Academia Sinica

Kaohsiung Medical University

National Health Research Institutes

Steve R Roffler

Tian-Lu Cheng

Pin-Yi Wu

Patrick C H Hsieh

Wen-Wei Lin

Bill Cheng

Pei-Jung Wu

I-Ju Chen

Chih-Hsiang Leng

Hsin-Wei Chen

Shih-Jen Liu

Kuo-Hsiang Chuang

Kuang-Wen Liao

Ming-Hsi Huang

Chia-Hung Wu

Yu-Lin Leu

Wolfgang Schechinger

Kai-Chuan Chen

Pierre-Alain Burnouf

Zeljko Prijovic

Huai-Yao Chuang

Zeljko M Prijovic

Described herein is a method for loading a hydrophilic compound into liposomes after addition of an alkylester group to form an esterified compound. After loading, the alkylester is hydrolyzed to reform the hydrophilic compound inside the liposomes. Also described is a method for loading drugs under a glucuronide methylester form into liposomes. The glucuronide methylester form of the drug is saponified to a glucuronide form of the drug inside the liposomes for better drug retention. The glucuronide residue conjugated to drugs can be removed inside cells to regenerate the parental drug upon cell uptake, liposomal degradation and enzyme hydrolysis. In case of cancer, this method can be used to safely deliver drugs to tumors.

Esterification/saponification-based method for liposomal encapsulation of hydrophilic glucuronides

Described herein are an immunogenic peptide containing the sequence of CLDSLGQWN (SEQ ID NO:2) and a method of using the peptide for treating cancer.

Immunogenic peptide containing a b cell epitope of tumor associated antigen L6

Disclosed herein is a multiple drugs delivery system and its uses in treating diseases. The multiple drugs delivery system includes, an anti-PEG antibody for directing the PEGylated therapeutic to the treatment site; and a hydrogel for retaining the anti-PEG antibody and/or the PEGylated therapeutic at the treatment site for at least 3 days. The hydrogel is selected from the group consisting of hyaluronan (HA) or a derivative of HA, collagen, gelatin, fibronectin, fibrinogen, alginate, chitosan, and a synthetic biocompatible polymer. The anti-PEG antibody and the hydrogel are present in the mixture in a ratio from about 1:1 (v/v) to 1:100 (v/v). At least two dosages of the PEGylated therapeutic, which may be the same or different, are administered to the subject, with each dosage being given at about 1 hour to about 1 week apart. Accordingly, a novel method of treating a subject having cancer or ischemia disease is also provided.

Multi-drug delivery system and uses thereof

An engineered enzyme, comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of a human beta-glucuronidase, wherein the engineered enzyme exhibits a higher level of alpha-iduronidase enzymatic activity as compared to the human beta-glucuronidase.

Engineered enzyme for enzyme replacement therapy

Disclosed herein is a multiple drugs delivery system and its uses in treating diseases. The multiple drugs delivery system includes, an anti-PEG antibody for directing the PEGylated therapeutic to the treatment site; and a hydrogel for retaining the anti-PEG antibody and/or the PEGylated therapeutic at the treatment site for at least 3 days. The hydrogel is selected from the group consisting of hyaluronan (HA) or a derivative of HA, collagen, gelatin, fibronectin, fibrinogen, alginate, chitosan, and a synthetic biocompatible polymer. The anti-PEG antibody and the hydrogel are present in the mixture in a ratio from about 1:1 (v/v) to 1:100 (v/v). At least two dosages of the PEGylated therapeutic, which may be the same or different, are administered to the subject, with each dosage being given at about 1 hour to about 1 week apart. Accordingly, a novel method of treating a subject having cancer or ischemic disease is also provided.

Multi-drug delivery system and use thereof

The present invention is related to a method for detecting a protein comprising: (1) providing a fusion protein, wherein the fusion protein comprises the protein which is fused with a secondary antibody detected protein tag, wherein the secondary antibody detected protein tag comprises at least one epitope selected from the Fc region of at least one primary antibody which is capable of being detected by a corresponding secondary antibody; (2) contacting the fusion protein with a secondary antibody which binds to the secondary antibody detected protein tag to form a protein/antibody complex; and (3) detecting the protein/antibody complex.

Method for detecting protein by using secondary antibody detected epitope tag

A method of preparing an epitope for a secondary antibody detected protein tag, comprising: constructing a expressing vector, comprising a nucleotide sequence for encoding the secondary antibody detected protein tag comprising at least one epitope selected from at least one primary antibody which is detected by corresponding secondary antibody; expressing the vector in a host cell; and obtaining the secondary antibody detected protein tag which is expressed in the host cell. Further, a method for constructing a protein molecular weight marker ladder, comprising constructing a plurality of recombinant protein tags with different molecular weights, wherein each the recombinant protein tag comprises at least one epitope of primary antibody. Besides, a secondary antibody detected protein tag comprises at least two peptide sequences of epitopes selected from primary antibodies of at least two different species.

Secondary antibody detected epitope and preparation of same

The invention relates to the synthesis of a second-generation camptothecin glucuronide prodrug (BQC-G) of a potent anticancer camptothecin derivative 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC). BQC-G was over 4000 times more water soluble than BQC, displayed good stability in human plasma and was an excellent substrate for enzymatic hydrolysis by bacterial and human &#x3b2;-glucuronidases. BQC-G was about 30 times less toxic than BQC, but was as toxic as BQC after hydrolysis of the glucuronide moiety by &#x3b2;-glucuronidase. In the presence of human serum albumin, BQC-G displayed lower cytotoxicity (IC=1080 nM) but could be activated by &#x3b2;-glucuronidase to display potent activity (IC=13.3 nM).

BQC-G, a tumor-selective anti-cancer prodrug

The invention provides a recombinant nucleotide sequence, including the sequence of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 or SEQ ID No. 4, wherein the recombinant nucleotide sequence encodes an anti-polyethylene glycol recombinant single chain membrane antibody.

Recombinant nucleotide sequence, cell or vector containing the same and method for using cell containing the same to encode anti-polyethylene glycol monoclonal antibodies

A number of human beta-glucuronidase variants having higher enzymatic activity at physiological pH as compared with wild-type beta-glucuronidase and uses thereof in prodrug therapy. Also disclosed herein is a method for identifying enzyme variants having elevated enzymatic activity using a mammalian surface display system.

Human beta-glucuronidase mutants with elevated enzymatic activity under physiological conditions and method for identifying such

A novel anti-polyethylene glycol monoclonal antibody and its preparation are disclosed. Such an antibody can be used for determining polyethylene glycol concentration in vitro or accelerating the clearance of a polyethylene glycol containing compound from the blood circulation in the human body thereby reducing the toxicity associated with the polyethylene glycol containing conjugate. The antibody is particularly useful in cancer therapy where the therapeutic agent is selectively delivered to the tumor by increasing the tumor/blood ratio of the polyethylene glycol containing compound.

Monoclonal antibody for analysis and clearance of polyethylene glycol and polyethylene glycol-modified molecules

A chimeric protein expressed from a transgene tranduced into a mammalian tumor cell and method of using the chimeric protein for cancer treatment. The chimeric protein comprises an effector and an anchor, which are linked by a spacer. The chimeric protein, when expressed and exposed on the tumor cell surface in vivo can activate T cells, which further lead to lysis of the tumor cells. The anti-tumor effects can be enhanced by co-expression of certain co-stimulators, such as CD80 or CD86.

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Taipei, Taiwan

Steve R Roffler