US 11,596,693 B2Granted

Antibody-drug conjugates and uses thereof

AssigneeMabplex International Co., Ltd.

InventorsLele Li, Changjiang Huang, Youxiang Sun, Lina Liu

Life of this patent

Estimating the term…

Loading patent…

Abstract

Provided is an antibody-drug conjugate (ADC) using one or more cysteine or derivatives thereof as linkers to couple one or more drugs at the limited binding sites of an antibody, making it possible to produce an ADC product with high drug payload, or to choose a drug with less toxicity, thereby obtaining an ADC product with wide therapeutic window. In addition, since a plurality of drugs may be coupled to one binding site, the ADC products obtained by the method of the present disclosure have better uniformity in the case of same DAR value. Moreover, the amount of antibody required for production may be greatly reduced, thereby lowering the cost. Compared with the antibody-drug conjugates coupled only one drug, the antibody-drug conjugates produced by the method of the present disclosure have the same inhibition or killing effect on tumor cells while using fewer drugs for coupling to the same site.

Claims19

Dependent claims

An antibody-drug conjugate represented by formula (II) to formula (IV):

or
or
wherein,
A is an antibody or a functional binding fragment thereof;
B1, B2, B3, . . . , and Bn are respectively represented by formula (V):
wherein p is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8;
L1, L2, L3, L4, . . . , and Ln+1 are each independently a linker, which may be the same or different;
L1 is covalently linked to the amino terminus of B1, L2 and B1, L3 and B2, L4 and B3, . . . , Ln+1 and Bn are covalently linked via a thiol group, and L2 and D1, L3 and D2, L4 and D3, . . . , Ln+1 and Dn are covalently linked;
D1, D2, D3, . . . , and Dn are each independently an active drug, which may be the same or different;
Z is a group covalently linked to the carbonyl group of B1 in formula (I), the carbonyl group of B2 in formula (II), the carbonyl group of B3 in formula (III) or the carbonyl group of Bn in formula (IV);
n is an integer greater than or equal to 4, which represents the number of branches linking to the active drugs;
and
m is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8;
wherein L2, L3, L4, . . . , and Ln+1 are selected from the group consisting of:

11 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/650,226Filed 23 Oct 2019
Priority: CN 201910723947.87 Aug 2019
Published: US 2021/0228728 A129 Jul 2021
Granted: 7 Mar 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

A61K 47/6801
The modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment: drug-antibody or immunoglobulin conjugates…
A61K 47/6855
The antibody targeting a determinant of a tumour cell: the tumour determinant being from breast cancer cell
A61K 47/6889
The modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment: conjugates wherein the antibody being the…
A61K
Medicines and medical preparations