DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement(s) filed June 20, 2023 has/have been considered by the Examiner.
Response to Arguments
Claim Objections
Applicant’s arguments, filed 02/24/2026, with respect to the 3, 8, 10, 17 and 19 objections have been fully considered and are persuasive. The claim objections of 08/26/2025 has been withdrawn.
35 USC § 103
Applicant’s arguments with respect to claim(s) 1, 9 and 18 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Specifically, newly cited reference as taught by Desai (US 20210000752 A1) teaches a similar method of reducing viability of cancer cells which administers the anti-angiogenic agents levantinib and ponatinib (paragraph 0357) as required by claims 1, 9 and 18, in combination with Gotlib (US 20200016067 A1 – hereinafter Gotlib).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 5-9, 11-12, 14-18, and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) [previously cited] in view of Desai (US 20210000752 A1 – hereinafter Desai) [NEW].
Re. claim 1, Gotlib teaches a method of reducing viability of cancer cells (abstract – “Viability of cancer cells (e.g., hepatocellular carcinoma cells) can be reduced by administering sorafenib to the cancer cells and applying an alternating electric field…”), the method comprising the steps of:
administering at least one composition to the cancer cells, wherein the at least one composition comprises at least one small molecule anti-angiogenic agent that specifically interacts with either a vascular endothelial growth factor (VEGF) or a VEGF receptor (VEGFR) and selectively inhibits interaction between VEGF and VEGFR and/or inhibits VEGFR signal transduction at an IC50 of less than about 10 nmol/L (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells…”, where sorafenib is a known anti-angiogenic agent and VEGF inhibitor, and has a molar mass of 464.8 g/mol, or about 468.8 Da and would read on the small molecule range of “about 1 Da to about 1.5 kDa” as explained in paragraph 0038 of the Applicant’s specification filed June 20, 2023);
and applying an alternating electric field to the cancer cells for a period of time (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”).
Gotlib does not explicitly teach wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, anlotinib,taxifolin,sulfatinib,dovitinib,ningetinib,vatalanib,AZD2932, LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof.
Desai teaches a similar method of reducing viability of cancer cells (abstract – “The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent)”), including using tumor-treating fields (paragraph 0055 – “…the method further comprises a non-invasive treatment (for example, a non-invasive treatment that interferes with cell (such as glioblastoma cancer cell division), for example by creating low-intensity, wave-like electric fields called tumor treating fields, e.g., Optune® treatment)”).
Desai further teaches administering at least one composition to the cancer cells (paragraph 0012 – “In some embodiments according to any one of the methods described herein, the method further comprising administering to the individual an effective amount of a second agent selected from the group consisting of an anti-VEGF antibody…”), and wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, nlotinib, taxifolin, sulfatinib, dovitinib, ningetinib, vatalanib, AZD2932, LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof (paragraph 0357 – “In some embodiments, the second agent is a VEGFR inhibitor…Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Since Gotlib and Desai both teach within the field of tumor-treating methods using electric fields, including anti-angiogenic agents, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Gotlib, specifically the anti-angiogenic agent Sorafenib as taught by Gotlib, and try substituting with the Ponatinib and/or lenvatinib as taught by Desai since such modification would predictably result in increased treatment efficacy in treating targeted cancerous tumors.
Re. claim 2, Gotlib of the combined invention further teaches wherein at least one of:
the alternating electric field is applied at a frequency in a range of from about 50 kHz to about 1 MHz (paragraph 0034 – “…the alternating electric field having a frequency between 100 and 400 kHz”);
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the cancer cells (paragraph 0035 - “…the sorafenib is administered to the cancer cells (e.g., HCC cells) at a therapeutically effective concentration, and the alternating electric field has a field strength of at least 1 V/cm in at least some of the cancer cells”);
and the period of time that the alternating electric field is applied is at least about 24 hours (paragraph 0043 – “…the applying step has a duration of at least 72 hours”; paragraph 0051 – “Both cell lines were grown at various sorafenib concentrations (0.1-3.0 μM), and were treated with TTFields for 72 hours”).
Re. claim 5, Gotlib of the combined invention further teaches wherein steps (1) and (2) are performed wholly or partially sequentially, and wherein the at least one composition is administered before the application of the alternating electric field has begun (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby sequentially administering the anti-angiogenic agent before delivering the electric fields).
Re. claim 6, Gotlib of the combined invention further teaches wherein steps (1) and (2) are performed wholly or partially sequentially (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby sequentially administering the anti-angiogenic agent before delivering the electric fields),
and wherein the at least one composition is administered after the application of the alternating electric field has begun (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby administering the anti-angiogenic agent after delivering the electric fields).
Re. claim 7, Gotlib of the combined invention further teaches wherein steps (1) and (2) are repeated one or more times (Step 1: paragraph 0036 – “…the dose of sorafenib provided to a patient in need of treatment is 400 mg in two tablets taken orally twice per day without food”; Step 2: paragraph 0069 – “…the AC voltage generator applies an AC voltage at the same frequency (or a different frequency) between the front and back electrodes for a second period of time (e.g. 1 second), which induces alternating electric fields where the most significant components of the field lines are parallel to the sagittal axis of the subject's body. This two-step sequence is then repeated for the duration of the treatment”).
Re. claim 8, Gotlib of the combined invention further teaches wherein the cancer cells are selected from the group consisting of hepatocellular carcinoma cells (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”), glioblastoma cells, pleural mesothelioma cells, differentiated thyroid cancer cells (paragraph 0063 – “But because sorafenib is indicated for certain types of thyroid cancer as well as hepatocellular carcinoma, alternative aspects include using TTFields combined with sorafenib to treat other types of cancers (e.g., thyroid cancer)”), advanced renal cell carcinoma cells, ovarian cancers, pancreatic cancers, lung cancer cells, breast cancer cells, and combinations thereof.
Re. claim 9, Gotlib teaches a method of treating cancer in a subject (abstract – “Viability of cancer cells (e.g., hepatocellular carcinoma cells) can be reduced by administering sorafenib to the cancer cells and applying an alternating electric field…”), the method comprising the steps of:
administering at least one composition to the subject, wherein the at least one composition comprises at least one small molecule anti-angiogenic agent that specifically interacts with either a vascular endothelial growth factor (VEGF) or a VEGF receptor (VEGFR) and selectively inhibits interaction between VEGF and VEGFR and/or inhibits VEGFR signal transduction at an IC50 of less than about 10 nmol/L (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells…”, where sorafenib is a known anti-angiogenic agent and VEGF inhibitor, and has a molar mass of 464.8 g/mol, or about 468.8 Da and would read on the small molecule range of “about 1 Da to about 1.5 kDa” as explained in paragraph 0038 of the Applicant’s specification filed June 20, 2023);
and applying an alternating electric field to a target region of the subject (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”).
Gotlib does not explicitly teach wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, anlotinib, taxifolin, sulfatinib, dovitinib, ningetinib, vatalanib, AZD2932,LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof.
Desai teaches a similar method of reducing viability of cancer cells (abstract – “The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent)”), including using tumor-treating fields (paragraph 0055 – “…the method further comprises a non-invasive treatment (for example, a non-invasive treatment that interferes with cell (such as glioblastoma cancer cell division), for example by creating low-intensity, wave-like electric fields called tumor treating fields, e.g., Optune® treatment)”).
Desai further teaches administering at least one composition to the cancer cells (paragraph 0012 – “In some embodiments according to any one of the methods described herein, the method further comprising administering to the individual an effective amount of a second agent selected from the group consisting of an anti-VEGF antibody…”), and wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, anlotinib,taxifolin,sulfatinib,dovitinib,ningetinib,vatalanib,AZD2932, LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof (paragraph 0357 – “In some embodiments, the second agent is a VEGFR inhibitor…Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Since Gotlib and Desai both teach within the field of tumor-treating methods using electric fields, including anti-angiogenic agents, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Gotlib, specifically the anti-angiogenic agent Sorafenib as taught by Gotlib, and try substituting with the Ponatinib and/or lenvatinib as taught by Desai since such modification would predictably result in increased treatment efficacy in treating targeted cancerous tumors.
Re. claim 11, Gotlib of the combined invention further teaches wherein the at least one composition is orally administered to the subject (paragraph 0036 – “…the dose of sorafenib provided to a patient in need of treatment is 400 mg in two tablets taken orally twice per day without food”; paragraph 0061 – “The administration of the sorafenib to the subject may be performed using any of a variety of approaches including but not limited to intravenously, orally, subcutaneously, intrathecal, intraventricularly, and intraperitoneally”).
Re. claim 12, Gotlib of the combined invention further teaches wherein at least one of:
the alternating electric field is applied at a frequency in a range of from about 50 kHz to about 1 MHz (paragraph 0034 – “…the alternating electric field having a frequency between 100 and 400 kHz”);
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the cancer cells (paragraph 0035 - “…the sorafenib is administered to the cancer cells (e.g., HCC cells) at a therapeutically effective concentration, and the alternating electric field has a field strength of at least 1 V/cm in at least some of the cancer cells”);
and the period of time that the alternating electric field is applied is at least about 24 hours (paragraph 0043 – “…the applying step has a duration of at least 72 hours”; paragraph 0051 – “Both cell lines were grown at various sorafenib concentrations (0.1-3.0 μM), and were treated with TTFields for 72 hours”).
Re. claim 14, Gotlib of the combined invention further teaches wherein steps (1) and (2) are performed wholly or partially sequentially, and wherein the at least one composition is administered before the application of the alternating electric field has begun (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby sequentially administering the anti-angiogenic agent before delivering the electric fields).
Re. claim 15, Gotlib of the combined invention further teaches wherein steps (1) and (2) are performed wholly or partially sequentially (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby sequentially administering the anti-angiogenic agent before delivering the electric fields),
and wherein the at least one composition is administered after the application of the alternating electric field has begun (paragraph 0059 – “…the alternating electric field can be applied before, during, or after the sorafenib treatment”, thereby administering the anti-angiogenic agent after delivering the electric fields).
Re. claim 16, Gotlib of the combined invention further teaches wherein steps (1) and (2) are repeated one or more times (Step 1: paragraph 0036 – “…the dose of sorafenib provided to a patient in need of treatment is 400 mg in two tablets taken orally twice per day without food”; Step 2: paragraph 0069 – “…the AC voltage generator applies an AC voltage at the same frequency (or a different frequency) between the front and back electrodes for a second period of time (e.g. 1 second), which induces alternating electric fields where the most significant components of the field lines are parallel to the sagittal axis of the subject's body. This two-step sequence is then repeated for the duration of the treatment”).
Re. claim 17, Gotlib of the combined invention further teaches wherein the cancer is selected from the group consisting of hepatocellular carcinoma (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”), glioblastoma, pleural mesothelioma, differentiated thyroid cancer (paragraph 0063 – “But because sorafenib is indicated for certain types of thyroid cancer as well as hepatocellular carcinoma, alternative aspects include using TTFields combined with sorafenib to treat other types of cancers (e.g., thyroid cancer)”), advanced renal cell carcinoma, ovarian cancer, pancreatic cancer, lung cancer, breast cancer, and combinations thereof.
Re. claim 18, Gotlib teaches a method of reducing a volume of a tumor and/or preventing an increase of volume of the tumor, wherein the tumor is present in a body of a living subject and includes a plurality of cancer cells (abstract – “Viability of cancer cells (e.g., hepatocellular carcinoma cells) can be reduced by administering sorafenib to the cancer cells and applying an alternating electric field…”), the method comprising the steps of:
administering at least one composition to the subject, wherein the at least one composition comprises at least one small molecule anti-angiogenic agent that specifically interacts with either a vascular endothelial growth factor (VEGF) or a VEGF receptor (VEGFR) and selectively inhibits interaction between VEGF and VEGFR and/or inhibits VEGFR signal transduction at an IC50 of less than about 10 nmol/L (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells…”, where sorafenib is a known anti-angiogenic agent and VEGF inhibitor, and has a molar mass of 464.8 g/mol, or about 468.8 Da and would read on the small molecule range of “about 1 Da to about 1.5 kDa” as explained in paragraph 0038 of the Applicant’s specification filed June 20, 2023);
and applying an alternating electric field to a target region of the subject (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”).
Gotlib does not explicitly teach wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, anlotinib, taxifolin, sulfatinib, dovitinib, ningetinib, vatalanib, AZD2932,LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof.
Desai teaches a similar method of reducing viability of cancer cells (abstract – “The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent)”), including using tumor-treating fields (paragraph 0055 – “…the method further comprises a non-invasive treatment (for example, a non-invasive treatment that interferes with cell (such as glioblastoma cancer cell division), for example by creating low-intensity, wave-like electric fields called tumor treating fields, e.g., Optune® treatment)”).
Desai further teaches administering at least one composition to the cancer cells (paragraph 0012 – “In some embodiments according to any one of the methods described herein, the method further comprising administering to the individual an effective amount of a second agent selected from the group consisting of an anti-VEGF antibody…”), and wherein the at least one small molecule anti-angiogenic agent is selected from the group consisting of lenvatinib, regorafenib, cabozantinib, anlotinib, pazopanib, albendazole, lucitanib, motesanib, aflibercept, ponatinib, cediranib, tivozanib, telatinib, apatinib, semaxanib, fruquintinib, lucitanib, anlotinib, taxifolin, sulfatinib, dovitinib, ningetinib, vatalanib, AZD2932, LY2874455, MGCD-265 analog, ZM 306416, ZM 323881, KRN 633, YF-452, ODM- 203, AEE 788, BMS 605541, MAZ51, Ki 8751, SU 5402, SU 5408, SU5205, SU5214, SU 6668, SU 14813, XL 092, XL 184, BAW2881, BFH772, A-13958, SKLB1002, WAY-340935, ZD-4190, hVEGF-IN-1, R1530, VEGF-Grab, Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3, VEGF decoy receptor fusion protein, a decoy receptor for VEGF, and combinations thereof (paragraph 0357 – “In some embodiments, the second agent is a VEGFR inhibitor…Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Since Gotlib and Desai both teach within the field of tumor-treating methods using electric fields, including anti-angiogenic agents, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Gotlib, specifically the anti-angiogenic agent Sorafenib as taught by Gotlib, and try substituting with the Ponatinib and/or lenvatinib as taught by Desai since such modification would predictably result in increased treatment efficacy in treating targeted cancerous tumors.
Re. claim 20, Gotlib of the combined invention further teaches wherein at least one of:
the alternating electric field is applied at a frequency in a range of from about 50 kHz to about 1 MHz (paragraph 0034 – “…the alternating electric field having a frequency between 100 and 400 kHz”);
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the cancer cells (paragraph 0035 - “…the sorafenib is administered to the cancer cells (e.g., HCC cells) at a therapeutically effective concentration, and the alternating electric field has a field strength of at least 1 V/cm in at least some of the cancer cells”);
and the period of time that the alternating electric field is applied is at least about 24 hours (paragraph 0043 – “…the applying step has a duration of at least 72 hours”; paragraph 0051 – “Both cell lines were grown at various sorafenib concentrations (0.1-3.0 μM), and were treated with TTFields for 72 hours”).
Re. claim 21, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type I VEGFR inhibitor selected from the group consisting of pazopanib, ponatinib, motesanib, and combinations thereof (Desai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Re. claim 22, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type II VEGFR inhibitor selected from the group consisting of carbozantinib, lenvatinib, regorafenib, lucitanib, and combinations thereof (Desai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Re. claim 23, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type I VEGFR inhibitor selected from the group consisting of pazopanib, ponatinib, motesanib, and combinations thereof (Desai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Re. claim 24, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type II VEGFR inhibitor selected from the group consisting of carbozantinib, lenvatinib, regorafenib, lucitanib, and combinations thereof (Desai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Re. claim 25, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type I VEGFR inhibitor selected from the group consisting of pazopanib, ponatinib, motesanib, and combinations thereof (Desai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Re. claim 26, Desai of the combined invention further teaches wherein the at least one small molecule anti-angiogenic agent is a Type II VEGFR inhibitor selected from the group consisting of carbozantinib, lenvatinib, regorafenib, lucitanib, and combinations thereof (Deshai paragraph 0357 – “Exemplary VEGFR inhibitors include, but not limited to, bevacizumab, pazopanib, sunitinib, axitinib, ponatinib, cabozantinib, lenvatinib, ramucirumab, regorafenib, vandetanib, and ziv-aflibercept”).
Claim(s) 4 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) [previously cited] in view of Desai (US 20210000752 A1 – hereinafter Desai) [NEW], and in further view of Maag (US 20200368525 A1 – hereinafter Maag) [previously cited].
Re. claim 4, Gotlib in view of Desai (hereinafter the combined invention), specifically Gotlib as stated above in claim 1 teaches administering the small-molecule anti-angiogenic agent Sorafenib (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells…”, where sorafenib is a known anti-angiogenic agent and VEGF inhibitor), and teaches applying an alternating electric field to the cancer cells for a period of time as stated above in claim 1 (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”). Gotlib also teaches that applying alternating electric fields can be performed simultaneously with at least (or no less than) a portion with administering the Sorafenib (paragraph 0059 – “…at least a portion of the applying step can be performed simultaneously with at least a portion of the administering step”).
The combined invention does not explicitly teach wherein the administering and applying steps are performed substantially simultaneously.
Maag teaches a similar system/method of treating cancer (Maag abstract – “The present disclosure provides a method for treating cancer…”). Maag further teaches the method comprises a combined treatment of tumor treating fields (TTFields) and the therapy drug depatuxizumab mafodotin (Maag paragraph 0009 – “FIGS. 1A and 1B show the efficacy of the combined treatment of TTFields and depatuxizumab mafodotin”), and further teaches the known technique of administering two therapies (drug therapy of depatuxizumab mafodotin and TTFields) simultaneously or substantially together (Maag paragraph 0028 – “The term “combination” or “combination therapy” refers to the administration of two or more therapies, e.g., depatuxizumab mafodotin and TTFields. The two therapies may be administered concomitantly in which case both therapies are administered together or substantially together, or sequentially in which case one therapy may be administered prior to the other therapy”).
The combined invention and Maag both teach within the field of cancer treatment methods simultaneously combining drug therapy and tumor-treating electric fields. Gotlib utilizes Sorafenib in combination with TTFields (Gotlib paragraph 0034) as stated above in claim 1. Maag utilizes depatuxizumab mafodotin in combination with TTFields (Maag abstract, paragraph 0028). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the combined invention, specifically the simultaneous combination therapy of Gotlib, to incorporate the known technique of substantially simultaneous combination therapy as taught by Maag since such modification would predictably result in increased efficacy in treating targeted cancerous tumors.
Re. claim 13, Gotlib in view of Desai (hereinafter the combined invention), specifically Gotlib as stated above in claim 1 teaches administering the small-molecule anti-angiogenic agent Sorafenib (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells…”, where sorafenib is a known anti-angiogenic agent and VEGF inhibitor), and teaches applying an alternating electric field to the cancer cells for a period of time as stated above in claim 1 (paragraph 0034 – “Aspects described herein provide methods of reducing the viability of cancer cells (e.g., hepatocellular carcinoma cells) by administering sorafenib to the cancer cells, and applying an alternating electric field to the cancer cells, the alternating electric field having a frequency between 100 and 400 kHz”). Gotlib also teaches that applying alternating electric fields can be performed simultaneously with at least (or no less than) a portion with administering the Sorafenib (paragraph 0059 – “…at least a portion of the applying step can be performed simultaneously with at least a portion of the administering step”).
The combined invention does not explicitly teach wherein the administering and applying steps are performed substantially simultaneously.
Maag teaches a similar system/method of treating cancer (Maag abstract – “The present disclosure provides a method for treating cancer…”). Maag further teaches the method comprises a combined treatment of tumor treating fields (TTFields) and the therapy drug depatuxizumab mafodotin (Maag paragraph 0009 – “FIGS. 1A and 1B show the efficacy of the combined treatment of TTFields and depatuxizumab mafodotin”), and further teaches the known technique of administering two therapies (drug therapy of depatuxizumab mafodotin and TTFields) simultaneously or substantially together (Maag paragraph 0028 – “The term “combination” or “combination therapy” refers to the administration of two or more therapies, e.g., depatuxizumab mafodotin and TTFields. The two therapies may be administered concomitantly in which case both therapies are administered together or substantially together, or sequentially in which case one therapy may be administered prior to the other therapy”).
The combined invention and Maag both teach within the field of cancer treatment methods simultaneously combining drug therapy and tumor-treating electric fields. Gotlib utilizes Sorafenib in combination with TTFields (Gotlib paragraph 0034) as stated above in claim 1. Maag utilizes depatuxizumab mafodotin in combination with TTFields (Maag abstract, paragraph 0028). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the combined invention, specifically the simultaneous combination therapy of Gotlib, to incorporate the known technique of substantially simultaneous combination therapy as taught by Maag since such modification would predictably result in increased efficacy in treating targeted cancerous tumors.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anh-Khoa N. Dinh whose telephone number is (571)272-7041. The examiner can normally be reach, ed Mon-Fri 7:00am-4:00pm EST.
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/ANH-KHOA N DINH/Examiner, Art Unit 3796
/CARL H LAYNO/Supervisory Patent Examiner, Art Unit 3796