Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12239720-B2
Publication Date
2025-03-04
Expiration Date
Abstract
The present invention relates to a method of necrosing, causing membranolysis, or causing poration of selective cancer cells. In some aspects, the method includes administering a peptide including PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG (SEQ ID NO:48) or ETFSDLWKLLKKWKMRRNQFWVKVQRG (SEQ ID NO:49) to a selective cancer cell to cause necrosis, membranolysis, or poration of said selective cancer cell.
Core Innovation
The invention provides a composition for treating cancer in a subject, where the composition comprises a human double minute binding domain (HDM-2) targeting component and a membrane resident component (MRC). The HDM-2 targeting component is attached to the MRC, and the composition comprises a peptide of one of two specified sequences (SEQ ID NO:48 or SEQ ID NO:49). The approach is used to induce necrosis, membranolysis, or poration of cancer cells.
A key aspect of the invention is monitoring selectivity using serum biomarker measurements performed pre-treatment and post-treatment. The method measures the amount or level of a serum biomarker, administers the composition to a subject or to a plurality of cells, and then re-measures the serum biomarker after administration. An increase in the amount of the serum biomarker from pre-treatment to post-treatment is indicative of necrosis, membranolysis, or poration of the cancer.
The invention further specifies selectivity by requiring that the necrosis, membranolysis, or poration does not affect normal cells while affecting cancer cells. The cancer is acute myeloid leukemia (AML), and the serum biomarker is cytokeratin. The HDM-2 targeting component is a peptide selected from PPLSQETFSDLWKLL (SEQ ID NO:1) or ETFSDLWKLL (SEQ ID NO:2), and the MRC is the peptide KKWKMRRNQFWVKVQRG (SEQ ID NO:25).
Claims Coverage
The partial content includes four independent claims (clm-00001 through clm-00004). Across these claims, the inventive features combine an HDM-2 targeting component attached to a membrane resident component with serum biomarker pre- and post-treatment measurement to indicate necrosis, membranolysis, or poration, with selectivity toward acute myeloid leukemia (AML) cells and cytokeratin as the serum biomarker.
HDM-2 targeting and membrane resident attachment for AML treatment
Administering to the subject a therapeutically effective amount of a composition comprising a human double minute binding domain (HDM-2) targeting component and a membrane resident component (MRC), wherein the HDM-2 targeting component is attached to the MRC and the composition comprises a peptide of (SEQ ID NO:48) PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG or (SEQ ID NO:49) ETFSDLWKLLKKWKMRRNQFWVKVQRG.
Cytokeratin pre-/post-measurement indicating necrosis, membranolysis, or poration
Measuring the amount of a serum biomarker pre-treatment and measuring the amount of the serum biomarker post-treatment, wherein an increase in the amount of the serum biomarker from pre-treatment to post-treatment is indicative of necrosis, membranolysis, or poration of said cancer, and wherein the serum biomarker is cytokeratin.
HDM-2 peptide selection and MRC peptide definition for selective AML cell effects
Wherein the HDM-2 targeting component is a peptide selected from the group consisting of PPLSQETFSDLWKLL (SEQ ID NO:1) and ETFSDLWKLL (SEQ ID NO:2), and wherein the MRC is the peptide KKWKMRRNQFWVKVQRG (SEQ ID NO:25).
Selective necrosis or membranolysis in a cell mixture using serum biomarker response
Providing a plurality of cells in a serum comprising at least one cancer cell and at least one normal cell, measuring the amount of a serum biomarker, administering to the plurality of cells a composition comprising an HDM-2 targeting component and an MRC, and measuring the amount of the serum biomarker after administering the composition, wherein necrosis or membranolysis of the at least one cancer cell results without affecting the at least one normal cell and an increase in the serum biomarker indicates necrosis or membranolysis of the cancer cells, wherein the at least one cancer cell is an acute myeloid leukemia (AML) cell and the serum biomarker is cytokeratin.
Necrosis or poration indicated by at least a twofold cytokeratin increase
Providing a plurality of cells in a serum comprising at least one cancer cell and at least one normal cell, measuring a level of a serum biomarker, administering a composition comprising an HDM-2 targeting component and a membrane resident component, and measuring the level of the serum biomarker after administering the composition, wherein an increase in the amount of the serum biomarker from pre-treatment to post-treatment of at least two times is indicative of necrosis or poration of said cancer cells, and wherein the serum biomarker is cytokeratin.
AML serum method using a specified peptide sequence variant and cytokeratin monitoring
Measuring a level of a serum biomarker, administering to a plurality of cells a peptide having a sequence of (SEQ ID NO:48) PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG or (SEQ ID NO:49) ETFSDLWKLLKKWKMRRNQFWVKVQRG, and measuring the level of the serum biomarker after administering the peptide, wherein the plurality of cells include at least one normal cell and one AML cell and an increase in the amount of the serum biomarker from pre-treatment to post-treatment is indicative of necrosis, membranolysis, or poration of said AML cell, wherein the serum biomarker is cytokeratin.
Across the independent claims, coverage centers on compositions that include an HDM-2 targeting peptide attached to a membrane resident component to form specified peptide sequence variants (SEQ ID NO:48 or SEQ ID NO:49), combined with pre-treatment and post-treatment serum cytokeratin measurement as an indicator of necrosis, membranolysis, or poration. The claims further require selectivity toward AML cells without affecting normal cells, with one claim requiring at least a twofold cytokeratin increase for poration or necrosis indication.
Stated Advantages
Selectively induces necrosis, membranolysis, or poration of cancer cells while not affecting normal cells.
Uses an increase in serum cytokeratin from pre-treatment to post-treatment as an indicator of necrosis, membranolysis, or poration.
Provides selectivity readouts in mixed cell serum by measuring serum biomarker levels pre- and post-treatment.
Documented Applications
Treating acute myeloid leukemia (AML) in a subject by administering a therapeutically effective composition and assessing serum cytokeratin changes indicative of necrosis, membranolysis, or poration.
Necrosing or causing membranolysis of selective cancer cells in a serum mixture containing at least one cancer cell and at least one normal cell, with AML cells as the at least one cancer cell and cytokeratin as the serum biomarker.
Necrosing or causing poration of selective cancer cells in a serum mixture, with necrosis or poration indicated by an increase in serum cytokeratin of at least two times, and AML cells as the at least one cancer cell.
Necrosing, causing poration, or causing membranolysis of acute myeloid leukemia (AML) cells in serum using administration of a peptide (SEQ ID NO:48 or SEQ ID NO:49) and measuring serum cytokeratin changes.
Interested in licensing this patent?