DETAILED ACTION
This office action is in response to applicant’s filing dated September 2, 2025.
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 .
Status of claims
Claims 1, 6 - 9, and 14 - 27 are pending in the instant application. Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on September 2, 2025 are acknowledged. Acknowledgement is made of Applicant's amendment of 1, 6, 8, 9, 14, and 15; cancelation of claims 2-5, and 10-13 and addition of new claims 17-27.
Claims under consideration in the instant office action are claims 1, 6 - 9, and 14 - 27.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on September 2, 2025, have been fully considered.
Acknowledgement is made of the Applicant’s amendment of claim 15 as shown herein: “The method of claim 9, wherein the chemotherapy composition is selected from FOLFIRINOX[…]”.
Accordingly, an objection of claim 15, for containing a typographical error is withdrawn.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
Claim Rejections - 35 USC § 103
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 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.
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.
Claims 1, 6 - 9, and 14 - 27 are rejected under 35 U.S.C. 103 as being unpatentable over Hendifar (WO 2021/163072 A1, priority application is US provisional No.62/972,345, filed February 10, 2020)
Instant claims are drawn to a composition and a method for the treatment of pancreatic cancer, such as exocrine (e.g. adenocarcinoma) and neuroendocrine pancreatic cancer (e.g. pancreatic neuroendocrine tumors (NETs)), where the method is comprising administering to the subject in need an effective amount of said composition, where the composition comprises an MK2 inhibitor, and an effective amount of chemotherapy composition, wherein an MK2 inhibitor is ATI-450 and the chemotherapy composition is at least one of folinic acid, 5-FU, irinotecan and oxaliplatin or any combination thereof. The chemotherapy composition further comprises gemcitabine, nab-paclitaxel, or a combination thereof.
Hendifar teaches a composition and method of treating pancreatic cancer in a subject in need thereof, comprising administering one or more MAPK pathway inhibitors to the subject, wherein the subject has a mutation in one or more genes in the MAPK signaling pathway (page 2, [0006]), where MAPK pathway inhibitor is ATI-450 (page 2, [0010] and claim 10). The method, taught by Hendifar, further comprises administering to the subject one or more chemotherapy drugs (e.g. 5-fluorouracil or paclitaxel), one or more PD-1 inhibitors or PD-L1 inhibitors, both a chemotherapy drug and a PD-1 inhibitor, or both a chemotherapy drug and a PD-L1 inhibitor (page 14, [0077] and [0078]). Hendifar teaches the method, useful for treating pancreatic adenocarcinoma, acinar cell carcinoma, mixed acinar/neuroendocrine carcinoma, or solid pseudopapillary neoplasm (page 12, [0059]).
Furthermore, Hendifar teaches an FDA approved therapy for treating specifically PC (pancreatic cancer) with FOLFIRINOX (combination of FOLinic acid, 5-Fluorouracil, IRINotecan and Oxaliplatin) or gemcitabine with nab-paclitaxel (page 1, [0004]).
Hendifar does not explicitly teach a combination therapy comprising ATI-450 and chemotherapy composition FOLFIRINOX or gemcitabine/nab-paclitaxel. However, since the method taught by Hendifar is comprising administering to the subject MAPK pathway inhibitor (e.g. ATI-450) and further comprising administering one or more chemotherapy drugs where the term “further” can be interpreted as “additional” (https://onelook.com/?w=further&related=1), where FOLFIRINOX or gemcitabine/nab-paclitaxel are known chemotherapy compositions, the use of MAPK inhibitor (ATI-450) in combination with chemotherapy regimen (e.g. FOLFIRINOX or gemcitabine/nab-paclitaxel) is suggested by Hendifar.
Moreover, since prior art teaches an agent ATI-450 is effective in the method of treatment of pancreatic cancer e.g. adenocarcinoma or acinar/neuroendocrine carcinoma, and a chemotherapy composition FOLFIRINOX or gemcitabine/nab-paclitaxel is an effective therapy for treatment of pancreatic cancer generically, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine known in the art compositions and apply them in combination in a method of treatment of pancreatic cancer since the prior art teaches methods of treatment with ATI-450 and chemotherapy combinations FOLFIRINOX or gemcitabine/nab-paclitaxel individually are effective therapies against pancreatic cancer. MPEP 2144.06 (I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
The one of ordinary skills would be motivated to do so in search of a more effective method of treatment of patients suffering from pancreatic cancer with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- Hendifar discloses methods for treating pancreatic cancers with specific BRAF mutations, but fails to provide any data or even to suggest that these methods would be effective for all pancreatic cancers;
- Hendifar merely discloses ATI-450, a p38MAPK/MK2 inhibitor, amongst a laundry list of MAPK inhibitors and discloses FOLFIRINOX as a current treatment for pancreatic cancer, there is no disclosure or suggestion of combining FOLIFIRINOX and ATI-450 for the treatment of PDAC;
- the instant application discloses that MK2 inhibition by ATI-450 augments the efficacy of the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin in Human PDAC Model and KPPC Mice by inactivating heat-shock protein 27 (Hsp27), which activation is a pro-survival mechanism following treatment with the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin in PDAC and which activation enables the cells to tolerate the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin (see paragraph [0127] of the instant publication and FIGS. 1F and 1G);
- Hendifar fails to teach the protective effect of Hsp27 in PDAC cells upon treatment with a chemotherapy agent, nor does Hendifar teach that Hsp27 can be inactivated via the inhibition of MK2;
- based upon the disclosure of Hendifar, one of skill in the art would not be aware of the protective effect of Hsp27 and therefore would not know to select an MK2 inhibitor (in this case ATI-450) to enhance the effects of the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin and thus one of skill in the art would not turn to the disclosure of Hendifar when seeking to develop the claimed invention.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, Hendifar teaches a method of treating pancreatic cancer mediated by mutation in one or more genes in the MAPK signaling pathway, where the method comprises administering to the subject in need MAPK pathway inhibitors and further comprises administering to the subject one or more chemotherapy drugs. These teachings of Hendifar clearly suggest that MAPK pathway inhibitors can be used in combination with chemotherapy. Furthermore, prior art teaches that MAPK pathway inhibitors and chemotherapeutic regimens are effective in treating pancreatic cancer individually, which gives to the skilled artisan reasonable expectation of success if said drugs will be used in combination.
In the list of known MAPK pathway inhibitors Hendifar names ATI-450. Thus, teachings of Hendifar clearly indicate that ATI-450, acting as MAPK pathway inhibitor is an effective agent in treating pancreatic cancer, driven by mutation in one or more genes in the MAPK signaling pathway. There is also known in the art that FOLFIRINOX or gemcitabine/nab-paclitaxel are approved chemotherapy combinations for treating pancreatic cancer generically without specifying mutations (see the rejection section).
Regarding argument that Hendifar only teaches a method for treating pancreatic cancer with specific BRAF mutations, but fails to teach that these methods would be effective for all pancreatic cancers is not persuasive, because Hendifar teaches a method for treating pancreatic cancer mediated by mutation in one or more genes in the MAPK signaling pathway. Furthermore, Hendifar asserts that 90-95% of all pancreatic cancer cases are driven by activation of the RAS/RAF/MEK/ERK pathway with preponderance of KRAS mutations (92-93%) (page 9, [0044]). It is well-known that activating mutations of KRAS and BRAF result in activation of MAPK signaling pathway, which is crucial for pancreatic cancer. In support of this statement Examiner sites Furukawa (Front. Oncol., 03 February 2015, hereinafter Furukawa).
Furukawa teaches that most pancreatic cancers produce constitutively active MAPK. For their proliferation and survival, pancreatic cancer cells are largely dependent on the activation of MAPK induced as a consequence of the synergistic effect of mutations in KRAS and an abrogation of DUSP6 (page 2, right column, 1st paragraph). Active MAPK induces a variety of genes involved in malignant cancer phenotypes. Therefore, the development of drugs targeting genes downstream of MAPK may provide a novel therapeutic option for pancreatic cancer (page 3, “conclusion”). Thus, since prior art teaches that activated MAPK is crucial for pancreatic cancer, where activated MAPK signaling pathway is activated in vast majority of pancreatic cancer phenotypes (>90%), and where activated MAPK further activate various genes promoting proliferation of pancreatic cancer cells, the method taught by Hendifar, where the method comprises administering to the subject suffering from pancreatic cancer a MAPK inhibitor (e.g. ATI-450) is reasonably expected to be successful for the treatment of nearly all pancreatic cancer types.
Regarding arguments that Hendifar fails to teach the protective effect of Hsp27 in PDAC cells upon treatment with a chemotherapy agent, nor does Hendifar teach that Hsp27 can be inactivated via the inhibition of MK2, the arguments are not persuasive, because although the prior art is silent regarding " MK2 inhibition by ATI-450 augments the efficacy of the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin by inactivating heat-shock protein 27 (Hsp27)". However: " MK2 inhibition by ATI-450 augments the efficacy of the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin by inactivating heat-shock protein 27 (Hsp27)" will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (MK2 inhibitor ATI-450) is being administered to the same subjects (subjects suffering from pancreatic cancer). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding " inactivation of heat-shock protein 27 (Hsp27) via the inhibition of MK2 by ATI-450”, by practicing the method made obvious by the prior art: "the administration of an effective amount of MK2 inhibitor ATI-450 to a patient suffering from pancreatic carcinoma", one will also be " augmenting the efficacy of the combination of leucovorin calcium (folinic acid), fluorouracil (5-FU), irinotecan, and oxaliplatin by inactivating heat-shock protein 27 (Hsp27)", even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("inactivation of heat-shock protein 27(Hsp27) via the inhibition of MK2 by ATI-450") of the method made obvious by the prior art ("the administration of an effective amount of MK2 inhibitor ATI-450 and one or more chemotherapeutic drugs (e.g. 5-fluorouracil) to a patient suffering from pancreatic cancer").
MPEP 2145 II states: "The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious". Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)).
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 1, 6 - 9, and 14 - 27 as obvious over teachings of Hendifar is maintained.
Conclusion
Claims 1, 6 - 9, and 14 - 27 are rejected. No claim is allowed.
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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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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