| 主权项 |
1. A crystalline insulin-conjugate of formula (I): wherein: each occurrence ofrepresents a potential branch within the conjugate;
each occurrence ofrepresents a potential repeat within a branch of the conjugate;
each occurrence ofis independently a covalent bond, a carbon atom, a heteroatom, or an optionally substituted group selected from the group consisting of acyl, aliphatic, heteroaliphatic, aryl, heteroaryl, and heterocyclic;
each occurrence of T is independently a covalent bond or a bivalent, straight or branched, saturated or unsaturated, optionally substituted C1-30 hydrocarbon chain wherein one or more methylene units of T are optionally and independently replaced by —O—, —S—, —N(R)—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, —N(R)SO2—, —SO2N(R)—, a heterocyclic group, an aryl group, or a heteroaryl group; each occurrence of R is independently hydrogen, a suitable protecting group, or an acyl moiety, arylalkyl moiety, aliphatic moiety, aryl moiety, heteroaryl moiety, or heteroaliphatic moiety; —B is -T-LB-X; each occurrence of X is independently a ligand that includes a mannose or branched trimannose; each occurrence of LB is independently a covalent bond or a group derived from the covalent conjugation of a T with an X; -D is -T-LD-W; WI is an insulin molecule; each occurrence of LD is independently a covalent bond or a group derived from the covalent conjugation of a T with a WI; k is an integer from 1 to 12, inclusive; each occurrence of p is independently an integer from 1 to 5, inclusive; and each occurrence of n is independently an integer from 0 to 5, inclusive; and each occurrence of m is independently an integer from 1 to 5, inclusive; and each occurrence of v is independently an integer from 0 to 5, inclusive, with the proviso that within each k-branch at least one occurrence of n is ≧1 and at least one occurrence of v is ≧1. |
