Long-acting coagulation factors and methods of producing same
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12203113-B2
Publication Date
2025-01-21
Expiration Date
Abstract
Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.
Core Innovation
The invention provides long-acting coagulation factor polypeptides engineered by attaching chorionic gonadotropin carboxy terminal peptides (CTPs) to coagulation factors in order to extend circulatory half-life. In particular, CTPs are attached to the C-terminus of the coagulation factor, and the disclosed CTP-modified coagulation factors include CTP-modified Factor VII (FVII) and CTP-modified Factor VIIa (FVIIa).
The disclosed CTP-modified coagulation factors are described as preserving biological activity while improving pharmacokinetic and exposure outcomes, including increases in Cmax/Tmax, AUC, and biological half-life, with reduced clearance. The patent positions these properties as enabling less frequent dosing through reduced administration frequency compared with an unmodified coagulation factor.
A method is disclosed for increasing patient compliance in the use of a coagulation factor therapy by reducing the frequency of administration. The method administers a chorionic gonadotropin CTP-modified coagulation Factor VII (FVII) polypeptide selected from CTP-modified FVII or activated CTP-modified FVIIa polypeptides, with sequence selections such as SEQ ID NO: 25 and amino acids 39-528 of SEQ ID NO: 25.
Claims Coverage
The independent claim coverage centers on a compliance-increasing method for coagulation factor therapy in a human subject, achieved by reducing administration frequency compared with an unmodified coagulation factor. Three inventive features are recited: CTP-modified Factor VII, activated CTP-modified Factor VIIa, and the compliance increase by reduced administration frequency.
Increasing patient compliance by reduced administration frequency
A method of increasing patient compliance in the use of a coagulation factor therapy in a human subject, comprising administering a CTP-modified coagulation Factor VII polypeptide to a subject in need thereof, wherein increasing patient compliance is achieved by reducing the frequency of administration compared to an unmodified coagulation factor.
CTP-modified coagulation Factor VII polypeptide selected by defined sequences
Administering a CTP-modified coagulation FVII polypeptide having an amino acid sequence selected from SEQ ID NO: 25 and amino acids 39-528 of SEQ ID NO: 25.
Activated CTP-modified coagulation Factor VII (FVIIa) polypeptide selected by defined sequences
Administering an activated CTP-modified Factor VII (FVIIa) polypeptide having an amino acid sequence selected from SEQ ID NO: 25 and amino acids 39-528 of SEQ ID NO: 25.
The inventive coverage is a compliance-increasing coagulation factor therapy method using a chorionic gonadotropin CTP-modified Factor VII or activated CTP-modified Factor VIIa polypeptide, with the compliance benefit linked to reduced frequency of administration versus an unmodified coagulation factor.
Stated Advantages
Increases patient compliance in coagulation factor therapy by reducing the frequency of administration compared to an unmodified coagulation factor.
Improved long-acting effect associated with increased half-life and AUC.
Preserving biological activity while improving pharmacokinetic and exposure outcomes, including reduced clearance.
Prolonged exposure and long-lasting activity are described for CTP-multimers.
Maintained serine protease activity and retained activity in TF/FVIIa-mediated Factor X activation are described for CTP-modified Factor VII/FVIIa variants.
Documented Applications
Preclinical evaluation in FVIII-deficient hemophilia mice, including prolonged hemostatic activity and comparisons versus NovoSeven®.
Rat pharmacokinetics after intravenous administration to characterize half-life and AUC for CTP-multimers.
Subcutaneous administration studies described with prolonged clotting activity and improved survival in tail vein transection and PT restoration models versus NovoSeven®.
PT/aPTT functional assays and thrombin-related activity characterization described for retained activity of CTP-modified Factor VII/FVIIa variants.
Hemophilia-related disorders and related coagulation factor needs.
Increasing patient compliance in the use of a coagulation factor therapy in a human subject.
Subcutaneous self-injection rationale and subcutaneous absorption.
Interested in licensing this patent?