Compositions comprising pharmaceutically acceptable salts of amylin analogs and uses thereof
Inventors
Assignees
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Publication Number
US-12233112-B2
Publication Date
2025-02-25
Expiration Date
Abstract
Provided herein are compounds having the structure of Formula Ia, 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 therapeutic compound compositions defined by Formula I/II/III variants, including Formula Ia-Ic and IIa-IIc, with ionic-liquid or salt forms and cationic modifications such as choline or choline-derivative cationic modifications. The conjugates include a therapeutic agent together with a linkage framework that incorporates defined anion and cation structures, chemically cleavable linker types including hydrazone and disulfide linkers, and related ionic composition features.
A central structural theme is a therapeutic agent configuration expressed as [diacid]-[linker]-[an amylin analog], where the amylin analog is defined by the amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide (SEQ ID NO: 20), with a proviso that the amino acid sequence comprises one or more specified amino acid substitutions including N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof. The document also includes linked amylin sequence embodiments and structural embodiments in which the therapeutic agent is an antibody, antibody fragment, GLP-1 analog, glucagon/GIP/amylin, or dual GIP/GLP-1 receptor agonist context.
The disclosure further specifies linker building blocks such as γGlu residues and/or OEG residues, fatty diacid carbon-chain options, and molar ratio ranges spanning from about 1:1 to about 1:60 and, in other embodiments, up to about 1:164. The therapeutic embodiments are stated to be directed to increasing solubility and delivery efficiency, and are associated with metabolic disease, diabetes, obesity, NASH, and autoimmune/immunological disorders.
Claims Coverage
The provided independent claims center on structurally defined therapeutic conjugates with an SEQ ID NO: 20 amylin-analog base sequence and a specified set of optional amino acid substitutions. Across the independent claims, the inventive features include the [diacid]-[linker]-[an amylin analog] configuration and a compound structure defined by the same substitution proviso, with one claim family also reciting a molar ratio constraint.
Diacid-linker-amylin analog therapeutic configuration with SEQ ID NO: 20 substitutions
A compound having the structure of Formula Ia, where the therapeutic agent has the configuration [diacid]-[linker]-[an amylin analog], and the amylin analog has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide (SEQ ID NO: 20) with a proviso that the amino acid sequence comprises one or more amino acid substitutions selected from N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof.
Therapeutic composition molar ratio constraint
The Formula Ia compound has a molar ratio of from about 1:1 to about 1:3.
Structured compound with SEQ ID NO: 20 substitution proviso
A compound having the following structure, with a proviso that the compound comprises one or more amino acid substitutions selected from N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof.
The claim coverage centers on therapeutic compounds defined by an SEQ ID NO: 20 amylin-analog sequence with specified optional substitutions, arranged in a [diacid]-[linker]-[an amylin analog] architecture in Formula Ia, and in one claim family constrained by a molar ratio of about 1:1 to about 1:3. Dependent refinements add linker composition options, fatty diacid carbon-chain options, disulfide bonding, and further substitution subsets.
Stated Advantages
Increasing solubility.
Increasing delivery efficiency.
Oral delivery.
Documented Applications
Metabolic disease, including diabetes and obesity.
NASH.
Autoimmune/immunological disorders, including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis/psoriatic arthritis, Behçet’s disease, multiple sclerosis, and eosinophilic esophagitis.
Therapeutic targeting of metabolic diseases such as type 2 diabetes mellitus and obesity.
Treatment of diabetes (Type 1/Type 2), NASH, and obesity.
Oral or mucus-membrane delivery of therapeutic peptides/proteins using ionic-liquid-based pharmaceutical formulations.
Administration routes include oral, subcutaneous, intravenous, and mucosal.
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