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Antibody-conjugates for targeting of tumours expressing trop-2

A technology of conjugates and antibodies, which can be used in anti-tumor drugs, drug combinations, medical preparations of inactive ingredients, etc., can solve the problems of instability, high cost, time-consuming, etc., and achieve the effect of improving the therapeutic index

Pending Publication Date: 2021-08-13
SYNAFFIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the latter approach has the disadvantage of having to redesign the native sequence of the antibody, which is not only time-consuming and expensive, but can also lead to instability problems

Method used

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  • Antibody-conjugates for targeting of tumours expressing trop-2
  • Antibody-conjugates for targeting of tumours expressing trop-2
  • Antibody-conjugates for targeting of tumours expressing trop-2

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Embodiment Construction

[0028] In a first aspect, the invention relates to antibody conjugates. In connection with this, in a second aspect, the present invention relates to a method of preparing an antibody conjugate of the invention. In a third aspect, the invention relates to methods for targeting cells expressing Trop-2. Related thereto is a first medical use of the antibody conjugates of the invention, and a second medical use for the treatment of cancer. In a last aspect, the present invention relates to the use of conjugation means for increasing the therapeutic index of antibody conjugates in the treatment of Trop-2 expressing tumors.

[0029] definition

[0030] As used in this specification and claims, the verb "to comprise" and its conjugations are used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded.

[0031] Also, reference to an element with the indefinite article "a" or "an" does not preclude the p...

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Abstract

The present invention concerns antibody-conjugate having general structure (2): AB-[(L 6 )-{Z-(L1) n -(L2 ) o -(L3 ) p-(L4 ) q-D} xx ] yy (2) wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

Description

technical field [0001] The present invention is in the field of bioconjugation. More specifically, the present invention relates to antibody-drug conjugates for the targeted therapy of patients with cancer, particularly Trop-2 expressing tumors. Background technique [0002] Proteins that play a role in the growth, differentiation, invasion and / or metastasis of breast cancer can affect the biological course of the tumor and thus provide important prognostic information. One such candidate is Trop-2 (GA733-1, EGP-1), a 45 kDa monomeric transmembrane glycoprotein belonging to the TACSTD gene family, specifically TACSTD2, which is expressed in human epithelial cells at various stages of differentiation. expressed in cells. Overexpression of Trop-2 has been shown to be necessary and sufficient to stimulate tumor growth and is associated with poor overall prognosis. Trop-2 expression is associated with poor prognosis in several human cancers, including oral, pancreatic, gastri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/68A61P35/00
CPCA61K47/6889A61K47/6851A61K47/6803A61P35/00
Inventor M·A·维基德文J·M·M·韦卡德J·胡根布姆S·S·范博凯尔F·L·范代尔夫特P·J·J·M·范德桑德
Owner SYNAFFIX
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