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 .
Claims 1-13, submitted on 8 August 2024, represent all claims currently under consideration.
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.
Priority
This application claims priority to KR10-2023-0189256, filed 22 December 2023. The effective filing date is 22 December 2023.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted 8 August 2024, is acknowledged and has been considered.
Specification
The disclosure is objected to because of the following informalities: The structure of Chemical Formula I in Paragraph 0026 is of poor quality and difficult to interpret, and should be replaced with a higher fidelity image.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1-8 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 the treatment of benign prostate hyperplasia (BPH), it does not reasonably provide enablement for the prevention of BPH. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth below:
The nature of the invention and breadth of the claims:
The claims are directed towards a composition for treating or preventing BPH, comprising mitoquinone or a pharmaceutically acceptable salt thereof. Thus, the claims are directed to a composition which can be used to prevent the development of BPH in a patient.
The state of the prior art and the predictability or unpredictability of the art:
Nagakura (Prostate International, 10, 2022, 200-206) performed a study on the prevention of BPH in Japan. The results demonstrated that healthy lifestyle habits, especially the avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are risk factors for BPH development (Abstract). WebMD (https://web.archive.org/web/20251210213859/https://www.webmd.com/men/prostate-enlargement-bph/can-i-prevent-bph) states that 9 in 10 men will have BPH by the time they are in their 80s, and there is nothing which can prevent it as the prostate gland will grow, and may lead to BPH. Exercise and a heart-healthy diet can help manage weight, which is great for the prostate, and exercise can help the bladder empty at a normal weight. Thus, in view of the current state of the art, there is no indication that BPH can be prevented pharmacologically, while the risk of development can be reduced by instituting healthy lifestyle choices such as reduced alcohol consumption, avoidance of smoking, and exercise.
The relative skill of those in the art:
The artisan would generally have a medical degree with further training in urology; however, their high level of training and knowledge would not be sufficient to overcome the lack of understanding of how to use the claimed composition for the prevention of BPH as there is no evidence in the current state of the art that BPH can be prevented pharmacologically.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification demonstrates that MitoQ is useful for the treatment of BPH as demonstrated by its ability to suppress prostate cell proliferation and oxidative stress in DHT-stimulated RWPE-1 cells (Paragraph 0096), as alleviating prostate enlargement and prostate cell proliferation in rats with BPH (Paragraph 00107). Thus, the specification enables the treatment of BPH as Applicant has demonstrated that administration of this compound targets pathways associated with BPH, and demonstrates a reduction in prostate size in a rat model of BPH. However, Applicant has not provided data demonstrating the prevention of the development of BPH.
The quantity of experimentation necessary:
Considering the state of the art as described above, in particular with regards to the lack of evidence in the current state of the art for the prevention of the development of BPH, and the high unpredictability of the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate with the scope of the claims.
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 9-13 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 9 is indefinite because of the limitation “a pharmaceutical composition including mitoquinone” (emphasis added). The claim is indefinite because it is unclear if the limitation of “mitoquinone” following “including” is merely exemplary or a required limitation of the claim. The Examiner suggests amending the claim to read “comprising” or similar rather than “including” to overcome this rejection. Claims 10-13 are similarly rejected as indefinite for depending upon an indefinite claim without resolving the underlying issue of indefiniteness.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 13 claims the method of Claim 9 wherein the administering is performed parenterally or orally. The only routes of administration of a therapeutic are orally or parenterally (which encompasses all non-oral routes of administration). Thus, Claim 13 does not further limit Claim 9. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Basu (WO 2010/121177; Publication Date: 21 October 2010) as evidenced by Jin (Redox Biology, 65, 2023, 102816).
Basu discloses pharmaceutical compositions and medicaments, and methods of using such compositions and medicaments in the treatment of inflammation and cancer (Abstract). The invention describes compositions that relate to oxidative stress modulators (OSM), uses of various forms of oxidative/reduction (redox), nitrosative or oxidative stress-induced conditions, inflammation, hyperplasia, and neoplasia, including but not limited to mammalian prostate, kidney, liver, brain, mouth, head and neck, pharynx, esophagus, stomach, colon, rectum, gonad, breast, lung, and pancreatic carcinomas (Paragraph 0002). In some embodiments, the antioxidant of the invention is
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(Page 32). This compound is a salt of mitoquinone. The effects of varying concentrations of Mito-Q on the growth of LNCaP and PC-3 (prostate cancer cell lines) over a period of 4 days was assayed. Mito-Q-C10 inhibits the growth of both LNCaP and PC-3 cells (Paragraph 00156). Mito-QC-10 was also shown to reduce oxidative stress in human prostate carcinoma cells (Paragraph 00157, Paragraph 00159). Results in Figure 5 clearly demonstrate that Mito-Q-C10 pretreatment at a sublethal dose (1 µM) can completely block the oxidative stress induced by androgen treatment in LNCaP cells. It has been demonstrated that androgen is the leading cause of oxidative stress generation, which is the primary causative agent of prostate cancer and other prostatic diseases, including, but not limited to, benign prostatic hyperplasia. Thus, the anti-oxidant effect of Mito-Q-C10 treatment is capable of removing one of the most important metabolic products that causes cancer, cancer progression, and cancer metastasis in general and prostate cancer in specific (Paragraph 00162). The compounds described herein can be administered as pure chemicals either singularly or plurally, it is preferable to present the active ingredient as a nutraceutical or pharmaceutical composition (Paragraph 00234). Pharmaceutical compositions include those suitable for oral administration (Paragraph 00247). The compounds can be formulated for parenteral administration (Paragraph 00252). The term “nutraceutical” or “nutraceutical composition” refers to a food item, or a part of a food item, that offers medical health benefits, including prevention and/or treatment of disease. A nutraceutical composition according to the disclosure may contain only a cationic anti-oxidant compound according to the present disclosure (Paragraph 00259). Such compositions generally include a “nutraceutically-acceptable carrier” which is any carrier suitable for oral delivery (Paragraph 00260). Claim 34 claims a pharmaceutical composition comprising an antioxidant and a therapeutic agent for the treatment of a prostate disease or disorder. Claim 35 claims the composition of claim 34, wherein the prostate disorder or disease is benign prostatic hyperplasia (Page 88).
Basu does not directly demonstrate that mitoquinone inhibits the AR-NLRP3 pathway.
Jin (See IDS, 8 August 2024) studied mitoquinone (MitoQ) in the context of benign prostatic hyperplasia (BPH). They determined that MitoQ inhibits DHT-induced cell proliferation and mitochondrial ROS by inhibiting the androgen receptor and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling in prostate epithelial cells (Abstract), demonstrating that this is an inherent property of MitoQ.
Regarding Claims 3, 4, 7, and 8, Jin demonstrates that MitoQ inherently possesses these properties. Thus, the prior art of Basu necessarily meets the limitations of these claims (See MPEP § 2112 I, II).
Regarding Claims 2 and 6, the claims are written with intended usage language. Basu anticipates these claims as Basu discloses both pharmaceutical and nutraceutical formulations of MitoQ, as well as their use for the treatment of BPH. The intended use of the claims does not result in a structural difference between the claimed invention and the prior art (See MPEP § 2112.02 (II)). As the formulations of Basu can be formulated in concentrations up to 25 µM, these anticipate the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Basu (WO 2010/121177; Publication Date: 21 October 2010) as evidenced by Jin (Redox Biology, 65, 2023, 102816).
The teachings of Basu and Jin are previously described and are fully incorporated into this rejection.
Basu does not directly disclose the treatment of BPH using MitoQ. However, it would be obvious to one of ordinary skill in the art to utilize MitoQ for the treatment of BPH in view of what is disclosed by Basu. Basu demonstrates that MitoQ is useful for blocking the oxidative stress within two prostate cancer cell lines, and directly states that blocking of this oxidative stress would be useful for the treatment of conditions including BPH. Basu then further claims a method of treating BPH using compositions which comprise antioxidant compounds, which includes MitoQ. Thus, the artisan would both be motivated, and have a reasonable expectation of success, in choosing MitoQ in methods for the treatment of BPH.
Conclusion
Claims 1-13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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