Long-acting polypeptides and methods of producing and administering same
Inventors
Assignees
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Publication Number
US-9884901-B2
Publication Date
2018-02-06
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 disclosed.
Core Innovation
The invention describes a method of treating a subject suffering from a fatigue syndrome following cancer chemotherapy or a chronic infection, where the subject is anemic. The method comprises administering a therapeutically effective amount of a polypeptide consisting of a chorionic gonadotropin carboxy terminal peptide (CTP)-modified erythropoietin (EPO), with one CTP attached to the amino terminus of the EPO and two CTPs attached to the carboxy terminus of the EPO.
The disclosed polypeptide can be a precursor or a mature polypeptide, and it can optionally include a signal peptide attached to the amino terminus of the one CTP. In this configuration, the administration is directed to treat the anemic subject suffering from fatigue syndrome following cancer chemotherapy or a chronic infection, including any combination thereof.
The document also describes CTP-modified protein constructs and compares polypeptides with different CTP attachment patterns in bioactivity and pharmacokinetic studies. It discusses CTP-modified EPO polypeptides, including EPO-0, EPO-1, EPO-2, EPO-3, and EPO-4 variants, and relates these to TF-1 bioactivity, in vivo pharmacokinetics, pharmacodynamic outcomes, glycosylation profiling, and comparative studies versus commercial epoetin formulations.
Claims Coverage
The relevant independent claim is directed to administering a therapeutically effective amount of a CTP-modified EPO polypeptide for treating anemic fatigue syndrome following cancer chemotherapy or chronic infection, with a defined CTP attachment pattern and optionally a signal peptide for the precursor form.
CTP-modified erythropoietin for anemic fatigue syndrome after chemotherapy or chronic infection
Administering to a subject an effective amount of chorionic gonadotropin carboxy terminal peptide (CTP)-modified erythropoietin (EPO), where the CTP-modified EPO consists of one CTP attached to the amino terminus of the EPO and two CTPs attached to the carboxy terminus of the EPO, wherein the polypeptide consists of a precursor or a mature polypeptide and optionally a signal peptide attached to the amino terminus of said one CTP, and wherein said administration treats the anemic subject suffering from fatigue syndrome following cancer chemotherapy or a chronic infection, or any combination thereof.
The claim coverage centers on a single independent claim requiring the defined CTP attachment architecture on EPO and applying it to treat anemic fatigue syndrome associated with cancer chemotherapy or a chronic infection, with optional inclusion of a signal peptide for precursor forms.
Stated Advantages
Protects peptides from degradation.
Extends circulatory half-life and clearance time.
Can enhance potency and pharmacokinetic exposure (AUC).
Provides pharmacokinetic and pharmacodynamic advantages versus rhEPO and Aranesp, including higher t1/2, favorable AUC and Cmax, and detectable duration for an EPO variant.
Documented Applications
Treating an anemic subject suffering from a fatigue syndrome following cancer chemotherapy.
Treating an anemic subject suffering from a chronic infection-related fatigue syndrome.
Treating chronic infections including HIV, inflammatory bowel disease, and septic episodes in an anemic subject with fatigue syndrome following cancer chemotherapy or chronic infection.
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