The present disclosure generally provides complexes including a pharmaceutically active agent and a functionalized polymer, wherein the functionalized polymer includes repeat units, the repeat units including ionizable repeat units having at least one ionizable side group and/or ionizable end group, a plurality of the at least one ionizable groups forming non-covalent bonds with the pharmaceutically active agent. Polymers which may be used to form such complexes as well as methods of making and using the complexes and related compositions are also provided.

The present invention relates a pharmaceutical formulation comprising a long-acting growth hormone for use in a method of treating growth hormone deficiency, wherein the long-acting growth hormone formulation is administered to a patient in a bracketed dosage regimen, to a multitude of unit dosage forms comprising a long-acting growth hormone formulation, wherein the unit dosage forms comprise increasing amounts of growth hormone equivalents and wherein the amount of growth hormone equivalents increases by at least 10% between one unit dosage form and the next higher dosage form; their use in a method of treating growth hormone deficiency and method of treating growth hormone deficiency in a bracketed dosing regimen.

The present invention relates a pharmaceutical formulation comprising a long-acting growth hormone for use in a method of treating growth hormone deficiency, wherein the long-acting growth hormone formulation is administered to a patient in a bracketed dosage regimen, to a multitude of unit dosage forms comprising a long-acting growth hormone formulation, wherein the unit dosage forms comprise increasing amounts of growth hormone equivalents and wherein the amount of growth hormone equivalents increases by at least 10% between one unit dosage form and the next higher dosage form; their use in a method of treating growth hormone deficiency and method of treating growth hormone deficiency in a bracketed dosing regimen.

Compositions for modulating the expression of a protein in a target cell comprising at least one RNA molecule which comprises at least one modification 5 conferring stability to the RNA, as well as related methods, are disclosed.

Compositions for modulating the expression of a protein in a target cell comprising at least one RNA molecule which comprises at least one modification 5 conferring stability to the RNA, as well as related methods, are disclosed.

The present invention relates to improved pharmaceutical formulations, uses and methods for the oral delivery of peptide or protein drugs with advantageously high bioavailability, safety and cost-effectiveness. In particular, the invention provides a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa for use as a medicament, wherein said peptide or protein drug is to be administered orally in combination with a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex, and with a pharmaceutically acceptable reducing agent. The invention also provides a pharmaceutical composition comprising: a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa; a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex; and a pharmaceutically acceptable reducing agent.

The present invention relates to improved pharmaceutical formulations, uses and methods for the oral delivery of peptide or protein drugs with advantageously high bioavailability, safety and cost-effectiveness. In particular, the invention provides a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa for use as a medicament, wherein said peptide or protein drug is to be administered orally in combination with a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex, and with a pharmaceutically acceptable reducing agent. The invention also provides a pharmaceutical composition comprising: a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa; a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex; and a pharmaceutically acceptable reducing agent.

The present invention refers to a GPR101 inhibitor, antagonist or inverse agonist or inverse agonist for use in preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism wherein to a subject GPR101 inhibitor, antagonist or inverse agonist is administered. Further, the present invention provides a GPR101 agonist for use in preventive and/or therapeutic treatment of disorders selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion wherein to a subject GPR101 agonist is administered. The present invention also provides GHRH inhibitors, antagonists or inverse agonists and GH antagonists for use in the therapeutic treatment of X-linked acrogigantism (X-LAG syndrome). In addition, the present invention refers to a method of increasing body mass and/or body size of livestock comprising administering to livestock an effective amount of GPR101 agonist. Further, the present invention is directed to a non-human transgenic animal, comprising as expressed transgene a gene encoding GPR101 or overexpressing endogenous GPR101 gene.

The present invention refers to a GPR101 inhibitor, antagonist or inverse agonist or inverse agonist for use in preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism wherein to a subject GPR101 inhibitor, antagonist or inverse agonist is administered. Further, the present invention provides a GPR101 agonist for use in preventive and/or therapeutic treatment of disorders selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion wherein to a subject GPR101 agonist is administered. The present invention also provides GHRH inhibitors, antagonists or inverse agonists and GH antagonists for use in the therapeutic treatment of X-linked acrogigantism (X-LAG syndrome). In addition, the present invention refers to a method of increasing body mass and/or body size of livestock comprising administering to livestock an effective amount of GPR101 agonist. Further, the present invention is directed to a non-human transgenic animal, comprising as expressed transgene a gene encoding GPR101 or overexpressing endogenous GPR101 gene.

An insulin molecule comprises an Asp substitution at position B10, Glu at one or more of positions corresponding to A8, B28, and B29, and a halogenated phenylalanine at position B24. The analogue may optionally include (i) N-terminal deletion of one, two or three residues from the B chain, (ii) a mono-peptide or dipeptide C-terminal extension of the B-chain containing at least one acidic residue, and (iii) other modifications known in the art to enhance the stability of insulin. Formulations of the above analogues at successive strengths U-100 to U-1000 in soluble solutions at at least pH value in the range 7.0-8.0 in the absence or presence of zinc ions at a molar ratio of 0.00-0.10 zinc ions per insulin analogue monomer. A method of lowering the blood sugar level of a patient comprises administering a physiologically effective amount of the insulin to a patient.