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 .
This Office action is responsive to Applicant’s amendment and remarks, filed 17 Sep 2025, in which claims 1, 3-4, and 10 are amended to change the scope and breadth of the claim, and claim 2 is canceled.
This application is the national stage entry of PCT/JP2021/025112, filed 02 July 2021; and claims benefit of foreign priority document JAPAN 2020-115074, filed 02 July 2020. This foreign priority document is not in English.
Claims 1, 3-6, and 10-12 are pending in the current application and are examined on the merits herein.
Objections Withdrawn
Applicant’s amendment, filed 17 Sep 2025, with respect that claim 10 is objected to because of informalities has been fully considered and is persuasive, as amended claim 10 ends in a period.
This objection has been withdrawn.
Claim Objections
Claim 10 is objected to because of the following informalities:
claim 10 at line 2 recites the selected disease “inflammatory”. To be consistent with the other diseases alternatives listed, this should be “inflammatory disease” or “inflammation”.
claim 10 at line 3 recites “cognitive function, heart disease …” This group listing should include an “and” before “heart disease.
Appropriate correction is required.
The following are new grounds of rejection necessitated by Applicant’s amendment, filed 17 Sep 2025, in which claims 1, 3-4, and 10 are amended to change the scope and breadth of the claim, and claim 2 is canceled.
Claim Rejections - 35 USC § 112
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.
Amended Claims 10-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer, inflammatory disease, elevated cholesterol, allergy, impaired cognitive function, or heart disease, does not reasonably provide enablement for the full scope of preventing said diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Nature of the invention: A method of treating or preventing a disease selected from the group consisting of cancer, inflammatory disease, elevated cholesterol, allergy, impaired cognitive function, heart disease with curcumin comprising administering the composition of claim 5
The state of the prior art: The ordinary definition of prevent encompasses the definition “To preclude the occurrence of (an anticipated event, state, etc.); to render (an intended, possible, or likely action or event) impractical or impossible by anticipatory action; to put a stop to.” See provided definition of prevent (definition 9a of prevent, Oxford English Dictionary Online, cited in PTO-892). There is no prior art disclosing making said diseases impossible by anticipatory action.
For example, regarding inflammatory diseases, Calder et al. (British Journal of Nutrition, 2009, 101(S1), p1-45, cited in PTO-892) teaches inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Various dietary components have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required. (page 1, abstract) Calder et al. teaches an overview of different disease states of different organs, having different triggering factors, antigens involved, cells involved, mediators involved, and different biomarkers. (page 15, table 1) Calder et al. teaches various dietary components have been suggested to impact on inflammatory conditions, but the number of studies assessing therapeutic benefits of dietary interventions in established inflammatory disorders is still fairly limited. These fatty acids are also beneficial in established CVD, but the extent to which this is attributable to their anti-inflammatory effects is not clear. The common mechanism of oxidative stress development in most of the described pathologies make the role of dietary antioxidants crucial for an optimal preventive action. Despite these considerations, trials in patients suggest little clinical benefit from antioxidant vitamins and polyphenolics in the disorders considered. (paragraph spanning pages 31-32)
For example, regarding cancer, Vogel (Vogel, V.G., Cancer J. Clin., 2000, 50, p156-170, cited in PTO-892) teaches breast cancer prevention in terms of reducing the risk of developing breast cancer. Vogel teaches no lifestyle modifications have yet been proven to prevent or definitively lower the risk of breast cancer. Vogel teaches prophylactic mastectomy offers at least a 90% reduction in the risk of breast cancer (page 156, abstract), suggesting the procedure of prophylactic mastectomy does not fully prevent breast cancer. Vogel teaches while there is no certain means of preventing breast cancer, all women may limit their risk factors for breast cancer, and women at high risk for the disease may be candidates for medical or surgical preventive measures (page 156, right column, first full paragraph). Vogel teaches chemoprevention with tamoxifen may reduce the risk of breast cancer (page 160, table 3), but does not fully prevent breast cancer.
For example, regarding cancer, Lowenfels et al. (Jpn. J. Clin. Oncol., 2004, 34(5), p238-244, cited in PTO-892) teaches pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors. (page 238, abstract) Lowenfels et al. teaches the inaccessibility of the pancreas makes the diagnosis of pancreatic cancer more difficult than diagnosing other digestive tract cancers (page 238, left column). Lowenfels et al. teaches because the disease is relatively rare, it would be inappropriate to subject the entire population to screening, but it may be appropriate to screen groups at high risk of pancreatic cancer (page 242, right column, paragraph 1). Lowenfels et al. teaches there are no entirely effective screening strategies currently available, even for persons with an exceptionally high risk of pancreatic cancer (page 243, left column).
The relative skill of those in the art: The relative skill of those in the art is high.
The predictability or unpredictability of the art: The lack of any prior art disclosing making said diseases impossible means that one skilled in the art cannot predict the usefulness of a product or method to make said diseases impossible. Therefore the claimed invention is unpredictable.
For example, the lack of any prior art disclosing making cancer impossible means that one skilled in the art cannot predict the usefulness of a method to make cancer impossible. For example, Vogel teaches there is no certain means of preventing breast cancer. Lowenfels et al. teaches there are no entirely effective screening strategies currently available for pancreatic cancer, suggesting it would have been unpredictable as to whether such cancer would develop or determine if any action then resulting in the cancer not developing. Therefore the claimed invention is unpredictable.
The Breadth of the claims: The scope of the claims specifically includes prevention of said diseases.
The amount of direction or guidance presented: The specification speaks generally about curcumin’s pharmacological actions. See, for example, paragraph 2 of the specification.
The presence or absence of working examples: The only working examples provided are for the physical properties of stability and solubility at examples 2-3.
Note that lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the full scope of preventing said diseases. See MPEP 2164.
The quantity of experimentation necessary: In order to practice the invention with the full range of all possible treatment methods beyond those known in the art, (such as treating said diseases according to curcumin’s known pharmacological actions) one skilled in the art would undertake a novel and extensive research program to show that the curcumin’s pharmacological actions made said diseases impossible. Because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of diseases and patient populations treated, it would constitute an undue and unpredictable experimental burden.
Genentech, 108 F.3d at 1366, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the breadth of the claims, Applicants fail to provide information sufficient to practice the claimed invention for prevention of said diseases.
The following are modified grounds of rejection necessitated by Applicant’s amendment, filed 17 Sep 2025, in which claims 1, 3-4, and 10 are amended to change the scope and breadth of the claim, and claim 2 is canceled.
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.
Amended Claims 10-12 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites “A method of treating or preventing a disease with curcumin comprising administering the composition of claim 5” (emphasis added). This recitation renders the claim indefinite because it is unclear to who or what the composition is administered, and how that act of administration is related to the disease. It is not clear that the claimed method requires that the composition is administered to the subject having the disease, or if the claimed method encompasses composition is administered to a cell culture for testing purposes or as part of a process of development of a disease treatment. Claim 12 recites the composition is administering intravenously, meaning that the target of the administration must have veins, however the language in claim 12 does not clarify how the target of the administration is related to the disease.
Response to Applicant’s Remarks:
Applicant’s remarks, filed 17 Sep 2025, have been fully considered and not found to be persuasive.
Applicant’s amendment is partially persuasive because amended claim 10 recites what disease is treated or prevented. However, Applicant’s amendment and remarks do not clarify to who or what the composition is administered, or how that act of administration is related to the disease. Therefore this aspect of the rejection is maintained and made final.
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.
Amended Claims 1, 5-6, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kakeya et al. (WO 2018/003857 A1, published 04 Jan 2018, English language equivalent US 2019/0224325, both provided by Applicant in IDS filed 30 Dec 2022) in view of Bastin et al. (Organic Process Research & Development, 2000, 4, p427-435, of record).
WO 2018/003857 A1 is not in English, therefore citations to Kakeya et al. will be found in US 2019/0224325. Kakeya et al. teaches a curcumin pharmaceutical preparation that is highly water soluble, can maintain the concentration of free curcumin in the blood sufficiently high by being administered parenterally, can effectively obtain a pharmacological action of curcumin, and is highly safe, and a pharmaceutical composition for parenteral administration including the water-soluble substance conjugate of curcumin as an active component (abstract). The working example of the conjugate of curcumin is the curcumin monoglucuronide
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(example 1 at paragraph 59 spanning page 3 to 5), corresponding to the free acid form of the claimed formula (I) rotated 180° along a vertical axis. Curcumin includes both of keto and enol forms of curcumin, which are tautomers (page 2, paragraph 44), and one of skill in the art would have understood that the enol form depicted in Kakeya et al. is necessarily in tautomeric equilibrium with the keto form depicted in claim 1. The composition for parenteral administration may also include water and an acid or an alkali, such as a water-soluble inorganic acid or a water-soluble inorganic acid salt (page 3, paragraphs 54-55), addressing limitations of claims 5-6 and 11. Kakeya et al. teaches a working example of administering the composition intravenously in order to treat the disease of cancer (example 2 at page 6, paragraphs 76-83), addressing limitations of claims 10-12. Kakeya et al. further teaches the curcumin therapy of the invention to be selected from cancer therapy, an anti-inflammatory therapy, a cholesterol-lowering therapy, an anti-allergic therapy, a cognitive function improving therapy, and a heart disease preventive therapy (page 2, paragraph 34), addressing limitations of claim 10.
Kakeya et al. does not specifically disclose a sodium salt of the curcumin monoglucuronide (claim 1).
Bastin et al. teaches selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability, and patient compliance. Salts are most commonly employed for modifying aqueous solubility (page 427, abstract). The choice of salt is governed largely by the acidity or basicity of the ionisable group of the drug substance, and common pharmaceutical salt cations include sodium (page 428).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Kakeya et al. in view of Bastin et al. in order to formulate the drug compound of Kakeya et al. as a sodium salt form. One of ordinary skill in the art would have been motivated to combine Kakeya et al. in view of Bastin et al. with a reasonable expectation of success because Kakeya et al. teaches the desire to prepare a curcumin pharmaceutical preparation that is highly water soluble with good bioavailability, and Bastin et al. teaches selection of the appropriate salt form for a drug permits the development of dosage forms with modified aqueous solubility and good bioavailability and stability, and teaches common pharmaceutical salts include sodium. It would have been obvious to apply the known technique of selection of an appropriate salt form for a drug to improve the invention of Kakeya et al. in the same way as the desired improvements of Kakeya et al.
Response to Applicant’s Remarks:
Applicant’s remarks, filed 17 Sep 2025, have been fully considered and not found to be persuasive.
Applicant remarks that Kakeya et al. does not specifically describe the stability of the curcumin glucuronide sodium salt, and that Bastin et al. does not describe the specific measure of improved stability for the sodium salt form of curcumin glucuronide, and that this improvement would have been unpredictable. However, the court of Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties, in response to Pfizer arguing that the results of forming amlodipine besylate would have been unpredictable and therefore nonobvious. By analogous reasoning, Kakeya et al. in view of Bastin et al. teaches a finite number of pharmaceutically acceptable salts to be tested for improved properties, where the improvements are predicted to be in the properties of bioavailability and stability. Therefore the evidence of improvement in stability described in the application would not have been an unexpected result, but rather the expected measurement of an optimized property from the selection within a finite number of pharmaceutically acceptable salts.
Applicant remarks post-filing art Wang et al. does not teach the selection of the sodium salt of curcumin monoglucuronide. However, a determination of obviousness is based on 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.
Further, Applicant remarks that Anderson (Wermuth ed., NPL reference 27) also does not teach the selection of the sodium salt of curcumin monoglucuronide. However, MPEP 2123 at II. provides ““[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).” In this case the prior art does not teach away from or discredit the solution claimed, and as detailed above the unpredictability regarding the selection within a finite number of pharmaceutically acceptable salts in order to give a reasonably predicted improvement is not equated with nonobviousness here.
Amended Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Kakeya et al. (WO 2018/003857 A1, published 04 Jan 2018, English language equivalent US 2019/0224325, both provided by Applicant in IDS filed 30 Dec 2022) in view of Bastin et al. (Organic Process Research & Development, 2000, 4, p427-435, of record) as applied to claims 1, 5-6, and 10-12 above, and further in view of Lam et al. (Ind. Eng. Chem. Res., 2010, 49(24), p12503-12512, of record).
Kakeya et al. in view of Bastin et al. teaches as above.
Kakeya et al. in view of Bastin et al. does not specifically teach reacting curcumin monoglucuronide with a base represented by chemical formula (II) (claim 3).
Lam et al. teaches salt formation is frequently employed to improve the solubility and bioavailability of pharmaceutical compounds (page 12503, abstract). Salt formation is the most common and effective method employed in the pharmaceutical industry to modify and optimize the physicochemical properties of these lead compounds (page 12503, left column, paragraph 2). Lam et al. teaches preparation of the salt by reacting a carboxylic acid-containing drug with a metal hydroxide such as NaOH or KOH (page 12504, right column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Kakeya et al. in view of Bastin et al. further in view of Lam et al. to prepare the salt by commonly used methods. One of ordinary skill in the art would have been motivated to combine Kakeya et al. in view of Bastin et al. further in view of Lam et al. with a reasonable expectation of success because Lam et al. teaches salt formation is the most common and effective method employed in the pharmaceutical industry and teaches preparation of the sodium or potassium salt of a carboxylic acid-containing drug by reaction with the metal hydroxide base.
Response to Applicant’s Remarks:
Applicant’s remarks, filed 17 Sep 2025, have been fully considered and not found to be persuasive.
Applicant remarks regarding Kakeya et al. and Bastin et al. are addressed above.
Applicant further notes that the salts of pemetrexed gave different results. However, this specific result is a function of the two carboxylic acid groups in pemetrexed and the formation of both the monosodium salt and the disodium salt, and would not have been expected by one of ordinary skill in the art for the curcumin monoglucuronide taught by Kakeya et al. because it contains only one carboxylic acid group. Further, as detailed above, the unpredictability regarding the selection within a finite number of pharmaceutically acceptable salts in order to give a reasonably predicted improvement is not equated with nonobviousness here. As detailed in the rejection of record, one of ordinary skill in the art would have been motivated to combine Kakeya et al. in view of Bastin et al. further in view of Lam et al. with a reasonable expectation of success because Lam et al. teaches common methods of salt formation of a pharmaceutical agent.
Conclusion
No claim is found to be allowable.
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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/JONATHAN S LAU/ Primary Examiner, Art Unit 1693