Compound for immunotherapy, and composition

A technology of compounds, chemical bonds, applied in the field of compounds for targeted immunotherapy

Inactive Publication Date: 2015-08-26
BIRDIE BIOPHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the strict technical requirements in terms of antibodies, linker molecules, toxin molecules, conjugation, and limited molecules that can bring toxins into the tumor microenvironment, there are still some difficulties in actual clinical research

Method used

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  • Compound for immunotherapy, and composition
  • Compound for immunotherapy, and composition
  • Compound for immunotherapy, and composition

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0351] Compound preparation

[0352] In general, activated moieties represented by structures of general formula (I) can be prepared using the synthetic steps outlined below. In step (1), 4-chloro-3-nitroquinoline of general formula A and general formula R 1 NH 2 The reaction of amines generates 3-nitroquinolin-4-amines of general formula B. In step 2, 3-nitroquinolin-4-amines of general formula B are reduced to yield quinoline-3-4-diamines of general formula C. In step 3, quinoline-3-4-diamine of general formula C is reacted with carboxylic acid or its equivalent to generate 1H-imidazo[4,5c]quinoline of general formula D.

[0353]

[0354] Alternatively, compounds of general formula (I) can be prepared according to the synthetic methods described in US6,331,539B1, US6,451,810B1, US7,157,452 and US7,301027B2.

[0355] On the other hand, compounds of general formula (Ia) and general formula (Ib) can be prepared by using a linker to link both the targeting moiety and th...

Embodiment 1

[0419] Generation of HER2 or EGFR transfected L cell lines

[0420] Reagents: L cells from ATCC (Manassas, VA; Cat No. CRL2648), Her2 / pEZ-Lv105 or egfr / pCMV purchased from Sino Biological Inc., (Cat No. H10004) or GeneCopoeia, (Cat No. Z2866) cDNA, glucose DMEM, L-glutamine, Lipofectamine 2000 (Invitrogen; Carlsbad, CA).

[0421] To generate cell lines for screening conjugated trastuzumab, L cells expressing tagged Her2 or EGFR were generated. Her2 / pEZ-Lv105 or egfr / pCMV cDNA constructs were transfected into L cells (the cells were grown in high concentration glucose DMEM+10%FBS+2mM L-glutamine) by standard Lipofectamine2000 operating procedures.

[0422] Binding analysis (FACS analysis)

[0423]To determine the binding capacity of conjugated trastuzumab, FACS analysis was performed on L cells expressing human her2. Briefly, 100 μl of approximately 10 6 L cells with transiently transfected her2 were incubated with varying amounts of trastuzumab-conjugated antibodies, u...

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Abstract

The present invention relates to a compound for targeting immunotherapy, and a composition containing the compound. The present invention further relates to applications of the compound in treatment of diseases such as cancers.

Description

technical field [0001] The present invention relates to compounds for use in targeted immunotherapy and compositions containing the compounds. The invention also relates to the use of said compounds in the treatment of diseases such as cancer. Background technique [0002] Therapeutic antibodies have been used in clinical applications for more than two decades. At present, there are fifteen kinds of anti-tumor antibody drugs used clinically, these drugs include: Rituxan (1997), Herceptin (1998), Mylotarg (2000), Campath (2001), Zevalin (2002), Bexxer (2003), Avastin ( 2004), Erbitux (2004), Vectibix (2006); Arzerra (2009); Benlysta (2011); Yervoy (2011); Adcetris (2011); Perjeta (2012); and Kadcyla (2013). These antibodies primarily target four molecules: EGFR, Her2, CD20 and VEGF. [0003] In general, therapeutic antibodies kill tumor cells through three mechanisms (Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. (2012), 12:278-87): (1) Antibody...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/32A61K31/4745A61K31/522A61K47/48A61P35/00A61P35/02
Inventor 李立新
Owner BIRDIE BIOPHARM INC
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