Patents Assigned to Ascendis Pharma A/S
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Publication number: 20160082123Abstract: 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.Type: ApplicationFiled: April 16, 2014Publication date: March 24, 2016Applicant: Ascendis Pharma A/SInventors: Harald RAU, Nora KALUZA, Ulrich HERSEL, Thomas KNAPPE, Burkhardt LAUFER
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Patent number: 9278139Abstract: The present invention relates to a terminal sterilization process for biodegradable PEG-based insoluble hydrogels using irradiation. The presence of a protective solvent ensures that the hydrogel remains intact with functionally preserved three-dimensional and physicochemical properties.Type: GrantFiled: January 26, 2015Date of Patent: March 8, 2016Assignee: Ascendis Pharma A/SInventors: Harald Rau, Tobias Voigt, Ulrich Hersel
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Publication number: 20150306239Abstract: The present invention relates to carrier-linked prostanoid prodrugs of formula (I) Z1—(X0-L0-PG0)y (I), wherein Z1, X0, L0, PG0 and y have the meaning as indicated in the description and claims; pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising the same. It further relates to their use as medicaments, especially for treating, controlling, delaying or preventing pulmonary arterial hypertension.Type: ApplicationFiled: December 6, 2013Publication date: October 29, 2015Applicant: ASCENDIS PHARMA A/SInventors: Harald Rau, Guillaume Maitro, Ulrich Hersel, Oliver Keil, Thomas Wegge
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Publication number: 20150238625Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.Type: ApplicationFiled: May 8, 2015Publication date: August 27, 2015Applicant: ASCENDIS PHARMA A/SInventors: Ulrich Hersel, Harald Rau, Robert Schnepf, Dirk Vetter, Thomas Wegge
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Patent number: 9056126Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker. The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.Type: GrantFiled: May 19, 2011Date of Patent: June 16, 2015Assignee: ASCENDIS PHARMA A/SInventors: Ulrich Hersel, Harald Rau, Robert Schnepf, Dirk Vetter, Thomas Wegge
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Patent number: 8986609Abstract: The present invention relates to a terminal sterilization process for biodegradable PEG-based insoluble hydrogels using irradiation. The presence of a protective solvent ensures that the hydrogel remains intact with functionally preserved three-dimensional and physicochemical properties.Type: GrantFiled: October 28, 2010Date of Patent: March 24, 2015Assignee: Ascendis Pharma A/SInventors: Harald Rau, Tobias Voigt, Ulrich Hersel
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Patent number: 8906847Abstract: 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.Type: GrantFiled: January 30, 2009Date of Patent: December 9, 2014Assignee: Ascendis Pharma A/SInventors: Felix Cleemann, Ulrich Hersel, Silvia Kaden, Harald Rau, Thomas Wegge
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Publication number: 20140303245Abstract: The present invention relates to sustained release compositions of prostacyclin, as well as uses thereof, in particular for the prevention and/or treatment of pulmonary arterial hypertension.Type: ApplicationFiled: August 10, 2012Publication date: October 9, 2014Applicant: Ascendis Pharma A/SInventors: Kennett Sprogøe, Harald Rau, Ulrich Hersel, Thomas Wegge, Oliver Keil, Joachim Zettler
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Publication number: 20140296150Abstract: The present invention relates to prodrugs or a pharmaceutically acceptable salt thereof comprising a covalent treprostinil carrier conjugate as well as pharmaceutical composition comprising said compounds. The compounds may be used as medicaments, especially for diseases or disorders which can be treated by treprostinil, such as pulmonary arterial hypertension (PAH).Type: ApplicationFiled: August 10, 2012Publication date: October 2, 2014Applicant: Ascendis Pharma A/SInventors: Ulrich Hersel, Harald Rau, Torben Lessmann, Nicola Bisek, Guillaume Maitro, Kennett Sprogøe, Thomas Wegge, Oliver Keil, Joachim Zettler
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Publication number: 20140296257Abstract: The present invention relates to water-soluble carrier-linked prodrugs of formula (I), wherein B, A and Hyp form the carrier, B is a branching core, each A is independently a poly(ethylene glycol)-based polymeric chain, each Hyp is independently a branched moiety, each SP is independently a spacer moiety, each L is independently a reversible prodrug linker moiety, each D is independently a biologically active moiety, each x is independently 0 or 1, each m is independently an integer of from 2 to 64, n is an integer from 3 to 32; or the pharmaceutically acceptable salt thereof. It further relates to pharmaceutical compositions comprising said water-soluble carrier-linked prodrugs, their use as medicament or diagnostic, and methods of treatment.Type: ApplicationFiled: August 10, 2012Publication date: October 2, 2014Applicant: Ascendis Pharma A/SInventors: Ulrich Hersel, Guillaume Maitro, Harald Rau, Dirk Vetter
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Publication number: 20140249093Abstract: The invention provides a carrier-linked prodrugs, wherein the biologically active moieties comprise at least one carboxylic acid and wherein the linkage between the drug moiety and linker is in the form of an ester wherein the hydroxyl group required for ester formation is provided by the linker moiety and the carboxyl group required for ester formation is provided by the drug moiety. The hydroxyl group of the linker is sterically hindered by the presence of an alkyl or aryl group on the carbon directly bound to or adjacent to the carbon carrying the hydroxyl group (?-carbon). The steric effect of the alkyl or aryl group enables greater control of the rate of hydrolytic degradation of such carrier-linked prodrugs.Type: ApplicationFiled: August 10, 2012Publication date: September 4, 2014Applicant: Ascendis Pharma A/SInventors: Dirk Vetter, Harald Rau
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Publication number: 20140243254Abstract: The present invention relates to water-soluble carrier-linked prodrugs of formula (I), wherein POL is a polymeric moiety, each Hyp is independently a hyperbranched moiety, each moiety SP is independently a spacer moiety, each L is independently a reversible prodrug linker moiety, m is 0 or 1, each n is independently an integer from 2 to 200 and each x is independently 0 or 1. It further relates to pharmaceutical compositions comprising said water-soluble carrier-linked prodrugs and methods of treatment.Type: ApplicationFiled: August 10, 2012Publication date: August 28, 2014Applicant: Ascendis Pharma A/SInventors: Ulrich Hersel, Guillaume Maitro, Herald Rau, Tobias Voigt
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Publication number: 20130053301Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof, comprising a drug linker conjugate D-L, wherein D being a biologically active moiety containing an aliphatic amine group is conjugated to one or more polymeric carriers via dipeptide-containing linkers L. Such carrier-linked prodrugs achieve drug releases with therapeutically useful half-lives. The invention also relates to pharmaceutical compositions comprising said prodrugs and their use as medicaments.Type: ApplicationFiled: January 21, 2011Publication date: February 28, 2013Applicant: Ascendis Pharma A/SInventors: Harald Rau, Torben Lessmann
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Publication number: 20130035635Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof, comprising a drug linker conjugate D-L, wherein D being a biologically active moiety containing an aromatic hydroxyl group is conjugated to one or more polymeric carriers via secondary carbamate-containing linkers L. Such carrier-linked prodrugs achieve drug releases with therapeutically useful half-lives. The invention also relates to pharmaceutical compositions comprising said prodrugs and their use as medicaments.Type: ApplicationFiled: January 21, 2011Publication date: February 7, 2013Applicant: ASCENDIS PHARMA A/SInventors: Harald Rau, Torben Lessmann
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Publication number: 20130030359Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof, comprising a drug linker conjugate D-L, wherein D being a biologically active moiety containing an aromatic amine group is conjugated to one or more polymeric carriers via dipeptide-containing linkers. Such carrier-linked prodrugs achieve drug releases with therapeutically useful half-lives. The invention also relates to pharmaceutical compositions comprising said prodrugs and their use as medicaments.Type: ApplicationFiled: January 21, 2011Publication date: January 31, 2013Applicant: Ascendis Pharma A/SInventors: Dirk Vetter, Harald Rau
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Publication number: 20120191039Abstract: The present invention relates to a carrier linked pramipexole prodrug or a pharmaceutical acceptable salt thereof, wherein pramipexole is bound via a linker to a polymeric carrier. The invention also relates to pharmaceutical compositions comprising said polymeric pramipexole prodrug and their use as medicaments.Type: ApplicationFiled: July 30, 2010Publication date: July 26, 2012Applicant: ASCENDIS PHARMA A/SInventors: Harald Rau, Julia Baron, Ulrich Hersel
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Publication number: 20120156259Abstract: 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.Type: ApplicationFiled: July 30, 2010Publication date: June 21, 2012Applicant: ASCENDIS PHARMA A/SInventors: Harald Rau, Ulrich Hersel, Mathias Krusch, Dirk Vetter, Tobias Voigt
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Publication number: 20120156260Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein an aromatic amine containing biologically active moiety is connected (bound) by an amido bound to a linker. The invention also relates to pharmaceutical compositions comprising said prodrugs and their use as medicaments.Type: ApplicationFiled: July 30, 2010Publication date: June 21, 2012Applicant: ASCENDIS PHARMA A/SInventors: Harald Rau, Julia Baron, Ulrich Hersel, Mathias Krusch
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Publication number: 20110223230Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker. The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.Type: ApplicationFiled: May 19, 2011Publication date: September 15, 2011Applicant: ASCENDIS PHARMA A/SInventors: Ulrich Hersel, Harald Rau, Robert Schnepf, Dirk Vetter, Thomas Wegge
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Publication number: 20110172390Abstract: The application relates to a composition comprising a hyperbranched polymer attached to a core and a biologically active moiety. The biologically active moiety is attached to the core by means of a substantially non-enzymatically cleavable linker L. The composition can be used to deliver the biologically active moiety to its target.Type: ApplicationFiled: December 14, 2010Publication date: July 14, 2011Applicant: Ascendis Pharma A/SInventors: Dirk Vetter, Ulrich Hersel, Harald Rau, Robert Schnepf, Thomas Wegge