Injectable solution at pH 7 comprising at least one basal insulin wherein the pI is comprised from 5.8 to 8.5 and a co-polyamino acid bearing carboxylate charges and hydrophobic radicals

Inventors

Chan, You-Ping • GEISSLER, Alexandre • Noel, Romain • ROGER, Walter • Charvet, Richard • LAURENT, Nicolas

Assignees

Adocia SAS

Abstract

A composition includes co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical -Hy that are chosen among the co-polyamino acids according to formula XXXb: wherein, D represents, independently, either a group —CH2— (aspartic acid) or a group —CH2—CH2— (glutamic acid),X represents a cationic entity chosen from the group comprising alkali cations,Rb and R′b, identical or different, are either a hydrophobic radical -Hy, or a radical chosen from the group consisting of an H, a C2 to C10 linear acyl group, a C3 to C10 branched acyl group, a benzyl, a terminal “amino acid” unit and a pyroglutamate,at least one of Rb and R′b is a hydrophobic radical -Hy,n+m represents the degree of polymerization DP of the co-polyamino acid, namely the mean number of monomeric units per co-polyamino acid chain and 5≤n+m≤250.

Core Innovation

The invention relates to an injectable aqueous solution comprising basal insulin having an isoelectric point pI comprised from 5.8 to 8.5, and a co-polyamino acid comprising glutamic or aspartic units. The composition has a pH comprised from 6.0 to 8.0, and the co-polyamino acid is defined according to formula I with two chains of glutamic or aspartic units PLG bound together by a divalent linear or branched radical or spacer Q.

The co-polyamino acid bears carboxylate charges and at least one hydrophobic radical -Hy. The spacer Q is bound to the two PLG chains by an amide function resulting from a reaction between an amine function and an acid function respectively borne either by Q or by a glutamic or aspartic unit, and 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.

The hydrophobic radical -Hy is defined as a radical according to formula X, with selectable sub-radicals GpR, GpG, GpH, GpA, GpL, and GpC. The structure further constrains the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units to 0<M≤0.5, the degree of polymerization DP in glutamic or aspartic units for the PLG chains to 5 to 250, and free carboxylic acid functions to alkali cation salts selected from Na+ and K+.

Claims Coverage

The consolidated claim coverage includes two independent claims. The inventive matter centers on an injectable aqueous insulin composition at pH 6.0 to 8.0 with basal insulin having pI 5.8 to 8.5, together with a glutamic/aspartic co-polyamino acid architecture defined by formulas I and X, amide-linked divalent spacer Q, hydrophobic radical -Hy, and quantitative ratio and polymerization constraints.

Overall, the independent claims cover an injectable aqueous insulin composition that includes a specifically defined glutamic/aspartic co-polyamino acid polymer architecture. The claimed polymer features two PLG chains linked by a divalent spacer Q through an amide function, hydrophobic radicals -Hy defined by formula X and selectable sub-radical groups, and constrained ratio, DP, and alkali salt forms.

Stated Advantages

Documented Applications