Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate
Inventors
JIKOH, Takahiro • OGITANI, Yusuke • YOSHIHARA, Kazutaka • ENDO, Seiko • FUJISAKI, Yoshihiko
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12698342-B2
Publication Date
2026-08-04
Expiration Date
Abstract
As treatment effective for HER2-expressing cancer having resistance or refractoriness to an existing anti-HER2 drug, there are provided a therapeutic agent and a treatment method using an antibody-drug conjugate in which a linker and a drug represented by the formula: -(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFG (SEQ ID NO: 5) —NH—CH2—O—CH2—C(═O)—(NH-DX) are conjugated to an anti-HER2 antibody.
Core Innovation
The invention relates to a method for treating HER2-expressing cancer having resistance to an existing anti-HER2 drug by administering an antibody-drug conjugate to a human patient in need. The antibody-drug conjugate includes a linker and a drug represented by a specified formula that are conjugated to an anti-HER2 antibody, and the conjugate is connected at position 3 of the anti-HER2 antibody via a thioether bond. The drug-linker structure includes a GGFG tetrapeptide residue (SEQ ID NO: 5).
The anti-HER2 antibody comprises either a heavy chain consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of amino acid residues 1 to 214 of SEQ ID NO: 2, or a heavy chain represented by SEQ ID NO: 1 and a light chain represented by SEQ ID NO: 2. The method includes administering a dose per administration of 5.4 mg/kg to 6.4 mg/kg of the antibody-drug conjugate. The regimen includes administration once every 3 weeks, and the treated cancer is limited to a defined set of cancer types.
The disclosed content also characterizes the antibody-drug conjugate by an average number of drug-linker structure units conjugated per antibody molecule, where n is 7 to 8. The patent frames the problem of resistance in HER2-expressing cancers to existing anti-HER2 drugs and states that the treatment is intended for cancers with secondary resistance.
Claims Coverage
The consolidated claim coverage centers on methods for treating HER2-expressing cancer resistant to an existing anti-HER2 drug using a specified anti-HER2 antibody-drug conjugate at a dose per administration of 5.4 mg/kg to 6.4 mg/kg. The inventive features repeatedly presented across the inputs are the defined linker-drug structure, the thioether bond attachment at position 3, the specified anti-HER2 antibody sequences, and the regimen and valency limitations in one claim set.
Dose range for HER2-expressing resistant cancer treatment
Administering a dose per administration of 5.4 mg/kg to 6.4 mg/kg of an antibody-drug conjugate to a human patient with HER2-expressing cancer having resistance to an existing anti-HER2 drug.
Specified linker-drug conjugate with GGFG (SEQ ID NO: 5) and thioether attachment
Using an antibody-drug conjugate in which a linker and a drug represented by a specified formula are conjugated to an anti-HER2 antibody, including a GGFG (SEQ ID NO: 5) tetrapeptide residue and a thioether bond connection to the anti-HER2 antibody at position 3.
Anti-HER2 antibody heavy/light chain sequences
Defining the anti-HER2 antibody such that it comprises either a heavy chain of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain of amino acid residues 1 to 214 of SEQ ID NO: 2, or a heavy chain represented by SEQ ID NO: 1 and a light chain represented by SEQ ID NO: 2.
Average drug-linker units per antibody molecule and regimen once every 3 weeks
Wherein the average number of units of the drug-linker structure conjugated per antibody molecule is 7 to 8, and wherein the antibody-drug conjugate is administered once every 3 weeks.
Cancer type limited to a defined group
Treating cancer at least one selected from the group consisting of breast cancer, gastric cancer, colorectal cancer, esophageal cancer, salivary gland cancer, pancreatic cancer, ovarian cancer, uterine cancer, lung cancer, and sarcoma.
The consolidated coverage is directed to treating HER2-expressing cancer resistant to an existing anti-HER2 drug with an anti-HER2 antibody-drug conjugate defined by the stated linker-drug structure, GGFG residue, thioether attachment at position 3, and specified anti-HER2 antibody sequences, at a dose per administration of 5.4 mg/kg to 6.4 mg/kg. One claim set further specifies n = 7 to 8, once-every-3-weeks administration, and limitation to the listed cancer types.
Stated Advantages
Excellent antitumor activity.
Favorable safety.
Excellent antitumor effect, including high activity on secondary resistant cancer, with favorable safety.
Documented Applications
Treatment of HER2-expressing cancer having resistance to an existing anti-HER2 drug in a human patient, including breast cancer, gastric cancer, colorectal cancer, esophageal cancer, salivary gland cancer, pancreatic cancer, ovarian cancer, uterine cancer, lung cancer, and sarcoma.
Treatment is directed to patients whose cancer has resistance to an existing anti-HER2 drug, including trastuzumab emtansine, trastuzumab, pertuzumab, or lapatinib.
Treatment of HER2-expressing cancer having resistance to an existing anti-HER2 drug in a human patient, including secondary resistance and resistance associated with T-DM1 or other anti-HER2 antibody exposure.
Interested in licensing this patent?