Therapeutic agents

Patent metadata

Field	Value
Publication number	US-11802143-B2
Application number	US-202017118045-A
Country	US
Kind code	B2
Filing date	Dec 10, 2020
Priority date	Jul 31, 2015
Publication date	Oct 31, 2023
Grant date	Oct 31, 2023

Abstract

An immunoresponsive cell, such as a T-cell expressing
(i) a second generation chimeric antigen receptor comprising:
(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) a chimeric costimulatory receptor comprising
(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.

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 and a second nucleic acid encoding a chimeric costimulatory receptor, wherein:
(i) the second generation chimeric antigen receptor comprises:
(a) a signalling region, wherein the signalling region comprises the intracellular domain of human CD3ζ chain or a variant thereof;
(b) a co-stimulatory signalling region, wherein the co-stimulatory signalling region is the co-stimulatory region of CD28;
(c) a transmembrane domain, wherein the transmembrane domain is a CD28 transmembrane domain; and
(d) a binding element that specifically interacts with a first epitope on a target antigen, wherein the binding element is T1E or a scFv; and

(ii) the chimeric costimulatory receptor comprises
(e) a co-stimulatory signalling region, wherein the costimulatory signalling region is the costimulatory signalling region of 4-1BB;
(f) a transmembrane domain, wherein the transmembrane domain is a CD8α transmembrane domain; and
(g) a binding element that specifically interacts with a second epitope on a target antigen, wherein the binding element is T1E or a scFv.

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 binding element (d) is a scFv.

4. The combination of claim 1 , wherein the binding element (d) is T1E.

5. The combination of claim 1 , wherein the binding element (g) is a scFv.

6. The combination of claim 1 , wherein the binding element (g) is T1E.

7. The combination of claim 3 , wherein the binding element (g) is a scFv.

8. The combination of claim 3 , wherein the binding element (g) is T1E.

9. The combination of claim 4 , wherein the binding element (g) is a scFv.

10. The combination of claim 4 , wherein the binding element (g) is T1E.

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

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

13. The combination of claim 12 , wherein the chimeric cytokine receptor is 4αβ.

14. The combination of claim 3 , which further encodes a chimeric cytokine receptor.

15. The combination of claim 14 , wherein the chimeric cytokine receptor is 4αβ.

16. The combination of claim 4 , which further encodes a chimeric cytokine receptor.

17. The combination of claim 16 , wherein the chimeric cytokine receptor is 4αβ.

18. The combination of claim 1 , wherein binding affinity of binding element (d) is lower than that of binding element (g).

19. A vector comprising the combination of claim 1 .

20. A vector comprising the single polynucleotide of claim 2 .

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