IP Library › Granted Patent US 12673985
Granted Patent B2
US 12673985 · App. 17/429,093 · Granted Jul 7, 2026

Method for the treatment or prophylaxis of cancer by targeting the extracellular portion of keratin 14 (KRT14) residing on cancer cells

Inventors: Andrew Nicholas Stephens (Knoxfield, AU); Maree Bilandzic (Endeavour Hills, AU)
Assignee: Hudson Institute of Medical Research
C07K16/18A61K33/243A61K39/0011A61K39/3955A61K39/39558A61K45/06A61K47/6843A61P35/00C07K14/4741G01N33/57545G01N33/57575G01N33/57585A61K2039/505C07K2317/33C07K2317/34C07K2317/565C07K2317/567C07K2317/76C07K2319/40C07K2319/60C07K2319/61G01N2333/4742
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12673985
App. No.
17/429,093
Granted
Jul 7, 2026
Kind
B2
Abstract

Disclosed herein are methods, uses and compositions for the treatment or prophylaxis of cancer in a mammalian subject comprising administering to the subject an amount of an agent which targets an extracellular portion of KRT14 or its functional homolog or variant thereof resident on cancer cells or an agent which induces production of an antagonist of the extracellular portion of KRT14 or its functional homolog or variant on cancer cells. The present disclosure also extends to methods of monitoring and/or diagnosing cancer in a subject.

Claims (44)

1 . A method for the treatment of a keratin-14 (KRT14)-positive cancer in a mammalian subject, said method comprising administering to said subject an amount of an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,

wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8; and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, the amount effective to prevent or reduce cancer cell invasion, migration and/or metastasis, thereby treating the KRT14-positive cancer in the subject.

2 . The method of claim 1 wherein the cancer is a gynecological cancer.

3 . The method of claim 2 wherein the gynecological cancer is ovarian cancer or a stage or form of ovarian cancer.

4 . The method of claim 1 wherein the antibody or antigen-binding fragment thereof is conjugated to a cytotoxic molecule.

5 . The method of claim 1 , wherein the VH comprises:

(a) a VH framework region 1 (FR1) comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 12;

(b) a VH FR2 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 13;

(c) a VH FR3 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 14; and

(d) a VH FR4 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 15;

and the VL comprises:

(e) a VL FR1 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 16;

(f) a VL FR2 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 17;

(g) a VL FR3 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 18; and

(h) a VL FR4 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 19.

6 . The method of claim 5 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO:3, and

(b) the VL comprises the amino acid sequence of SEQ ID NO:5.

7 . The method of claim 1 , further comprising administering to the subject, simultaneously or sequentially, an additional anti-cancer agent and/or exposing the subject to immunotherapy, radiation therapy, and/or surgical intervention.

8 . The method of claim 7 , wherein the additional anti-cancer agent is selected from the group consisting of dactinomycin, daunorubicin, doxorubicin (adriamycin), idarubicin and mitoxantrone, a platinum based agent, an antimetabolite, primed T-cells, and a cytokine.

9 . The method of claim 8 , wherein the antimetabolite is selected from the group consisting of azaserine, D-cycloserine, nycophenolic acid, trimethoprim, 5-fluorouracil, capecitabine, methotrexate, gemcitabine, cytarabine (ara-C) and fludarabine.

10 . A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,

wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8; and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, and

wherein said antibody or antigen-binding fragment thereof directly induces cytotoxicity or cytostasis of the cancer cells.

11 . A diagnostic reagent comprising an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,

wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8; and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, and

wherein the antibody or antigen-binding fragment thereof is conjugated to a reporter molecule.

12 . A method for detecting circulating KRT14-positive cancer cells in a patient, the method comprising:

(a) providing a blood sample from the patient;

(b) contacting the blood sample with an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells, wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8; and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11 to determine the presence of KRT14 positive cancer cells in the sample.

13 . An antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells, wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8; and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11.

14 . The antibody or antigen-binding fragment thereof of claim 13 , wherein the VH comprises:

(a) a VH framework region 1 (FR1) comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 12;

(b) a VH FR2 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 13;

(c) a VH FR3 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 14; and

(d) a VH FR4 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 15;

and the VL comprises:

(e) a VL FR1 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 16;

(f) a VL FR2 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 17;

(g) a VL FR3 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 18; and

(h) a VL FR4 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 19.

15 . The antibody or antigen-binding fragment thereof of claim 14 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO:3, and

(b) the VL comprises the amino acid sequence of SEQ ID NO:5.