US Patent 11583572 Encapsulation of ultra-stable insulin analogues with polymer melts

An insulin composition comprises an insulin analogue and polymer blend. The insulin analogue contains cysteine substitutions at positions B4 and A10 (to form cystine B4-A10), and one or more additional substitutions selected from the group consisting of: a connecting domain of 5-11 amino acids between insulin A- and B domains; a non-beta-branched amino-acid substitution at position A8; a non-beta-branched acidic or polar side chain at position A14; a halogenic modification of PheB24 at the ortho position; and substitution of lysine at position B29 by Glu, Ala, Val, Ile, Leu, amino-propionic acid, amino-butryic acid, or Norleucine. The insulin analogue is compatible with a process of manufacture that includes one or more steps within the temperature range 90-120° C. The encapsulated insulin analogue may optionally contain free PEG or be PEGylated. The insulin analogue-encapsulated polymer blend may be cast as a microneedle patch for topical administration or as micropellets for subcutaneous injection.