Long-acting polypeptides and methods of producing and administering same
Inventors
Assignees
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Publication Number
US-10221228-B2
Publication Date
2019-03-05
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 disclosure relates to long-acting polypeptides and methods in which a glucagon-like peptide 1 (GLP-1) peptide of interest is modified by attaching chorionic gonadotropin carboxy terminal peptides. A GLP-1 peptide with an amino acid sequence consisting of SEQ ID NO: 25 is provided as the peptide of interest, and the described constructs are associated with insulinotropic activity for the GLP-1 peptide.
Three chorionic gonadotropin carboxy terminal peptides are attached in a defined arrangement, including a first chorionic gonadotropin carboxy terminal peptide attached to the amino terminus of the GLP-1 peptide of interest, a second chorionic gonadotropin carboxy terminal peptide attached to the carboxy terminus, and a third chorionic gonadotropin carboxy terminal peptide attached in tandem to the second chorionic gonadotropin carboxy terminal peptide. An optional signal peptide can be attached at the N-terminal end of the first chorionic gonadotropin carboxy terminal peptide.
The biological problem addressed is the need to improve biological half life and associated pharmacological performance of a GLP-1 peptide of interest. The disclosure states that attaching three chorionic gonadotropin carboxy terminal peptides in the defined arrangement improves a biological half life.
Claims Coverage
Two independent claims are present. The inventive features center on a defined three-CTP attachment architecture to a GLP-1 peptide of interest with a specified SEQ ID, optionally including an N-terminal signal peptide.
Three CTPs attached in defined N-terminus, C-terminus, and tandem arrangement to SEQ ID NO: 25 GLP-1
A polypeptide comprising a glucagon-like peptide 1 (GLP-1) peptide of interest with an amino acid sequence consisting of SEQ ID NO: 25, wherein three chorionic gonadotropin carboxy terminal peptides are attached to the GLP-1 peptide of interest with a first attached to an amino terminus, a second attached to a carboxy terminus, and a third attached in tandem to the second chorionic gonadotropin carboxy terminal peptide.
Improving biological half life by attaching three CTPs to SEQ ID NO: 25 GLP-1 with optional signal peptide
A method of improving a biological half life of a GLP-1 peptide of interest, comprising attaching three chorionic gonadotropin carboxy terminal peptides with a first attached to an amino terminus, a second attached to a carboxy terminus, and a third attached in tandem to the second chorionic gonadotropin carboxy terminal peptide, wherein the amino acid sequence of said peptide of interest consists of SEQ ID NO: 25 and optionally a signal peptide is attached at the N-terminal end of the first chorionic gonadotropin carboxy terminal peptide.
Claim coverage is centered on the same inventive attachment architecture: three chorionic gonadotropin carboxy terminal peptides arranged as N-terminal attachment plus C-terminal attachment with an additional tandem CTP, applied to a GLP-1 peptide whose amino acid sequence consists of SEQ ID NO: 25. The claims further cover the optional attachment of a signal peptide at the N-terminal end of the first attached CTP.
Stated Advantages
Improving a biological half life of a GLP-1 peptide of interest.
Long-acting effects with reduced dosing frequency are described in the provided document summary.
The GLP-1 peptide is defined to exhibit insulinotropic activity.
Documented Applications
A method for improving a biological half life of a GLP-1 peptide of interest by attaching three chorionic gonadotropin carboxy terminal peptides with an optional signal peptide.
Phase II clinical evaluation in GHD patients using weekly/twice-monthly dosing for hGH-CTP-CTP products described in the document summary.
Evaluation of long-acting effects supported by pharmacokinetics/pharmacodynamics and glycan/sialic acid profiling for CTP-hGH-CTP-CTP and EPO-CTP variants as described in the document summary.
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