# US 11,305,011 B2 · Kappa myeloma antigen chimeric antigen receptors and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,305,011 B2
- Document ID: US11305011B2
- Status: Granted
- Kind: B2
- Application number: 15/568,271
- Filed: 2016-04-25
- Published: 2018-08-16
- Granted: 2022-04-19
- Earliest claimed: 2015-04-23
- Assignees: HaemaLogix Pty Ltd
- Applicants: HaemaLogix Pty. LTD.
- Inventors: Kenneth Micklethwaite; Rosanne Dunn; David Gottlieb; Grant Logan
- Web page: https://patentgrep.com/patent/US11305011B2

## CPC

- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 38/204: {IL-6}
- 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 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/5412: {IL-6}
- C07K 14/5434: {IL-12}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70521: {CD28, CD152}
- C07K 16/2887: {against CD20}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/30: from tumour cells
- C12N 5/0636: {T lymphocytes}
- 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 2239/46: characterised by the cancer treated
- C07K 2317/526: CH3 domain
- C07K 2317/53: Hinge
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/035: containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins
- C12N 2510/00: Genetically modified cells
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides compositions and methods for treating KMA-expressing malignancies including chimeric antigen receptors (CARs) and T cells containing CARs (CAR T-cells). The invention also provides methods and compositions comprising CAR T-cells co-expressing other anti-tumoral agents including cytokines and antibodies.

## Claims

### Claim 1

A chimeric antigen receptor (CAR) comprising one or more intracellular signaling domains and an extracellular antigen binding domain, wherein the extracellular antigen binding domain comprises a single chain variable fragment (scFv) that specifically binds kappa myeloma antigen (KMA) and does not bind immunoglobulin (Ig) kappa light chain associated with an Ig heavy chain, wherein the scFv comprises the VL chain and VH chain from KappaMab, wherein the VL chain comprises the VL chain of SEQ ID NO: 2 and the VH chain comprises the VH chain of SEQ ID NO: 1.

### Claim 2

A chimeric antigen receptor (CAR) comprising one or more intracellular signaling domains and an extracellular antigen binding domain, wherein the extracellular antigen binding domain specifically recognizes kappa myeloma antigen (KMA), wherein the extracellular binding domain comprises a single chain variable fragment (scFv) that specifically recognizes KMA, wherein the scFv comprises the VL chain and VH chain from KappaMab wherein the VL chain comprises the VL chain of SEQ ID NO: 2 and the VH chain comprises the VH chain of SEQ ID NO: 1.

### Claim 3 (depends on 2)

The CAR of claim 2, wherein the one or more intracellular signaling domains comprises one or more co-stimulatory endodomains.

### Claim 4 (depends on 3)

The CAR of claim 3, wherein the one or more co-stimulatory endodomains is one or more of a CD28 domain, a CD3ζ domain, a 4-1BB domain or OX-40 domain or combinations thereof.

### Claim 5 (depends on 2)

The CAR of claim 2, wherein the VL chain and VH chain from KappaMab are attached via a glycine-serine linker.

### Claim 6 (depends on 5)

The CAR of claim 5, wherein the glycine-serine linker is a 15-20 amino acid linker, wherein the glycine-serine linker comprises (Gly4Ser)3 (SEQ ID NO: 23).

### Claim 7 (depends on 2)

The CAR of claim 2, wherein the scFv is attached to the one or more intracellular signaling domains via a spacer.

### Claim 8 (depends on 7)

The CAR of claim 7, wherein the spacer is an immunoglobulin constant region or a CD8α chain.

### Claim 9 (depends on 8)

The CAR of claim 8, wherein the immunoglobulin constant region comprises one or more of an IgG hinge domain, an IgG CH2 domain and an IgG CH3 domain.

### Claim 10 (depends on 8)

The CAR of claim 8, wherein the spacer is attached to the scFV via a glycine-serine linker.

### Claim 11 (depends on 10)

The CAR of claim 10, wherein the glycine-serine linker is a 15-20 amino acid linker, wherein the glycine-serine linker comprises (Gly4Ser)3 (SEQ ID NO: 23).

### Claim 12 (depends on 2)

A genetically modified T cell engineered to express the CAR of claim 2.

### Claim 13 (depends on 12)

The genetically modified T cell of claim 12, further engineered to express one or more additional biological molecules, and, optionally, a selectable marker.

### Claim 14 (depends on 13)

The genetically modified T cell of claim 13, wherein the one or more additional biological molecules comprises one or more of an HGF Binding protein, IL-12, GAL3C or SANT7.

### Claim 15 (depends on 13)

The genetically modified T cell of claim 13, wherein the one or more additional biological molecules is IL-12 and the IL-12 is expressed by a single chain polypeptide comprising one IL-12 p35 subunit and one IL-12 p40 subunit joined by a flexible linker.

### Claim 16

A method for producing a genetically modified T cell comprising introducing into a T cell an expression vector encoding a CAR comprising one or more intracellular signaling domains and an extracellular antigen binding domain, wherein the extracellular antigen binding domain specifically recognizes kappa myeloma antigen (KMA), wherein the extracellular binding domain comprises a single chain variable fragment (scFv) that specifically recognizes KMA, wherein the scFv comprises the VL chain and VH chain from KappaMab wherein the VL chain comprises the VL chain of SEQ ID NO: 2 and the VH chain comprises the VH chain of SEQ ID NO: 1.

### Claim 17

A method of treating a KMA-expressing malignancy in a subject in need thereof comprising administering genetically modified T cells engineered to express one or more intracellular signaling domains and an extracellular antigen binding domain, wherein the extracellular antigen binding domain specifically recognizes kappa myeloma antigen (KMA), wherein the extracellular binding domain comprises a single chain variable fragment (scFv) that specifically recognizes KMA, wherein the scFv comprises the VL chain and VH chain from KappaMab wherein the VL chain comprises the VL chain of SEQ ID NO: 2 and the VH chain comprises the VH chain of SEQ ID NO: 1.

### Claim 18 (depends on 14)

The genetically modified T cell of claim 14, wherein the HGF binding protein is an HGF antibody or fragment thereof.