IP Library › Granted Patent US 12,428,491
Granted Patent B2
US 12,428,491 · App. 16/994,953 · Granted Sep 30, 2025

PSMA and CD3 bispecific T cell engaging antibody constructs

Inventors: Tobias Raum (Munich, DE); Markus Münz (Munich, DE); Johannes Brozy (Munich, DE); Peter Kufer (Munich, DE); Patrick Hoffmann (Munich, DE); Matthias Friedrich (Munich, DE); Benno Rattel (Munich, DE); Pamela Bogner (Munich, DE); Andreas Wolf (Munich, DE); Cornelius Pompe (Munich, DE)
Assignee: AMGEN RESEARCH (MUNICH) GMBH
C07K16/3069C07K16/2809A61K39/395A61K2039/505A61P13/08A61P35/00C07K2317/31C07K2317/52C07K2317/524C07K2317/526C07K2317/53C07K2317/622C07K2317/64C12N15/62C12N2510/00
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Quick Facts
Patent No.
US 12,428,491
App. No.
16/994,953
Granted
Sep 30, 2025
Kind
B2
Abstract

The present invention provides bispecific antibody constructs of a specific Fc modality characterized by comprising a first domain binding to PSMA, a second domain binding to an extracellular epitope of the human and the Macaca CD3ε chain and a third domain, which is the specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Claims (41)

1. A polypeptide comprising, in amino to carboxyl order:

(i) a first single-chain variable fragment (scFv) that binds to human prostate-specific membrane antigen (PSMA) comprising a VH region and a VL region, wherein the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3, wherein CDR-H1 comprises the sequence of SEQ ID NO: 372, CDR-H2 comprises the sequence of SEQ ID NO: 373, and CDR-H3 comprises the sequence of SEQ ID NO: 374, and wherein CDR-L1 comprises the sequence of SEQ ID NO: 375, CDR-L2 comprises the sequence of SEQ ID NO: 376, and CDR-L3 comprises the sequence of SEQ ID NO: 377;

(ii) a second scFv that binds to human CD3 epsilon (CD3ε) chain comprising a VH region and a VL region; and

(iii) a single chain Fc domain comprising two Fc monomers, each Fc monomer comprising an immunoglobulin hinge region, a CH2 domain, and a CH3 domain, wherein the Fc monomers are fused to each other via a peptide linker.

2. The polypeptide of claim 1 , wherein each Fc monomer comprises the hinge region, the CH2 domain, and the CH3 domain from an IgG1 immunoglobulin.

3. The polypeptide of claim 1 , wherein the peptide linker between the two Fc monomers comprises the amino acid sequence of any one of SEQ ID NOs: 5-8.

4. The polypeptide of claim 1 , wherein each Fc monomer comprises the amino acid sequence of any one of SEQ ID NOs: 17-24.

5. The polypeptide of claim 1 , wherein the VH region and VL region of the first scFv and/or the second scFv are humanized VH and VL regions.

6. The polypeptide of claim 1 , wherein the polypeptide comprises in an amino to carboxyl order: the first scFv, a first peptide linker, the second scFv, a second peptide linker, and the single chain Fc domain.

7. The polypeptide of claim 1 , wherein the first scFv comprises a VH region comprising a sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 378 and a VL region comprising a sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 379.

8. The polypeptide of claim 1 , wherein the polypeptide comprises in an amino to carboxyl order:

(a) the first scFv;

(b) a first peptide linker having a sequence selected from the group consisting of SEQ ID NOs: 1-3;

(c) the second scFv;

(d) a second peptide linker having a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 9, 10, 11 and 12;

(e) the first Fc monomer of the single chain Fc domain;

(f) a third peptide linker having a sequence selected from the group consisting of SEQ ID NOs: 5, 6, 7 and 8; and

(g) the second Fc monomer of the single chain Fc domain.

9. The polypeptide of claim 1 , wherein the first scFv comprises a sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 380.

10. The polypeptide of claim 1 , wherein the second scFv comprises the amino acid sequence of any one of SEQ ID NOs: 488-507.

11. The polypeptide of claim 1 , wherein the polypeptide comprises a sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 381, and wherein the VH region of the second scFv comprises a CDR-H1 comprising the sequence of SEQ ID NO: 544, a CDR-H2 comprising the sequence of SEQ ID NO: 545, and a CDR-H3 comprising the sequence of SEQ ID NO: 546, and the VL region of the second scFv comprises a CDR-L1 comprising the sequence of SEQ ID NO: 514, a CDR-L2 comprising the sequence of SEQ ID NO: 515, and a CDR-L3 comprising the sequence of SEQ ID NO: 516.

12. A polynucleotide encoding the polypeptide of claim 1 .

13. A vector comprising the polynucleotide of claim 12 .

14. A host cell transformed or transfected with the polynucleotide of claim 12 .

15. A host cell transformed or transfected with the vector of claim 13 .

16. A process for producing a polypeptide, comprising culturing a host cell comprising a polynucleotide encoding the polypeptide under conditions allowing the expression of the polypeptide, wherein the polypeptide comprises in an amino to carboxyl order:

(i) a first single-chain variable fragment (scFv) that binds to human prostate-specific membrane antigen (PSMA) comprising a VH region and a VL region, wherein the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3, wherein CDR-H1 comprises the sequence of SEQ ID NO: 372, CDR-H2 comprises the sequence of SEQ ID NO: 373, and CDR-H3 comprises the sequence of SEQ ID NO: 374, and wherein CDR-L1 comprises the sequence of SEQ ID NO: 375, CDR-L2 comprises the sequence of SEQ ID NO: 376, and CDR-L3 comprises the sequence of SEQ ID NO: 377;

(ii) a second scFv that binds to human CD3 epsilon (CD3ε) chain comprising a VH region and a VL region; and

(iii) a single chain Fc domain comprising two Fc monomers, each Fc monomer comprising an immunoglobulin hinge region, a CH2 domain, and a CH3 domain, wherein the Fc monomers are fused to each other via a peptide linker; and recovering the polypeptide from the culture.

17. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

18. A method for treating or ameliorating cancer in a subject having a PSMA-expressing tumor comprising administering to the subject an effective amount of the polypeptide of claim 1 .

19. The method of claim 18 , wherein the cancer is prostate cancer.

20. The polypeptide of claim 1 , wherein the first scFv comprises a VH region comprising the amino acid sequence of SEQ ID NO: 378 and a VL region comprising the amino acid sequence of SEQ ID NO: 379.

21. The polypeptide of claim 1 , wherein the first scFv comprises the amino acid sequence of SEQ ID NO: 380.

22. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 381.

23. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 382-386, and wherein the VH region of the second scFv comprises a CDR-H1 comprising the sequence of SEQ ID NO: 544, a CDR-H2 comprising the sequence of SEQ ID NO: 545, and a CDR-H3 comprising the sequence of SEQ ID NO: 546, and the VL region of the second scFv comprises a CDR-L1 comprising the sequence of SEQ ID NO: 514, a CDR-L2 comprising the sequence of SEQ ID NO: 515, and a CDR-L3 comprising the sequence of SEQ ID NO: 516.

24. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 382-386.

25. The polypeptide of claim 24 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 382.

26. A pharmaceutical composition comprising the polypeptide of claim 25 and a pharmaceutically acceptable carrier.

27. A method for treating or ameliorating cancer in a subject having a PSMA-expressing tumor comprising administering to the subject an effective amount of the polypeptide of claim 25 .

28. The method of claim 27 , wherein the cancer is prostate cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 19, 2020
From: RAUM, TOBIAS; MÜNZ, MARKUS; BROZY, JOHANNES; KUFER, PETER; HOFFMANN, PATRICK; FRIEDRICH, MATTHIAS; RATTEL, BENNO; BOGNER, PAMELA; WOLF, ANDREAS; POMPE, CORNELIUS
To: AMGEN RESEARCH (MUNICH) GMBH
Reel/Frame 054416/0785 →
Continuity (3)
Continuation 15422661 · Feb 2, 2017
Provisional Application 62290875 · Feb 3, 2016
Related Publication 20210070878A1 · Mar 11, 2021
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