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 .
Status of the Claims and Response to Restriction Requirement
Claims 1, 3-12, 14 and 16-20 are pending as of the response filed 05/15/2026. Claims 2, 13 and 15 are cancelled. Applicant’s election of group I claims without traverse is acknowledged. Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of a species of the administered agent as a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists, wherein mitoquinol is selected as the species of the one or more mitochondrial targeted antioxidants, and dimethyl fumarate (DMF) is selected as the species of the one or more Nrf2 agonists, is acknowledged. Claims 1, 3-11, 14 and 16 encompass the elected species. Claim 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Therefore, claims 1, 3-11, 14 and 16 have been examined to the extent to which they are readable on the above identified elected species.
Because Applicant did not distinctly and specifically point out the supposed errors in the election of species requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
In view of the pending claims, the following objections and rejections are made as discussed below.
Priority
This application is a 371 of PCT/US2022/021511 filed 03/23/2022 and claims priority to PRO 63/166,207 filed 03/25/2021.
The subject matter of the instant claims are supported by the provisional application, PRO 63/166,207. Accordingly the effective filing date of instant claims 1, 3-11, 14 and 16 is 03/25/2021.
Information Disclosure Statement
The information disclosure statements submitted on 06/10/2026, 03/10/2025, 07/25/2024 and 09/20/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 1 and 5-6 are objected to because of the following informalities:
In claim 1, lines 1-4 should be written as follows “A method of preventing, inhibiting, or reducing (1) an infection by, (2) an inflammatory response caused by infection by, [[or]] (3) apoptosis caused by infection by a virus in a cell or a subject, or (4) treating a[[the]] subject for a viral disease caused by infection by the virus, which comprises …” for clarity of claim language.
Sections of claims 5 and 6 appear to be inadvertently deleted.
Claim 5, should read “The method according to claim 1, wherein about 0.05 mg/kg to about 15 mg/kg of the one or more mitochondrial targeted antioxidants per weight of the subject is administered to the subject”.
Claim 6, should read “The method according to claim 1, wherein about 0.02 - 8.0 mg/kg, about 0.15 - 8.0 mg/kg, about 4.0 - 8.0 mg/kg, about 0.01 - 4.0 mg/kg, about 0.1 - 4.0 mg/kg, or about 2.0 - 4.0 mg/kg of the one or more Nrf2 agonists per weight of the subject is administered to the subject”.
Appropriate correction is required.
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 1, 3-11, 14 and 16 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.
Regarding instant claim 1, the claim recites “A method of preventing, inhibiting, or reducing infection by, … which comprises, consists essentially of, or consists of …”. The transitional phrases “comprising”, “consisting essentially of” and “consisting of” define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim (See MPEP § 2111.03). The transitional phrase “comprising” is open-ended and does not exclude additional, unrecited elements or method steps; whereas the transitional phrase “consisting of” is closed and excludes any element, step, or ingredient not specified in the claim; the transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. The inclusion of all three transitional phrases in the claim contradict each other and renders the scope of the claim indefinite. Therefore, the metes and bounds of claim 1 are indefinite.
Claims 3-11, 14 and 16 depend from claim 1 and are similarly rejected since they do not remedy the indefiniteness.
For the purpose of applying prior art, claim 1 has been interpreted to have the transitional phrase “comprises” appearing in the claim (without consists essentially of, or consists of).
Further regarding claim 11, the claim recites “wherein the virus (a) belongs to the Orthomyxoviridae family, preferably … more preferably … even more preferably … (b) belongs to the Picornaviridae family, preferably … more preferably … even more preferably …most preferably …(c) belongs to the Pneumoviridae family, preferably … more preferably … even more preferably …most preferably …”. The claim includes multiple instances of exemplary claim language, “preferably … more preferably … even more preferably …most preferably”. This renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Therefore, the metes and bounds of claim 11 are indefinite.
For the purpose of applying prior art, claim 11 has been interpreted to
exclude the language that follows the limitation “preferably”, “more preferably”, “even more preferably” or “most preferably”.
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.
Claims 1, 3-4, 7-11, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS) in view of Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS) and Olagnier et al. (SARS-CoV2-mediated suppression of NRF2 signaling reveals potent antiviral and antiinflammatory activity of 4-octyl-itaconate and dimethyl fumarate, published 02 October 2020, hereinafter Olagnier, in the IDS), as evidenced by Smith et al. (Animal and human studies with the mitochondria-targeted antioxidant MitoQ, published 2010, hereinafter Smith).
Claim interpretation : Claim 1 has been interpreted with respect to the elected species of the therapeutic agent being administered, as a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists. Therefore, the claim requires the prior art to either anticipate or render obvious section (c) of claim 1, wherein the virus is not a coronavirus. Therefore, claim 12 drawn to section (a) of claim 1, is withdrawn.
Regarding instant claims 1, 3-4, 11, 14 and 16, Hu teaches the mitochondrial ROS scavenger MitoQ can be a potent inhibitor of respiratory syncytial virus (RSV) infection, wherein primary human bronchial epithelial cells (pBECs) infected with RSV were treated with either DMSO (vehicle) or MitoQ (Pg. 16, first full paragraph). Hu teaches RSV infection of the cells treated with MitoQ showed significantly (p<0.001) reduced numbers of viral genomes compared to the vehicle (Pg. 16, first full paragraph). Hu teaches mice treated with MitoQ (Figure 9AB, grey bars) showed significantly (p<0.001) reduced (>4 fold) viral replication and infectious virus production compared to the vehicle control for days 4–7 (Pg. 16, second full paragraph). Hu teaches MitoQ is able to decrease viremia and airway inflammation in mice (Pg. 17, last paragraph). Hu teaches MitoQ to be mitoquinone mesylate, a mitochondrially-targeted antioxidant (Pg. 26, third paragraph). Therefore, Hu discloses a method of inhibiting, or reducing infection by, an inflammatory response caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus comprising administering a mitochondrial targeted antioxidant to the subject.
Hu do not teach administering a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject.
Cho teaches the Nrf2-ARE mediated antioxidant pathways to be implicated in host defense against respiratory syncytial virus (RSV) infection (Abstract; Pg. 149, first column, last paragraph). Cho teaches Nrf2 deficiency enhanced respiratory syncytial virus (RSV)-induced nasal airway injury (Pg. 142, Figure 5). Sulforaphane pretreatment of wild-type (Nrf2+/+) mice significantly limited lung RSV replication and virus-induced inflammation (Abstract; Pg. 146, second column, second paragraph). Sulforaphane, by virtue of its inherent property, is a Nrf2 agonist.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Hu and Cho to have administered an Nrf2 agonist, as taught by Cho, in combination with a mitochondrial targeted antioxidant, say MitoQ, as taught by Hu in a method of inhibiting, or reducing infection by, an inflammatory response caused by infection by a virus (i.e., RSV) in a cell or a subject or treating the subject for a viral disease caused by infection by the virus (i.e., RSV), wherein the virus is not a coronavirus, to arrive at the method of the instant claims with a reasonable expectation of success.
Hu teaches that the mitochondrial ROS scavenger MitoQ can be a potent inhibitor of respiratory syncytial virus (RSV) infection. Hu teaches RSV infection of the cells treated with MitoQ showed significantly (p<0.001) reduced numbers of viral genomes compared to the vehicle. Hu teaches mice treated with MitoQ (Figure 9AB, grey bars) showed significantly (p<0.001) reduced (>4 fold) viral replication and infectious virus production compared to the vehicle. Hu teaches MitoQ is a mitochondrially-targeted antioxidant. Hu emphasizes that there are no effective anti-RSV therapeutics generally available (Pg. 1, last paragraph). Cho teaches the Nrf2-ARE mediated antioxidant pathways to be implicated in host defense against respiratory syncytial virus (RSV) infection. Cho teaches sulforaphane pretreatment significantly limited lung RSV replication and virus-induced inflammation in of wild-type (Nrf2+/+) mice.
Therefore, one of ordinary skill in the art would have been motivated to use a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists in a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus, according to the instant claims. The motivation being to provide an effective ant-RSV treatment, thereby improving treatment outcomes (Cho, Pg. 149, first column, last paragraph).
According to MPEP 2144.06 (I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In the instant case, both the MitoQ of Hu (a mitochondrially-targeted antioxidant) and the sulforaphane of Cho (an Nrf2 agonist) are taught to be useful for the same purpose, inhibiting respiratory syncytial virus (RSV) infection and virus-induced inflammation. This renders the use of a combination of a mitochondrial targeted antioxidant and an Nrf2 agonist in a method of treating an infection by a virus prima facie obvious.
With regards to the elected species of mitoquinol and dimethyl fumarate (DMF) as the species of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists, respectively, Hu teaches MitoQ to be mitoquinone mesylate. Smith evidences that MitoQ exerts its antioxidant effect through its active antioxidant quinol form (Pg. 96, second column, last paragraph – Pg. 97, first column, continued paragraph; Figure 2), thus showing that the disclosure of Hu meets the instantly elected species of one or more mitochondrial targeted antioxidants, mitoquinol (i.e., MitoQ undergoes continuous redox recycling between its oxidized (quinone) and reduced (quinol) forms inside the cells and mitochondria).
While Hu and Cho do not teach the elected species of DMF, Olagnier teaches DMF, an Nrf2 agonist, induces a cellular antiviral program that inhibits SARs-CoV2 replication and exhibits inhibitory activity against replication of several other pathogenic viruses (i.e., non-coronavirus pathogens) (Abstract; Pg. 2, first column, fifth paragraph). Olagnier teaches the Nrf2agonists are plausible broad-spectrum antiviral and anti-inflammatory agents (Pg. 2, first column, fifth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Hu, Cho and Olagnier, to have substituted the sulforaphane of Cho with DMF of Olagnier or alternatively included DMF with sulforaphane (the transitional phrase “comprises” allows for additional agents to be included), to arrive at the method of the instant claims comprising administering the instantly elected species of combination therapy, with a reasonable expectation of success. The motivation being to extend the therapeutic benefit to other pathogenic viruses (Olagnier, Pg. 2, first column, fifth paragraph).
According to MPEP 2144.06 (II), “An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)”. In the instant case, the sulforaphane of Cho and the DMF of Olagnier are both Nrf2 agonists and are considered equivalents in the art. Thus, rendering their substitution prima facie obvious.
The claim also recites “one or more Nrf2 agonists”, allowing the inclusion of both sulforaphane and DMF in the method of treating RSV infection.
Therefore, the combined teachings of Hu and Cho render the method of instant claim 1 with respect to the broader recitation of administering a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists, prima facie obvious AND the combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) render the method of instant claim 1 with respect to the elected species of a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists, prima facie obvious.
The combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) further render obvious the limitations of instant claims 3-4, 11, 14 and 16 since RSV belongs to the Pneumoviridae family.
Regarding instant claims 7-10, the combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) renders obvious the method of instant claim 1. Hu teaches the MitoQ is administered daily for at least 7 days, given with water containing the mitochondria-specific ROS scavenger (i.e., via the oral route) BALB/c mice infected intranasally with recombinant RSV (Pg. 25, last paragraph). Cho teaches mice were treated with R-sulforaphane via oral gavage prior to intranasal instillation with RSV (Pg. 139, first column, first full paragraph). Thus, the mitochondrial targeted antioxidant, MitoQ taught by Hu and the Nrf2 agonist, sulforaphane of Cho are administered to the subject orally either before/after exposure to the virus and occurs for at least 1 day after exposure to the virus.
Therefore, the combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) render obvious the limitations of instant claims 7-10.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS) in view of Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS) and Olagnier et al. (SARS-CoV2-mediated suppression of NRF2 signaling reveals potent antiviral and antiinflammatory activity of 4-octyl-itaconate and dimethyl fumarate, published 02 October 2020, hereinafter Olagnier, in the IDS), as evidenced by Smith et al. (Animal and human studies with the mitochondria-targeted antioxidant MitoQ, published 2010, hereinafter Smith) as applied to claims 1, 3-4, 7-11, 14 and 16 above, and further in view of Smith et al. (Animal and human studies with the mitochondria-targeted antioxidant MitoQ, published 2010, hereinafter Smith).
The teachings of Hu, Cho and Olagnier (as evidenced by Smith) are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claim 5, the combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) renders obvious the method of instant claim 1. Hu, Cho and Olagnier do not explicitly teach administering about 0.05 mg/kg to about 15 mg/kg of the one or more mitochondrial targeted antioxidants.
Smith teaches MitoQ showed good pharmacokinetic behavior with oral dosing at 80 mg (1 mg/kg) resulting in a plasma maximal concentration of 33.15 ng/mL and after ∼1h (Pg. 99, second column, second full paragraph).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount of the one or more mitochondrial targeted antioxidants, in the absence of any criticality of the recited amounts. The optimal dosing would have been determined taking into consideration a variety of factors, such as the age, weight, sex, diet, severity of the medical condition of the patient and pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles. This is well within the skill of a person of ordinary skill in the pharmaceutical arts.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS) in view of Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS) and Olagnier et al. (SARS-CoV2-mediated suppression of NRF2 signaling reveals potent antiviral and antiinflammatory activity of 4-octyl-itaconate and dimethyl fumarate, published 02 October 2020, hereinafter Olagnier, in the IDS), as evidenced by Smith et al. (Animal and human studies with the mitochondria-targeted antioxidant MitoQ, published 2010, hereinafter Smith) as applied to claims 1, 3-4, 7-11, 14 and 16 above and further in view of Boulas et al. (WO 2016/205270, publication date 22 December 2016, hereinafter Boulas).
The teachings of Hu, Cho and Olagnier (as evidenced by Smith) are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claim 6, the combined teachings of Hu, Cho and Olagnier (as evidenced by Smith) renders obvious the method of instant claim 1.
Hu, Cho and Olagnier do not explicitly teach administering about 0.02 - 8.0 mg/kg, about 0.15 - 8.0 mg/kg, about 4.0 - 8.0 mg/kg, about 0.01 - 4.0 mg/kg, about 0.1 - 4.0 mg/kg, or about 2.0 - 4.0 mg/kg of the one or more Nrf2 agonists.
Boulas teaches pharmaceutical compositions of diemthyl fumarate (DMF) (Abstract). Boulas teaches a daily amount of DMF ranging from about 1 mg/kg to about 50 mg/kg (Pg. 24, continued paragraph).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount of the one or more Nrf2 agonists, in the absence of any criticality of the recited amounts. The optimal dosing would have been determined taking into consideration a variety of factors, such as the age, weight, sex, diet, severity of the medical condition of the patient and pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles. This is well within the skill of a person of ordinary skill in the pharmaceutical arts.
Note to Applicant: The examiner notes Applicant’s indication of a synergistic inhibition of RSV replication in lung epithelial cells for a combination of Mito-MES (MITO-MES also stands for mitoquinol) and DMF (Figure 6) in the specification. However, this synergistic result is not commensurate in scope with claim 16 drawn broadly to the instantly elected combination of mitoquinol and DMF at any concentration range, OR to the scope of claim 1, drawn broadly to a method of treatment comprising administering any combination of mitochondrial targeted antioxidants and Nrf2 agonists and its dependent claims 3-11 and 14.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
11. Claims 1, 3-11, 14 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 9-10, 12, 14-16, 20, 23-24 of co-pending Application No 17/570,737 in view of Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS) and Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus, comprising administering one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject.
The instant claims are drawn to a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus, which comprises, consists essentially of, or consists of: (a) administering one or more mitochondrial targeted antioxidants to the cell or the subject, wherein the virus is not a coronavirus or a respiratory syncytial virus (RSV); or (b) administering one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus; or (c) administering a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus.
The claims of the co-pending ‘737 application are drawn to a method of preventing, inhibiting, or reducing (a) an infection by, (b) an inflammatory response caused by, (c) apoptosis caused by a coronavirus in a cell or a subject, or (d) treating a subject for a coronavirus disease caused by infection by a coronavirus, which comprises administering the composition according to claim 14 to the cell or the subject.
Claims 1, 9, 14 and 24 of the co-pending ‘737 application teaches the use of a combination of a mitochondrial targeted antioxidant (mitoquinol mesylate) and an Nrf2 agonist (DMF) (claims 9 and 24) in a method of preventing, inhibiting, or reducing (a) an infection by, (b) an inflammatory response caused by, (c) apoptosis caused by a coronavirus in a cell or a subject, or (d) treating a subject for a coronavirus disease caused by infection by a coronavirus.
The co-pending ‘737 application does not teach treating a virus that is not a coronavirus.
Hu teaches that the mitochondrial ROS scavenger MitoQ can be a potent inhibitor of respiratory syncytial virus (RSV) infection, wherein primary human bronchial epithelial cells (pBECs) infected with RSV were treated with either DMSO (vehicle) or MitoQ (Pg. 16, first full paragraph). Hu teaches RSV infection of the cells treated with MitoQ showed significantly (p<0.001) reduced numbers of viral genomes compared to the vehicle (Pg. 16, first full paragraph). Hu teaches mice treated with MitoQ (Figure 9AB, grey bars) showed significantly (p<0.001) reduced (>4 fold) viral replication and infectious virus production compared to the vehicle control for days 4–7 (Pg. 16, second full paragraph). Hu teaches MitoQ is able to decrease viremia and airway inflammation in mice (Pg. 17, last paragraph). Hu teaches MitoQ to be mitoquinone mesylate, a mitochondrially-targeted antioxidant (Pg. 26, third paragraph).
Cho teaches the Nrf2-ARE mediated antioxidant pathways to be implicated in host defense against respiratory syncytial virus (RSV) infection (Abstract; Pg. 149, first column, last paragraph). Cho teaches Nrf2 deficiency enhanced respiratory syncytial virus (RSV)-induced nasal airway injury (Pg. 142, Figure 5). Sulforaphane pretreatment of wild-type (Nrf2+/+) mice significantly limited lung RSV replication and virus-induced inflammation (Abstract; Pg. 146, second column, second paragraph). Sulforaphane, by virtue of its inherent property, is a Nrf2 agonist.
The teachings of Hu and Cho establish that the combination of a mitochondrial targeted antioxidant and an Nrf2 agonist can be applied to the treatment of viruses other than a coronavirus, say, RSV. RSV belongs to the Pneumoviridae family (satisfying instant claim 11).
Claims 4-5 of the co-pending ‘737 application anticipates the dosage mitochondrial targeted antioxidant as in instant claim 5. Claims 6-7 and 10 of the co-pending ‘737 application anticipates the dosing schedule (administered daily), the route of administration (orally, subcutaneously, or intravenously) and the timing of administration (before, during, and/or after the subject was exposed or likely exposed to the virus, and the administration occurs for at least 1 - 10 days after the exposure or likely exposure to the virus), as in instant claims 7-10.
Moreover, given that the combination of a mitochondrial targeted antioxidant and Nrf2 agonist is taught by the reference application, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount of the Nrf2 agonist as in instant claim 6, in the absence of any criticality of the recited amounts.
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Overall, the teachings of the ‘737 application in view of Hu and Cho render the method of the instant claims prima facie obvious.
The instant claims 1, 3-11, 14 and 16 and claims 1-2, 4-7, 9-10, 12, 14-16, 20, 23-24 of co-pending Application No 17/570,737 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. Claims 1, 3-11, 14 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 9-11, 14-15 of co-pending Application No 18/004,556 in view of Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS) and Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject, comprising administering one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject.
The instant claims are drawn to a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus, which comprises, consists essentially of, or consists of: (a) administering one or more mitochondrial targeted antioxidants to the cell or the subject, wherein the virus is not a coronavirus or a respiratory syncytial virus (RSV); or (b) administering one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus; or (c) administering a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus.
The claims of the co-pending ‘556 application are drawn to a method of preventing, inhibiting, or reducing (a) an infection by, (b) an inflammatory response caused by, (c) apoptosis caused by a coronavirus in a cell or a subject, which comprises administering one or more mitochondrial targeted antioxidants in the form of the composition according to claim 14 to the cell or the subject.
Claims 1, 9, 14 and 15 of the co-pending ‘556 application teaches the use of a combination of a mitochondrial targeted antioxidant (mitoquinol mesylate or mitoquinone mesylate) and an Nrf2 agonist (DMF) (claims 14 and 15) in a method of preventing, inhibiting, or reducing (a) an infection by, (b) an inflammatory response caused by, (c) apoptosis caused by a coronavirus in a cell or a subject.
The co-pending ‘556 application does not teach treating a virus that is not a coronavirus.
Hu teaches that the mitochondrial ROS scavenger MitoQ can be a potent inhibitor of respiratory syncytial virus (RSV) infection, wherein primary human bronchial epithelial cells (pBECs) infected with RSV were treated with either DMSO (vehicle) or MitoQ (Pg. 16, first full paragraph). Hu teaches RSV infection of the cells treated with MitoQ showed significantly (p<0.001) reduced numbers of viral genomes compared to the vehicle (Pg. 16, first full paragraph). Hu teaches mice treated with MitoQ (Figure 9AB, grey bars) showed significantly (p<0.001) reduced (>4 fold) viral replication and infectious virus production compared to the vehicle control for days 4–7 (Pg. 16, second full paragraph). Hu teaches MitoQ is able to decrease viremia and airway inflammation in mice (Pg. 17, last paragraph). Hu teaches MitoQ to be mitoquinone mesylate, a mitochondrially-targeted antioxidant (Pg. 26, third paragraph).
Cho teaches the Nrf2-ARE mediated antioxidant pathways to be implicated in host defense against respiratory syncytial virus (RSV) infection (Abstract; Pg. 149, first column, last paragraph). Cho teaches Nrf2 deficiency enhanced respiratory syncytial virus (RSV)-induced nasal airway injury (Pg. 142, Figure 5). Sulforaphane pretreatment of wild-type (Nrf2+/+) mice significantly limited lung RSV replication and virus-induced inflammation (Abstract; Pg. 146, second column, second paragraph). Sulforaphane, by virtue of its inherent property, is a Nrf2 agonist.
The teachings of Hu and Cho establish that the combination of a mitochondrial targeted antioxidant and an Nrf2 agonist can be applied to the treatment of viruses other than a coronavirus, say, RSV. RSV belongs to the Pneumoviridae family (satisfying instant claim 11).
Claims 4-5 of the co-pending ‘556 application anticipates the dosage mitochondrial targeted antioxidant as in instant claim 5. Claims 6-7 and 10-11 of the co-pending ‘556 application anticipates the dosing schedule (administered daily), the route of administration (orally, subcutaneously, or intravenously) and the timing of administration (before, during, and/or after the subject was exposed or likely exposed to the virus, and the administration occurs for at least 1 - 10 days after the exposure or likely exposure to the virus), as in instant claims 7-10.
Moreover, given that the combination of a mitochondrial targeted antioxidant and Nrf2 agonist is taught by the reference application, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount of the Nrf2 agonist as in instant claim 6, in the absence of any criticality of the recited amounts.
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Overall, the teachings of the ‘556 application in view of Hu and Cho render the method of the instant claims prima facie obvious.
The instant claims 1, 3-11, 14 and 16 and claims 1-2, 4-7, 9-11, 14-15 of co-pending Application No 18/004,556 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
13. Claims 1, 3-11, 14 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-7, 10, 18-19 of co-pending Application No 18/353,069 in view of Hu et al. (Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production, published 27 June 2019, hereinafter Hu, in the IDS), Cho et al. (Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, published 17 October 2008, hereinafter Cho, in the IDS), Smith et al. (Animal and human studies with the mitochondria-targeted antioxidant MitoQ, published 2010, hereinafter Smith) and Boulas et al. (WO 2016/205270 A1, publication date 22 December 2016, hereinafter Boulas).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of treating, inhibiting, or reducing infection by a virus in a subject, comprising administering a mitochondrial targeted antioxidant and one or more Nrf2 agonists to the cell or the subject.
The instant claims are drawn to a method of preventing, inhibiting, or reducing infection by, an inflammatory response caused by infection by, or apoptosis caused by infection by a virus in a cell or a subject or treating the subject for a viral disease caused by infection by the virus, which comprises, consists essentially of, or consists of: (a) administering one or more mitochondrial targeted antioxidants to the cell or the subject, wherein the virus is not a coronavirus or a respiratory syncytial virus (RSV); or (b) administering one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus; or (c) administering a combination of one or more mitochondrial targeted antioxidants and one or more Nrf2 agonists to the cell or the subject, wherein the virus is not a coronavirus.
The claims of the co-pending ‘069 application are drawn to a method of treating, inhibiting, and/or reducing an infection by a virus or a symptom caused by the infection in a subject, which comprises administering one or more mitochondrial targeted antioxidants in the form of the composition according to claim 1 to the subject and compositions thereof.
Claims 1-2, 6-7 and 18-19 of the co-pending ‘069 application teaches the use of a combination of a mitochondrial targeted antioxidant (mitoquinol mesylate or mitoquinone mesylate) and an Nrf2 agonist (DMF) in a method of treating, inhibiting, or reducing an infection by a virus in a subject and anticipates the scope of the instant claims with respect to “treating, inhibiting, or reducing an infection by a virus in a subject” (instant claims 1, 3-4, 14 and 16).
The claims of the co-pending ‘069 application does not teach the limitations of instant claims 5-11.
Hu teaches that the mitochondrial ROS scavenger MitoQ can be a potent inhibitor of respiratory syncytial virus (RSV) infection (Pg. 16, first full paragraph). Hu teaches the MitoQ is administered daily for at least 7 days, given with water containing the mitochondria-specific ROS scavenger (i.e., via the oral route) BALB/c mice infected intranasally with recombinant RSV (Pg. 25, last paragraph). Cho teaches mice were treated with R-sulforaphane via oral gavage prior to intranasal instillation with RSV (Pg. 139, first column, first full paragraph). Thus, the mitochondrial targeted antioxidant, MitoQ taught by Hu and the Nrf2 agonist, sulforaphane of Cho are administered to the subject orally either before/after exposure to the virus and occurs for at least 1 day after exposure to the virus (i.e., RSV virus, which belongs to the Pneumoviridae family).
Smith teaches MitoQ showed good pharmacokinetic behavior with oral dosing at 80 mg (1 mg/kg) resulting in a plasma maximal concentration of 33.15 ng/mL and after ∼1h (Pg. 99, second column, second full paragraph).
Boulas teaches pharmaceutical compositions of diemthyl fumarate (DMF) (Abstract). Boulas teaches a daily amount of DMF ranging from about 1 mg/kg to about 50 mg/kg (Pg. 24, continued paragraph).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount of the one or more mitochondrial targeted antioxidants and/or one or more Nrf2 agonists, in the absence of any criticality of the recited amounts. The optimal dosing would have been determined taking into consideration a variety of factors, such as the age, weight, sex, diet, severity of the medical condition of the patient and pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles. This is well within the skill of a person of ordinary skill in the pharmaceutical arts.
Overall, the teachings of the ‘069 application in view of Hu, Cho, Smith and Boulas render the method of the instant claims prima facie obvious.
The instant claims 1, 3-11, 14 and 16 and claims 1-2, 5-7, 10, 18-19 of co-pending Application No 18/353,069 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 3-11, 14 and 16 are rejected.
Claims 1 and 5-6 are objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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