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US 2023/0414768 A1Published application
Compositions and methods of treatment for severe hypertriglyceridemia
Assignee89Bio Ltd
InventorsHank Mansbach, Leo Tseng
Life of this patent
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Abstract
Compositions, methods and therapeutic regimens of mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugates for the treatment of severe hypertriglyceridemia are provided.
Claims27
A method of treating severe hypertriglyceridemia (SHTG) in a subject in need thereof, comprising:
- administering once a week to the subject in need thereof a pharmaceutical composition comprising from 9 mg to 30 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier,
- wherein the mutant FGF-21 peptide conjugate comprises:
- i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO:
- 2,
- ii) a glycosyl moiety, and
- iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO:
- 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG,
- wherein administration of the pharmaceutical composition results in a reduction of triglyceride levels by at least 20% from baseline.
5 more elements
A method of treating severe hypertriglyceridemia (SHTG) in a subject in need thereof, comprising:
- administering once every two weeks to the subject in need thereof a pharmaceutical composition comprising from 31 mg to 44 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier,
- wherein the mutant FGF-21 peptide conjugate comprises:
- i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO:
- 2,
- ii) a glycosyl moiety, and
- iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO:
- 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG,
- wherein administration of the pharmaceutical composition results in a reduction of triglyceride levels by at least 20% from baseline.
5 more elements
A method of treating severe hypertriglyceridemia (SHTG) in a subject in need thereof, comprising:
- administering once a week to the subject in need thereof a pharmaceutical composition comprising from 27 mg to 30 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier,
- wherein the mutant FGF-21 peptide conjugate comprises:
- i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO:
- 2,
- ii) a glycosyl moiety, and
- iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO:
- 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG,
- wherein administration of the pharmaceutical composition results in a reduction of triglyceride levels by at least 20% from baseline, and
- wherein administration of the pharmaceutical composition results in one or more of the following:
- reduction of alanine transaminase (ALT) marker by at least 10% from baseline,
- reduction of aspartate aminotransferase (AST) marker by at least 10% from baseline,
- median reduction of High-sensitivity C-reactive protein (hsCRP) marker by at least 10% from baseline,
- reduction of fasting plasma glucose by at least 10% from baseline,
- reduction of HBA lc by at least 0. 3% from baseline,
- reduction of non-HDL cholesterol levels by at least 10% from baseline,
- reduction of apoB levels by at least 10% from baseline,
- reduction of apoC3 levels by at least 10% from baseline,
- increase of HDL cholesterol levels by at least 10% from baseline,
- increase of adiponectin levels by at least 10% from baseline, and
- reduction greater than 30% in liver fat from baseline.
17 more elements
A method of treating severe hypertriglyceridemia (SHTG) in a subject in need thereof, comprising:
- administering once every two weeks to the subject in need thereof a pharmaceutical composition comprising from 36 mg to 44 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier,
- wherein the mutant FGF-21 peptide conjugate comprises:
- i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO:
- 2,
- ii) a glycosyl moiety, and
- iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO:
- 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG,
- wherein administration of the pharmaceutical composition results in a reduction of triglyceride levels by at least 20% from baseline, and
- wherein administration of the pharmaceutical composition results in one or more of the following:
- median reduction of High-sensitivity C-reactive protein (hsCRP) marker by at least 10% from baseline,
- reduction of non-HDL cholesterol levels by at least 10% from baseline,
- reduction of apoB levels by at least 10% from baseline,
- reduction of apoC3 levels by at least 10% from baseline,
- increase of HDL cholesterol levels by at least 10% from baseline,
- increase of adiponectin levels by at least 10% from baseline, and
- reduction greater than 30% in liver fat from baseline.
13 more elements
Dependencies are inferred from the claim text.