US 12,037,407 B2Granted

Immune cells having co-expressed shRNAS and logic gate systems

AssigneeArsenal Biosciences, Inc.

InventorsJasper Williams, Michelle Nguyen, Anzhi Yao, Stephen Santoro, Aaron Cooper, John Gagnon, Adam Litterman, Omar Khan, Natalie Bezman, Katherine Harris, Harbani Kaur Malik Chaudhry, Nicole Allen

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Abstract

Provided herein are recombinant nucleic acids encoding chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX. Also provided are systems of chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX, cells expressing such proteins and shRNA, and methods of use thereof.

Claims71

Dependent claims

One or more recombinant nucleic acid molecule(s), wherein the one or more recombinant nucleic acid molecules(s) encode:

a. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds to Alkaline Phosphatase, Germ Cell (ALPG/P), wherein the first extracellular antigen-binding domain comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
1,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
2,
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
3,
iv. CDR-L1 comprises the sequence set forth in SEQ ID NO:
4,
v. CDR-L2 comprises the sequence set forth in SEQ ID NO:
5, and
vi. CDR-L3 comprises the sequence set forth in SEQ ID NO:
6;
and
b. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to mesothelin (MSLN), wherein the second extracellular antigen-binding domain comprises a VHH comprising a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
14,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
15, and
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
16.

18 more elements

A polypeptide system comprising

a. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds to Alkaline Phosphatase, Germ Cell (ALPG/P), wherein the first extracellular antigen-binding domain comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
1,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
2,
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
3,
iv. CDR-L1 comprises the sequence set forth in SEQ ID NO:
4,
v. CDR-L2 comprises the sequence set forth in SEQ ID NO:
5, and
vi. CDR-L3 comprises the sequence set forth in SEQ ID NO:
6;
and
b. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to mesothelin (MSLN), wherein the second extracellular antigen-binding domain comprises a VHH comprising a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
14,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
15, and
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
16.

18 more elements

A primary human T cell comprising one or more recombinant nucleic acid molecule(s), wherein the one or more recombinant nucleic acid molecule(s) encode:

a. a first chimeric polypeptide comprising a priming receptor comprising a first extracellular antigen-binding domain that specifically binds to Alkaline Phosphatase, Germ Cell (ALPG/P), wherein the first extracellular antigen-binding domain comprises a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
1,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
2,
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
3,
iv. CDR-L1 comprises the sequence set forth in SEQ ID NO:
4,
v. CDR-L2 comprises the sequence set forth in SEQ ID NO:
5, and
vi. CDR-L3 comprises the sequence set forth in SEQ ID NO:
6;
and
b. a second chimeric polypeptide comprising a chimeric antigen receptor (CAR) comprising a second extracellular antigen-binding domain that specifically binds to mesothelin (MSLN), wherein the second extracellular antigen-binding domain comprises a VHH comprising a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, wherein:
i. CDR-H1 comprises the sequence set forth in SEQ ID NO:
14,
ii. CDR-H2 comprises the sequence set forth in SEQ ID NO:
15, and
iii. CDR-H3 comprises the sequence set forth in SEQ ID NO:
16.

18 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/311,856Filed 3 May 2023 · continuation
Priority: 14 Oct 2021
Published: US 2023/0340139 A126 Oct 2023
Granted: 16 Jul 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification31 codes

A61K 48/005
Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy:…
C07K 16/2878
Against receptors, cell surface antigens or cell surface determinants: against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/31
Characterised by the recombinant expression of specific molecules in the cells of the immune system: chimeric antigen receptors [CAR]

Family

Application63/255,889Us provisional application · filed 14 Oct 2021
Application63/255,887Us provisional application · filed 14 Oct 2021
Application63/255,891Us provisional application · filed 14 Oct 2021
Application63/303,422Us provisional application · filed 26 Jan 2022
PCT/US2022/078158Parent of this continuation · filed 14 Oct 2022
US 2023/0340139 A1Pre-grant publication · published 26 Oct 2023
US 12,037,407 B2This patent

From the US filing history. Foreign family members aren’t listed.