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 January 09, 2024 and May 14, 2024 has/have been considered by the Examiner.
Response to Arguments
Claims 1-20 are canceled. Claims 21-40 are new and pending in this action.
Claim Objections
Applicant’s arguments, filed 03/09/2026, with respect to the claim objections of claims 3, 8, 10, 17 and 19 have been fully considered and are persuasive. The claim objections of 10/17/2025 has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 03/09/2026 have been fully considered but they are not persuasive. Applicant’s arguments rely on language solely recited in preamble recitations in independent claim(s) 21 and 30. When reading the preamble in the context of the entire claim, the recitation, “A method of counteracting pro-angiogenic effects of alternating electric field administration when treating cancer cells…” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). Furthermore, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction, see MPEP § 2111.02. In the instant case, the preamble of the claim merely recites the intended use and/or statement of effect of the claimed method (i.e. counteracting pro-angiogenic effects of alternating electric field administration), and bears no patentable weight as opposed to the positively recited steps (1) and (2) of independent claims 21 and 30, in which the combination of Gotlib and Chan as stated in the rejection below teaches the positively recited steps of (1) applying an alternating electric field to the cancer cells; and (2) administering at least one composition to the cancer cells, wherein the at least one composition comprises at least one antibody that specifically binds to a vascular endothelial growth factor receptor-2 (anti-VEGFR-2 antibody).
Despite the Applicant’s assertion in this application that TTFields (which are known to have anti-angiogenic effects) now apparently has a pro-angiogenic effects, the combination of Gotlib and Chan as stated in the rejection below meet all the positively recited steps of the claimed invention and thus should inherently yield any intended results, including counteracting (supposed) pro-angiogenic effects of alternating electric fields, unless the claims are incomplete for failing to include aspects that are essential to achieving the claimed intended results. Therefore, the combination of Gotlib and Chan as stated in the rejection below is considered to read on independent claims 21 and 30 and are rejected as obvious over the prior art of record.
Claim Interpretation
According to MPEP 2112.02, a prior art device anticipates a claimed process if the device carries out the process during normal operation. Under the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device. When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process. In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986). Furthermore, where a reference discloses the terms of the recited method steps, and such steps necessarily result in the desired and recited effect, that the reference does not describe the recited effect in haec verba is of no significance as the reference meets the claim under the doctrine of inherency. Ex parte Novitski, 26 USPQ2d 1389, 1390-91 (BdPatApp & Inter 1993). Furthermore, the employment of the claimed steps must inherently produce the same intended results else the claims are incomplete for failing to recite a critical aspect of the invention.
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.
Claim(s) 21-25, 29-33, 36-37, 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) [previously cited] in view of Chan (US 20170173013 A1 – hereinafter Chan) [NEW].
Re. claim 21, 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 (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-2 inhibitor), and
applying an alternating electric field to the cancer 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”).
Gotlib teaches does not explicitly teach wherein the at least one composition comprises at least one antibody that specifically binds to a vascular endothelial growth factor receptor-2 (anti-VEGFR-2 antibody).
Chan teaches a method of reducing viability of cancer cells (Chan abstract – “The present invention provides preparation of medicaments for use in treating and methods of treating non-small cell lung cancer in a patient…”), and further teaches administering at least one composition to the cancer cells, wherein the at least one composition comprises at least one antibody that specifically binds to a vascular endothelial growth factor receptor-2 (anti-VEGFR-2 antibody) (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”).
Gotlib and Chan all teach within the field of reducing viability in cancer cells as stated above, specifically with use of anti-angiogenic and anti-VEGFR-2 inhibitors. Gotlib teaches use of the VEGFR-2 inhibitor Sorafenib in conjunction with alternating electric fields; Chan uses the known VEGFR-2 inhibitor antibody of Ramucirumab to treat cancer cells. 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 Sorafenib VEGFR-2 inhibitor of Gotlib, to try substituting with the Ramucirumab VEGFR-2 inhibitor antibody, as taught by Chan, since such modification would predictably result in increased efficacy in reducing viability of tumor/cancer cells during treatment.
Re. claim 22, the combined invention of Gotlib and Chan (hereinafter 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 (Gotlib 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 (Gotlib 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 (Gotlib 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 23, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody is a monoclonal antibody selected from the group consisting of:
ramucirumab (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”),
DC101 (Chan paragraph 0030 – “As used herein, the term “DC101” refers to a rat monoclonal antibody directed against mouse VEGFR2 that may be used in experiments as a surrogate in mice for an anti-VEGFR2 Ab…”; paragraph 0104 – “Results: Treatment with 10, 20, or 40 mg/kg of DC101 resulted in a significant inhibition of tumor growth”),
and combinations thereof.
Re. claim 24, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody comprises ramucirumab (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”).
Re. claim 25, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody comprises DC101 (Chan paragraph 0030 – “As used herein, the term “DC101” refers to a rat monoclonal antibody directed against mouse VEGFR2 that may be used in experiments as a surrogate in mice for an anti-VEGFR2 Ab…”; paragraph 0104 – “Results: Treatment with 10, 20, or 40 mg/kg of DC101 resulted in a significant inhibition of tumor growth”).
Re. claim 29, the combined invention further teaches wherein the cancer cells are selected from the group consisting of hepatocellular carcinoma cells (Gotlib 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 (Gotlib 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 30, 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 (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-2 inhibitor), 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 composition comprises at least one anti-VEGFR-2 antibody.
Chan teaches a method of reducing viability of cancer cells (Chan abstract – “The present invention provides preparation of medicaments for use in treating and methods of treating non-small cell lung cancer in a patient…”), and further teaches administering at least one composition to the cancer cells, wherein the at least one composition comprises at least one antibody that specifically binds to a vascular endothelial growth factor receptor-2 (anti-VEGFR-2 antibody) (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”).
Gotlib and Chan all teach within the field of reducing viability in cancer cells as stated above, specifically with use of anti-angiogenic and anti-VEGFR-2 inhibitors. Gotlib teaches use of the VEGFR-2 inhibitor Sorafenib in conjunction with alternating electric fields; Chan uses the known VEGFR-2 inhibitor antibody of Ramucirumab to treat cancer cells. 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 Sorafenib VEGFR-2 inhibitor of Gotlib, to try substituting with the Ramucirumab VEGFR-2 inhibitor antibody, as taught by Chan, since such modification would predictably result in increased efficacy in reducing viability of tumor/cancer cells during treatment.
Re. claim 31, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody is a monoclonal antibody selected from the group consisting of:
ramucirumab (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”),
DC101 (Chan paragraph 0030 – “As used herein, the term “DC101” refers to a rat monoclonal antibody directed against mouse VEGFR2 that may be used in experiments as a surrogate in mice for an anti-VEGFR2 Ab…”; paragraph 0104 – “Results: Treatment with 10, 20, or 40 mg/kg of DC101 resulted in a significant inhibition of tumor growth”),
and combinations thereof.
Re. claim 32, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody comprises ramucirumab (Chan paragraph 0014 – “Another aspect of the present invention is a method of treating non-small cell lung cancer in a patient, comprising administering to a non-small cell lung cancer patient in need of treatment: [0015] a) ramucirumab at 10 mg/kg on day 1 of a 21-day cycle…”; paragraph 0059 – “Where ramucirumab is administered at repeated intervals…”).
Re. claim 33, the combined invention further teaches wherein the at least one anti-VEGFR-2 antibody comprises DC101 (Chan paragraph 0030 – “As used herein, the term “DC101” refers to a rat monoclonal antibody directed against mouse VEGFR2 that may be used in experiments as a surrogate in mice for an anti-VEGFR2 Ab…”; paragraph 0104 – “Results: Treatment with 10, 20, or 40 mg/kg of DC101 resulted in a significant inhibition of tumor growth”).
Re. claim 36, 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 (Gotlib 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 (Gotlib 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 (Gotlib 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 37, the combined invention further teaches wherein step (1) is repeated one or more times (Chan paragraph 0059 – “Where ramucirumab is administered at repeated intervals (e.g. during a standard course of treatment), [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine can be administered prior to each administration of ramucirumab”),
and wherein step (2) is repeated one or more times (Gotlib 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 40, the combined invention further teaches wherein the cancer is selected from the group consisting of hepatocellular carcinoma (Gotlib 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 (Gotlib 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.
Claim(s) 26 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) in view of Chan (US 20170173013 A1 – hereinafter Chan), and in further view of Sakamoto (US 20160082032 A1 – hereinafter Sakamoto) [NEW].
Re. claim 26, the combined invention of Gotlib and Chan (hereinafter the combined invention) teaches the method of claim 25 as stated above, but does not explicitly teach wherein the at least one composition further comprises trifluridine/tipiracil (FTD/TPI).
Sakamoto teaches a similar method of reducing viability of cancer cells (Sakamoto abstract – “The present invention provides a method for predicting the therapeutic effect of chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride …”),
and further teaches administering at least one composition to the cancer cells (Sakamoto paragraph 0033 – “(4) administering the antitumor agent to the patient who is predicted to be likely to sufficiently respond to the chemotherapy in step (3)”),
wherein the at least one composition further comprises trifluridine/tipiracil (FTD/TPI) (Sakamoto paragraph 0004 – “Meanwhile, a combination drug containing FTD and TPI at a molar ratio of 1:0.5 (hereinafter also referred to as “FTD-TPI combination drug”) is under development as a new antitumor agent against colorectal cancer”; paragraph 0076 – “Progressive recurring colorectal cancer patients…were divided into a group (112 cases) administered with an antitumor agent containing FTD and TPI…; paragraph 0082 – “The above results demonstrated that although the FTD-TPI combination drug was clinically useful for colorectal cancer patients regardless of the expression of TK1 protein, the FTD-TPI combination drug particularly showed a significantly excellent therapeutic effect on patients in which the percentage of tumor cells evaluated…”).
The combined invention and Sakamoto all teach within the field of reducing viability in cancer cells as stated above. 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 VEGFR-2 inhibitor antibody composition of the combined invention, to try incorporating with the FTD-TPI as taught by Sakamoto, since such modification would predictably result in increased efficacy in reducing viability of tumor/cancer cells during treatment.
Re. claim 34, the combined invention of Gotlib and Chan (hereinafter the combined invention) teaches the method of claim 33 as stated above, but does not explicitly teach wherein the at least one composition further comprises trifluridine/tipiracil (FTD/TPI).
Sakamoto teaches a similar method of reducing viability of cancer cells (Sakamoto abstract – “The present invention provides a method for predicting the therapeutic effect of chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride …”),
and further teaches administering at least one composition to the cancer cells (Sakamoto paragraph 0033 – “(4) administering the antitumor agent to the patient who is predicted to be likely to sufficiently respond to the chemotherapy in step (3)”),
wherein the at least one composition further comprises trifluridine/tipiracil (FTD/TPI) (Sakamoto paragraph 0004 – “Meanwhile, a combination drug containing FTD and TPI at a molar ratio of 1:0.5 (hereinafter also referred to as “FTD-TPI combination drug”) is under development as a new antitumor agent against colorectal cancer”; paragraph 0076 – “Progressive recurring colorectal cancer patients…were divided into a group (112 cases) administered with an antitumor agent containing FTD and TPI…; paragraph 0082 – “The above results demonstrated that although the FTD-TPI combination drug was clinically useful for colorectal cancer patients regardless of the expression of TK1 protein, the FTD-TPI combination drug particularly showed a significantly excellent therapeutic effect on patients in which the percentage of tumor cells evaluated…”).
The combined invention and Sakamoto all teach within the field of reducing viability in cancer cells as stated above. 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 VEGFR-2 inhibitor antibody composition of the combined invention, to try incorporating with the FTD-TPI as taught by Sakamoto, since such modification would predictably result in increased efficacy in reducing viability of tumor/cancer cells during treatment.
Claim(s) 27-28 and 38-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) in view of Chan (US 20170173013 A1 – hereinafter Chan), and in further view of Desai (20210000752 – hereinafter Desai) [NEW].
Re. claim 27, the combined invention of Gotlib and Chan (hereinafter the combined invention) teaches the method of claim 21 as stated above, but does not explicitly teach the method further comprising the step of: (3) administering at least a second composition to the cancer cells, wherein the second composition comprises at least one chemotherapeutic agent
Desai teaches a similar method of reducing viability of cancer cells (Desai 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 a second 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…”; paragraph 0037 – “The present application also provides methods for treating a CNS disorder (e.g., glioblastoma, epilepsy, cortical dysplasia) in an individual, comprising a) systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising an mTOR inhibitor (e.g., a limus drug, e.g., sirolimus or a derivative thereof) and an albumin; b) administering to the individual a second agent…”),
and wherein the second composition comprises at least one chemotherapeutic agent (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”; paragraph 0012 – “In some embodiments, the alkylating agent is administered orally. In some embodiments, the alkylating agent is a nitrosourea compound. In some embodiments, the compound is lomustine”).
The combined invention and Desai both teach within the field of tumor-treating methods using electric fields, including anti-angiogenic agents. 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, to incorporate the known technique of administering a second chemotherapeutic agent as taught by Desai since such modification would predictably result in increased treatment efficacy in treating targeted cancerous tumors.
Re. claim 28, Desai of the combined invention further teaches wherein the at least one chemotherapeutic agent is selected from the group consisting of lenvatinib, paclitaxel, docetaxel, ifosamide, etoposide, gemcitabine, lomustine, nab-paclitaxel, temozolomide, carboplatin, and combinations thereof (Desai 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”; paragraph 0012 – “In some embodiments, the alkylating agent is administered orally. In some embodiments, the alkylating agent is a nitrosourea compound. In some embodiments, the compound is lomustine”).
Re. claim 38, the combined invention of Gotlib and Chan (hereinafter the combined invention) teaches the method of claim 21 as stated above, but does not explicitly teach the method further comprising the step of: (3) administering at least a second composition to the cancer cells, wherein the second composition comprises at least one chemotherapeutic agent
Desai teaches a similar method of reducing viability of cancer cells (Desai 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 a second 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…”; paragraph 0037 – “The present application also provides methods for treating a CNS disorder (e.g., glioblastoma, epilepsy, cortical dysplasia) in an individual, comprising a) systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising an mTOR inhibitor (e.g., a limus drug, e.g., sirolimus or a derivative thereof) and an albumin; b) administering to the individual a second agent…”),
and wherein the second composition comprises at least one chemotherapeutic agent (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”; paragraph 0012 – “In some embodiments, the alkylating agent is administered orally. In some embodiments, the alkylating agent is a nitrosourea compound. In some embodiments, the compound is lomustine”).
The combined invention and Desai both teach within the field of tumor-treating methods using electric fields, including anti-angiogenic agents. 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, to incorporate the known technique of administering a second chemotherapeutic agent as taught by Desai since such modification would predictably result in increased treatment efficacy in treating targeted cancerous tumors.
Re. claim 39, Desai of the combined invention further teaches wherein the at least one chemotherapeutic agent is selected from the group consisting of lenvatinib, paclitaxel, docetaxel, ifosamide, etoposide, gemcitabine, lomustine, nab-paclitaxel, temozolomide, carboplatin, and combinations thereof (Desai 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”; paragraph 0012 – “In some embodiments, the alkylating agent is administered orally. In some embodiments, the alkylating agent is a nitrosourea compound. In some embodiments, the compound is lomustine”).
Claim(s) 35 is rejected under 35 U.S.C. 103 as being unpatentable over Gotlib (US 20200016067 A1 – hereinafter Gotlib) in view of Chan (US 20170173013 A1 – hereinafter Chan), and in further view of Thorpe (US 20030175276 A1 – Thorpe) [previously cited].
Re. claim 35, the combined invention of Gotlib and Chan (hereinafter the combined invention) teaches the method of claim 9 as stated above, but does not explicitly teach wherein the at least one composition is orally administered to the subject.
Thorpe teaches a similar method of reducing viability of cancer cells (Thorpe abstract - “Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity”). Thorpe further teaches the known technique of administrating at least one composition to the subject, wherein the at least one composition comprises at least one anti-VEGFR-2 antibody, and wherein the at least one composition is orally administered to the subject (Thorpe paragraph 0667 – “Formulations of VEGFR2-blocking, anti-VEGF antibody-based or 2C3-based antibodies or immunoconjugate solutions are easily administered in a variety of dosage forms, such as the type of injectable solutions described above, but other pharmaceutically acceptable forms are also contemplated, e.g., tablets, pills, capsules or other solids for oral administration…”).
The combined invention and Thorpe all teach within the field of methods for reducing viability of cancer cells, particularly with anti-VEGFR-2 antibodies. 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, to incorporate the orally administered anti-VEGFR-2 antibodies as taught by Thorpe, since such modification would predictably result in inhibiting angiogenesis and induce tumor regression (Thorpe paragraph 0004 – “The present invention relates generally to the fields of antibodies, angiogenesis and tumor treatment. More particularly, it provides anti-VEGF antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. Such antibodies inhibit angiogenesis and induce tumor regression”).
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 reached Mon-Fri 7:00am-4:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CARL LAYNO can be reached at 571-272-4949. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANH-KHOA N DINH/Examiner, Art Unit 3796
/CARL H LAYNO/Supervisory Patent Examiner, Art Unit 3796