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 .
Response to Arguments
Applicant’s arguments, see page 7, filed 06/22/2026, with respect to specification objections have been fully considered and are persuasive. The specification objections have been obviated by Applicant’s newly-submitted abstract. The specification objections have been withdrawn.
Applicant’s arguments, see page 7, filed 06/22/2026, with respect to claim objections have been fully considered and are persuasive. The claim objections have been obviated by amendments to the claims. The claim objections have been withdrawn.
Applicant’s arguments, see pages 7-8, filed 06/22/2026, with respect to 35 U.S.C. 112(a) rejections have been fully considered and are persuasive. The 35 U.S.C. 112(a) rejections have been obviated by amendments to the claims. The 35 U.S.C. 112(a) rejections have been withdrawn.
Applicant’s arguments, see page 8, filed 06/22/2026, with respect to 35 U.S.C. 112(b) rejections have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejections have been obviated by amendments to the claims. The 35 U.S.C. 112(b) rejections have been withdrawn.
Applicant’s arguments, see page 9, filed 06/22/2026, with respect to 35 U.S.C. 112(d) rejections have been fully considered and are persuasive. The 35 U.S.C. 112(d) rejections have been obviated by cancellation of claim 13. The previously-held 35 U.S.C. 112(d) rejections have been withdrawn. However, new 35 U.S.C. 112(d) rejections are now made due to Applicant’s amendments. Please see 35 U.S.C. 112(d) rejections hereinbelow.
Applicant’s arguments, see pages 9-11, filed 06/22/2026, with respect to 35 U.S.C. 102 rejections of claims 3-6, 16, and 21 have been fully considered and are persuasive. The 35 U.S.C. 102 rejections of claims 3-6, 16, and 21 have been obviated by amendments to the claims. The 35 U.S.C. 102 rejections of claims 3-6, 16, and 21 have been withdrawn.
Applicant’s arguments, see pages 10-11, filed 06/22/2026, with respect to the 35 U.S.C. 102 rejection of claim 28 has been fully considered but is not persuasive. The Applicant argues that Weinberg describes inclusion criteria for their study as based on “1st disease progression (RECIST 1.1), ECOG 0-1, no prior surgery or radiation therapy, no electronic medical devices in the upper torso, and absence of brain metastasis”. The Applicant argues that Weinberg therefore discloses treating subjects that had not previously been treated with systemic therapy. The Applicant argues that Weinberg, like Tran, therefore fails to teach the claimed methods at least because Weinberg fails to teach treating a subject “wherein the subject was previously treated for non-small cell lung cancer with systemic therapy.”
This is not found persuasive. Weinberg is directed to TTFields combined with PD-1 inhibitors or docetaxel for 2nd line treatment of non-small cell lung cancer (NSCLC) (Title). The Examiner notes that Weinberg’s disclosure that subjects much have no prior surgery or radiation therapy does not constitute that Weinberg discloses treating subjects that had not previously been treated with systemic therapy. Surgery and radiation treatments are not considered systemic therapies. As previously indicated “systemic therapy” is being interpreted as cancer treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body (National Cancer Institute – please see previously attached) (see pages 3-4 of 3/20/2026 Non-Final Rejection). In fact, Weinberg’s teaching that the first line treatment wasn’t surgery or radiation therapy implies that the first line treatment would have been systemic therapy (e.g., immunotherapy or chemotherapy). Therefore, Examiner disagrees with Applicant’s argument that Weinberg doesn’t teach the added claim limitation “wherein the subject was previously treated for non-small cell lung cancer with systemic therapy” and maintains the 35 U.S.C. 102 rejection of claim 28. Please see 35 U.S.C. 102 rejections below.
Applicant’s arguments, see pages 11-15, filed 06/22/2026, with respect to 35 U.S.C. 103 rejections have been fully considered but they are not persuasive. As the Applicant notes, claim 7 was previously rejected over Tran and Pless. The limitation or previous claim 7 is now recited in independent claims 3 and 4. The Examiner notes that the 35 U.S.C. 103 rejections have been updated to reflect the Applicant’s claim amendments. The Applicant argues that Pless at most teaches administering a chemotherapy (pemetrexed) to a subject that was previously treated with a chemotherapy. The Applicant argues that like Tran, Pless fails to teach or suggest administering an alternating electric field and a checkpoint inhibitor to a subject previously treated for non-small cell lung cancer with systemic therapy. The Applicant argues that the Office Action appears to have overlooked the discussion of Pless, where the authors replacing one chemotherapy with another chemotherapy. The Applicant further argues that one of skill in the art would not have been motivated to combine the subject population taught in Pless with the method of treating in Tran. The Applicant argues that Pless fails to teach or suggest treating a subject with a non-chemotherapy, such as a checkpoint inhibitor, wherein the subject was previously treated with a chemotherapy. The Applicant argues that how one subject population reacts or responds to one therapy (e.g., pemetrexed) does not give any indication how the same subject population would react or respond to a completely different therapy (e.g., a chemotherapy vs. a checkpoint inhibitor). The Applicant argues that the fact that a subject who previously received one chemotherapy may be treated with, or may respond to, a different chemotherapy (e.g., pemetrexed) does not suggest that the same subject would be an ideal candidate for a fundamentally different therapeutic, such as an immune checkpoint inhibitor. The Applicant argues that because chemotherapies and immune checkpoint inhibitors act through different biological mechanisms, Pless’ teaching regarding treating a subject with chemotherapy when the subject has previously undergone chemotherapy would not provide motivation and certainly not a reasonable expectation of success to treat a subject with a checkpoint inhibitor therapy when the subject has previously undergone chemotherapy. The Applicant further argues the Pless fails to provide any teaching or suggestion that the status of a subject having previously received a chemotherapy could predict, enhance, or otherwise indicate responsiveness to a completely different type of therapy, such as an immune checkpoint inhibitors. The Applicant argues that at most, Pless suggests that a prior chemotherapy treatment may be relevant when choosing another chemotherapy, such as pemetrexed. The Applicant again argues that Pless does not provide any motivation to select their subjects previously treated with a chemotherapy for treatment with any non-chemotherapy, much less a checkpoint inhibitor.
This is not found persuasive. The Examiner first notes that with regards to Applicant’s argument that Pless does not teach the limitations of independent claims 3 and 4 including checkpoint inhibitors, Pless was not relied on to teach this limitation. Specifically, Tran was and is relied on to teach the limitation “administering a checkpoint inhibitor to the subject”. Pless was relied upon for the limitation “wherein the subject was previously treated for non-small cell lung cancer with systemic therapy”. The Examiner also disagrees with the Applicant’s assessment of Pless. In particular, the Examiner disagrees with the Applicant’s assessment that Pless at most teaches administering a chemotherapy (pemetrexed) to a subject that was previously treated with a chemotherapy. As previously indicated, Pless teaches Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (see Title and Abstract). The Applicant did not mention Pless’ teaching of TTFields. The Examiner contends that Pless’ teaching of second line treatment including TTFields, following chemotherapy treatment, further makes Pless relevant and analogous art in view of Tran. As previously indicated, Tran teaches the limitation of the independent claims “applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells”. As previously noted, Tran also teach that TTFields were recently approved in combination with chemotherapy for newly diagnosed GBM patients (Par. [0038] of Tran). One of ordinary skill in the art would have therefore concluded that TTFields could be applied after or with chemotherapy, which is further disclosed in Pless. As previously indicated, one of ordinary skill in the art would generally desire trying well-known chemotherapy treatments first before trying newer approved TTFields treatments, such as the TTFields treatments disclosed in Tran and Pless, that have less data for treatment results, including long-term data and potential unforeseen side-effects. The Examiner maintains that Pless’ teaching of first line treatment of chemotherapy (2. Patients and methods (2.1 Patients)) before treatment involving TTFields treatment is ample motivation for combining the teachings of Tran and Pless to render obvious independent claims 3 and 4 under 35 U.S.C. 103. Please see 35 U.S.C. 103 rejections hereinbelow. The Examiner notes that Applicant’s further arguments to 35 U.S.C. 103 rejections of dependent claims involving Addeo and Weinberg are based on the same arguments presented for the independent claims 3-4. Therefore, since these arguments are not found persuasive and the 35 U.S.C. 103 rejections are maintained, the 35 U.S.C. 103 rejections for the claims depending from claim 4 are also maintained. Please see 35 U.S.C. 103 rejections hereinbelow.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8-12 and 14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 8-12 and 14 are written to be dependent on claim 1, which is a canceled claim. Therefore, these claims are in improper dependent form as they fail to further limit the subject matter of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
*For the purposes of examination, claims 8-11 and 14 will be examined as if they were dependent on claim 4. This is what is believed to have been intended by the Applicant.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 28 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Weinberg, et al. (“TTFields combined with PD-A inhibitors or docetaxel for 2nd line treatment of non-small cell lung cancer (NSCLC): Phase 3 LUNAR study” – cited on IDS).
Regarding claim 28, Weinberg teaches a method of treating a subject having cancer (Trial Design – adding TTFields to 2nd line therapies in advance NSCLC will increase overall survival) comprising:
a) applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells (Trial Design – TTFields are applied to the upper torso for at least 18 hours/day), and
b) administering docetaxel to the subject (Trial Design – Docetaxel is given at a standard dose),
wherein the subject was previously treated for non-small cell lung cancer with systemic therapy (Title –; Trial Design – Key inclusion criteria are 1st disease progression (RECIST 1.1), ECOG 0-1, no prior surgery or radiation therapy; Examiner notes that Weinberg teaching 2nd line treatment on patient’s not previously treated with surgery or radiation therapy, necessarily teaches that the 1st line treatment was systemic therapy, such as chemotherapy or immunotherapy).
Therefore, claim 28 is unpatentable over Weinberg, et al.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 3-6, 8, 10, 14, 16, 18, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Tran, et al. (U.S. PGPub No. 2021/0069503 – cited on IDS) in view of Pless, et al. (“A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer” – cited on IDS).
Regarding claim 3, Tran teaches a method of increasing survival from cancer of a subject having cancer (Par. [0010] – methods described herein reduce the viability of cancer cells (i.e., increase survival); Par. [0038]) comprising:
a) applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells (Abstract; Par. [0003]; Par. [0010] – Methods describe herein reduce the viability of cancer cells by applying alternating electric fields to the cancer at a frequency between 100 and 500 kHz for 3 days (alternating electric field necessarily has a field strength); Par. [0053] – The cancer cells can be selected from the group consisting of glioblastoma cells, pancreatic cancer cells, ovarian cancer cells, non-small cell lung cancer (NSCLC) cells, and mesothelioma.), and
b) administering a checkpoint inhibitor to the subject (Par. [0010] – Methods describe herein reduce the viability of cancer cells by applying alternating electric fields to the cancer at a frequency between 100 and 500 kHz for 3 days and administering a checkpoint inhibitor to the cancer cells.; Par. [0011]; Par. [0043]; Par. [0054]). Tran does not explicitly teach the limitation of instant claim 3, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy.
Pless teaches a phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (Title, Abstract). Pless teaches the limitation of instant claim 3, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy (2. Patients and methods (2.1 Patients) – Inclusion criteria were: at least one line of prior chemotherapy).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Pless’ feature of having the subject previously be treated with systemic therapy (e.g., chemotherapy) into Tran’s method, because doing so would allow for the patient to first exhaust the well-known option of trying chemotherapy treatment prior to trying this newer strategy involving applying an alternating electric field. It is noted that Tran does not provide direction either way about whether the patient was treated previously with chemotherapy, but does explain that Tumor Treating Fields (TTFields) was recently approved in combination with chemotherapy for newly diagnosed GBM patients (Par. [0038] of Tran), and so one of ordinary skill in the art would conclude that the electric field could be applied after or with chemotherapy. One of ordinary skill in the art would generally desire to try well-known chemotherapy treatments first before trying newer approved TTFields treatments that have less data for treatment results, including long-term data and potential unforeseen side-effects.
Therefore, claim 3 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 4, Tran teaches a method of treating a subject having cancer (Par. [0010-0011] – Thus, exposing cancer cells to TTFields continuously, discontinuously, or intermittently can make cancer cells susceptible to further treatment by inducing the STING pathway followed by treatment with one or more checkpoint inhibitors and/or other oncology drugs) comprising:
a) applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells (Abstract; Par. [0003]; Par. [0010] – Methods describe herein reduce the viability of cancer cells by applying alternating electric fields to the cancer at a frequency between 100 and 500 kHz for 3 days (alternating electric field necessarily has a field strength); Par. [0053] – The cancer cells can be selected from the group consisting of glioblastoma cells, pancreatic cancer cells, ovarian cancer cells, non-small cell lung cancer (NSCLC) cells, and mesothelioma.), and
b) administering a checkpoint inhibitor to the subject (Par. [0010] – Methods describe herein reduce the viability of cancer cells by applying alternating electric fields to the cancer at a frequency between 100 and 500 kHz for 3 days and administering a checkpoint inhibitor to the cancer cells.; Par. [0011]; Par. [0043]; Par. [0054]). Tran does not explicitly teach the limitation of instant claim 4, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Pless’ feature of having the subject previously be treated with systemic therapy (e.g., chemotherapy) into Tran’s method, because doing so would allow for the patient to first exhaust the well-known option of trying chemotherapy treatment prior to trying this newer strategy involving applying an alternating electric field. It is noted that Tran does not provide direction either way about whether the patient was treated previously with chemotherapy, but does explain that Tumor Treating Fields (TTFields) was recently approved in combination with chemotherapy for newly diagnosed GBM patients (Par. [0038] of Tran), and so one of ordinary skill in the art would conclude that the electric field could be applied after or with chemotherapy. One of ordinary skill in the art would generally desire to try well-known chemotherapy treatments first before trying newer approved TTFields treatments that have less data for treatment results, including long-term data and potential unforeseen side-effects.
Therefore, claim 4 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 5, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 5, that is wherein the checkpoint inhibitor is Nivolumab, Pembrolizumab, or Atezolizumab (Par. [0054] – The checkpoint inhibitor can be selected, for example from the group consisting of ipilimumab, pembrolizumab, and nivolumab.).
Therefore, claim 5 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 6, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 6, that is wherein the cancer is metastatic non-small cell lung cancer (Par. [0053] – The cancer cells can be selected from the group consisting of glioblastoma cells, pancreatic cancer cells, ovarian cancer cells, non-small cell lung cancer (NSCLC) cells, and mesothelioma. In a further aspect, the cancer cells are glioblastoma cells.).
Therefore, claim 6 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 8, Tran, in view of Pless, renders obvious the method of claim 4 *(interpreted as being dependent on claim 4 instead of canceled claim 1 for purposes of examination), as indicated hereinabove. Pless also teaches the limitation of instant claim 8, that is wherein the systemic therapy did not comprise treatment with a checkpoint inhibitor (2. Patients and methods (2.1 Patients) – No mention of using a checkpoint inhibitor with chemotherapy).
Therefore, claim 8 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 10, Tran, in view of Pless, renders obvious the method of claim 4 *(interpreted as being dependent on claim 4 instead of canceled claim 1 for purposes of examination), as indicated hereinabove. Pless also teaches the limitation of instant claim 10, that is wherein the systemic therapy comprised platinum-based-chemotherapy (3. Results (3.1 Patient Characteristics) – the majority (90%) were previously treated with platinum agents).
Therefore, claim 10 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 14, Tran, in view of Pless, renders obvious the method of claim 4 *(interpreted as being dependent on claim 4 instead of canceled claim 1 for purposes of examination), as indicated hereinabove. Pless also teaches the limitation of instant claim 14, that is wherein the non-small cell lung cancer in the subject progressed on or after the previous systemic treatment (1. Introduction – A phase I trial in patients with NSCLC who had progressed after a first line treatment and were eligible for second line pemetrexed was conducted to test the safety profile and tolerability of the proposed TTFields regimen).
Therefore, claim 14 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 16, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 16, that is wherein the frequency of the alternating electric field is between 100 kHz and 1 MHz (Abstract; Par. [0010] – Methods describe herein reduce the viability of cancer cells by applying alternating electric fields to the cancer at a frequency between 100 and 500 kHz for 3 days).
Therefore, claim 16 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 18, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 18, that is wherein the cancer is metastatic non-small cell lung cancer (Par. [0053] – The cancer cells can be selected from the group consisting of glioblastoma cells, pancreatic cancer cells, ovarian cancer cells, non-small cell lung cancer (NSCLC) cells, and mesothelioma. In a further aspect, the cancer cells are glioblastoma cells.), wherein the frequency of the alternating electric field is 150 kHz (Abstract – a frequency between 100 and 500 kHz; Par. [0003]).
Tran does not explicitly teach the limitations of instant claim 18, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy including platinum-based-chemotherapy, and wherein the non- small cell lung cancer in the subject progressed on or after the previous systemic treatment.
Pless teaches a phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (Title, Abstract). Pless teaches the limitation of instant claim 18, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy (2. Patients and methods (2.1 Patients) – Inclusion criteria were: at least one line of prior chemotherapy) including platinum-based-chemotherapy (3. Results (3.1 Patient Characteristics) – the majority (90%) were previously treated with platinum agents), and wherein the non- small cell lung cancer in the subject progressed on or after the previous systemic treatment (1. Introduction – A phase I trial in patients with NSCLC who had progressed after a first line treatment and were eligible for second line pemetrexed was conducted to test the safety profile and tolerability of the proposed TTFields regimen).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Pless’ feature of having the subject previously be treated with systemic therapy (e.g., chemotherapy) into Tran’s method, because doing so would allow for the patient to first exhaust the well-known option of trying chemotherapy treatment prior to trying this newer strategy involving applying an alternating electric field. It is noted that Tran does not provide direction either way about whether the patient was treated previously with chemotherapy, but does explain that Tumor Treating Fields (TTFields) was recently approved in combination with chemotherapy for newly diagnosed GBM patients (Par. [0038] of Tran), and so one of ordinary skill in the art would conclude that the electric field could be applied after or with chemotherapy. One of ordinary skill in the art would generally desire to try well-known chemotherapy treatments first before trying newer approved TTFields treatments that have less data for treatment results, including long-term data and potential unforeseen side-effects.
Therefore, claim 18 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 20, Tran, in view of Pless, renders obvious the method of claim 18, as indicated hereinabove. Tran also teaches the limitation of instant claim 20, that is wherein the checkpoint inhibitor of the systemic therapy was a PD-1/PD-L1 inhibitor (Par. [0054] – The checkpoint inhibitor can be selected, for example from the group consisting of ipilimumab, pembrolizumab, and nivolumab – It is noted that pembrolizumab and nivolumab are PD-1/PD-L1 inhibitors).
Therefore, claim 20 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 21, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 21, that is wherein applying the alternating electric field to the target site of the subject for the period of time comprises applying the electric field to the target site continuously for an average of at least 18 hours per day (Par. [0004] – The therapy is designed to be worn for as many hours as possible throughout the day and night; Par. [0041] – The alternating electric fields can be applied to the cancer cells continuously for 3 to 10 days).
Therefore, claim 21 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 22, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran does not explicitly teach the limitation of instant claim 22, that is wherein applying the alternating electric field to the target site of the subject for the period of time comprises applying the electric field to the target site continuously until progression of the cancer or until intolerable toxicity.
Pless teaches a phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (Title, Abstract). Pless teaches the limitation of instant claim 22, that is wherein applying the alternating electric field to the target site of the subject for the period of time comprises applying the electric field to the target site continuously until progression of the cancer or until intolerable toxicity (2.3 Treatment – Treatment was terminated upon disease progression or excessive toxicity).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Pless’ feature of applying the electric field until progression of the cancer or until intolerable toxicity into Tran’s method, because it would be understood that subjecting the patient to further electric field treatment would be unnecessary and non-beneficial once the cancer shows to build up an intolerance or the patient is experiencing intolerable toxicity. One of ordinary skill in the art would recognize that this is a well-understood and appropriate time to discontinue treatment.
Therefore, claim 22 is unpatentable over Tran, et al. and Pless, et al.
Claims 9, 11-12, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Tran, et al. (U.S. PGPub No. 2021/0069503 – cited on IDS) and Pless, et al. (“A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer” – cited on IDS), further in view of Addeo, et al. (Chemotherapy in Combination With Immune Checkpoint Inhibitors for the First-Line Treatment of Patients With Advanced Non-small Cell Lung Cancer: A Systematic Review and Literature-Based Meta-Analysis).
Regarding claim 9, Tran, in view of Pless, renders obvious the method of claim 4 *(interpreted as being dependent on claim 4 instead of canceled claim 1 for purposes of examination), as indicated hereinabove. Pless does not explicitly teach the limitation of claim 9, that is wherein the systemic therapy comprised treatment with a checkpoint inhibitor.
Addeo teaches chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer (Title, Abstract). Addeo teaches the limitation of instant claim 9, that is wherein the systemic therapy comprised treatment with a checkpoint inhibitor (Background – checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC)).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Addeo’s feature of the first line chemotherapy comprising treatment with a checkpoint inhibitor with Pless’ first line chemotherapy treatment, because doing so has shown to increase Overall Survival (OS) (Addeo – Results).
Therefore, claim 9 is unpatentable over Tran, et al., Pless, et al., and Addeo, et al.
Regarding claim 11, Tran, in view of Pless, rendered obvious the method of claim 4 *(interpreted as being dependent on claim 4 instead of canceled claim 1 for purposes of examination), as indicated hereinabove. Pless also teaches the limitation of instant claim 11, that is wherein the systemic therapy comprised chemotherapy (2. Patients and methods (2.1 Patients) – Inclusion criteria were: at least one line of prior chemotherapy). Pless does not explicitly teach the limitation of instant claim 11, that is wherein the systemic therapy comprised treatment with a checkpoint inhibitor.
Addeo teaches chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer (Title, Abstract). Addeo teaches the limitation of instant claim 9, that is wherein the systemic therapy comprised treatment with a checkpoint inhibitor (Background – checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC)).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Addeo’s feature of the first line chemotherapy comprising treatment with a checkpoint inhibitor with Pless’ first line chemotherapy treatment, because doing so has shown to increase Overall Survival (OS) (Addeo – Results).
Therefore, claim 11 is unpatentable over Tran, et al., Pless, et al., and Addeo, et al.
Regarding claim 12, Tran, in view of Pless and Addeo, renders obvious the method of claim 11, as indicated hereinabove. Pless also teaches the limitation of instant claim 12, that is wherein chemotherapy comprised platinum-based-chemotherapy (3. Results (3.1 Patient Characteristics) – the majority (90%) were previously treated with platinum agents).
Therefore, claim 12 is unpatentable over Tran, et al., Pless, et al., and Addeo, et al.
Regarding claim 19, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran also teaches the limitation of instant claim 19, that is wherein the cancer is metastatic non-small cell lung cancer (Par. [0053] – The cancer cells can be selected from the group consisting of glioblastoma cells, pancreatic cancer cells, ovarian cancer cells, non-small cell lung cancer (NSCLC) cells, and mesothelioma. In a further aspect, the cancer cells are glioblastoma cells.),
wherein the frequency of the alternating electric field is 150 kHz (Abstract – a frequency between 100 and 500 kHz; Par. [0003]), and
wherein the checkpoint inhibitor administered in the step of administering the therapeutically effective amount of the checkpoint inhibitor to the subject is Pembrolizumab (Par. [0054] – The checkpoint inhibitor can be selected, for example from the group consisting of ipilimumab, pembrolizumab, and nivolumab.)
Tran does not explicitly teach the limitation of instant claim 19, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy including treatment with a checkpoint inhibitor and platinum- based-chemotherapy, and wherein the non-small cell lung cancer in the subject progressed on or after the previous systemic treatment.
Pless teaches a phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (Title, Abstract). Pless also teaches the limitations of instant claim 19, that is wherein the subject was previously treated for non-small cell lung cancer with systemic therapy (2. Patients and methods (2.1 Patients) – Inclusion criteria were: at least one line of prior chemotherapy) including treatment with platinum- based-chemotherapy (3. Results (3.1 Patient Characteristics) – the majority (90%) were previously treated with platinum agents), and wherein the non-small cell lung cancer in the subject progressed on or after the previous systemic treatment (1. Introduction – A phase I trial in patients with NSCLC who had progressed after a first line treatment and were eligible for second line pemetrexed was conducted to test the safety profile and tolerability of the proposed TTFields regimen).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Pless’ feature of having the subject previously be treated with systemic therapy (e.g., chemotherapy) into Tran’s method, because doing so would allow for the patient to first exhaust the well-known option of trying chemotherapy treatment prior to trying this newer strategy involving applying an alternating electric field. It is noted that Tran does not provide direction either way about whether the patient was treated previously with chemotherapy, but does explain that Tumor Treating Fields (TTFields) was recently approved in combination with chemotherapy for newly diagnosed GBM patients (Par. [0038] of Tran), and so one of ordinary skill in the art would conclude that the electric field could be applied after or with chemotherapy. One of ordinary skill in the art would generally desire to try well-known chemotherapy treatments first before trying newer approved TTFields treatments that have less data for treatment results, including long-term data and potential unforeseen side-effects.
Neither Tran nor Pless explicitly teach the limitation of instant claim 19, that is wherein the systemic therapy includes treatment with a checkpoint inhibitor.
Addeo teaches chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer (Title, Abstract). Addeo teaches the limitation of instant claim 19, that is wherein the systemic therapy includes treatment with a checkpoint inhibitor (Background – checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC)).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Addeo’s feature of the first line chemotherapy comprising treatment with a checkpoint inhibitor with Pless’ first line chemotherapy treatment, because doing so has shown to increase Overall Survival (OS) (Addeo – Results).
Therefore, claim 19 is unpatentable over Tran, et al., Pless, et al., and Addeo, et al.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Tran, et al. (U.S. PGPub No. 2021/0069503 – cited on IDS) and Pless, et al. (“A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer” – cited on IDS), further in view of Weinberg, et al. (“TTFields combined with PD-A inhibitors or docetaxel for 2nd line treatment of non-small cell lung cancer (NSCLC): Phase 3 LUNAR study” – cited on IDS).
Regarding claim 24, Tran, in view of Pless, renders obvious the method of claim 4, as indicated hereinabove. Tran does not explicitly teach the limitation of instant claim 24, that is wherein the method is further comprising administering docetaxel to the subject.
Weinberg teaches TTFields combined with PD-1 inhibitors or docetaxel for 2nd line treatment of non-small cell lung cancer (NSCLC) (Title). Weinberg teaches the limitation of instant claim 24, that is wherein the method is further comprising administering docetaxel to the subject (Trial Design – The primary endpoint is superiority in OS between patients treated with TTFields in combination with either docetaxel or PD-1 inhibitors, compared to docetaxel or PD-1 inhibitors alone. A co-primary endpoint compares the OS in patients treated with TTFields and docetaxel to those treated with PD-1 inhibitors alone in a non-inferiority analysis.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented Weinberg’s method step of administering docetaxel to the subject into Tran’s method because doing so is a considered alternative to using a PD-1 inhibitor (e.g., nivolumab or pembrolizumab), as used in Tran’s method, in combination with Tumor Treating Fields (TTFields). Therefore, one of ordinary skill in the art would consider combining TTFields while administering docetaxel to be a known treatment.
Therefore, claim 24 is unpatentable over Tran, et al., Pless, et al., and Weinberg, et al.
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.
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/MICHAEL T. HOLTZCLAW/Primary Examiner, Art Unit 3796
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