Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Immunosuppression-reverting oligonucleotides inhibiting the expression of cd39

An oligonucleotide and immunosuppressive technology, applied in the field of pharmaceutical compositions of excipients and/or diluents, can solve problems such as lack of enzyme activity

Pending Publication Date: 2019-08-23
SECARNA PHARMA GMBH & CO KG
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] To inhibit several immunosuppressive mechanisms, common approaches using antibodies and / or small molecules are not or barely suitable because the molecular targets are intracellular or not enzymatically active

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Immunosuppression-reverting oligonucleotides inhibiting the expression of cd39
  • Immunosuppression-reverting oligonucleotides inhibiting the expression of cd39
  • Immunosuppression-reverting oligonucleotides inhibiting the expression of cd39

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Embodiment 1: the design of human CD39 antisense oligonucleotide

[0070] For the design of antisense oligonucleotides specific for human (h)CD39, the hCD39 mRNA sequence with SEQ ID No. 1 (sequence reference ID NM_001776.5) was used. 14, 15, 16 and 17mers were designed according to internal standards, neg1 (described in WO2014154843 A1 ) was used as control antisense oligonucleotide in all experiments (Table 1). The distribution of antisense oligonucleotide binding sites on hCD39 mRNA is as follows: figure 1 shown.

Embodiment 2

[0071] Example 2: Efficacy screening of hCD39 antisense oligonucleotides in human cancer cell lines

[0072] In order to analyze the efficacy of the hCD39 antisense oligonucleotides of the present invention on the knockdown of hCD39 mRNA expression in cancer cell lines, HDLM- 2 (human Hodgkin's lymphoma, DSMZ) and A-172 (human glioblastoma, ATCC) cells (concentration: 10 μM, without adding any transfection reagent; this process is called autonomous delivery). hCD39 and HPRT1 mRNA expression was analyzed three days later using the QuantiGene Singleplex assay (Affymetrix), and hCD39 expression values ​​were normalized to HPRT1 values. Strikingly, knockout efficiencies of >90% were observed for 23 and 18 (HDLM-2 cells; see Figures 2A and 2B ), and for 8 and 10 (A-172 cells) antisense oligonucleotides. to >90% knockout efficiency (see Figures 2C and 2D). Listed below for A-172 (Table 4 is the first round of screening and Table 5 is the second round of screening) and HDLM-2 cells...

Embodiment 3

[0086] Example 3: Correlation analysis of antisense oligonucleotide efficacy in HDLM-2 and A-172 cells

[0087] To further select the candidate with the highest activity in the two tested cell lines HDLM-2 and A-172, a correlation analysis was performed (data from Figures 2B and 2D). Such as image 3 As indicated, seven effective antisense oligonucleotides were selected for the determination of IC in HDLM-2 and A-172 cells 50 , namely A04019H (SEQ ID No.23), A04033H (SEQ ID No.37), A04039H (SEQ ID No.43), A04040H (SEQ ID No.3), A04042H (SEQ ID No.45), A04044H (SEQ ID No. 47) and A04045H (SEQ ID No. 4) (marked in black). Importantly, the control antisense oligonucleotide neg1 had no negative effect on hCD39 expression in both cell lines.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of an ectonucleotidase (NTPdase; CD73) of SEQ ID NO.1 (human), wherein the oligonucleotide inhibits at least 50 % of the CD39 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Description

technical field [0001] The present disclosure relates to an immunosuppressive restoration oligonucleotide hybridized to the nucleic acid sequence of exonucleoside triphosphate diphosphate hydrolase-1 (ENTPD1 or CD39), and the immunosuppressive restoration oligonucleotide comprising the immunosuppressive restoration oligonucleotide and a pharmaceutically acceptable carrier, endowed Pharmaceutical compositions with excipients and / or diluents. Background technique [0002] Several different diseases such as malignancies have been treated with great success in recent years by the application of immunotherapy, in particular by inhibitors of so-called "immune checkpoints". These checkpoints are molecules in the immune system that upregulate (co-stimulatory molecules) or downregulate signals. The concept of the therapeutic approach is based on the activation of the endogenous antitumor immune response. For example, many cancers protect themselves from the immune system by suppres...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61K31/712A61K31/7125C07H21/00
CPCC12N15/1137C12N15/1138C12N2310/11C12N2310/315C12N2310/3231C12N2310/341C12N2310/346C12N2320/31A61P1/00A61P19/02A61P29/00A61P35/00A61P37/00A61P37/02A61P37/04A61P37/06A61P43/00A61P9/00A61K31/712A61K31/7125A61K48/00
Inventor 弗兰克·亚申斯基塔玛拉·希尔梅纽克
Owner SECARNA PHARMA GMBH & CO KG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com