工業技術研究院

技術簡介

本技術為開發一種能穩定高濃度抗體的長效釋放載體技術，在不增加皮下給藥體積的前提下，透過生物相容、生物可分解之高分子水膠載體所形成的孔隙結構作為裝載並穩定抗體藥物，藉以調控抗體釋放速度，避免血液中高抗體濃度所引發的抗體快速清除，如此可延長療效並降低治療所需之抗體藥量，具潛力可成為具藥動與安全性優勢之次世代抗體產品。所開發之抗體水膠技術可裝載>150mg/mL抗體藥物，水膠所釋放之抗體亦維持高結構穩定性、鍵結活性以及細胞毒性，重要的是抗體水膠配方於大鼠具明顯緩釋效果，與原藥比較，抗體水膠配方可降低Cmax及延長T1/2，明顯具備藥動性質優勢。此技術可擴充應用至其它蛋白質藥物。

Abstract

ITRI’s hydrogel technology is specially designed to locally deliver the active pharmaceutical ingredients consisting of biologics, such as antibodies and proteins, in controlled or sustained release. Unlike existing protein delivery systems with significantly limited clinical uses due to insufficient drug loading (<15 mg/mL), our hydrogel technology has a high protein loading capacity (>150 mg/mL). This technology has also overcome many technical challenges including protein stability and bioactivity during fabrication and release period, incomplete release from the matrix, product injectability issue and so on. Most of all, our in vivo studies used HerceptinR as an example and showed that ITRI’s novel hydrogel systems given by subcutaneous injection reduced Cmax of the antibody in blood plasma and offered at least four times prolongation of the half-life through controlling its sustained release from the hydrogel matrix. In addition, the efficacy result (PD) in a xenograft model of human breast cancer in mice showed that HerceptinR formulated with the hydrogel exhibited the enhanced efficacy of suppressing tumor growth, indicating that the antibody released from the hydrogels can retain its native anti-tumor potency. We believe these breakthrough technology will bring more broad application for biologics.

技術規格

水膠組合物由低濃度(2~5 wt%)具生物相容性之polypeptide及poly(ethylene glycol)構成，具有多孔結構且能包覆高濃度蛋白質藥物(高達200 mg/mL)，並應用於蛋白質藥物控制釋放。

Technical Specification

A hydrogel composition comprising polypeptide and poly(ethylene glycol) of low polymer concentration (2~5 wt%), which has the porous structure and can load high-concentration (up to 200 mg/mL) protein drugs, can be applied to the controlled release of protein drugs.

技術特色

1.100% drug encapsulation efficiency 2.High antibody loading concentration (up to 200 mg/mL) 3.Sustained release over 5 weeks (in vitro and in vivo) 4.Intact stability and antigen binding affinity of antibody released from hydrogel 5.Unchanged anti-proliferation and ADCC capability of antibody released from hydrogel 6.Alterable release rate of antibody by changing composition of the formulation 7.Cmax reduction (40-70%) and T1/2 extension (up to 4.2 fold) for the trastuzumab antibody

應用範圍

適用於抗體、蛋白藥物、胜?等藥物，以產生其控釋劑型。

接受技術者具備基礎建議（設備）

具備抗體生產所需設備

接受技術者具備基礎建議（專業）

具備抗體生產所需能力

聯絡資訊