Agents for clearing biomolecules from circulation

A combination of an administration agent to be administered to a subject and a clearing agent to be administered to the same subject that is configured to remove circulating administration agent from the subject's blood, wherein the administration agent includes a linkage by which said administration agent is linked to a first reactive group, and wherein the clearing agent includes a linkage by which said clearing agent is linked to a second reactive group, said first and second reactive groups being bio-orthogonal reactive groups selected so as to be bio-orthogonally reactive towards each other wherein either of the bio-orthogonal reactive groups is a dienophile and the other is a diene, wherein the dienophile is an 8-member ring dienophile satisfying formula (1):

• wherein each R independently denotes H, or, in at most six instances, a substituent selected from the group consisting of alkyl, aryl, O-aryl, O-alkyl, S-aryl, S-alkyl, S(O)-aryl, S(O)-alkyl, S(O)2-aryl, S(O)2-alkyl, Si-aryl, Si-alkyl, Si—O-alkyl, OCO-alkyl, OCO-aryl, SCO-alkyl, SCO-aryl, OCS-alkyl OCS-aryl, SCS-alkyl, SCS-aryl, F, Cl, Br, I, N3, SO2H, SO3H, SO4H, PO3H, PO4H, OH, SH, NO2, NO, CN, OCN, SCN, NCO, NCS, CF3, NR′R″ with R′ and R″ each independently being H or alkyl, aryl, C(═O)O-alkyl, C(═O)O-aryl, C(═S)O-alkyl, C(═S)O-aryl, C(═O)S-alkyl, C(═O)S-aryl, C(═S)S-alkyl, C(═S)S-aryl, C(═O)NR′R″ with R′ and R″ each independently being H, aryl or alkyl, NR′ CO-alkyl with R′ being H, alkyl or aryl, NR′CO-aryl with R′ being H, alkyl or aryl, NR′C(═O)O-alkyl with R′ being H, alkyl, or aryl, NR′C(═O)O-aryl with R′ being H, alkyl or aryl, OCONR′-alkyl with R′ being H, alkyl or aryl, OCONR′-aryl with R′ being H, alkyl or aryl, NR′CONR″-alkyl with R′ and R″ each independently being H, alkyl or aryl, NR′CONR″-aryl with R′ and R″ each independently being H, alkyl or aryl, NR′CSNR″-alkyl with R′ and R″ each independently being H, alkyl or aryl, and NR′CSNR″-aryl with R′ and R″ each independently being H, alkyl or aryl, CR′NR″ with R′ and R″ each independently being H, alkyl or aryl, wherein two R moieties together may form a ring, and wherein X and Y each independently denote H, or a substituent selected from the group consisting of alkyl, O-alkyl, S-alkyl, F, Cl, Br, I, SO2, NO2, and NRR′ with R and R′ each independently being H or alkyl, or together form a bond, with one R forming said linkage, optionally via a spacer, to the respective administration agent or clearing agent.