IP Library › Granted Patent US 12686725
Granted Patent B2
US 12686725 · App. 17/997,907 · Granted Jul 21, 2026

Anti-DLL3 antibodies and methods of use

Inventors: Gholamreza Hassanzadeh Ghassabeh (Ghent, BE); Lorena Lerner (Andover, MA); Sonia Feau (Chestnut Hill, MA); Christophe Quéva (Cambridge, MA)
Assignee: Mythic Therapeutics, Inc.
C07K16/3023A61P35/00C07K16/2809C12N15/63C07K2317/31C07K2317/52C07K2317/565
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Quick Facts
Patent No.
US 12686725
App. No.
17/997,907
Granted
Jul 21, 2026
Kind
B2
Abstract

The present disclosure provides anti-DLL3 binding constructs, such as anti-DLL3 single domain antibodies, as well as polynucleotide encoding the same. Further provided are multispecific binding constructs comprising the DLL3 binding domains described herein and polynucleotides encoding the same. Methods of production of the anti-DLL3 binding constructs and their use in the treatment of cancer are also provided herein.

Claims (99)

1 . A protein binding construct comprising a DLL3-binding domain that is capable of specifically binding DLL3 or an epitope of DLL3 comprising a heavy chain variable region (VH) comprising a complementarity determining region (CDR) 1, a CDR2, and a CDR3, wherein the CDR1, CDR2, and CDR3 comprise the amino acid sequences as set forth in any one of the following sets of SEQ ID NOs:

a) SEQ ID NOs: 46, 47, and 48, respectively;

b) SEQ ID NOs: 52, 53, and 54, respectively;

c) SEQ ID NOs: 18, 19, and 20, respectively;

d) SEQ ID NOs: 83, 2, and 84, respectively;

e) SEQ ID NOs: 60, 61, and 62, respectively;

f) SEQ ID NOs: 65, 66, and 67, respectively;

g) SEQ ID NOs: 69, 23, and 24, respectively;

h) SEQ ID NOs: 14, 43, and 71, respectively;

i) SEQ ID NOs: 73, 74, and 75, respectively;

j) SEQ ID NOs: 77, 78, and 79, respectively;

k) SEQ ID NOs: 1, 2, and 3, respectively;

l) SEQ ID NOs: 6, 7, and 8, respectively;

m) SEQ ID NOs: 10, 11, and 12, respectively;

n) SEQ ID NOs: 14, 15, and 16, respectively;

o) SEQ ID NOs: 22, 23, and 24, respectively;

p) SEQ ID NOs: 26, 27, and 28, respectively;

g) SEQ ID NOs: 30, 2, and 31, respectively;

r) SEQ ID NOs: 33, 81, and 34, respectively;

S) SEQ ID NOs: 36, 82, and 37, respectively;

t) SEQ ID NOs: 39, 40, and 41, respectively; and

u) SEQ ID NOs: 14, 43, and 44, respectively.

2 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 52;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 53; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 54.

3 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 18;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 19; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 20.

4 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 83;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 2; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 84.

5 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 60;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 61; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 62.

6 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 65;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 66; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 67.

7 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 69;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 23; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 24.

8 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 14;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 43; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 71.

9 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 73;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 74; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 75.

10 . The protein binding construct of claim 1 , comprising or consisting of an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from SEQ ID NOs: 4, 5, 9, 13, 17, 21, 25, 29, 32, 35, 38, 42, 45, 49, 55, 59, 63, 64, 68, 70, 72, and 76.

11 . The protein binding construct of claim 1 , further comprising a human framework region sequence.

12 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 46;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 47; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 48.

13 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 52;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 53; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 54.

14 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 18;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 19; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 20.

15 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 83;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 2; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 84.

16 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 60;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 61; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 62.

17 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 65;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 66; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 67.

18 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 69;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 23; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 24.

19 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 14;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 43; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 71.

20 . The protein binding construct of claim 11 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 73;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 74; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 75.

21 . The protein binding construct of claim 11 , comprising or consisting of an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from SEQ ID NOs: 50, 51, 56, 57 and 58.

22 . A chimeric antigen receptor (CAR) comprising the protein binding construct of claim 1 .

23 . A method of treating cancer in a subject in need thereof, comprising administering an effective amount of the protein binding construct of claim 11 to the subject, thereby treating the subject.

24 . The protein binding construct of claim 1 , wherein:

the CDR1 comprises an amino acid sequence of SEQ ID NO: 46;

the CDR2 comprises an amino acid sequence of SEQ ID NO: 47; and

the CDR3 comprises an amino acid sequence of SEQ ID NO: 48.