DETAILED CORRESPONDENCE
Application 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 .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/08/2026 has been entered.
3. Applicant’s amendment to the claims filed on 02/08/2026 in response to the Final Rejection mailed on 08/07/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. Claims 1-2, 5, 7, 12, 15, 17, 19, 25, 27-28, 30, 32, and 34 are pending.
5. Claims 27-28, 30, 32, and 34 stand withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks filed on 02/08/2026 in response to the Final Rejection mailed on 08/07/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 103
7. The rejection of claims 1-2, 5, 7, 12, 15, 19, and 25 under 35 U.S.C. 103 as being unpatentable over Elixir et al. (WO 2004/050898 A2; cited on IDS filed on 04/28/2022) in view of Li et al. (Oncotarget, 2015; cited on PTO-892 mailed 08/07/2025), Blagih et al. (Immunity, 2015; cited on IDS filed on 04/28/2022), and Lee et al. (Cellular Signaling, 2012; cited on IDS filed on 04/28/2022) is withdrawn in favor of the new rejection set forth below.
8. The rejection of claim 17 under 35 U.S.C. 103 as being unpatentable over Elixir et al. (WO 2004/050898 A2; cited on IDS filed on 04/28/2022) in view of Li et al. (Oncotarget, 2015; cited on PTO-892 mailed 08/07/2025), Blagih et al. (Immunity, 2015; cited on IDS filed on 04/28/2022), and Lee et al. (Cellular Signaling, 2012; cited on IDS filed on 04/28/2022) as applied to claims 1-2, 5, 7, 12, 15, 19, and 25 above, and further in view of Frigault et al. (US Patent Application Publication 2018/0371068 A1; cited on IDS filed on 04/28/2022) is withdrawn in favor of the new rejection set forth below.
9. Claims 1-2, 5, 7, 12, 15, 17, 19, and 25 are newly rejected under 35 U.S.C. 103 as being unpatentable over Elixir et al. (WO 2004/050898 A2; cited on IDS filed on 04/28/2022) in view of Li et al. (Oncotarget, 2015; cited on PTO-892 mailed 08/07/2025) and Hildegund et al. (WO 2017/123911 A1; examiner cited). This new grounds of rejection is necessitated upon further consideration of the prior art.
10. Claims 1-2, 5, 7, 12, 15, 17, 19 and 25 are drawn to a method of treating a cancer in a subject, said method comprising: modifying immune cells of the subject in vitro, wherein modifying comprises increasing the AMPK activity of the immune cells relative to unmodified immune cells, wherein the increasing comprises: over-expressing an AMPK protein in the immune cells, exposing the immune cells to an AMPK activator selected from the group consisting of sodium butyrate, trehalose, metformin, phenformin, 5-aminoimidazole-4-carboxamide ribonucleotide, aspirin, A-769662, resveratrol, MT 68-73, PF-06409577, PF-249, 5-(5-hydroxy-isoxazol-3-yl)-furan-2-phosphonic acid, and combinations thereof, wherein the increasing enhances the longevity of the modified immune cells relative to unmodified immune cells; expanding the modified immune cells in vitro; and administering the modified and expanded immune cells to the subject.
11. With respect to claim 1, Elixir et al. teach a method of modifying cells comprising increasing the AMPK activity of the cells to produce modified cells by cloning a transgene encoding a heterologous AMPK polypeptide to overexpress an AMPK protein in the immune cells [see Abstract; p. 2; p. 4, top; p. 34]. Elixir et al. teach wherein the activation of AMPK activity increases longevity of the cells [see p. 20, lines 19-28]. Elixir et al. teach the method wherein the increasing comprises exposing the cells to an AMPK activator such as metformin in a regimen for at least one month, six months, one year, three years, five years or a decade [see p. 7, lines 13-22; p. 8]. Elixir et al. teach the method comprising obtaining the cells from a subject [see p. 3 bottom to top of p. 4], wherein the increasing occurs in vitro and further comprises a step of culturing the modified cells in vitro [see p. 28, bottom; p. 58], and administering the modified cells to a subject, wherein the increasing occurs in vivo [see p. 76, bottom].
With respect to claims 2, 5, and 7, Elixir et al. teach a method of modifying cells comprising increasing the AMPK activity of the cells to produce modified cells [see Abstract; p. 2] and wherein the modified cells can include a transgene encoding a heterologous AMPK polypeptide [see p. 4, top]. Elixir et al. further teach the truncation of AMPKalpha (catalytic subunit) that renders the AMPK constitutively active [see p. 34].
With respect to claim 12, Elixir et al. teach a method of modifying cells comprising increasing the AMPK activity of the cells to produce modified cells [see Abstract; p. 2]. Elixir et al. further teach the truncation of AMPKalpha (catalytic subunit) that renders the AMPK constitutively active [see p. 34]. Regarding the limitation “wherein the enhanced longevity of the modified immune cells is determined by factors selected from the group consisting of…”, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between activation of AMPK activity and its usefulness in enhancing the longevity of the immune cells. Nevertheless, Elixir et al. teach wherein the activation of AMPK activity increases fatty acid oxidation (oxidative metabolism) [see p. 34, bottom].
With respect to claim 19, Elixir et al. teach the method further comprising obtaining the cells from a subject [see p. 3 bottom to top of p. 4].
However, Elixir et al. does not teach the method of claim 1 of treating a cancer in a subject; the method of the claims wherein the cells are immune cells and wherein the immune cells comprise lymphocytes selected from the group consisting of T-cells, CD8+ T-cells, CD4+ T-cells, NK-cells, B-cells, and combinations thereof; the method of claim 17, wherein the lymphocytes comprises T-cells that have been engineered to express one or more immunoreceptors, wherein the one or more immunoreceptors comprise chimeric antigen receptors (CAR) and the method of claim 25, wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, pancreatic cancers, glioblastoma, acute lymphocytic leukemia, chronic myeloid leukemia, lymphomas, leukemias, and combinations thereof.
Li et al. teach that AMPK is an important mediator in maintaining cellular energy homeostasis and that recent epidemiological studies indicate that treatment with metformin, reduces the incidence of cancer [see Abstract]. Li et al. teach that recent studies have shown that in CML, BCL-ABL transformed cells exhibit overly expressed mTOR activity, by which activating AMPK may provide therapeutic advantages [see p. 7367, column 2].
Hildegund et al. teach methods to treat cancer comprising administering to a subject T-cells that have been pretreated ex vivo or in vitro with a fatty acid catabolism promoter to condition the T-cells to use fatty acids rather than glucose for energy production wherein the T-cells have been pretreated in vitro with an AMPK activator [see Abstract; p. 19, lines 8-14]. Hildegund et al. teach genetically modified T-cells expressing chimeric antigen receptors [see p. 18, top]. Hildegund et al. further teach these methods improve the T-cell ability to combat tumor progression in glucose and oxygen deprivation environments such as a tumor [see p. 2, top]. Hildegund et al. further teach wherein the cancer is breast cancer, prostate cancer, and pancreatic cancer [see p. 18, bottom].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Elixir et al., Li et al., and Hildegund et al. in a method of increasing the AMPK activity in immune cells for the treatment of cancer because Elixir et al. teach methods of modifying cells comprising increasing the AMPK activity of the cells to produce modified cells using agonists, recombinant expression of AMPK in cells and administering agonists or cells expressing AMPK to a subject in need thereof that increase the longevity of the cells. Li et al. teach that recent epidemiological studies indicate that treatment with metformin, reduces the incidence of cancer. Hildegund et al. teach methods to treat cancer comprising administering to a subject T-cells that have been pretreated ex vivo or in vitro with an AMPK activator to condition the T-cells to use fatty acids rather than glucose for energy production. One of ordinary skill in the art would have a reasonable expectation of success, a reasonable level of predictability, and would be motivated to combine the teachings of Elixir et al., Li et al., and Hildegund et al. because Li et al. acknowledges that the activation of AMPK activity can reduce incidence of cancer and Hildegund et al. acknowledges that treating T-cells in vitro with an AMPK activator prior to administering to a subject with cancer improve the T-cell ability to combat tumor progression in glucose and oxygen deprivation environments such as a tumor . Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
12. Applicants’ remarks filed on 02/08/2026 in response to the Final Rejection mailed on 08/07/2025 have been fully considered by the examiner; however, they are rendered moot in view of the new rejection set forth above, which is necessitated upon further consideration of the claims.
Conclusion
13. Status of the claims:
Claims 1-2, 5, 7, 12, 15, 17, 19, 25, 27-28, 30, 32, and 34 are pending.
Claims 27-28, 30, 32, and 34 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-2, 5, 7, 12, 15, 17, 19, and 25 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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