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 Application
The Preliminary Amendment filed on 12/15/23 is acknowledged.
Claims 8-9, 11, 13-19, 24-25, and 28-37 were cancelled.
Claims 3-7, 10, 20, 22, 26-27, and 38-39 were amended.
Claims 1-7, 10, 12, 20-23, 26-27, and 38-39 are pending and are included in the prosecution.
Priority
This Application is a 371 of PCT/ES2021/070738 filed on 10/11/21. This Application also claims foreign priority to ES P202031034 filed on 10/13/20. Receipt is acknowledged of certified copies of papers submitted under 35 U.S.C. 119 (a)-(d), which papers have been placed of record in the file.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) an English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 05/31/23 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the examiner is considering the information disclosure statement. Please see the attached copy of PTO-1449.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Please see Page 4, lines 12, 24, 27, and 29; and Page 17, lines 28, 33, and 34 of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 10, 12, and 22 are objected to because of the following informalities:
Claims 10 and 12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
In claim 22, line 1, the article “an” should be replaced with the article “the.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) - Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26-27 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C., first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. Instant claim 26 is directed to a method of treating cancer comprising administration of the pharmaceutical composition of claim 22 wherein the cancer is selected from the group of colorectal cancer, pancreatic cancer and glioblastoma. Instant claim 27 is directed to the method according to claim 26, wherein the type of cancer is selected from the group of colon adenocarcinoma, including chemotherapy-resistant colon adenocarcinoma, pancreatic adenocarcinoma and glioblastoma multiforme. Thus, the claimed method is for treating the recited cancers.
The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, Paragraph 1, “Written Description” Requirement, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. This should include the following considerations: (1) actual reduction to practice, (2) disclosure of drawings or structural chemical formulas, (3) sufficient relevant identifying characteristics such as complete structure, partial structure, physical and/or chemical properties and functional characteristics when coupled with a known or disclosed correlation between function and structure, (4) method of making the claimed invention, (5) level of skill and knowledge in the art and (6) predictability of the art. For each claim drawn to a single embodiment or species, each of these factors is to be considered with regard to that embodiment or species. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
First, what do the claims as a whole cover? Instant claim 26 is directed to a method of treating cancer comprising administration of the pharmaceutical composition of claim 22 wherein the cancer is selected from the group of colorectal cancer, pancreatic cancer and glioblastoma. Instant claim 27 is directed to the method according to claim 26, wherein the type of cancer is selected from the group of colon adenocarcinoma, including chemotherapy-resistant colon adenocarcinoma, pancreatic adenocarcinoma and glioblastoma multiforme.
Second, how does the scope of the claims compare to the scope of the disclosure? The disclosure states that “The potent antitumor activity of Solanum melongena seed extracts appears when tested in human and murine colon cancer cell cultures (T84 of metastatic human colorectal cancer, HCT15 of colorectal cancer with multidrug resistance (MOR) mechanisms, and MC38 of murine colorectal cancer developed in C57BL6 mice) using the HepG2 line of human hepatocytes as a control, also allows the determination of their therapeutic range. Similarly, the mechanisms of action by which the extracts act on tumor cells were studied to elucidate the molecular pathways that activate cell death” (¶ bridging Pages 14-15). Also, the extracts show antiproliferative capacity against glioblastoma multiforme or pancreatic adenocarcinoma (Page 15, lines 24-28).
Third, the factors need to be considered.
(1) What was actually reduced to practice?
Clearly, the method of preparing the extract was actually reduced to practice. However, there is no disclosure of any human subjects who were administered the claimed extract in order to treat cancer.
(2) Is there disclosure of drawings or structural chemical formulas?
There is no disclosure of the therapeutic dose, the patient population, the treatment regimen etc.
(3) Are there sufficient relevant identifying characteristics disclosed?
The only identifying characteristics relate to the extracts showing antiproliferative activity in cancer cell lines (Example 2, Tables 8 and 9 – Pages 28-31).
(4) Is there at least one method of making the claimed invention disclosed?
Given the steps of preparing the extract, one of skill in the art could easily prepare the extract. However, given the lack of guidance regarding specific human subjects having a specific cancer and the corresponding chemotherapeutically effective dosage and dosing regimen of the extract, there is a significant gap in the written description.
(5) What is the level of skill in the art and what knowledge is present in the art?
The level of skill in the art of treating cancer is very high, about that of a PhD and MD scientist with several years’ experience with administering chemotherapy.
(6) What is the level of predictability of the art?
The level of predictability in this art is very low since there are numerous patient populations, cancer subpopulations, previous therapies, dosing and cytotoxicity concerns that need to be resolved.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of treatments to human subjects in need of cancer treatment which would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 112(b)
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 2, 4-5, and 27 are 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 pre-AIA the applicant regards as the invention.
Claim 2, part a) ends with “and/or” and part b) recites “the meal obtained in step a) is …” It is unclear how there is an option with the term “or” of having either part a) or part b), i.e., not requiring part a), but part b) requires the meal obtained in step a). Furthermore, steps a) and b) are recited in claim 1 and in claim 2, which are different steps and are confusing. It is recommended that the steps in claim 2 be identified with different letters to distinguish over the steps in claim 1. Claim 4 is included since it is dependent on claim 2 and doesn’t correct the defects in claim 2.
Claim 5 recites “the ethanol” in line 2. Claim 5 is dependent on claim 1. Although claim 1 recites “an ethanolic extract” in the preamble, and “a cold hydroalcoholic solution” in part b), claim 1 does not positively recite the inclusion of “ethanol.” There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the term “partially” with respect to evaporating the ethanol from the ethanolic extract. The term “partially” is a relative term which renders the claim indefinite. The term "partially" 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. It is unclear how much ethanol evaporation would be considered partial evaporation.
Claim 27 recites both a broad limitation together with a narrow limitation. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 27 recites the broad recitation “colon adenocarcinoma,” and the claim also recites “including chemotherapy-resistant colon adenocarcinoma,” which is the narrower statement of the limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Interpretation
Claim 26 recites “A method of treating cancer comprising administration of the pharmaceutical composition of claim 22 wherein the cancer is …” It is recommended that claim 26, should be amended to insert the phrase “to a patient in need thereof” after the term “claim 22” in order to state the intentional purpose for which the method must be performed. Please see MPEP 2111.02(II).
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
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 of this title, 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, 3, 5-7, 20-22, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Asmah et al. (J. Trop. Agric. and Fd. Sc. 35 (1)(2007):91-97 – “Asmah”) in view of Okada et al. (Plant Foods Hum Nutr (2010) 65:225-232 – “Okada”) and Nakamura (WO 2018/070545 A1 – English Espacenet Translation).
The claimed invention is a method for obtaining an ethanolic plant extract from the mature seed meal of Solanum melongena, which comprises the steps of:
a) grinding the seeds to obtain meal;
b) extracting the meal from step a) using a cold hydroalcoholic extraction solution at acid pH,
c) optionally, defatting the mature seeds by mechanical cold pressing before
carrying out steps a) and b).
Asmah teaches the cytotoxic effects of eggplant ethanolic extracts against selected cancer cell lines such as non-hormone dependent breast cancer cell line (MDA-MB-231), cervical cancer cell line (CaOV3) and liver cancer cell line (HEpG2) (Abstract, Page 94, Col. 2, 3rd ¶ and Table 1, Page 95, Col. 2, 3rd and 4th ¶s, and Page 96, Col. 1, 2nd ¶). Figure 1 shows the free radical scavenging activity (%) of ethanol extracts of various types of eggplant, including long eggplant (Solanum melongena), and Figure 2 shows the total phenolic content of ethanolic extracts of various types of eggplant species (Page 94). Asmah teaches that long eggplant (Solanum melongena) has a phenolic content of 1,697 ± 46.67 mg (Page 94, Col. 2, 2nd ¶). Table 1 shows the IC50 values of long eggplant (Solanum melongena) against selected cancer cell lines (Page 94). Long eggplant (Solanum melongena) had the second highest free radical scavenging and the second highest phenolic content (Page 95, Col. 1, 3rd ¶).
Asmah does not expressly teach that the extract is from the seeds of long eggplant (Solanum melongena) or an acid pH.
Okada teaches ethanol extracts of dried plant seeds (Abstract), wherein the seeds include those of eggplant (Solanum melongena) (Page 227 - Table 1). Fig. 1 shows the total phenolic content (Page 228 – Fig. 1), Table 2 shows the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity (Page 229), Fig. 2 shows the effects on adiponectin production in 3T3-L1 adipocytes (Page 230), and Fig. 3 shows the effects on TNF α levels in 3T3-L1 adipocytes (Page 231) of ethanol extracts from the seeds of various plants, including eggplant (Solanum melongena).
Nakamura teaches a composition containing as an active ingredient a choline ester ([0001]) wherein edible plants are suitable as raw materials for efficiently supplying choline esters ([0009], [0011]). A method for producing the composition includes producing an extract by freeze drying an edible plant into a powder and extracting with ethanol or aqueous ethanol, the edible plant is Solanum melongena, the freeze dried powder is suspended in water and the pH is adjusted by adding an acid in order to have a pH between 5.5 and 4.5 ([0011], [0013]-[0014], [0029]-[0030]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an ethanolic extract of long eggplant (Solanum melongena), as taught by Asmah, in view of the extract prepared from the seeds of Solanum melongena, as taught by Okada, and the method of producing an ethanol extract of Solanum melongena by adjusting the pH to be an acidic pH between 5.5 and 4.5, as taught by Nakamura, and arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do this because all the references teach preparing extracts of long eggplant, and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claims 1 and 6, the limitations of a method for obtaining an ethanolic plant extract from the mature seed meal of Solanum melongena and the ethanolic extract, respectively, would have been obvious over the ethanolic extracts of various types of eggplant, including long eggplant (Solanum melongena) (Abstract, Page 94, Col. 2, 3rd ¶ and Table 1, Page 95, Col. 2, 3rd and 4th ¶s, and Page 96, Col. 1, 2nd ¶, Figures 1 and 2), as taught by Asmah, in view of the ethanol extracts of dried plant seeds (Abstract), wherein the seeds include those of eggplant (Solanum melongena) (Tables 1 and 2 and Figures 1-3), as taught by Okada.
Regarding instant claim 1, the limitation of step a) grinding the seeds to obtain meal would have been obvious over the step of grinding the plant ([0029]) as taught by Nakamura.
Regarding instant claim 1, the limitation of step b) extracting the meal from step a) using a cold hydroalcoholic extraction solution at acid pH would have been obvious over the ethanol extracts (Page 92, Col. 2, 4th ¶, Page 93, Col. 1, 3rd ¶), as taught by Asmah in view of the extraction with ethanol or aqueous ethanol of Solanum melongena, wherein the freeze dried powder is suspended in water and the pH is adjusted by adding an acid in order to have a pH between 5.5 and 4.5 ([0011], [0013]-[0014], [0029]-[0030]), as taught by Nakamura.
Regarding instant claims 1, 3, and 20-21, the limitations of step c) defatting the mature seeds by mechanical cold pressing before carrying out steps a) and b) would have been obvious over the extracts which were filtered and evaporated at 40°C under reduced pressure and subsequently air dried (Page 93, Col. 1, 3rd ¶), as taught by Asmah. One of ordinary skill in the art would have found it obvious to modify the steps and use an extraction rate based on the desired attributes of the final extract (particle size, water content, stability, powder flow rate, density, etc.). MPEP 2144.04(IV)(C) states that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results.
Regarding instant claim 5, the limitation of partially or totally evaporating the ethanol would have been obvious over the extracts which were evaporated at 40°C under reduced pressure and subsequently air dried (Page 93, Col. 1, 3rd ¶), as taught by Asmah.
Regarding instant claim 7, the limitations of a total polyphenol content ranging between 11.16 and 27.59 μg gallic acid equivalents (GAE) /mg extract and/or the reducing capacity ranges between 5.33 and 6.31 μg gallic acid equivalents/mg extract would have been obvious over the total phenolic content (mg GAE/100 g dry weight) of 1,697 mg) of long eggplant (Solanum melongena) (Abstract), as taught by Asmah, absent evidence of criticality or unexpected results.
Regarding instant claim 22, the limitation of a pharmaceutical formulation would have been obvious over the pharmaceutical product used in various dosage forms such as powders, granules, capsules, pills and tablets ([0033]), as taught by Nakamura.
Regarding instant claims 38 and 39, the limitations of a food supplement would have been obvious over the food product ([0008]) and food composition ([0010]), as taught by Nakamura.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Asmah et al. (J. Trop. Agric. and Fd. Sc. 35 (1)(2007):91-97 – “Asmah”) in view of Okada et al. (Plant Foods Hum Nutr (2010) 65:225-232 – “Okada”) and Nakamura (WO 2018/070545 A1 – English Espacenet Translation), as applied to claims 1, 3, 5-7, 20-22, and 38-39 above, further in view of Sharma et al. (Current Medicinal Chemistry, 2018, 25, 4740-4757 – “Sharma”).
Instant claim 23 is drawn to the pharmaceutical composition according to claim 22, which is a combined pharmaceutical composition that additionally comprises at least one anticancer agent in addition to those present in the extract.
The teachings of Asmah, Okada, and Nakamura are discussed above.
Asmah, Okada, and Nakamura do not expressly teach an additional anticancer agent.
Sharma teaches that plant polyphenols have antioxidant properties that provide protection against cancer (Abstract) and that dietary polyphenols given as adjunct drug along with chemotherapy can decrease chemoresistance and cytotoxicity, and also increase the efficacy of treatment (¶ bridging Pages 4752 and 4753).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an ethanolic extract of long eggplant or Solanum melongena, as taught by Asmah, in view of the extract prepared from the seeds of Solanum melongena, as taught by Okada, the method of producing an ethanol extract of Solanum melongena by adjusting the pH to be between 5.5 and 4.5, as taught by Nakamura, further in view of the dietary polyphenols given as adjunct drug along with chemotherapy to decrease chemoresistance and cytotoxicity, and also increase the efficacy of treatment, as taught by Sharma, and arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do this because all the references teach plant extracts, and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A). One of ordinary skill in the art would have had a reasonable expectation of success in treating cancer by administering the eggplant extract taught by Asmah, Okada, and Nakamura, as an adjunct drug along with chemotherapy because of the advantages of a decrease in chemoresistance and cytotoxicity, and also an increase the efficacy of treatment, as taught by Sharma (¶ bridging Pages 4752 and 4753).
Regarding instant claim 23, the limitation of an additional anticancer agent would have been obvious over the dietary polyphenols given as adjunct drug along with chemotherapy that can decrease chemoresistance and cytotoxicity, and also increase the efficacy of treatment (¶ bridging Pages 4752 and 4753), as taught by Sharma.
Allowable Subject Matter
Claims 10 and 12 contain allowable subject matter since a prior art search did not uncover a reference that teaches or suggests an ethanolic extract from the mature seed meal of Solanum melongena that comprises at least salannin and/or capsianoside II as recited in claim 10 or at least one additional compound selected from the group of kaempferol-3-sophorotrioside, myricomplanoside and arillatose B, or combinations thereof as recited in claim 12. Claims 10 and 12 are only objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615