Compositions in the form of an injectable aqueous solution comprising amylin, an amylin agonist receptor or an amylin analogue and a co-polyamino acid
Inventors
Chan, You-Ping • GEISSLER, Alexandre • Noel, Romain • Charvet, Richard • LAURENT, Nicolas
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12186373-B2
Publication Date
2025-01-07
Expiration Date
Abstract
A composition in the form of an injectable aqueous solution, for which the pH is comprised from 6.0 to 8.0, includes at least: a) amylin, an amylin receptor agonist or an amylin analogue;b) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, said co-polyamino acid being constituted of glutamic or aspartic units and said hydrophobic radicals Hy chosen according to formula X as defined below:c) characterized in that the composition does not include basal insulin for which the isoelectric point IP is comprised from 5.8 to 8.5. The composition also includes a prandial insulin.
Core Innovation
The invention relates to an injectable aqueous solution having a pH of from 6.0 to 8.0 that comprises amylin, an amylin receptor agonist or an amylin analogue, and a co-polyamino acid bearing carboxylate charges. The co-polyamino acid is constituted of glutamic or aspartic units and bears at least one hydrophobic radical Hy, wherein Hy comprises a radical according to formula X and is covalently bound to the co-polyamino acid so that amide functions are formed.
The hydrophobic radical Hy is defined through selectable radicals GpR, GpG and GpH, GpA, GpL and GpC chosen among the cited formula classes, with attachment-site notation and integer or range constraints defining permissible combinations. The covalent linkage is expressed as amide-forming covalent bonds between a carbonyl of the hydrophobic radical Hy and a nitrogen atom borne by the co-polyamino acid, and/or between a nitrogen atom of the hydrophobic radical Hy and a carbonyl borne by the co-polyamino acid.
The co-polyamino acid is further constrained by a ratio M between the number of hydrophobic radicals Hy and the number of glutamic or aspartic units of 0<M≤0.5, a degree of polymerization DP from 5 to 250, and free carboxylic acids in the form of an alkaline cation salt chosen from Na+ and K+. The disclosure also encompasses a precursor Hy′ of the hydrophobic radical Hy having a formula according to formula X′, with the same classes of selectable radicals and carbon-count limits for the alkyl radical Cx depending on the number of −GpC groups.
Claims Coverage
The provided material identifies three independent claim categories covering an injectable aqueous composition, a co-polyamino acid structure, and a precursor Hy′ structure. The inventive features center on the defined hydrophobic radical Hy of formula X, its amide-function covalent attachment to a glutamic or aspartic co-polyamino acid bearing carboxylate charges, and quantitative constraints on M, DP, and Cx.
Injectable aqueous amylin composition with defined hydrophobic radical Hy and co-polyamino acid
An injectable aqueous solution having a pH of from 6.0 to 8.0 comprising amylin, an amylin receptor agonist or an amylin analogue, and a co-polyamino acid bearing carboxylate charges and constituted of glutamic or aspartic units, wherein the co-polyamino acid comprises at least one hydrophobic radical Hy according to formula X and the hydrophobic radical Hy is bound to the co-polyamino acid via amide-forming covalent bonds.
Hydrophobic radical Hy structural definition by selectable radicals
A hydrophobic radical Hy comprising a radical according to formula X, with GpR chosen among formulas VII, VII′ or VII″, GpG and GpH chosen among formulas XI or XI′, GpA as a radical according to formula VIII with A′ chosen among formulas VIII′, VIII″ or VIII″′, GpL as a radical according to formula XII, and GpC as a radical according to formula IX, together with attachment-site notation and integer or range constraints.
Covalent amide-function binding with quantitative constraints
The hydrophobic radical Hy according to formula X is covalently bound to the co-polyamino acid so that amide functions are formed, with the ratio M between the number of hydrophobic radicals Hy and the number of glutamic or aspartic units being 0<M≤0.5, the degree of polymerization DP being from 5 to 250, and free carboxylic acids present as an alkaline cation salt chosen from Na+ and K+.
Precursor Hy′ of hydrophobic radical Hy
A precursor Hy′ of a hydrophobic radical Hy having a formula according to formula X′, with the same classes of selectable radicals GpR, GpG/GpH, GpA/A′, GpL and GpC, the same attachment-site marker “*”, and carbon-count limits for the monovalent linear or branched alkyl radical Cx depending on how many −GpC groups are borne.
Across the independent claims, coverage centers on a formula-defined hydrophobic radical Hy, covalent attachment of Hy to a glutamic or aspartic co-polyamino acid through amide functions, and the quantitative constraints M, DP, and Cx. The injectable composition claim further adds amylin, an amylin receptor agonist or an amylin analogue, and the pH range of 6.0 to 8.0.
Stated Advantages
Increases fibrillation latency measured by ThT for amylin and combinations with prandial insulin at neutral pH.
Yields clear, soluble injectable solutions.
Documented Applications
Stabilization of amylin and combinations with prandial insulin at neutral pH in an injectable aqueous solution.
Use in injectable antidiabetic compositions comprising amylin or an amylin receptor agonist/analogue in pH 6.0 to 8.0 solutions.
Pramlintide formulations containing pramlintide and excipients including m-cresol and glycerin, using the disclosed co-polyamino acids at stated ratios and around pH 6.6.
Formulations that may further include insulin and optionally NaCl and/or ZnCl2 in combination with pramlintide and the disclosed co-polyamino acids.
Assessment of fibrillation behavior of the formulations using ThT-based measurements reported as fibrillation latency time (LT).
Physical stability evaluation of the formulations in vial/cartridge storage at 30°C and 37°C.
Interested in licensing this patent?