Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising an insulin linker conjugate D-L, wherein D represents the insulin moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I), wherein the dashed line indicates the attachment to one of the amino groups of the insulin by forming an amide bond. The invention further relates to pharmaceutical compositions comprising said prodrugs as well as their use as a medicament for treating or preventing diseases or disorders which can be treated by insulin.

Abstract: The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.

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 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.

Abstract: The present invention relates to a pharmaceutical composition comprising a water-soluble polymeric carrier linked prodrug of interferon alpha, wherein the prodrug is capable of releasing free interferon alpha, wherein the release half life under physiological conditions is at least 4 days. The invention further relates to prodrugs for said pharmaceutical composition and their use for treating, controlling, delaying or preventing a condition that can benefit from interferon alpha treatment, such as hepatitis C.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to binding surfaces for the immobilization of ligands, ligand surfaces and structured surface arrays which present a plurality of identical or different ligands. The invention further relates to a process for the production and the use of such surfaces and to specific binder molecules which can be used for the preparation thereof.

Abstract: A chemically modified human Growth Hormone (rhGH) prepared by attaching a transient linker which comprises a polyethylene glycol. The chemically modified protein may have a much longer lasting rhGH activity than that of the unmodified rhGH, enabling reduced dose and scheduling opportunities and the modified rhGH may not cause lipoatrophy. Also includes methods of use for the treatment and/or prevention of diseases or disorders in which use of growth hormone is beneficial.

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 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.

Abstract: Long-acting polymer exendin-4 or exendin agonist derivatives of the formula Pol-L-E are provided wherein Pol is a polymer, L is a releasing linker undergoing slow autohydrolysis and E is an exendin or exendin agonist. These exendin or exendin agonists are slowly released from Pol-L upon administration to a living organism. The derivatives are useful e.g. for the treatment of diabetes mellitus.

Abstract: A polymeric prodrug is described which comprises at least one polymer attached via at least one permanent bond to a bicine linker. The bicine linker is attached via a temporary linkage to an amine containing biologically active moiety. The amine containing biologically active moiety—such as a drug—can be released by cleaving the temporary linkage.

Abstract: A flatbed punching module for punching a printing material includes an upper platen and a lower platen which can be moved by a drive relative to the upper platen that is fixed to a frame, in order to perform a punching stroke for punching the printing material passing between the upper platen and the lower platen, resulting in the lower platen engaging with or being thrown onto the upper platen. As a result, the printing material can be processed through the use of at least one punching die. At least one printing material transport device for guiding the printing material, is held fixedly on the movable lower platen. The flatbed punching module can advantageously be used in a flatbed punch for processing a printing material web.

Abstract: Single stroke text entry via a telephone keypad is subject to ambiguities resulting from the overloading of three letters on one key. After text is entered the three letter per position code block represented by the key strokes for a word position is hashed to all matches in a stored dictionary type word list. The resulting word group of alternative word choices for that word position is subjected to probability analysis. Probabilities of usage of specific words are evaluated based on frequency of usage in the selected language, such as English. Syntax type probabilities of word sequencing are evaluated through (i) rules based on transitional probability of use of two particular words in sequence in English usage and (ii) rules based on probability of relative positioning of words of particular word categories (e.g., nouns and adjectives) in a sentence structure in English usage. A word trellis or lattice represents choice paths for alternative sentence structures.

Abstract: A cascade carrier linked prodrug is described which comprises 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 binding surfaces for the immobilization of ligands, ligand surfaces and structured surface arrays which present a plurality of identical or different ligands. The invention further relates to a process for the production and the use of such surfaces and to specific binder molecules which can be used for the preparation thereof.