Compositions comprising pharmaceutically acceptable salts of amylin analogs and uses thereof
Inventors
Assignees
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Publication Number
US-12337029-B2
Publication Date
2025-06-24
Expiration Date
Abstract
Provided herein are compounds having the structure of Formula I, wherein the compounds comprise a therapeutic agent having the configuration of [diacid]-[linker]-[an amylin analog], in which the amylin analog has the amino acid sequence of SEQ ID NO: 20, with a proviso that the amino acid sequence comprises one or more of the following amino acid substitutions: N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof, and the compounds have an anion: cation molar ratio of from about 1:1 to about 1:3, and methods of using thereof for the treatment of metabolic diseases or disorders, including type 1 diabetes, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis, and for reducing weight in a subject in need thereof.
Core Innovation
The invention relates to compounds having the structure of Formula I, where the therapeutic agent has the configuration of [diacid]-[linker]-[an amylin analog]. The amylin analog comprises the amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide corresponding to SEQ ID NO:20, with one or more amino acid substitutions selected from N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof. The compound is further defined by a molar ratio of from about 1:1 to about 1:3.
The Formula I framework specifies structural elements for the diacid and related components, including substituent-defined alkyl groups R1, R2, R3, and R4 selected within C1-C5 alkyl ranges, with at least one of R1, R2, and R3 being C2-C5 alkyl and R4 being C2-C5 alkyl. The C2-C5 alkyl for R4 is unsubstituted or substituted with 1 or more hydroxyl. In described embodiments, the amylin analog further includes cysteines at positions 2 and 7 forming a disulfide bond.
The invention also defines linker composition for connecting the diacid and the amylin analog, using linker residues that include one or more gamma glutamate (γGlu) residues, one or more 8-amino-3,6-dioxaoctanoic acid (OEG) residues, or a combination thereof. Additional described refinements select fatty diacids having chain lengths including C10, C12, C14, C16, C18, and C20.
Claims Coverage
The consolidated claim coverage includes one independent claim directed to a Formula I compound comprising a therapeutic agent configured as [diacid]-[linker]-[an amylin analog], with the amylin analog defined by SEQ ID NO:20 and a stated molar ratio range. The inventive features below combine the overlapping claim limitations explicitly present across the input items.
Formula I therapeutic agent with [diacid]-[linker]-[amylin analog] structure
A compound having the structure of Formula I, where the therapeutic agent has the configuration [diacid]-[linker]-[an amylin analog].
Amylin analog with SEQ ID NO:20 and optional substitutions
The amylin analog comprises the amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide corresponding to SEQ ID NO:20, with one or more amino acid substitutions selected from N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof.
Molar ratio range defining the compound
The compound has a molar ratio of from about 1:1 to about 1:3.
Alkyl substituent constraints for Formula I components
R1, R2, and R3 are independently C1-C5 alkyl, wherein at least one of R1, R2, and R3 is C2-C5 alkyl; R4 is C2-C5 alkyl, wherein the C2-C5 alkyl is unsubstituted or substituted with 1 or more hydroxyl.
Linker defined by γGlu and/or OEG residues
The linker includes one or more gamma glutamate (γGlu) residues, one or more 8-amino-3,6-dioxaoctanoic acid (OEG) residues, or a combination thereof.
Fatty diacid chain length selection for the diacid component
The diacid component is a fatty diacid having C10, C12, C14, C16, C18, or C20 carbon chain length.
Optional disulfide bond in the amylin analog
The amylin analog includes cysteines at positions 2 and 7 forming a disulfide bond.
Use narrowed to specific metabolic diseases or disorders
The metabolic disease or disorder is selected from type 1 diabetes, type 2 diabetes, obesity, overweight, or nonalcoholic steatohepatitis (NASH).
The consolidated claim coverage centers on a Formula I compound with a [diacid]-[linker]-[an amylin analog] therapeutic-agent configuration, an amylin analog defined by SEQ ID NO:20 with optional specified substitutions, and a molar ratio from about 1:1 to about 1:3. Dependent features further narrow the alkyl substituents, linker building blocks, fatty diacid chain length, disulfide bond, and the specified metabolic disease or disorder set.
Stated Advantages
Increasing solubility.
Enhancing delivery efficiency.
Improving solubility and delivery by including ionic liquids.
Increasing delivery efficiency by adding permeation enhancers.
Reducing body weight.
Ionic liquids increase solubility and/or enhance delivery efficiency compared with compositions without ionic liquid.
Documented Applications
Treating metabolic diseases or disorders selected from type 1 diabetes, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis (NASH).
Reducing body weight.
Oral administration.
Oral delivery using permeation enhancer SNAC (salcaprozate sodium) in ionic-liquid-based oral delivery concepts.
Treatment of metabolic disorders including diabetes mellitus, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis (NASH).
Therapeutic use using the disclosed therapeutic constructs with associated receptor-signaling/biological effects [procedural detail omitted for safety].
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