DETAILED CORRESPONDENCE
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 15, 2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment to the claims, filed June 15, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 1, 2, and 4-19 are pending in the application.
Applicant’s remarks filed June 15, 2026 in response to the final rejection filed April 13, 2026 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 40 has been canceled by applicant’s amendment filed June 15, 2026 and rejections previously applied to claim 40 are withdrawn.
Restriction/Election
In view of applicant’s amendment to claim 1 to limit the route of administration to intranasal administration and applicant’s amendments to claims 1 and 19 to limit the lung cell targeting segment to SEQ ID NO: 9, the requirement for an election of species between inhalation and intranasal administration and the requirement for an election of species between SEQ ID NO: 2 and SEQ ID NO: 9 as set forth at pp. 3-6 of the Office action filed September 11, 2025, is withdrawn.
Claims 1, 2, and 4-19 are being examined on the merits.
Claim Objections
Claims 1, 4, 18, and 19 are objected to because of the following informalities:
Claims 1, 4, and 19 are objected to in the recitation of “an amino acid sequence that is at least 90% identical” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite (with markings to show changes made) “an amino acid sequence that has[[is]] at least 90% sequence identity
Claim 18 is objected to in the recitation of “and the additional antiviral therapeutic agent” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite (with markings to show changes made) “and the at least one additional antiviral therapeutic agent.”
Claim Rejections - 35 USC § 112(b)
The rejection of claim 17 under 35 U.S.C. 112(b) as being indefinite in the recitation of “about” is withdrawn in view of applicant’s amendment to claim 17 to delete the term “about.”
Claims 1, 2, and 4-19 are newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 (claims 2 and 4-19 dependent therefrom) recites the limitation "the virus induced dysregulated inflammatory response." There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution, the phrase “wherein the treatment inhibits and/or ameliorates at least one symptom of the virus induced dysregulated inflammatory response” in claim 1 is interpreted as meaning wherein the treatment inhibits and/or ameliorates at least one symptom of the Coronavirus or Influenza virus infection.
Claim 1 recites “administering intranasally” in lines 3-5 and claim 2, which depends from claim 1, is confusing in the recitation of “administered by inhalation or instillation.” In the interest of advancing prosecution, applicant may consider an amendment to cancel claim 2.
Claim 2 recites the limitation "the composition comprising the NEIL2 fusion peptide." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites “administering a Nei-like DNA glycosylase 2 (NEIL2) fusion peptide” in lines 3-6 and claim 7 (claims 8-10 dependent therefrom), which depends from claim 1, is confusing in the recitation of “wherein the NEIL2 peptide is a fusion peptide or peptide complex comprising a targeting segment.” In the interest of advancing prosecution, applicant may consider an amendment to cancel claim 7.
Claim 1 recites “fused to (ii) a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9” in lines 8-9 and claim 9, which depends from claim 1, is confusing in the recitation of “wherein the lung targeting segment has an amino acid sequence of SEQ ID NO: 2…” In the interest of advancing prosecution, applicant may consider an amendment to cancel claims 9 and 10.
Claim 1 recites “treating Coronavirus or Influenza virus” and claim 13 (claim 14 dependent therefrom), which depends from claim 1, is confusing in the recitation of “wherein the virus is from Coronaviridae, Pneumoviridae, Orthomyxoviridae, Filoviridae, Flaviviridae, or Poxviridae families.” In the interest of advancing prosecution, applicant may consider an amendment to cancel claim 13.
Claim 1 recites “treating Coronavirus or Influenza virus” and claim 14, which depends from claim 1, is confusing in the recitation of “wherein the virus is a Coronavirus or Pneumovirus.” In the interest of advancing prosecution, applicant may consider an amendment to delete the alternative of “Pneumovirus.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 6-10, and 13 are newly rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 2, claim 1 has been amended to recite “administering intranasally” and claim 2, which depends from claim 1, recites “administered by inhalation or instillation” and does not further limit claim 1 as amended.
Regarding claim 6, the recitation of “an amino acid sequence of SEQ ID NO: 1” is interpreted as any two or more contiguous amino acids of SEQ ID NO: 1. Claim 1 has been amended to recite “a NEIL2 peptide having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 1 or a functional fragment thereof having DNA glycosylase activity” and claim 6, which depends from claim 1, does not further limit claim 1 as amended.
Regarding claim 7, claim 1 has been amended to recite “(NEIL2) fusion peptide” and claim 7, which depends from claim 1, recites “wherein the NEIL2 peptide is a fusion peptide or peptide complex comprising a targeting segment” and does not further limit claim 1 as amended.
Regarding claim 8, claim 1 has been amended to recite “fused to (ii) a lung cell targeting segment” and claim 8, which ultimately depends from claim 1, recites “wherein the targeting segment is a lung cell targeting segment” and does not further limit claim 1 as amended.
Regarding claim 9, claim 1 has been amended to recite “fused to (ii) a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9” and claim 9, which ultimately depends from claim 1, recites “wherein the lung targeting segment has an amino acid sequence of SEQ ID NO: 2…” and does not further limit claim 1 as amended.
Regarding claim 10, the recitation of “an amino acid sequence of SEQ ID NO: 9” is interpreted as any two or more contiguous amino acids of SEQ ID NO: 9. Claim 1 has been amended to recite “fused to (ii) a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9” and claim 10, which ultimately depends from claim 1, does not further limit claim 1 as amended.
Regarding claim 13, claim 1 has been amended to recite “treating Coronavirus or Influenza virus” and claim 13, which depends from claim 1, recites “wherein the virus is from Coronaviridae, Pneumoviridae, Orthomyxoviridae, Filoviridae, Flaviviridae, or Poxviridae families” and does not further limit claim 1 as amended.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
Claims 1, 2, and 4-19 are newly rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
This rejection is necessitated by applicant’s amendments to claims 1 and 19 to recite “wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.”
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
According to MPEP 2163.II.A.3.(a).ii), [s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and (5) the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
As amended, claims 1 and 9 recite a genus of NEIL2 fusion peptides comprising a NEIL2 peptide having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 or a functional fragment thereof having DNA glycosylase activity, fused to a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9, wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
The specification discloses a single representative species of the genus of recited NEIL2 fusion peptides – a NEIL2 fusion peptide comprising the NEIL2 peptide of SEQ ID NO: 1 fused to the lung targeting segment of SEQ ID NO: 9, which binds to the 5’-untranslated region of SARS-CoV-2 genomic RNA. Other than this single representative species, the specification fails to disclose the domain or motif of NEIL2 that binds to SARS-CoV-2 genomic RNA and further fails to disclose any modifications to the NEIL2 peptide of SEQ ID NO: 1 that maintain activity to bind to viral genomic RNA and reduce viral replication. Rather, the specification discloses the RNA binding domain of NEIL2 has not been characterized and discloses an “experimental plan” to identify the NEIL2 RNA binding domain and analyze protein-RNA 5’-UTR interactions (beginning at paragraph [00133] of the substitute specification filed March 19, 2026).
In this case, it appears that applicant is relying on a “make and test” rationale to show possession of the recited genus of NEIL2 fusion peptides that bind to viral genomic RNA and reduce viral replication. However, according to MPEP 2163.II.3, “An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed.” In this case, such a “make and test” rationale is not sufficient to describe the members of the genus so that one of skill can 'visualize or recognize' the members of the genus one of skill in the art would reasonably conclude that applicant was not in possession of the recited genus of NEIL2 fusion peptides.
For these reasons, it is the examiner’s position that the specification fails to satisfy the written description requirement of 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 103
The rejection of claims 1, 2, 4-9, 11-13, and 16-18 under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US 2011/0110908 A1; cited on Form PTO-892 filed December 19, 2025; hereafter “Wilson”) in view of Li et al. (Cell. Mol. Life Sci. 72:2973-2988, 2015; cited on Form PTO-892 filed December 19, 2025; hereafter “Li”), To et al. (Antioxid. Redox Signal. 32:929-942, 2020; cited on Form PTO-892 filed December 19, 2025; hereafter “To”), and Hazra et al. (US 2020/0102358 A1; cited on Form PTO-892 filed December 19, 2025; hereafter “Hazra”) as applied to claim 19, and further in view of Tavares et al. (Inflamm. Res. 66:283-302, 2017; cited on Form PTO-892 filed December 19, 2025; hereafter “Tavares”),
the rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Li, To, Hazra, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-18, and further in view of Prasun, P. (DNA Cell Biol. 40:713-719, 2021; cited on Form PTO-892 filed December 19, 2025; hereafter “Prasun”),
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, and Hazra as applied to claim 19, and further in view of Tavares, and
the rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, Hazra, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-18, and further in view of Prasun
are withdrawn in view of applicant’s amendment to claim 1 to delete the phrase “virus induced dysregulated inflammatory response,” applicant’s amendment to claim 1 to recite “treating a Coronavirus or Influenza virus infection,” and upon further consideration of the rejections.
Claims 1, 2, 4-13, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson in view of Li, To, and Hazra.
The instant rejection was previously applied only to claim 19 but has been modified to include claims 1, 2, 4-13, and 16-18 in view of applicant’s amendment to claim 1.
As amended, claims 1, 2, 4-13, and 16-18 are drawn to a method for treating a Coronavirus or Influenza virus infection in a subject in need of such treatment, the method comprising the step of administering intranasally a therapeutically effective amount of a Nei-like DNA glycosylase 2 (NEIL2) fusion peptide comprising (i) a NEIL2 peptide having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 or a functional fragment thereof having DNA glycosylase activity, fused to (ii) a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9 wherein the treatment inhibits and/or ameliorates at least one symptom of the virus induced dysregulated inflammatory response and wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
As amended, claim 19 is drawn to a method for treating a subject having a Coronavirus or Influenza virus infection comprising the step of administering a therapeutically effective amount of a NEIL2 fusion peptide comprising a NEIL2 peptide having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 fused to a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9 to the subject by inhalation or instillation to the lungs, wherein the NEIL2 fusion peptide binds to viral genomic RNA and the administration reduces viral replication.
Wilson hypothesizes that an acceptable lesion equilibrium is normally maintained in mitochondrial DNA (mtDNA) in all cells through a balance between the damage to mtDNA caused by the normal endogenous production of reactive oxygen species (ROS) as a byproduct of oxidative phosphorylation and its subsequent repair (paragraph [0018]). According to Wilson, this equilibrium is altered during various pathologies due to increased exposure to elevated levels of ROS and reactive nitrogen species (RNS), resulting in increased damage to mtDNA (paragraph [0018]) and the increased production of ROS exacerbates the ongoing stress in the cells leading to intensified oxidative stress in the cell and when this process reaches a critical level, the cell will die (paragraph [0018]). Wilson teaches that the present invention, which is administering a DNA repair enzyme including NEIL2, aborts this vicious cycle in its initial stages, and normalizes or at least inhibits further damage to mtDNA, thus enhancing cell viability (paragraphs [0018] and [0048]; claim 10).
Wilson teaches a method of treating a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA, comprising administering to a patient in need thereof, a composition comprising a multi-domain conjugate or fusion protein comprising a protein transduction domain, a mitochondrial targeting sequence and a DNA repair enzyme, in a therapeutically effective amount, wherein the disease or condition is inflammatory bowel disease, ischemic heart disease, acute lung injury or acute respiratory distress syndrome, or radiation-induced brain injury (claim 10).
The differences between Wilson and instant claims 1 and 19 are:
Wilson does not teach treating a Coronavirus or Influenza virus infection with NEIL2; and
Wilson does not teach administering a NEIL2 fusion peptide comprising a NEIL2 peptide having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 fused to a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9 intranasally or by inhalation to the lungs, wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
Regarding difference 1), Li teaches inflammation-induced reactive oxygen and nitrogen species (RONS) constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo (p. 2974, column 1, middle).
To reports on the role of mitochondrial ROS in the context of viral infections in vivo (p. 929, Abstract). To teaches influenza virus infection promotes mitochondrial ROS production, which drives innate immune inflammation and exacerbates viral pathogenesis (p. 929, Abstract). To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
Regarding difference 2), Hazra teaches delivering recombinant NEIL2 into the lungs of a host to reduce ROS damage to the transcribed genome in the lungs (paragraph [0008]). Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1, and teaches the NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9, and teaches covalent coupling of NEIL2 to a carrier peptide (paragraphs [0048] and [0055]). Hazra teaches pulmonary delivery of a pharmaceutical composition of NEIL2 intranasally or by inhalation (paragraphs [0128], [0136], [0141], and [0142]).
In view of Wilson, Li, To, and Hazra, it would have been obvious to one of ordinary skill in the art to treat influenza A virus infection by administering the NEIL2 fusion protein of Hazra intranasally or by inhalation.
One would have been motivated and would have expected success to treat influenza A virus infection with NEIL2 because Wilson taught administering NEIL2 to treat a disease or disorder by inhibiting ROS-mediated damage to mitochondrial DNA, Li taught inflammation-induced RONS constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo, and To taught influenza virus infection promotes ROS production in the mitochondrion, which drives innate immune inflammation and exacerbates viral pathogenesis, while mitochondrion-targeted pharmacological inhibition of ROS-mediated damage and oxidative stress to the mitochondrion alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
One would have been motivated and would have expected success to administer the NEIL2 fusion protein of Hazra intranasally or by inhalation because Wilson taught administering NEIL2 to treat a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA, To taught localized delivery of a pharmacologic to the lung to treat the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection, and Hazra taught delivering a fusion of NEIL2 coupled to the lung targeting segment of SEQ ID NO: 9 into the lungs of a host to reduce ROS damage and taught pulmonary delivery of NEIL2 by inhalation.
Regarding the limitation “wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication,” the combination of Wilson, Li, To, and Hazra does not teach or suggest the function or property of binding to viral genomic RNA and reducing viral replication. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent (MPEP 2112.01). Given that the structure of the NEIL2 fusion protein of Hazra is substantially identical to recited NEIL2 fusion protein of claims 1 and 19, it the examiner’s position that the NEIL2 fusion protein of Hazra would inherently bind to viral genomic RNA and reduce viral replication when administered to treat influenza A virus by inhalation. Since the Office does not have the facilities for examining and comparing applicants' NEIL2 fusion peptide with the fusion protein of Hazra, the burden is on the applicant to show an unobvious difference between the recited NEIL2 fusion peptide and the fusion protein of Hazra. See MPEP 2112.IV and 2112.V.
Regarding claim 2, as stated above, claim 2 is confusing in view of the amendment to claim 1, which limits the administration to intranasal administration. Nonetheless, as stated above, it would have been obvious to one of ordinary skill in the art to treat influenza A virus by administering the NEIL2 fusion protein of Hazra by inhalation.
Regarding claims 4 and 6, as stated above, Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1.
Regarding claim 5, Hazra teaches using a functional segment of NEIL2 (paragraph [0014]).
Regarding claims 7-10, as previously stated, Hazra teaches NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9.
Regarding claims 11, 12, and 18, as stated above, To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
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 – the idea of combining them flows logically from their having been individually taught in the prior art. In accordance with MPEP 2144.06.I, in view of the combined teachings of Wilson, Li, To, and Hazra, it would have been obvious to treat influenza A virus and its clinical symptoms by administering a composition comprising the NEIL2 fusion protein of Hazra and Mito-TEMPO of To intranasally or by inhalation.
Regarding claim 13, as stated above, claim 13 is confusing in view of amended claim 1, which is limited to treating Coronavirus or Influenza virus infection and in the interest of advancing prosecution, claim 13 is included in the rejection.
Regarding claim 16, Wilson teaches the term “patient” is used to describe a human (paragraph [0064]), and To and Tavares are related to influenza A virus infection in a human.
Regarding claim 17, Hazra teaches doses between 0.001 mg/kg and 10 mg/kg body weight, most preferably between 0.5 and 1 mg/kg body weight (paragraph [0147]).
Therefore, the method of claims 1, 2, 4-13, and 16-19 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson in view of Li, To, and Hazra as applied to claims 1, 2, 4-13, and 16-19 above, and further in view of Prasun.
Claim 14 is drawn to the method of claim 13, wherein the virus is a Coronavirus or Pneumovirus.
Claim 15 is drawn to the method of claim 1, wherein the Coronavirus is a SARS-CoV-2 virus.
The relevant teachings of Wilson, Li, To, and Hazra as applied to claims 1, 2, 4-13, and 16-19 are set forth above.
The difference between the combination of Wilson, Li, To, and Hazra and claims 14 and 15 is that the combination does not teach or suggest a Coronavirus or a SARS-CoV-2 virus.
Prasun examines pathogenesis of COVID-19 from a mitochondrial perspective (p. 713, abstract). Prasun teaches SARS-CoV-2 is the causative agent of COVID-19 (p. 713, column 2, bottom) and that after SARS-CoV-2 enters the cell, it hijacks the mitochondrial machinery, which may lead to increased oxidative stress (p. 714, column 2, top) and causing increased ROS generation and release of oxidized mitochondrial DNA (p. 716, column 1, bottom). Prasun teaches amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients (p. 717, column 1, middle).
In view of the additional teachings of Prasun, it would have been obvious to one of ordinary skill in the art before the effective filing date to treat SARS-CoV-2 infection by administering the NEIL2 fusion protein of Hazra intranasally. One would have been motivated and would have expected success to do so because the combination of Wilson, Li, To, and Hazra taught and/or suggested administering the NEIL2 fusion protein of Hazra intranasally to reduce ROS production, oxidative DNA damage, and oxidative stress in order to treat influenza A virus infection, Prasun taught that SARS-CoV-2 infection may lead to increased oxidative stress and cause increased ROS generation and release of oxidized mitochondrial DNA into the cytoplasm, and Prasun suggests amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients.
Therefore, the method of claims 14 and 15 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 1, 2, 4-13, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, and Hazra.
The instant rejection was previously applied only to claim 19 but has been modified to include claims 1, 2, 4-13, and 16-18 in view of applicant’s amendment to claim 1.
Wilson hypothesizes that an acceptable lesion equilibrium is normally maintained in mitochondrial DNA (mtDNA) in all cells through a balance between the damage to mtDNA caused by the normal endogenous production of reactive oxygen species (ROS) as a byproduct of oxidative phosphorylation and its subsequent repair (paragraph [0018]). According to Wilson, this equilibrium is altered during various pathologies due to increased exposure to elevated levels of ROS and reactive nitrogen species (RNS), resulting in increased damage to mtDNA (paragraph [0018]) and the increased production of ROS exacerbates the ongoing stress in the cells leading to intensified oxidative stress in the cell and when this process reaches a critical level, the cell will die (paragraph [0018]). Wilson teaches that the present invention, which is administering a DNA repair enzyme including NEIL2, aborts this vicious cycle in its initial stages, and normalizes or at least inhibits further damage to mtDNA, thus enhancing cell viability (paragraphs [0018] and [0048]; claim 10).
Wilson teaches a method of treating a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA, comprising administering to a patient in need thereof, a composition comprising a multi-domain conjugate or fusion protein comprising a protein transduction domain, a mitochondrial targeting sequence and a DNA repair enzyme, in a therapeutically effective amount, wherein the disease or condition is inflammatory bowel disease, ischemic heart disease, acute lung injury or acute respiratory distress syndrome, or radiation-induced brain injury (claim 10).
The differences between Wilson and instant claims 1 and 19 are:
Wilson does not teach treating a Coronavirus or Influenza virus infection with NEIL2; and
Wilson does not teach administering a NEIL2 fusion peptide comprising a NEIL2 peptide having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 fused to a lung cell targeting segment having the amino acid sequence of SEQ ID NO: 9 intranasally or by inhalation to the lungs, wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
Regarding difference 1), Sarker teaches infection with viruses can induce inflammation and cause the accumulation oxidative DNA damage through induction of ROS (paragraph bridging pp. 75-76), teaches viral infection-induced inflammation may be modulated by NEIL2 and viral infections are associated with neutrophilic infiltration in the lung, which is a major source of ROS at the site of injury (p. 76, column 1, middle), and teaches DNA glycosylases play an important role in mitochondrial DNA repair, since targeting DNA glycosylases to mitochondria leads to enhanced repair and increased survival following exposure of cells to oxidative stress (p. 78, column 1, top).
Li teaches inflammation-induced reactive oxygen and nitrogen species (RONS) constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo (p. 2974, column 1, middle).
To reports on the role of mitochondrial ROS in the context of viral infections in vivo (p. 929, Abstract). To teaches influenza virus infection promotes mitochondrial ROS production, which drives innate immune inflammation and exacerbates viral pathogenesis (p. 929, Abstract). To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
Regarding difference 2), Hazra teaches delivering recombinant NEIL2 into the lungs of a host to reduce ROS damage to the transcribed genome in the lungs (paragraph [0008]). Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1, and teaches the NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9, and teaches covalent coupling of NEIL2 to a carrier peptide (paragraphs [0048] and [0055]). Hazra teaches pulmonary delivery of a pharmaceutical composition of NEIL2 intranasally or by inhalation (paragraphs [0128], [0136], [0141], and [0142]).
In view of Wilson, Sarker, Li, To, and Hazra, it would have been obvious to one of ordinary skill in the art to treat influenza A virus infection by administering the NEIL2 fusion protein of Hazra intranasally or by inhalation.
One would have been motivated and would have expected success to treat influenza A virus infection with NEIL2 because Wilson taught administering NEIL2 to treat a disease or disorder by inhibiting ROS-mediated damage to mitochondrial DNA; Sarker taught infection with viruses can induce inflammation and cause the accumulation oxidative DNA damage through induction of ROS, viral infection-induced inflammation may be modulated by NEIL2 and viral infections are associated with neutrophilic infiltration in the lung, which is a major source of ROS at the site of injury, and DNA glycosylases play an important role in mitochondrial DNA repair, since targeting DNA glycosylases to mitochondria leads to enhanced repair and increased survival following exposure of cells to oxidative stress; Li taught inflammation-induced RONS constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo; and To taught influenza virus infection promotes ROS production in the mitochondrion, which drives innate immune inflammation and exacerbates viral pathogenesis, while mitochondrion-targeted pharmacological inhibition of ROS-mediated damage and oxidative stress to the mitochondrion alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
One would have been motivated and would have expected success to administer the NEIL2 fusion protein of Hazra intranasally or by inhalation because Wilson taught administering NEIL2 to treat a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA; Sarker taught viral infection-induced inflammation may be modulated by NEIL2; Hazra taught delivering a fusion of NEIL2 coupled to the lung targeting segment of SEQ ID NO: 9 into the lungs of a host to reduce ROS damage and taught pulmonary delivery of NEIL2 by inhalation; and To taught localized delivery of a pharmacologic to the lung to treat the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
Regarding the limitation “wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication,” the combination of Wilson, Li, To, and Hazra does not teach or suggest the function or property of binding to viral genomic RNA and reducing viral replication. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent (MPEP 2112.01). Given that the structure of the NEIL2 fusion protein of Hazra is substantially identical to recited NEIL2 fusion protein of claims 1 and 19, it the examiner’s position that the NEIL2 fusion protein of Hazra would inherently bind to viral genomic RNA and reduce viral replication when administered to treat influenza A virus by inhalation. Since the Office does not have the facilities for examining and comparing applicants' NEIL2 fusion peptide with the fusion protein of Hazra, the burden is on the applicant to show an unobvious difference between the recited NEIL2 fusion peptide and the fusion protein of Hazra. See MPEP 2112.IV and 2112.V.
Regarding claim 2, as stated above, claim 2 is confusing in view of the amendment to claim 1, which limits the administration to intranasal administration. Nonetheless, as stated above, it would have been obvious to one of ordinary skill in the art to treat influenza A virus by administering the NEIL2 fusion protein of Hazra by inhalation.
Regarding claims 4 and 6, as stated above, Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1.
Regarding claim 5, Hazra teaches using a functional segment of NEIL2 (paragraph [0014]).
Regarding claims 7-10, as previously stated, Hazra teaches NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9.
Regarding claims 11, 12, and 18, as stated above, To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
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 – the idea of combining them flows logically from their having been individually taught in the prior art. In accordance with MPEP 2144.06.I, in view of the combined teachings of Wilson, Li, To, and Hazra, it would have been obvious to treat influenza A virus and its clinical symptoms by administering a composition comprising the NEIL2 fusion protein of Hazra and Mito-TEMPO of To intranasally or by inhalation.
Regarding claim 13, as stated above, claim 13 is confusing in view of amended claim 1, which is limited to treating Coronavirus or Influenza virus infection and in the interest of advancing prosecution, claim 13 is included in the rejection.
Regarding claim 16, Wilson teaches the term “patient” is used to describe a human (paragraph [0064]), and To and Tavares are related to influenza A virus infection in a human.
Regarding claim 17, Hazra teaches doses between 0.001 mg/kg and 10 mg/kg body weight, most preferably between 0.5 and 1 mg/kg body weight (paragraph [0147]).
Therefore, the method of claims 1, 2, 4-13, and 16-19 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, and Hazra as applied to claims 1, 2, 4-13, and 16-19 above, and further in view of Prasun.
The relevant teachings of Wilson, Sarker, Li, To, and Hazra as applied to claims 1, 2, 4-13, and 16-19 are set forth above.
The difference between the combination of Wilson, Sarker, Li, To, and Hazra and claims 14 and 15 is that the combination does not teach or suggest a Coronavirus or a SARS-CoV-2 virus.
Prasun examines pathogenesis of COVID-19 from a mitochondrial perspective (p. 713, abstract). Prasun teaches SARS-CoV-2 is the causative agent of COVID-19 (p. 713, column 2, bottom) and that after SARS-CoV-2 enters the cell, it hijacks the mitochondrial machinery, which may lead to increased oxidative stress (p. 714, column 2, top) and causing increased ROS generation and release of oxidized mitochondrial DNA (p. 716, column 1, bottom). Prasun teaches amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients (p. 717, column 1, middle).
In view of the additional teachings of Prasun, it would have been obvious to one of ordinary skill in the art before the effective filing date to treat SARS-CoV-2 infection by administering the NEIL2 fusion protein of Hazra intranasally. One would have been motivated and would have expected success to do so because the combination of Wilson, Li, To, and Hazra taught and/or suggested administering the NEIL2 fusion protein of Hazra intranasally to reduce ROS production, oxidative DNA damage, and oxidative stress in order to treat influenza A virus infection, Prasun taught that SARS-CoV-2 infection may lead to increased oxidative stress and cause increased ROS generation and release of oxidized mitochondrial DNA into the cytoplasm, and Prasun suggests amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients.
Therefore, the method of claims 14 and 15 would have been obvious to one of ordinary skill in the art before the effective filing date.
RESPONSE TO REMARKS: In summary, applicant argues no single reference or combination of references teaches and/or suggests the recited combination of elements; the combination of references fails to provide a motivation or a reasonable expectation of success to practice the claimed invention; Tavares teaches away from treating Influenza A virus infection by characterizing inflammation as a “double-edged sword”; and the alleged unexpected results of the Hazra Declaration filed March 19, 2026 are commensurate in scope with the claimed invention.
Applicant’s arguments are not found persuasive. Contrary to applicant’s position, for the reasons set forth above, the combination of cited prior art teaches all claim limitations and provides motivation and a reasonable expectation of success to practice the claimed invention.
Regarding applicant’s argument that Tavares teaches away from the claimed invention, contrary to applicant’s position, Tavares is not cited in the rejections set forth above and even assuming the rejections relied on Tavares, the reference of Tavares does not criticize, discredit, or otherwise discourage a person of ordinary skill in the art from combining the cited prior art to treat influenza A virus infection by administering the NEIL2 fusion protein of Hazra intranasally or by inhalation.
Regarding applicant’s argument that the alleged unexpected results are commensurate in scope with the claimed invention, contrary to applicant’s position, the alleged unexpected results are not commensurate in scope with the claimed invention. According to MPEP 716.02(d), unexpected results must be reasonably commensurate in scope with the claimed invention. “Commensurate in scope” means that the evidence provides a reasonable basis for concluding that the untested embodiments encompassed by the claims would behave in the same manner as the tested embodiments. See In re Lindner, 457 F.2d 506, 508 (CCPA 1972). Although not expressly stated by applicant, the alleged unexpected results appear to be based on inhalation therapy with a specific NEIL2 fusion protein (NEIL2 protein of SEQ ID NO: 1 and a lung cell targeting segment of SEQ ID NO: 9) to a subject infected with a specific virus, SARS-CoV-2. While nonobviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range (MPEP 716.02(d).I), there is no evidence of record that the untested embodiments encompassed by the claims. For example, as noted above, applicant’s results appear to be based in-part on treating SARS-CoV-2 viral infection, while at least independent claims 1 and 19 recite treatment of any Coronavirus or Influenza virus infection and there is no evidence of record that applicant’s results would be expected to extend to treatment of any Coronavirus or Influenza virus infection. Also, as noted above, applicant’s results appear to be based in-part on NEIL2 fusion protein comprising NEIL2 of SEQ ID NO: 1 and lung targeting segment of SEQ ID NO: 9 binding to the 5’-untranslated region of SARS-CoV-2 genomic RNA, however, the recited “viral genomic RNA” to which the recited NEIL2 fusion protein binds in claims 1 and 19 is unlimited and is not required to correspond to the viral genomic RNA of the virus infection that is being treated.
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date and applicant’s alleged unexpected results fail to rebut a prima facie case of obviousness.
Claim Rejections - 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
The rejection of claim 19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, and To, and
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, and To as applied to claim 19 above, and further in view of Tavares,
the rejection of claims 14 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, To, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-19 above, and further in view of Prasun,
the rejection of claim 19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, and To,
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, and To as applied to claim 19 above, and further in view of Tavares, and
the rejection of claims 14 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, To, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-19 above, and further in view of Prasun
are withdrawn in view of applicant’s amendments to claims 1 and 19 to recite administering a NEIL2 fusion peptide because the claims of the patent recite “a NEIL2 polypeptide…non-covalently coupled to a lung targeting moiety.”
Claims 1, 2, 4-13, and 16-19 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, To, and Hazra. Although the claims at issue are not identical, they are not patentably distinct from each other.
This rejection is necessitated by applicant’s amendments to claims 1 and 19 to recite administering a NEIL2 fusion peptide.
Regarding instant claims 1 and 19, claim 1 of the patent recites a method of treating bacterial infection or allergen induced rhinitis or allergen induced asthma comprising administering to a subject having a bacterial infection of the lungs or allergen induced rhinitis or allergen induced asthma a NEIL2 polypeptide comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1 non-covalently coupled to a lung targeting moiety, the lung targeting moiety localizing the NEIL2 polypeptide in the cytosol or nucleus of the targeted cell, wherein damage to transcribed genomic DNA in the lung is reduced relative to a subject not treated with said NEIL2 polypeptide, thereby ameliorating the negative effect of bacterial infection of the lung on an innate immune response in the subject;
claim 2 of the patent recites (in relevant part) the method of claim 1, wherein the lung targeting moiety is a peptide consisting of the amino acid sequence of SEQ ID NO: 9;
claim 3 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide comprises the amino acid sequence of SEQ ID NO: 1;
claim 4 of the patent recites (in relevant part) the method of claim 1, wherein the NEIL2 polypeptide complex is administered to the lungs by inhalation; and
claim 5 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide complex is administered intranasally.
SEQ ID NO: 1 of the patent is identical to instant SEQ ID NO: 1 and SEQ ID NO: 9 of the patent is identical to instant SEQ ID NO: 9.
The differences between claims 1-5 of the patent and instant claims 1 and 19 are:
The claims of the patent do not recite treating a Coronavirus or Influenza virus infection with NEIL2; and
The claims of the patent do not recite a fusion of the NEIL2 polypeptide and the lung targeting moiety, wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
Regarding difference 1), Wilson hypothesizes that an acceptable lesion equilibrium is normally maintained in mitochondrial DNA (mtDNA) in all cells through a balance between the damage to mtDNA caused by the normal endogenous production of reactive oxygen species (ROS) as a byproduct of oxidative phosphorylation and its subsequent repair (paragraph [0018]). According to Wilson, this equilibrium is altered during various pathologies due to increased exposure to elevated levels of ROS and reactive nitrogen species (RNS), resulting in increased damage to mtDNA (paragraph [0018]) and the increased production of ROS exacerbates the ongoing stress in the cells leading to intensified oxidative stress in the cell and when this process reaches a critical level, the cell will die (paragraph [0018]). Wilson teaches that the present invention, which is administering a DNA repair enzyme including NEIL2, aborts this vicious cycle in its initial stages, and normalizes or at least inhibits further damage to mtDNA, thus enhancing cell viability (paragraphs [0018] and [0048]; claim 10).
Wilson teaches a method of treating a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA, comprising administering to a patient in need thereof, a composition comprising a multi-domain conjugate or fusion protein comprising a protein transduction domain, a mitochondrial targeting sequence and a DNA repair enzyme, in a therapeutically effective amount, wherein the disease or condition is inflammatory bowel disease, ischemic heart disease, acute lung injury or acute respiratory distress syndrome, or radiation-induced brain injury (claim 10).
Sarker teaches infection with viruses can induce inflammation and cause the accumulation oxidative DNA damage through induction of ROS (paragraph bridging pp. 75-76), teaches viral infection-induced inflammation may be modulated by NEIL2 and viral infections are associated with neutrophilic infiltration in the lung, which is a major source of ROS at the site of injury (p. 76, column 1, middle), and teaches DNA glycosylases play an important role in mitochondrial DNA repair, since targeting DNA glycosylases to mitochondria leads to enhanced repair and increased survival following exposure of cells to oxidative stress (p. 78, column 1, top).
Li teaches inflammation-induced reactive oxygen and nitrogen species (RONS) constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo (p. 2974, column 1, middle).
To reports on the role of mitochondrial ROS in the context of viral infections in vivo (p. 929, Abstract). To teaches influenza virus infection promotes mitochondrial ROS production, which drives innate immune inflammation and exacerbates viral pathogenesis (p. 929, Abstract). To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
Regarding difference 2), Hazra teaches delivering recombinant NEIL2 into the lungs of a host to reduce ROS damage to the transcribed genome in the lungs (paragraph [0008]). Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1, and teaches the NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9, and teaches covalent coupling of NEIL2 to a carrier peptide (paragraphs [0048] and [0055]). Hazra teaches pulmonary delivery of a pharmaceutical composition of NEIL2 intranasally or by inhalation (paragraphs [0128], [0136], [0141], and [0142]).
In view of Wilson, Sarker, Li, To, and Hazra, it would have been obvious to one of ordinary skill in the art to modify the method of the claims of the patent to treat influenza A virus infection by administering the NEIL2 fusion protein of Hazra intranasally or by inhalation.
One would have been motivated and would have expected success to treat influenza A virus infection with NEIL2 because the claims of the patent recite a method of treatment by administering NEIL2; Wilson taught administering NEIL2 to treat a disease or disorder by inhibiting ROS-mediated damage to mitochondrial DNA; Sarker taught infection with viruses can induce inflammation and cause the accumulation oxidative DNA damage through induction of ROS, viral infection-induced inflammation may be modulated by NEIL2 and viral infections are associated with neutrophilic infiltration in the lung, which is a major source of ROS at the site of injury, and DNA glycosylases play an important role in mitochondrial DNA repair, since targeting DNA glycosylases to mitochondria leads to enhanced repair and increased survival following exposure of cells to oxidative stress; Li taught inflammation-induced RONS constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo; and To taught influenza virus infection promotes ROS production in the mitochondrion, which drives innate immune inflammation and exacerbates viral pathogenesis, while mitochondrion-targeted pharmacological inhibition of ROS-mediated damage and oxidative stress to the mitochondrion alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
One would have been motivated and would have expected success to administer the NEIL2 fusion protein of Hazra intranasally or by inhalation because Wilson taught administering NEIL2 to treat a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA; Sarker taught viral infection-induced inflammation may be modulated by NEIL2; Hazra taught delivering a fusion of NEIL2 coupled to the lung targeting segment of SEQ ID NO: 9 into the lungs of a host to reduce ROS damage and taught pulmonary delivery of NEIL2 by inhalation; and To taught localized delivery of a pharmacologic to the lung to treat the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
Regarding the limitation “wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication,” the combination of Wilson, Li, To, and Hazra does not teach or suggest the function or property of binding to viral genomic RNA and reducing viral replication. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent (MPEP 2112.01). Given that the structure of the NEIL2 fusion protein of Hazra is substantially identical to recited NEIL2 fusion protein of claims 1 and 19, it the examiner’s position that the NEIL2 fusion protein of Hazra would inherently bind to viral genomic RNA and reduce viral replication when administered to treat influenza A virus by inhalation. Since the Office does not have the facilities for examining and comparing applicants' NEIL2 fusion peptide with the fusion protein of Hazra, the burden is on the applicant to show an unobvious difference between the recited NEIL2 fusion peptide and the fusion protein of Hazra. See MPEP 2112.IV and 2112.V.
Regarding instant claim 2, claim 4 of the patent recites (in relevant part) the method of claim 1, wherein the NEIL2 polypeptide complex is administered to the lungs by inhalation.
Regarding instant claims 4 and 6, claim 3 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide comprises the amino acid sequence of SEQ ID NO: 1. SEQ ID NO: 1 of the patent is identical to instant SEQ ID NO: 1.
Regarding instant claim 5, claim 1 of the patent recites “a NEIL2 polypeptide comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1,” which encompasses a functional fragment of SEQ ID NO: 1.
Regarding instant claims 7-10, as previously stated, Hazra teaches NEIL2 is covalently coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9.
Regarding instant claims 11, 12, and 18, as stated above, To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
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 – the idea of combining them flows logically from their having been individually taught in the prior art. In accordance with MPEP 2144.06.I, in view of the combined teachings of Wilson, Li, To, and Hazra, it would have been obvious to modify the claims of the patent to treat influenza A virus and its clinical symptoms by administering a composition comprising the NEIL2 fusion protein of Hazra and Mito-TEMPO of To intranasally or by inhalation.
Regarding instant claim 13, as stated above, claim 13 is confusing in view of amended claim 1, which is limited to treating Coronavirus or Influenza virus infection and in the interest of advancing prosecution, claim 13 is included in the rejection.
Regarding instant claim 16, Wilson teaches the term “patient” is used to describe a human (paragraph [0064]), and To and Tavares are related to influenza A virus infection in a human.
Regarding instant claim 17, Hazra teaches doses between 0.001 mg/kg and 10 mg/kg body weight, most preferably between 0.5 and 1 mg/kg body weight (paragraph [0147]).
Therefore, claims 1, 2, 4-13, and 16-19 are unpatentable over claims 1-5 of the patent in view of Wilson, Sarker, Li, To, and Tavares.
Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, To, and Tavares as applied to claims 1, 2, 4-13, and 16-19 above, and further in view of Prasun.
The claims of the patent do not recite and Wilson, Sarker, Li, To, and Tavares do not teach or suggest treating a SARS-CoV-2 virus.
Prasun examines pathogenesis of COVID-19 from a mitochondrial perspective (p. 713, abstract). Prasun teaches SARS-CoV-2 is the causative agent of COVID-19 (p. 713, column 2, bottom) and that after SARS-CoV-2 enters the cell, it hijacks the mitochondrial machinery, which may lead to increased oxidative stress (p. 714, column 2, top) and causing increased ROS generation and release of oxidized mitochondrial DNA (p. 716, column 1, bottom). Prasun teaches amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients (p. 717, column 1, middle).
In view of the additional teachings of Prasun, it would have been obvious to one of ordinary skill in the art before the effective filing date to administer NEIL2 to treat hyperinflammation due to SARS-CoV-2 infection. One would have been motivated and expected success to do so because the claims of the patent recite a method of treatment by administering NEIL2, the combination of Wilson, Sarker, Li, and To taught and/or suggested administering NEIL2 to reduce ROS production, oxidative DNA damage, and oxidative stress in order to treat influenza A virus, Prasun taught that SARS-CoV-2 infection may lead to increased oxidative stress and cause increased ROS generation and release of oxidized mitochondrial DNA into the cytoplasm, and Prasun suggests amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients.
Therefore, claims 14 and 15 are unpatentable over claims 1-5 of the patent in view of Wilson, Sarker, Li, To, Tavares, and Prasun.
Claims 1, 2, 4-13, and 16-19 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, To, and Hazra. Although the claims at issue are not identical, they are not patentably distinct from each other.
This rejection is necessitated by applicant’s amendments to claims 1 and 19 to recite administering a NEIL2 fusion peptide.
Regarding instant claims 1 and 19, claim 1 of the patent recites a method of treating bacterial infection or allergen induced rhinitis or allergen induced asthma comprising administering to a subject having a bacterial infection of the lungs or allergen induced rhinitis or allergen induced asthma a NEIL2 polypeptide comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1 non-covalently coupled to a lung targeting moiety, the lung targeting moiety localizing the NEIL2 polypeptide in the cytosol or nucleus of the targeted cell, wherein damage to transcribed genomic DNA in the lung is reduced relative to a subject not treated with said NEIL2 polypeptide, thereby ameliorating the negative effect of bacterial infection of the lung on an innate immune response in the subject;
claim 2 of the patent recites (in relevant part) the method of claim 1, wherein the lung targeting moiety is a peptide consisting of the amino acid sequence of SEQ ID NO: 9;
claim 3 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide comprises the amino acid sequence of SEQ ID NO: 1;
claim 4 of the patent recites (in relevant part) the method of claim 1, wherein the NEIL2 polypeptide complex is administered to the lungs by inhalation; and
claim 5 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide complex is administered intranasally.
SEQ ID NO: 1 of the patent is identical to instant SEQ ID NO: 1 and SEQ ID NO: 9 of the patent is identical to instant SEQ ID NO: 9.
The differences between claims 1-5 of the patent and instant claims 1 and 19 are:
The claims of the patent do not recite treating a Coronavirus or Influenza virus infection with NEIL2; and
The claims of the patent do not recite a fusion of the NEIL2 polypeptide and the lung targeting moiety, wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication.
Wilson hypothesizes that an acceptable lesion equilibrium is normally maintained in mitochondrial DNA (mtDNA) in all cells through a balance between the damage to mtDNA caused by the normal endogenous production of reactive oxygen species (ROS) as a byproduct of oxidative phosphorylation and its subsequent repair (paragraph [0018]). According to Wilson, this equilibrium is altered during various pathologies due to increased exposure to elevated levels of ROS and reactive nitrogen species (RNS), resulting in increased damage to mtDNA (paragraph [0018]) and the increased production of ROS exacerbates the ongoing stress in the cells leading to intensified oxidative stress in the cell and when this process reaches a critical level, the cell will die (paragraph [0018]). Wilson teaches that the present invention, which is administering a DNA repair enzyme including NEIL2, aborts this vicious cycle in its initial stages, and normalizes or at least inhibits further damage to mtDNA, thus enhancing cell viability (paragraphs [0018] and [0048]; claim 10).
Wilson teaches a method of treating a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA, comprising administering to a patient in need thereof, a composition comprising a multi-domain conjugate or fusion protein comprising a protein transduction domain, a mitochondrial targeting sequence and a DNA repair enzyme, in a therapeutically effective amount, wherein the disease or condition is inflammatory bowel disease, ischemic heart disease, acute lung injury or acute respiratory distress syndrome, or radiation-induced brain injury (claim 10).
Li teaches inflammation-induced reactive oxygen and nitrogen species (RONS) constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo (p. 2974, column 1, middle).
To reports on the role of mitochondrial ROS in the context of viral infections in vivo (p. 929, Abstract). To teaches influenza virus infection promotes mitochondrial ROS production, which drives innate immune inflammation and exacerbates viral pathogenesis (p. 929, Abstract). To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
Regarding difference 2), Hazra teaches delivering recombinant NEIL2 into the lungs of a host to reduce ROS damage to the transcribed genome in the lungs (paragraph [0008]). Hazra teaches the amino acid sequence of NEIL2 (paragraph [0014]), which is identical to instant SEQ ID NO: 1, and teaches the NEIL2 is coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9, and teaches covalent coupling of NEIL2 to a carrier peptide (paragraphs [0048] and [0055]). Hazra teaches pulmonary delivery of a pharmaceutical composition of NEIL2 intranasally or by inhalation (paragraphs [0128], [0136], [0141], and [0142]).
In view of Wilson, Li, To, and Hazra, it would have been obvious to one of ordinary skill in the art to modify the method of the claims of the patent to treat influenza A virus infection by administering the NEIL2 fusion protein of Hazra intranasally or by inhalation.
One would have been motivated and would have expected success to treat influenza A virus infection with NEIL2 because the claims of the patent recite a method of treatment by administering NEIL2; Wilson taught administering NEIL2 to treat a disease or disorder by inhibiting ROS-mediated damage to mitochondrial DNA; Li taught inflammation-induced RONS constitute one of the key contributors of pathogenicity in severe influenza A viral infections and hypothesizes that oxidative DNA damage is induced by influenza-induced inflammation, which may contribute to cytotoxicity in vivo; and To taught influenza virus infection promotes ROS production in the mitochondrion, which drives innate immune inflammation and exacerbates viral pathogenesis, while mitochondrion-targeted pharmacological inhibition of ROS-mediated damage and oxidative stress to the mitochondrion alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
One would have been motivated and would have expected success to administer the NEIL2 fusion protein of Hazra intranasally or by inhalation because Wilson taught administering NEIL2 to treat a disease or disorder characterized by oxidative-stress induced damage to mitochondrial DNA; Sarker taught viral infection-induced inflammation may be modulated by NEIL2; Hazra taught delivering a fusion of NEIL2 coupled to the lung targeting segment of SEQ ID NO: 9 into the lungs of a host to reduce ROS damage and taught pulmonary delivery of NEIL2 by inhalation; and To taught localized delivery of a pharmacologic to the lung to treat the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection.
Regarding the limitation “wherein the NEIL2 fusion peptide binds to viral genomic RNA and reduces viral replication,” the combination of Wilson, Li, To, and Hazra does not teach or suggest the function or property of binding to viral genomic RNA and reducing viral replication. However, inherent disclosures of a prior art reference may be relied upon in a rejection under 35 U.S.C. 103 (MPEP 2112) and when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent (MPEP 2112.01). Given that the structure of the NEIL2 fusion protein of Hazra is substantially identical to recited NEIL2 fusion protein of claims 1 and 19, it the examiner’s position that the NEIL2 fusion protein of Hazra would inherently bind to viral genomic RNA and reduce viral replication when administered to treat influenza A virus by inhalation. Since the Office does not have the facilities for examining and comparing applicants' NEIL2 fusion peptide with the fusion protein of Hazra, the burden is on the applicant to show an unobvious difference between the recited NEIL2 fusion peptide and the fusion protein of Hazra. See MPEP 2112.IV and 2112.V.
Regarding instant claim 2, claim 4 of the patent recites (in relevant part) the method of claim 1, wherein the NEIL2 polypeptide complex is administered to the lungs by inhalation.
Regarding instant claims 4 and 6, claim 3 of the patent recites the method of claim 1, wherein the NEIL2 polypeptide comprises the amino acid sequence of SEQ ID NO: 1. SEQ ID NO: 1 of the patent is identical to instant SEQ ID NO: 1.
Regarding instant claim 5, claim 1 of the patent recites “a NEIL2 polypeptide comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1,” which encompasses a functional fragment of SEQ ID NO: 1.
Regarding instant claims 7-10, as previously stated, Hazra teaches NEIL2 is covalently coupled to a lung cell targeting moiety comprising SEQ ID NO: 9 (paragraph [0015]), which is identical to instant SEQ ID NO: 9.
Regarding instant claims 11, 12, and 18, as stated above, To teaches pharmacological inhibition of mitochondrial ROS with localized delivery of Mito-TEMPO (a mitochondria-targeted antioxidant compound) to the lung by intranasal administration resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with influenza A virus (p. 929, abstract). To teaches that a partial suppression of mtROS generation with Mito-TEMPO facilitates a more effective innate immune response to influenza A virus, which limits lung pathology, improves survival, while preserving adaptive immunity and facilitating viral clearance (p. 938, column 1, middle). To concludes that mitochondrion-targeted pharmacological inhibition of ROS-mediated damage to the mitochondrion and oxidative stress alleviates the clinical symptoms, lung inflammation, and influenza virus pathology during influenza A virus infection (p. 929, Abstract, bottom; p. 930, column 1, top; p. 938, column 2, bottom).
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 – the idea of combining them flows logically from their having been individually taught in the prior art. In accordance with MPEP 2144.06.I, in view of the combined teachings of Wilson, Li, To, and Hazra, it would have been obvious to modify the claims of the patent to treat influenza A virus and its clinical symptoms by administering a composition comprising the NEIL2 fusion protein of Hazra and Mito-TEMPO of To intranasally or by inhalation.
Regarding instant claim 13, as stated above, claim 13 is confusing in view of amended claim 1, which is limited to treating Coronavirus or Influenza virus infection and in the interest of advancing prosecution, claim 13 is included in the rejection.
Regarding instant claim 16, Wilson teaches the term “patient” is used to describe a human (paragraph [0064]), and To and Tavares are related to influenza A virus infection in a human.
Regarding instant claim 17, Hazra teaches doses between 0.001 mg/kg and 10 mg/kg body weight, most preferably between 0.5 and 1 mg/kg body weight (paragraph [0147]).
Therefore, claims 1, 2, 4-13, and 16-19 are unpatentable over claims 1-5 of the patent in view of Wilson, Li, To, and Tavares.
Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, To, and Tavares as applied to claims 1, 2, 4-13, and 16-19 above, and further in view of Prasun.
The claims of the patent do not recite and Wilson, Li, To, and Tavares do not teach or suggest treating a SARS-CoV-2 virus.
Prasun examines pathogenesis of COVID-19 from a mitochondrial perspective (p. 713, abstract). Prasun teaches SARS-CoV-2 is the causative agent of COVID-19 (p. 713, column 2, bottom) and that after SARS-CoV-2 enters the cell, it hijacks the mitochondrial machinery, which may lead to increased oxidative stress (p. 714, column 2, top) and causing increased ROS generation and release of oxidized mitochondrial DNA (p. 716, column 1, bottom). Prasun teaches amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients (p. 717, column 1, middle).
In view of the additional teachings of Prasun, it would have been obvious to one of ordinary skill in the art before the effective filing date to administer NEIL2 to treat hyperinflammation due to SARS-CoV-2 infection. One would have been motivated and expected success to do so because the claims of the patent recite a method of treatment by administering NEIL2, the combination of Wilson, Li, and To taught and/or suggested administering NEIL2 to reduce ROS production, oxidative DNA damage, and oxidative stress in order to treat influenza A virus, Prasun taught that SARS-CoV-2 infection may lead to increased oxidative stress and cause increased ROS generation and release of oxidized mitochondrial DNA into the cytoplasm, and Prasun suggests amelioration of oxidative stress contributed by dysfunctional mitochondria may be an effective adjuvant strategy to treat hyperinflammation in critically sick patients.
Therefore, claims 14 and 15 are unpatentable over claims 1-5 of the patent in view of Wilson, Li, To, Tavares, and Prasun.
RESPONSE TO REMARKS: In summary, applicant argues the claims of the patent are patentably distinct from the claims of this application.
Applicant’s arguments are not found persuasive. Contrary to applicant’s position, for the reasons set forth above, the claims of this application are not patentably distinct from the claims of the patent in view of the cited prior art.
Conclusion
Status of the claims:
Claims 1, 2, and 4-19 are pending.
Claims 1, 2, and 4-19 are rejected.
No claim is in condition for allowance.
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/David Steadman/Primary Examiner, Art Unit 1656
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