses 182 - 183 or a salt, hydrate, or solvate thereof; where y1 is 1. Petition 870250092139, dated 08 / 10 / 2025, pp. 158 / 254 151 / 246

[523] Clause 185. A compound according to any of Clauses 182 - 184 or a salt, hydrate, or solvate thereof; where y2 is an integer from 1 to 4.

[524] Clause 186. A compound according to any of Clauses 182 - 185 or a salt, hydrate, or solvate thereof; where y2 is an integer from 1 to 3.

[525] Clause 187. A compound according to any of Clauses 182 - 186 or a salt, hydrate, or solvate thereof; where y2 is an integer from 1 to 2.

[526] Clause 188. A compound according to any of Clauses 182 - 187 or a salt, hydrate, or solvate thereof; where y2 is 1.

[527] Clause 189. A compound according to any of Clauses 182 - 188 or a salt, hydrate, or solvate thereof; where y3 is an integer from 1 to 4.

[528] Clause 190. A compound according to any of Clauses 182 - 189 or a salt, hydrate, or solvate thereof; where y3 is an integer from 1 to 3.

[529] Clause 191. A compound according to any of Clauses 182 - 190 or a salt, hydrate, or solvate thereof; where y3 is an integer from 1 to 2.

[530] Clause 192. A compound according to any of Clauses 182 - 191 or a salt, hydrate, or solvate thereof; where y3é 1.

[531] Clause 193. A compound according to any of Clauses 182 - 192 or a salt, hydrate, or solvate thereof; wherein each of X1, X2, X3, X4, X5, and X6 is independently a substituted or unsubstituted carbon atom.

[532] Clause 194. A compound according to any of Clauses 182 - 193 or a salt, hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 159 / 254 152 / 246 of the same; wherein at least three of X1, X2, X3, X4, X5, and X6 are independently a substituted carbon atom.

[533] Clause 195. A compound according to any of Clauses 182 - 194 or a salt, hydrate, or solvate thereof; wherein each substituted carbon atom is independently substituted by R48, T1, TL, and / or a moiety according to any of Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5.

[534] Clause 196. A compound according to any of Clauses 182 - 195 or a salt, hydrate, or solvate thereof; wherein each substituted carbon atom is independently substituted by R48, T1, TL, and / or a moiety according to Radical Group 1.

[535] Clause 197. A compound according to any of Clauses 182 - 196 or a salt, hydrate, or solvate thereof; wherein each substituted carbon atom is independently substituted by R48, T1e / or TL.

[536] Clause 198. A compound according to any of Clauses 182 - 197 or a salt, hydrate, or solvate thereof; wherein at most three of X1, X2, X3, X4, X5, and X6 are independently a substituted carbon atom.

[537] Clause 199. A compound according to any of Clauses 182 - 198 or a salt, hydrate, or solvate thereof; wherein X1e / or X6 are independently a carbon atom substituted by R48.

[538] Clause 200. A compound according to any of Clauses 182 - 199 or a salt, hydrate, or solvate thereof; wherein one of X1 and X6 is a carbon atom substituted by R48.

[539] Clause 201. A compound according to any of Clauses 182 - 200 or a salt, hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 160 / 254 153 / 246 of the same; where X1 is a carbon atom substituted by R4 8 ·

[540] Clause 202. A compound according to any of Clauses 182 - 201 or a salt, hydrate, or solvate thereof; where X1 is -CHR48-.

[541] Clause 203. A compound according to any of Clauses 182 - 202 or a salt, hydrate, or solvate thereof; wherein at least one of X2, X3, X4, and X5 is independently a carbon atom substituted with T1 and / or TL.

[542] Clause 204. A compound according to any of Clauses 182 - 204 or a salt, hydrate, or solvate thereof; wherein one of X2, X3, X4, and X5 is independently a carbon atom substituted with T1 and / or TL.

[543] Clause 205. A compound according to any of Clauses 182 - 204 or a salt, hydrate, or solvate thereof; wherein one of X2, X3, X4, and X5 is independently a carbon atom substituted with T1 and TL.

[544] Clause 206. A compound according to any of Clauses 182 - 205 or a salt, hydrate, or solvate thereof; where X4 is a carbon atom substituted with T1 and / or TL.

[545] Clause 207. A compound according to any of Clauses 182 - 206 or a salt, hydrate, or solvate thereof; where X4 is a carbon atom substituted with T1 and TL.

[546] Clause 208. A compound according to any of Clauses 182 - 206 or a salt, hydrate, or solvate thereof; wherein X1 is a carbon atom substituted with R48, and X4 is a carbon atom substituted with T1 and / or TL.

[547] Clause 209. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 161 / 254 154 / 246 one of Clauses 182 - 208 or a salt, hydrate, or solvate thereof; where X1 is a carbon atom substituted with R48, and X4 is a carbon atom substituted with T1 and TL.

[548] Clause 210. A compound according to any of Clauses 182 - 209 or a salt, hydrate, or solvate thereof; where X1 is -CHR48-, and X4 is -CT1TL-.

[549] Clause 211. A compound according to any of Clauses 182 - 210 or a salt, hydrate, or solvate thereof; wherein X2, X3, X5, and X6 are unsubstituted carbon atoms.

[550] Clause 212. A compound according to any of Clauses 182 - 211 or a salt, hydrate, or solvate thereof; wherein X2, X3, X5, and X6 are -CH2-.

[551] Clause 213. A compound according to any of Clauses 182 - 212 or a salt, hydrate, or solvate thereof; wherein X1 is -CHR48-, X4 is -CT1TL-, and X2, X3, X5, and X6 are -CH2-.

[552] Clause 214. A compound of Clause 213 or a salt, hydrate, or solvate thereof; where R48 is:

[553] Clause 215. A compound according to any of Clauses 213 - 214 or a salt, hydrate, or solvate thereof; where T1 is -OH.

[554] Clause 216. A compound according to any of Clauses 213 - 215 or a salt, hydrate, or solvate thereof; wherein TLé Petition 870250092139, dated 08 / 10 / 2025, pp. 162 / 254 155 / 246 NH x HNO NH Oy ; where is an integer in a range from 4 to 12; It is an integer in the range of 15 to 35; and T2 is selected from the group that consists of salt, a THE O, starting from , where CB is a protein.

[555] Clause 217. hydrate, or solvate 6.

[556] Clause 218. from Clause 216 of the same; where x is 5.

[557] Clause 219. one of Clauses 216 of the same; where y is a

[558] Clause 220. one of Clauses 216 of the same; where y is a

[559] Clause 221. one of Clauses 216 of the same; where y is 24. One of One 217 One 218 HO THE NH O CB composed of the same Clause; where x is a compound of or a salt, compound of or a salt, integer from 20 to A compound of 219 or a whole salt of 23 to A compound of 220 or a salt, 216 or an entire unit according to any hydrate, or solvate according to any hydrate, or solvate 30. in accordance with any hydrate, or solvate 25. in accordance with any hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 163 / 254 156 / 246

[560] Clause 222. A compound according to any of Clauses 216–221 or a salt, hydrate, or solvate thereof; wherein T2 is composed of One

[561] Clause 223. in accordance with any of Clauses 216 222 or a salt, hydrate, or solvate thereof; wherein T2 is THE CB

[562] Clause 224. A compound according to any of Clauses 216 - 223 or a salt, hydrate, or solvate thereof; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[563] Clause 225. A compound of Clause 223 or a salt, hydrate, or solvate thereof; wherein CB is linked to the maleimidyl group by means of a sulfur atom that is part of CB, wherein the sulfur atom is part of a cysteine.

[564] Clause 226. A compound of Clause 225 or a salt, hydrate, or solvate thereof; wherein CBé AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[565] Clause 227. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 164 / 254 157 / 246 one of Clauses 216 of the same; in which T2 is 221 or a salt, hydrate, or solvate

[566] Clause 228. A compound according to any of Clauses 1 - 227 or a salt, hydrate, or solvate thereof; wherein said compound is according to Formula (C): t2_l ^l2A^l2_^t31 LLL 1Formula (C); where R48 is as defined in any of Clauses 147 - 166; T1 is as defined in any of Clauses 167-179; T2 is as defined in any of Clauses 1, and 49 - 69; T3 is as defined in any of Clauses 1, and 70-89; L1 is as defined in any of the Clauses 1 - 29; L2a is as defined in any of Clauses 90-99; L2bé as defined in any of the Clauses Petition 870250092139, dated 08 / 10 / 2025, pp. 165 / 254 158 / 246 90, 91, and 100 - 107; L2cé as defined in any of Clauses 90, 91, and 116-128; and L2 is as defined in any of Clauses 90, 91, and 108-115.

[567] Clause 229. A compound of Clause 228 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[568] Clause 230. A compound of Clause 229 or a salt, hydrate, or solvate thereof; where L1 is a linear or branched C4-C12 alkylene.

[569] Clause 231. A compound of Clause 230 or a salt, hydrate, or solvate thereof; wherein L1 is a linear or branched C4-C10 alkylene.

[570] Clause 232. A compound of Clause 231 or a salt, hydrate, or solvate thereof; where L1 is a linear C5-C6 alkylene.

[571] Clause 233. A compound of Clause 232 or a salt, hydrate, or solvate thereof; where L1 is a linear C5 alkylene.

[572] Clause 234. A compound of Clause 233 or a salt, hydrate, or solvate thereof; wherein L1 is an unsubstituted C5 linear alkylene.

[573] Clause 235. A compound according to any of Clauses 228 - 234 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected and are each independently a ligand.

[574] Clause 236. A compound according to any of Clauses 228 - 235 or a salt, hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 166 / 254 159 / 246 of the same; wherein L2a, L2b, and L2d are each independently selected as a ligand containing at most twenty atoms.

[575] Clause 237. A compound according to any of Clauses 228 - 236 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected independently from the group consisting of C(O)NL2T-, -NL2tC(O)-, -O-, -S-, -NL2t-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl.

[576] Clause 238. A compound of Clause 237 or a salt, hydrate, or solvate thereof; wherein L2T is hydrogen.

[577] Clause 239. A compound according to any of Clauses 228 - 238 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected independently from the group consisting of -C(O)NH-, and -NHC(O)-.

[578] Clause 240. A compound according to any of Clauses 228 - 239 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenotriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl.

[579] Clause 241. A compound according to any of Clauses 228 - 240 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 (hetero) alkanetriyl.

[580] Clause 242. A compound according to any of Clauses 228 - 241 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 alkanetriyl.

[581] Clause 243. A compound according to any of Clauses 228 - 242 or a salt, hydrate, or solvate thereof; wherein L2 is a C4-C6 alkanetriyl.

[582] Clause 244. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 167 / 254 160 / 246 one of Clauses 228 - 243 or a salt, hydrate, or solvate thereof; wherein L2 is an alkanotriyl C5.

[583] Clause 245. A compound according to any of Clauses 228 - 244 or a salt, hydrate, or solvate thereof; where L2cé >CH-CH2-CH2-CH2-CH2-.

[584] Clause 246. A compound according to any of Clauses 228 - 245 or a salt, hydrate, or solvate thereof; wherein T1 is selected from the group consisting of -OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5C12 alkyl (hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, N(T1a)2, -ST1a, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1AC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3; Each T1A is independently selected from the group consisting of hydrogen, (hetero) alkyl, (hetero) alkenyl, (hetero) alkynyl, (hetero) aryl, and an amino acid residue;

[585] preferably each T1A is independently selected from the group consisting of hydrogen, (hetero) C1-C6 alkyl, (hetero) C1-C6 alkenyl, (hetero) C1-C6 alkynyl, C2-C5 heteroaryl, phenyl, and an amino acid residue; even more preferably each T1A is independently selected from the group consisting of hydrogen, (hetero) C1-C4 alkyl, (hetero) C1C4 alkenyl, (hetero) C1-C4 alkynyl, C3-C5 heteroaryl, phenyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; even more preferably each T1A is independently selected from the group consisting of hydrogen, C1-C3 alkyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; and most preferably T1A is hydrogen.

[586] Clause 247. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 168 / 254 161 / 246 one of Clauses 228 - 246 or a salt, hydrate, or solvate thereof; where T1 is -OT1A.

[587] Clause 248. A compound according to any of Clauses 246 - 247 or a salt, hydrate, or solvate thereof; wherein T1A is hydrogen or methyl.

[588] Clause 249. A compound according to any of Clauses 246 - 248 or a salt, hydrate, or solvate thereof; wherein T1A is hydrogen.

[589] Clause 250. A compound according to any of Clauses 228 - 249 or a salt, hydrate, or solvate thereof; where T1 is -OH.

[590] Clause 251. A compound according to any of Clauses 228 - 250 or a salt, hydrate, or solvate thereof; wherein T2 is a bioconjugation moiety or group -L3-CB; in which L3 is a residue of a bioconjugation moiety, and CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells, and combinations thereof.

[591] Clause 252. A compound of Clause 251 or a salt, hydrate, or solvate thereof; wherein the conjugating biomotive is selected from the group consisting of N-maleimidyl, halogenated N-alkylamido, sulfonyloxy N-alkylamido, vinyl sulfone, carboxylic acids (activated), active ester, benzenesulfonyl halides, ester, carbonate, sulfonyl halide, thiol or derivatives thereof, C2-C6 alkenyl, C2-C6 alkynyl, C7-C18 cycloalkynyl, C5-C18 heterocycloalkynyl, bicyclo[6.1.0]non-4-yn-9-yl], C3-C12 cycloalkenyl, azido, phosphine, nitrile oxide, Petition 870250092139, dated 08 / 10 / 2025, pp. 169 / 254 162 / 246 nitrone, nitrile imine, isonitrile, diazo, ketone, (O-alkyl)hydroxylamino, hydrazine, N-maleimidyl halogenated, aryloxymaleimides, dithiophenolmaleimides, bromo- and dibromopyridazinediones, 2,5-dibromohexanediamide, alcinone, 3-arylpropiolonitrile, 1,1-bis(sulfonylmethyl)-methylcarbonyl or elimination derivatives thereof, carbonyl halide, alenamide, 1,2-quinone, isothiocyanate, isocyanate, aldehyde, triazine, squaric acids, 2-imino-2-methoxyethyl, (oxa)norbornene, (oxa)norbornadiene, (imino)sidnones, methylsulfonyl phenyloxadiazole, aminooxy, 2-aminobenzamidoxime, Ethinylphosphonamidates, reactive agents at the Pictet-Spengler linkage and hydrazine-Pictet-Spengler linkage (HIPS), DNA intercalators, tetrazine, trans-cyclooctene, and photocrosslinkers.

[592] Clause 253. A compound of Clause 252 or a salt, hydrate, or solvate thereof; wherein the conjugation bioportion is selected from the group consisting of N-maleimidyl, halogenated N-alkylamido, sulfonyloxy N-alkylamido, vinyl sulfone, carboxylic acids, benzenesulfonyl halides, ester, carbonate, sulfonyl halide, thiol, C2-C6 alkenyl, C2-C6 alkynyl, C7-C18 cycloalkynyl, C5-C18 heterocycloalkynyl, bicyclo[6.1.0]non-4-yn-9-yl, C3-C12 cycloalkenyl, azido, phosphine, nitrile oxide, nitrone, nitrile imine, isonitrile, diazo, ketone, (O-alkyl)hydroxylamino, hydrazine, halogenated N-maleimidyl, aryloxymaleimides, dithiophenolmaleimides, bromo- and dibromopyridazinediones, 2,5-dibromohexanediamide, alcinone, 3-arylpropiolonitrile, 1,1-bis(sulfonylmethyl)-methylcarbonyl, carbonyl halide, alenamide, 1,2-quinone, isothiocyanate, isocyanate, aldehyde, triazine, squaric acids, 2-imino-2-methoxyethyl, (oxa)norbornene, (oxa)norbornadiene, Petition 870250092139, dated 08 / 10 / 2025, pp. 170 / 254 163 / 246 (imino)sydnones, methylsulfonylphenyloxadiazole, aminooxy, 2aminobenzamidoxime, and ethinylphosphonamidates.

[593] Clause 254. A compound of Clause 253 or a salt, hydrate, or solvate thereof; wherein the conjugating biomotive is N-maleimidil.

[594] Clause 255. A compound according to any of Clauses 228 - 254 or a salt, hydrate, or solvate thereof; wherein T2 is a bioconjugation moiety.

[595] Clause 256. A salt, hydrate, or solvate of

[596] Clause 257. A salt, hydrate, or solvate of the compound in Clause 255 or the same; wherein T2 is N-maleimidil. composed of Clause 256 or the same; wherein T2 is

[597] Clause 258. A compound according to any of Clauses 228 - 254 or a salt, hydrate, or solvate thereof; where T2 is an -L3-CB group.

[598] Clause 259. A compound according to any of Clauses 228 - 254, and 258, or a salt, hydrate, or solvate thereof; wherein L3 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety.

[599] Clause 260. A compound according to any of Clauses 228 - 254, and 258 - 259, or a salt, hydrate, or solvate thereof; wherein L3 is a residue of a maleimidyl moiety.

[600] Clause 261. A compound according to any of Clauses 228–254 and 258–260, or a salt, hydrate, or solvate thereof; wherein T2 is selected from Petition 870250092139, dated 08 / 10 / 2025, pp. 171 / 254 164 / 246 group consisting of

[601] Clause 262. A compound according to any of Clauses 228 - 254, and 258 - 261, or a salt, hydrate, or solvate thereof; wherein CB is a protein.

[602] Clause 263. A compound according to any of Clauses 228 - 254, and 258 - 262, or a salt, hydrate, or solvate thereof; wherein CB is an antibody or a diabody.

[603] Clause 264. A compound according to any of Clauses 228 - 254, and 258 - 263, or a salt, hydrate, or solvate thereof; wherein CB is a diacorporeal.

[604] Clause 265. A compound according to any of Clauses 228 - 254, and 258 - 264, or a salt, hydrate, or solvate thereof; wherein CBé AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[605] Clause 266. A compound according to any of Clauses 228 - 254, and 258 - 265, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom or a nitrogen atom, wherein the sulfur atom or nitrogen atom is part of CB.

[606] Clause 267. A compound according to any of Clauses 228 - 254, and 258 - 266, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom, wherein the sulfur atom is part of CB. Petition 870250092139, dated 08 / 10 / 2025, pp. 172 / 254 165 / 246

[607] Clause 268. A compound according to any of Clauses 228 - 254, and 258 - 267, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom that is part of CB, wherein the sulfur atom is part of a cysteine ​​residue.

[608] Clause 269. A compound according to any of Clauses 228 - 268, or a salt, hydrate, or solvate thereof; where T3 is a polymer.

[609] Clause 270. A compound according to any of Clauses 228 - 269, or a salt, hydrate, or solvate thereof; wherein T3 is a polymer comprising a polyethylene glycol moiety.

[610] Clause 271. A compound according to any of Clauses 228 - 270, or a salt, hydrate, or solvate thereof; wherein T3 comprises a portion -(CH2CH2-O-)y-T4, wherein y is an integer in a range from 1 to 50, and T4 is according to Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5 as defined herein; preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, even more preferably in a range from 20 to 30, even more preferably in a range from 23 to 25, and most preferably y is 24.

[611] Clause 272. A compound according to any of Clauses 228 - 271, or a salt, hydrate, or solvate thereof; where T3 is a -(CH2CH2-O-)y-T4 moiety.

[612] Clause 273. A compound according to any of Clauses 271 - 272, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 10 to 40.

[613] Clause 274. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 173 / 254 166 / 246 one of Clauses 271 - 273, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 12 to 37.

[614] Clause 275. A compound according to any of Clauses 271 - 274, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 15 to 35.

[615] Clause 276. A compound according to any of Clauses 271 - 275, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 20 to 30.

[616] Clause 277. A compound according to any of Clauses 271 - 276, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 23 to 25.

[617] Clause 278. A compound according to any of Clauses 271 - 277, or a salt, hydrate, or solvate thereof; where y is 24.

[618] Clause 279. A compound according to any of Clauses 271 - 278, or a salt, hydrate, or solvate thereof; wherein T4 is methyl.

[619] Clause 280. A compound according to any of Clauses 228 - 279, or a salt, hydrate, or solvate thereof; where T3 is a -(CH2CH2-O-)24-CH3 moiety.

[620] Clause 281. A compound according to any of Clauses 228 - 280, or a salt, hydrate, or solvate thereof; wherein R48 is selected from the group consisting of -OH, -O-acetyl, -O-C1-4alkyl, halogen, active carbonate, and a releasable group.

[621] Clause 282. A compound according to any of Clauses 228 - 281, or a salt, hydrate, or solvate thereof; wherein R48 is a releasable group.

[622] Clause 283. A compound according to any of Clauses 228 - 282, or a salt, hydrate, or solvate thereof; wherein the said releasable group is -(Y1-C(=Y2))i Petition 870250092139, dated 08 / 10 / 2025, pp. 174 / 254 167 / 246 (SP)j-CA; wherein each of Y1 and Y2 are selected independently of O and S; CA is the construct A, which is a payload; SP is a ligand; j is 0 or 1; i is 0 or 1; if i is 0, -(SP)j-CA is linked to the rest of the compound by means of O or S, which is part of -(SP)j-CA; if i is 1, -(SP)j-CA is linked to -C(=Y2)- by means of O, S, a secondary N, or a tertiary N, which is part of -(SP)j-CA.

[623] Clause 284. A compound according to any of Clauses 228 - 283, or a salt, hydrate, or solvate thereof; wherein the said releasable group is -(OC(=O))i(SP)j-CA.

[624] Clause 285. A compound according to any of Clauses 228 - 284, or a salt, hydrate, or solvate thereof; wherein the said releasable group is -OC(=O)-(SP)jCA.

[625] Clause 286. A compound according to any of Clauses 228 - 285, or a salt, hydrate, or solvate thereof; where SP is according to Radical Group 2.

[626] Clause 287. A compound according to any of Clauses 228 - 286, or a salt, hydrate, or solvate thereof; wherein SP is a self-immolating ligand.

[627] Clause 288. A compound according to any of Clauses 228 - 287, or a salt, hydrate, or solvate thereof; wherein the said releasable group is -OC(=O)-CA.

[628] Clause 289. A compound according to any of Clauses 228 - 288, or a salt, hydrate, or solvate thereof; wherein CA is linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of CA, forming a carbamate.

[629] Clause 290. A compound according to any of Clauses 228–289, or a salt, hydrate, or solvate Petition 870250092139, dated 08 / 10 / 2025, pp. 175 / 254 168 / 246 of the same; where CA is a drug.

[630] Clause 291. A compound according to any of Clauses 228 - 290, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE).

[631] Clause 292. A compound according to any of Clauses 228 - 291, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE) linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[632] Clause 293. A compound according to any of Clauses 228 - 292, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE) linked to the -OC(=O)- portion by means of a tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[633] Clause 294. A compound according to any of Clauses 228 - 293, or a salt, hydrate, or solvate thereof; wherein said group R48 is in an axial position.

[634] Clause 295. A compound according to any of Clauses 228 - 294, or a salt, hydrate, or solvate thereof; wherein said group R48 is:

[635] Clause 296. A compound according to any of Clauses 1 - 295, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (1): Petition 870250092139, dated 08 / 10 / 2025, pp. 176 / 254 169 / 246 t2_l1rv 1' r1 1Formula (1); wherein L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene; L2a, L2b, and L2d are each independently selected ligands; L2c is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenotriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl; T1 is selected from the group consisting of -OT1A, hydrogen, C2-C6 alkyl, aryl C6, heteroaryl C4-C5, cycloalkyl C3-C6, alkyl (hetero)aryl C5-C12, (hetero)aryl alkyl C5-C12, alkylcycloalkyl C4-C12, -N(T1a)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1AC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3; each T1A is independently selected from the group consisting of hydrogen, (hetero)alkyl, (hetero)alkenyl, (hetero)alkynyl, (hetero)aryl, and an amino acid residue; T2 is a -L3-CB bioconjugation moiety or group; wherein L3 is a residue of a bioconjugation moiety, and CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells and combinations thereof; T3 is a polymer; and R48 is Petition 870250092139, dated 08 / 10 / 2025, pp. 177 / 254 170 / 246 selected from the group consisting of -OH, -O-acetyl, -O-C1_4alkyl, halogen, active carbonate, and a releasable group; and preferably L1 is linear or branched C4-C12 alkylene, more preferably L1 is linear or branched C4-C10 alkylene, and most preferably L1 is linear C5-C6 alkylene; preferably L2a, L2b, and L2d are each independently selected from a ligand containing at most twenty atoms; more preferably L2a, L2b, and L2d are each independently selected from the group consisting of -C(O)NL2T-, -NL2TC(O)-, -O-, -S-, NL2t-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl, preferably L2T is hydrogen; preferably L2e (hetero) C1-C8 alkanetriyl, more preferably L2e C1-C8 alkanetriyl, and most preferably L2e C4-C6 alkanetriyl; preferably T1e -OT1A; and most preferably T1e -OH; preferably T1Ae hydrogen or methyl, most preferably T1Ae hydrogen;Preferably T2 is maleimidyl, N-hydroxysuccinimidyl, or -L3-Cb; preferably L3 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety; preferably CB is a protein, more preferably CB is an antibody or a diabody, even more preferably CB is a diabody, and most preferably CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably T3 is a polymer comprising a polyethylene glycol moiety; and preferably R48 is a releasable group.

[636] Clause 297. A compound of Clause 296, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position. Petition 870250092139, dated 08 / 10 / 2025, pages 178 / 254 171 / 246

[637] Clause 298. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (D): Formula (D), where R48 is as defined in any of Clauses 147-166, and 281-295; T1 is as defined in any of Clauses 167-179, and 246-250; T2 is as defined in any of Clauses 1, 49-69, and 251-268; T3 is as defined in any of Clauses 1, 70-89, and 269-280; L1 is as defined in any of Clauses 1-29, and 229-234; L2a is as defined in any of Clauses 90-99, and 235-239; L2bé is defined in any of Clauses 90, 91, 100-107, and 235-239; L2cé is defined in any of Clauses 90, 91, 116-128, and 240-245; and L2d is defined in any of Clauses 90, 91, 108-115, and 235-239.

[638] Clause 299. A compound of Clause 298, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[639] Clause 300. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (E): Petition 870250092139, dated 08 / 10 / 2025, pp. 179 / 254 172 / 246 τ2 / iEi2! 1 1Formula (E), where R48 is as defined in any of Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; T3 is as defined in any of Clauses 1, 70 - 89, and 269 - 280; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé as defined in any of Clauses 90, 91, 100-107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and 235-239.

[640] Clause 301. A compound of Clause 300, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[641] Clause 302. A compound according to any of Clauses 1 - 301, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (F): Petition 870250092139, dated 08 / 10 / 2025, pp. 180 / 254 173 / 246 Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; T3 is as defined in any of Clauses 1, 70 - 89, and 269 - 280; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé is as defined in any of Clauses 90, 91, 100 - 107, and 235 - 239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and 235-239.

[642] Clause 303. A compound of Clause 302, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[643] Clause 304. A compound according to any of Clauses 1 - 302, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (G): Petition 870250092139, dated 08 / 10 / 2025, pp. 181 / 254 174 / 246 y Formula (G), where R48 is as defined in any of Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; y is as defined in any of Clauses 271, and 273 - 278; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé as defined in any of Clauses 90, 91, 100, 107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and 235-239.

[644] Clause 305. A compound of Clause 304, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[645] Clause 306. A compound of Clause 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (2): Petition 870250092139, dated 08 / 10 / 2025, pp. 182 / 254 175 / 246 formula (2); where y is an integer in a range from 1 to 50; preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, even more preferably in a range from 20 to 30, and most preferably in a range from 23 to 25.

[646] Clause 307. A compound of Clause 306, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[647] Clause 308. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (H): Formula (H), where R48 is as defined in any of Clauses 147-166 and 281-295; T1 is as defined in any of Clauses 167-179 and 246-250; T2 is as defined in any of Clauses 1, 49-69, and Petition 870250092139, dated 08 / 10 / 2025, pp. 183 / 254 176 / 246 251 - 268; y is as defined in any of Clauses 271, and 273 - 278; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé is as defined in any of Clauses 90, 91, 100-107, and 235 - 239; L2cé is as defined in any of Clauses 90, 91, 116 - 128, and 240 - 245; and L2dé is as defined in any of Clauses 90, 91, 108 - 115, and 235 - 239.

[648] Clause 309. A compound of Clause 308, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[649] Clause 310. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (I): ^lL^Í^^l^^t3 Formula (I), where R48 is as defined in any of Clauses 147-166 and 281-295; T1 is as defined in any of Clauses 167-179 and 246-250; T2 is as defined in any of Clauses 1, 49-69, and 251-268; y is as defined in any of Clauses 271 and 273-278; L1 is as defined in any of Clauses 1-29 and 229-234; L2a is as defined in any of Clauses 90-99 and 235-239; L2bé such Petition 870250092139, dated 08 / 10 / 2025, pp. 184 / 254 177 / 246 as defined in any of Clauses 90, 91, 100, 107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and 235-239.

[650] Clause 311. A compound of Clause 310, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[651] Clause 312. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (J): _2 1 2b 12c 2d _3 T—L—L—L—L--T . Formula (J), where R48 is as defined in any of Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; y is as defined in any of Clauses 271, and 273 - 278; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé as defined in any of Clauses 90, 91, 100, 107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and Petition 870250092139, dated 08 / 10 / 2025, pp. 185 / 254 178 / 246 235 - 239.

[652] Clause 313. A compound of Clause 312, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[653] Clause 314. A compound according to any of Clauses 312 - 313, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[654] Clause 315. A compound according to any of Clauses 312 - 314, or a salt, hydrate, or solvate thereof; wherein T1 is -OH and R48 is in an axial position.

[655] Clause 316. A compound of Clause 315, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[656] Clause 317. A compound of Clause 316, or a salt, hydrate, or solvate thereof; where R48 is:

[657] Clause 318. A compound according to any of Clauses 1 - 296, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (K): Petition 870250092139, dated 08 / 10 / 2025, pp. 186 / 254 179 / 246 1 2b 12c 2d 3 T—L—L—L—L--T1 1Formula (K), where R48 is as defined in any of Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; y is as defined in any of Clauses 271, and 273 - 278; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé as defined in any of Clauses 90, 91, 100, 107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2dé as defined in any of Clauses 90, 91, 108-115, and 235-239.

[658] Clause 319. A compound of Clause 318, or a salt, hydrate, or solvate thereof; wherein R48 is in an axial position.

[659] Clause 320. A compound according to any of Clauses 318 - 319, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[660] Clause 321. A compound according to any of Clauses 318 - 320, or a salt, hydrate, or solvate thereof; wherein T1 is -OH and R48 is in an axial position.

[661] Clause 322. A compound of Clause 321, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, Petition 870250092139, dated 08 / 10 / 2025, pp. 187 / 254 180 / 246 where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[662] Clause 323. A compound of Clause 322, or a salt, hydrate, or solvate thereof; where R48 is:

[663] Clause 324. A compound according to any of Clauses 1 - 323, or a salt, hydrate, or solvate thereof; wherein said compound has a structure according to Formula (L), where R48 is as defined in any of Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; y is as defined in any of Clauses 271, and 273 - 278; L1 is as defined in any of Clauses 1 - 29, and 229 - 234; L2a is as defined in any of Clauses 90 - 99, and 235 - 239; L2bé as defined in any of Clauses 90, 91, 100, 107, and 235-239; L2cé as defined in any of Clauses 90, 91, 116-128, and 240-245; and L2d as Petition 870250092139, dated 08 / 10 / 2025, pp. 188 / 254 181 / 246 defined in any of Clauses 90, 91, 108 - 115, and 235 - 239.

[664] Clause 325. A compound of Clause 324, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[665] Clause 326. A compound of Clause 325, or a salt, hydrate, or solvate thereof; wherein R48 is -OC(O)-CA, wherein CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[666] Clause 327. A compound of Clause 326, or a

[667] Clause 328. A compound according to any of Clauses 324 - 327 or a salt, hydrate, or solvate thereof; wherein L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene.

[668] Clause 329. A compound according to any of Clauses 324 - 328 or a salt, hydrate, or solvate thereof; where L1 is a linear or branched C4-C12 alkylene.

[669] Clause 330. A compound according to any of Clauses 324 - 329 or a salt, hydrate, or solvate thereof; where L1 is a linear or branched C4-C10 alkylene.

[670] Clause 331. A compound according to any of Clauses 324 - 330 or a salt, hydrate, or solvate thereof; where L1 is a linear C5-C6 alkylene.

[671] Clause 332. A compound according to any of Clauses 324 - 331 or a salt, hydrate, or solvate thereof; where L1 is a linear C5 alkylene. Petition 870250092139, dated 08 / 10 / 2025, pp. 189 / 254 182 / 246

[672] Clause 333. A compound according to any of Clauses 324 - 332 or a salt, hydrate, or solvate thereof; where L1 is an unsubstituted linear C5 alkylene.

[673] Clause 334. A compound according to any of Clauses 324 - 333 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected and are each independently a ligand.

[674] Clause 335. A compound according to any of Clauses 324 - 334 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected and are each independently a ligand containing at most twenty atoms.

[675] Clause 336. A compound according to any of Clauses 324 - 335 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected independently from the group consisting of C(O)NL2t-, -NL2tC(O)-, -O-, -S-, -NL2t-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl.

[676] Clause 337. A compound according to any of Clauses 324 - 336 or a salt, hydrate, or solvate thereof; wherein L2T is hydrogen.

[677] Clause 338. A compound according to any of Clauses 324 - 337 or a salt, hydrate, or solvate thereof; wherein L2a, L2b, and L2d are each selected independently from the group consisting of -C(O)NH-, and -NHC(O)-.

[678] Clause 339. A compound according to any of Clauses 324 - 338 or a salt, hydrate, or solvate thereof; wherein L2 is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenotriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl. Petition 870250092139, dated 08 / 10 / 2025, pp. 190 / 254 183 / 246

[679] Clause 340. A compound according to any of Clauses 324 - 339 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 (hetero) alkanetriyl.

[680] Clause 341. A compound according to any of Clauses 324 - 340 or a salt, hydrate, or solvate thereof; wherein L2 is a C1-C8 alkanetriyl.

[681] Clause 342. A compound according to any of Clauses 324 - 341 or a salt, hydrate, or solvate thereof; wherein L2 is a C4-C6 alkanetriyl.

[682] Clause 343. A compound according to any of Clauses 324 - 342 or a salt, hydrate, or solvate thereof; wherein L2 is an alkanetriyl C5.

[683] Clause 344. A compound according to any of Clauses 324 - 343 or a salt, hydrate, or solvate thereof; where L2cé >CH-CH2-CH2-CH2-CH2-.

[684] Clause 345. A compound according to any of Clauses 324 - 344 or a salt, hydrate, or solvate thereof; wherein T1 is selected from the group consisting of -OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5C12 alkyl (hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, N(T1a)2, -ST1a, -SO3H, -C(O)T1a, -C(O)Ot1A, -OC(O)T1aC(O)N(T1A)2, -N(T1A)2-CO-T1A, and -Si(T1A)3; Each T1A is independently selected from the group consisting of hydrogen, (hetero) alkyl, (hetero) alkenyl, (hetero) alkynyl, (hetero) aryl, and an amino acid residue;

[685] preferably each T1A is independently selected from the group consisting of hydrogen, C1-C6 (hetero)alkyl, C1-C6 (hetero)alkenyl, C1-C6 (hetero)alkynyl, C2-C5 heteroaryl, phenyl, and an amino acid residue; even more preferably each T1A is Petition 870250092139, dated 08 / 10 / 2025, pp. 191 / 254 184 / 246 independently selected from the group consisting of hydrogen, C1-C4 (hetero)alkyl, C1C4 (hetero)alkenyl, C1-C4 (hetero)alkynyl, C3-C5 heteroaryl, phenyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; even more preferably each T1A is independently selected from the group consisting of hydrogen, C1-C3 alkyl, an aspartic acid residue, a glutamic acid residue, and a glycine residue; and most preferably T1A is hydrogen.

[686] Clause 346. A compound according to any of Clauses 324 - 345 or a salt, hydrate, or solvate thereof; where T1 is -OT1A.

[687] Clause 347. A compound according to any of Clauses 324 - 346 or a salt, hydrate, or solvate thereof; wherein T1A is hydrogen or methyl.

[688] Clause 348. A compound according to any of Clauses 324 - 347 or a salt, hydrate, or solvate thereof; wherein T1A is hydrogen.

[689] Clause 349. A compound according to any of Clauses 324 - 348 or a salt, hydrate, or solvate thereof; where T1 is -OH.

[690] Clause 350. A compound according to any of Clauses 324 - 349 or a salt, hydrate, or solvate thereof; wherein T2 is a bioconjugation moiety or group -L3-CB; in which L3 is a residue of a bioconjugation moiety, and CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells, and combinations thereof. Petition 870250092139, dated 08 / 10 / 2025, pp. 192 / 254 185 / 246

[691] Clause 351. A compound of Clause 350 or a salt, hydrate, or solvate thereof; wherein the conjugating bioportion is selected from the group consisting of N-maleimidil, halogenated N-alkylamido, sulfonyloxy N-alkylamido, vinyl sulfone, carboxylic acids (activated), active ester, benzenesulfonyl halides, ester, carbonate, sulfonyl halide, thiol or derivatives thereof, C2-C6 alkenyl, C2-C6 alkynyl, C7-C18 cycloalkynyl, C5-C18 heterocycloalkynyl, bicyclo [6.1.[0] non-4-yn-9-yl], cycloalkenyl C3-C12, azido, phosphine, nitrile oxide, nitrone, nitrile imine, isonitrile, diazo, ketone, (O-alkyl)hydroxylamino, hydrazine, N-maleimidyl halogenated, aryloxymaleimides, dithiophenolmaleimides, bromo- and dibromopyridazinediones, 2,5-dibromohexanediamide, alcinone, 3-arylpropiolonitrile, 1,1-bis(sulfonylmethyl)-methylcarbonyl or elimination derivatives thereof, carbonyl halide, alenamide, 1,2-quinone, isothiocyanate, isocyanate, aldehyde, triazine, squaric acids, 2-imino-2-methoxyethyl, (oxa)norbornene, (oxa)norbornadiene, (imino)sidnones, Methylsulfonyl phenyloxadiazole, aminooxy, 2-aminobenzamidoxime, ethinylphosphonamidates, Pictet-Spengler linkage and hydrazine-Pictet-Spengler linkage (HIPS) reactants, DNA intercalators, tetrazine, trans-cyclooctene, and photocrosslinkers.

[692] Clause 352. A compound of Clause 351 or a salt, hydrate, or solvate thereof; wherein the conjugating biomotive is selected from the group consisting of N-maleimidyl, N-alkylamido halogenated, sulfonyloxy N-alkylamido, vinyl sulfone, carboxylic acids, benzenesulfonyl halides, ester, carbonate, sulfonyl halide, thiol, C2-C6 alkenyl, C2-C6 alkynyl, C7-C18 cycloalkynyl, Petition 870250092139, dated 08 / 10 / 2025, pp. 193 / 254 186 / 246 heterocycloalkynyl C5-C18, bicyclo[6.1.0]non-4-yn-9-yl], cycloalkenyl C3-C12, azido, phosphine, nitrile oxide, nitrone, nitrile imine, isonitrile, diazo, ketone, (O-alkyl)hydroxylamino, hydrazine, N-maleimidil halogenated, aryloxymaleimides, dithiophenolmaleimides, bromo- and dibromopyridazinediones, 2,5-dibromohexanediamide, alcinone, 3-arylpropiolonitrile, 1,1-bis(sulfonylmethyl)-methylcarbonyl, carbonyl halide, alenamide, 1,2-quinone, isothiocyanate, isocyanate, aldehyde, triazine, squaric acids, 2-imino-2-methoxyethyl, (oxa)norbornene, (oxa)norbornadiene, (imino)sydnones, methylsulfonylphenyloxadiazole, aminooxy, 2aminobenzamidoxime, and ethinylphosphonamidates.

[693] Clause 353. A compound of Clause 352 or a salt, hydrate, or solvate thereof; wherein the conjugating biomotive is N-maleimidil.

[694] Clause 354. A compound according to any of Clauses 324 - 353 or a salt, hydrate, or solvate thereof; wherein T2 is a bioconjugation moiety.

[695] Clause 355. A compound of Clause 354 or a salt, hydrate, or solvate thereof; wherein T2 is N-maleimidil.

[696] Clause 356. A compound of Clause 355 or a salt, hydrate, or solvate thereof; wherein T2 is

[697] Clause 357. A compound according to any of Clauses 324 - 353 or a salt, hydrate, or solvate thereof; where T2 is an -L3-CB group.

[698] Clause 358. A compound according to any of Clauses 324 - 353, and 357, or a salt, hydrate, or Petition 870250092139, dated 08 / 10 / 2025, pp. 194 / 254 187 / 246 solvate of the same; wherein L3 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety.

[699] Clause 359. A compound according to any of Clauses 324 - 353, and 357 - 358, or a salt, hydrate, or solvate thereof; wherein L3 is a residue of a maleimidyl moiety. compound according to any and 357 - 359, or a salt, hydrate, T2 is selected from

[700] Clause 360. One of Clauses 324 - 353, or solvato thereof; in which group consisting of THE

[701] Clause 361. One of Clauses 324 - 353, or solvato of the same; in which

[702] Clause 362. One of Clauses 324 - 353, composed according to any and 357 - 360, or a salt, hydrate, CB is a protein. compound according to any and 357 - 361, or a salt, hydrate, or solvate thereof; wherein CB is an antibody or a diabody.

[703] Clause 363. A compound according to any of Clauses 324 - 353, and 357 - 362, or a salt, hydrate, or solvate thereof; wherein CB is a diacorporeal.

[704] Clause 364. A compound according to any of Clauses 324 - 353, and 357 - 363, or a salt, hydrate, or solvate thereof; wherein CBé AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[705] Clause 365. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 195 / 254 188 / 246 one of Clauses 324 - 353, and 357 - 364, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom or nitrogen atom, wherein the sulfur atom or nitrogen atom forms part of CB.

[706] Clause 366. A compound according to any of Clauses 324 - 353, and 357 - 365, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom, wherein the sulfur atom is part of CB.

[707] Clause 367. A compound according to any of Clauses 324 - 353, and 357 - 365, or a salt, hydrate, or solvate thereof; wherein CB is linked to the remainder of T2 by means of a sulfur atom that is part of CB, wherein the sulfur atom is part of a cysteine ​​residue.

[708] Clause 368. A compound according to any of Clauses 324 - 353, and 357 - 367, or a salt, hydrate, or solvate thereof; wherein T3 is a polymer.

[709] Clause 369. A compound according to any of Clauses 324 - 353, and 357 - 368, or a salt, hydrate, or solvate thereof; wherein T3 is a polymer comprising a polyethylene glycol moiety.

[710] Clause 370. A compound according to any of Clauses 324 - 353, and 357 - 369, or a salt, hydrate, or solvate thereof; wherein T3 comprises a portion -(CH2CH2O-)y-T4, wherein y is an integer in a range from 1 to 50, and T4 is according to Radical Group 1, Radical Group 3, Radical Group 4, or Radical Group 5 as defined herein; preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, more Petition 870250092139, dated 08 / 10 / 2025, pp. 196 / 254 189 / 246 preferably still in a range of 20 to 30, even more preferably in a range of 23 to 25, and most preferably y is 24.

[711] Clause 371. A compound according to any of Clauses 324 - 370, or a salt, hydrate, or solvate thereof; where T3 is a -(CH2CH2-O-)y-T4 moiety.

[712] Clause 372. A compound according to any of Clauses 324 - 371, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 10 to 40.

[713] Clause 373. A compound according to any of Clauses 324 - 372, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 12 to 37.

[714] Clause 374. A compound according to any of Clauses 324 - 373, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 15 to 35.

[715] Clause 375. A compound according to any of Clauses 324 - 374, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 20 to 30.

[716] Clause 376. A compound according to any of Clauses 324 - 375, or a salt, hydrate, or solvate thereof; where y is an integer in a range from 23 to 25.

[717] Clause 377. A compound according to any of Clauses 324 - 376, or a salt, hydrate, or solvate thereof; where y is 24.

[718] Clause 378. A compound according to any of Clauses 324 - 377, or a salt, hydrate, or solvate thereof; wherein T4 is methyl.

[719] Clause 379. A compound according to any of Clauses 324 - 378, or a salt, hydrate, or solvate thereof; where T3 is a -(CH2CH2-O-)24-CH3 moiety.

[720] Clause 380. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 197 / 254 190 / 246 one of Clauses 324 - 379, or a salt, hydrate, or solvate thereof; wherein R48 is selected from the group consisting of -OH, -O-acetyl, -O-C1-4alkyl, halogen, active carbonate, and a releasable group.

[721] Clause 381. A compound according to any of Clauses 324 - 380, or a salt, hydrate, or solvate thereof; where R48 is a releasable group.

[722] Clause 382. A compound according to any of Clauses 324 - 381, or a salt, hydrate, or solvate thereof; wherein said releasable group is -(Y1-C(=Y2))i(SP)j-CA; wherein each of Y1 and Y2 are selected independently of O and S; CA is the construct A, which is a payload; SP is a ligand; j is 0 or 1; i is 0 or 1; if i is 0, -(SP)j-CA is linked to the rest of the compound by means of O or S, which is part of -(SP)j-CA; if i is 1, -(SP)j-CA is linked to -C(=Y2)- by means of O, S, a secondary N, or a tertiary N, which is part of -(SP)j-CA.

[723] Clause 383. A compound according to any of Clauses 324 - 382, ​​or a salt, hydrate, or solvate thereof; wherein the said releasable group is -(OC(=O))i(SP)j-CA.

[724] Clause 384. A compound according to any of Clauses 324 - 383, or a salt, hydrate, or solvate thereof; wherein the said releasable group is -OC(=O)-(SP)jCA.

[725] Clause 385. A compound according to any of Clauses 324 - 384, or a salt, hydrate, or solvate thereof; where SP is according to Radical Group 2.

[726] Clause 386. A compound according to any of Clauses 324 - 385, or a salt, hydrate, or solvate thereof; wherein SP is a self-immolating ligand. Petition 870250092139, dated 08 / 10 / 2025, pp. 198 / 254 191 / 246

[727] Clause 387. A compound according to any of Clauses 324 - 386, or a salt, hydrate, or solvate thereof; wherein the said releasable group is —O—C(=O)—CA.

[728] Clause 388. A compound according to any of Clauses 324 - 387, or a salt, hydrate, or solvate thereof; wherein CA is linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of CA, forming a carbamate.

[729] Clause 389. A compound according to any of Clauses 324 - 388, or a salt, hydrate, or solvate thereof; wherein CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[730] Clause 390. A compound according to any of Clauses 324 - 389, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE).

[731] Clause 391. A compound according to any of Clauses 324 - 390, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE) linked to the -OC(=O)- portion by means of a secondary or tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[732] Clause 392. A compound according to any of Clauses 324 - 391, or a salt, hydrate, or solvate thereof; wherein CA is monomethyl auristatin E (MMAE) linked to the -OC(=O)- portion by means of a tertiary nitrogen atom that is part of MMAE, forming a carbamate.

[733] Clause 393. A compound according to any of Clauses 324 - 392, or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (M): Petition 870250092139, dated 08 / 10 / 2025, pp. 199 / 254 192 / 246 τ2L' l'l Cd τ Formula (M).

[734] Clause 394. A compound of Clause 393, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[735] Clause 395. A compound according to any of Clauses 393 - 394, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[736] Clause 396. A compound according to any of Clauses 393 - 395, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[737] Clause 397. A compound according to any of Clauses 393 - 396, or a salt, hydrate, or solvate thereof; where R48 is:

[738] Clause 398. A compound according to any of Clauses 393 - 397, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is: Petition 870250092139, dated 08 / 10 / 2025, pp. 200 / 254 193 / 246

[739] Clause 399. A compound according to any of Clauses 324 - 392, or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (N): tu-LL~L—T3 Formula (N).

[740] Clause 400. A compound of Clause 399, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[741] Clause 401. A compound according to any of Clauses 399 - 400, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[742] Clause 402. A compound according to any of Clauses 399 - 401, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[743] Clause 403. A compound according to any of Clauses 399 - 402, or a salt, hydrate, or solvate thereof; where R48 is: Petition 870250092139, dated 08 / 10 / 2025, pp. 201 / 254 194 / 246

[744] Clause 404. A compound according to any of Clauses 399 403, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is:

[745] Clause 405 A compound according to any of Clauses 324–392, or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (O): R48H^ The ( Ti-fN' XJOFormula (O).

[746] Clause 406. A compound of Clause 405, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[747] Clause 407. A compound according to any of Clauses 405 - 406, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[748] Clause 408. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 202 / 254 195 / 246 one of Clauses 405 - 407, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[749] Clause 409. A compound according to any of Clauses 405 - 408, or a salt, hydrate, or solvate thereof; where R48 is:

[750] Clause 410 A compound according to any of Clauses 405–409, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is:

[751] Clause 411. A compound according to any of Clauses 324 - 392, and 405 - 410 or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (3): Petition 870250092139, dated 08 / 10 / 2025, pp. 203 / 254 196 / 246 Formula (3);

[752] where y is such as is an integer in a range from 4 to an integer in a range from 4 to defined in Clause 306; xa 12; preferably x is 8, more preferably x is an integer in a range from 4 to 6.

[753] Clause 412. A compound according to any of Clauses 324 - 411, or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (P): Formula (P).

[754] Clause 413. A compound of Clause 412, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[755] Clause 414. A compound according to any of Clauses 412 - 413, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, Petition 870250092139, dated 08 / 10 / 2025, pp. 204 / 254 197 / 246 preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[756] Clause 415. A compound according to any of Clauses 412 - 414, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[757] Clause 416. A compound according to any of Clauses 412 - 414, or a salt, hydrate, or solvate thereof; where R48 is:

[758] Clause 417. A compound according to any of Clauses 412 - 416, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is:

[759] Clause 418. A compound according to any of Clauses 412 - 417, or a salt, hydrate, or solvate thereof; where x is an integer from 3 to 8.

[760] Clause 419. A compound according to any of Clauses 412 - 418, or a salt, hydrate, or solvate thereof; where x is an integer from 4 to 6.

[761] Clause 420. A compound according to any of Clauses 412 - 419, or a salt, hydrate, or solvate thereof; where x is 5. Petition 870250092139, dated 08 / 10 / 2025, pp. 205 / 254 198 / 246

[762] Clause 421. A compound according to any of Clauses 412 - 420, or a salt, hydrate, or solvate thereof; where y is an integer from 12 to 37.

[763] Clause 422. A compound according to any of Clauses 412 - 420, or a salt, hydrate, or solvate thereof; where y is an integer from 20 to 30.

[764] Clause 423. A compound according to any of Clauses 412 - 422, or a salt, hydrate, or solvate thereof; where y is an integer from 23 to 25.

[765] Clause 424. A compound according to any of Clauses 412 - 423, or a salt, hydrate, or solvate thereof; where y is 24.

[766] Clause 425. A compound according to any of Clauses 324 - 411, or a salt, hydrate, or solvate thereof; wherein said compound is of Formula (Q): Formula (Q).

[767] Clause 426. A compound of Clause 425, or a salt, hydrate, or solvate thereof; where T1 is -OH.

[768] Clause 427. A compound according to any of Clauses 425-426, or a salt, hydrate, or solvate thereof; where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), Petition 870250092139, dated 08 / 10 / 2025, pp. 206 / 254 199 / 246 exatecane, or an exatecane derivative.

[769] Clause 428. A compound according to any of Clauses 425 - 427, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[770] Clause 429. A compound according to any of Clauses 425 - 428, or a salt, hydrate, or solvate thereof; where R48 is:

[771] Clause 430. A compound according to any of Clauses 425 - 429, or a salt, hydrate, or solvate thereof; where T1 is -OH, and R48 is:

[772] Clause 431. A compound according to any of Clauses 425 - 430, or a salt, hydrate, or solvate thereof; where x is an integer from 3 to 8.

[773] Clause 432. A compound according to any of Clauses 425 - 431, or a salt, hydrate, or solvate thereof; where x is an integer from 4 to 6.

[774] Clause 433. A compound according to any of Clauses 425 - 432, or a salt, hydrate, or solvate thereof; where x is 5.

[775] Clause 434. A compound according to any Petition 870250092139, dated 08 / 10 / 2025, pp. 207 / 254 200 / 246 one of Clauses 425 - 433, or a salt, hydrate, or solvate thereof; where y is an integer from 12 to 37.

[776] Clause 435. A compound according to any of Clauses 425 - 434, or a salt, hydrate, or solvate thereof; where y is an integer from 20 to 30.

[777] Clause 436. A compound according to any of Clauses 425 - 435, or a salt, hydrate, or solvate thereof; where y is an integer from 23 to 25.

[778] Clause 437. A compound according to any of Clauses 425 - 436, or a salt, hydrate, or solvate thereof; where y is 24.

[779] Clause 438. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein the said compound is: OH NH N' . NH Egg HOHNXO

[780] Clause 439. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein the said compound is: Petition 870250092139, dated 08 / 10 / 2025, pp. 208 / 254 201 / 246

[781] Clause 440. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein the said compound is:

[782] Clause 441. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein said compound is: hoi W THE THE THE NH7OH

[783] Clause 442. A compound of Clause 441, or a salt, hydrate, or solvate thereof; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers Petition 870250092139, dated 08 / 10 / 2025, pp. 209 / 254 202 / 246 has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the maleimidyl group through a sulfur atom that is part of CB, preferably the sulfur atom is part of a cysteine ​​residue.

[784] Clause 443. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein the said compound is:

[785] Clause 444. A compound of Clause 443, or a salt, hydrate, or solvate thereof; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the maleimidyl group by means of a sulfur atom that is part of CB, preferably the sulfur atom is part of a cysteine ​​residue.

[786] Clause 445. A compound of Clause 1, or a salt, hydrate, or solvate thereof; wherein the said compound is: Petition 870250092139, dated 08 / 10 / 2025, pp. 210 / 254 203 / 246 OH NH N' NH HO'7 H' O. O CBHN O

[787] Clause 446. A compound of Clause 445, or a salt, hydrate, or solvate thereof; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the maleimidyl group by means of a sulfur atom that is part of CB, preferably the sulfur atom is part of a cysteine ​​residue.

[788] Clause 447. A conjugate, or a salt, hydrate, or solvate thereof, wherein the conjugate comprises a protein conjugated to at least one compound according to any one of Clauses 1–446, wherein T2 is a residue of a bioconjugation moiety, and said protein and said compound are conjugated by means of T2.

[789] Clause 448. A conjugate of Clause 447, or a salt, hydrate, or solvate thereof; wherein the protein is a diabody or an antibody.

[790] Clause 449. A conjugate according to any of Clauses 447 - 448, or a salt, hydrate, or solvate thereof; wherein the protein is a diacorporeal.

[791] Clause 450. A conjugate according to any of Clauses 447–449, or a salt, hydrate, or solvate thereof; wherein the protein is AVP0458 consisting of two monomers, wherein each of the two monomers has a Petition 870250092139, dated 08 / 10 / 2025, pp. 211 / 254 204 / 246 amino acid sequence according to SEQ ID NO: 1.

[792] Clause 451. A conjugate according to any of Clauses 447 - 450, or a salt, hydrate, or solvate thereof; wherein the protein is conjugated to a maximum of 12 of said compounds.

[793] Clause 452. A conjugate according to any of Clauses 447 - 451, or a salt, hydrate, or solvate thereof; wherein the protein is conjugated to a maximum of 8 of said compounds.

[794] Clause 453. A conjugate according to any of Clauses 447 - 452, or a salt, hydrate, or solvate thereof; wherein the protein is conjugated to a maximum of 4 of said compounds.

[795] Clause 454. A conjugate according to any of Clauses 447 - 452, or a salt, hydrate, or solvate thereof; wherein the protein is conjugated to about 4 of said compounds.

[796] Clause 455. A conjugate according to any of Clauses 447 - 454, or a salt, hydrate, or solvate thereof; wherein said protein and said compound are conjugated by means of T2e a sulfhydryl residue of said protein, a hydroxyl residue of said protein, or an amine residue of said protein.

[797] Clause 456. A conjugate according to any of Clauses 447 - 455, or a salt, hydrate, or solvate thereof; wherein said protein and said compound are conjugated by means of T2 and a sulfhydryl residue of said protein.

[798] Clause 457. A conjugate according to any of Clauses 447 - 456, or a salt, hydrate, or solvate thereof; wherein T2 is a residue of a maleimidyl moiety or Petition 870250092139, dated 08 / 10 / 2025, pp. 212 / 254 205 / 246 a residue of an N-hydroxysuccinimidyl moiety.

[799] Clause 458. A conjugate according to any of Clauses 447 - 457, or a salt, hydrate, or solvate thereof; wherein T2 is a residue of a maleimidyl moiety.

[800] Clause 459. A conjugate according to any of Clauses 447 - 458, or a salt, hydrate, or solvate thereof; wherein said protein and said compound are conjugated by means of T2 and a sulfhydryl residue of said protein; and T2 is a residue of a maleimidyl moiety.

[801] Clause 460. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 1 - 181.

[802] Clause 461. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 182 - 227.

[803] Clause 462. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 228 - 295.

[804] Clause 463. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 296 - 297.

[805] Clause 464. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 298 - 299.

[806] Clause 465. A conjugate in accordance with any Petition 870250092139, dated 08 / 10 / 2025, pp. 213 / 254 206 / 246 one of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 300 - 301.

[807] Clause 466. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 302 - 303.

[808] Clause 467. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 304 - 305.

[809] Clause 468. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 306 - 307.

[810] Clause 469. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 308 - 309.

[811] Clause 470. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 310 - 311.

[812] Clause 471. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 312 - 317.

[813] Clause 472. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 318 - 323. Petition 870250092139, dated 08 / 10 / 2025, pp. 214 / 254 207 / 246

[814] Clause 473. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 324 - 392.

[815] Clause 474. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 393 - 404.

[816] Clause 475. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 405 - 410.

[817] Clause 476. A conjugate in accordance with any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in Clause 411.

[818] Clause 477. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 412 - 424.

[819] Clause 478. A conjugate according to any of Clauses 447 - 459, or a salt, hydrate, or solvate thereof; wherein said compound is as defined in any of Clauses 425 - 437.

[820] Clause 479. A conjugate according to any of Clauses 447 - 478, or a salt, hydrate, or solvate thereof; wherein the conjugate is Petition 870250092139, dated 08 / 10 / 2025, pp. 215 / 254 208 / 246 CB NH HO. HN NH THE -1CJ where CJ is in a range of 1 to 12, where preferably CJ is from 1 to 10, more preferably from 2.5 to 8, even more preferably 3 to 6, and most preferably 3.5 to 4.

[821] Clause 480. A conjugate of Clause 479, or a salt, hydrate, or solvate thereof; wherein CB is a protein.

[822] Clause 481. A conjugate of Clause 480, or a salt, hydrate, or solvate thereof; wherein the protein is an antibody or a diabody.

[823] Clause 482. A conjugate of Clause 481, or a salt, hydrate, or solvate thereof; wherein the protein is a diacorporeal.

[824] Clause 483. A conjugate of Clause 482, or a salt, hydrate, or solvate thereof; wherein the protein is AVP0458 consists of two monomers, each of which has an amino acid sequence according to SEQ ID NO: 1.

[825] Clause 484. A conjugate according to any of Clauses 479 - 483, or a salt, hydrate, or solvate thereof; where CJ is from 2 to 10.

[826] Clause 485. A conjugate according to any of Clauses 479 - 484, or a salt, hydrate, or solvate thereof; where CJ is from 2.5 to 8. Petition 870250092139, dated 08 / 10 / 2025, pp. 216 / 254 209 / 246

[827] Clause 486. A conjugate according to any of Clauses 479 - 485, or a salt, hydrate, or solvate thereof; where CJ is from 3 to 6.

[828] Clause 487. A conjugate according to any of Clauses 479 - 486, or a salt, hydrate, or solvate thereof; where CJ is 3.5 to 4.

[829] Clause 488. A conjugate according to any of Clauses 479 - 487, or a salt, hydrate, or solvate thereof; where CJ is about 4.

[830] Clause 489. A conjugate according to any of Clauses 479 - 488, or a salt, hydrate, or solvate thereof; wherein CB is linked to each maleimidyl group by means of a sulfur atom.

[831] Clause 490. A conjugate according to any of Clauses 479 - 489, or a salt, hydrate, or solvate thereof; wherein the sulfur atom forms part of a cysteine ​​residue.

[832] Clause 491. A conjugate according to any of Clauses 447 - 490, or a salt, hydrate, or solvate thereof; wherein the conjugate is where CJ is in a range from 1 to 12.

[833] Clause 492. A conjugate of Clause 491, or a salt, hydrate, or solvate thereof; wherein CB is a protein. Petition 870250092139, dated 08 / 10 / 2025, pp. 217 / 254 210 / 246

[834] Clause 493. A conjugate of Clause 492, or a salt, hydrate, or solvate thereof; wherein the protein is an antibody or a diabody.

[835] Clause 494. A conjugate of Clause 493, or a salt, hydrate, or solvate thereof; wherein the protein is a diacorporeal.

[836] Clause 495. A conjugate of Clause 494, or a salt, hydrate, or solvate thereof; wherein the protein is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[837] Clause 496. A conjugate according to any of Clauses 491 - 495, or a salt, hydrate, or solvate thereof; where CJ is from 2 to 10.

[838] Clause 497. A conjugate according to any of Clauses 491 - 496, or a salt, hydrate, or solvate thereof; where CJ is from 2.5 to 8.

[839] Clause 498. A conjugate according to any of Clauses 491 - 497, or a salt, hydrate, or solvate thereof; where CJ is from 3 to 6.

[840] Clause 499. A conjugate according to any of Clauses 491 - 498, or a salt, hydrate, or solvate thereof; where CJ is 3.5 to 4.

[841] Clause 500. A conjugate according to any of Clauses 491 - 499, or a salt, hydrate, or solvate thereof; where CJ is about 4.

[842] Clause 501. A conjugate according to any of Clauses 491 - 500, or a salt, hydrate, or solvate thereof; wherein CB is linked to each maleimidyl group by means of a sulfur atom.

[843] Clause 502. A conjugate in accordance with any Petition 870250092139, dated 08 / 10 / 2025, pp. 218 / 254 211 / 246 one of Clauses 491 - 501, or a salt, hydrate, or solvate thereof; wherein the sulfur atom forms part of a cysteine ​​residue.

[844] Clause 503. A conjugate according to any of Clauses 447 - 490, or a salt, hydrate, or solvate thereof; wherein the conjugate is CJ

[845] where CJ is in a range of 1 to 12.

[846] Clause 504. A conjugate of Clause 503, or a salt, hydrate, or solvate thereof; wherein CB is a protein.

[847] Clause 505. A conjugate of Clause 504, or a salt, hydrate, or solvate thereof; wherein the protein is an antibody or a diabody.

[848] Clause 506. A conjugate of Clause 505, or a salt, hydrate, or solvate thereof; wherein the protein is a diacorporeal.

[849] Clause 507. A conjugate of Clause 506, or a salt, hydrate, or solvate thereof; wherein the protein is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1.

[850] Clause 508. A conjugate according to any of Clauses 503 - 507, or a salt, hydrate, or solvate thereof; where CJ is from 2 to 10. Petition 870250092139, dated 08 / 10 / 2025, pp. 219 / 254 212 / 246

[851] Clause 509. A conjugate according to any of Clauses 503 - 508, or a salt, hydrate, or solvate thereof; where CJ is from 2.5 to 8.

[852] Clause 510. A conjugate according to any of Clauses 503 - 509, or a salt, hydrate, or solvate thereof; where CJ is from 3 to 6.

[853] Clause 511. A conjugate according to any of Clauses 503 - 510, or a salt, hydrate, or solvate thereof; where CJ is 3.5 to 4.

[854] Clause 512. A conjugate according to any of Clauses 503 - 511, or a salt, hydrate, or solvate thereof; where CJ is about 4.

[855] Clause 513. A conjugate according to any of Clauses 503 - 512, or a salt, hydrate, or solvate thereof; wherein CB is linked to each maleimidyl group by means of a sulfur atom.

[856] Clause 514. A conjugate according to any of Clauses 503 - 513, or a salt, hydrate, or solvate thereof; wherein the sulfur atom forms part of a cysteine ​​residue.

[857] Clause 515. A composition comprising: (a) a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; and / or (b) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof.

[858] Clause 516. A composition of Clause 515, wherein the composition is a pharmaceutical composition.

[859] Clause 517. A composition according to any of Clauses 515-516, wherein said composition comprises a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate of Petition 870250092139, dated 08 / 10 / 2025, pp. 220 / 254 213 / 246 same.

[860] Clause 518. A composition in accordance with any of Clauses 515 - 517, wherein said composition comprises the conjugate in accordance with any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof.

[861] Clause 519. A composition according to any of Clauses 515 - 518, wherein said composition comprises: (a) a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; and (b) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof.

[862] Clause 520. A composition in accordance with any of Clauses 515–519, wherein said composition comprises (a) a compound in accordance with any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; and (b) the enantiomer of said compound, or the salt, hydrate, or solvate thereof.

[863] Clause 521. A composition of Clause 520, wherein said composition comprises said compound and said enantiomer in a weight ratio of 1:10 to 10:1, preferably 1:8 to 8:1, more preferably 1:7 to 7:1, even more preferably 1:6 to 6:1, even more preferably 1:5 to 5:1, even more preferably 1:4 to 4:1, even more preferably 1:3 to 3:1, even more preferably 1:2 to 2:1, even more preferably 1:1.5 to 1.5:1, and most preferably about 1:1.

[864] Clause 522. A composition of Clause 521, wherein said composition is a racemic mixture of said compound and said enantiomer. Petition 870250092139, dated 08 / 10 / 2025, pp. 221 / 254 214 / 246

[865] Clause 523. A composition in accordance with any of Clauses 515 - 522, wherein said composition further comprises a carrier.

[866] Clause 524. A composition in accordance with any of Clauses 515 - 523, wherein said composition further comprises a pharmaceutically acceptable carrier.

[867] Clause 525. A combination of (A1) a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; (A2) a conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; and / or (A3) a composition according to any of Clauses 515 - 524; with (B) a diene or salt, solvate, or hydrate thereof.

[868] Clause 526. The combination according to Clause 525 of (A1)

[869] Clause and (B). 527. The combination according to Clause 525 of (A2)

[870] Clause and (B). 528. The combination according to Clause 525 of (A3)

[871] Clause and (B). 529. The combination according to Clause 525 of (A1)

[872] Clause, (A2), and 530. A (B). combination according to Clause 525 of (A1)

[873] Clause, (A3), and 531. A (B). combination according to Clause 525 of (A2)

[874] Clause , (A3), and 532. A (B). combination according to Clause 525 of (A1), (A2), (A3), and (B).

[875] Clause 533. The combination in accordance with any of Clauses 525 - 532, where the diene is a tetrazine.

[876] Clause 534. The combination in accordance with any Petition 870250092139, dated 08 / 10 / 2025, pp. 222 / 254 215 / 246 one of Clauses 525 - 535, where the diene is selected from the group consisting of: or a salt, hydrate, and / or solvate thereof.

[877] Clause 535. The combination of Clause 534, where the diene is:

[878] or a salt, hydrate, and / or solvate thereof.

[879] Clause 536. The combination of Clause 534, where the diene is: Petition 870250092139, dated 08 / 10 / 2025, pp. 223 / 254 216 / 246 O

[880] or a salt, hydrate, and / or solvate thereof.

[881] Clause 537. The combination of Clause 534, which the diene is: in

[882] or a salt, hydrate, and / or solvate thereof.

[883] Clause 538. The combination of Clause 534, which the diene is: in Petition 870250092139, dated 08 / 10 / 2025, pp. 224 / 254 217 / 246

[884] or a salt, hydrate, and / or solvate thereof.

[885] Clause 539. The combination of Clause 534, where the diene is:

[886] or a salt, hydrate, and / or solvate thereof.

[887] Clause 540. The compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; the composition according to any of Clauses 515-524; or the combination according to any of Clauses 525-539; for use as a medicament.

[888] Clause 541. The compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; for use as a medicament.

[889] Clause 542. The conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; for use as a medicine.

[890] Clause 543. The composition in accordance with any of Clauses 515 - 524 for use as a medicament.

[891] Clause 544. The combination in accordance with any of Clauses 525 - 539 for use as a medicine.

[892] Clause 545. The compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate of Petition 870250092139, dated 08 / 10 / 2025, pp. 225 / 254 218 / 246 itself; the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; the composition according to any of Clauses 515-524; or the combination according to any of Clauses 525-539; for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[893] Clause 546. The compound or the salt, hydrate, or solvate thereof; conjugate or the salt, hydrate, or solvate thereof; the composition; or the combination; for use in accordance with Clause 545, where the individual is a human.

[894] Clause 547. The compound or the salt, hydrate, or solvate thereof; conjugated or the salt, hydrate, or solvate thereof; the composition; or the combination; for use in accordance with any of Clauses 545 - 546, wherein the disease is cancer.

[895] Clause 548. The compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[896] Clause 549. The conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[897] Clause 550. The composition according to any of Clauses 515 - 524 for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[898] Clause 551. The combination in accordance with any Petition 870250092139, dated 08 / 10 / 2025, pages 226 / 254 219 / 246 one of Clauses 525 - 539; for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

[899] Clause 552. A method of treating a disease in an individual, wherein said method comprises the step of administering to said individual: (a) the compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; (b) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; (c) the composition according to any of Clauses 515 - 524; and / or (d) the combination according to any of Clauses 525 - 539; preferably the individual is a human; preferably the disease is cancer.

[900] Clause 553. Use of (a) a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; (b) a conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; (c) a composition according to any of Clauses 515 to 524; and / or (d) a combination according to any of Clauses 525 to 539;

[901] for the manufacture of a medicament for the treatment of a disease in an individual; preferably the individual is a human; preferably the disease is cancer.

[902] Clause 554. Use of a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; for the manufacture of a medicament for the treatment of a disease in an individual; preferably the individual is a human; preferably the disease is cancer.

[903] Clause 555. Use of a conjunction in accordance with Petition 870250092139, dated 08 / 10 / 2025, pages 227 / 254 220 / 246 any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; for the manufacture of a medicament for the treatment of a disease in an individual; preferably the individual is a human; preferably the disease is cancer.

[904] Clause 556. Use of a composition in accordance with any of Clauses 515 - 524 for the manufacture of a medicament for the treatment of a disease in an individual; preferably the individual is a human; preferably the disease is cancer.

[905] Clause 557. Use of the combination in accordance with any of Clauses 525 - 539 for the manufacture of a medicament for the treatment of a disease in an individual; preferably the individual is a human; preferably the disease is cancer.

[906] Clause 558. A non-therapeutic method of responding:

[907] (ia) the compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; (iia) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; and / or (iiia) the composition according to any of Clauses 515 - 524; with a diene or salt, solvate, or hydrate thereof, wherein the said method comprises the step of contacting (ia), (iia), or (iiia) the said diene or salt, solvate, or hydrate thereof; preferably the said non-therapeutic method is an in vitro method; and preferably the said diene is a tetrazine.

[908] Clause 559. A non-therapeutic method for reacting the compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; with a diene or salt, solvate, or hydrate thereof, in which the Petition 870250092139, dated 08 / 10 / 2025, pp. 228 / 254 221 / 246 said method comprises the step of contacting (ia) said diene or salt, solvate, or hydrate thereof; preferably said non-therapeutic method is an in vitro method; and preferably said diene is a tetrazine.

[909] Clause 560. A non-therapeutic method for reacting (iia) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; with a diene or salt, solvate, or hydrate thereof, wherein said method comprises the step of contacting (iia) said diene or salt, solvate, or hydrate thereof; preferably said non-therapeutic method is an in vitro method; and preferably said diene is a tetrazine.

[910] Clause 561. A non-therapeutic method for reacting (iiia) the composition according to any of Clauses 515 - 524; with a diene or salt, solvate, or hydrate thereof, wherein said method comprises the step of contacting (iiia) said diene or salt, solvate, or hydrate thereof; preferably said non-therapeutic method is an in vitro method; and preferably said diene is a tetrazine.

[911] Clause 5 62. A non-therapeutic use of: (a) the compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; (b) the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; (c) the composition according to any of Clauses 515 - 524; and / or (d) the combination according to any of Clauses 525 - 539; in a click reaction.

[912] Clause 563. A non-therapeutic use of the compound Petition 870250092139, dated 08 / 10 / 2025, pp. 229 / 254 222 / 246 in accordance with any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; in a click reaction.

[913] Clause 564. A non-therapeutic use of the conjugate according to any of Clauses 447 to 514, or the salt, hydrate, or solvate thereof; in a click reaction.

[914] Clause 565. A non-therapeutic use of the composition in accordance with any of Clauses 515-524; in a click reaction.

[915] Clause 566. A non-therapeutic use of the combination in accordance with any of Clauses 525-539; in a click reaction.

[916] Clause 567. A non-therapeutic use of any of Clauses 562 - 566, wherein the click reaction occurs between a compound according to any of Clauses 1 to 446, or the salt, hydrate, or solvate thereof; and a diene; wherein the diene is preferably a tetrazine.

[917] Clause 5 68. A method for the synthesis of a compound according to any of Clauses 1 - 446, wherein said method comprises coupling a compound of Formula (R) to a compound of Formula (S): R48HN o h2n Formula (R);

[918] where R48 is as defined in any of Clauses 147 - 166, and 281 - 295, T1 is as defined in any of Clauses 167 - 179, and 246 - 250, and is such Petition 870250092139, dated 08 / 10 / 2025, pp. 230 / 254 223 / 246 as defined in any of Clauses 271, and 273 27 8; tL >S10xFormula (S);

[919] where T2 is as defined in any of Clauses 1, 49 - 69, and 251 - 268; x is as defined in any of Clauses 216 - 218; and where S10 is -COOH or an active ester.

[920] Clause 569. A method of Clause 568, where T2 is a bioconjugation moiety.

[921] Clause 570. A method of Clause 568, in which T2é:

[922] Clause 571. A method according to any of Clauses 568 - 570, where T1 is -OH.

[923] Clause 572. A method according to any of Clauses 568 - 571, where R48 is -OC(O)-CA, where CA is a drug, preferably CA is monomethyl auristatin E (MMAE), exatecan, or an exatecan derivative.

[924] Clause 573. A method according to any of Clauses 568 - 572, where R48 is: OH NH N' NH O. O

[925] Clause 574. A method in accordance with any of Clauses 568 - 573, where x is an integer from 4 to 6. Petition 870250092139, dated 08 / 10 / 2025, pp. 231 / 254 224 / 246

[926] Clause 575. A method in accordance with any of Clauses 568 - 574, where x is 5.

[927] Clause 576. A method according to any of Clauses 568 - 575, where y is an integer in a range from 10 to 40.

[928] Clause 577. A method conforming to any of Clauses 568 - 576, where y is an integer in a range from 15 to 35.

[929] Clause 578. A method in accordance with any of Clauses 568 - 577, where y is an integer in a range of 20 to 30.

[930] Clause 579. A method according to any of Clauses 568 - 578, where y is an integer in a range from 23 to 25.

[931] Clause 580. A method in accordance with any of Clauses 568 - 579, where y is 24.

[932] Clause 581. A method according to any of Clauses 568 - 580, wherein in Formula (S), S10 is COOH.

[933] Clause 582. A method of Clause 581, in which the compound of Formula (S) is brought into contact with at least one coupling reagent, preferably in the presence of a base.

[934] Clause 583. A method of Clause 582, wherein at least one coupling reagent is selected from the group consisting of dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), ethyl(N',N'-dimethylamino)propylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt), 4-(N,N-dimethylamino)pyridine (DMAP), (benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), (benzotriazole hexafluorophosphate) Petition 870250092139, dated 08 / 10 / 2025, pages 232 / 254 225 / 246 1-yloxy)tripyrrolidinophosphonium, (7azabenzotriazole-1-ylloxy)tripyrrolidinophosphonium hexafluorophosphate (PyAOP), bromotripyrrolidinophosphonium hexafluorophosphate (PyBrOP), O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), tetrafluoroborate of O(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium (TBTU), O(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), O-(7-Azabenzotriazol-1-yl)N,N,N,,N,-tetramethyluronium tetrafluoroborate (TATU), O-(6Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HCTU), O-[(Ethoxycarbonyl)cyanomethyl enamine]-N,N,N,,N'-tetramethyluronium tetrafluoroborate (TOTU), (1-cyano-2-ethoxy-2-oxoethyldenoaminose) dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), O-(N-succinimidyl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TSTU), O-(5-Norbornene-2,3-dicarboximide)N,N,N,,N'-tetramethyluronium tetrafluoroborate (TNTU), O(1,2-Dihydro-2-oxo-1-pyridyl-N,N,N',N'-tetramethyluronium,N,tetrafluoroborate,N,TPN,N,NTetramethyl-O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl)uronium tetrafluoroborate (TDBTU), 3-(Diethylphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT), carbonyldiimidazole (CDI), N,N,N',N'-tetramethylchloroform-amide hexafluorophosphate (TCFH), thionyl chloride, oxalyl chloride, cyanuric chloride, cyanuric fluoride, phosphorus trichloride, phosphorus pentachloride, N-hydroxysuccinimide, N-hydroxysulfosuccinimide, and combinations thereof.

[935] Clause 584. A method according to any one of Clauses 568–580, wherein the active ester is selected from the group consisting of -C(O)O-Nsuccinimidyl, -C(O)O-pentafluorophenyl, -C(O)O Petition 870250092139, dated 08 / 10 / 2025, pages 233 / 254 226 / 246 tetrafluorophenyl, -C(O)O-4-nitrophenyl, and -C(O)Cl; preferably the active ester is -C(O)ON-succinimidyl, or -C(O)O-pentafluorophenyl.

[936] Clause 585. A method according to any of Clauses 568 - 580, and 584, wherein in Formula (S), S10 is an active ester.

[937] Clause 586. A method according to any of Clauses 568 - 585, wherein coupling is performed in the presence of a basis.

[938] Clause 587. A method of Clause 586, in which coupling is performed in the presence of a non-nucleophilic base.

[939] Clause 588. A method according to any of Clauses 568 - 587, wherein the coupling is carried out at a temperature of -20 °C to 80 °C, preferably 0 °C to 60 °C, more preferably 4 °C to 50 °C, more preferably still 10 °C to 40 °C, and most preferably 15 °C to 30 °C.

[940] Clause 589. A method according to any of Clauses 568 - 587, wherein the coupling is carried out in the presence of a solvent, wherein the solvent is preferably an organic solvent.

[941] Clause 590. A method for the synthesis of a compound according to any of Clauses 1 - 446, wherein said method comprises coupling a compound of Formula (T) to a compound of Formula (U): t\. s11

[942] where R48 R48 Formula (T); ; is as defined in any of the Petition 870250092139, dated 08 / 10 / 2025, pp. 234 / 254 227 / 246 Clauses 147 - 166, and 281 - 295; T1 is as defined in any of Clauses 167 - 179, and 246 - 250; and S11 is COOH or an active ester; nh2 THE y Formula (U);

[943] where T2 is as defined in any of the Clauses 1, 49 69, and 251-268; x is as defined in any of Clauses 216-218; ey is as defined in any of Clauses 271, and 273-278.

[944] Clause 591. A method of Clause 590, in which T2 is a bioconjugation moiety.

[945] ...

Claims

CLAIMS 1. Compound characterized in that it has a structure according to Formula (1): 2 1 T—L- Formula (1); wherein: L1 is selected from the group consisting of linear or branched C4-C12 alkylene, C3-C8 (hetero)cycloalkylene, C6-C12 arylene, and C4-C11 heteroarylene; L2a, L2b, and L2d are each independently a ligand; L2c is selected from the group consisting of C1-C8 (hetero)alkanetriyl, C5-C6 (hetero)arenetriyl, C3-C7 cycloalkanetriyl, and C2-C7 heterocycloalkanetriyl; T1 is selected from the group consisting of OT1A, hydrogen, C2-C6 alkyl, C6 aryl, C4-C5 heteroaryl, C3-C6 cycloalkyl, C5-C12 alkyl(hetero)aryl, C5-C12 (hetero)aryl alkyl, C4-C12 alkylcycloalkyl, -N(T1A)2, -ST1A, -SO3H, -C(O)T1A, -C(O)OT1A, -OC(O)T1A, -C(O)N(T1a)2, -N(T1a)2-CO-T1a, and -Si(T1A)3;Each T1A is independently selected from the group consisting of hydrogen, (hetero)alkyl, (hetero)alkenyl, (hetero)alkynyl, (hetero)aryl, and an amino acid residue; T2 is a bioconjugation moiety or group -L3-CB; wherein L3 is a residue of a bioconjugation moiety, and Petition 870250080942, dated 09 / 09 / 2025, p. 26 / 40 2 / 13 CB is selected from the group consisting of proteins, nucleic acids, peptides, carbohydrates, aptamers, lipids, small organic molecules, polymers, LNA, PNA, amino acids, peptoids, chelating fractions, fluorescent dyes, phosphorescent dyes, organic particles, gels, cells, and combinations thereof; T3 is a polymer; and R48 is selected from the group consisting of OH, -O-acetyl, -O-C1-4 alkyl, halogen, active carbonate, and a releasable group;and preferably L1 is linear or branched C4-C12 alkylene, more preferably L1 is linear or branched C4-C10 alkylene, and most preferably L1 is linear C5-C6 alkylene; preferably L2a, L2b, and L2d are each independently a ligand containing at most twenty atoms; most preferably L2a, L2b, and L2d are each independently selected from the group consisting of -C(O)NL2T-, -NL2TC(O)-, -O-, -S-, -NL2T-, -N=N-, and -C(O)-; wherein L2T is hydrogen or methyl, preferably L2T is hydrogen; preferably L2c is C1-C8 (hetero)alkanetriyl, more preferably L2c is C1-C8 alkanetriyl, and most preferably L2c is C4-C6 alkanetriyl; Preferably T1 is -OT1A; and most preferably T1 is -OH; preferably T1A is hydrogen or methyl, most preferably T1A is hydrogen; preferably T2 is maleimidil, N-hydroxysuccinimidyl, or -L3-CB;Preferably L3 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety; Petition 870250080942, dated 09 / 09 / 2025, page 27 / 40 3 / 13 preferably CB is a protein, more preferably CB is an antibody or a diabody, even more preferably CB is a diabody, and most preferably CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably T3 is a polymer comprising a polyethylene glycol moiety; and preferably R4s is a releasable group.

2. A composite, according to claim 1, characterized in that said composite is such that y is an integer in a range from 1 to 50; preferably y is an integer in a range from 10 to 40, more preferably in a range from 12 to 37, even more preferably in a range from 15 to 35, even more preferably in a range from 20 to 30, and most preferably is an integer in a range from 23 to 25.

3. Compound, according to either of claims 1 or 2, characterized in that said compound is in accordance with Formula (3): Petition 870250080942, dated 09 / 09 / 2025, p. 28 / 40 4 / 13 where y is as defined in claim 2; x is an integer in a range from 4 to 12; preferably x is an integer in a range from 4 to 8, more preferably x is an integer in a range from 4 to 6.

4. A compound according to any one of claims 1 to 3, characterized in that R4s is a releasable group, and said releasable group is -O-CO-CA; where CA is a drug; preferably the drug is linked to the -O-CO portion by means of a secondary or tertiary nitrogen atom that is part of the drug, forming a carbamate; preferably the drug is monomethyl auristatin E (MMAE).

5. Compound, according to any one of claims 1 to 4, characterized in that T2 is selected from the group consisting of wherein CB is a protein; Petition 870250080942, dated 09 / 09 / 2025, p. 29 / 40 5 / 13 preferably CB is an antibody or a diabody, more preferably a diabody, and most preferably AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the remainder of T2 by means of S or N which is part of CB, more preferably S.

6. Compound, of claims 1 to 5, said compound is: O II O^^N^ HO'T\___^ HN\ W0 o / , V n^^Jy“Vo); O o 24 7. Compound, of claims 1 to 6, said compound is O ΐ O^'N H 1 1 H'X HOj\^ / >-H HN^O NL^nhÇp^ OO 24 or ; according to any of the characterized by the fact that the C nhJLXXQ i „ r |T : Jlí ΙϊΎΥ> O 1 OO i I \ o O * . i according to any of the characterized by the fact that oo / 'X 1 II \ f oh X . NH 11 N ( I 1 < VN^X II Ξ । i II í π i η 4 o 1 OO * II í X \ \ oo * Petition 870250080942, of 09 / 09 / 2025, p.

8. Compound, according to any one of claims 1 to 5, characterized in that said compound is: p B__ / l C--\^N / / OOO NH£ O HO HN 'O wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CB is linked to the maleimidyl group by means of a sulfur atom that is part of CB, preferably the sulfur atom is part of a cysteine.

9. Compound, according to claim 8, characterized in that said CB OOO compound is: or Petition 870250080942, dated 09 / 09 / 2025, p. 31 / 40 7 / 13 OO 10. Compound characterized in that it comprises an eight-membered non-aromatic cyclic monoalkenylene moiety, wherein said moiety comprises a non-vinyl carbon atom, wherein said non-vinyl carbon atom is substituted by at least one structure according to Formula (A): Formula (A); where L1 and L2 are each independently a ligand; and T2 and T3 are organic moieties.

11. Conjugate characterized in that it comprises a protein conjugated to at least one compound according to Formula (1) as defined in any one of claims 1 to 9, wherein L1, L2a, L2b, L2c, L2d, T1, T3, and R48 are as defined in any one of claims 1 to 9, and wherein T2 is a residue of a bioconjugation moiety, and said protein and said compound are conjugated via T2; preferably the protein is a diabody or an antibody; more preferably the protein is a diabody; and most preferably the protein is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; Petition 870250080942, dated 09 / 09 / 2025, p.32 / 40 8 / 13 preferably the protein is conjugated to a maximum of 12 of said compounds; more preferably the protein is conjugated to a maximum of 8 of said compounds; most preferably the protein is conjugated to a maximum of 4 of said compounds; preferably said protein and said compound are conjugated by means of T2 and a sulfhydryl residue of said protein, a hydroxyl residue of said protein, or an amine residue of said protein; more preferably said protein and said compound are conjugated by means of T2 and a sulfhydryl residue of said protein; preferably T2 is a residue of a maleimidyl moiety or a residue of an N-hydroxysuccinimidyl moiety; most preferably T2 is a residue of a maleimidyl moiety.

12. Conjugate, according to claim 11, characterized in that the conjugate is: CJ wherein CJ is in a range of 1 to 12; wherein CB is AVP0458 consisting of two monomers, wherein each of the two monomers has an amino acid sequence according to SEQ ID NO: 1; preferably CJ is from 2 to 10, more preferably from 2.5 to 8, even more preferably from 3 to 6, even more preferably from 3.5 to 4, and most preferably about 4; Petition 870250080942, dated 09 / 09 / 2025, page 33 / 40 9 / 13 preferably CB is linked to each maleimidyl group by means of a sulfur atom, preferably the sulfur atom is part of a cysteine.

13. Conjugate, according to claim 12, characterized in that the conjugate is: OO or CJ CJ 14. Composition characterized by comprising: (a) a compound as defined in any one of claims 1 to 10; and / or (b) the conjugate as defined in any one of claims 11 to 13; preferably the composition is a pharmaceutical composition.

15. Composition according to claim 14, characterized in that it comprises: (a) a compound as defined in any one of claims 1 to 10; and (b) the enantiomer of said compound; Petition 870250080942, dated 09 / 09 / 2025, page 34 / 40 10 / 13 preferably said composition is a racemic mixture of (a) and (b).

16. Combination characterized in that it is of: (A1) a compound as defined in any one of claims 1 to 10; (A2) a conjugate as defined in any one of claims 11 to 13; and / or (A3) a composition as defined in claim 14 or 15; with (B) a diene; preferably the diene is a tetrazine.

17. Combination according to claim 16, characterized in that the diene is selected from the group consisting of: Petition 870250080942, dated 09 / 09 / 2025, page 35 / 40 11 / 13 18. Compound as defined in any one of claims 1 to 10, conjugate as defined in any one of claims 11 to 13, composition as defined in any one of claims 14 to 15, or combination as defined in any one of claims 16 to 17, characterized in that it is for use as a medicament.

19. A compound as defined in any one of claims 1 to 10, a combination as defined in any one of claims 11 to 13, a composition as defined in any one of claims 14 to 15, or a combination as defined in any one of claims 16 to 17, characterized in that it is for use in the treatment of a disease in an individual, preferably the individual is a human; preferably the disease is cancer.

20. A method for treating a disease in an individual, characterized in that said method comprises the step of administering to said individual: (a) the compound as defined in any one of claims 1 to 10; (b) the conjugate as defined in any one of claims 11 to 13; (c) the composition as defined in any one of claims 14 to 15; and / or (d) the combination as defined in any one of claims 16 to 17; preferably the individual is a human; preferably the disease is cancer.

21. Non-therapeutic method characterized in that it is for reacting: (ia) the compound as defined in any one of claims 1 to 10; Petition 870250080942, dated 09 / 09 / 2025, p. 36 / 40 12 / 13 (iia) the conjugate as defined in any one of claims 11 to 13; and / or (iiia) the composition as defined in any one of claims 14 to 15; with a diene, wherein said method comprises the step of contacting (ia), (iia), or (iiia) said diene, preferably said non-therapeutic method is an in vitro method; and preferably said diene is a tetrazine.

22. Non-therapeutic use characterized by being (a) the compound as defined in any one of claims 1 to 10; (b) the conjugate as defined in any one of claims 11 to 13; (c) the composition as defined in any one of claims 14 to 15; and / or (d) the combination as defined in any one of claims 16 to 17; in a click reaction.

23. Method for the synthesis of a compound as defined in any one of claims 1 to 10; characterized in that said method comprises: (A) coupling a compound of Formula (R) to a compound of Formula (S): Formula (R); Petition 870250080942, dated 09 / 09 / 2025, p. 37 / 40 13 / 13 where R4s, T1, and y are as defined in any one of claims 1 to 10; t^_^s10x Formula (S); where T2, ex, are as defined in any one of claims 1 to 10, and S10 is -COOH or an active ester, preferably S10 is -COOH; or (B) coupling a compound of Formula (T) to a compound of Formula (U): where R4s, and T1 are as defined in any one of claims 1 to 10; and S11 is -COOH or an active ester, preferably S11 is an active ester; NH20 IX II y θ Formula (U); where T2, x, and y are as defined in any one of claims 1 to 10.

24. Method for the synthesis of a conjugate, according to any one of claims 11 to 13, characterized in that said method comprises the step of coupling a protein to a compound as defined in any one of claims 1 to 10; wherein, in that compound, T2 is a bioconjugation moiety; in which, preferably in said protein, the disulfide bonds have been reduced.