Long-acting polypeptides and methods of producing and administering same
Inventors
Assignees
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Publication Number
US-9908924-B2
Publication Date
2018-03-06
Expiration Date
Abstract
A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also discarded.
Core Innovation
A chorionic gonadotropin carboxy terminal peptide (CTP)-modified polypeptide is provided in which a peptide of interest is an erythropoietin (EPO) peptide. A first chorionic gonadotropin carboxy terminal peptide (CTP) is attached to the amino terminus of the EPO peptide, and a second and third chorionic gonadotropin carboxy terminal peptide are attached to the carboxy terminus of the EPO peptide. The amino acid sequence of the resulting polypeptide is set forth in SEQ ID NO: 51.
The described constructs use chorionic gonadotropin CTPs to protect against degradation and to extend circulatory half-life. The attachment of CTPs to both the amino and carboxy termini is associated with improved pharmacokinetic and pharmacodynamic measures. The disclosure emphasizes that this end-to-end CTP modification supports reduced dosing frequency while maintaining biological activity.
The invention also relates to systemically administering CTP-modified growth hormone (GH) comprising a growth hormone fused to a chorionic gonadotropin carboxy terminal peptide (CTP). The disclosed embodiments include intravenous, intramuscular, or subcutaneous injection, and describe lyophilized and liquid pharmaceutical compositions, together with delivery formats including liposomes, polymeric microparticles, nanoparticles or lipid nanoparticles, microspheres, and lipid emulsions.
Claims Coverage
The provided set includes two independent claims. Across them, the core inventive features are end-functionalization of an EPO peptide with chorionic gonadotropin carboxy terminal peptides at the amino terminus and carboxy terminus, and specifying the amino acid sequence as SEQ ID NO: 51 to improve biological half life.
CTP-modified EPO with N- and C-terminal CTP attachment
A chorionic gonadotropin carboxy terminal peptide (CTP)-modified polypeptide consisting of a peptide of interest, wherein a first chorionic gonadotropin carboxy terminal peptide (CTP) is attached to the amino terminus of said peptide of interest, and a second and third chorionic gonadotropin carboxy terminal peptide are attached to the carboxy terminus of said peptide of interest, wherein said peptide of interest is an erythropoietin (EPO) peptide, and wherein the amino acid sequence of said polypeptide is set forth in SEQ ID NO: 51.
Improving biological half life by attaching terminal CTPs to an EPO peptide
A method of improving a biological half life of a peptide of interest, wherein said peptide of interest is an erythropoietin peptide (EPO), said method comprising attaching a first chorionic gonadotrophin carboxy terminal peptide (CTP) to an amino terminus of said peptide of interest and a second and third chorionic gonadotrophin carboxy terminal peptide (CTP) to a carboxy terminus of said peptide of interest, wherein the amino acid sequence of said CTP-modified peptide of interest is set forth in SEQ ID NO: 51, thereby improving a biological half life of a peptide of interest.
The independent claims define an EPO peptide modified at both ends with chorionic gonadotropin carboxy terminal peptides, with the CTP-modified sequence specified as SEQ ID NO: 51. A corresponding independent method claim improves biological half life of an EPO peptide by the same terminal CTP attachment and sequence specification.
Stated Advantages
Improving a biological half life of a peptide of interest.
Protect against degradation and extend circulatory half-life.
Improved pharmacokinetic and pharmacodynamic measures.
Reduced dosing frequency while maintaining biological activity.
Documented Applications
Long-acting polypeptides comprising CTP-modified erythropoietin (EPO) peptides.
Liquid pharmaceutical formulations for the CTP-modified polypeptide.
Supporting constructs for EPO-CTP and growth hormone (GH)-CTP.
Systemically administering CTP-modified growth hormone (GH) by intravenous, intramuscular, or subcutaneous injection.
Lyophilized and liquid pharmaceutical compositions for injectable delivery.
Delivery formats including liposomes, polymeric microparticles, nanoparticles or lipid nanoparticles, microspheres, and lipid emulsions.
Kit/dispenser packaging concepts with labeling and instructions for use.
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