Granted Patent
B2
US 12,344,651 · App. 18/617,912 · Granted Jul 1, 2025
CD19 and CD22 chimeric antigen receptors and uses thereof
Assignee:
Novartis AG
C07K14/70503A61K40/11A61K40/31A61K40/4211A61K40/4212C12N5/0636A61K2239/29A61K2239/31A61K2239/38A61K2239/48
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Abstract
The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.
Claims (42)
1. A method of making a cell comprising transducing an immune effector cell with a vector comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR) molecule, wherein said CAR molecule comprises:
(a) a first CAR comprising a first antigen binding domain which binds to CD22; a first transmembrane domain; a first co-stimulatory signaling domain; and/or a first primary signaling domain; and
(b) a second CAR comprising a second antigen binding domain which binds to CD19; a second transmembrane domain; a second co-stimulatory domain; and/or a second primary signaling domain,
wherein the first CAR and the second CAR each comprise an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3; and
wherein the CAR molecule comprising the first CAR and the second CAR comprises the amino acid sequence of SEQ ID NO: 12 or 16, or an amino acid having at least 95%, 96%, 97%, 98%, or 99% identity thereto.
2. The method of claim 1 , wherein:
(a) the first CAR comprises:
a first antigen binding domain which binds to CD22, a first transmembrane domain, and a first co-stimulatory signaling domain;
a first antigen binding domain which binds to CD22, a first transmembrane domain; and a first primary signaling domain; or
a first antigen binding domain which binds to CD22, a first transmembrane domain, a first co-stimulatory signaling domain, and a first primary signaling domain; and
(b) wherein the second CAR comprises:
a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second co-stimulatory signaling domain;
a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second primary signaling domain; or
a second antigen binding domain which binds to CD19; a second transmembrane domain; a second co-stimulatory signaling domain; and a second primary signaling domain.
3. The method of claim 1 , wherein:
(i) a nucleotide sequence that encodes the first transmembrane domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second transmembrane domain and is comprised in the nucleic acid molecule;
(ii) a nucleotide sequence that encodes the first co-stimulatory signaling domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second co-stimulatory signaling domain and is comprised in the nucleic acid molecule; and/or
(iii) a nucleotide sequence that encodes the primary signaling domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second primary signaling domain and is comprised in the nucleic acid molecule.
4. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encoding the first CAR is disposed on a first vector and the nucleotide sequence encoding the second CAR is disposed on a second vector.
5. The method of claim 1 , wherein the immune effector cell is a T cell or an NK cell.
6. The method of claim 1 , wherein the vector is chosen from a DNA, a RNA, a plasmid, a lentivirus vector, adenoviral vector, or a retrovirus vector.
7. The method of claim 1 , wherein the immune effector cell was previously isolated from a frozen or fresh leukapheresis product.
8. A method of making a cell comprising introducing a nucleic acid molecule encoding a CAR molecule, into an immune effector cell, wherein said CAR molecule comprises:
(a) a first CAR comprising a first antigen binding domain which binds to CD22; a first transmembrane domain; a first co-stimulatory signaling domain; and/or a first primary signaling domain; and
(b) a second CAR comprising a second antigen binding domain which binds to CD19; a second transmembrane domain; a second co-stimulatory domain; and/or a second primary signaling domain,
wherein the first CAR and the second CAR each comprise an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3; and
wherein the CAR molecule comprising the first CAR and the second CAR comprises the amino acid sequence of SEQ ID NO: 12 or 16, or an amino acid having at least 95%, 96%, 97%, 98%, or 99% identity thereto.
9. The method of claim 8 , wherein:
(a) the first CAR comprises:
a first antigen binding domain which binds to CD22, a first transmembrane domain, and a first co-stimulatory signaling domain;
a first antigen binding domain which binds to CD22, a first transmembrane domain; and a first primary signaling domain; or
a first antigen binding domain which binds to CD22, a first transmembrane domain, a first co-stimulatory signaling domain, and a first primary signaling domain; and
(b) wherein the second CAR comprises:
a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second co-stimulatory signaling domain;
a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second primary signaling domain; or
a second antigen binding domain which binds to CD19; a second transmembrane domain; a second co-stimulatory signaling domain; and a second primary signaling domain.
10. The method of claim 8 , wherein:
(i) a nucleotide sequence that encodes the first transmembrane domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second transmembrane domain and is comprised in the nucleic acid molecule;
(ii) a nucleotide sequence that encodes the first co-stimulatory signaling domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second co-stimulatory signaling domain and is comprised in the nucleic acid molecule; and/or
(iii) a nucleotide sequence that encodes the primary signaling domain and is comprised in the nucleic acid molecule is different from a nucleotide sequence that encodes the second primary signaling domain and is comprised in the nucleic acid molecule.
11. The method of claim 8 , wherein the immune effector cell is a T cell or an NK cell.
12. The method of claim 8 , wherein the immune effector cell was previously isolated from a frozen or fresh leukapheresis product.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 3, 2024
From: ENGELS, BORIS; GUIMARAES, CARLA
To: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
Reel/Frame 067309/0514 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 3, 2024
From: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
To: NOVARTIS AG
Reel/Frame 067309/0612 →
Continuity (3)
Provisional Application
62940600
· Nov 26, 2019
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