Antibody-conjugates for targeting of tumours expressing PTK7

Patent metadata

Field	Value
Publication number	US-12440573-B2
Application number	US-202418892253-A
Country	US
Kind code	B2
Filing date	Sep 20, 2024
Priority date	Mar 23, 2022
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):

AB -[( L 6 ) b -{ Z - L - D} x ] y   1

Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L 6 is -GlcNAc(Fuc) w -(G) j -S-(L 7 ) w′ -, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L 7 is —N(H)C(O)CH 2 —, —N(H)C(O)CF 2 — or —CH 2 —; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).

First claim

The invention claimed is:

1. An antibody-conjugate according to general structure (1):
AB-[(L 6 ) b -{Z-L-D} x ] y   (1)

wherein:
AB is an anti-PTK7 antibody comprising a light chain and a heavy chain comprising the amino acid sequences set forth in SEQ ID NO: 20 and 19, respectively;
L 6 is -GlcNAc(Fuc) w -(G) j -S-(L 7 ) w′ -;
G is selected from galactose, glucose, N-acetylgalactosamine, N-acetylglucosamine, mannose or N-acetylneuraminic acid;
j is an integer in the range of 0-10;
S is GalNAc;
GlcNAc is N-acetylglucosamine;
Fuc is fucose;
w is 0 or 1;
w′ is 0, 1 or 2;
b is 0 or 1;
x is 1 or 2;
y is 1, 2, 3 or 4;
L 7 is —N(H)C(O)CH 2 —, —N(H)C(O)CF 2 — or —CH 2 —; and
—Z-L-D is:

wherein * is the point of attachment of —Z-L-D to L 6 ,
or a pharmaceutically acceptable salt thereof.

2. The antibody-conjugate of claim 1 , wherein j is 0.

3. The antibody-conjugate of claim 1 , wherein w′ is 0.

4. The antibody-conjugate according to claim 1 , wherein x is 1.

5. The antibody-conjugate according to claim 1 , wherein y is 2.

6. The antibody-conjugate of claim 1 , wherein said antibody-conjugate is of the following formula:

or a pharmaceutically acceptable salt thereof.

7. The antibody-conjugate of claim 1 , wherein said antibody-conjugate is of the following formula:

or a pharmaceutically acceptable salt thereof.

8. The antibody-conjugate according to claim 1 , wherein w is 0.

9. The antibody-conjugate according to claim 1 , wherein w is 1.

Assignees

• Synaffix Bv

Inventors

• Lelieveldt Lianne
• Van Geel Remon
• Van Berkel Sander Sebastiaan
• Van Delft Floris Louis

Classifications

• C07K16/40

  against enzymes · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6815

  Enzymes · CPC title

• A61K47/6889 Primary

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title