Claims for Patent: 10,300,121

Summary for Patent: 10,300,121

Title:	Early cancer detection and enhanced immunotherapy
Abstract:	A method of therapy for a tumor or other pathology by administering a combination of thermotherapy, immunotherapy, and vaccination optionally combined with gene delivery. The combination therapy beneficially treats the tumor and prevents tumor recurrence, either locally or at a different site, by boosting the patient\'s immune response both at the time or original therapy and/or for later therapy. With respect to gene delivery, the inventive method may be used in cancer therapy, but is not limited to such use; it will be appreciated that the inventive method may be used for gene delivery in general. The controlled and precise application of thermal energy enhances gene transfer to any cell, whether the cell is a neoplastic cell, a pre-neoplastic cell, or a normal cell.
Inventor(s):	Peyman; Gholam A. (Sun City, AZ)
Assignee:
Application Number:	15/853,821
Patent Claims:	1. A cancer therapeutic method comprising administering to a patient having a tumor a combination of thermotherapy and immunotherapy, where thermotherapy comprises systemically administering a plurality of tumor-antibody-coated nanoparticles coated with a thermosensitive polymer, the thermotherapy further comprises heating the tumor-antibody-coated nanoparticles using an energy source at the site of the tumor so as to damage one or more tumor cell membranes and release antigenic material in vivo that activates and stimulates an immunogenic response of the patient at the site of the tumor; and immunotherapy comprises systemically administering the patient's natural killer (NK) cells/dendritic cells pre-sensitized in vitro to the tumor, and further administering tumor-antibody-coated nanoparticles conjugated with viral-like particles (VLP) while simultaneously administering tumor-antibody-coated nanoparticles conjugated with at least one of checkpoint inhibitors, Rock inhibitors, or Wnt inhibitors to prevent the proliferation of tumor cells or metastatic cells, and/or prevent the tumor cells or metastatic cells from being disguised from T-lymphocytes of the patient or the patient's natural killer (NK) cells. 2. The method of claim 1 where the tumor-antibody-coated nanoparticles are conjugated with checkpoint inhibitors, the checkpoint inhibitors selected from the group consisting of PD-1, PD-L1, CTLA-4, jagged 1 inhibitor 15D11, and combinations thereof. 3. The method of claim 1 where the tumor-antibody-coated nanoparticles are conjugated with Rock inhibitors, the Rock inhibitors selected from the group consisting of Fasudil, exoenzyme, Y27632, Botox, and combinations thereof, the Rock inhibitors reducing an inflammatory response of the patient and preventing an autoimmune reaction or cytokine storm. 4. The method of claim 1 where the tumor-antibody-coated nanoparticles are conjugated with Wnt inhibitors, the Wnt inhibitors selected from the group consisting of niclosamide, ivermectin, and combinations thereof. 5. The method of claim 1 further comprising the step of: repeating administration of the tumor-antibody-coated nanoparticles conjugated with the VLP and the tumor-antibody-coated nanoparticles conjugated with the at least one of the checkpoint inhibitors, Rock inhibitors, or Wnt inhibitors once or twice a year, thereby reducing an autoimmune reaction; and further administering tumor-antibody-coated nanoparticles conjugated with polylactic acid or polyglycolic acid. 6. The method of claim 1 where the tumor-antibody-coated nanoparticles administered during thermotherapy are conjugated with a medication, and where thermotherapy includes exposing the tumor-antibody-coated nanoparticles and medication to a light pulse at a frequency in the range of 20 Hz to 60 Hz to decrease proliferation of the tumor cells. 7. The method of claim 1 where immunotherapy is administered at intervals to the patient after the initial therapy acting as a booster to the original immunotherapy and reduce or prevent tumor recurrences at a same or different site. 8. The method of claim 1 where immunotherapy further comprises obtaining NK cells/dendritic cells grown in culture under light pulses with a tumor biomarker from blood or a tumor biopsy specimen containing tumor lysate, killed circulating tumor cells (ct cell), and tumor extracellular vesicles (ECV). 9. The method of claim 1 where thermotherapy includes exposing the tumor-antibody-coated nanoparticles to a light pulse at a frequency in the range of 20 Hz-60 Hz to decrease proliferation of the tumor cells. 10. The method of claim 1 where the step of heating the tumor-antibody-coated nanoparticles using the energy source comprises using a thermoacoustic unit to control a thermal energy delivery unit using a processor to maintain the tumor-antibody-coated nanoparticles at a predetermined temperature as a closed circuit once the tumor-antibody-coated nanoparticles have attached to the tumor cells, then controllably increasing the temperature to which the tumor-antibody-coated nanoparticles are exposed from 37.degree. C. to 41.degree. C.-43.degree. C. for the predetermined time period resulting in melting the thermosensitive polymer coating of the tumor-antibody-coated nanoparticles, and further releasing under control a medication or gene, which are attached to the thermosensitive tumor-antibody-coated nanoparticles locally at the desired site. 11. The method of claim 1 where the anti-tumor antibody is specific for at least one tumor biomarker in the patient's blood. 12. The method of claim 1 further comprising performing precision nanoparticle assisted thermotherapy and generating a photoacoustic image of the cells to which the nanoparticles bind at an early cellular stage of the tumor, the tumor having a size between one and two millimeters in diameter not easily detectable by radiographic imaging. 13. The method of claim 1 where the tumor-antibody-coated nanoparticles administered during thermotherapy are further conjugated with a toxin to further damage the one or more tumor cell membranes, the toxin selected from the group consisting of snake venom, scorpion venom, and bee venom. 14. The method of claim 1 where the tumor-antibody-coated nanoparticles administered during thermotherapy are further conjugated with cell penetrating peptides (CPP) or activatable cell penetrating peptides (ACPP) to facilitate penetration of the tumor-antibody-coated nanoparticles into the tumor cells. 15. The method of claim 1, further comprising: applying light energy to a tube containing the patient's blood cells post-therapy to achieve a temperature up to 60.degree. C. to kill immune cells containing nanoparticles; passing the pulsed blood cells through a dielectrophoresis system to characterize and remove dead or live T-cells, sensitized killer cells, and tumor cells; and re-infusing the dielectrophoresis treated blood in the patient while simultaneously administering immunosuppressive agents, thus reducing the likelihood of a severe post-therapy autoimmune response in the patient. 16. A cancer therapeutic method comprising administering to a patient having a tumor a combination of thermotherapy and immunotherapy, where thermotherapy comprises systemically administering a plurality of tumor-antibody-coated nanoparticles coated with a thermosensitive polymer, the thermotherapy further comprises heating the tumor-antibody-coated nanoparticles using an energy source at the site of the tumor so as to damage one or more tumor cell membranes and release antigenic material in vivo that activates and stimulates an immunogenic response of the patient at the site of the tumor; immunotherapy comprises systemically administering the patient's natural killer (NK) cells/dendritic cells pre-sensitized in vitro to the tumor; and the method further comprises performing precision nanoparticle assisted thermotherapy and generating a photoacoustic image of the cells to which the tumor-antibody-coated nanoparticles bind at an early cellular stage of the tumor, the tumor having a size between one and two millimeters in diameter not easily detectable by radiographic imaging.

Details for Patent 10,300,121

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	BOTOX COSMETIC	onabotulinumtoxina	For Injection	103000	December 09, 1991		2035-12-21
Abbvie Inc.	BOTOX	onabotulinumtoxina	For Injection	103000	December 09, 1991		2035-12-21