The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:

##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:

##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

The invention provides a new enzimatic process for the preparation of chiral carboxylic acids, their salts and acid derivatives of the general formula (I) by enzymatic hydrolysis of racemic carboxylic acid ester of the general formula (II) and optionally subsequent esterification or acylation.

The present disclosure provides a bifunctional linker for coupling at least one functional moiety, preferably a bis-allyl propionic acid (BAPA), to a polymer-containing matrix. Also disclosed by the present disclosure are anhydrides of the bifunctional linker, processes for preparing the bifunctional linker and such anhydride, as well as surfaces, such as cellulose containing matrices, coupled with the bifunctional linker, at times, the latter carrying a functional agent.

An object of the present invention is to provide a novel complex having at least two carbon-carbon double bonds and/or carbon-carbon triple bonds. The present invention provides a complex represented by a structural formula (2): ##STR00001## [In the structural formula (2), M.sup.1 to M.sup.4 are identical to or different from each other and represent a metal atom, R.sup.1 to R.sup.6 are identical to or different from each other and represent a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an alkenyl group having 2 to 18 carbon atoms or an alkynyl group having 2 to 18 carbon atoms, and at least two of R.sup.1 to R.sup.6 are the alkenyl group having 2 to 18 carbon atoms or the alkynyl group having 2 to 18 carbon atoms.].

An object of the present invention is to provide a novel complex having at least two carbon-carbon double bonds and/or carbon-carbon triple bonds. The present invention provides a complex represented by a structural formula (2): ##STR00001## [In the structural formula (2), M.sup.1 to M.sup.4 are identical to or different from each other and represent a metal atom, R.sup.1 to R.sup.6 are identical to or different from each other and represent a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an alkenyl group having 2 to 18 carbon atoms or an alkynyl group having 2 to 18 carbon atoms, and at least two of R.sup.1 to R.sup.6 are the alkenyl group having 2 to 18 carbon atoms or the alkynyl group having 2 to 18 carbon atoms.].

The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:

##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:

##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

The present invention relates to an additive for a non-aqueous electrolyte solution, which may suppress the generation of metallic foreign matter causing a side effect in a battery while forming a stable film on the surface of an electrode, a non-aqueous electrolyte solution for a lithium secondary battery which includes the additive, and a lithium secondary battery including the non-aqueous electrolyte solution.

The present invention relates to an additive for a non-aqueous electrolyte solution, which may suppress the generation of metallic foreign matter causing a side effect in a battery while forming a stable film on the surface of an electrode, a non-aqueous electrolyte solution for a lithium secondary battery which includes the additive, and a lithium secondary battery including the non-aqueous electrolyte solution.