Method for administering a sustained release formulation
Inventors
Arnold, Susan • Prior, Christopher • Georgopoulos, Lynne
Assignees
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Publication Number
US-9919032-B2
Publication Date
2018-03-20
Expiration Date
Abstract
The present invention provides pharmaceutical formulations for sustained release when administered at cold temperatures, and methods for delivering a treatment regimen with a combination of sustained release and long half-life formulations. The invention provides improved pharmacokinetics for peptide and small molecule drugs.
Core Innovation
The invention relates to sustained release systemic delivery formulations comprising a therapeutic agent and one or more pharmaceutically acceptable excipients and/or diluents. The therapeutic agent comprises a Vasoactive Intestinal Peptide (VIP) and an elastin-like peptide (ELP), and the ELP comprises at least 90 repeating units of VPGXG (SEQ ID NO: 3). The formulation is administered at a temperature from about 2 to about 8 C, and administration at about 2 to about 8 C slows absorption of the therapeutic agent compared to absorption of the same therapeutic agent administered at room temperature.
The reversible sustained release behavior is based on a reversible hydrogen-bonded/hydrophobic matrix formed by elastin-like proteins (ELPs). Cold storage and administration enable slow reversal at body temperature, producing a flat pharmacokinetic profile with a long Tmax and reduced peak-to-trough variation. The matrix behavior is tied to phase transition/turbidity and transition temperature (Tt), supported by elastin-like protein structural design.
ELP structural units are defined using VPGXG repeat units (SEQ ID NO: 3), including compositions of [VPGXG]90 and [VPGXG]120 with X in {V,G,A} and an approximately V:G:A ratio of 5:3:2. The documented payloads include GLP-1/ELP fusions and VIP/ELP fusions, including VIP/ELP fusions described as VPAC2 selective agonist constructs such as PB1023 and PB1046/M-VIP. The patent also indicates that cold administration decreases absorption (lower Cmax/AUC) versus room temperature while maintaining bioequivalence between specified concentrations at room temperature.
Claims Coverage
Two independent claims are presented. Each independent claim centers on a sustained release systemic delivery method in which the therapeutic agent is a VIP combined with an elastin-like peptide meeting defined repeating-unit requirements, together with administration at a temperature from about 2 to about 8 C to slow absorption compared to room temperature.
Cold administration to slow absorption of a VIP–ELP sustained release formulation
A method for administering to a subject a sustained release formulation for systemic delivery comprising a therapeutic agent and one or more pharmaceutically acceptable excipients and/or diluents, wherein the therapeutic agent comprises a Vasoactive Intestinal Peptide (VIP) and an elastin-like peptide comprising at least 90 repeating units of VPGXG (SEQ ID NO: 3), and wherein the formulation is administered at a temperature from about 2 to about 8 C, wherein administration at about 2 to about 8 C slows absorption compared to absorption of the same therapeutic agent administered at room temperature.
VPAC-2 selective VIP with additional N-terminal methionine and defined ELP repeat composition
A method for administering to a subject a sustained release formulation for systemic delivery comprising a therapeutic agent and one or more pharmaceutically acceptable excipients and/or diluents, wherein the therapeutic agent comprises a VPAC-2 selective Vasoactive Intestinal Peptide (VIP) comprising an additional Methionine at the N-terminus and an elastin-like peptide comprising 120 repeating units of SEQ ID NO: 3 with each X selected from V, G, and A, and wherein the ratio of V:G:A is about 5:3:2, and wherein the formulation is administered at a temperature from about 2 to about 8 C, wherein administration at about 2 to about 8 C slows absorption compared to absorption of the same therapeutic agent administered at room temperature.
Across both independent claims, the inventive concept is a sustained release systemic delivery method using a VIP–ELP therapeutic agent with specified VPGXG repeat-unit requirements, where administering the formulation at about 2 to about 8 C slows absorption relative to room-temperature administration.
Stated Advantages
Slows absorption of the therapeutic agent compared to absorption of the same therapeutic agent administered at room temperature.
Produces a flat pharmacokinetic (PK) profile with reduced peak-to-trough variation and a long Tmax.
Decreases absorption exposure (lower Cmax/AUC) versus room temperature.
Maintains bioequivalence between specified formulation concentrations at room temperature.
Documented Applications
Systemic delivery in adult subjects with type 2 diabetes mellitus (T2DM) using subcutaneous (SC) administration of VIP/ELP fusion formulations such as PB1023 and PB1046/M-VIP, supported by pharmacokinetic comparisons between cold and room temperature administration.
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