# US 11,440,958 B2 · Blockade of CD7 expression and chimeric antigen receptors for immunotherapy of T-cell malignancies

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,440,958 B2
- Document ID: US11440958B2
- Status: Granted
- Kind: B2
- Application number: 15/821,153
- Filed: 2017-11-22
- Published: 2018-06-28
- Granted: 2022-09-13
- Earliest claimed: 2016-11-22
- Assignees: National University of Singapore
- Applicants: National University of Singapore
- Inventors: Yi Tian Png; Natasha Vinanica; Takahiro Kamiya; Dario Campana
- Web page: https://patentgrep.com/patent/US11440958B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/421: {Immunoglobulin superfamily}
- A61K 40/4211: {CD19 or B4}
- A61P 35/02: specific for leukemia
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/3061: {Blood cells}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/804: {Blood cells [leukemia, lymphoma]}
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/04: containing an ER retention signal such as a C-terminal HDEL motif
- C07K 2319/05: containing a GOLGI retention signal
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in cancer therapy.

## Claims

### Claim 1

An engineered immune cell comprising
i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said first single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, and wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive; and
ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the engineered immune cell.

### Claim 2

An engineered immune cell comprising
i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said a first single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive; and
ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the engineered immune cell.

### Claim 3

An engineered immune cell comprising
i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said first single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, and wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive; and
ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:14 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:15, wherein the second scFv expressed on the surface of the engineered immune cell.

### Claim 4

An engineered immune cell comprising:
i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said a first single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence of SEQ ID NO:8, wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive; and
ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the immune cell surface.