# US 12,215,162 B2 · BAFF-R targeted chimeric antigen receptor-modified T-cells and uses thereof

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- Number: US 12,215,162 B2
- Document ID: US12215162B2
- Status: Granted
- Kind: B2
- Application number: 17/466,968
- Filed: 2021-09-03
- Published: 2022-01-13
- Granted: 2025-02-04
- Earliest claimed: 2016-06-06
- Assignees: City of Hope; Board of Regents, The University of Texas System
- Applicants: City of Hope; Board of Regents, the University of Texas System
- Inventors: Hong Qin; Larry W. Kwak
- Web page: https://patentgrep.com/patent/US12215162B2

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4211: {CD19 or B4}
- A61K 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61P 7/06: Antianaemics
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70514: {CD4}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/3061: {Blood cells}
- C12N 5/0636: {T lymphocytes}
- C12N 5/163: {one of the fusion partners being a B or a T lymphocyte}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/77: Internalization into the cell
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided herein are T cells expressing a chimeric antigen receptor (CAR) targeted to B cell activating factor receptor (BAFF-R). The CAR targeted to BAFF-R (BAFF-R CAR) described herein includes a domain that binds BAFF-R. Methods of making and using the BAFF-R CAR are also provided.

## Claims

### Claim 1

A nucleic acid molecule encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises an scFv targeted to BAFF-R, wherein the scFv includes a light chain variable region and a heavy chain variable region, wherein the light chain variable region includes CDR L1 (SEQ ID NO:1), CDR L2 (SEQ ID NO:2) and CDR L3 (SEQ ID NO: 3); and the heavy chain variable region includes CDR H1 (SEQ ID NO:4), CDR H2 (SEQ ID NO:5), and CDR H3 (SEQ ID NO:6); a CD4 transmembrane domain or variant thereof having 1-5 amino acid modifications; a costimulatory domain comprising a 4-1BB costimulatory domain or a variant thereof having 1-5 amino acid modifications; and CD3ζ signaling domain or a variant thereof having 1-5 amino acid modifications.

### Claim 2 (depends on 1)

The nucleic acid molecule of claim 1, wherein the scFv includes a spacer between the heavy chain variable region and the light chain variable region.

### Claim 3 (depends on 1)

The nucleic acid molecule of claim 1, comprising a spacer region located between the scFv and the transmembrane region.

### Claim 4 (depends on 1)

The nucleic acid molecule of claim 1, wherein the 4-1BB signaling domain comprises an amino acid sequence of SEQ ID NO:41.

### Claim 5 (depends on 1)

The nucleic acid molecule of claim 1, wherein the CD3ζ signaling domain comprises an amino acid sequence of SEQ ID NO:42.

### Claim 6 (depends on 1)

The nucleic acid molecule of claim 1 wherein a linker of 3 to 15 amino acids is located between the co-stimulatory domain and the CD3ζ signaling domain or variant thereof.

### Claim 7 (depends on 1)

The nucleic acid molecule of claim 1, wherein the scFv includes a heavy chain variable region having an amino acid sequence selected from SEQ ID NOs: 16, 24, 26, and 28.

### Claim 8 (depends on 1)

The nucleic acid molecule of claim 1, wherein the scFv includes a light chain variable region having an amino acid sequence selected from SEQ ID NOs: 14, 18, 20, and 22.

### Claim 9 (depends on 1)

A population of human T cells transduced by a vector comprising an expression cassette comprising the nucleic acid molecule of claim 1.

### Claim 10 (depends on 9)

A method of treating cancer in a subject in need thereof comprising administering to a subject a therapeutically effective amount of a composition comprising the population of human T cells of claim 9.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cancer is lymphoma, leukemia or myeloma.

### Claim 12 (depends on 11)

The method of claim 11, wherein the lymphoma is mantle cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma or Burkitt's lymphoma.

### Claim 13 (depends on 11)

The method of claim 11, wherein the leukemia is lymphoblastic leukemia, chronic lymphocytic leukemia or hairy cell leukemia.

### Claim 14 (depends on 11)

The method of claim 11, wherein the myeloma is multiple myeloma.

### Claim 15 (depends on 10)

The method of claim 10, wherein the method further comprises administering to said subject a second therapeutic agent.

### Claim 16 (depends on 10)

The method of claim 10, wherein the population of T cells are autologous or allogeneic to the subject.

### Claim 17 (depends on 10)

The method of claim 10, wherein the population of human T cells comprises CD4+ TN cells and CD8+ TN cells.