Nof Corporation

Takuma Tsubusaki

Yuji Yamamoto

Kohei Yoshimura

Mika Hamura

Hiroki Yoshioka

Masaki Kamiya

Kota Tange

Tsuyoshi Takehana

Takashi Ichikawa

Masaki Ota

Shinya Tamagawa

Yuki Matsuno

Mika Shishido

Koichi Ogi

Akiko Doi

A heterobifunctional monodispersed polyethylene glycol represented by the formula (1): wherein Xand Yare each an atomic group containing a functional group capable of forming a covalent bond upon a reaction with a functional group present in a biofunctional molecule, the functional group contained in the atomic group Xand the functional group contained in the atomic group Yare different from each other; Ris a hydrocarbon group having from 1 to 7 carbon atoms or a hydrogen atom; n is an integer of 3 to 72; 1 is an integer of 2 to 72; and A, Band Care as defined herein.

Heterobifunctional compound having monodispersed polyethylene glycol in main chain and side chain

A method for purifying a specific trityl group-containing monodispersed polyethylene glycol from a mixture containing the trityl group-containing monodispersed polyethylene glycol and a specific ditritylated impurity. The method includes performing steps (A), (B) and (C). Step (A): a step of esterifying the hydroxyl group of the trityl group-containing monodispersed polyethylene glycol by a specific method; Step (B): a step of extracting the esterified compound by a specific method; and Step (C): a step of hydrolyzing the esterified compound to obtain the trityl group-containing monodispersed polyethylene glycol.

Method for purifying trityl group-containing monodispersed polyethylene glycol

A biodegradable polyethylene glycol derivative in which a polyethylene glycol chain is linked by an acetal linker capable of accurately controlling the hydrolysis rate under different pH environments in the living body, and whose division rate into a polyethylene glycol chain of low molecular weight in the living body can be accurately controlled. The biodegradable polyethylene glycol derivative is represented by formula (1) or formula (2) as described.

Biodegradable polyethylene glycol derivative having cyclic benzylidene acetal linker

A hydrophilic polymer derivative having a cyclic benzylidene acetal linker represented by the following formula (1): wherein Rand Rare each independently a hydrogen atom or a hydrocarbon group; R, R, Rand Rare each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; Xis a chemically reactive functional group; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 8; and Zand Zare each independently a selected divalent spacer.

Hydrophilic polymer derivative having cyclic benzylidene acetal linker

A heterobifunctional monodispersed polyethylene glycol represented by formula (1) which has two adjacent monodispersed polyethylene glycol side chains and does not have a chiral center in the molecular structure: wherein Xand Yare each an atomic group containing a functional group capable of forming a covalent bond upon a reaction with a functional group present in a biofunctional molecule. Ris a hydrocarbon group or the like. n is an integer of 3 to 72. Arepresents -L-(CH)&#x2014; or the like, Land Lrepresent each an ether bond or the like, and m1 and m2 each independently represent an integer of 1 to 5. Brepresents -L-(CH)&#x2014; or the like, Land Lrepresent an amide bond or the like, and m3 and m4 each independently represent an integer of 1 to 5. Also disclosed is an antibody-drug conjugate including the heterobifunctional monodispersed polyethylene glycol.

Heterobifunctional monodispersed polyethylene glycol and conjugate using same

To provide a hydrophilic polymer derivative having a novel linker technique which is able to from a hydrophilic polymer pro-drug of a drug containing an amino group or the like in order to overcome the restrictions of conventional hydrophilic polymer pro-drugs. A hydrophilic polymer derivative containing a hydrophilic polymer moiety and an acetal moiety, wherein the hydrophilic polymer derivative contains a structure represented by formula (1) or formula (2): 

Hydrophilic polymer derivative having self-immolative acetal linker and conjugate using same

A degradable polyethylene glycol derivative represented by formula (1). R, R, and Rrepresent each independently a hydrogen atom or a hydrocarbon group having from 1 to 6 carbon atoms, and at least one of R, R, Rand Ris the hydrocarbon group; Pis a straight-chain or branched polyethylene glycol chain having a number of ethylene glycol units of 3 or more; Pis a straight-chain polyethylene glycol chain having a number of ethylene glycol units of 3 or more; w is an integer of 1 to 8; u is an integer of 1 to 10; Xis a chemically reactive functional group; and Z, Zand Zare each independently a selected divalent spacer. 

Degradable polyethylene glycol derivative having disulfide linker

A biodegradable hydrogel having an acetal structure whose hydrolysis rate under different pH environments in the living body can be accurately controlled. The hydrogel is obtained by crosslinking a polyalkylene glycol derivative having a cyclic benzylidene acetal structure represented by formula (1) shown below with a crosslinking agent: where Rand R; R, R, Rand R; s; t; s+t; P; Zand Z; Wand Xare as defined herein.

Biodegradable hydrogel having cyclic benzylidene acetal structure

An antibody-drug conjugate having a cyclic benzylidene acetal linker represented by formula (1) or formula (2), wherein Y is an antibody; D is a drug; Rand Rare each independently a hydrogen atom or a hydrocarbon group; R, R, Rand Rare each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 20; and Zand Zare each independently a selected divalent spacer: 

Antibody-drug conjugate having cyclic benzylidene acetal linker

A hydrophilic polymer derivative having a benzylidene acetal linker whose hydrolysis rate at the pH of a weakly acidic environment in the living body can be accurately controlled. A hydrophilic polymer derivative having a benzylidene acetal linker, which is represented by the following formula (1): wherein Ris a hydrogen atom or a hydrocarbon group; R, R, R, R, and Rare each independently a hydrogen atom or a substituent and at least one of R, R, and Ris an electron-withdrawing substituent or at least one of Rand Rrepresents a substituent; Xis a chemically reactive functional group; P is a hydrophilic polymer; w is an integer of 1 to 8; and Zand Zare an independently selected divalent spacer.

Hydrophilic polymer derivative having benzylidene acetal linker

A lipid derivative in which a hydrophilic polymer is bound through a cyclic benzylidene acetal linker, and which can accurately control a hydrolysis rate in the weakly acidic environment of a living body to detach the hydrophilic polymer from a lipid membrane structure. The lipid derivative is represented by formula (1): wherein, Rand Rare each independently a hydrogen atom or a hydrocarbon group; R, R, Rand Rare each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; Ris a hydrocarbon group having from 8 to 24 carbon atoms, an acyl group having from 8 to 24 carbon atoms, a cholesterol derivative, a glycerolipid, a phospholipid or a sphingolipid; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; and Zand Zare each independently a selected divalent spacer.

Lipid derivative in which hydrophilic polymer is bound through cyclic benzylidene acetal linker

A method for producing polyethylene glycol having a terminal carboxyl group including oxidizing polyethylene glycol represented by formula (I): CHO(CHCHO)(CH)&#x2014;CHO with potassium peroxymonosulfate in water whose pH is adjusted to be from 6 to 8 with at least one selected from a carbonate, a phosphate, a citrate and an acetate at 5 to 40&#xb0; C. to produce polyethylene glycol represented by formula (II): CHO(CHCHO)(CH)&#x2014;COOH, wherein n is a number from 10 to 1,100, and m is 2 or 3.

Method for producing polyethylene glycol having terminal carboxyl group

A method of producing a medical polyoxypropylene polymer and a polyoxypropylene/polyoxyethylene block copolymer including (A) adding to a polyoxypropylene polymer which is obtained by ring-opening polymerization of propylene oxide to a starting substance having an active hydrogen reacting with the propylene oxide and contains allyl ether as an impurity, a tertiary alkoxide of alkali metal in an excess amount based on a molar number of the active hydrogen of the starting substance and heat treating at 115&#xb0; C. or less to isomerize the allyl ether to propenyl ether; and (B) adding a mineral acid to the product obtained in step (A) to adjust pH to 4 or less and treating at 70&#xb0; C. or less to hydrolyze the propenyl ether. Also disclosed is a method of producing a medical polyoxypropylene/polyoxyethylene block copolymer which includes performing ring-opening polymerization of ethylene oxide to the polyoxypropylene polymer obtained above.

Growing community of inventors

Kawasaki, Japan

Takuma Tsubusaki