Abstract: This invention is in the field of IGF-1 modifications. In particular, it relates to modified IGF-polypeptides and modified IGF-1 precursor polypeptides wherein the cleavage of E-peptide is prevented. The invention also relates to the use of such polypeptides for treating muscle diseases and disorders.

Abstract: The invention relates to methods for the production of therapeutic proteins in mammalian cells. In one embodiment, the method comprises producing a therapeutic protein such as IGF-1 in a mammalian cell endogenously expressing a cognate receptor of said recombinant therapeutic protein and wherein binding of said therapeutic protein to said cognate receptor results in a low titer of the therapeutic protein, the method comprising with a mammalian cell being deficient in the expression of the cognate receptor of said therapeutic protein and being transformed with an expression vector comprising a nucleic acid molecule encoding the therapeutic protein: a. Cultivating said cell under conditions allowing the expression of the therapeutic protein; and b. Harvesting the therapeutic protein from the mammalian cell cultivated in step a, wherein said mammalian cell produces at least 1.5 fold more therapeutic protein than a cell in which the expression of the cognate receptor has not been so modified.

Abstract: The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

Abstract: This invention is in the field of IGF-1 modifications. In particular, it relates to modified IGF-polypeptides and modified IGF-1 precursor polypeptides wherein the cleavage of E-peptide is prevented. The invention also relates to the use of such polypeptides for treating muscle diseases and disorders.

Abstract: The invention relates to methods for the production of therapeutic proteins in mammalian cells. In one embodiment, the method comprises producing a therapeutic protein such as IGF-1 in a mammalian cell endogenously expressing a cognate receptor of said recombinant therapeutic protein and wherein binding of said therapeutic protein to said cognate receptor results in a low titer of the therapeutic protein, the method comprising with a mammalian cell being deficient in the expression of the cognate receptor of said therapeutic protein and being transformed with an expression vector comprising a nucleic acid molecule encoding the therapeutic protein: a. Cultivating said cell under conditions allowing the expression of the therapeutic protein; and b. Harvesting the therapeutic protein from the mammalian cell cultivated in step a, wherein said mammalian cell produces at least 1.5 fold more therapeutic protein than a cell in which the expression of the cognate receptor has not been so modified.

Abstract: High-specificity antibodies can distinguish between modified (e.g, hIGF-1/Ea 3mut) and endogenous wild-type human IGF-1 proteins. These antibodies have little or no cross-reactivity with hIGF-1 or hIGF-2. They also have little or no cross-reactivity with rodent IGF-1 or IGF-2. The antibodies can be used in pharmacokinetic (PK)/pharamcodynamic (PD) assessments of IGF-1/E peptides that have been administered to humans or animals. A sandwich ELISA assay, using the antibody of the invention as a capture antibody, can quantify the mutant IGF-1/E proteins in samples.

Abstract: The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

Abstract: High-specificity antibodies can distinguish between modified (e.g, hIGF-1/Ea 3mut) and endogenous wild-type human IGF-1 proteins. These antibodies have little or no cross-reactivity with hIGF-1 or hIGF-2. They also have little or no cross-reactivity with rodent IGF-1 or IGF-2. The antibodies can be used in pharmacokinetic (PK)/pharamcodynamic (PD) assessments of IGF-1/E peptides that have been administered to humans or animals. A sandwich ELISA assay, using the antibody of the invention as a capture antibody, can quantify the mutant IGF-1/E proteins in samples.

Abstract: The invention relates to stabilized polypeptides having an IGF-1 sequence and an Ea peptide sequence, where the natural physiological cleavage of the Ea peptide from the IGF-1 is prevented.

Abstract: The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

Abstract: High-specificity antibodies can distinguish between modified (e.g, hIGF-1/Ea 3mut) and endogenous wild-type human IGF-1 proteins. These antibodies have little or no cross-reactivity with hIGF-1 or hIGF-2. They also have little or no cross-reactivity with rodent IGF-1 or IGF-2. The antibodies can be used in pharmacokinetic (PK)/pharamcodynamic (PD) assessments of IGF-1/E peptides that have been administered to humans or animals. A sandwich ELISA assay, using the antibody of the invention as a capture antibody, can quantify the mutant IGF-1/E proteins in samples.

Abstract: The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.