IP Library › Granted Patent US 12,686,726
Granted Patent B2
US 12,686,726 · App. 17/785,825 · Granted Jul 21, 2026

Anti-MUC1 compositions and methods of use

Inventors: Eric M. Ostertag (San Diego, CA); Devon Shedlock (San Diego, CA)
Assignee: Poseida Therapeutics, Inc.
C07K16/3092A61K40/11A61K40/31A61K40/4257A61P35/00C07K14/7051C07K14/70517C07K14/70564C07K14/70578C07K14/70589C12N5/0636C12N15/625A61K38/00A61K2239/31A61K2239/38A61K2239/49C07K2317/24C07K2317/622
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Quick Facts
Patent No.
US 12,686,726
App. No.
17/785,825
Granted
Jul 21, 2026
Kind
B2
Abstract

Disclosed are antibodies against MUC1, MUC1-CAR compositions and methods for use of these antibodies and compositions to target a MUC1 protein, wherein a cell expressing the MUC1 protein may be targeted and killed by, for instance, a cytotoxic T cell.

Claims (50)

1 . A chimeric antigen receptor (CAR) comprising

(a) an ectodomain comprising an antigen recognition region, wherein the antigen recognition region comprises at least one anti-MUC1 single chain variable fragment (scFv) comprising a heavy chain variable region comprising the amino acid sequence of

QVQLVQSGAEVKKPGSSVKVSCKTSGYAFSNFWMNWVRQAPGOGLEWIGQIYPGDGDTNYNAKFKGRVTLTADKSTSTAYMELSSLRSEDTAVYFCARSYYRSAWFAYWGOGTLVTVSS (SEQ ID NO:4); and

a light chain variable region comprising the amino acid sequence of

EILLTOSPDFQSVTPKEKVTFTCRASQSIGTSIHWYQQKPNQSPKLLIKYASESISGVPSRFSGSGSGTDFTLTINSLESEDIATYYCQQSNNWPLTFGOGTKLEIK (SEQ ID NO:9), wherein the scFv comprises a linker between the heavy chain variable region and the light chain variable region;

(b) a transmembrane domain, and

(c) an endodomain comprising at least one signal transduction domain.

2 . The CAR of claim 1 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 59.

3 . The CAR of claim 1 , wherein the scFv comprises the amino acid sequence of SEQ ID NO: 125.

4 . The CAR of claim 1 , wherein the ectodomain further comprises a signal peptide.

5 . The CAR of claim 4 , wherein the signal peptide comprises the amino acid sequence of SEQ ID NO: 57.

6 . The CAR of claim 1 , wherein the CAR further comprises a hinge region between the antigen recognition region and the transmembrane domain.

7 . The CAR of claim 6 , wherein the hinge region comprises the amino acid sequence of SEQ ID NO: 61.

8 . The CAR of claim 1 , wherein the transmembrane domain comprises a sequence encoding a CD8 transmembrane domain.

9 . The CAR of claim 8 , wherein the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 63.

10 . The CAR of claim 1 , wherein the at least one signal transduction domain comprises a CD3ζ intracellular signaling domain, a 4-1BB intracellular signaling domain, or a combination thereof.

11 . The CAR of claim 1 , wherein the at least one signal transduction domain comprises a CD3ζ intracellular signaling domain and a 4-1BB intracellular signaling domain, and wherein the 4-1BB intracellular signaling domain is located between the transmembrane domain and the CD3ζ costimulatory-intracellular signaling domain.

12 . The CAR of claim 11 , wherein the 4-1BB intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 65.

13 . The CAR of claim 11 , wherein the CD3ζ intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 67.

14 . The CAR of claim 1 , wherein

the ectodomain comprises a signal peptide,

the CAR further comprises a hinge region between the antigen recognition region and the transmembrane domain,

the transmembrane domain comprises a sequence comprising a CD8 transmembrane domain; and

the at least one signal transduction domain comprises a CD3ζ intracellular signaling domain and a 4-1BB intracellular signaling domain, and wherein the 4-1BB intracellular signaling domain is located between the transmembrane domain and the CD3ζ intracellular signaling domain.

15 . The CAR of claim 14 , wherein

the scFv comprises an amino acid sequence of SEQ ID NO: 125;

wherein the signal peptide comprises SEQ ID NO: 57;

wherein the hinge region comprises SEQ ID NO: 61;

wherein the CD8 transmembrane domain comprises SEQ ID NO: 63;

wherein the 4-1BB intracellular signaling domain comprises SEQ ID NO: 65; and

wherein the CD3ζ intracellular signaling domain comprises SEQ ID NO: 67.

16 . The CAR of claim 14 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 13.

17 . The CAR of claim 14 , wherein the amino acid sequence of the CAR is encoded by a polynucleotide comprising the nucleic acid sequence of SEQ ID NO: 31 or SEQ ID NO: 167.

18 . The CAR of claim 17 , wherein the amino acid sequence of the CAR is encoded by a polynucleotide comprising the nucleic acid sequence of SEQ ID NO: 167.

19 . A polynucleotide comprising a nucleic acid sequence encoding the CAR of claim 1 .

20 . A vector comprising the polynucleotide of claim 19 .

21 . A cell comprising the CAR of claim 1 .

22 . A population of cells, wherein a plurality of the population of cells are modified to express the CAR of claim 1 .

23 . The population of cells of claim 22 , wherein the plurality of modified cells is a plurality of modified immune cells.

24 . The population of cells of claim 22 , wherein the plurality of modified cells is a plurality of modified T-cells.

25 . The population of cells of claim 22 , wherein the plurality of the population of cells comprises at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of cells that express the CAR of claim 1 .

26 . A composition comprising the cell of claim 21 .

27 . A composition comprising the population of cells of claim 23 .

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

29 . A method of treating a MUC1 positive cancer in a subject in need thereof comprising administering a therapeutically effective amount of the composition of claim 27 .

30 . The method of claim 29 , wherein the cancer is a MUC1-C positive cancer.

31 . The method of claim 29 , wherein the cancer is a lung cancer, a brain cancer, a head and neck cancer, a breast cancer, a skin cancer, a liver cancer, a pancreatic cancer, a stomach cancer, a colon cancer, a rectal cancer, a uterine cancer, a cervical cancer, an ovarian cancer, a prostate cancer, a testicular cancer, a skin cancer or an esophageal cancer.

32 . The cell of claim 21 further comprising a a gene encoding a dihydrofolate reductase (DHFR) protein.

33 . The cell of claim 32 , wherein the gene encoding the DHFR protein comprises the sequence of SEQ ID NO: 93 or 174.

34 . The cell of claim 32 , wherein the DHFR protein comprises the sequence of SEQ ID NO: 92.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2023
From: OSTERTAG, ERIC M.; SHEDLOCK, DEVON
To: POSEIDA THERAPEUTICS, INC.
Reel/Frame 065631/0581 →
Continuity (2)
Provisional Application 62951257 · Dec 20, 2019
Related Publication 20230079955A1 · Mar 16, 2023
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