Heterodimeric antibodies that bind CD3 and PSMA

Patent metadata

Field	Value
Publication number	US-10227410-B2
Application number	US-201615372360-A
Country	US
Kind code	B2
Filing date	Dec 7, 2016
Priority date	Dec 7, 2015
Publication date	Mar 12, 2019
Grant date	Mar 12, 2019

Abstract

The present invention is directed to heterodimeric antibodies that bind CD3 and PSMA.

First claim

What is claimed is:

1. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first Fc domain; and
ii) an anti-CD3 scFv comprising a first heavy variable domain, an scFv linker and a first variable light domain; wherein said scFv is covalently attached to the N-terminus of said Fc domain using a domain linker;

b) a second monomer comprising a heavy chain comprising:
i) a second heavy variable domain; and
ii) a heavy constant domain comprising a second Fc domain; and

c) a light chain comprising a second variable light domain and a constant light domain;
wherein said second heavy variable domain comprises a vhCDR1 having SEQ ID NO: 111, a vhCDR2 having SEQ ID NO: 112, and a vhCDR3 having SEQ ID NO: 113,
and said second variable light domain comprises a vlCDR1 having SEQ ID NO: 107, a vlCDR2 having SEQ ID NO: 108, and a vlCDR3 having SEQ ID NO: 109, and wherein said second heavy variable domain and said second variable light domain bind PSMA.

2. A heterodimeric antibody according to claim 1 , where said second heavy variable domain comprises amino acid sequence SEQ ID NO: 110 and said second variable light domain comprises amino acid sequence SEQ ID NO: 106.

3. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 1 and said first variable light domain comprises SEQ ID NO: 5.

4. A heterodimeric antibody according to claim 3 , wherein said first monomer comprises SEQ ID NO: 64, said second monomer comprises SEQ ID NO: 65, and said light chain comprises SEQ ID NO: 66.

5. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 10 and said first variable light domain comprises SEQ ID NO: 14.

6. A heterodimeric antibody according to claim 5 , wherein said first monomer comprises SEQ ID NO: 124, said second monomer comprises SEQ ID NO: 125, and said light chain comprises SEQ ID NO: 126.

7. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 37 and said first variable light domain comprises SEQ ID NO: 41.

8. A heterodimeric antibody according to claim 7 , wherein said first monomer comprises SEQ ID NO: 118, said second monomer comprises SEQ ID NO: 119, and said light chain comprises SEQ ID NO: 120.

9. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 46 and said first variable light domain comprises SEQ ID NO: 50.

10. A heterodimeric antibody according to claim 9 , wherein said first monomer comprises SEQ ID NO: 121, said second monomer comprises SEQ ID NO: 122, and said light chain comprises SEQ ID NO: 123.

11. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 19 and said first variable light domain comprises SEQ ID NO: 23.

12. A heterodimeric antibody according to claim 1 , wherein said first variable heavy domain comprises SEQ ID NO: 28 and said first variable light domain comprises SEQ ID NO: 32.

13. A heterodimeric antibody according to claim 1 , wherein said first Fc domain and said second Fc domain comprise a set of variants selected from the group consisting of S364K/E357Q: L368D/K370S; L368D/K370S: S364K; L368E/K370S: S364K; T411T/E360E/Q362E: D401K; L368D/K370S: S364K/E357L and K370S: S364K/E357Q.

14. A heterodimeric antibody according to claim 1 , wherein said scFv linker is a charged linker.

15. A heterodimeric antibody according to claim 13 , wherein said heavy chain constant domain comprises the amino acid substitutions N208D/Q295E/N384D/Q418E/N421D.

16. A heterodimeric antibody according to claim 13 , wherein said first and second Fc domains further comprise the amino acid substitutions E233P/L234V/L235A/G236del/S267K.

17. A nucleic acid composition encoding the heterodimeric antibody according to claim 1 , said composition comprising:
a) a first nucleic acid encoding said first monomer;
b) a second nucleic acid encoding said second monomer; and
c) a third nucleic acid encoding said light chain.

18. An expression vector composition comprising the nucleic acid composition of claim 17 .

19. A host cell comprising the nucleic acid composition of claim 17 .

20. A host cell comprising the expression vector composition of claim 19 .

21. A method of making a heterodimeric antibody comprising culturing the host cell of claim 19 or 20 under conditions wherein said antibody is expressed, and recovering said heterodimeric antibody.

22. A heterodimeric antibody comprising:
a) a first monomer comprising SEQ ID NO: 125;
b) a second monomer comprising SEQ ID NO: 124; and
c) a light chain comprising SEQ ID NO: 126.

23. A nucleic acid composition encoding the heterodimeric antibody according to claim 22 , said composition comprising:
a) a first nucleic acid encoding said first monomer;
b) a second nucleic acid encoding said second monomer; and
c) a third nucleic acid encoding said light chain.

24. An expression vector composition comprising the nucleic acid composition of claim 23 .

25. A host cell comprising the nucleic acid composition of claim 23 .

26. A host cell comprising the expression vector composition of claim 24 .

27. A method of making a heterodimeric antibody comprising culturing the host cell of claim 25 or 26 under conditions wherein said antibody is expressed, and recovering said heterodimeric antibody.

Assignees

• Xencor Inc

Inventors

• Moore Gregory
• Desjarlais John
• Chu Seung

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title