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 .
Status of the Application
Claims 1-17 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 09/12/2025 are acknowledged. Claims 14-17 remain withdrawn, as being drawn to an unelected invention or specie. Claims under consideration in the instant office action are claims 1-13.
Applicants' arguments, filed 09/12/2025, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Roth (WO 2010/009332) in view of Sarrouilhe et al. (Serotonin and Cancer: What Is the Link?, Current Molecular Medicine, 2015, 15, pp. 62-77).
Roth teaches “compositions that bind to 5-HT4 receptors and inhibit proliferation of activated
lymphocytes.” (see abstract). Roth teaches compound ICI-738, which reads on Compound C (pg. 24, lines 10-15):
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Roth teaches “Methotrexate (MTX) is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases…Cyclophosphamide (Endoxan ™/Cytoxan ™/Neosar ™/Revimmune ™), also known as cytophosphane, is a nitrogen mustard alkylating agent, used to treat various types of cancer and autoimmune disorders such as RA.” (pg. 44, lines 3-7, 20-25).
Roth does not teach a method of treating a tumor comprising administering a compound of formula (I).
Sarrouilhe et al. is drawn towards the link between serotonin receptors (see abstract). Sarrouilhe et al. teaches “serotonin has been shown to be a mitogenic factor for a wide range of normal and tumoral cells. Serotonin exhibits a growth stimulatory effect in aggressive cancers and carcinoids more often through 5-HT1 and 5-HT2 receptors. In contrast, low doses of serotonin can inhibit tumour growth via the decrease of blood supply to the tumour, suggesting that the role of serotonin on tumour growth is concentration-dependent. Data are also available on serotonin involvement in cancer cell migration, metastatic processes and as a mediator of angiogenesis. Moreover, the progression of some tumours is accompanied by a dysregulation of the pattern of serotonin receptor expressions. Serum serotonin level was found to be suitable for prognosis evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma. In some cases, antagonists of serotonin receptors, inhibitors of selective serotonin transporter and of serotonin synthesis have been successfully used to prevent cancer cell growth.” (see abstract). Sarrouilhe et al. teaches “The action of serotonin on PC is mediated through several receptor subtypes that are present at various tumour stages. 5-HT1A, 5-HT1B, 5-HT2B and 5-HT4 receptors were identified in three human prostatic carcinoma cell lines, PC3, DU145 (androgen-unresponsive cells) and LNCaP (androgen-responsive cells) and serotonin was involved in their growth [21-24] (Table 2).” (pg. 65, left column, first paragraph). Sarrouilhe et al. teaches “serotonin has been already used as tumour marker of gastrointestinal carcinoids, and to some extent of bronchial, hepatic and ovarian carcinoids [16]. Moreover, for neuroendocrine tumours of the pancreatic islet cells and intestinal tract, serotonin could be also used as specific tumour marker [79].” (pg. 74, right column, third paragraph).
It would have been obvious to one of ordinary skill in the art to treat a tumor comprising administering a compound of formula (I), as suggested by Sarrouilhe et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since prostate tumors can be mediated via the 5-HT4 receptor pathway, and compound ICI-738 (i.e. Compound C) is an effective 5-HT4 receptor ligand as taught by Roth, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Response to Arguments
Applicant argues that the prior art is not analogous art. The Examiner respectfully disagrees since Roth is drawn towards compounds that bind to 5-HT4 receptors (see abstract), which is implicated in a number of cancers (pg. 44, lines 3-7, 20-25). Sarrouilhe et al. is drawn towards the link between serotonin and cancer, which may be mediated via the 5-HT4 receptor pathway (see abstract; pg. 65, left column, first paragraph). There is thus a reasonable nexus between the teachings of Roth and Sarrouilhe et al.
Applicant also argues that the teachings of Roth teach away from the claimed invention. The Examiner respectfully disagrees since although Roth may teach mediating the proliferation of activated lymphocytes (see abstract), Roth does teach mediating immune responses in the treatment of various diseases including myeloma, a cancer (pg. 8, 5th paragraph), and thus would not amount to a teaching away of the claimed invention, which is drawn towards a method of treating a tumor.
Applicant also argues that “Sarrouilhe does not fill the motivation or predictability gap; it catalogues the heterogeneity and context dependence of serotonin signaling in oncology and does not identify the Roth compound class, the Roth mechanism, or the 5-HT4 pathway as a reliable, generalizable route to tumor treatment.” The Examiner respectfully disagrees since Sarrouilhe et al. teaches “The action of serotonin on PC is mediated through several receptor subtypes that are present at various tumour stages. 5-HT1A, 5-HT1B, 5-HT2B and 5-HT4 receptors were identified in three human prostatic carcinoma cell lines, PC3, DU145 (androgen-unresponsive cells) and LNCaP (androgen-responsive cells) and serotonin was involved in their growth [21-24] (Table 2).” (pg. 65, left column, first paragraph). One of ordinary skill in the art would have thus be motivated to select the 5-HT4 receptor as a therapeutic target for the treatment of tumors given their presence in a number of tumor types as taught by Sarrouilhe et al.
Conclusion
Claims 1-13 are rejected.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691