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Publication Number
US-9353156-B2
Publication Date
2016-05-31
Expiration Date
Abstract
The present invention relates to novel agents, pharmaceutical compositions containing them, and their use in therapy, particularly anti-microbial and anti-cancer therapy. In particular, the present invention relates to novel peptide-based compounds based on SEQ ID NO: 40 which have surprisingly been shown to have inhibitory effects on the growth and/or viability of cells, particularly bacterial and cancer cells. Also provided are therapeutic and non-therapeutic methods which include the use of peptides of the invention.
Core Innovation
The invention relates to oligopeptidic compounds for treating a bacterial infection and/or treating a neoplastic condition by administering to a subject in need thereof an oligopeptidic compound comprising the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40) or an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40. The described compounds have activity in inhibiting the growth and/or viability of bacterial cells and/or neoplastic cells.
The neoplastic condition is selected from brain cancer, breast cancer, melanoma, neuroblastoma, sarcoma, colon cancer, prostate cancer and a neoplastic condition of the skin. The disclosed scope is supported by described peptide-based antimicrobial and anti-cancer (anti-tumor) agents centered on oligopeptidic sequences, including variants/reverses, and optionally constructs with cell-penetrating peptides (HIV-TAT/CPPs).
The described compositions and methods further correspond to activity relating to membrane disruption/lysis and apoptosis, along with preferred cationic physicochemical properties including net charge, isoelectric point, and hydrophilicity. The disclosed examples include in vitro/in vivo efficacy such as cancer cell line cytotoxicity, tumor growth inhibition in a mouse model with improved survival, and bacteriocidal activity against gram+ and gram- bacteria.
Claims Coverage
The patent includes three independent claims that cover treatment of bacterial infection and/or neoplastic conditions in a subject using a defined oligopeptidic compound, and in vitro or ex vivo contacting methods to inhibit viability and/or growth of bacterial cells or selected neoplastic condition cells. The inventive scope is centered on the sequence requirement of SEQ ID NO: 40 or a sequence with at least 95% sequence identity, together with activity in inhibiting growth and/or viability for the relevant cells.
Treating bacterial infection or neoplastic condition with SEQ ID NO: 40 sequence oligopeptidic compound
Administering to a subject an oligopeptidic compound comprising the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40) or an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40, wherein the compound has activity in inhibiting the growth and/or viability of bacterial cells and/or neoplastic cells, and wherein the neoplastic condition is selected from brain cancer, breast cancer, melanoma, neuroblastoma, sarcoma, colon cancer, prostate cancer and a neoplastic condition of the skin.
In vitro or ex vivo inhibiting bacterial viability and/or growth by contacting with SEQ ID NO: 40 sequence oligopeptidic compound
An in vitro or ex vivo method comprising contacting a bacterial cell with an oligopeptidic compound comprising the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40) or an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40, wherein the compound has activity in inhibiting the growth and/or viability of the bacterial cell.
In vitro or ex vivo inhibiting viability and/or growth of selected neoplastic condition cells by contacting with SEQ ID NO: 40 sequence oligopeptidic compound
An in vitro or ex vivo method for inhibiting the viability and/or growth of cells of a neoplastic condition selected from the group consisting of brain cancer cells, breast cancer cells, melanoma cells, neuroblastoma cells, sarcoma cells, colon cancer cells, prostate cancer cells, and non-malignant skin tumor cells, comprising contacting the cells with an oligopeptidic compound comprising the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40) or an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40, wherein the compound has activity in inhibiting the growth and/or viability of the cells of the neoplastic condition.
Overall, the independent claims consistently require the oligopeptidic compound to be defined by SEQ ID NO: 40 or a sequence with at least 95% identity, and require that the compound has activity that inhibits growth and/or viability for either bacterial cells or specified neoplastic condition cells, implemented either as subject treatment or as in vitro/ex vivo contacting methods.
Stated Advantages
Inhibits the growth and/or viability of bacterial cells and/or neoplastic cells.
Treats bacterial infection and/or treats a neoplastic condition.
Provides in vitro or ex vivo methods for inhibiting viability and/or growth of bacterial cells.
Provides in vitro or ex vivo methods for inhibiting viability and/or growth of selected neoplastic condition cells.
Documented Applications
Treating a bacterial infection in a subject by administering an oligopeptidic compound comprising SEQ ID NO: 40 or a sequence having at least 95% sequence identity to SEQ ID NO: 40.
Treating a neoplastic condition in a subject selected from brain cancer, breast cancer, melanoma, neuroblastoma, sarcoma, colon cancer, prostate cancer, and a neoplastic condition of the skin.
In vitro or ex vivo inhibition of the viability and/or growth of a bacterial cell by contacting the bacterial cell with the defined oligopeptidic compound.
In vitro or ex vivo inhibition of the viability and/or growth of cells of selected neoplastic conditions (brain, breast, melanoma, neuroblastoma, sarcoma, colon, prostate, and non-malignant skin tumor cells) by contacting the cells with the defined oligopeptidic compound.
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