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 .1
This application has been reassigned from Examiner Shterengarts to Examiner William Lee, in Art Unit 1623. In order to expedite accurate processing of the application papers, all future correspondence with the office should reflect this change.
Status of the Claims
Claim(s) 1-16, 18-29, 46 and 54 is/are pending in this application. Claims 1-12 are under examination. Claims 13-16, 18-29 and 46 and 54 are withdrawn.
Election/Restrictions
Claims 13-16, 18-29, 46 and 54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II and III there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 1, 2026.
Applicant’s election without traverse of Group I (claims 1-12) and below species Compound 3-1 in the reply filed on April 1, 2026 is acknowledged.
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Applicant elected without traverse, the species, (S,E)-2-(3-hydroxy-3, 7, 11-trimethyldodeca-6,10-dien-1-yl)-3,5,6-trimethylcyclohexa-2,5-diene-14-dione (aka "Compound 3-1").2 Note, the examined species has been expanded to include Compound 1-1, noted to be first compound of claim 1 and found in Table 1 of the specification on page 89.
Information Disclosure Statements
The information disclosure statement(s) (IDSs) submitted on May 14, 2025, January 2, 2025 and May 14, 20243 are in compliance with the provisions of 37 CFR § 1.97. Enclosed with this Office Action is a return-copy of the PTO-1449 Forms with the Examiner's initials and signature indicating those references that have been considered.
Specification
The disclosure is objected to because of the following informalities: at paragraph 32, is one of numerous instances where Compound 1-1 is repeated twice, as reproduced below.
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It appears that the second recitation of 1-1 should be 1-2, for example see paragraph 44, where it lists Compounds 1-1, 1-2, 2-1 etc.
Appropriate correction is required.
Claim Objections
Claim(s) 1 and 5 are objected to because of the following informalities:
Claim 1, line 3 recites “a said” where it should just recite “said” for proper antecedent and precedent basis.
Claim 5 recites “wherein the disease, disorder or condition is (proliferative, non-proliferative, diabetic or hypertensive) retinopathy.” To avoid confusion, it is suggested the claim be amended to recite “wherein the disease, disorder or condition is proliferative retinopathy, non-proliferative retinopathy, diabetic retinopathy or hypertensive retinopathy.”
Appropriate correction is required.
Claim Interpretation
Claim 1 is directed to a method of treating, preventing, inhibiting, ameliorating or delaying the onset of a disease, disorder or condition associated with ferroptosis in a mammalian subject suffering from a said disease, disorder or condition comprising administering to the subject a therapeutically effective amount of one or more compounds such as Compound 1-14 having Formula (X)
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With regard to the prevention aspect of the claimed method, prior art disclosing administration of the claimed compounds to a subject will inherently possess and teach the prevention of the claimed diseases, disorders and conditions associated with ferroptosis, as all subjects, including mammalian human subjects are in need of prevention of such diseases, disorders and conditions.
With regard to the first named compound of claims 1 and 10-11, it is identified as compound 1-1 at Table 1, page 89, paragraph 238 of the specification reproduced below. Throughout the action it will be referred to as compound 1-1. Compound 1-1 is a 3S isomer/enantiomer of vatiquinone, see below.
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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.
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for the first compound of claims 1 and 10-11, aka compound 1-1 (the 3S-enantiomer of known FDA investigated drug vatiquinone) for the treatment of Friedreich Ataxia, does not reasonably provide enablement for the full scope of treating, preventing, inhibiting, ameliorating or delaying the onset of a disease, disorder or condition associated with ferroptosis, with the full scope of compounds recited in the claims.
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.
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.
The predictability or unpredictability of the art: The instant claimed invention is highly unpredictable since a person having ordinary skill in the art (PHOSITA) recognizes the challenges in treating and preventing diseases, disorders and conditions associated with ferroptosis.
For just a single treatment aspect of disease associated with ferroptosis, Friedreich Ataxia, (see above reference to Table 1 for its structure and similarity to claimed compound 1-1), the art recognizes that Vatiquinone has completed pivotal clinical rials and entered regulatory evaluation for the treatment Friedreich Ataxia, a species of disease associated with ferroptosis. See page 1 of Lees et al.5 Lees notes the MOVE-FA trial, a Vatiquinone to treat Friedreich Ataxia clinical trial, revealed statistically significant benefits on important secondary patient outcomes, including fatigue and upright stability, as well as significant slowing of disease progression. See page 1 last paragraph. However, the MOVE-FA trial did not meet a primary endpoint, a change in the modified Friedreich Ataxia Rating Scale. Id. Further, the FDA declined to approve the Vatiquinone New Drug Application (NDA), citing insufficient efficacy data and requesting a new well-controlled study. Id. At best, the art notes an unpredictability of treatment of Friedreich Ataxia, even with a leading clinical candidate such as the quinone compound, Vatiquinone.
Note that claimed compound 1-1 is recognized as the particular S-enantiomer of Vatiquinone, see Table 1 on page 89 of the specification. This fact lends credence that it may have similar clinical activity to treat Friedreich Ataxias as Vatiquinone does. Also noted is the statement from the specification regarding its compounds 1-1, 1-2, 2-1, 2-1, 3-1, 3-1, 4-1, 4-2, 5-1, 5-2, have never been evaluated in the clinic for the treatment of any of these diseases/disorders/conditions. See paragraph 9. These ten compounds are the only ten claimed and disclosed in the specification.
Therefore, the unpredictability in the art is a Wands factor against the enablement of the full scope of the claimed invention.
The breadth of the claims: The instant claims are deemed very broad since these claims read on treatment, prevention, amelioration, etc., of any disease, disorder and condition of claim 1. Note that even claims 2-9 that purport to limit the diseases and disorders to a particular scope, these claims are still broadly directed classes of conditions, such as ischemic stroke, a plethora of neurological disease (Alzheimer’s and Parkinson’s among others), renal injury, etc. Further, the prevention aspect of the claimed method is unduly broad as it is generally recognized that absent evidence the administered treatment is a vaccine of sorts, prevention of diseases by medical intervention is unduly broad.
The broad scope of the claims is a Wands factor against the enablement of the full scope of the claimed invention.
The amount of direction or guidance presented, and the presence or absence of working examples: It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
It is pointed out that there is no working example, either in vivo or in vitro to enable the treatment, prevention, amelioration etc. of any diseases, disorders or conditions associated with ferroptosis, let alone the treatment of Friedreich Ataxia, in Applicant’s specification.
At best, Table 1, starting at page 89, notes compounds 1-1, 2-1, 3-1 4-1, 5-1 were tested for blood concentration analysis that merely suggests the pharmacokinetics of the compounds, i.e. as molecular weight of the compound decreases, the gut absorption decreases. See paragraph 237, noting the drop in plasma concentration of the 5 compounds compared to Vatiquinone, molecular weight decreases. Id. Paragraph 238 notes Table 1 provides blood and brain concentration data for these compounds. There is no clinical data to support treatment for Friedreich Ataxia, let alone treatment or prevention of any of the claimed diseases, disorders or conditions associated with ferroptosis.
The lack of working examples is a Wands factor against the enablement of the full scope of the claimed invention.
Therefore, in view of the Wands factors as discussed above, Applicant fails to provide information sufficient to practice the claimed method, with the exception of compound 1-1, due to it being an enantiomer of clinical candidate vatiquinone, for the treatment of Friedreich Ataxia.
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.
Claim(s) 1-10 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Pub 2010/0222436 (US Pub 436).
US Pub 436 is cited on the IDS dated May 14, 2024 as Ref No. A2.
This novelty rejection is limited solely to the prevention aspect of disease, disorder or condition associated with ferroptosis in a mammalian subject comprising administering, a therapeutically effective amount of claimed compound 1-1, the first compound listed in claims 1, 10 and 11, aka Formula X as per the specification.
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Regarding claims 1 and 10-12, preventing the diseases/disorders/conditions in a mammal subject suffering from such, US Pub 436 teaches vatiquinone as compound VII-i
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, (see claims 17-18 and 30) where claimed compound 1-1 is known to be the vatiquinone S-enantiomer, as detailed above in Table 1 of Applicant’s specification.
The US Pub 436 compound VII-i (the racemic form) encompasses and inherently contains the particular 3S enantiomeric form of compound 1-1.
Regarding claims 1 and 10-12, US Pub 436 teaches a mammalian (human) subject in need (see paragraph 94), the treatment of the various claimed diseases Friedreich’s Ataxia, Leigh syndrome, Leber’s, etc., see summary of in Abstract.
These disease/disorders of US Pub 436’s abstract are generically claimed by Applicant’s claims 1 and 10-12, and specifically named in claims 2-9.
Note that US Pub 436 does NOT explicitly recite the prevention of the claimed diseases, etc. associated with ferroptosis. But because US Pub 436 teaches the administration of claimed compound 1-1 (inherently found in racemic mixture of compound VII-i) to treat a human subject, such property of prevention of the diseases/conditions are inherent to the teachings of treatment of US Pub 436.
The various diseases, disorder and conditions of claims 2-9 are inherently prevented by the method of administering compound VII-I of US Pub 436.
Regarding claim 10 and the claimed routes of administration, US Pub 436 teaches administration of therapeutically effective amounts of its claimed compounds (see paragraph 28), including but not limited to oral, intravenous, subcutaneous, transdermal, etc., administration, see paragraphs 166-171.
Regarding claim 12, as detailed above, US Pub 436 teaches treatment of a human subject, see above.
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.
Claim(s) 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over US Pub 2010/0222436 (US Pub 436).
US Pub 436 is cited on the IDS dated May 14, 2024 as Ref No. A2.
Regarding claims 1 and 10-12 and the claimed method of treating, inhibiting, ameliorating or delaying the onset of a disease or disorder or condition associated with ferroptosis, in a mammal subject in need of treatment, US 436 teaches vatiquinone as compound VII-i
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. See claims 17-18 and 30 Claimed compound 1-1 is known to be a 3S enantiomer of vatiquinone, see above in Table 1 of Applicant’s specification.
Regarding claims 1 and 10-12 (where the specific diseases recited in claims 2-9), US Pub 436 teaches a mammalian (human) subject in need (see paragraph 94), the treatment, inhibition, etc., of the various claimed diseases, see Abstract noting Friedreich’s Ataxia, etc. See also rejection of claims 2-9 below, where each disease and/or disorder claimed is specifically addressed and rejected.
While US Pub 436 does not teaches the purification or the isolation of specific 3S enantiomer of compound 1-1 for the aspect of a method of treatment, see Table 1, it does teach the racemic form compound V-ii, which necessarily contains the claimed 3S enantiomer compound 1-1.
Prior to the filing of the instant application a person having ordinary skill in the art (PHOSITA) following the teachings of US Pub 436 to treat, inhibit, etc., the claimed diseases and disorders in a mammalian subject in need would have found it prima facie obvious to look towards isolating both R and S isomers (or administering a racemic mixture containing the S isomer), per MPEP 2143 (e), obvious to try.6 There are a finite number of identified predictable isomers (R or S) to administer as a mixture, or purify and then administer.
Regarding claims 2-9, US Pub 436 teaches a mammalian (human) subject in need (see paragraph 94), the treatment Friedreich’s Ataxia, Leigh Syndrome and Leber’s Hereditary Optic Neuropathy (LHON), see claim 30; a pigmentary degeneration of the retina caused by Kearns-Sayre Syndrome (KSS), either proliferative or non-proliferative as these are the only two choices, see paragraph 11; epilepsy and (Myoclonic Epilepsy with Ragged Red Fibers (MERRF), see claim 30; Parkinson’s Disease (PD), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), see claim 30; cardiomyopathy, see claim 30; and renal injury in form of renal tubular acidosis, see paragraph 11.
Regarding claim 10 and the routes of administration, US Pub 436 teaches administration of therapeutically effective amounts of its claimed compounds (see paragraph 28), including but not limited to oral, intravenous, subcutaneous, transdermal, etc., administration, see paragraph 166 generally but also paragraphs 167-171, for specifics.
Regarding claim 11 and the timing of such administration for periods of greater than 6 weeks up to periods of ten years and greater, as many if not all the conditions of claims 2-9 are lifetime afflictions, Friedreich’s Ataxia, Leigh Syndrome, Parkinson’s disease, Alzheimer’s disease, Huntington’s, ALS, epilepsy, etc. US Pub 436 teaches the amount and timing of administration will be readily determined by routine experimentation with the skill and judgement of the ordinary skilled clinician for any particular patient will depend upon a variety of factors listed therein. See paragraph 175. Because the various conditions taught by US Pub 436 are life time afflictions a PHOSITA will routinely administer treatment for periods of treater than up to 6 weeks and ten years. Therefore, the timing limitations of claim 11 are obvious based on a PHOSITA skill and judgment.
Regarding claim 12, as detailed above, US Pub 436 teaches treatment of a human subject, see above.
Conclusion and Correspondence
In conclusion no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. 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.
/WILLIAM Y LEE/Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
1 CONTINUING DATA
This application is a 371 of PCT/US22/32866 06/09/2022
PCT/US22/32866 has PRO 63/313,149 02/23/2022
PCT/US22/32866 has PRO 63/209,159 06/10/2021
This application has published as US Pub 20240293339.
2 The elected species is recited paragraphs [0002], [0013], [0120], [0121], [0140], [0141], [0145], [0146], [0149], [0181 ], and [0189] of the Application, and paragraphs [0 181 ]-[0191] describe the synthesis of the elected species. The elected species is also recited in claims 1, 10, 11, 13, 15, 16, and 18.
Per SciFinder CAS Registry Number: 2881062-12-8
(S,E)-2-(3-Hydroxy-3,7,11-trimethyldodeca-6,10-dien-1-yl)-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione
3 With regard to the May 14, 2024 IDS the citations of considered NPL references A10, A15 and A17 have been edited as detailed therein. With regard to the January 2, 2025 IDS the citations of considered NPL references B2 and B3 have been edited as detailed therein.
4 2-[(3S,6E,10E)-3-hydroxy-3,7, 11, 15-tetramethyl-6, 10, 14-hexadecatrien-1-yl ]-3,5,6-trimethyl-2,5-cyclohexadiene-1 ,4-dione (; CAS# 1213269-99-8)
5 Lees et al. (2025) Emerging therapies for Friedreich Ataxia and the prospect of future combination treatments, Future Rare Diseases, 5:1, 2563497, DOI: 10.1080/23995270.2025.2563497
6 MPEP 2143 (e) "obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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