Compositions comprising pharmaceutically acceptable salts of glucagon-like peptide-1 analogs and pharmaceutically acceptable salts of amylin analogs, and uses thereof

Inventors

Brown, Tyler • IBSEN, Kelly

Assignees

I2O Therapeutics Inc

Abstract

Provided herein are compositions comprising a first compound having the structure of first Formula Ia, wherein the first compound comprises a first 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 first compound has an anion: cation molar ratio of from about 1:1 to about 1:3, and a second compound having the structure of second Formula Ia, wherein the second compound comprises a second therapeutic agent having the sequence of SEQ ID NO: 35, and the second compound has an anion: cation molar ratio of from about 1:1 to about 1:7, 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 compositions comprising a first compound and an additional agent, where the first compound has the structure of first Formula Ia and is configured as [diacid]-[linker]-[an amylin analog]. The amylin analog has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide (SEQ ID NO: 20) and comprises one or more amino acid substitutions selected from N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof. The first compound is combined with a second therapeutic agent defined by SEQ ID NO: 35, and the compositions specify defined molar ratios for the first and second compounds.

The disclosure further defines embodiments with specific substitution patterns for the amylin analog, including N14E, V17R, and Y37P. It also describes ionic-liquid-based formulations, choline or choline derivative-modified antibody structures, carboxylic acid anions, and linker-type options including non-cleavable, maleimide-based, hydrazone, and disulfide linkers. The document includes structural formula definitions with variable substituents and related ionic therapeutic conjugate or compound formats.

The compositions are described in the context of pharmaceutical compositions and treatment methods for metabolic diseases or disorders, including type 1 diabetes, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis (NASH), and also for reducing body weight. The document further states that ionic-liquid-based formulations can support improved formulation and delivery, including oral delivery, mucus or mucosal delivery, solubilization, and delivery efficiency, and that administration routes include subcutaneous, intravenous, and oral administration.

Claims Coverage

The independent claims identified in the provided material are clm-00001, clm-00015, and clm-00016. Across these claims, the inventive coverage centers on compositions comprising a first compound with a defined amylin-analog configuration and an additional agent that is a second therapeutic compound, with optional molar-ratio constraints, specific amino-acid substitutions, and dependent limitations on therapeutic indications and administration routes.

Across the independent claims, the coverage is directed to compositions that pair a first compound configured as an amylin analog with specified substitution options or fixed substitutions with a second compound defined by SEQ ID NO: 35, with claim 1 further specifying molar-ratio ranges for both compounds. Dependent claims further narrow the substitution patterns and specify treatment indications and administration routes.

Stated Advantages

Documented Applications