# US 2019/0167803 A1 · Tlr9 targeted cytotoxic agents

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- Number: US 2019/0167803 A1
- Document ID: US20190167803A1
- Status: Published application
- Kind: A1
- Application number: 16/266,461
- Filed: 2019-02-04
- Published: 2019-06-06
- Earliest claimed: 2014-10-31
- Applicants: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- Inventors: Alan F. List; Sheng Wei
- Web page: https://patentgrep.com/patent/US20190167803A1

## CPC

- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 51/06: Macromolecular compounds {, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules (peptides, proteins, polyamino acids A61K51/08; antibodies A61K51/10)}
- A61K 51/065: {conjugates with carriers being macromolecules}
- A61P 35/00: Antineoplastic agents
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/3519: Fusion with another nucleic acid
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target cytotoxic agents to TLR9-expressing malignant cells are disclosed.

## Claims

### Claim 1

A molecule comprising a toll like receptor-9 (TLR9) targeting ligand conjugated to a cytotoxic agent, wherein the cytotoxic agent is not a polynucleotide.

### Claim 2 (depends on 1)

The molecule of claim 1, wherein the molecule is defined by the formula:
TTL-CA,
wherein “TTL” represents the TLR9 targeting ligand,
wherein “CA” represents the cytotoxic agent, and
wherein “-” represents a bivalent linker.

### Claim 3 (depends on 1)

The molecule of claim 1, wherein the cytotoxic agent comprises a lytic peptide.

### Claim 4 (depends on 1)

The molecule of claim 1, wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide, or an analogue or derivative thereof that binds TLR9.

### Claim 5 (depends on 3)

The molecule of claim 3, wherein the lytic peptide comprises the amino acid sequence PNPNNNPNPN (SEQ ID NO:48), wherein “P” is any polar amino acid, and wherein “N” is any non-polar amino acid.

### Claim 6 (depends on 5)

The molecule of claim 5, wherein the lytic peptide comprises the amino acid sequence KIKMVISWKG (SEQ ID NO:1).

### Claim 7

(canceled)

### Claim 8

(canceled)

### Claim 9 (depends on 1)

A pharmaceutical composition comprising the molecule of claim 1 in a pharmaceutically acceptable carrier.

### Claim 10 (depends on 9)

A method for treating a TLR9-positive cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 9.

### Claim 11 (depends on 10)

The method of claim 10, wherein the TLR9-positive cancer comprises a meylodysplastic syndrome (MDS).

### Claim 12 (depends on 11)

The method of claim 11, wherein the TLR9-positive cancer comprises non-del(5q) MDS.

### Claim 13 (depends on 10)

The method of claim 10, further comprising assaying a biopsy sample from the subject for TLR9 expression prior to treatment.