US 2026/0098075 A1 · CHIMERIC ANTIGEN RECEPTOR SPACERS

Abstract

The present disclosure related to chimeric antigen receptors (CARs) comprising immunoglobulin (Ig) derived spacers, e.g., hinge or loop regions, fragments thereof, or combinations thereof. Ig derived spacer confers improved properties to the CARs, e.g., increased cytokine release with respect the CARs with spacers not derived from hinge regions and fragments thereof, loop regions from constant domains and fragments thereof, and combinations thereof. Also provided are cells expressing CARs comprising Ig derived spacers regions and methods to use the CARs to treat diseases or disorders, e.g., cancer. Some of the disclosed Ig derived spacers are fragments from, e.g., IgAQ1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM. In some aspects, the disclosed Ig derived spacers are derived from non-human immunoglobulins, e.g., mouse immunoglobulins such IgG2A. Other Ig derived spacer disclosed are modular constructs comprising several concatenated Ig hinges or fragments thereof.

Claims21

Dependent claims

1-154. (canceled)

A polynucleotide comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) comprising

(i) an antigen-binding domain that binds to an epitope on a tumor antigen expressed on a target cell;
(ii) a transmembrane domain;
(iii) an intracellular domain;
and,
(iv) a CAR spacer located between the antigen-binding domain and the transmembrane domain comprising an amino acid sequence derived from a human immunoglobulin hinge and/or constant region or a functional fragment thereof,
wherein
(a) the CAR spacer is between about 150 amino acids and about 125 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is less than about 10 Å;
(b) the CAR spacer is between about 125 amino acids and about 100 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is less than about 10 Å;
(c) the CAR spacer is between about 100 amino acids and about 75 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is less than about 10 Å;
(d) the CAR spacer is between about 75 amino acids and about 36 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is less than about 15 Å;
(e) the CAR spacer is between about 35 amino acids and about 21 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is between about 15 Å and about 25 Å;
(f) the CAR spacer is between about 20 amino acids and about 16 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is between about 25 Å and about 35 Å;
(g) the CAR spacer is between about 15 amino acids and about 11 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is between about 35 Å and about 45 Å;
or,
(h) the CAR spacer is between about 10 amino acids and about 5 amino acids in length;
and, the distance between the epitope and the surface of the target cell membrane is more than about 45 Å.

20 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/322,325Filed 8 Sep 2025

Priority

12 May 2020

Published

9 Apr 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex
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]
A61K 40/4205
Receptors for growth factors: her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4

Chimeric antigen receptor spacers

Life of this patent

Chimeric antigen receptor spacers

Life of this patent

Abstract

Claims21