Therapeutic agents

Patent metadata

Field	Value
Publication number	US-10865231-B2
Application number	US-202016877035-A
Country	US
Kind code	B2
Filing date	May 18, 2020
Priority date	Jul 31, 2015
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

First claim

The invention claimed is:

1. A combination of a first nucleic acid encoding a second generation chimeric antigen receptor (CAR) and a second nucleic acid encoding a chimeric costimulatory receptor, wherein:
(i) the second generation CAR comprises:
(a) a signalling region;
(b) a co-stimulatory signalling region;
(c) a transmembrane domain; and
(d) a binding element that specifically interacts with a first epitope on a target antigen; and

(ii) the chimeric costimulatory receptor comprises:
(e) a co-stimulatory signalling region which is different to that of (b);
(f) a transmembrane domain; and
(g) a binding element that specifically interacts with a second epitope on a target antigen.

2. The combination of claim 1 , wherein the first and second nucleic acids are included within a single polynucleotide.

3. The combination of claim 1 , wherein the signalling region (a) comprises the intracellular domain of human CD3ζ [zeta] chain or a variant thereof.

4. The combination of claim 1 , wherein the co-stimulatory signalling regions (b) and (e) are chosen from CD28, CD27, ICOS, 4-1BB, OX40, CD30, GITR, HVEM, DR3, and CD40.

5. The combination of claim 4 , wherein one of (b) or (e) is CD28 and the other of (b) or (e) is 4-1BB or OX40.

6. The combination of claim 5 , wherein (b) is CD28.

7. The combination of claim 5 , wherein (e) is 4-1BB or CD28.

8. The combination of claim 1 , wherein the transmembrane domains (c) and (f) independently are CD8α or CD28 transmembrane domains.

9. The combination of claim 1 , wherein the first and second epitopes are associated with the same antigen.

10. The combination of claim 1 , which further encodes a chimeric cytokine receptor.

11. The combination of claim 10 , wherein the chimeric cytokine receptor is 4αβ.

12. The combination of claim 1 , wherein at least one of the binding elements (d) or (g) is a ligand for an ErbB dimer, a receptor for colony stimulating factor-1 (CSF-1R), or an α v β 6 integrin-specific binding agent.

13. The combination of claim 1 , wherein the binding element (d) comprises CSF-1 and the binding element (g) comprises IL-34.

14. The combination of claim 1 , wherein the binding element (d) is an α v β 6 integrin-specific binding agent which is a peptide comprising the sequence motif

(SEQ ID NO 7)

RGDLX 5 X 6 L

or

(SEQ ID NO 8)

RGDLX 5 X 6 I,

wherein LX 5 X 6 L or LX 5 X 6 I is contained within an alpha helical structure, X 5 and X 6 are helix promoting residues; and the binding element (g) is a T1E peptide.

15. The combination of claim 1 wherein the binding element (b) has a binding affinity that is lower than that of the binding element (g).

Assignees

• King S College London

Inventors

• Maher John
• Achkova Daniela Yordanova
• Whilding Lynsey May
• Draper Benjamin Owen

Classifications

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K40/4234

  Interleukins [IL] · CPC title

• A61K40/4216

  Receptors for colony stimulating factors [CSF] · CPC title

• A61K40/4215

  Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30 · CPC title

• A61K40/4205

  Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4 · CPC title