# US 12,595,303 B2 · Antibodies and chimeric antigen receptors that target TACI

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- Number: US 12,595,303 B2
- Document ID: US12595303B2
- Status: Granted
- Kind: B2
- Application number: 17/616,274
- Filed: 2020-06-04
- Published: 2022-10-13
- Granted: 2026-04-07
- Earliest claimed: 2019-06-04
- Assignees: The General Hospital Corporation
- Applicants: The General Hospital Corporation
- Inventors: Marcela V. Maus; Rebecca Larson
- Web page: https://patentgrep.com/patent/US12595303B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- 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 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/804: {Blood cells [leukemia, lymphoma]}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/46: characterised by the cancer treated
- 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 2317/31: multispecific
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- 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

## Abstract

The invention provides antibodies, antibody-drug conjugates, bispecific T cell engagers (BiTEs), and chimeric antigen receptors (CARs) that target transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Such antibodies, antibody-drug conjugates, BiTEs, and CARs can be used, e.g., in methods for treating a cancer (e.g., multiple myeloma), an autoimmune disorder (e.g., characterized by a high titer of antibodies contributing to the disorder), or a plasma cell disease disorder (e.g., plasma cell dyscrasias) in a subject in need thereof.

## Claims

### Claim 1

An antibody that specifically binds to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), wherein the antibody comprises:
(i) a heavy chain complementarity-determining region 1 (CDR-H1), a heavy chain complementarity-determining region 2 (CDR-H2), and a heavy chain complementarity-determining region 3 (CDR-H3) of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 1; and
(ii) a light chain complementarity-determining region 1 (CDR-L1), a light chain complementarity-determining region 2 (CDR-L2), and a light chain complementarity-determining region 3 (CDR-L3) of a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 2.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the antibody comprises:
(i) a CDR-H1 as set forth in SEQ ID NO: 26, a CDR-H2 as set forth in SEQ ID NO: 27, and a CDR-H3 as set forth in SEQ ID NO: 28; a CDR-L1 as set forth in SEQ ID NO: 29, a CDR-L2 as set forth in SEQ ID NO: 30, and a CDR-L3 as set forth in SEQ ID NO: 31;
(ii) a CDR-H1 as set forth in SEQ ID NO: 32, a CDR-H2 as set forth in SEQ ID NO: 33, and a CDR-H3 as set forth in SEQ ID NO: 34; a CDR-L1 as set forth in SEQ ID NO: 35, a CDR-L2 as set forth in SEQ ID NO: 36, and a CDR-L3 as set forth in SEQ ID NO: 31; or
(iii) a CDR-H1 as set forth in SEQ ID NO: 37, a CDR-H2 as set forth in SEQ ID NO: 38, and a CDR-H3 as set forth in SEQ ID NO: 39; a CDR-L1 as set forth in SEQ ID NO: 40, a CDR-L2 as set forth in SEQ ID NO: 30, and a CDR-L3 as set forth in SEQ ID NO: 41.

### Claim 3 (depends on 1)

A composition comprising the antibody of claim 1.

### Claim 4 (depends on 1)

A polynucleotide encoding the antibody of claim 1.

### Claim 5 (depends on 4)

A vector comprising the polynucleotide of claim 4.

### Claim 6 (depends on 5)

A host cell comprising the vector of claim 5.

### Claim 7 (depends on 6)

A method of producing an antibody that specifically binds TACI, the method comprising culturing the host cell claim 6 in a culture medium.

### Claim 8 (depends on 1)

An antibody-drug conjugate comprising the antibody of claim 1.

### Claim 9 (depends on 1)

A chimeric antigen receptor (CAR) polypeptide comprising an extracellular target binding domain comprising the antibody of claim 1 or an antigen binding fragment thereof.

### Claim 10 (depends on 9)

The CAR polypeptide of claim 9 comprising an amino acid sequence of any one of SEQ ID NOs: 12, 13, or 18-25.