Pharmaceutical composition comprising polypeptide
Inventors
Lee, Kang Choon • PARK, OG YI • AN, HYOUNG TAE • PARK, Eun Ji • Shin, Jae Hee • Lim, Sung Mook
Assignees
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Publication Number
US-12338270-B2
Publication Date
2025-06-24
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition including a polypeptide, and more particularly, to a pharmaceutical composition for preventing or treating obesity, diabetes, or non-alcoholic fatty liver disease. The pharmaceutical composition is safe without any side effects such as vomiting or nausea, and has effects of reducing food intake, enhancing insulin secretion, suppressing gastric emptying, promoting lipolysis, and lowering a level of triglycerides.
Core Innovation
The invention relates to a pharmaceutical composition that includes a polypeptide having an amino acid sequence represented by General Formula 1 (SEQ ID NOs. 8-9) as an oxynthomodulin/glucagon derivative framework, where the sequence includes the pattern R1-X1-QGTFTSDYSKYLD-R2-EFVQWLMNT-R3. The General Formula 1 defines R1 as histidine, desamino-histidyl, N-dimethyl-histidyl, beta-hydroxy-imidazopropionyl, 4-imidazoacetyl, or beta-carboxy-imidazo-propionyl, and defines X1 as a deletion, glycine, or aminoisobutyric acid (Aib).
The General Formula 1 further defines R2 as EQAAK (SEQ ID NO. 11) or EEAVK (SEQ ID NO. 12), and defines R3 as a deletion, cysteine, lysine, or methionine. In particular, one described structural option is that R2 comprises glutamic acid (E) and lysine (K), with the glutamic acid and lysine forming a ring via an amide bond. This polypeptide is used as the core component for improved pharmacological performance in the stated therapeutic targets.
The composition also includes a non-peptidic polymer that can be covalently bound or can form microspheres with a non-peptidic polymer, preferably polyethylene glycol (PEG). The non-peptidic polymer conjugates are described as improving in vivo half-life while retaining receptor activity, with the documented polymer examples focusing on PEG derivatives and PEG architecture as linear or branched. The invention also supports a method of preparing the pharmaceutical composition by mixing the polypeptide defined by Formula 1 with the non-peptidic polymer so the two react with each other.
Claims Coverage
Two independent claims are identified: one covering a specific polypeptide defined by General Formula 1, and a second covering a method of preparing a pharmaceutical composition comprising that polypeptide and a non-peptidic polymer. The inventive features emphasize strict sequence-variant definition via General Formula 1 and residue substitutions, and reaction-based formation of a pharmaceutical composition by mixing a polypeptide with a non-peptidic polymer.
Polypeptide defined by General Formula 1
A polypeptide having an amino acid sequence represented by General Formula 1 (SEQ ID NOs. 8-9) as R1-X1-QGTFTSDYSKYLD-R2-EFVQWLMNT-R3, wherein R1 is histidine, desamino-histidyl, N-dimethyl-histidyl, beta-hydroxy-imidazopropionyl, 4-imidazoacetyl, or beta-carboxy-imidazo-propionyl; X1 is a deletion, glycine, or aminoisobutyric acid (Aib); R2 is EQAAK (SEQ ID NO. 11), or EEAVK (SEQ ID NO. 12); and R3 is a deletion, cysteine, lysine, or methionine.
Prepare a pharmaceutical composition by mixing a general formula 1 polypeptide with a non-peptidic polymer
A method of preparing a pharmaceutical composition comprising a polypeptide having an amino acid sequence represented by Formula 1; and a non-peptidic polymer, the method comprising mixing the non-peptidic polymer with the polypeptide to react with each other, wherein Formula 1 is (SEQ ID NOs: 8-9) R1-X1-QGTFTSDYSKYLD-R2-EFVQWLMNT-R3 with R1, X1, R2, and R3 as recited in the claim.
Overall, claim coverage centers on a polypeptide defined by the residue-variant pattern of General Formula 1 and on composing that polypeptide with a non-peptidic polymer by a mixing step to react the two into a pharmaceutical composition. Additional refinements shown in the dependent-claim set include a ring-forming R2 option via an amide bond and constraints and examples for non-peptidic polymer selection, including PEG derivative selection and PEG structure as linear or branched.
Stated Advantages
Improved in vivo half-life while retaining receptor activity.
Improved receptor activity/selectivity in GLP-1R/GCGR assays.
Reduced food intake and body weight.
Reduced blood glucose, including effects in glucose tolerance and HbA1c changes.
Improved NAFLD endpoints including serum cholesterol, liver weight, hepatic triglycerides, liver histology/steatosis, and NAFLD activity score.
Reduced side effects, with no vomiting/nausea asserted.
Documented Applications
Treatment or management of obesity using a pharmaceutical composition including the defined polypeptide and a non-peptidic polymer.
Treatment or management of diabetes using the pharmaceutical composition, including effects on blood glucose and glucose tolerance and HbA1c changes.
Treatment or management of non-alcoholic fatty liver disease (NAFLD), including improved NAFLD endpoints such as serum cholesterol, liver weight, hepatic triglycerides, and histology/steatosis.
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