# US 11,111,303 B2 · Compositions and methods for activation of NK cells killing of prostate cancer and breast cancer cells

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- Number: US 11,111,303 B2
- Document ID: US11111303B2
- Status: Granted
- Kind: B2
- Application number: 16/125,091
- Filed: 2018-09-07
- Published: 2019-03-07
- Granted: 2021-09-07
- Earliest claimed: 2017-09-07
- Assignees: University of North Texas Health Science Center
- Applicants: University of North Texas Health Science Center
- Inventors: Purunelloor A. Mathew; Stephen O. Mathew
- Web page: https://patentgrep.com/patent/US11111303B2

## CPC

- C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 47/6809: {Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 51/1027: {against receptors, cell-surface antigens or cell-surface determinants}
- A61P 35/00: Antineoplastic agents
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/572: {cytotoxic response}
- C07K 2317/20: characterized by taxonomic origin
- C07K 2317/21: from primates, e.g. man
- 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 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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

Certain embodiments are directed to methods of treating LLT1 expressing cancer by administering to a subject having an LLT1 expressing cancer an LLT1 inhibitor.

## Claims

### Claim 1

A method for treating breast cancer or prostate cancer in a patient in need of such treatment, comprising administering to the patient an antibody or antibody fragment that binds LLT1, the antibody or antibody fragment comprising heavy chain complementarity-determining regions (CDRs) having an amino acid sequence of SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13, and light chain CDRs having an amino acid sequences of SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17, wherein the antibody or antibody fragment binds to cancer cells and inhibits cancer growth or progression.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody has a heavy chain variable region having an amino acid sequence of SEQ ID NO:10.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment thereof is humanized.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment thereof is chimeric.

### Claim 5 (depends on 1)

The method of claim 1, wherein said antibody or antibody fragment thereof is an antibody fragment, and the antibody fragment is an ScFv.

### Claim 6 (depends on 5)

The method of claim 5, wherein the ScFv is murine or humanized.

### Claim 7 (depends on 6)

The method of claim 6, wherein the antibody further comprises a heterologous moiety.

### Claim 8 (depends on 7)

The method of claim 7, wherein the heterologous moiety is a therapeutic moiety.

### Claim 9 (depends on 8)

The method of claim 8, wherein the therapeutic moiety is a cytotoxic moiety.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cytotoxic moiety is a cytotoxic agent or radiotoxic agent.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cytotoxic moiety is selected from taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, fludarabin, 5-fluorouracil decarbazine, mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, cis-dichlorodiamine platinum (II) (DDP), daunorubicin, doxorubicin, vincristine, or vinblastine.

### Claim 12 (depends on 1)

The method of claim 1, wherein the patient is a human.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment thereof is administered parenterally, intraperitoneally, intravenously, subcutaneously, orally, nasally, via inhalation or rectally.

### Claim 14 (depends on 1)

The method of claim 1, wherein the antibody or antibody fragment thereof is administered intravenously at a dosage of from 5 mg/m2 to 2000 mg/m2.

### Claim 15

An anti-LLT1 antibody comprising heavy chain CDRs having an amino acid sequence of SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13, and light chain CDRs having an amino acid sequence of SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17, wherein the antibody binds to cancer cells and inhibits cancer growth or progression.

### Claim 16 (depends on 15)

The antibody of claim 15, wherein the antibody is a human antibody.

### Claim 17 (depends on 15)

The antibody of claim 15, wherein the antibody has a heavy chain variable region having an amino acid sequence of SEQ ID NO:10.

### Claim 18 (depends on 15)

The antibody of claim 15, further comprising a heterologous moiety.

### Claim 19 (depends on 18)

The antibody of claim 18, wherein the heterologous moiety is a therapeutic moiety.

### Claim 20 (depends on 19)

The antibody of claim 19, wherein the therapeutic moiety is a cytotoxic moiety.

### Claim 21 (depends on 20)

The antibody of claim 20, wherein the cytotoxic moiety is a cytotoxic agent or radiotoxic agent.

### Claim 22 (depends on 20)

The antibody of claim 20, wherein the cytotoxic moiety is selected from taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, fludarabin, 5-fluorouracil decarbazine, mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, cis-dichlorodiamine platinum (II) (DDP), daunorubicin, doxorubicin, vincristine, or vinblastine.