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EP-4735492-A1 - POLYMER-ENABLED DELIVERY OF PHARMACEUTICAL AGENTS

EP4735492A1EP 4735492 A1EP4735492 A1EP 4735492A1EP-4735492-A1

Abstract

Disclosed herein is a bioactive polymer for forming a solution and/or hydrogel to stabilise one or more pharmaceutically active agents prior to, during or post-administration, the polymer comprising a first monomer for binding water, a second monomer for imparting mechanical properties to the scaffold; optionally, a third monomer for binding to a natural or synthetic peptide or protein (NSPP); and a fourth monomer for imparting phase-transition behaviour. Preferably, the first monomer is OEGMA; the second monomer is PLA/HEMA; the third monomer is NAS; and the fourth monomer is NIPAAm, and the polymer comprises: OEGMA in an amount of from about 1 to about 15 mol%; PLA/HEMA in an amount of from 5 to about 50 mol%; NAS in an amount of from 0 to about 15 mol%; and NIPAAm in an amount of up to about 85 mol%.

Inventors

  • FATHI, Ali
  • Abrams, Terence
  • KNOX, Will
  • MALEKNIA, Simin
  • YOUNG, PAUL
  • TRAINI, DANIELA
  • ONG, Hui Xin
  • AL-MAZI, Juhura

Assignees

  • Trimph IP Pty Ltd

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A polymer for forming a solution and/or hydrogel to stabilise one or more pharmaceutically active agents prior to, during or post-administration, the polymer comprising: a first monomer for binding water; a second monomer for imparting mechanical properties to the scaffold; optionally, a third monomer for binding to a natural or synthetic peptide or protein (NSPP); and a fourth monomer for imparting phase-transition behaviour.
  2. 2. A polymer according to claim 1, wherein the administration is by way of intravascular, intramuscular, subcutaneous, inhalable respiratory, oral inhaled or intranasal administration.
  3. 3. A polymer according to claim 2, wherein the administration is intranasal.
  4. 4. A polymer according to any one of the preceding claims, wherein the first monomer is one or more poly ethers, selected from: polyethylene glycol (PEG), oligo(ethylene glycol) (OEG), polyethylene oxide (PEG), polyethylene oxide-co -propylene oxide (PPG), co-poly ethylene oxide block or random copolymers thereof.
  5. 5. A polymer according to claim 4, wherein the first monomer is oligo (ethylene) glycol monomethyl ether methacrylate (OEGMA).
  6. 6. A polymer according to any one of the preceding claims, wherein the second monomer is a methacrylate, or a random co-polymer comprising a methacrylate, selected from: hydroxy ethyl methacrylate (HEMA), a hydroxy ethyl methacrylate poly(lactic acid) copolymer (PLA/HEMA), poly(lactic acid), poly (caprolactone), poly (glycolide), poly(glycolide-colactide) or poly(glycolide-co-caprolactone).
  7. 7. A polymer according to claim 6, wherein the second monomer is hydroxyethyl methacrylate poly (lactic acid) (PLA/HEMA).
  8. 8. A polymer according to any one of the preceding claims, wherein the third monomer has electrophilic functional groups for binding to the NSPP.
  9. 9. A polymer according to claim 8, wherein the third monomer is selected from: N- hydroxysulfosuccinimide (SNHS), N-hydroxy ethoxylated succinimide (ENHS), and N-acryloxysuccinimide (NAS).
  10. 10. A polymer according to any claim 9, wherein the third monomer is N- acryloxysuccinimide (NAS).
  11. 11. A polymer according to any one of the preceding claims, wherein the fourth monomer has a lower critical solution temperature (LCST) less than about 37 °C.
  12. 12. A polymer according to claim 11, wherein the fourth monomer is selected from: poly (ethylene oxide )/poly (propylene oxide) and poly(N-isopropylacrylamide) (PNIPAAm) homopolymers and copolymers.
  13. 13. A polymer according to claim 12, wherein the fourth monomer is (N- isopropylacrylamide) (NIPAAm).
  14. 14. A polymer according to any one of the preceding claims, wherein the polymer comprises the first monomer in an amount of from about 1 to about 15 mol%; the second monomer in an amount of from about 5 to about 50 mol%; the third monomer in an amount of from about 0 to about 15 mol%; and the fourth monomer in an amount which makes up the remainder to 100% of the polymer.
  15. 15. A polymer according to any one of the preceding claims, wherein: the first monomer is OEGMA; the second monomer is PLA/HEMA; the third monomer is NAS; and the fourth monomer is NIPAAm, wherein the polymer comprises: OEGMA in an amount of from about 1 to about 15 mol%; PLA/HEMA in an amount of from 5 to about 50 mol%; NAS in an amount of from 0 to about 15 mol%; and NIPAAm in an amount of up to about 85 mol%.
  16. 16. A polymer according to any one of the preceding claims, wherein the one or more pharmaceutically-active agents comprise a vaccine otherwise restricted to delivery via intramuscular injection.
  17. 17. A polymer according to claim 16, wherein the vaccine otherwise restricted to delivery via intramuscular injection is a COVID- 19 (SARS-CoV-2) vaccine.
  18. 18. A polymer according to claim 17, wherein the COVID- 19 vaccine is the Pfizer- BioNTech (Comirnaty/Tozinameran) vaccine.
  19. 19. A polymer according to any one of the preceding claims, wherein the polymer is present in a concentration greater than or equal to about 15 mg/mL.
  20. 20. A polymer according to claim 19, wherein the polymer is present in a concentration between about 25 and about 35 mg/mL.

Description

POLYMER-ENABLED DELIVERY OF PHARMACEUTICAL AGENTS Related Application [001] This application claims convention priority from Australian patent application 2023902095, fded 30 June 2023. The content of AU’095 is incorporated herein by reference. Field of the Invention [002] The present invention relates to biologically-compatible polymers and the present inventors’ surprising discovery that such polymers stabilise certain pharmaceutical agents for a period sufficient to allow for their administration to a subject via modes of delivery such as intravascular, intramuscular, subcutaneous, oral inhaled or intranasal [003] The present invention further relates to a method of enabling the delivery of one or more pharmaceutically active agents and the use of the biologically-compatible polymer in the manufacture of a medicament for the delivery of one or more pharmaceutically active agents. Preferred embodiments relate to intranasal delivery. [004] In another embodiment, the present invention relates to a kit for enabling the intravascular, intramuscular, subcutaneous, oral inhaled or intranasal delivery of one or more pharmaceutically active agents. [005] The present invention is envisaged to be useful in providing an alternative means of administration for a vaccine or medicament otherwise restricted to intramuscular injectable delivery. It is surprisingly found that the stabilising effect of the polymer enables delivery of the one or more pharmaceutically-active agents to a subject wherein intravascular, intramuscular, subcutaneous, oral inhaled or intranasal administration may not have been previously viable. [006] The present invention is envisaged to be useful in providing an alternative means for the formulation, stabilisation, manufacture and storage of vaccines or medicaments otherwise restricted to cold shipment, cold storage and complex manufacturing steps that may involve microfluidic devices or other costly steps. [007] Although the present invention will be described hereinafter with reference to its preferred embodiment, it will be appreciated by those of skill in the art that the spirit and scope of the invention may be embodied in many other forms. Background of the Invention [008] Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. [009] The constant development of RNA-based actives, including but not limited to vaccines for infectious disease control and oncological purposes as well as the ongoing COVID- 19 (SARS-CoV-2) pandemic has driven societal awareness of and interest in such technologies. Several COVID-19 vaccines, such as the Pfizer-BioNTech and Moderna vaccines, use RNA to stimulate an immune response. When introduced into human tissue, the vaccine contains either self-replicating RNA or messenger RNA (mRNA), which both cause cells to express the SARS-CoV-2 spike protein. This teaches the body how to identify and destroy the corresponding pathogen. RNA vaccines often use nucleo side-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles (LNPs) which protect the RNA strands and help their absorption into the cells. [0010] The stability of LNPs and the incorporated RNA component/s over the intended shelf life of the vaccine are critical to achieving the intended biological activity. This usually limits such vaccines to limited shelf life at specific temperature, cold-shipment and storage. Such strict requirements cause challenges in achieving a broader deployment of such technologies. [0011] As noted, a preferred embodiment of the present invention relates to Applicant’s proprietary polymers that may act to stabilise the active/s in an mRNA vaccine, preferably a COVID- 19 vaccine, across conditions thereby enabling and supporting intranasal administration. Whereas the ensuing discussion focusses upon such embodiments, the skilled person will appreciate that within the context of the overall invention, these are merely exemplary. [0012] All presently-approved coronavirus vaccines are administrated by intramuscular injection. However, with injection not being preferred or tolerated amongst a significant proportion of the population, various other types of vaccine delivery methods have been studied for future coronavirus vaccines. One such mode is that of intranasal delivery. [0013] Intranasal vaccines target mucosal immunity in the nasal mucosa which is a portal for viral entrance to the body. These vaccines are designed to stimulate nasal immune factors, such as IgA. In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (e.g., needle phobia) are involved. Nasal vaccines have been approved for influenza, but not as yet for COVID- 19. [0014] A recent publication by Carvalho (Nature Medicine, Vol.28, December 2022, pp.2439- 2440) has pinp