DETAILED ACTION
This office action is in response to the Applicant’s filing dated November 5th, 2025.
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 Claims
Claims 1-17 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on November 5th, 2025. Acknowledgement is made of the withdrawal of claims 3, 5-6, 14 and 16-17 in the remarks filed on November 5th, 2025.
Election/Restrictions
Applicant’s election of species of the compound SkQ1 in it’s reduced form (shown below) and infection as the inflammatory condition in the reply filed on November 5th, 2025 is acknowledged.
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Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-2, 4, 7-13 and 15 read on the elected species and will be examined herein.
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.
Claim 1-2, 4, 7-13 and 15 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 preventing destruction of cell-to-cell contacts between endothelial cells with SkQ1 in Example 2 on pages 28-29, treating mice with H5N1 influenza with SkQ1 in Example 3 on page 29, protecting mice from death when subjected to toxic conditions with pre or post treatment with SkQ1 in Examples 5 and 6 on pages 30-32 and suppressing TNFα and IL-6 cytokines in mice with SKQ1 in Example 7 on page 32, does not reasonably provide enablement for preventing an inflammatory condition in a subject in need thereof, including preventing the subject from contracting COVID-19. 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. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention of claims 1-2, 4, 7-13 and 15 relate to a method of preventing a subject from an inflammatory condition, including preventing a subject from contracting COVID-19, comprising administering a mitochondrially-targeted antioxidant compound of Formula (I).
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites:
Tabas et al (Science, (2013), 339(6116), 166-172), cited for evidentiary purposes, teaches “Inflammation is orchestrated by many molecules, and targeting one or a few may not be enough. Inflammation is also a finely tuned process that has inherent sensors and feedback pathways, and so inhibition of a critical component of inflammation may simply trigger a compensatory proinflammatory response involving another pathway. The inflammatory response is critical for host defense, and thus when the previous two challenges are successfully overcome, the risk:benefit profile is often unacceptable” (page 2, second paragraph). Baden et al (New England Journal of Medicine, (2020), 382(19), 1851-52), cited for evidentiary purposes, teaches “Covid-19 is spreading rapidly through Europe and North America, but we have few specific tools to control the growing epidemic and treat those who are sick. We rely on quarantine, isolation, and infection-control measures to prevent disease spread and on supportive care for those who become ill. What we lack is a specific antiviral agent to treat the infected and, optimally, decrease viral shedding and subsequent transmission” (page 1851, right column, first paragraph). Cao et al (New England Journal of Medicine, (2020), 382(19), 1787-99), cited for evidentiary purposes, teaches that “No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2” (page 1787, Background section). Cao further teaches, “The full spectrum of Covid-19 ranges from mild, self-limiting respiratory tract illness to severe progressive pneumonia, multiorgan failure, and death. Thus far, there are no specific therapeutic agents for coronavirus infections.” (page 1788, left column, first paragraph).
“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 of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for preventing destruction of cell-to-cell contacts between endothelial cells with SkQ1 in Example 2 on pages 28-29, treating mice with H5N1 influenza with SkQ1 in Example 3 on page 29, protecting mice from death when subjected to toxic conditions with pre or post treatment with SkQ1 in Examples 5 and 6 on pages 30-32 and suppressing TNFα and IL-6 cytokines in mice with SKQ1 in Example 7 on page 32, but it is not sufficient to provide support for the full scope of compounds encompassed by the claims or for the full scope of conditions or disorders associated with preventing an inflammatory condition in a subject, including preventing a subject from contracting COVID-19.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to prevent inflammatory conditions in a subject or to prevent a subject from contracting COVID-19. While experimentation is presented for treatment of H5N1 influenza in mice, there is no experimentation or mechanism or action presented or discussed in the specification regarding preventing inflammatory conditions in a subject or preventing a subject from contracting COVID-19.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound of Formula (I) could be predictably used as a preventative for all inflammatory conditions in a subject, including preventing a subject from contracting COVID-19, particularly in humans.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a 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" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding the use of any compound of Formula (I) to prevent inflammatory conditions in a subject, including preventing a subject from contracting COVID-19. Determining if any particular claimed compound would prevent inflammatory conditions in a subject, including preventing a subject from contracting COVID-19, would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the invention of claims 1-2, 4, 7-13 and 15 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
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 1-2, 4, 7-9, 11-13 and 15 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.
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, claims 1, 11 and 12 recite the broad recitation “wherein L is a linker group, comprising: a) straight or branched hydrocarbon chain… and/or”, and the claim also recites “b) a natural isoprene chain” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because, due to the use of the “and/or” language, 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. Claims 2, 4, 7-9, 13, and 15 depend from or rely on claims 1 or 12.
Claim Rejections - 35 USC § 102
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 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 1-2, 4, 8, 12-13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skulachev et al (WO 2014/116591 A2).
Regarding claim 1-2 and 4, Skulachev teaches a method of treating an inflammatory disorder in a patient comprising administering to the patient a therapeutically effective amount of a mitochondrially targeted antioxidant (pages 5-7, paragraph [0012]; page 42, claim 11); wherein the antioxidant compound is SkQ1H2 (page 7, paragraph [0013]; page 43, claim 12) which is the reduced form of SkQ1 (pages 14-15, paragraph [0067]); wherein the inflammatory disorder is caused by infection (page 7, paragraph [0014]; page 43, claim 13).
Regarding claim 8, Skulachev teaches a method of preventing the disassembly of endothelial cell-to-cell contact in a mammal comprising administering a therapeutically effective amount of a mitochondrially targeted antioxidant (pages 7-8, paragraphs [0015]; page 44-45, claim 18); wherein the antioxidant compound is SkQ1H2 (page 8, paragraph [0016]; page 45, claim 19) which is the reduced form of SkQ1 (pages 14-15, paragraph [0067])
Regarding claims 12-13 and 15, Skulachev teaches SkQ1 in a concentration of 100 nmol/kg which should be prepared in a solution, and thus a composition administered via intraperitoneal injection (page 29, paragraphs [0013-0014]), used to obtain the results in Figures 8F and 8G.
Thus, the teachings of Skulachev anticipate the method and composition of instant claims 1-2, 4, 8, 12-13 and 15.
Claims 1-2, 4, 7-9, 11-13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skulachev et al (WO 2012/167236 A2).
Regarding claim 1-2, 4, 7 and 9, Skulachev teaches a method of treating an inflammatory disorder in a patient comprising administering to the patient a therapeutically effective amount of a mitochondrially targeted antioxidant (page 2, paragraph [0004]; page 4, paragraph [0013]); wherein the antioxidant compound is SkQ1H2 (page 4, paragraph [0012]) which is the reduced form of SkQ1 (pages 13-14, paragraph [0044]); administered via injection (page 4, paragraph [0015]); further comprising ascorbic acid which is an additional therapeutic agent (page 4, paragraph [0017]).
Regarding claim 8, Skulachev teaches the method as described in the above rejection, preventing deconstruction of cell-to-cell contacts between endothelial cells of the subject is the consequence after administering the effective amount of the SkQ compound, including SkQ1H2.
MPEP 2112 (I) states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Regarding claim 11, Skulachev teaches a stable, liquid MTA-based pharmaceutical composition applicable in clinical practice, and is thus equivalent to a kit or a package seen in clinical practice (page 6, paragraph [0032]; page 11, paragraph [0036]).
Regarding claims 12-13 and 15, Skulachev teaches a composition comprising the reduced form of SkQ1, known as SkQ1H2, ascorbic acid and lactose monohydrate (pages 13-14, paragraph [0044]; page 38, paragraph [0139]). Skulachev teaches the composition comprising the reduced form of SkQ1, known as SkQ1H2 is useful in the treatment of inflammatory conditions (page 41, claims 1 and 4; page 43, claim 20).
Furthermore, regarding the use of the composition of the instant claims, such limitations of the instant claims fail to patentably distinguish the instant claims over the cited prior art because such a limitation is an intended use of the composition comprising the reduced form of SkQ1, known as SkQ1H2 (i.e. an intent to use the disclosed composition as treatment for an inflammatory condition), which does not impart any physical or material characteristics to the composition that is not already present in the cited prior art. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Pitney Bowes Inc. v. Hewlett-Packard Co., 182 F.2d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 378, 42 USPQ2d 1550, 1554 and MPEP 2112.02(II). In the instant case, the claims are directed to a composition comprising the reduced form of SkQ1, known as SkQ1H2 and, thus, would be reasonably expected to be capable of performing the intended use as instantly claimed, absent factual evidence to the contrary and further absent any apparent structural difference between the composition of the prior art and that of the instant claims.
Thus, the teachings of Skulachev anticipate the method and composition of instant claims 1-2, 4, 7-9, 11-13 and 15.
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.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Skulachev et al (WO 2014/116591 A2); in view of Prompetchara et al (Asian Pacific Journal of Allergy and Immunology, (2020), 38(1), 1-9).
Regarding claim 10, Skulachev (WO 2014/116591 A2) anticipates the method and composition of claims 1-2, 4, 8, 12-13 and 15 as described in the above rejection.
Skulachev further teaches that human neutrophils are activated by components of pathogens and disrupted human cells, as well as proinflammatory cytokines. MMP-9 is a metalloproteinase released from activated neutrophils. Excess neutrophil activation leads to massive tissue damage. Activated MMP-9 is known to be involved in pulmonary disorders such as bronchial asthma and chronic obstructive pulmonary disease (page 19, paragraph [0081]). Skulachev discloses that SkQ1 treatment prevents human neutrophil activation (page 19, paragraph [0080]); further stating that SkQ1 was shown to be effective in protecting human tissues against MMP-9 related damage, and damage caused by pathogens and/or inflammatory cytokines; thus, SkQ1 is useful for prevention and treatment of the pulmonary disorders bronchial asthma and chronic obstructive pulmonary disorder (page 20, paragraph [0082]).
Skulachev does not teach a method of treating an inflammatory condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a mitochondrially-targeted antioxidant (SkQ), wherein the method prevents the subject from contracting COVID-19.
Prompetchara teaches that out of 99 cases of COVID-19 investigated, 38% had increased total neutrophils (page 3, right column, last paragraph); and there is a correlation with increased total neutrophils and disease severity and death (page 4, left column, first paragraph). Prompetchara further teaches that uncontrolled SARS-CoV-2 viral replication leads to an influx of neutrophils and monocytes/macrophages, resulting in hyperproduction of pro-inflammatory cytokines (page 4, Figure 2).
It would have been prima facie obvious to a person of ordinary skill in the art to combine the teachings of Skulachev with the teachings of Prompetchara because the references are directed to the same underlying biological problem, cytokine driven inflammatory responses mediated by neutrophil activation. Skulachev teaches the use of SkQ to mitigate neutrophil-mediated inflammatory tissue damage in pulmonary disorders by suppressing neutrophil activation and downstream protease and cytokine effects. Prompetchara teaches that COVID-19 results an excessive influx of neutrophils, cytokine hyperproduction, and inflammatory tissue damage. Applying the known anti-inflammatory method disclosed by Skulachev to a disease state exhibiting the same inflammatory mediators and cellular mechanisms as disclosed by Prompetchara represents the predictable use of prior art elements according to their established functions. One of ordinary skill in the art would have had a reasonable expectation of success in mitigating inflammation associated with COVID-19 based on the shared inflammatory pathways disclosed in the references.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Taken together, all of this would result in the method of instant claim 10 with a reasonable expectation of success.
Conclusion
Claims 1-2, 4, 7-13 and 15 are rejected.
No claim is allowed
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/C.L.J./Examiner, Art Unit 1691
/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691