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. Election/Restrictions Applicant’s election without traverse of election of species inhibitory nucleic acid molecule, specifically shRNA in the reply filed on 25 Sept, 2025 is acknowledged. Claims 9, 10, 12-17, 30, 31, 33-38 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Accordingly, claims 1-8, 11, 18-29, and 32 are examined herein. Priority Acknowledgment is made of applicant's claim for priority based on a US Provisional A pplication No. 63/215,882 filed on 28 June, 2021 Claim Objections Claims 18 and 20 are objected to because of the following informalities: Claims recite “reduces or decreases”, and these terms are interchangeable synonyms that do not provide distinct alternative scopes and fail to claim the invention in concise terms. Appropriate correction is required. Specification The drawings are objected to under 37 CFR 1.83(a) because they fail to show multi-list Reactome enrichment of DEPs at each time point after virus infection in Figure 3D as described in the specification since the text in Figure 3D is illegible. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-8, 11, 18-29, and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Step 1 Claims 1 and 25 are directed to a method of reducing, improving or treating a viral infection in a subject comprising…". Claim 23 is directed to a method of identifying a subject having a coronavirus infection…comprising”. Thus, the claimed invention is directed to a process, which is one of the statutory categories of invention. Step 2A, Prong 1 Claims 1, 23, and 25 recites “ identifying ” , “ detecting ” , and “ comparing ” , which is abstract mental concept that belong to numerated group (c) of the Abstract Idea Groupings described in MPEP § 2106.04(a)(2): Mental processes - concepts that performed in the human mind (including an observation, evaluation, judgement, opinion). Thus, the claims recite a judicial exception. Claims 2-6, 18-22 , 24, 26-29, and 32 are dependent claims of claims 1, 23, or 25, and thus recite the judicial exception identified for corresponding independent claims. Step 2A, Prong 2 The additional steps/elements in the claims are next evaluated with considerations set forth in MPEP 2106.5 (a) through (c), (e), and (h). Further, MPEP 2106.04(d)(2) states: "in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for disease or medical condition". MPEP 2106.04(d)(2)(a) further states the treatment or prophylaxis limitation must be 'particular'. For example, an administration step of “administering a lower-than-normal dosage of a beta blocker medication to a pa tient identified as having the poor metabolizer genotype” is particular, and it integrates the mental analysis step into a practical application. Conversely, an administration step is not particular in a claim reciting "administering a suitable medication to a patient". This administration step is instead merely instructions to 'apply' the exception in a generic way , and it does not integrate the mental analysis step into a practical application. Regarding claim 1, recitation of "administering an effective amount of an agent that promotes inhibition of p97 in the subject" is NOT particular. The dosage and the drug administered are not specified as the example particular claim stated above. Thus, this additional element cannot integrate the judicial exception into a practical application. Regarding claim 23, recitation of “detecting at least one of: a level of a product or expression of a gene…” is an additional mental analysis step which cannot integrate the judicial exception into a practical application. Regarding claim 25, recitation of “detecting” and “administering” steps do not integrate the judicial exception into a practical application for the same reasons stated above for claims 1 and 23. The recitation of “comparing” constitutes an additional mental analysis step which still cannot integrate the judicial exception into a practical application. For claims 1, 23, and 25, there are no additional elements that reflect an improvement within the technical field; there are no additional elements that apply the natural correction/phenomena judicial exception to a particular treatment or which utilize a particular machine; there are no additional elements that effect a transformation; and, there are no additional elements that apply the judicial exception in some other meaningful way beyond generally linking it to a field, namely, viral infection. While dependent claims 2-6, 18-22, 24, 26-29, and 32 recite additional elements limiting viral infection to coronavirus, proteins expressed in a subject having a coronavirus infection, results post-administration of inhibitor of p97, and a shRNA inhibitor of p97, these additional elements still do not integrate the judicial exception into a practical application. Step 2B Claims 1-8, 11, 18-29, and 32 do NOT recite any additional elements, and therefore, they do not include additional elements that are sufficient to amount to significantly more than the judicial exception. 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 appl icant regards as his invention. Claim s 1-8, 11, 18-29, and 32 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. For compact prosecution, claims reciting relative terms are discussed together. Regarding claims 1, 5, 6, 18, 20-22, 24, 25, 28, and 29, it is noted that the claim s recite relative terms which are considered to be indefinite because these terms are not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The relative terms include: " improving a viral infection " : the specification does not define this means. It is unclear what constitutes as improvements. For example, does one of ordinary skill in the art compare viral load, symptom severity, infection duration, or biomarkers to determine if there’s an improvement? The specification does not provide criteria or thresholds by which improvement is measured. " an agent that promotes inhibition" : the baseline to which “promotes” is relative to is not clear. How much increase in inhibition is required to be considered as an agent that “promotes” inhibition? Does inhibition must meet a threshold ? " differently " : the specification does not define this relative term nor it teaches the differences between proteins expressed by a normal subject versus a subject having coronavirus infection , such as expression levels, folding structures, amino acid sequences, and size. “ normal ” and “ abnormal ”: the specification does not define what constitutes “normal” or “abnormal”, nor does it provide criteria to determine normalcy. For example, a “normal” subject could reasonably be i) a healthy subject not having a viral infection, ii) an infected-subject but asymptomatic, iii) a subject at early stage of infection, iv) an infected-subject with symptoms. Further, the specification does not provide a standard to measure the degree for levels of biomarkers to be considered as “abnormal”. Without reference values or thresholds relevant to viral infections, it is unclear which level and/or expression of biomarkers is considered abnormal. “a symptom thereof is reduced ” : It is unclear of which symptom is being evaluated , which baseline used for comparison, and the magnitude of change required to be considered as “reduced”. A subject having a viral infection have symptoms that naturally fluctuate over time and may be assessed using different clinical standards. One of ordinary skill in the art could reasonably reach different conclusions as to whether a symptom has been ”reduced”. Thus, without specific guidance, one would not be able to determine or ascertain that a symptom is reduced. Regarding claim 3, there is insufficient antecedent basis for the recitation of “the members” and “the Coronavirinae subfamily of viruses” in claim 2. It is noted that the first recitation of these terms is in the instant claim. Regarding claim 6 , t here is insufficient antecedent basis for the recitation of "the cell cycle pathway" in claim 1. It is noted that the first recitation of this term is in the instant claim. Thus, it is unclear which cell cycle pathway is being further defined in the instant claim. Regarding claim 7, t here is insufficient antecedent basis for the recitation of "the proteasome and the anaphase promoting complex or cyclosome" in claim 6. It is noted that the first recitation of these terms is in the instant claims. Thus, it is unclear which the proteasome and the anaphase promoting complex or cyclosome is being further defined in the instant claim. Regarding claim 25, it is noted that the claim recites "the method comprising: detecting the level and/or expression… " of biomarkers in a subject (line 3) . It is not clear whether the level of expression is detected in the subject as a whole or from a biological sample obtained from the subject (e.g., blood, tissue, or cells). Thus, it is not clear whether the claim requires determining the entire expression in the subject as a whole or determining expression in a biological sample obtained from the subject. Claim 25 f urther recites "the subject" (lines 6, 8-11) and "the normal subject" (lines 7 and 8) . It is not clear whether the subject and the normal subject are referring to the same or different subject. It is unclear how "the normal subject" is related to "the subject". Regarding claim 26, it is noted that the claim recites "the members" . There is insufficient antecedent basis for the recitation of "members" in claim 25 . It is noted that the first recitation of these terms is in the instant claims. Thus, it is unclear which members are being further defined in the instant claim. Regarding claim 29, it is noted that the claim recites "the cell cycle pathway" . There is insufficient antecedent basis for the recitation of "the cell cycle pathway " in claim 25 . It is noted that the first recitation of these terms is in the instant claims. Thus, it is unclear which members are being further defined in the instant claim. C laim Rejections - 35 USC § 112 – Written Description The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 1-8, 11, 18-29, and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. MPEP 2163.II.A.3(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 couple with a known or disclosed correlation between structure and function, and the method of making the claimed invention”. Claim 1 and 25 are drawn to the possession of a method for treating a viral infection in a subject by administering an agent that promotes inhibition of p97 in the subject . Although claim 23 is not directly drawn to possession of a method for treating a viral infection in a subject, it is directed to possession of a method for identifying a subject having a coronavirus infection, which is one of the recited steps in the methods of claims 1 and 25. Therefore, claims 1, 23, and 25 are discussed together. In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. The claims require methods of claims 1, 23, and 25 to be practiced in a subject, and t he specification defines “subject” as a human or a non-human mammal ([0028]). The specification does not disclose any administration of an agent to a subject, any therapeutic efficacy in vivo , any therapeutic protocols including route of administration, dosage specific to the agent, formulation, delivery of agent into target cell in a subject, or detection of any biomarkers to identify a subject having a viral infection. A s of the filling date , there is no prior art disclosing any successful therapeutic treatment of viral infection using any agents that promotes inhibition of p97 in a subject . Thus, claims 1 and 25 are rejected for insufficient written description of a method to treat a viral infection in a subjec t . Further, there is no prior art disclosing diagnosis of coronavirus infection in a subject by detection of biomarkers CDC20, CDC27, PSMD14, and PSMB3 . Thus, claim 23 is rejected for insufficient written description of a method to identify a subject having coronavirus infection, and this deficiency extends to its dependent claim 24 because claim 24 merely recites detecting a level of biomarkers expressed differently in normal and subjects with coronavirus infections, and specification does not provide written description supporting detection of biomarkers in subjects. Further, t he claims do not require that an agent is a direct inhibitor of p97. Instead, the claims recite “an agent that promotes inhibition of p97”, which is interpreted to encompass any agent that directly inhibits p97 and any agent that has upstream or downstream effects capable of indirectly promoting inhibition of p97. In order to provide adequate written description and evidence of possession of this claimed genus of agents, the specification must provide sufficient distinguishing identifying characteristics of the genus (see MPEP 2163.II.A.3(a).i) statement above). In the instant case, the specification teaches that inhibition of p97 could be achieved using a nucleic acid molecule, an antagonist, a genetic tool, and a small molecule ([0042]-[0062]). The specification further teaches inhibition of p97 in vitro in two lung cancer cell lines A549 and H1299 using a shRNA SEQ ID NO:1 (Examples 1-4), and a small molecule CB-5083 (Example 5). The state of the art teaches two types of inhibitors for p97 for viral therapies : siRNA and small molecule. Phongphaew et al ( Virus Res, 2017, 228: 114-123) teaches inhibition of p97 using siRNA requires rational design of siRNA complementary to various conserved regions of p97 and possible screening of effective siRNA as results demonstrated that one of the designed siRNA failed to inhibit p97 in West Nile virus-infected cells (pg. 117, section 3.2). Similarly, Wong et al ( J Virol., 2015, 89: 11116-11128) teaches only one of the “custom-designed siRNAs” successfully inhibited p97 in HCoV-229E-infected cells (pg. 11120, right-column). Furthermore, Wang et al ( Medicinal Chemistry Research, 2021, 30:440-448) teaches only three small molecule s LC-1310, NMS-873 and CB-5083 act as inhibitors of p97 in cytomegalovirus-infected cells ( Abstract ). Together, the art establishes that inhibition of p97 by siRNA cannot be predicted solely from sequence complementary, and effective species must be identified through screening and validation. In addition, significantly limited species of small molecule inhibitor of p97 has been evaluated in the context of viral infection . This further underscore the unpredictability of p97 inhibition in antiviral therapies. In addition, it is unknown in the art and is not discussed in the specification regarding any agent that has upstream or downstream effects capable of indirectly promoting inhibition of p97. No structure, chemical properties, functional characteristics, or working examples are provided for agents that indirectly promote inhibition of p97. Thus, claims 1 and 25 are rejected for insufficient written description of the agent that promotes inhibition of p97. The dependent claims recite additional limitations to the method of claim 1 and the method of claim 25, such as shRNA inhibitory nucleic acid molecule, viral infection type, viral proteins , and results of the inhibition of p97 . However, SEQ ID NO:1 is the only shRNA sequence disclosed by Applicant with no additional sequence variants, no structure-function guidance, no loop nucleotide sequence . Therefore, this shRNA is characterized as a siRNA. While Baroy et al ( Mol Biotechnol (2010) 45:116-120) teaches strategies to design shRNAs from siRNA sequences, it was demonstrated that only 19 out of the 25 shRNA constructs were efficient in reducing target expression (Abstract), indicating that designing shRNA constructs directly from siRNA is unpredictable . Therefore, the specification does not provide adequate written description of the underlying shRNA sequence species and most importantly, prosecution of claimed method in a subject . Thus, t he written description deficiencies of claims 1 and 25 extends to dependent claims 2 -8, 11, 18 -22, 26- 29, and 32 . Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and the state of prior art including the knowledge of agents that promote inhibition of p97 and administration of said agents in a subject to treat viral infection, Applicant was not in possession of the full scope of inhibitors of p97, including the genus of shRNA recited in the claims , and the claimed method s of treating a viral infection in a subject and identifying a subject having coronavirus infection by detection of biomarkers CDC20, CDC27, PSMD14, and PSMB3 . Claim Rejections - 35 USC § 112 - Enablement Claim s 1-8, 11, 18- 22 , 26-29, and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for the use of a method to treat a viral infection in a subject by administering an agent, specifically an inhibitory shRNA nucleic acid molecule that promotes inhibition of p97. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims. The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant factors are indicated below: Nature of the Invention and Breadth of Claims With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails determining what the claims recite and what claims mean as a whole . The nature of the invention is directed to a method of treating Coronavirus infection in a subject by administering an agent, specifically a shRNA, that promotes inhibition of p97, leading to reduction of Coronavirus viral titer, cytopathic effects, and replication, as well as reduction of Coro navirus infection or a symptom thereof . Accordingly, the claims require three key structures : 1) shRNA nucleic acid molecules that promote inhibition of host fact or p97, 2) inhibition of p97 affects Coronavirus replication, and 3) administration in vivo, to a subject. The claim s broadly recite any shRNA inhibitors of p97 and administered to any subject human or non-human mammal, as defined in the specification (see [0028]). The claims encompass a broad genus of shRNA sequences . Guidance of the Specification The specification does not teach how to make and use additional species across the genus of shRNA that promotes inhibition of p97. Further, the specification does not enable any person skilled in the art to which it pertains (i.e. administering an shRNA that promotes inhibition of p97 in a subject to treat a coronavirus infection ) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual method comprising inhibitory shRNA or any inhibitory nucleic acid molecule of p97 capable of treating coronavirus infection in a subject . Regarding route of administration, the specification teaches “inhibitors of p97 can be administered by any suitable route of administration”, including oral administration, rectum administration, transdermal administration, intranasal administration, inhalation, by injection or in the form of a tablet, capsule, patch or a drink ([0068]) Regarding treatment dosage, the specification teaches i) an “effective amount” of an agent to administer depends “upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, a physical or veterinarian will decide the appropriate amount and dosage regime” ([0032], ii) doses of p97 inhibitors can be readily determined for a given subject based on their body mass, disease type and state, and desired aggressiveness of treatment” ([0067]) , and iii) “p97 inhibiting agent is administered to the subject until a coronavirus infection, or a symptom thereof in the subject is reduced” ([0061]). These general statements do not provide any specific guidance regarding how to administer an agent to a subject. Regarding methods of treating a coronavirus infection , the specification teaches “an ATP-competitor can be used to inhibit the enzyme activity of p97” ([0055]), “the coronavirus infection is caused by the members of the Coronavirinae subfamily of viruses” [0056], “identifying a subject who would benefit from inhibiting p97” ([0058]). The specification further teaches generation of stable H1299 cell lines expressing one shRNA SEQ ID NO:1 for inhibition of p97 in vitro upon infection with two viruses HCo V-229E and HCoV-OC43 (Examples 1-4), and proteomic analysis of viral proteins post-inhibition. However, there is no specific guidance on how to practice the present invention. The specificatio n does not provide the following evidence : i) any representative working examples of in vivo treatment of coronavirus infection using shRNA, including animal or human data showing antiviral efficacy of any shRNA sequences ii) guidance on selecting shRNA inhibitors of p97 that will reliably reduce viral load in vivo iii) disclosure of delivery systems, formulations, and routes of administration for effective shRNA expression in respiratory tissues in a subject considering host immune responses. Disclosure could include AAV vector serotypes, viral titers, nanoparticle or plasmid compositions, administration method and frequency. vi) disclosure of dosing ranges or pharmacokinetic data that would allow a person ordinary skill in the art to make and/or use the claimed method Thus, such disclosure does not teach a method of treating a coronavirus infection by administering the claimed genus of shRNA inhibitors of p97, and let alone an agent that promotes inhibition of p97. The working embodiments of reducing viral titers of two coronavirus species do not support the claimed scope of reducing a viral infection. Lastly, the working embodiments of treatment in two lung cancer cell lines do not support the claimed scope of treatment in a subject. State of the Art At the time of filing, the state of the art relating to p97 inhibition-based antiviral therapies demonstrated that p97 inactivation could suppress virus at the cellular level. Arita et al ( J. Virol., 2012, 86 , 10: 5541-5553) demonstrated siRNA-mediated inhibition of valosin-containing protein (referred as p97 in the instant case) host factor successfully suppress ed replication of poliovirus in vitro because ATPase activity of p97 is essential for viral replication (Fig. 1A , Table S1 , and pg. 5543). Arita further teaches that knockdown of p97 did not suppress replication of other virus in the same genus or family , and a mutant poliovirus, which has a secretion inhibition- negative phenotype, resisted p97 knockdown compared to wild-type poliovirus (pg. 5542, left-column, second paragraph). Lin et al ( PloS Pathog. , 2017, 15 , 5: e1006329) also demonstrated siRNA-mediated inhibition of p97 successfully suppressed replication of human cytomegalovirus in vitro because ATPase activity of p97 is essential for the expression of virus gene IE2 (Fig. 2 and 4, pg.3-11). Lin further teaches a small molecule inhibitor of p97, NMS-873, is also a potent antiviral for human cytomegalovirus (Fig. 10, pg. 13) but it shows additional off target effects compared to siRNA-mediated knockdown of p97. Phongphaew et al ( Virus Res, 2017, 228 : 114-123) also demonstrated siRNA-mediated inhibition of p97 successfully suppressed replication of West Nile virus in vitro by reducing expression levels of virus E protein (Fig. 2, pg. 117). Phongphaew further teaches that only two of the three siRNAs targeting three different regions of the p97 gene successfully knockdown endogenous p97 (pg. 117, section 3.2), indicating that rational design and experimental optimizations of siRNAs are required to achieve effective inhibition of p97 . Wong et al ( J Virol., 2015, 89: 11116-11128) applied siRNA screening and identified p97 is also essential for human coronavirus HCoV-229E replication as loss of p97 inhibits nucleocapsid N protein in vitro , reduced viral titers, cytopathic effects, and rate of viral replication (Fig 3, pg. 11120-11121). Wong also teaches custom-designed siRNAs are required for effective inhibition of p97 (pg. 11120, right-column). Separately, Kristijan et al (WO 2021/023973 A1; Published Date: 11 Feb 2021; Filed Date: 30 Jul 2020) has demonstrated that the siRNA-mediated depletion of p97 (using the same sequence as the instant SEQ ID NO: 1 disclosed in specification [0067]) could be used in vitro to indirectly regulate expression topoisomerase 1 (Figure 1, pg. 27 “sip97#3) , which serves as a biomarker for metastatic colorectal cancer therapy ( pg. 1). Asides from RNA interference-mediated inhibition of p97, Wang et al ( Medicinal Chemistry Research, 2021, 30:440-448) teaches inhibition of p97 by three small molecules LC-1310, NMS-873 and CB-5083 cytomegalovirus-infected cells (Table 1). Wang further teaches that “ overall cellular toxicity for p97 compounds provides a challenge for antivirals targeting p97 ” (pg. 441, left-column, third paragraph). Further, Zhou et al ( J. Med. Chem. 2015, 58:9480-9497) teaches the first selective inhibitor of p97, a small molecule CB-5083, and its treatment of tumor cells in vitro (Abstract). Zhou also discloses that CB-5083 exhibits requisite pharmacological properties to allow for testing in clinical trials. However, this study was not directed to treatment for viral infection. Further, The Food and Drug Administration (hereinafter, FDA ) (Antiviral Product Development – Conducting and Submitting Virology Studies to the Agency, Guidance for Industry, Center for Drug Evaluation and Research ; Published Date: June 2006 ; Content current as of: 24 Apr 2020 ) recommends preclinical development plans for antiviral products that sponsors should generate before moving into preclinical stage studies for antiviral products, including coronavirus. The FDA guidance makes it clear that in vitro studies alone are not sufficient to support clinical development (see section V. “Virology study reports”), and regulators highlight the following information should be included on nonclinical studies: “(i.e., mechanism of action, antiviral activity in vitro, cytotoxicity and therapeutic indexes, effects of serum protein binding on antiviral activity… in vitro selection of resistant viruses to the investigational product , the phenotypic and genotypic characterization of resistant viruses, cross-resistance before initiation of clinical studies ” (pg. 3) Considering the guidance from the FDA, it can be concluded that that extrapolating from in vitro inhibition of p97 to effective and safe treatment of viral infection in a subject is not routine or predictable because transition from in vitro to in vivo efficacy and safety is highly uncertain. In summary, as of the filling date, there is no prior art disclosing any successful in vivo therapeutic treatment of viral infection using any agents that promotes inhibition of p97 . The state of the art did not provide guidance on delivery systems, dosing regimens, expression control, or safety considerations that are necessary to achieve effective inhibition of p97 in a subject with coronavirus infection without substantial and unpredictable experimentation. Experimentation Required For example, it would be necessary for one of ordinary skill in the art to conduct the following experimentation in order to practice the claimed invention : 1) designing and screening inhibitors that effectively inhibit p97 in a subject (see teachings of Phongphaew and Wong regarding different siRNAs showing various degree of inhibitions) 2) developing a suitable delivery system, such as nanoparticles, viral vectors, and chemical modifications, capable of transporting the inhibitor to relevant tissues (e.g., lung tissues for coronavirus) in a subject 3) determining in vivo dosing, pharmacokinetics, formulations, and drug stability for therapeutic inhibition of p97 in a subject 4) evaluating therapeutic efficacy and safety in a subject, including reduction of viral load, mitigation of infection symptoms, host-immune response, and off-target effects (see teachings of Lin and Wang ) Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclu ded that an unreasonable amount experimentation would be required to make and use the invention as claimed . Claims 23-29, and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Claims 23 and 24 are directed to a method to identify a subject having coronavirus infection by detection of biomarkers CDC20, CDC27, PSMD14, and PSMB3 . This method is also recited as one of the steps in the method of claim 25. The specification does not reasonably provide enablement for the use of a method to identify a subject having coronavirus infection by detection of listed biomarkers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims. The most relevant factors in a test for enablement are below: Nature of the Invention and Breadth of Claims The claims are directed to a method of identifying a subject having coronavirus infection by detecting the level of one of the biomarkers CDC20, CDC27, PSM14, or PSMB3 in a subject. Claim 25 further recites comparing the detected levels to indicate the presence of coronavirus infection. Guidance of the Specification The specification does not enable any person skilled in the art to which it pertains (i.e. detecting the level of a product or expression of a gene from the listed biomarkers) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual method comprising detecting expression of these biomarkers in a subject. Regarding detection of biomarkers, the specification teaches the use of TMT-label proteomics for analyzing protein expression changes before and after coronavirus infection in two lung cancer cell lines, followed by proteomic data processing ([0072]-[0075]). The specification further teaches CDC27, CDC20, PSMD14, and PSMB3 expression level increases or decreases by only upon depletion of p97 ([0070]). Experimental data supported this statement wherein two proteasome related proteins, PSMD14 and PSMB3, and two components of the anaphase promoting complex or cyclosome (APC/C), CDC27 and CDC20 had different expression levels in coronavirus infected-cells that were treated with p97 inhibitor versus untreated cells (Fig. 3F). There is no teaching of how to adapt these in vitro proteomic methods for detecting of biomarkers in a subject, or how to obtain a biological sample from a subject to then apply these methods for detection of biomarkers. The specification does not disclose any steps for detecting these biomarkers in the absence of p97 depletion in vitro, let alone in a subject. State of the Art As of the filling date, Auwul et al ( Briefings in Bioinformatics, 2021, 22(5): 1-13) teaches analysis of RNA-Sequencing datasets of SARS-CoV-2 showed that CDC20 is a key gene module and hub target involved in COVID-19 (Abstract), indicating that it could be potential biomarker for detection of presence of coronavirus in cells. Further, the state of the art teaches standard protocols for detecting biomarker expressions levels in cells, such as Western Blotting for protein detection, RT-qPCR or RNA-seq for gene expression detection, and high-throughput proteomics for relative quantification of overall protein expressions. While some differentially expressed genes associated with coronavirus and methods for expression analysis are known, art does not teach a routine method for detecting these biomarkers in a subject for the purpose of diagnosing coronavirus infection. Thus, undue experimentation is required to practice the claimed method. Experimentation Required For example, it would be necessary for one of ordinary skill in the art to conduct the following experimentation in order to practice the claimed invention: i) designing and validating assays capable of detecting expression of these biomarkers in biological samples from subjects ii) optimization of assays including biological sample type, assay sensitivity, assay format, appropriate controls for comparison of expression levels iii) establishing baseline expression levels in subjects not infected with coronavirus, and defining criteria that can reliably determine the presence of coronavirus Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the concluded that an unreasonable amount experimentation would be required to make and use the invention as claimed . Conclusion No claims are allowable. 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