Compositions in the form of an injectable aqueous solution comprising amylin, an amylin receptor agonist or an amylin analog and a co-polyamino acid
Inventors
Chan, You-Ping • GEISSLER, Alexandre • Noel, Romain • ROGER, Walter • Charvet, Richard • LAURENT, Nicolas
Assignees
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Publication Number
US-11173109-B2
Publication Date
2021-11-16
Expiration Date
Abstract
A composition in the form of an injectable aqueous solution, wherein the pH is comprised from 6.0 to 8.0, includes at least:a) amylin, an amylin receptor agonist or an amylin analog; andb) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, wherein the composition does not comprise a basal insulin wherein the isoelectric point pI is comprised from 5.8 to 8.5. The composition may further include a prandial insulin.
Core Innovation
The invention relates to an injectable aqueous solution having a pH comprised from 6.0 to 8.0, comprising amylin, an amylin receptor agonist or an amylin analog, together with a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical -Hy according to formula X. The co-polyamino acid is chosen among co-polyamino acids according to formula I, where at least two chains of glutamic or aspartic units are bound together by a divalent linear or branched radical or spacer Q by an amide function.
The hydrophobic radical -Hy is covalently bound either to a terminal amino acid unit or to a carboxyl function borne by one of the chains, and the co-polyamino acid bears free carboxylic acid functions in the form of alkali cation salt chosen from Na+ and K+. The hydrophobic radical -Hy is defined by formula X with nested choices for GpR, GpG, GpA, GpL, GpH and GpC, binding sites indicated by an asterisk or , and associated parameter constraints.
The co-polyamino acid structure is further constrained by a ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units, with 0<M2640.5, and by a degree of polymerization DP in glutamic or aspartic units comprised from 5 to 250. A hydrophobic radical precursor Hy2 is also defined by formula X2, with covalent amide-function attachment to the co-polyamino acid.
Claims Coverage
The consolidated claim coverage identifies three independent inventive features: the injectable aqueous composition, the co-polyamino acid structure, and the hydrophobic radical precursor Hy2. The coverage centers on amylin, an amylin receptor agonist or an amylin analog combined with a formula-defined carboxylate-charged co-polyamino acid bearing hydrophobic radical -Hy, with formula-based structural and quantitative constraints.
Injectable aqueous solution with amylin and formula-defined co-polyamino acid
An injectable aqueous solution having a pH comprised from 6.0 to 8.0 comprising amylin, an amylin receptor agonist or an amylin analog, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical -Hy according to formula X, the co-polyamino acid being chosen among co-polyamino acids according to formula I.
Co-polyamino acid framework with glutamic or aspartic unit chains linked by amide-bound spacer Q
A co-polyamino acid according to formula I comprising at least two chains of glutamic or aspartic units bound together by a divalent linear or branched radical or spacer Q, where Q is bound to the chains by an amide function, the hydrophobic radical -Hy is bound either to a terminal amino acid unit or to a carboxyl function borne by one of the chains, and free carboxylic acid functions are in the form of alkali cation salt chosen from Na+ and K+.
Hydrophobic radical -Hy defined by formula X and precursor Hy2 defined by formula X2
The at least one hydrophobic radical -Hy is defined by formula X with nested selections for GpR, GpG, GpA, GpL, GpH and GpC, binding sites indicated by or an asterisk, a ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units, and a degree of polymerization DP comprised from 5 to 250; the corresponding hydrophobic radical precursor Hy2 is chosen among compounds according to formula X2 and is bound to the co-polyamino acid through covalent amide functions.
The independent claims collectively cover an injectable aqueous amylin composition combined with a carboxylate-charged co-polyamino acid of formula I and a hydrophobic radical -Hy of formula X, together with the corresponding precursor Hy2 of formula X2. The claims further include the amide-linked spacer Q architecture, the formula-based selection of -Hy, and quantitative constraints including ratio M, DP, and Na+ or K+ salt forms.
Stated Advantages
Improved stability, as measured by ThT, greater than a reference composition lacking a co-polyamino acid bearing carboxylate charges and hydrophobic radicals -Hy.
Increased Thioflavin T (ThT) latent period, indicating delayed fibril formation.
Stabilization of amylin or amylin analog compositions at neutral pH 6.0 to 8.0.
Clear particle-free solution.
Enhanced fibrillation stability for compositions combining prandial insulin with amylin or amylin analog.
Documented Applications
Injectable aqueous formulations for amylin, an amylin receptor agonist, or an amylin analog.
Compositions that optionally co-formulate prandial insulin while excluding basal insulin.
Formulation of an injectable aqueous solution comprising amylin or an amylin receptor agonist or analog with the defined co-polyamino acid and hydrophobic radical -Hy at pH 6.0 to 8.0.
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