Long-acting polypeptides and methods of producing and administering same

Inventors

Fima, Udi Eyal • Hart, Gili

Assignees

Opko Biologics Ltd

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 disclosure relates to polypeptides consisting of chorionic gonadotropin carboxy terminal peptide (CTP)-modified erythropoietin (EPO) for use in treating an EPO-associated condition and for stimulating erythropoiesis. The CTP-modified EPO polypeptides include a specific attachment pattern in which one CTP is attached to the amino terminus of EPO and two CTPs are attached to the carboxy terminus of EPO, optionally with a signal peptide attached to the amino terminal CTP.

The disclosure addresses treatment of an EPO-associated condition, specifically anemia, and stimulation of erythropoiesis through administration of a therapeutically effective amount of a CTP-modified EPO polypeptide. The claimed embodiments are defined by CTP attachment sites and, in some embodiments, by a signal peptide attached to the amino terminal CTP.

The described embodiments include sequence-defined polypeptides and processing features such as truncation of at least one chorionic gonadotrophin carboxy terminal peptide, and glycosylation status of EPO or other components. The disclosure also describes long-acting constructs for CTP-modified proteins using biological potency and pharmacokinetics/pharmacodynamics, including data comparing CTP-modified EPO variants.

Claims Coverage

The partial content provides two independent claims. Both center on administering a therapeutically effective amount of a CTP-modified EPO polypeptide with a defined CTP attachment pattern, and the second claim further requires specified sequence identities via SEQ ID numbers. Across the independent claims, there are 2 main inventive features.

The independent claims cover administering a therapeutically effective amount of a CTP-modified EPO polypeptide with a defined CTP attachment pattern. The second independent claim further narrows the covered constructs by requiring the administered CTP-modified EPO amino acid sequence to correspond to a specified sequence set forth in SEQ ID NO: 51 or SEQ ID NO: 3, with embodiments that also include a signal peptide attached to the amino terminal CTP.

Stated Advantages

Documented Applications