IP Library › Granted Patent US 12,590,136
Granted Patent B2
US 12,590,136 · App. 17/608,860 · Granted Mar 31, 2026

Engineered T cells

Inventors: Jasdeep Mann (Lake Forest Park, WA); Christian Ellinger (Munich, DE); Daniel Sommermeyer (Munich, DE); Benjamin Boyerinas (Brookline, MA)
Assignees: Regeneron Pharmaceuticals, Inc.; MEDIGENE IMMUNOTHERAPIES GMBH
C07K14/7051A61K35/17A61K39/001134A61K39/001136A61K39/001186A61K40/11A61K40/32A61K40/4229A61K40/4234A61K40/4268A61P35/00C07K14/005C07K14/70596C07K14/71C07K14/7155C07K14/7156C12N5/0636A61K38/00A61K2239/31A61K2239/38C07K2319/02C07K2319/03C07K2319/33
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Quick Facts
Patent No.
US 12,590,136
App. No.
17/608,860
Granted
Mar 31, 2026
Kind
B2
Abstract

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Claims (75)

1 . A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR; and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3 or 6, and wherein the fusion polypeptide comprises:

(a) a first polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR2;

(ii) an IL-12Rβ2 transmembrane domain or an IL-12Rβ1 transmembrane domain; and

(iii) an IL-12Rβ2 intracellular signaling domain or an IL-12Rβ1 intracellular signaling domain;

(b) a polypeptide cleavage signal; and

(c) a second polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR1;

(ii) an IL-12Rβ2 transmembrane domain or an IL-12Rβ1 transmembrane domain; and

(iii) an IL-12Rβ2 intracellular signaling domain or an IL-12Rβ1 intracellular signaling domain.

2 . The method of claim 1 , wherein the solid cancer comprises liver cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, brain cancer, sarcoma, head and neck cancer, bone cancer, thyroid cancer, kidney cancer, esophageal cancer, or skin cancer.

3 . The method of claim 1 , wherein the solid cancer is an esophageal cancer.

4 . The method of claim 1 , wherein the solid cancer is synovioma.

5 . The method of claim 1 , wherein the solid cancer is ovarian cancer.

6 . The method of claim 1 , wherein the solid cancer is non-small cell lung cancer.

7 . The method of claim 1 , wherein the solid cancer expresses MAGEA4.

8 . The method of claim 1 , wherein the first polypeptide comprises the IL-12Rβ2 intracellular signaling domain and the second polypeptide comprises the IL-12Rβ1 intracellular signaling domain.

9 . The method of claim 8 , wherein the first polypeptide comprises the IL-12Rβ2 transmembrane domain and/or the second polypeptide comprises the IL-12Rβ1 transmembrane domain.

10 . The method of claim 1 , wherein the first polypeptide comprises the IL-12Rβ1 intracellular signaling domain and the second polypeptide comprises the IL-12Rβ2 intracellular signaling domain.

11 . The method of claim 10 , wherein the first polypeptide comprises the IL-12Rβ1 transmembrane domain and/or the second polypeptide comprises the IL-12Rβ2 transmembrane domain.

12 . The method of claim 1 , wherein the polypeptide cleavage signal is a viral self-cleaving polypeptide.

13 . The cell of claim 12 , wherein the polypeptide cleavage signal is a viral self-cleaving 2A polypeptide.

14 . The method of claim 1 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3.

15 . The method of claim 1 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 6.

16 . The method of claim 1 , wherein the fusion polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 8.

17 . The method of claim 1 , wherein the source of the T cell is peripheral blood mononuclear cells, bone marrow, lymph nodes tissue, cord blood, thymus issue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, or tumors.

18 . A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR; and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3 or 6, and wherein the fusion polypeptide comprises:

(a) a TGFβR2 polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR2;

(ii) an IL-12Rβ2 transmembrane domain; and

(iii) an IL-12Rβ2 intracellular signaling domain;

(b) a viral self-cleaving 2A peptide; and

(c) a TGFβR1 polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR1;

(ii) an IL-12Rβ1 transmembrane domain; and

(iii) an IL-12Rβ1 intracellular signaling domain.

19 . The method of claim 18 , wherein the solid cancer comprises liver cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, brain cancer, sarcoma, head and neck cancer, bone cancer, thyroid cancer, kidney cancer, esophageal cancer, or skin cancer.

20 . The method of claim 18 , wherein the solid cancer is an esophageal cancer.

21 . The method of claim 18 , wherein the solid cancer is synovioma.

22 . The method of claim 18 , wherein the solid cancer is ovarian cancer.

23 . The method of claim 18 , wherein the solid cancer is non-small cell lung cancer.

24 . The method of claim 18 , wherein the solid expresses MAGEA4.

25 . The method of claim 18 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3.

26 . The method of claim 18 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 6.

27 . The method of claim 18 , wherein the source of the T cell is peripheral blood mononuclear cells, bone marrow, lymph nodes tissue, cord blood, thymus issue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, or tumors.

28 . A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR; and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3 or 6, and wherein the fusion polypeptide comprises:

(a) a TGFβR2 polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR2;

(ii) an IL-12Rβ1 transmembrane domain; and

(iii) an IL-12Rβ1 intracellular signaling domain;

(b) a viral self-cleaving 2A peptide; and

(c) a TGFβR1 polypeptide comprising:

(i) an extracellular TGFβ1-binding domain of TGFβR1;

(ii) an IL-12Rβ2 transmembrane domain; and

(iii) an IL-12Rβ2 intracellular signaling domain.

29 . The method of claim 28 , wherein the solid cancer comprises liver cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, brain cancer, sarcoma, head and neck cancer, bone cancer, thyroid cancer, kidney cancer, esophageal cancer, or skin cancer.

30 . The method of claim 28 , wherein the solid cancer is an esophageal cancer.

31 . The method of claim 28 , wherein the solid cancer is synovioma.

32 . The method of claim 28 , wherein the solid cancer is ovarian cancer.

33 . The method of claim 28 , wherein the solid cancer is non-small cell lung cancer.

34 . The method of claim 28 , wherein the solid cancer expresses MAGEA4.

35 . The method of claim 28 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3.

36 . The method of claim 28 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 6.

37 . The method of claim 28 , wherein the source of the T cell is peripheral blood mononuclear cells, bone marrow, lymph nodes tissue, cord blood, thymus issue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, or tumors.

38 . A T cell comprising a first polynucleotide encoding a MAGEA4 TCR; and a second polynucleotide encoding a fusion polypeptide wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3 or 6, and wherein the fusion polypeptide comprises SEQ ID NO: 8.

39 . The cell of claim 38 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 2 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 3.

40 . The cell of claim 38 , wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO: 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO: 6.

41 . The cell of claim 38 , wherein the source of the T cell is peripheral blood mononuclear cells, bone marrow, lymph nodes tissue, cord blood, thymus issue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, or tumors.

42 . A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of the T cell of claim 38 .

43 . The method of claim 42 , wherein the solid cancer comprises liver cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, brain cancer, sarcoma, head and neck cancer, bone cancer, thyroid cancer, kidney cancer, esophageal cancer, or skin cancer.

44 . The method of claim 42 , wherein the solid cancer is an esophageal cancer.

45 . The method of claim 42 , wherein the solid cancer is synovioma.

46 . The method of claim 42 , wherein the solid cancer is ovarian cancer.

47 . The method of claim 42 , wherein the solid cancer is non-small cell lung cancer.

48 . The method of claim 42 , wherein the solid cancer expresses MAGEA4.

Assignments (3)
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 Oct 26, 2022
From: ELLINGER, CHRISTIAN; SOMMERMEYER, DANIEL
To: MEDIGENE IMMUNOTHERAPIES GMBH
Reel/Frame 061545/0585 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 22, 2022
From: MANN, JASDEEP; BOYERINAS, BENJAMIN
To: 2SEVENTY BIO, INC.
Reel/Frame 059337/0549 →
Continuity (2)
Provisional Application 62845311 · May 8, 2019
Related Publication 20230044580A1 · Feb 9, 2023
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