Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
This application is a national stage application of PCT/US2022/080566, filed November 29, 2022. Claims 1-18 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted May 24, 2024 is acknowledged wherein claim 10 is amended and claims 17-18 are canceled.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 and 7-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite a composition comprising at least one of a number of compounds which include the natural products (+) and (-) epicatechin, 11-beta-hydroxypregnenolone, 11-hydroxyprogesterone, glucose, nicotinic acid, niacin, and nicotinamide. This judicial exception is not integrated into a practical application because while the base claim 1 describes an intended use for treatment of mitochondrial disease, this does not correlate with any objective structural limitation that would differentiate the composition from the compound as it occurs in nature so as to transform the nature of the composition or provide the composition with markedly different characteristics than the naturally occurring substance. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only other element recited by the claims is a generically defined pharmaceutically acceptable carrier. In the absence of a specifically defined carrier that adds some particular novel feature to the claimed composition, the recitation of a pharmaceutically acceptable carrier is merely well-understood, routine, conventional activity in the pharmaceutical art.
Regarding claims 5, 7, and 8, these claims require that the composition contain what is defined as a synergistic amount of two naturally occurring compounds. However, the present disclosure neither provides a specific definition of what a synergistic amount is nor provides actual evidence that a combination of these two compounds in any ratio has any additional effect different than either of the compounds individually that would amount to markedly different characteristics. While figure 18 in the drawings provides evidence that the combination of (-)-epicatechin and 11-beta-hydroxypregnenolone (EP03+EP06, corresponding to claim 6) has an enhanced effect on rescuing the swimming activity of zebrafish treated with rotenone, other combinations corresponding to claims 5, 7, and 8 are not effective and appear to have no markedly different characteristics from the individual natural products.
Regarding claim 9, while this claim requires another compound be included, this compound is selected from a list including many generically defined classes of compounds, including for example “steroids” which is a class containing various naturally occurring compounds. Therefore this claim merely adds another judicial exception to the composition and does not add significantly more to the claim. Furthermore there is no evidence that this composition has markedly different characteristics from any of the compounds individually.
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 17-18 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 17 is a dependent claim referring to “the composition of claim 10.” However, claim 10 is in fact directed to a method, not a composition, thereby creating uncertainty as to what the scope of claim 17, and its dependent claim 18, actually is.
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, 10, 11, 14, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tanabe et al. (Reference included with PTO-1449)
Independent claim 1 is directed to a composition comprising one of a number of compounds in a pharmaceutically acceptable carrier. Tanabe et al. discloses a composition which comprises (-)-epicatechin in a pharmaceutically acceptable carrier. (p. F1265 left column first paragraph) This composition anticipates present claim 1. Regarding claims 10, 14, and 15, this composition was administered to rats who exhibited drug induced mitochondrial dysfunction and kidney injury due to administration of cisplatin. (-)-epicatechin alleviated the damage to mitochondria caused by cisplatin. (p. F1267 left column last paragraph – right column first paragraph) Therefore Tanabe anticipates these claims.
Claims 1, 2, and 10-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gavrilova et al. (Reference included with PTO-1449)
Independent claim 1 is directed to a composition comprising one of a number of compounds in a pharmaceutically acceptable carrier. Claim 2 specifies that the compound is (+)-epicatechin. Gavrilova et al. discloses a study of the effect of the compound (+)-epicatechin (EPI) on patients suffering from Friedrich’s Ataxia (FA). (pp. 7-8 section 1) The (+)-epicatechin is provided as 25mg gelatin capsules. (p. 23 section 5.1) Since gelatin is a pharmaceutically acceptable carrier this dosage form anticipates present claims 1 and 2.
Regarding claims 10, 12, 14, 15, and 17 these claims requires that the composition be administered to a patient in need of alleviation of symptoms associated with a mitochondrial disease. The third paragraph on P. 8 of Gavrilova discloses that FA is a mitochondrial disease. FA is also specifically listed among the mitochondrial diseases in claim 12. Regarding claim 11, the same section of Gavrilova discloses that FA produces symptoms including muscle weakness and cardiomyopathy.
Regarding claim 13, while Gavrilova does not specifically disclose that FA is a complex I mitochondrial disease, Heidari et al. (Reference included with PTO-1449) further discloses that FA is a type I mitochondrial disease, (p. 27 left column first paragraph) providing evidence that the study described by Gavrilova inherently anticipates claim 13. Regarding claim 16, while Gavrilova does not specifically describe inhibiting acute decompensation form mitochondrial dysfunction, the reference does describe cardiomyopathy as a symptom of FA, (p. 8 third paragraph) and furthermore describes epicatechin as ameliorating congestive heart failure. (p. 8 fourth paragraph) Joseph et al. (Reference included with PTO-1449) describes acute decompensated heart failure as being defined as the sudden or gradual onset of the signs or symptoms of heart failure. (p. 510 second paragraph) Therefore one skilled in the art would reasonably conclude that treating cardiomyopathy and congestive heart failure in FA as described by Gavrilova would be expected to inherently involve inhibiting possible episodes of acute decompensation.
For these reasons Gavrilova et al. anticipates the present claims.
Claims 1, 4, 9, 10, 14, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barranco. (US pre-grant publication 2008/0045487, cited in PTO-892)
Independent claim 1 is directed to a composition comprising one of a number of compounds in a pharmaceutically acceptable carrier. Claim 4 specifies that the compound is 11-hydroxyprogesterone.
Barranco discloses a formulation for treatment of skin disorders such as psoriasis. (p. 1 paragraph 10) These compositions contain 11-alpha-hydroxyprogesterone, as well as minoxidil and the steroid clobetasolpropionate, as well as a pharmaceutical carrier, thereby anticipating present claims 1, 4, and 9. While Barranco et al. does not specifically describe treating mitochondrial disease, claims 1, 4, and 9 are directed to compositions described in terms of an intended use. Such an intended use does not serve to differentiate the claims from identical compositions described for a different use.
Furthermore, regarding claims 10, 14, and 17, Natarelli et al. (Reference included with PTO-892) discloses that psoriasis is associated with increased mitochondrial ROS, and well as increased mitochondrial DNA in serum, indicating the role of some sort of mitochondrial dysfunction in this condition. (pp. 8-9 section 2.2) Therefore, treating psoriasis is seen to inherently fall within the scope of treating mitochondrial dysfunction.
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.
Claims 9 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Gavrilova et al. as applied to claims 1, 2, and 10-17 above, and further in view of Clay et al. (Reference included with PTO-892)
The disclosure of Gavrilova et al. is discussed above. Gavrilova et al. does not specifically describe compositions of (+)-epicatechin further comprising one of the ingredients recited in claim 9 or 18.
However, Clay et al. discloses a review of therapeutic agents being tested for the treatment of FA. (p. 1857 left column fourth paragraph) Therapeutic agents being considered include corticosteroids (pp. 1857-1858 section 3.2) and nicotinamide. (p. 1862 section 5.5) It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the therapies described by Gavrilova with corticosteroids or nicotinamide for the treatment of FA. One of ordinary skill in the art would have found this to be obvious because both (+)-epicatechin and the therapeutic agents described by Clay ae disclosed as usable for the same purpose, namely treating the same population of patients with FA.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Dugar et al. (Reference included with PTO-892)
Independent claim 1 is directed to a composition comprising one of a number of compounds in a pharmaceutically acceptable carrier. Claim 2 specifies that the compound is (+)-epicatechin. Claim 3 specifies that it is 11-beta-hydroxypregnenolone.
Dugar et al. discloses that both (+) and (-) stereoisomers of epicatechin stimulate mitochondrial biogenesis and can potentially be used to mediate the effects of exercise. (p. 1 left column first paragraph – right column second paragraph) The steroid 11-beta-hydroxypregnenolone was predicted by molecular modeling to also be effective for this purpose. (p. 6 right column second paragraph) This compound was indeed seen to be effective at improving various markers of mitochondrial biogenesis. (pp. 6-8 section 3.2) Agents increasing mitochondrial biogenesis are described as potentially being useful for treating diseases associates with aging, such as neurodegenerative disease, cardiovascular disease, metabolic disease, and sarcopenia. (p. 8 right column fifth paragraph)
It would have been obvious to one of ordinary skill in the art at the time of the invention to make pharmaceutical compositions of (+)-epicatechin, (-)-epicatechin, or 11-beta-hydroxypregnenolone, or combinations thereof, for the purpose of treating diseases associated with mitochondrial decline in aging. One of ordinary skill in the art would have seen this as being directly suggested by the teaching of Dugar that these compounds are useful for improving mitochondrial biogenesis.
By the same reasoning, the method of claims 10, 11, 14, and 17 would be infringed by the use of such compounds for treating mitochondrial decline in aging.
Regarding claim 6, any prima facie case of obviousness against this claim is overcome by evidence in the present disclosure (e.g. figure 18) of a synergistic effect between these two specific compounds.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 2, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Barranco as applied to claims 1, 9, 10, 14, and 17 above, and further in view of Epstein. (US pre-grant publication 2020/0016116, cited in PTO-892)
The disclosure of Barranco is discussed above. Barranco does not disclose compositions further comprising (+) and (-) epicatechin. However, Epstein discloses a method of treating an inflammatory skin condition such as psoriasis comprising a composition comprising catechins to the affected area. (p. 6 paragraphs 60-61) A specific catechin composition that can be used is tea catechins comprising among others epicatechin, which is interpreted as being a mixture of both (-)-epicatechin and (+)-epicatechin. (p. 12 paragraphs 141-142) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to include tea catechins including (-)-epicatechin and (+)-epicatechin in the compositions of Barranco. One of ordinary skill in the art would have found this to be obvious because they would have considered the addition of this composition as being useful for the same purpose of treating psoriasis.
Therefore the invention taken as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 9-16 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10-12 of copending Application No. 18/871587 (reference application, US pre-grant publication 2025/0345296, cited in PTO-892, herein referred to as ‘587). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘587 claims a composition comprising an ingredient selected from a list including for example N-acetylcysteine and nicotinamide as recited in present claim 1, dexamethasone which is a steroid as recited in present claim 9, and a pharmaceutically acceptable carrier, thereby anticipating claims 1 and 9. Furthermore regarding claims 10-16, claims 10-12 of ‘587 claim methods of treating mitochondrial disease which include all of the specific limitations recited in these claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7-12, 14, 17, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 27, and 28 of copending Application No. 19/518535 (reference application, unpublished, cited in PTO-892, herein referred to as ‘515). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-3 claim a pharmaceutically acceptable composition for treating mitochondrial disease containing various active agents listed in claim 3 which include for example nicotinamide, niacin, N-acetylcysteine, 11-hydrocyprogesterone, 1-hysroxypregenenolone, and (-) and (=) epicatechin, thereby anticipating claims 1-5 and 7-9 as well as for example a MAPK modulator. Furthermore claims 27 and 28 claim methods of treating a mitochondrial disease using these compositions, including limitations recited in present claims 10-12, 14, 17, and 18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 10, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/794145 (reference application, US pre-grant publication 2025/0000817, cited in PTO-892, herein referred to as ‘145). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘145 is directed to a method of treating mitochondrial disease comprising administering a composition comprising probucol, which would anticipate present claims 10 and 14. This method would furthermore anticipate the composition used therein, namely claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-5 and 7-18 are rejected. Claim 6 is objected to for depending form a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANDREA OLSON/ Primary Examiner, Art Unit 1693 9/14/2026
Prosecution Insights