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Cell targeting conjugates

A technology of cell targeting and conjugates, which is applied in drug combinations, medical preparations of non-active ingredients, anti-tumor drugs, etc., and can solve problems such as toxicity and affecting the immunological characteristics of antibodies

Inactive Publication Date: 2019-07-02
LINXIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antibody modifications may affect the immunological properties of the antibody, leading to undesired toxicity

Method used

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  • Cell targeting conjugates
  • Cell targeting conjugates
  • Cell targeting conjugates

Examples

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Embodiment

[0072] Materials and methods

[0073] general material

[0074] The cell lines used were breast cancer cell lines MDA-MB231, JIMT, BT-474 and SKBR3, ovarian cancer cell line SKOV and gastric cancer cell line NCI-N87. JIMT-1 was obtained from DSMZ Germany on March 19, 2012, after cytogenetic testing and used within 6 months of resuscitation. NCI-N87 was obtained at ATCC UK on 29 February 2012, following cytogenetic testing and used within 6 months of resuscitation. SKBR3 was obtained from Dr. T. Oude Munnink (Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands), MDA-MB-231 from Roche, and SK-OV-3 from Department of Medical Oncology, VU University Medical Center Amsterdam. All cell lines were examined for primary growth characteristics (morphology and growth rate) and HER2 expression. MDA-MB231 is a cell line with low HER2 expression; SKBR3, BT-474, SKOV-3, and NCI-N87 overexpress HER2; and JIMT-1 is developed from tumor cells of...

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Abstract

The present invention relates to cell targeting conjugates, which conjugates comprise a targeting moiety and one or more functional moieties bound thereto via a linker, wherein the linker comprises atransition metal complex and wherein at least 90% of the conjugates have a ratio of functional moieties to targeting moieties (DAR) of 4 or lower. The invention further relates to a pharmaceutical composition comprising said cell targeting conjugates and to the use of said conjugates and composition as a medicament, in particular in the treatment of cancer.

Description

technical field [0001] The present invention relates to cell-targeting conjugates comprising a targeting moiety and one or more functional moieties bound to the targeting moiety by a linker, wherein the linker comprises a transition metal complex. The present invention also relates to a pharmaceutical composition comprising said cell-targeted conjugate, and the medical use of said pharmaceutical composition and said cell-targeted conjugate. Background technique [0002] The vast majority of available bioconjugation techniques rely on the covalent coupling of organic linkers to proteins. Primary examples are linkers comprising reactive esters or maleimides for coupling to lysine or cysteine ​​residues, respectively. In the field of cell-targeting conjugates (also known as antibody drug conjugates or ADCs), two linkers have been successfully used in the clinically approved ADCKadcyla TM (ado-trastuzumab emtansine, T-DM1) and Adcetris TM (Brentuzumab-vedotin). [0003] Desp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P35/00A61K47/68
CPCA61K47/6803A61K47/6849A61P31/00A61P35/00A61K47/68031
Inventor 奥古斯蒂努斯·安东尼厄斯·马里亚·西尔韦斯特·范东恩尼尔斯·于里安·赛布兰迪丹尼斯·克里斯蒂安·约翰内斯·瓦尔布尔亨德里克·扬·豪特霍夫
Owner LINXIS