Granted Patent
B2
US 12,642,792 · App. 17/753,594 · Granted Jun 2, 2026
CA2-IL15 fusion proteins for tunable regulation
Inventors:
Kutlu Goksu Elpek (Arlington, MA); Dhruv Kam Sethi (Cambridge, MA); Meghan C. Langley (Cambridge, MA); Tucker Read Ezell (Cambridge, MA); Dexue Sun (Cambridge, MA); Jennifer Leah Gori (Jamaica Plain, MA); Geetha Hanna Mylvaganam (Boston, MA); Michelle Ols (Northborough, MA); Michelle Fleury (Cambridge, MA); Celeste Richardson (Brookline, MA); James A. Storer (Medford, MA); Vipin Suri (Belmont, MA); Shyamsundar Subramanian (Downingtown, PA); Colleen Foley (Cambridge, MA); Molly Reed Perkins (Milton, MA); Jeremy Hatem Tchaicha (Belmont, MA); Scott Francis Heller (Stoughton, MA)
Assignee:
OBSIDIAN THERAPEUTICS, INC.
A61K31/433A61K31/427A61K40/11A61K40/15A61K40/31A61K40/35A61K40/4211A61P35/00C07K14/5443C07K14/7051C12N5/0636C12N9/88C12N15/625C12N15/86C12N15/861C12N15/8645C12N15/867C12N15/869A61K2239/31A61K2239/38A61K2239/48C07K2319/00C07K2319/02C07K2319/03C12N2740/15043C12Y402/01001
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Abstract
The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.
Claims (17)
1 . A method of treating a disease or disorder responsive to regulated IL 15 in a subject in need thereof, said method comprising:
(a) administering to the subject a therapeutically effective amount of a cell comprising a nucleic acid molecule comprising a polynucleotide encoding a recombinant protein comprising a drug responsive domain (DRD) operably linked to an IL15 payload, wherein the DRD is derived from human carbonic anhydrase II (CA2) and comprises the amino acid sequence of SEQ ID NO:4 and wherein the IL15 payload is a membrane-bound IL15 polypeptide, wherein the cell is a tumor infiltrating lymphocyte (TIL), a human T cell or a human NK cell; and
(b) administering a therapeutically effective amount of a stimulus to the subject, wherein the DRD is stabilized by the stimulus to enable expression of the IL15 payload, wherein the stimulus is acetazolamide, and wherein the disease or disorder is a cancer.
2 . The method of claim 1 , wherein the TIL or human T cell is a CD4+ or CD8+ T cell.
3 . The method of claim 1 , wherein the membrane-bound IL 15 polypeptide comprises the amino acid sequence of SEQ ID NO:8.
4 . The method of claim 1 , wherein the membrane-bound IL15 polypeptide is N-terminal to the DRD.
5 . The method of claim 3 , wherein the recombinant protein further comprises a transmembrane domain and an intracellular tail.
6 . The method of claim 5 , wherein the transmembrane domain is C-terminal to the amino acid sequence of SEQ ID NO:8 and the intracellular tail is C-terminal to the transmembrane domain.
7 . The method of claim 5 , wherein the recombinant protein further comprises a linker between the amino acid sequence of SEQ ID NO:8 and the transmembrane domain and a leader sequence N-terminal to the amino acid sequence of SEQ ID NO:8.
8 . The method of claim 1 , wherein the polynucleotide encodes the amino acid sequence of SEQ ID NO:24.
9 . The method of claim 1 , wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO:25.
10 . The method of claim 1 , wherein the cell further comprises a second polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR).
11 . The method of claim 10 , wherein the CAR or TCR comprises an antigen-binding domain specific to an antigen of interest.
12 . The method of claim 10 , wherein the second polynucleotide encodes a CAR comprising an antigen-binding domain specific to an antigen of interest.
13 . The method of claim 12 , wherein the CAR comprises an antigen-binding domain specific to CD19.
14 . The method of claim 1 , wherein the polynucleotide is introduced into the cell by viral transduction.
15 . The method of claim 14 , wherein the viral transduction comprises using a lentiviral vector comprising the polynucleotide.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 11, 2022
From: SETHI, DHRUV KAM
To: OBSIDIAN THERAPEUTICS, INC.
Reel/Frame 060787/0146 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 9, 2022
From: ELPEK, KUTLU GOKSU; SETHI, DHRUV KAM; LANGLEY, MEGHAN C.; EZELL, TUCKER READ; SUN, DEXUE; GORI, JENNIFER LEAH; MYLVAGANAM, GEETHA HANNA; OLS, MICHELLE; FLEURY, MICHELLE; RICHARDSON, CELESTE; STORER, JAMES A.; SURI, VIPIN; SUBRAMANIAN, SHYAMSUNDAR; FOLEY, COLLEEN; PERKINS, MOLLY REED; TCHAICHA, JEREMY HATEM; HELLER, SCOTT FRANCIS
To: OBSIDIAN THERAPEUTICS, INC.
Reel/Frame 059355/0384 →
Continuity (2)
Provisional Application
62898520
· Sep 10, 2019
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