US 2025/0018040 A1Published application

Anti-mesothelin polypeptides, proteins, and chimeric antigen receptors

AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Servic

InventorsIra H. Pastan, Masanori Onda, Mitchell Ho, Xiu-fen Liu, Tapan Bera, Anirban Chakraborty

Life of this patent

Estimating the term…

Abstract

Polypeptides, proteins, and chimeric antigen receptors (CARs) that specifically bind to human mesothelin582-598 (IP-NGYLVLDLSMQEALS) (SEQ ID NO: 1) are disclosed. Anti-mesothelin binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the poly peptides, proteins, and CARS are disclosed. Methods of reducing mesothelin shed from cell membranes, methods of detecting the presence of cancer, and methods of treating or preventing cancer are also disclosed.

Claims47

Dependent claims

A polypeptide which specifically binds to human mesothelin582-598 (IPNGYLVLDLSMQEALS) (SEQ ID NO:

1) and which comprises:
(A) the light chain complementary determining region (VL CDR) 1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
the VL CDR3 amino acid sequence of SEQ ID NO:
21;
the heavy chain complementary determining region (VH CDR) 1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and
the VH CDR3 amino acid sequence of SEQ ID NO:
28;
(B) the VL CDR1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
the VL CDR3 amino acid sequence of SEQ ID NO:
21;
the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and
the VH CDR3 amino acid sequence of SEQ ID NO:
35;
(C) the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
the VL CDR3 amino acid sequence of SEQ ID NO:
42;
the VH CDR1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and
the VH CDR3 amino acid sequence of SEQ ID NO:
28;
or (D) the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
the VL CDR3 amino acid sequence of SEQ ID NO:
42;
the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and
the VH CDR3 amino acid sequence of SEQ ID NO:
35.

50 more elements

A protein which specifically binds to human mesothelin582-598 (IPNGYLVLDLSMQEALS) (SEQ ID NO:

1) and which comprises:
(A) a first polypeptide chain comprising the light chain complementary determining region (VL CDR) 1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
and the VL CDR3 amino acid sequence of SEQ ID NO:
21;
and
a second polypeptide chain comprising the heavy chain complementary determining region (VH CDR) 1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and the VH CDR3 amino acid sequence of SEQ ID NO:
28;
(B) a first polypeptide chain comprising the VL CDR1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
and the VL CDR3 amino acid sequence of SEQ ID NO:
21;
and
a second polypeptide chain comprising the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and the VH CDR3 amino acid sequence of SEQ ID NO:
35;
(C) a first polypeptide chain comprising the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
and the VL CDR3 amino acid sequence of SEQ ID NO:
42;
and
a second polypeptide chain comprising the VH CDR1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and the VH CDR3 amino acid sequence of SEQ ID NO:
28;
or
(D) a first polypeptide chain comprising the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
and the VL CDR3 amino acid sequence of SEQ ID NO:
42;
and
a second polypeptide chain comprising the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and the VH CDR3 amino acid sequence of SEQ ID NO:
35.

51 more elements

A chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane (TM) domain, and an intracellular T cell signaling domain, wherein the antigen binding domain has antigen specificity for human mesothelin582-598 (IPNGYLVLDLSMQEALS) (SEQ ID NO:

1), and wherein the antigen binding domain comprises:
(A) the light chain complementary determining region (VL CDR) 1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
the VL CDR3 amino acid sequence of SEQ ID NO:
21;
the heavy chain complementary determining region (VH CDR) 1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and the VH CDR3 amino acid sequence of SEQ ID NO:
28;
(B) the VL CDR1 amino acid sequence of SEQ ID NO:
17;
the VL CDR2 amino acid sequence of SEQ ID NO:
19;
the VL CDR3 amino acid sequence of SEQ ID NO:
21;
the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and the VH CDR3 amino acid sequence of SEQ ID NO:
35;
(C) the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
the VL CDR3 amino acid sequence of SEQ ID NO:
42;
the VH CDR1 amino acid sequence of SEQ ID NO:
24;
the VH CDR2 amino acid sequence of SEQ ID NO:
26;
and the VH CDR3 amino acid sequence of SEQ ID NO:
28;
(D) the VL CDR1 amino acid sequence of SEQ ID NO:
38;
the VL CDR2 amino acid sequence of SEQ ID NO:
40;
the VL CDR3 amino acid sequence of SEQ ID NO:
42;
the VH CDR1 amino acid sequence of SEQ ID NO:
31;
the VH CDR2 amino acid sequence of SEQ ID NO:
33;
and the VH CDR3 amino acid sequence of SEQ ID NO:
35;
or
(E) the VL CDR1 amino acid sequence of SEQ ID NO:
3;
the VL CDR2 amino acid sequence of SEQ ID NO:
5;
the VL CDR3 amino acid sequence of SEQ ID NO:
7;
the VH CDR1 amino acid sequence of SEQ ID NO:
10;
the VH CDR2 amino acid sequence of SEQ ID NO:
12;
and the VH CDR3 amino acid sequence of SEQ ID NO:
14.

59 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/710,726Filed 16 Dec 2022
Priority: 17 Dec 2021
Published: 16 Jan 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 40/4255
Adhesion molecules, e.g. NRCAM, EpCAM or cadherins: mesothelin [MSLN]
C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
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]

Family

Application63/290,761Us provisional application · filed 17 Dec 2021
US 2025/0018040 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

18/710,726Filed 16 Dec 2022

Priority

17 Dec 2021

Published

16 Jan 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 40/4255
Adhesion molecules, e.g. NRCAM, EpCAM or cadherins: mesothelin [MSLN]
C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
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]