Compositions in the form of an injectable aqueous solution comprising human glucagon 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-10987426-B2
Publication Date
2021-04-27
Expiration Date
Abstract
Physically stable compositions in the form of an injectable aqueous solution, wherein the pH is from 6.0 to 8.0, includes at least: a) human glucagon andb) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy. In one embodiment, the compositions further comprise a gut hormone.
Core Innovation
The invention relates to a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical -Hy. The co-polyamino acid is chosen from co-polyamino acids according to formula I and includes at least two chains of glutamic or aspartic units PLG bound together by an at least divalent linear or branched radical or spacer Q[-*]k by amide functions.
The hydrophobic radical -Hy is bound to the PLG either to a terminal amino acid unit or to a carboxyl function borne by one of the PLG chains, with covalent attachment through amide functions. The hydrophobic radical -Hy is according to formula X and is defined by selected sub-radicals GpR, GpG, GpH, GpA, GpL, and GpC.
The invention further specifies quantitative constraints, including a ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units between 0<M≤0.5, a degree of polymerization DP in glutamic or aspartic units for the PLG chains from 5 to 250, and free carboxylic acid functions in the form of alkali cation salts chosen from Na+ and K+. One claim also defines an injectable aqueous solution comprising human glucagon and the co-polyamino acid at pH from 6.0 to 8.0.
Claims Coverage
The consolidated claim coverage includes two independent claims: one directed to an injectable aqueous glucagon composition and one directed to the co-polyamino acid structure itself. The independent claims together define the core inventive features as a PLG-based co-polyamino acid framework, amide-linked spacer Q[-*]k, hydrophobic radical -Hy according to formula X, and composition constraints including pH, ratio M, DP, and salt form.
Injectable aqueous glucagon composition with PLG co-polyamino acid
An injectable aqueous solution having pH from 6.0 to 8.0 comprising human glucagon and a co-polyamino acid according to formula I, bearing carboxylate charges and at least one hydrophobic radical -Hy, with at least two chains of glutamic or aspartic units PLG bound together by an at least divalent linear or branched radical or spacer Q[-*]k bound by amide functions.
Co-polyamino acid with PLG chains linked by spacer Q[-*]k through amide functions
A co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical, including at least two chains of glutamic or aspartic units PLG bound together by an at least divalent linear or branched radical or spacer Q[-*]k, where the radical or spacer Q[-*]k is bound to the PLG by an amide function.
Hydrophobic radical -Hy bound to PLG via amide-forming covalent bonds
The hydrophobic radical -Hy is bound either to a terminal amino acid unit or to a carboxyl function borne by one of the PLG chains, and is bound to the PLG via covalent bonds forming amide functions.
Hydrophobic radical -Hy defined by formula X with selected sub-radicals
The at least one hydrophobic radical is according to formula X, with GpR chosen from formulas VII, VII′ or VII″; GpG and GpH chosen from formulas XI or XI′; GpA chosen from formula VIII with A′ chosen from VIII′, VIII″ or VIII‴; GpL chosen from formula XII; and GpC chosen from formula IX.
Composition constraints on hydrophobe loading, degree of polymerization, and salt form
The ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0<M≤0.5, the degree of polymerization DP in glutamic or aspartic units for the PLG chains is from 5 to 250, and the free carboxylic acid functions are in the form of alkali cation salt chosen from Na+ and K+.
The independent claims collectively require a PLG-based co-polyamino acid with carboxylate charges, a divalent spacer Q[-*]k linked by amide functions, hydrophobic radicals -Hy attached through amide-forming covalent bonds, and formula X-based structural selection. The composition claim additionally requires human glucagon in an injectable aqueous solution at pH 6.0 to 8.0, while the structure claim imposes the stated limits on M, DP, and Na+ or K+ salt form.
Stated Advantages
Not explicitly described in patent.
Documented Applications
An injectable aqueous solution comprising human glucagon.
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