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 .
DETAILED ACTION
Claims 1-15 are pending and are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/22/2026 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application is a U.S. National phase application under 35 U.S.C 371 of PCT application PCT/US2023/015813, filed 3/21/2023, which claims priority under 35 U.S.C 119 (e) from provisional application serial No. 63489221 filed 3/9/2023.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Modi et al. (Scientific forum: 2016 clinical congress, volume 223, no 452, 2016), Wang et al. (Meeting Abstracts,:2014 gastrointestinal cancers symposium, January 2014, abstract), , Zheng et al. (Cancer Chemother Pharmacol. 2013, 71: 1065-1072) and Desai et al. (2017/0020824) (all references are already of record).
Instant claims are drawn to a method for treating pancreatic cancer in a cancer subject, the method which comprises administering to the cancer patient during a 28 day cycle a therapeutically effective combination of:
a) about 0.15 mg to about 2.0 mg of minnelide and/or triptolide according to a first regimen wherein a dose is given once per day on days 1 to 5, 8 to 12, and 15 to 19 of the cycle;
b) about 40 mg/ m2 to about 125 mg/m2 of nab-paclitaxel according to a second regimen wherein a dose is given once per day on days 1, 8, and 15 of the cycle; and
c) about 450 mg/ m2 to about 1000 mg/m2 of gemcitabine according to the second regimen of the cycle; wherein the cycle is repeated one or more times and the combination effectively treats the pancreatic cancer.
Modi et al. discloses that in patients with pancreatic cancer (PDAC) gemcitabine with nab-paclitaxel provide a survival benefit of about 6 weeks over gemcitabine alone. They disclose that the combination of low-dose triptolide and paclitaxel was very effective in inducing M-phase arrest, activating apoptosis and inducing cell death and the combination of Minnelide and low dose of gemcitabine and nab-paclitaxel was effective in decreasing the tumor burden, increasing survival and decreasing metastases in subcutaneous and orthotopic xenografts as well as in STIM model of PDAC. They disclose that in addition this combination therapy effectively targeted both cancer and stromal parts of PDAC leading to a better treatment response (full abstract).
Wang et al. discloses that the combination of Triptolide and paclitaxel enhanced the cytotoxicity of triptolide on pancreatic cell lines and combination index indicated that the effect of triptolide plus paclitaxel was synergistic, They further concludes that the antitumor effect of triptolide plus paclitaxel on pancreatic cancer is mediated by the induction of apoptosis and triptolide enhances paclitaxel-mediated apoptosis via suppression of NF-kB activity (abstract).
Zheng et al. discloses that patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDA) were treated with nab-paclitaxel followed by gemcitabine (1000ng/m2) administered IV for 30 min on days 1 and 8 and repeated every 21 days (abstract). This regimen was well tolerated for the treatment of metastatic PDA, the recommended dose of nab-Paclitaxel was 120 mg/ m2, because of the favorable safety profile and encouraging antitumor activity (page 1071, col.2, 1st para).
Zheng et al. also discloses that Gemcitabine as the only approved single agent for pancreatic cancer (page 1071, col.1, 3rd para).
Desai et al. discloses methods of treatment of metastatic pancreatic cancer comprising administration of Paclitaxel and gemcitabine (see claims 1-2). They gemcitabine is administered to the individual at about 1000 mg/m2and the nab- paclitaxel is about 125mg/m2 (claims 6-7 and 13-14 [0198-0200][0209]). They disclose that the method comprises more than one treatment cycle, wherein at least one of the treatment cycles comprises the administration of (i) an effective amount of a composition comprising nanoparticles comprising a taxane (such as paclitaxel) and a carrier protein (e.g., an albumin); and (ii) an effective amount of gemcitabine. In some embodiments, the treatment cycle comprises no less than about (such as about) 21 days (e.g., 4 weeks). In some embodiments, the treatment cycle comprises less than about 21 days (for example weekly or daily). In some embodiments, the treatment cycle comprises about 28 days [0218]. Desai et al. discloses various different methods of treatment, and various regimens which can be used in the combination treatment of Gemcitabine and nab-paclitaxel [0193-0229].
In view of the forgoing references, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine Triptolide with nab-paclitaxel and gemcitabine the treatment of pancreatic ductal cancer. The skilled artisan would have been motivated to do so because (i) the combination of Minnelide and low dose of gemcitabine and nab-paclitaxel was effective in decreasing the tumor burden, increasing survival and decreasing metastases in subcutaneous and orthotopic xenografts as well as in STIM model of PDAC (ii) Wang et al. explicitly teaches that the combination of Triptolide and paclitaxel enhanced the cytotoxicity of triptolide on pancreatic cell lines. (iii) Zheng et al. discloses that patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDA) were treated with nab-paclitaxel followed by gemcitabine (1000ng/m2) administered IV for 30 min on days 1 and 8 and repeated every 21 days and (iv) Desai et al. discloses methods of treatment of metastatic pancreatic cancer comprising administration of Paclitaxel and gemcitabine (see claims 1-2). They gemcitabine is administered to the individual at about 1000 mg/m2and the nab- paclitaxel is about 125mg/m2 . As such it is would have been obvious to a person of ordinary skill in the art that the combination of these three agents will provide a synergistic option in the treatment of pancreatic cancer. One skilled in the art would have been imbued with at least a reasonable expectation that a combination of Triptolide, Nab-paclitaxel and gemcitabine would be an effective treatment for pancreatic ductal adenocarcinoma.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that 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. The idea of combining them flows logically from their having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering Triptolide in combination with paclitaxel and gemcitabine all of which are individually and in combination already known in the art to be useful in treatment of pancreatic cancer, would achieve a synergistic effect in treating pancreatic cancer. While In re Kerkoven is limited to the mechanical arts, the holdings in this case are pertinent to the present claims because the idea of combining known anticancer drugs to treat pancreatic cancer flows logically from the individual drugs being taught to be useful in treating pancreatic cancer. As such, one skilled in the art would reasonably expect the combination of drugs to also be effective in treating pancreatic cancer. This is especially true in the present case where the prior art explicitly teaches that combinations of Triptolide and paclitaxel and gemcitabine having different mechanisms of action are effective to treating pancreatic cancer.
Secondly, the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). In the present case, it is expressly recognized in the prior art that combining these three agents together would be expected to result in a synergistic effect in treatment of pancreatic cancer. .
In re Diamond and Kellman, 149 USPQ 562 (C.C.P.A. 1966), supports the obviousness of combining two drugs known to be useful for the same purpose. In Diamond, Appellants were claiming a combination of adenosine-5-monophosphate (A5MP) and a glucocorticoid. The Examiner cited prior art teaching that A5MP and glucocorticoids were known in the art to be useful for treating collagen diseases and that combining drugs for the treatment of disease is suggested by the prior art. Appellants argued that the combination of the two drugs is non-obvious since there is no teaching to combine these two out of all known anti-inflammatory agents. The Court was not persuaded by this argument, stating that: explicitly from the reference itself.
“...we think it clear that it is a standard practice in this art to combine ingredients.”
“We are not convinced of non-obviousness of the combination of the two drugs, A5MP and a glucocorticoid such as hydrocortisone, for use as an anti-inflammatory composition, particularly since the record supports the solicitor's contention that the drugs selected are two of the commonly used drugs in the treatment of such collagen diseases.”
With regards to the instantly claimed concentrations and regiments, it is noted that Desai et al., teaches the same dosage of Paclitaxel and gemcitabine which is instantly claimed and also gives guidance in terms of developing regiments of the treatment of pancreatic cancer with these two agents, As such it would have been obvious to a person of skill in the clinical arts to develop a method or regimen of treatment which gives the maximum effectiveness, absence of evidence to the contrary. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
Claims 1-15 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691
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