Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein -D is an amine containing biologically active moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I): wherein the dashed line indicates the attachment to the amine of the biologically active moiety and wherein R1, R1a, R2, R2a, R3, R3a, X, X1, X2, X3 have the meaning as indicated in the description and the claims and wherein L1 is substituted with one to four groups L2-Z and optionally further substituted, provided that the hydrogen marked with the asterisk in formula (I) is not replaced by a substituent; wherein L2 is a single chemical bond or a spacer; and Z is a carrier group. The invention also relates to A-L, wherein A is a leaving group, pharmaceutical composition comprising said prodrugs and their use as medicaments.

Abstract: The present invention relates to biodegradable polyethylene glycol based water-insoluble hydrogels comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. The invention further relates to conjugates of such hydrogels with ligands or ligating groups, prodrugs and pharmaceutical compositions as well as their use in a medicament.

Abstract: The present invention relates to prodrugs of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising such CNP prodrugs and their uses. In an embodiment, the CNP prodrugs are conjugates of CNP peptides to poly(ethylene glycol) through a reversible linker.

Abstract: The present invention relates to a controlled-release CNP agonist from which CNP agonist is released with a release half-life of at least 6 hours under physiological conditions and which controlled-release CNP agonist has an EC50 that is at least 20-fold higher than the EC50 of the corresponding free CNP agonist and which released CNP agonist has an EC50 that is at most 3-fold higher than the EC50 of the corresponding free CNP agonist; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.

Abstract: The present invention relates to biodegradable polyethylene glycol based water-insoluble hydrogels comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. The invention further relates to conjugates of such hydrogels with ligands or ligating groups, prodrugs and pharmaceutical compositions as well as their use in a medicament.

Abstract: The present invention relates a pharmaceutical composition comprising a controlled-release CNP agonist which reduces CNP agonist-associated side-effects, the use of such controlled-release CNP agonist and to methods of treatment.

Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein -D is an amine containing biologically active moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I): wherein the dashed line indicates the attachment to the amine of the biologically active moiety and wherein R1, R1a, R2, R2a, R3, R3a, X, X1, X2, X3 have the meaning as indicated in the description and the claims and wherein L1 is substituted with one to four groups L2-Z and optionally further substituted, provided that the hydrogen marked with the asterisk in formula (I) is not replaced by a substituent; wherein L2 is a single chemical bond or a spacer; and Z is a carrier group. The invention also relates to A-L, wherein A is a leaving group, pharmaceutical composition comprising said prodrugs and their use as medicaments.

Abstract: The present invention relates to CNP prodrugs in which the carrier is covalently and reversibly attached to the ring moiety of a CNP moiety, to pharmaceutical compositions comprising such CNP prodrugs, to their uses and to methods of treating diseases that can be treated with the CNP prodrugs of the present invention.

Abstract: The present invention relates to a CNP prodrug or a pharmaceutically acceptable salt thereof comprising a CNP moiety -D; and a carrier moiety —Z that is conjugated through a moiety -L2- to a reversible prodrug linker moiety -L1-, which reversible prodrug linker moiety -L1- is covalently and reversibly conjugated to -D; wherein -L2- is a chemical bond or a spacer; and —Z is a polymer having a molecular weight of at least 10 kDa. It further relates to pharmaceutical compositions comprising the CNP prodrug or a pharmaceutically acceptable salt thereof, their use as a medicament and to methods of treatment.

Abstract: The present invention relates to CNP prodrugs in which the carrier is covalently and reversibly attached to the ring moiety of a CNP moiety, to pharmaceutical compositions comprising such CNP prodrugs, to their uses and to methods of treating diseases that can be treated with the CNP prodrugs of the present invention.

Abstract: The present invention relates a pharmaceutical composition comprising a controlled-release CNP agonist which reduces CNP agonist-associated side-effects, the use of such controlled-release CNP agonist and to methods of treatment.

Abstract: The present invention relates to a controlled-release CNP agonist from which CNP agonist is released with a release half-life of at least 6 hours under physiological conditions and which controlled-release CNP agonist has an EC50 that is at least 20-fold higher than the EC50 of the corresponding free CNP agonist and which released CNP agonist has an EC50 that is at most 3-fold higher than the EC50 of the corresponding free CNP agonist; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.

Abstract: The present invention relates to a controlled-release CNP agonist having low NPR-C affinity; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.

Abstract: The present invention relates to a controlled-release CNP agonist having low NPR-C affinity; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.

Abstract: A dry pharmaceutical formulation, wherein the pharmaceutical formulation comprises a CNP conjugate, a buffering agent and a bulking agent and wherein the CNP conjugate comprises a CNP moiety that is covalently and reversibly conjugated to a polymeric moiety.

Abstract: The present invention relates to controlled-release CNP agonists having an at least 5-fold longer degradation half-life in an in vitro NEP degradation assay than the corresponding released CNP agonist, to pharmaceutical compositions comprising said controlled-release CNP agonist, their use and to methods of treatment.

Abstract: The present invention relates to controlled-release CNP agonists having an at least 5-fold longer degradation half-life in an in vitro NEP degradation assay than the corresponding released CNP agonist, to pharmaceutical compositions comprising said controlled-release CNP agonist, their use and to methods of treatment.

Abstract: The present invention relates to a CNP prodrug or a pharmaceutically acceptable salt thereof comprising a CNP moiety -D; and a carrier moiety —Z that is conjugated through a moiety -L2- to a reversible prodrug linker moiety -L1-, which reversible prodrug linker moiety -L1- is covalently and reversibly conjugated to -D; wherein -L2- is a chemical bond or a spacer; and —Z is a polymer having a molecular weight of at least 10 kDa. It further relates to pharmaceutical compositions comprising the CNP prodrug or a pharmaceutically acceptable salt thereof, their use as a medicament and to methods of treatment.

Abstract: A cascade carrier linked prodrug is described comprising a biologically active moiety and a masking group having at least one nucleophile and being distinct from the carrier.

Abstract: The present invention relates to a process for the preparation of a hydrogel-linked prodrug releasing a tag moiety-biologically active moiety conjugate, to a hydrogel-linked prodrug releasing a tag moiety-bio logically active moiety conjugate obtainable by such process, to pharmaceutical compositions comprising said prodrug and their use as a medicament.