IP Library › Granted Patent US 12,344,654
Granted Patent B2
US 12,344,654 · App. 17/441,861 · Granted Jul 1, 2025

Mage A4 T cell receptors

Inventors: Christian Ellinger (Munich, DE); Daniel Sommermeyer (Munich, DE); Geoffrey Parsons (Jamaica Plain, MA); Jasdeep Mann (Lake Forest Park, WA)
Assignees: MEDIGENE IMMUNOTHERAPIES GMBH; Regeneron Pharmaceuticals, Inc.
C07K14/7051A61K35/17A61P35/00C12N5/0636A61K38/00C07K2319/00
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Quick Facts
Patent No.
US 12,344,654
App. No.
17/441,861
Granted
Jul 1, 2025
Kind
B2
Abstract

The present invention relates to an isolated T cell receptor (TCR) specific for MAGE-A4 and a polypeptide comprising a functional portion of the TCR. Further implicated are a multivalent TCR complex, a nucleic acid encoding a TCR, a cell expressing the TCR and a pharmaceutical composition comprising the TCR. The invention also refers to the TCR for use as a medicament, in particular to the TCR for use in the treatment of cancer.

Claims (32)

1. A host cell comprising a T cell receptor (TCR) specific for MAGE-A4, wherein the TCR comprises a TCR α chain comprising a variable TCR α region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 12, a CDR2 having the amino acid sequence of SEQ ID NO: 13 and a CDR3 having the amino acid sequence of SEQ ID NO: 14; and a TCR β chain comprising a variable TCR β region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 15, a CDR2 having the amino acid sequence of SEQ ID NO: 16 and a CDR3 having the amino acid sequence of SEQ ID NO: 17.

2. The host cell of claim 1 , wherein the variable TCR α region comprises the amino acid sequence of SEQ ID NO: 18; and the variable TCR β region comprises the amino acid sequence of SEQ ID NO: 19.

3. The host cell of claim 1 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 20; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 21.

4. The host cell of claim 1 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 89; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 90.

5. The host cell of claim 1 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 108; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 109.

6. The host cell of claim 1 , wherein the TCR is a fusion protein comprising the TCR α chain and the TCR β chain.

7. The host cell of claim 6 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 96.

8. The host cell of claim 6 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 110.

9. The host cell of claim 1 , wherein the TCR specifically recognizes:

a) the amino acid sequence SEQ ID NO: 1 or a fragment thereof;

b) the HLA-A2 bound form of the amino acid sequence of SEQ ID NO: 1; and/or

c) the amino acid sequence of SEQ ID NO: 1, which is presented by the HLA-A*02:01 encoded molecule.

10. A cell comprising one or more vectors encoding a T cell receptor (TCR) specific for MAGE-A4, wherein the TCR comprises a TCR α chain comprising a variable TCR α region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 12, a CDR2 having the amino acid sequence of SEQ ID NO: 13 and a CDR3 having the amino acid sequence of SEQ ID NO: 14; and a TCR β chain comprising a variable TCR β region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 15, a CDR2 having the amino acid sequence of SEQ ID NO: 16 and a CDR3 having the amino acid sequence of SEQ ID NO: 17.

11. The cell of claim 10 , wherein the variable TCR α region comprises the amino acid sequence of SEQ ID NO: 18; and the variable TCR β region comprises the amino acid sequence of SEQ ID NO: 19.

12. The cell of claim 10 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 20; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 21.

13. The cell of claim 12 , wherein the vector comprises a nucleic acid comprising the nucleotide sequences of SEQ ID Nos: 46 and 47.

14. The cell of claim 10 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 89; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 90.

15. The cell of claim 14 , wherein the vector comprises a nucleic acid comprising the nucleotide sequences of SEQ ID Nos: 77 and 78.

16. The cell of claim 10 , wherein the TCR α chain comprises the amino acid sequence of SEQ ID NO: 108; and the TCR β chain comprises the amino acid sequence of SEQ ID NO: 109.

17. The cell of claim 16 , wherein the vector comprises a nucleic acid comprising the nucleotide sequences of SEQ ID Nos: 105 and 106.

18. The cell of claim 10 , wherein the TCR is a fusion protein comprising the TCR α chain and the TCR β chain.

19. The cell of claim 18 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 96.

20. The cell of claim 19 , wherein the vector comprises a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 95.

21. The cell of claim 18 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 110.

22. The cell of claim 21 , wherein the vector comprises a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 107.

23. The cell of claim 10 , wherein the TCR specifically recognizes:

a) the amino acid sequence SEQ ID NO: 1 or a fragment thereof;

b) the HLA-A2 bound form of the amino acid sequence of SEQ ID NO: 1; and/or

c) the amino acid sequence of SEQ ID NO: 1, which is presented by the HLA-A*02:01 encoded molecule.

24. The cell of claim 10 , wherein the vector is a viral vector.

25. The cell of claim 24 , wherein the viral vector is a lentiviral vector.

26. The cell of claim 10 , wherein the one or more vectors is a single vector.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 5, 2024
From: 2SEVENTY BIO, INC.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067626/0305 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 7, 2022
From: PARSONS, GEOFFREY BLACKBURN; MANN, JASDEEP
To: BLUEBIRD BIO, INC.
Reel/Frame 058908/0427 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 7, 2022
From: ELLINGER, CHRISTIAN; SOMMERMEYER, DANIEL
To: MEDIGENE IMMUNOTHERAPIES GMBH
Reel/Frame 058908/0459 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 10, 2021
From: BLUEBIRD BIO, INC.
To: 2SEVENTY BIO, INC.
Reel/Frame 058479/0365 →
Priority Claims (1)
EP 19165387 · Mar 27, 2019 · regional
Continuity (1)
Related Publication 20230159612A1 · May 25, 2023
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