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Last Updated: March 29, 2024

Claims for Patent: 9,238,682


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Summary for Patent: 9,238,682
Title:Anti-cancer therapeutic strategy to overcome cancer resistance and to enable tailoring treatment to patients
Abstract: A gene construct comprising a programmed-cell-death executioner gene having a nuclear localization signal, a deleted signal peptide, an inhibitor-resistant binding site, a promoter, and an activator. A method of making a gene construct, by modifying a programmed-cell-death executioner gene by adding a nuclear localization signal, deleting a signal peptide, mutating a binding site for an inhibitor to make it inhibitor-resistant, adding a promoter for exclusive expression in selected cells, and adding an activator. A method of eliminating undesired cells from a patient. A method of treating cancer. An array comprising at least two gene constructs wherein all of the gene constructs differ with respect to the programmed-cell-death executioner gene and the nuclear localization signal. A method of personalizing anti-cancer treatment. A method of increasing DNase 1 resistance to actin binding. A method of increasing catalytic activity of DNase 1 binding.
Inventor(s): Rosner; Karli (Bloomfield Township, MI)
Assignee:
Application Number:13/392,233
Patent Claims:1. A gene construct comprising a nucleotide sequence encoding a DNAse 1 protein operatively linked to a nucleotide sequence encoding a nuclear localization signal (NLS), wherein said nucleotide sequence encoding said DNAse 1 protein includes at least one mutation rendering an actin binding site of said DNAse 1 protein resistant to the binding of actin, said gene construct lacking the nucleotide sequence encoding a secretion signal peptide, said gene construct additionally including at least one promoter operatively linked to said nucleotide sequence encoding said DNAse 1 protein and to said nucleotide sequence encoding said NLS.

2. The gene construct of claim 1, wherein said at least one promoter is chosen from the group consisting of the promoter from the prostate-specific antigen (PSA) gene; the promoter from the prostate-specific membrane antigen (PSMA) gene; the promoter from the prostatic acid phosphatase (PAP) gene; the probasin promoter ARR2PB; the promoter from the human secretoglobin family 2A member 2 (hSCGB2A2) gene; the promoter from the DF3/MUC1 gene; the promoter from the thyroglobulin gene; the promoter from the calcitonin (CT) gene; a nucleotide encoding the TTF1 gene operatively linked to a promoter of the human telomerase reverse transcriptase (hTERT) gene and to 5 tandem copies of at least a portion of a nucleotide encoding the human signal-induced proliferation-associated gene 1 (hSPA1); the promoter from the hexokinase II gene; the promoter from the phosphoenolpyrovate carboxykinase gene; the promoter from the albumin gene; the promoter RIP from the rat insulin gene; the promoter from the GFAP gene; the promoter from the gametophytic factor 2 (gfa2) gene; the promoter from the neuron specific enolase (NSE) gene; the 2nd intron of the Nestin gene operatively linked upstream to the 5' upstream region (2iNP) of the Nestin gene; the promoter from the HLA-Dr alpha gene; the promoter from the CD4 gene; the promoter from the CD19 gene; the promoter from the Ig kappa gene; the long terminal repeat (LTR) promoter of HIV-1; and the promoter from cytomegalovirus (CMV).

3. The gene construct of claim 1, wherein said nuclear localization signal is chosen from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5.

4. The gene construct of claim 1, wherein said at least one promoter is a melanocyte-specific promoter.

5. The gene construct of claim 4, wherein said melanocyte-specific promoter is chosen from the group consisting of the promoter from the tyrosinase gene, the promoter from the melanoma inhibitory activity (MIA) gene, the promoter from the SILV/PMEL17/GP100 gene, the promoter from the Melan-A/MART-1 gene, the promoter from the melanocortin-1 receptor (MC1R) gene, and the promoter from the microphthalmia-associated transcription factor (MITF) gene.

6. The gene construct of claim 1 or claim 4, additionally including an enhancer operatively linked to said promoter, said enhancer being chosen from the group consisting of the enhancer of the PSA gene, operatively linked to a rat probasin promoter; the 1455 bp PSA enhancer; the prostate-specific chimeric enhancer PSES; and the enhancer of the DF3/MUC1 gene, said enhancer of said DF3/MUC1 gene operatively linked to the promoter from said DF3/MUC1 gene.

7. The gene construct of claim 1, additionally including, operatively linked to said nucleotide sequence encoding said DNAse 1 protein and to said nucleotide sequence encoding said NLS, an activator binding sequence, and said gene construct including a nucleotide sequence encoding an inducible transcriptional activator system chosen from the group consisting of a transcriptional activator system inducible by an antibiotic, and a transcriptional activator system inducible by radiation.

8. The gene construct of claim 7 additionally including a promoter operatively linked to said gene construct encoding an inducible transcriptional activator system.

9. The gene construct of claim 1, wherein said actin-resistant binding site is an actin binding site including a mutation chosen from the group consisting of Glu-13, His-44, Asp-53, Tyr-65, Val-66, Val-67, Glu-69, Ala-114, and combinations thereof.

10. The gene construct of claim 1, additionally including, operatively linked to said nucleotide sequence encoding said DNAse 1 protein and to said nucleotide sequence encoding said NLS, a nucleotide sequence encoding the translation regulator Musashi.

Details for Patent 9,238,682

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 06/04/1986 ⤷  Try a Trial 2039-02-26
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2039-02-26
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2039-02-26
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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