IP Library › Granted Patent US 12,435,139
Granted Patent B2
US 12,435,139 · App. 18/069,704 · Granted Oct 7, 2025

Antibody constructs for DLL3 and CD3

Inventors: Tobias Raum (Munich, DE); Claudia Blümel (Munich, DE); Christoph Dahlhoff (Munich, DE); Patrick Hoffmann (Munich, DE); Peter Kufer (Munich, DE); Ralf Lutterbüse (Munich, DE); Elisabeth Nahrwold (Munich, DE); Jochen Pendzialek (Munich, DE)
Assignee: AMGEN RESEARCH (MUNICH) GMBH
C07K16/2809A61K39/3955A61K39/39558A61K40/11A61K40/4225C07K16/18C07K16/28C12N5/06C12N15/63A61K2039/505A61K2239/31A61K2239/38A61K2239/55A61K2239/57C07K16/22C07K16/30C07K2317/31C07K2317/33C07K2317/34C07K2317/51C07K2317/515C07K2317/56C07K2317/622C07K2317/73C07K2317/76C07K2317/77C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,435,139
App. No.
18/069,704
Granted
Oct 7, 2025
Kind
B2
Abstract

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising the polynucleotide and a host cell transformed or transfected with the polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of the antibody construct and a kit comprising the antibody construct.

Claims (24)

1. A bispecific antibody construct comprising a first binding domain which binds an epitope of human Delta-like Ligand 3 (DLL3) on the surface of a target cell within the amino acid sequence of SEQ ID NO: 269 and a second binding domain which binds human CD3 on the surface of a T cell, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:

a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 171, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 172, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 173, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 174, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 175 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 176;

b) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 181, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 182, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 183, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 184, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 185 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 186;

c) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 191, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 192, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 193, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 194, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 195 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 196; and

d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 201, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 202, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 203, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 204, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 205 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 206.

2. The antibody construct of claim 1 , wherein the first binding domain comprises a VH region comprising an amino acid sequence comprising:

a) at least 85% identity to an amino acid sequence of SEQ ID NO: 177, SEQ ID NO: 187, SEQ ID NO: 197, or SEQ ID NO: 207; or

b) the amino acid sequence of SEQ ID NO: 177, SEQ ID NO: 187, SEQ ID NO: 197, or SEQ ID NO: 207.

3. The antibody construct of claim 1 , wherein the first binding domain comprises a VL region comprising an amino acid sequence comprising:

a) at least 85% identity to an amino acid sequence of SEQ ID NO: 178, SEQ ID NO: 188, SEQ ID NO: 198, or SEQ ID NO: 208; or

b) the amino acid sequence of SEQ ID NO: 178, SEQ ID NO: 188, SEQ ID NO: 198, or SEQ ID NO: 208.

4. The antibody construct of claim 1 , wherein the first binding domain comprises a VH region and VL region comprising a pair of amino acid sequences, respectively, comprising:

a) at least 85% identity to the amino acid sequences of SEQ ID NOs: 177 and 178, SEQ ID NOs: 187 and 188, SEQ ID NOs: 197 and 198, or SEQ ID NOs: 207 and 208; or

b) the amino acid sequences of SEQ ID NOs: 177 and 178, SEQ ID NOs: 178 and 188, SEQ ID NOs: 197 and 198, or SEQ ID NOs: 207 and 208.

5. The antibody construct of claim 1 , wherein the first binding domain comprises an amino acid sequence comprising:

a) at least 85% identity to an amino acid sequence of SEQ ID NO: 179, SEQ ID NO: 189, SEQ ID NO: 199, or SEQ ID NO: 209; or

b) the amino acid sequence of SEQ ID NO: 179, SEQ ID NO: 189, SEQ ID NO:199, or SEQ ID NO: 209.

6. The antibody construct of claim 1 , wherein the antibody construct comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 180, SEQ ID NO: 190, SEQ ID NO: 200, or SEQ ID NO: 210.

7. The antibody construct of claim 1 , wherein antibody construct is in a format of (scFv) 2 .

8. The antibody construct of claim 1 , wherein antibody construct is in a format of scFv-single domain monoclonal antibody (mAb).

9. The antibody construct of claim 1 , wherein the first binding domain, the second binding domain, or both is in a Fab format.

10. A composition comprising the antibody construct of claim 1 and an excipient or a combination of excipients.

11. A kit comprising the composition of claim 10 .

12. The kit of claim 11 further comprising instructions for use in treating or ameliorating a tumor or cancer disease expressing Delta-like Ligand 3 (DLL3).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2024
From: RAUM, TOBIAS; BLÜMEL, CLAUDIA; DAHLHOFF, CHRISTOPH; HOFFMANN, PATRICK; KUFER, PETER; LUTTERBÜSE, RALF; NAHRWOLD, ELISABETH; PENDZIALEK, JOCHEN, MR.
To: AMGEN RESEARCH (MUNICH) GMBH
Reel/Frame 066313/0514 →
Continuity (6)
Continuation 16868257 · May 6, 2020
Division 16291826 · Mar 4, 2019
Division 15225107 · Aug 1, 2016
Provisional Application 62290896 · Feb 3, 2016
Provisional Application 62199930 · Jul 31, 2015
Related Publication 20230312717A1 · Oct 5, 2023
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