# US 2019/0315879 A1 · Adapter chimeric antigen receptor expressing cells for targeting of multiple antigens

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- Number: US 2019/0315879 A1
- Document ID: US20190315879A1
- Status: Published application
- Kind: A1
- Application number: 16/343,162
- Filed: 2017-10-27
- Published: 2019-10-17
- Earliest claimed: 2016-10-29
- Applicants: Miltenyi Biotec GmbH
- Inventors: Andrew Kaiser; Joerg Mittelstaet; Volker Huppert; Stefan Miltenyi; Patrick Schlegel; Christian Seitz; Peter Lang; Rupert Handgretinger
- Web page: https://patentgrep.com/patent/US20190315879A1

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 31/4188: condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/18: against material from animals or humans
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- 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)

## Abstract

The present invention provides an extracellular anti-linker/label epitope chimeric antigen receptor (anti-LLE CAR) comprising I) a linker/label epitope (LLE) binding domain, II) a transmembrane domain, and III) a signal transduction domain, wherein said extracellular LLE binding domain binds a target cell binding molecule (TCBM) comprising i) an antigen binding moiety (ABM), wherein said ABM binds specifically to an antigen expressed on a target cell, ii) a label moiety (LaM), wherein said LaM is a naturally occurring molecule in a subject or a derivative thereof, iii) a linker moiety (LiM) conjugating said ABM and said LaM, thereby forming a linker/label epitope (LLE), wherein said extracellular LLE binding domain binds said LLE with a higher preference than said naturally occurring molecule.

## Claims

### Claim 1

An extracellular anti-linker/label epitope chimeric antigen receptor (anti-LLE CAR) comprising
I) a linker/label epitope (LLE) binding domain,
II) a transmembrane domain, and
III) a signal transduction domain,
wherein said extracellular LLE binding domain binds a target cell binding molecule (TCBM) comprising
i) an antigen binding moiety (ABM), wherein said ABM binds specifically to an antigen expressed on a target cell,
ii) a label moiety (LaM), wherein said LaM is a naturally occurring molecule in a subject or a derivative thereof,
iii) a linker moiety (LiM) conjugating said ABM and said LaM, thereby forming a linker/label epitope (LLE),
wherein said extracellular LLE binding domain binds said LLE with a higher preference than said naturally occurring molecule.

### Claim 2 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said extracellular LLE binding domain binds with an at least twofold higher affinity to said LLE than to said naturally occurring molecule.

### Claim 3 (depends on 1)

The anti-LLE CAR according to claim 1, wherein the k(off) value for the binding between said extracellular LLE binding domain is higher to a monomeric LLE and said naturally occurring molecule than to a multimeric LLE.

### Claim 4 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said naturally occurring molecule is in the circulatory system of said subject.

### Claim 5 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said LLE is generated site-specifically, thereby forming an epitope comprising a part of said LaM and a part of said LiM.

### Claim 6 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said LaM is selected from the group consisting of amino acids, peptides, proteins, creatinine, biotin, biocytin, lipids, hormones, vitamins, carbohydrates or a derivative thereof.

### Claim 7 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said LiM is a molecule capable of generating said LLE.

### Claim 8 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said LiM is selected from the group consisting of peptides, proteins, nucleic acids, carbohydrates, polyhydroxyalkanoates, alkyl chains, alkanoic acids, carboxylic acids, famesyls, polyethylene glycols, lipids or a derivative thereof.

### Claim 9 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said LaM is biotin or a derivative thereof and said LiM is a 6-(6-aminohexanamido) hexanoyl moiety or a 6-aminohexanoyl moiety.

### Claim 10 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said extracellular LLE binding domain comprises the sequence of SEQ ID NO: 1 and SEQ ID NO:2.

### Claim 11 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said antigen that is bound by said ABM is expressed on the surface of a cancer cell.

### Claim 12 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said antigen is selected from the group consisting of CD33 (Siglec-3), CD123 (IL3RA), CD135 (FLT-3), CD44 (HCAM), CD44V6, CD47, CD184 (CXCR4), CLEC12A (CLLI), LeY, FRβ, MICA/B, CD305 (LAIR-i), CD366 (TIM-3), CD96 (TACTILE), CD133, CD56, CD29 (ITGB1), CD44 (HCAM), CD47 (IAP), CD66 (CEA), CD112 (Nectin2), CD117 (c-Kit), CD133, CD146 (MCAM), CD155 (PVR), CD171 (L1CAM), CD221 (IGF1), CD227 (MUC1), CD243 (MRD1), CD246 (ALK), CD271 (LNGFR), CD19, CD20, GD2, and EGFR.

### Claim 13 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said ABM is an antibody or an antigen-binding fragment thereof.

### Claim 14 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said anti-LLE CAR comprises the sequence of SEQ ID NO: 11, and wherein said extracellular LLE binding domain binds to a 6-[6-(biotinamido)hexanamido] hexanoyl moiety.

### Claim 15 (depends on 1)

The anti-LLE CAR according to claim 1, wherein said anti-LLE CAR is expressed in a T cell, NK cell, NKT cell, gamma/delta T cell, Treg cell, or stem cell.