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 .
Election/Restrictions
Applicant’s election of water (Species A, claim 3), hot water extraction (Species B, claim 4), and liver cancer (Species C, claim 6) in the reply filed on August 10th, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). The species election requirements for Species A and Species C are both withdrawn for compact prosecution. Regarding Species B: non-elected extraction methods of “ultrasonic extraction”, “reflux cooling extraction”, and “vapor extraction” for Species B are withdrawn as being drawn to a non-elected species, but the species of “hot water extraction”, “room temperature extraction”, and “cold-immersion extraction” are currently read into claim 4 for compact prosecution.
Claims 1-6, 8, and 9 are pending and were examined on the merits.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in the instant application. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The priority date is November 17th, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 16th, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because it is not clear what is meant by negative concentration in the graphs in Figures 1A, 1C, and 4B; the graphs in Figure 1A for Pancreatic and Melanoma lack horizontal axis labels; the graphs in Figure 4A lack any axis labels; and the graphs in Figures 6C and 6F are not fully comprehensible because of illegible axis labels, possibly a result of shrinking the graph size combined with limited resolution, resulting in pixelation. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The use of the terms ATCC, GIBCO, abcam, Cell signaling (registered as "Cell Signaling Technology"), Operetta, Sigma-Aldrich, and Matrigel, each of which is a trade name or a mark used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore, each term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The applicant’s assistance is requested in properly reciting any trademarks and tradenames they encounter in the disclosure, even if not explicitly pointed out by the examiner.
Claim Objections
Claims 1-3 are objected to because of the following informalities: the Latin phrase "Curcumae Radix" should be italicized. Appropriate correction is recommended.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The term “improving” in claim 1 is a relative term which renders the claim indefinite.
The term “improving”, recited in claim 1, is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The effect of the claimed method on cancer is rendered indefinite by the use of the term "improving"; it is not clear what aspect of the cancer is improved or if the term "improving" is to be understood as synonymous with the term "treating".
The term “improving” in claim 1 is a relative term which renders the claim indefinite.
The term “hot”, recited in claim 4, is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The .
The term “cold”, recited in claim 4, is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The .
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.
Claims 1-6, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al. (Biomedicine & Pharmacotherapy 2020, 132, 110820), abbreviated "Fan" (Cite No. 6 on the IDS received on May 16th, 2024).
Claim 1 recites “A method for improving or treating cancer, comprising: administering a composition consisting essentially of an extract of Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix to a subject in need thereof”. Claim 2 recites “The method of claim 1, wherein the extract is prepared by extracting 40 to 150 parts by weight of Prunella vulgaris, 30 to 120 parts by weight of Akebia quinata, 20 to 80 parts by weight of Curcuma zedoaria, and 20 to 80 parts by weight of Curcumae Radix with respect to 100 parts by weight of Hedyotis diffusa”. Claim 3 recites “The method of claim 2, wherein the extract is prepared by extracting Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix with water, a C1-C4 alcohol, or a mixed solvent thereof”. Claim 4 recites “The method of claim 3, wherein the extract is prepared by hot water extraction, ultrasonic extraction, room temperature extraction, cold- immersion extraction, reflux cooling extraction, or vapor extraction”. Claim 5 recites “The method of claim 1, wherein the extract has cancer cell killing and cancer cell metastasis inhibitory activity”. Claim 6 recites “The method of claim 1, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, pancreatic cancer, stomach cancer, colorectal cancer, breast cancer, and melanoma”. Claim 8 recites “The method of claim 6, wherein the cancer is metastatic cancer”. Claim 9 recites “The method of claim 6, wherein the cancer has resistance to an anticancer drug”.
Regarding the language “consisting essentially of” in claim 1: for the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355 ("PPG could have defined the scope of the phrase ‘consisting essentially of’ for purposes of its patent by making clear in its specification what it regarded as constituting a material change in the basic and novel characteristics of the invention" (MPEP § 2111.03 III).
Hedyotis diffusa
Fan discloses the ingredient Hedyotis diffusa in Qingjie Fuzheng Granules implied as treating colorectal cancer by inducing apoptosis through increasing the expression levels of Bax, Fas and FasL, decreasing the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9 (Fan, Table 2). Fan discloses Hedyotis diffusa as a component of the Qi Zhu Formula, implied as treating gastric cancer by inducing caspase-3, an apoptosis-related protease, in the core position, and decreasing the protein and mRNA expression of the IAP survivin gene (Fan, Table 2). Fan discloses Hedyotis diffusa as a component of the Jiedu Xiaozheng Yin composition, inhibiting the growth of hepatocellular carcinoma and regulating the expression of cyclin D and cyclin E to arrest cells in G0/G1 phase (Fan, Table 3).
Prunella vulgaris
Fan discloses Prunella vulgaris as a component of the Bushen Shugan Formula (BSF) that has been used for the treatment of human lung carcinoma, tumor recurrence and lung cancer metastasis, and recites anti-cancer mechanisms of BSF “BSF could significantly suppress proliferation of A549 cells, promote apoptosis, block the cell cycle in G2/M phase, and suppress A549 cells epithelial-mesenchymal transition (EMT) via PI3K/AKT/NF-κB pathway” (Fan, subheading 3.3, paragraph 2). Fan recites Prunella vulgaris as a component of Jiedu Xiaozheng Yin (JXY), and further recites the anti-cancer mechanisms of an ethanol extract of JXY: “ethanol extract of Jiedu Xiaozheng Yin (EE-JXY) may significantly inhibit the growth of tumor cells. EE-JXY could also reduce tumor microvessel density (MVD), angiogenesis of chick chorioallantoic membrane (CAM), and the tube formation of human umbilical vein endothelial cells (HUVECs) in vivo. In addition, EE-JXY may inhibit vascular endothelial growth factor receptor 2 (VEGFR-2) and vascular endothelial growth factor A (VEGF-A) expression in HUVECs and HepG2 cells” (Fan, subheading 3.5.1, paragraph 3). Fan also discloses Prunella vulgaris as a component of Wei Chang An (WCA), reciting activity of WCA against the metastasis of colorectal cancer: “WCA could reduce the 1-year and 2-year metastasis rates and improve the 5-year survival rate of CRC. The combination of 5-FU and WCA could significantly suppress the growth and hepatic metastases of colon tumor via decreasing the MMP-7 and β-catenin expression” (Fan, subheading 3.9.1, paragraph 3).
Akebia quinata
Fan discloses Akebia quinata as a component of Chang Wei Qing (CWQ) and recites certain anti-tumor effects and mechanisms of CWQ: “Studies have found that high concentration of CWQ could significantly reduce the size and number of tumor, and inhibit NF-κB and STAT3 signaling pathways to improve colitis-associated tumor development” (Fan, subheading 3.1, paragraph 4). Fan also discloses Akebiae Fructus as a component of Ru Yi Ping (RYP), reporting that RYP “could suppress the growth of breast cancer cells via inducing cell cycle arrest at the G2 phase, inhibit cancer cells migration and invasion by diminishing epithelial-to-mesenchymal transition (EMT) phenotype and MMP9” (Fan, subheading 3.5.2, paragraph 2).
Curcuma zedoaria
Fan discloses Curcuma zedoaria as a component of Ru Yi Ping (RYP), reporting that RYP “could suppress the growth of breast cancer cells via inducing cell cycle arrest at the G2 phase, inhibit cancer cells migration and invasion by diminishing epithelial-to-mesenchymal transition (EMT) phenotype and MMP9” (Fan, subheading 3.5.2, paragraph 2). Fan discloses Zedoary, understood as Curcuma zedoaria, as a component of the Yiqi Jianpi Huaji Decoction (YJHD), and recites anti-cancer effects of YJHD on SGC7901/VCR cells: “low-dose YJHD suppressed cell proliferation, induced apoptosis, increased sensitivity to chemotherapeutic agents, and reversed multiple drug resistance (MDR) by downregulating MRP, P-gp, STMN1, and TUBB3 expression” (Fan, subheading 3.6, paragraph 3). Fan discloses Curcuma zedoaria as a component of the Xiaoai Jiedu recipe (XJR), and recites the results of a study discussing the anti-cancer effects and mechanisms of XJR: “after XJR treatment, the growth of A549 cells was suppressed. Cell apoptosis was pronounced, and cell migration and invasion were suppressed. Treatment of XJR reduced the expression of Bcl-2, decreased the expression levels of phosphorylated p38 (p-p38), p-ERK, and p-JNK, increased the expression of Bax, cleaved caspase-3, and cleaved caspase-9, which shows that XJR is a new therapy for non-small cell lung cancer (NSCLC)” (Fan, subheading 3.17, paragraph 3).
Radix Curcumae
Fan discloses the ingredient radix curcumae (equivalent to “Curcumae radix”) as a component of the Shu Gan Liang Xue Decoction, a formula inhibiting cell proliferation, implied as treating breast cancer by inhibiting steroid sulfatase and aromatase enzymes (Fan, Table 1). Fan also discloses radix curcumae as a component of the Qi Ge San composition inhibiting tumor cell invasion and metastasis, implied as treating esophageal cancer by inhibiting migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function (Fan, Table 4).
Addressing the Instant Claim Limitations
The instant claims are distinguished from Fan in that Fan does not disclose combining material from Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix and administering an extract of these combined materials to a subject. However, as presented above, Fan has disclosed compositions with anti-cancer effects comprising these ingredients, and discloses multiple mechanisms of action among these compositions. A person of skill in the art would have been motivated to combine compositions comprising Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix as recited by Fan, and administer them to a subject, to treat cancer through multiple mechanisms at once, to improve the health of a subject; and from the teachings of Fan recited above, would have had a reasonable expectation of success, even if not absolute certainty (instant claim 1). A composition comprising Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix could reasonably be administered through an oral route, or an intravenous route if plant fiber and solid particles are removed through extraction. A person of skill in the art would have been motivated to extract the bioactive components of the claimed plant materials disclosed by Fan, to separate these components from fibrous plant material that cannot be safely administered through an intravenous route (instant claim 1). The extraction of bioactive components could be performed by contacting the plant materials with a liquid solvent, and an effective extraction solvent could be selected through optimization of the polarity of the solvent. A person of skill in the art would have a reasonable expectation of success at performing this optimization by using extraction solvents covering a range of polarities; including water, C1-C4 alcohols (less polar than water), and hexane (non-polar); and by varying temperature using a thermometer and hot plate. A person of skill in the art could complete this optimization by observing and comparing the effects of each of the resulting extracts (varying by extraction solvent and temperature) on the proliferation, viability, and motility of cultured cancer cells (instant claims 1, 3, and 4).
A person of skill in the art would have been motivated to kill cancer cells and inhibit metastasis to treat cancer, to improve the health of a subject. A person of skill in the art would have had a reasonable expectation of success at doing so by incorporating into the administered composition the Yiqi Jianpi Huaji Decoction, recited by Fan as suppressing cell proliferation and inducing apoptosis in gastric cancer cells (SGC7901/VCR cells) (Fan, subheading 3.6; instant claims 5 and 6); furthermore, inhibiting metastasis implies that the cancer being treated is a metastatic cancer (instant claim 8).
A person of skill in the art would have been motivated to treat a cancer that has drug resistance in order to treat the cancer, to improve the health of a subject. A person of skill in the art would have had a reasonable expectation of success at treating a cancer that has drug resistance by incorporating the into the administered composition the Yiqi Jianpi Huaji Decoction, recited by Fan as suppressing SGC7901/VCR cell proliferation, inducing apoptosis, increasing sensitivity to chemotherapeutic agents, and reversing multiple drug resistance, implying that the cancer cells treated already demonstrated drug resistance (Fan, subheading 3.6; instant claim 9).
The instant claims are distinguished from the teachings of Fan in that Fan does not explicitly recite the parts by weight recited in instant claim 2 for Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix. However, a person of skill in the art could adjust these parts by wight by weighing each ingredient before combining them and observing and comparing the effects of each of the resulting extracts on the proliferation, viability, and motility of cultured cancer cells (instant claim 2). Therefore, the parts by weight parameters recited in claim 2 are currently considered obvious to a person of skill in the art over routine optimization. If the applicant holds the opinion that the parts by weight parameters recited in claim 2 correspond to an unexpected result, then the applicant is encouraged to explain how these parameters relate to the unexpected result, in the reply to this office action.
Fan is relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teachings provided by the references with respect to providing the ingredients administered to a subject, the adjustments of particular conventional working conditions (e.g., the selection from among known components and determining one or more suitable ranges (amounts, proportions, ratios thereof) in which to provide the method comprising administering an extract of Hedyotis diffusa, Prunella vulgaris, Akebia quinata, Curcuma zedoaria, and Curcumae Radix), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the
skilled artisan.
From the teachings of Fan, the invention as a whole, drawn to a method comprising administering an extract of as described in Claims 1-6, 8, and 9, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ methods with the methods (including compositions thereof) of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed methods and the methods of the prior art (and compositions thereof). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Relevant and Prior Art Made of Record
The relevant and/or prior art made of record and not relied upon is considered pertinent to applicant's disclosure, including the following:
KR 100573375 B1 recites a composition having an extract of Akebia quinata seed for treating or preventing cancer (Description, paragraph 1). To make the extract, KR 100573375 B1 recites crushing seeds in the presence of water, aging by adding water, then extracting with a C1-C4 alcohol (machine translation page 3 of 10, lines 8-13 from the top).
Kwon et al. (KR 20100054599 A) recites “An anti-cancer composition containing methanol extract of Prunella vulgaris is provided to suppress the proliferation of cervical cancer, colon cancer, lung cancer, and prostate cancer” (Abstract).
Li, M. et al. Turmeric extract, with absorbable curcumin, has potent anti-metastatic effect in vitro and in vivo. Phytomedicine, 2018, 46, 131–141. DOI: 10.1016/j.phymed.2018.03.065. Li et al. recites “Curcumin, a well-studied component in turmeric, exhibits potent antitumor effects in colorectal cancer. Previous studies showed that turmerones raised the accumulation of curcumin inside colonic cells, and curcumin present in turmeric ethanolic extract had enhanced anti-tumor activities in mice. ... Turmeric extract was demonstrated for the first time for its anti-tumor and anti-metastatic effects in both colorectal cancer cells and orthotopic mouse model through regulation of multiple targets. These findings strongly suggested the promising use of turmeric extract as chemopreventive or chemotherapeutic agent for colorectal cancer patients with metastasis” (Abstract). Regarding the method of making the extract, Li et al. recite “Briefly, 1 kg dried rhizome of Curcuma longa was extracted twice using 95% ethanol for 1 h under reflux. The crude filtered ethanolic extract was evaporated under reduced pressure at 60 °C to dryness, stored at 4 °C and protected from light. Curcumin (Fig. 1(b) and (c)) content was 18.8% w/w in turmeric ethanolic extract (named “turmeric extract” used throughout this manuscript) detected by UPLC” (Materials and Methods, Preparation of turmeric extract and quantification of curcumin).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert F Spaine whose telephone number is (571)272-9099. The examiner can normally be reached 8:00 AM - 4:00 PM United States Eastern Time, Monday-Friday.
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/R.F.S./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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