DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Information Disclosure Statement
2. The Information Disclosure Statements submitted on 28 March 2024 and 15 October 2024 have been considered by the Examiner.
Claim Objections
3. Claims 2, 3, 11, 12, and 20 are objected to because of the following informalities.
Claims 2, 11, and 20 recite “applied voltage of at least 50 V p2p”. The Examiner respectfully submits that the acronym “p2p” should be defined.
Claims 3 and 12 recite “MHC Class 1 expression”. The Examiner respectfully submits that the acronym “MHC” should be defined.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
4. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
5. Claims 1, 9, 10, and 18 are rejected under 35 U.S.C. 102 (a) (1) and (a) (2) as being anticipated by Narain et al. (US 2021/0322339 A1).
Regarding claims 1 and 10, Narain teaches a method of treating cancer in a subject ([abstract, 0178-0179]) and a method of reducing a volume of a tumor and/or preventing an increase of volume of the tumor ([abstract, 0179]), wherein the tumor is present in a body of a living subject and includes a plurality of cancer cells ([0179]), the method comprising the steps of:
(1) applying an alternating electric field to a target region of the subject for a period of time (the additional cancer therapies consists of applying an alternating electric field and administering a biologic anticancer agent [0177-0180, 0184]); and
(2) administering at least one composition to the subject, wherein the at least one composition comprises at least one natural killer (NK) cell (the additional cancer therapies consists of applying an alternating electric field and administering a biologic anticancer agent [0177-0180, 0184]. Specifically, the biologic anticancer agent is an interferon that stimulates natural killer (NK) cells to fight cancer cells [0180, 0183, 0184]).
Regarding claims 9 and 18, Narain teaches wherein the cancer is glioblastoma ([0179]).
Claim Rejections - 35 USC § 103
6. 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.
7. Claims 2, 7-8, 11, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Narain et al. in view of Schmidt (US 2020/0330758 A1).
Regarding claims 2 and 11, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach 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;
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the target region of the subject;
the alternating electric field is induced by an applied voltage of at least 50 V p2p; and
the period of time that the alternating electric field is applied is at least about 50% of at least about a 24 consecutive hour time period.
The prior art by Schmidt is analogous to Narain, as they both teach an alternating electric field therapy to treat a cancerous tumor ([abstract, 0049, 0126-0128]).
Schmidt 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 (the alternating electric field may range from 50 Khz to 1 MHz [0049, 0069]); and
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the target region of the subject (the alternating electric field may have a field strength of at least about 1 V/cm [0049, 0068]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify the Narain’s alternating electric field to have a frequency ranging from 50 kHz to about 1 MHz and a field strength of about 1 V/cm, as further taught by Schmidt. The advantage of such modification will enhance the treatment of the cancerous tumor by causing mitotic synchronization within a portion of the cancerous cell population (see paragraphs [0007, 0049-0050, 0068-0069] by Schmidt).
Regarding claims 7 and 16, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach wherein steps (1) and (2) are performed wholly or partially sequentially, and wherein the at least one composition is administered after the application of the alternating electric field has begun.
However, Schmidt teaches wherein steps (1) and (2) are performed wholly or partially sequentially, and wherein the at least one composition is administered after the application of the alternating electric field has begun (the agent or composition may be administered after the alternating electric field therapy has begun [0007, 0126-0128]. Similar to Narain, Schmidt also teaches the agents to include interferons [0126-0128]. As stated previously in claims 1, Narain teaches that the interferons stimulate natural killer (NK) cells to fight cancer cells [0180, 0184]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify Narain’s composition to be administered after the application of alternating electric field has begun, as taught by Schmidt. The advantage of such modification will enhance the treatment of the cancerous tumor by causing mitotic synchronization within a portion of the cancerous cell population (see paragraphs [0007, 0126-0128] by Schmidt).
Regarding claims 8 and 17, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach wherein steps (1) and (2) are repeated one or more times.
However, Schmidt teaches wherein steps (1) and (2) are repeated one or more times (the compositions or agents may be administered after one or more alternating electric fields have been applied or removed [0007, 0126-0128]. In this case, a first alternating electric field may be applied for 1 minute to 24 hours and then a first agent will be administered [0007-0008, 0126-0128]. Furthermore, a second alternating electric field may be applied for 1 minute to 24 hours and then a second agent will be administered [0007-0008, 0126-0128]. Similar to Narain, Schmidt also teaches the agents to include interferons [0126-0128]. As stated previously in claims 1 and 10, Narain teaches that the interferons stimulate natural killer (NK) cells to fight cancer cells [0180, 0184]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify Narain’s method to consist of repeating steps (1) and (2), as taught by Schmidt. The advantage of such modification will enhance the treatment of the cancerous tumor by causing mitotic synchronization within a portion of the cancerous cell population (see paragraphs [0007-0008, 0126-0128] by Schmidt).
8. Claims 4-5 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Narain et al. in view of Swaminathan et al. (WO 2022/236181 A1, with citations to the corresponding US Publication No. 2025/0027162 A1).
Regarding claims 4 and 13, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach wherein the at least one NK cell comprises at least one autologous NK cell.
The prior art by Swaminathan is analogous to Narain, as they both teach a method for treating cancer ([0114, 0116]).
Swaminathan teaches wherein the at least one NK cell comprises at least one autologous NK cell ([0101]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify Narain’s method to consist of an autologous NK cell, as taught by Swaminathan. The advantage of such modification may enhance or improve the cancer treatment (see paragraphs [0101, 0114] by Swaminathan).
Regarding claims 5 and 14, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach wherein the at least one NK cell comprises at least one allogeneic NK cell.
However, Swaminathan teaches wherein the at least one NK cell comprises at least one allogeneic NK cell ([abstract, 0114, 0200]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify Narain’s method to consist of an allogeneic NK cell, as taught by Swaminathan. The advantage of such modification may enhance or improve the cancer treatment (see the [abstract] and paragraphs [0114, 0200] by Swaminathan).
9. Claims 6 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Narain et al. in view of Chapman et al. (US 2017/0276679 A1).
Regarding claims 6 and 15, Narain teaches the method of claim 1 and the method of claim 15. Narain does not explicitly teach wherein at least one of:
the at least one NK cell is derived from ex vivo differentiation of pluripotent stem cells;
the at least one NK cell is derived from an interleukin-2 (IL-2) dependent cell line; and/or
the at least one NK cell comprises a chimeric antigen receptor-engineered NK (CAR-NK) cell.
The prior art by Chapman is analogous to Narain, as they both teach a method of treating cancer cells ([0002, 0012, 0065]).
Chapman teaches at least one of:
wherein the at least one NK cell comprises a chimeric antigen receptor-engineered NK (CAR-NK) cell ([0277]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify the Narain’s method to consist of a chimeric antigen receptor engineered NK cell, as taught by Chapman. The advantage of such modification may enhance the treatment of cancer cells (see paragraphs [0002, 0012, 0065, 0277] by Chapman).
10. Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Narain et al. in view of Cheung (US 2004/0001860 A1).
Regarding claim 19, Narain teaches a method ([abstract, 0178-0179]), the method comprising the steps of:
(1) applying an alternating electric field to a target region of the subject for a period of time (the additional cancer therapies consists of applying an alternating electric field and administering a biologic anticancer agent [0177-0180, 0184]); and
(2) administering at least one composition to the subject, wherein the at least one composition comprises at least one natural killer (NK) cell (the additional cancer therapies consists of applying an alternating electric field and administering a biologic anticancer agent [0177-0180, 0184]. Specifically, the biologic anticancer agent is an interferon that stimulates natural killer (NK) cells to fight cancer cells [0180, 0184]).
Although Narain teaches combination of applying the alternating electric field and administering the at least one composition to the subject (the additional cancer therapies consists of applying an alternating electric field and administering a biologic anticancer agent [0177-0180, 0184]), Narain does not explicitly teach wherein administration of the alternating electric field increases the cytotoxicity of the NK cells against cancer cells in the subject when compared to the administration of NK cells to the subject in the absence of alternating electric field application.
The prior art by the Cheung is analogous to Narain, as they both alternating electric fields and compositions (e.g., agents) that are administered to a patient to treat cancer ([abstract, 0002, 0011, claim 1]).
Cheung teaches wherein administration of the alternating electric field increases the cytotoxicity of the NK cells against cancer cells in the subject when compared to the administration of NK cells to the subject in the absence of alternating electric field application (the composition comprises a plurality of yeast cells that are cultured in the presence of an alternating electric field to increase the cytotoxicity of natural killer cells in a subject (e.g., human or mammal) [abstract, 0011, claim 1]. In comparison, the yeast cells that are not cultured in the presence of an alternating electric field do not increase the cytotoxicity of natural killer cells in a subject [claim 1]. The Examiner respectfully submits that the NK cells improve the subject’s immune functions to fight against cancer cells [abstract, 0002, 0011]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify Narain’s administration of the alternating electric field to increase the cytotoxicity of the NK cells against the cancer cells in the subject when compared to the administration of NK cells to the subject in the absence of alternating electric field application, as taught by Cheung. The advantage of such modification will improve the subject’s immune functions against cancer cells, viral infections, or bacterial infections by increasing the activity levels of the NK cells (see the [abstract], paragraphs [0002, 00011], and [claim 1] by Cheung).
11. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Narain et al. in view of Cheung, further in view of Schmidt.
Regarding claim 20, Narain in view of Cheung suggests the method of claim 19. Narain and Cheung do not explicitly teach 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;
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the target region of the subject;
the alternating electric field is induced by an applied voltage of at least 50 V p2p; and
the period of time that the alternating electric field is applied is at least about 50% of at least about a 24 consecutive hour time period.
The prior art by Schmidt is analogous to Narain, as they both teach an alternating electric field therapy to treat a cancerous tumor ([abstract, 0049, 0126-0128]).
Schmidt 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 (the alternating electric field may range from 50 Khz to 1 MHz [0049, 0069]); and
the alternating electric field has a field strength of at least about 1 V/cm in at least a portion of the target region of the subject (the alternating electric field may have a field strength of at least about 1 V/cm [0049, 0068]).
Therefore, it would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to modify the alternating electric field suggested by Narain in view of Cheung to have a frequency ranging from 50 kHz to about 1 MHz and a field strength of about 1 V/cm, as further taught by Schmidt. The advantage of such modification will enhance the treatment of the cancerous tumor by causing mitotic synchronization within a portion of the cancerous cell population (see paragraphs [0007, 0049-0050, 0068-0069] by Schmidt).
Allowable Subject Matter
12. Claims 3 and 12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The following description demonstrates how the prior art of record fails to suggests the corresponding claims.
Regarding claims 3 and 12, Narain teaches the method of claim 1 and the method of claim 10. Narain does not explicitly teach wherein the alternating electric field is applied to the target region of the subject for a period of time sufficient to reduce MHC Class I expression in the cancer cells compared to control cancer cells that have not been exposed to alternating electric fields.
The prior art by Voloshin-Sela (US 2021/0395722 A1) is analogous to Narain, as they both teach a method of applying alternating electric fields to treat cancer cells ([0048, 0066-0067]).
Voloshin-Sela teaches wherein the alternating electric field is applied to the target region of the subject for a period of time sufficient to increase MHC Class I expression in the cancer cells (the tumor treating fields (TTFields) consist of alternating electric fields which are applied to cause an enrichment or upregulation in MHC-binding [abstract, 0002, 0137]).
However, Narain and Voloshin-Sela do not explicitly teach wherein the alternating electric field is applied to the target region of the subject for a period of time sufficient to reduce MHC Class I expression in the cancer cells compared to control cancer cells that have not been exposed to alternating electric fields.
The Examiner concludes that prior art does not provide the requisite teaching, suggestion, and motivation to suggest the recited claim limitation. Therefore, the inventive features recited in the pending claims are not disclosed by the prior art and are not suggested by an obvious combination of the most analogous prior art elements.
Conclusion
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA BRENDON SOLOMON whose telephone number is (571)270-7208. The examiner can normally be reached on 7:30am -4:30pm.
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/JOSHUA BRENDON SOLOMON/Examiner, Art Unit 3792
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