METHODS AND COMPOSITIONS FOR INCREASING ENZYME ACTIVITIES IN CNS

• Main Authors: WILLIAM M PARDRIDGE, RUBEN J BOADO
• Format: Patent
• Language: English; Japanese
• Published: 22.10.2020
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

To provide fusion antibodies, and pharmaceutical compositions comprising the fusion antibodies for treating subjects afflicted with enzyme-deficiency in the central nervous system (CNS).SOLUTION: A bifunctional fusion antibody disclosed herein comprises an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in mucopolysaccharidosis III (MPS-III). The disclosed fusion antibody comprises N-sulfoglucosamine sulfohydrolase (SGSH), α-N-acetylglucosaminidase (NAGLU), heparin-α-glucosaminide N-acetyltransferase (HGSNAT), or N-acetylglucosamine-6-sulfatase (GNS). The therapeutic method for enzyme deficiency in the CNS comprises systemic administration of the fusion antibody provided herein.SELECTED DRAWING: Figure 12 【課題】中枢神経系（ＣＮＳ）における酵素欠損症に罹患した対象を治療するための融合抗体、及び融合抗体を含む医薬組成物の提供。【解決手段】本明細書の二機能性の融合抗体は、内因性血液脳関門（ＢＢＢ）受容体に対する抗体、および、ムコ多糖症ＩＩＩ型（ＭＰＳ−ＩＩＩ）で欠損している酵素を含む。本明細書の融合抗体は、Ｎ−スルフォグルコサミンスルフォヒドロラーゼ（ＳＧＳＨ）、α−Ｎ−アセチルグルコサミニダーゼ（ＮＡＧＬＵ）、ヘパリン−α−グルコサミニドＮ−アセチルトランスフェラーゼ（ＨＧＳＮＡＴ）、またはＮ−アセチルグルコサミン−６−スルファターゼ（ＧＮＳ）を含む。ＣＮＳにおける酵素欠損症の治療方法は、本明細書の融合抗体の全身投与を含む。【選択図】図１２