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Cancer markers and methods of use thereof

A cancer, cancer cell technology, applied in vaccines, carbohydrase inhibitor compounds and compositions thereof, treatment or detection of hyperproliferative diseases and/or conditions, selection of markers for cancer stem cells, antibody and/or immunogenic binding It can solve the problem of insufficient concentration of CSC, etc.

Inactive Publication Date: 2021-03-02
ACAD SINIC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, current markers used to isolate CSCs are often not selective enough to enrich CSCs for studies of this particular cell population

Method used

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  • Cancer markers and methods of use thereof
  • Cancer markers and methods of use thereof
  • Cancer markers and methods of use thereof

Examples

Experimental program
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preparation example Construction

[0514] Preparation of antibody-drug conjugates

[0515] In the antibody-drug conjugate (ADC) of the present invention, the antibody (Ab) is bound to one or more drug moieties (D) via a linker (L), eg, about 1 to about 20 drug moieties per antibody. ADCs of formula I can be prepared by several routes using organic chemistry reactions, conditions and reagents known to those skilled in the art, including: (1) reaction of the nucleophilic group of the antibody with a divalent linker reagent, via co- A valent bond forms Ab-L, which subsequently reacts with the drug moiety D; and (2) the nucleophilic group of the drug moiety reacts with a divalent linker reagent to form D-L via a covalent bond, which subsequently reacts with the nucleophilic group of the antibody reaction. Additional methods of making ADCs are described herein.

[0516] Ab-(L-D)pI

[0517]A connector can consist of one or more connector components. Exemplary linker components include 6-maleimidocaproyl ("MC"), m...

example

[0583] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of ordinary skill in the art should, in light of the present invention, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or a similar result without departing from the spirit and scope of the invention.

example 1

[0584] Example 1: Exemplary Synthesis of SSEA3 Analogs

[0585] Process 1.

[0586] Compound Gb4 analogs, ATP, UTP, galactose analogs, phosphoenolpyruvate, magnesium chloride and enzymes galactokinase (GalK), UDP sugar pyrophosphorylase (AtUSP), β-1,3-galactosyl Transferase (LgtD), pyruvate kinase (PK) and inorganic pyrophosphatase (PPA) were combined in solution, the reaction was initiated at room temperature with pH controlled at 7.0, and the reaction was monitored by TLC until no more product was observed. After the reaction was complete, the protein in the reaction mixture was removed by heating for 30 minutes, followed by centrifugation and filtration with a 0.22 μΜ filter. The filtrate was then purified by C-18 gel chromatography. Fractions were collected and monitored by TLC.

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Abstract

The invention relates to cancer markers and methods of use thereof. The present invention relates to methods and compositions that modulate globular glycosphingolipid synthesis. In particular, the present invention relates to glycoenzyme inhibitor compounds and compositions and methods of use thereof that can modulate globular series glycosphingolipid SSEA-3 / SSEA-4 / GloboH synthesis in the biosynthetic pathway; specifically speaking, the glycosidase inhibitor targets alpha-4GalT in a ball series synthesis path; beta- < 4 > GalNAcT-I; or a [beta] -3 GalT-V enzyme. Furthermore, the present invention also relates to vaccines, antibodies and / or immunogenic conjugate compositions targeting the SSEA3 / SSEA4 / GLOBO H-associated antigenic determinants (native and modified) that induce antibody and / orbinding fragment production for modulating globular glycosphingolipid synthesis. In addition, the present invention also relates to methods of treating or detecting hyperproliferative diseases and / orconditions using the compositions described herein. In addition, the present invention also relates to cancer stem cell biomarkers for diagnostic and therapeutic use.

Description

[0001] Related applications [0002] This application claims priority to USSN 62 / 107378, filed January 24, 2015, and USSN 62 / 266514, filed December 11, 2015. The content of each of these is incorporated herein. technical field [0003] The present invention relates to a method and a composition suitable for regulating the synthesis of globular glycosphingolipids and a marker suitable for selecting cancer stem cells. Specifically, the present invention relates to a carbohydrase inhibitor compound and its composition and method of use that can regulate the synthesis of globular glycosphingolipids SSEA-3 / SSEA-4 / GloboH in the biosynthetic pathway; specifically, carbohydrase inhibitory The agents target the α-4GalT; β-4GalNAcT-I; or β-3GalT-V enzymes in the synthesis pathway of the sphere series. In addition, the present invention also relates to vaccines, antibodies and / or immunogenic conjugate compositions targeting SSEA-3 / SSEA-4 / Globo H related epitopes (natural and modified)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18C07K16/30C07K16/28G01N33/574A61K39/395A61P35/00
CPCC07K16/18C07K16/30C07K16/2884C07K16/2896G01N33/57492G01N33/57415G01N33/56966A61P35/00C07K2317/732C07K2317/734C07K2317/76G01N2800/52G01N2800/56A61K2039/507A61K39/00A61K39/001169A61K39/001129A61K39/001128G01N33/574G01N33/57484C07K2317/33A61K39/39558G01N2500/10
Inventor 翁启惠吴宗益S·K·C·程庄博凯徐翠玲
Owner ACAD SINIC