US 12,214,037 B2Granted

Treatment of cancer using humanized anti-BCMA chimeric antigen receptor

AssigneesNovartis AG, The Trustees of the University of Pennsylvania

InventorsJennifer Brogdon, Eugene Choi, Hilmar Erhard Ebersbach, David Jonathan Glass, Heather Huet, Carl H. June, Joan Mannick, Michael C. Milone, Leon Murphy, Gabriela Plesa, Celeste Richardson, Marco Ruella, Reshma Singh, Yongqiang Wang, Qilong Wu

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Abstract

The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.

Claims16

Dependent claims

A method of providing an anti-tumor immunity in a mammal comprising administering to the mammal an effective amount of a cell comprising an isolated nucleic acid molecule encoding a chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an anti-B-cell maturation antigen (BCMA) binding domain, a transmembrane domain, and an intracellular signaling domain, and wherein said anti-BCMA binding domain comprises:

(i) a heavy chain complementarity determining region 1 (HC CDR1) comprising the amino acid sequence of SEQ ID NO:
394, a heavy chain complementarity determining region 2 (HC CDR2) comprising the amino acid sequence of SEQ ID NO:
434, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the amino acid sequence of SEQ ID NO:
474, a light chain complementarity determining region 1 (LC CDR1) comprising the amino acid sequence of SEQ ID NO:
514, a light chain complementarity determining region 2 (LC CDR2) comprising the amino acid sequence of SEQ ID NO:
554, and a light chain complementarity determining region 3 (LC CDR3) comprising the amino acid sequence of SEQ ID NO:
594;
(ii) a HC CDR1 comprising the amino acid sequence of SEQ ID NO:
634, a HC CDR2 comprising the amino acid sequence of SEQ ID NO:
674, a HC CDR3 comprising the amino acid sequence of SEQ ID NO:
714, a LC CDR1 comprising the amino acid sequence of SEQ ID NO:
754, a LC CDR2 comprising the amino acid sequence of SEQ ID NO:
794, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO:
834;
or
(iii) a HC CDR1 comprising the amino acid sequence of SEQ ID NO:
874, a HC CDR2 comprising the amino acid sequence of SEQ ID NO:
914, a HC CDR3 comprising the amino acid sequence of SEQ ID NO:
954, a LC CDR1 comprising the amino acid sequence of SEQ ID NO:
994, a LC CDR2 comprising the amino acid sequence of SEQ ID NO:
1034, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO:
1074;
and
wherein the encoded intracellular signaling domain comprises the amino acid sequence of SEQ ID NO:
7 and the amino acid sequence of SEQ ID NO:
9 or SEQ ID NO:
10.

24 more elements

A method of treating a mammal having a disease associated with expression of B-cell maturation antigen (BCMA), comprising administering to the mammal an effective amount of a cell comprising an isolated nucleic acid molecule encoding a chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an anti-BCMA binding domain, a transmembrane domain, and an intracellular signaling domain, and wherein said anti-BCMA binding domain comprises:

(i) a heavy chain complementarity determining region 1 (HC CDR1) comprising the amino acid sequence of SEQ ID NO:
394, a heavy chain complementarity determining region 2 (HC CDR2) comprising the amino acid sequence of SEQ ID NO:
434, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the amino acid sequence of SEQ ID NO:
474;
a light chain complementarity determining region 1 (LC CDR1) comprising the amino acid sequence of SEQ ID NO:
514, a light chain complementarity determining region 2 (LC CDR2) comprising the amino acid sequence of SEQ ID NO:
554, and a light chain complementarity determining region 3 (LC CDR3) comprising the amino acid sequence of SEQ ID NO:
594;
(ii) a HC CDR1 comprising the amino acid sequence of SEQ ID NO:
634, a HC CDR2 comprising the amino acid sequence of SEQ ID NO:
674, a HC CDR3 comprising the amino acid sequence of SEQ ID NO:
714, a LC CDR1 comprising the amino acid sequence of SEQ ID NO:
754, a LC CDR2 comprising the amino acid sequence of SEQ ID NO:
794, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO:
834;
or
(iii) a HC CDR1 comprising the amino acid sequence of SEQ ID NO:
874, a HC CDR2 comprising the amino acid sequence of SEQ ID NO:
914, a HC CDR3 comprising the amino acid sequence of SEQ ID NO:
954, a LC CDR1 comprising the amino acid sequence of SEQ ID NO:
994, a LC CDR2 comprising the amino acid sequence of SEQ ID NO:
1034, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO:
1074;
and
wherein the encoded intracellular signaling domain comprises the amino acid sequence of SEQ ID NO:
7 and the amino acid sequence of SEQ ID NO:
9 or SEQ ID NO:
10.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/359,211Filed 25 Jun 2021 · division
Priority: WO PCT/CN2014/08258621 Jul 2014
Published: US 2022/0064316 A13 Mar 2022
Granted: 4 Feb 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification33 codes

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 39/39558
Against materials from animals: against tumor tissues, cells, antigens
A61P 35/02
Antineoplastic agents: specific for leukemia
C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex

Family

Application14/805,193Parent of this division · filed 21 Jul 2015
Application16/197,565Parent of this division · filed 21 Nov 2018
US 10,174,095 B2Parent of this division · filed 8 Jan 2019
US 2022/0064316 A1Pre-grant publication · published 3 Mar 2022
US 11,084,880 B2Parent of this division
US 2016/0046724 A1Published application
US 2019/0153061 A1Published application
US 12,214,037 B2This patent

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

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