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 Statements filed 01/08/2025 (x2) have been considered by the Examiner.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The disclosure is objected to because of the following informalities:
Abstract is ~290 words in length, and is therefore too long. Abstract is limited to a single paragraph within the range of 50 to 150 words in length.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 3-4 and 28 are objected to because of the following informalities:
“a.” and “b.” must be removed. According to MPEP 608.01(m), each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Appropriate correction is required.
Claim Interpretation
The term “checkpoint inhibitor” is described in the Applicant’s specification as a type of immunotherapy, approved for the treatment of different cancers such as melanoma, cervical, colorectal, and lung cancer (Par. [0004]). Applicant also explains that a “checkpoint inhibitor” is a drug that blocks checkpoint proteins such as CTLA-4, PD-1, and PD-L1 (Par. [0004]).
It is also noted that the term “systemic therapy” is interpreted using its well-known meaning relating to cancer treatment. That is, “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 attached).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 3 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for increasing a subject’s chances of survival from cancer (Par. [0089] of Applicant’s Specification), does not reasonably provide enablement for increasing overall survival of a subject who has cancer. For instance, the Applicant’s specification does not reasonably provide enablement for increasing a cancer patient’s survival from a heart attack or automobile accident. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The Applicant’s specification is not enabling for the claim limitation of instant claim 3 of “A method of increasing survival of a subject having cancer”. The Wands factors detailed in MPEP 2164.01(a) have been considered. For example, (A) the breadth of the claims was considered. The breadth associated with “increasing survival of a subject having cancer” is very large and encapsulates many subcategories (i.e., survival from cancer, general survival, survival from a heart attack, survival from an automobile accident, survival from a freak accident, etc.). Also, (G) the existence of working examples has been considered. The limited examples of increasing survival from cancer in the Applicant’s specification (Par. [0089] – the disclosed methods of increasing survival of a subject having non-small cell lung cancer increases survival by 4, 5, 6, 7, 8, 9 or more months when compared to a subject not treated according to the disclosed methods) are not enabling for this broad limitation encapsulating survival from other non-cancer causes. An excessive amount of experimentation (Wands Factor (H)) would be necessary to make or use the invention that is commensurate with the scope of increasing survival for a cancer patient from all other non-cancer causes. The limited examples of increasing survival of a subject from cancer specifically do not provide enough direction (Wands Factor (F)) to extrapolate out to the numerous non-cancer causes of death that can affect a patient’s survival.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-14, 16, 18-22, 24, and 28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “therapeutically effective amount of a checkpoint inhibitor” in claim 3 (line 5) is a relative term which renders the claim indefinite. The term “therapeutically effective amount of a checkpoint inhibitor” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how much of a checkpoint inhibitor would need to be administered to the subject in order to be considered a “therapeutically effective amount”.
The term “therapeutically effective amount of a checkpoint inhibitor” in claim 4 (line 5) is a relative term which renders the claim indefinite. The term “therapeutically effective amount of a checkpoint inhibitor” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how much of a checkpoint inhibitor would need to be administered to the subject in order to be considered a “therapeutically effective amount”.
Claim 12 recites the limitation “chemotherapy” in line 2, whereas chemotherapy was already introduced in a claim that claim 12 depends from (claim 11). It is unclear whether the Applicant intended to claim the same or a different chemotherapy. Consider changing to “the chemotherapy”.
The term “therapeutically effective amount of a checkpoint inhibitor” in claim 28 (line 5) is a relative term which renders the claim indefinite. The term “therapeutically effective amount of a checkpoint inhibitor” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how much of a checkpoint inhibitor would need to be administered to the subject in order to be considered a “therapeutically effective amount”.
*All other claims are rejected due to their dependency on a rejected claim.
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.
Claim 13 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. Claim 13 is identical to claim 9, and therefore fails to further limit the subject matter of the claim upon which it depends since claim 9 already limits the subject matter of claim 7 in the same way. 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.
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.
Claims 3-6, 16, and 21 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Tran, et al. (U.S. PGPub No. 2021/0069503 – cited on IDS).
Regarding claim 3, Tran teaches a method of increasing survival 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 therapeutically effective amount of 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]).
Therefore, claim 3 is unpatentable over Tran, 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 therapeutically effective amount of 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]).
Therefore, claim 4 is unpatentable over Tran, et al.
Regarding claim 5, Tran teaches the method of claim 4, 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.
Regarding claim 6, Tran teaches the method of claim 4, 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.
Regarding claim 16, Tran teaches the method of claim 4, 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.
Regarding claim 21, Tran teaches the method of claim 4, 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.
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 a therapeutically effective amount of docetaxel to the subject (Trial Design – Docetaxel is given at a standard dose).
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 7-8, 10, 14, 18, 20, and 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 7, Tran teaches the method of claim 6, as indicated hereinabove. Tran does not explicitly teach the limitation of instant claim 7, 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 7, 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 7 is unpatentable over Tran, et al. and Pless, et al.
Regarding claim 8, Tran, in view of Pless, renders obvious the method of claim 7, 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 7, 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 7, 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 18, Tran teaches the method of claim 4, 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 22, Tran teaches 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, 11-13, 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 7, 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 7. 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 13, Tran, in view of Pless, renders obvious the method of claim 7, as indicated hereinabove. Pless does not explicitly teach the limitation of claim 13, 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 13, 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 13 is unpatentable over Tran, et al., Pless, et al., and Addeo, et al.
Regarding claim 19, Tran teaches the method of claim 4, 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) 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 teaches 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. and Weinberg, et al.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Sharma (U.S. PGPub No. 2022/0288407)
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/MICHAEL T. HOLTZCLAW/Primary Examiner, Art Unit 3796