US 2023/0055644 A1 · T-CELL MODULATORY CHIMERIC MOLECULES AND METHODS OF USE THEREOF

Abstract

The present disclosure provides a chimeric molecule comprising: a) a T-cell modulatory multimeric polypeptide (TMMP); and b) a nucleic acid component, where the nucleic acid component comprises a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising an antibody that binds a cancer-associated antigen. The TMMP binds to and activates a target T cell; the nucleic acid component is taken up by the target T cell such that the target T cell expresses the CAR on its surface. The present disclosure provides methods of making the chimeric molecule. The present disclosure provides treatment methods comprising administering the chimeric molecule.

Claims21

Dependent claims

-70. (canceled)

A chimeric molecule comprising:

A) a T-cell modulatory multimeric polypeptide (TMMP) comprising at least one heterodimer comprising:
a) a first polypeptide comprising
i) a peptide epitope, and
ii) a β2-microglobulin polypeptide;
b) a second polypeptide comprising an MHC class I heavy chain polypeptide;
c) at least one immunomodulatory polypeptide, wherein the first and/or the second polypeptide comprises the at least one immunomodulatory polypeptide;
and, optionally,
d) an immunoglobulin (Ig) Fc polypeptide or a non-Ig scaffold, wherein the first and/or the second polypeptide comprises the Ig Fc polypeptide or the non-Ig scaffold,
wherein one or more independently selected linkers may be interposed between one or more of the components of the first and second polypeptides,
and
(B) a nucleic acid component covalently attached to the TMMP, wherein the nucleic acid component comprises one or more nucleic acids comprising nucleotide sequences encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen-binding domain specific for a cancer-associated antigen.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/678,748Filed 23 Feb 2022

Priority

23 Oct 2019

Published

23 Feb 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification23 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 40/32
Characterised by the recombinant expression of specific molecules in the cells of the immune system: t-cell receptors [TCR]

T-cell modulatory chimeric molecules and methods of use thereof

Life of this patent

T-cell modulatory chimeric molecules and methods of use thereof

Life of this patent

Abstract

Claims21