Researchers Submit Patent Application, "Cyclic Peptide Production Method", for Approval (USPTO 20220177512).

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Date: June 27, 2022
Publisher: NewsRX LLC
Document Type: Article
Length: 3,450 words
Lexile Measure: 2080L

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2022 JUN 27 (NewsRx) -- By a News Reporter-Staff News Editor at Pharma Business Week -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors INOMATA, Tatsuji (Yokkaichi-shi, JP); TAKAHASHI, Daisuke (Kawasaki-shi, JP), filed on December 23, 2021, was made available online on June 9, 2022.

The patent's assignee is Ajinomoto Co. Inc. (Tokyo, Japan).

News editors obtained the following quote from the background information supplied by the inventors: "

"Field of the Invention

"The present invention relates to production methods of cyclic peptides.

"Discussion of the Background

"In recent years, drug discovery development aiming at improving blood stability and the like by cyclizing peptide has been actively performed, and various forms of cyclic peptides have been reported. As an intramolecular S-S-cyclized S-S type cyclic peptide in which the SH groups in the side chains of cysteine, which is a constituent amino acid, and cysteine derivatives are linked to each other by disulfide bonds, the SH group extending from the N-terminal of the peptide chain is linked to the SH group in the side chain of cysteine or a cysteine derivative by a disulfide bond, somatostatin, octreotide, linaclotide, plecanatide, ziconotide, atosiban, eptifibatide and the like are known. In addition, cyclosporine, cyclic RGD peptide and the like are known as lactam-type cyclic peptides in which an amino group and a carboxyl group at the terminal or in the side chain of the peptide chain are linked by an amide bond. Furthermore, peptide compounds with cyclic thioether bonds such as carbetocin, barusiban, merotocin and the like are known as C-S type cyclic peptides with a carbonylalkylene group between the N-terminal of the peptide chain, and the side chain SH group of cysteine, which is a constituent amino acid, or a cysteine derivative.

"However, when conventional production methods are applied to any of the cyclic peptides, multimeric impurities bonded between molecules such as dimer, trimer, oligomer, and the like are by-produced during a cyclization reaction, and the yield of the cyclic peptide of interest becomes low. Moreover, it was difficult to remove these multimeric impurities. Therefore, to suppress the by-production of multimeric impurities, a method having extremely low production efficiency, such as carrying out a cyclization reaction under dilute conditions, and the like is generally adopted. To remove multimeric impurities, WO 2017/134687, which is incorporated herein by reference in its entirety, describes that, in a peptide having two or more SH groups in a molecule, all protecting groups at the N-terminal and C-terminal of the peptide chain and in the side chains of the constituent amino acids are removed, and then intramolecular S-S cyclization is performed in an aqueous solvent under oxidizing conditions, the peptide is treated at a low temperature under acidic conditions (pH 2 to 4) to cause precipitation of dimer, trimer and the like, which are non-polar high-molecular-weight impurities, and the above-mentioned impurities are removed by centrifugation or filtration."

As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors' summary...

Source Citation

Source Citation   

Gale Document Number: GALE|A708304387