Abstract: Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a residue of a camptothecin active covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimer, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

Abstract: Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a cabazitazel residue covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimers, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

Abstract: Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a cabazitazel residue covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimers, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

Abstract: Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a cabazitazel residue covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimers, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

Abstract: A macromolecule includes i) a dendrimer comprising a core and at least one generation of building units, the outermost generation of building units having surface amino groups wherein at least two different terminal groups are covalently attached to the surface amino groups of the dendrimer, ii) a first terminal group which is a residue of a pharmaceutically active agent comprising a hydroxyl group, and iii) a second terminal group which is a pharmacokinetic modifying agent. The pharmaceutically active agent is cabazitaxel. The first terminal group is covalently attached to the surface amino group of the dendrimer through a diacid linker, the diacid linker comprising an alkyl chain interrupted by one or more oxygen, sulfur or nitrogen atoms, or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a cabazitazel residue covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimers, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

Abstract: A macromolecule includes i) a dendrimer with a core and at least one generation of lysine residue building units, the outermost generation of building units having surface amino groups, ii) a first terminal group covalently attached to a first surface amino group of a building unit, which includes a residue of docetaxel (DTX), and iii) a second terminal group covalently attached to a second surface amino group of a building unit, which includes a pharmacokinetic modifying agent. The pharmacokinetic modifying agent can be a polyethylene glycol (PEG). The first terminal group can be covalently attached to the surface amino group of the dendrimer through a diacid linker. The diacid linker can include a 2,2?-thiodiacetic acid residue. The diacid linker can form an ester bond with a hydroxyl group of the DTX and an amide bond with the surface amino group. A pharmaceutically acceptable salt of the macromolecule can be prepared.

Abstract: A macromolecule includes i) a dendrimer comprising a core and at least one generation of building units, the outermost generation of building units having surface amino groups wherein at least two different terminal groups are covalently attached to the surface amino groups of the dendrimer, ii) a first terminal group which is a residue of a pharmaceutically active agent comprising a hydroxyl group, and iii) a second terminal group which is a pharmacokinetic modifying agent. The pharmaceutically active agent is cabazitaxel. The first terminal group is covalently attached to the surface amino group of the dendrimer through a diacid linker, the diacid linker comprising an alkyl chain interrupted by one or more oxygen, sulfur or nitrogen atoms, or a pharmaceutically acceptable salt thereof.

Abstract: A macromolecule includes i) a dendrimer with a core and at least one generation of lysine residue building units, the outermost generation of building units having surface amino groups, ii) a first terminal group covalently attached to a first surface amino group of a building unit, which includes a residue of docetaxel (DTX), and iii) a second terminal group covalently attached to a second surface amino group of a building unit, which includes a pharmacokinetic modifying agent. The pharmacokinetic modifying agent can be a polyethylene glycol (PEG). The first terminal group can be covalently attached to the surface amino group of the dendrimer through a diacid linker. The diacid linker can include a 2,2?-thiodiacetic acid residue. The diacid linker can form an ester bond with a hydroxyl group of the DTX and an amide bond with the surface amino group. A pharmaceutically acceptable salt of the macromolecule can be prepared.

Abstract: The present invention relates to a macromolecule comprising a dendrimer having surface amino groups to which at least two different terminal groups are attached including a pharmaceutically active agent and a pharmacokinetic modifying agent, the pharmaceutically active agent comprising a hydroxyl group and being attached to the surface amino group of the dendrimer through a diacid linker. Pharmaceutical compositions comprising the macromolecules and methods of treatment using the macromolecules are also described.

Abstract: A macromolecule comprising a dendrimer having surface amino groups to which at least one platinum-containing moiety is attached is provided. The macromolecule may have a plurality of platinum-containing moieties attached to the surface amino groups. Alternatively, the macromolecule may comprise a dendrimer having surface amino groups to which at least two different moieties are attached, a first moiety being a platinum-containing moiety and the second moiety being a pharmacokinetic modifying agent or targeting agent. Pharmaceutical compositions comprising the macromolecules and uses of the macromolecules for treating or suppressing the growth of a cancer is also described.

Abstract: The present invention relates to a macromolecule comprising a dendrimer having surface amino groups to which at least two different terminal groups are attached including a pharmaceutically active agent and a pharmacokinetic modifying agent, the pharmaceutically active agent comprising a hydroxyl group and being attached to the surface amino group of the dendrimer through a diacid linker. Pharmaceutical compositions comprising the macromolecules and methods of treatment using the macromolecules are also described.

Abstract: The present invention relates to a macromolecule having a controlled terminal group stoichiometry, the macromolecule including a surface layer, at least one subsurface layer and at least two terminal groups including: a first terminal group which is a residue of a pharmaceutically active agent, a derivative thereof or precursor therefor; and a second terminal group selected to modify the pharmacokinetics of the pharmaceutically active agent and/or macromolecule, wherein terminal group stoichiometry refers to the number and type of terminal groups.

Abstract: Axial fluid control valves having linear actuators are described herein. An example axial fluid control valve described herein includes a valve body defining a passageway between an inlet and an outlet. The example axial fluid valve includes a plug linkage assembly movable relative to the axial valve body and along a first axis substantially aligned with the passageway. The example axial fluid valve includes a linear actuator having a stem operatively coupled to the plug linkage assembly. The linear actuator is to move at least a portion of the plug linkage assembly along the first axis within the passageway to vary a flow of fluid through the passageway, wherein the stem of the linear actuator moves along a second axis different than the first axis.

Abstract: The following invention is directed to macromolecules having controlled stoichiometry and topology, processes for their production, and applications for their use. The macromolecules have a controlled functional moiety stoichiometry and include at least one dendritic motif having a surface layer formed from at least one surface building unit and at least one subsurface layer formed from at least one building unit, the surface building unit and building units having a hydrocarbon backbone bearing a carbonyl group and at least one amine group; and at least two different functional moieties on the building unit and/or surface building unit; where functional moiety stoichiometry refers to the number and type of functional moieties.

Abstract: The present invention relates generally to branched macromolecules bearing functional moieties. In particular, the invention relates to dendrimers, derived from lysine or lysine analogues, bearing a plurality of functional moieties. The invention further relates to the use of such macromolecules, particularly in therapeutic applications, and compositions comprising them.

Abstract: The present invention relates to a macromolecule having a controlled terminal group stoichiometry, the macromolecule including a surface layer, at least one subsurface layer and at least two terminal groups including: a first terminal group which is a residue of a pharmaceutically active agent, a derivative thereof or precursor therefor; and a second terminal group selected to modify the pharmacokinetics of the pharmaceutically active agent and/or macromolecule, wherein terminal group stoichiometry refers to the number and type of terminal groups.

Abstract: The following invention is directed to macromolecules having controlled stoichiometry and topology, processes for their production, and applications for their use. The macromolecules have a controlled functional moiety stoichiometry and include at least one dendritic motif having a surface layer formed from at least one surface building unit and at least one subsurface layer formed from at least one building unit, the surface building unit and building units having a hydrocarbon backbone bearing a carbonyl group and at least one amine group; and at least two different functional moieties on the building unit and/or surface building unit; where functional moiety stoichiometry refers to the number and type of functional moieties.

Abstract: The following invention is directed to macromolecules having controlled stoichiometry and topology, processes for their production, and applications for their use. The macromolecules have a controlled functional moiety stoichiometry and include at least one dendritic motif having a surface layer formed from at least one surface building unit and at least one subsurface layer formed from at least one building unit, the surface building unit and building units having a hydrocarbon backbone bearing a carbonyl group and at least one amine group; and at least two different functional moieties on the building unit and/or surface building unit; where functional moiety stoichiometry refers to the number and type of functional moieties.

Abstract: The present invention relates generally to branched macromolecules bearing functional moieties. In particular, the invention relates to dendrimers, derived from lysine or lysine analogues, bearing a plurality of functional moieties. The invention further relates to the use of such macromolecules, particularly in therapeutic applications, and compositions comprising them.