DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 1
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Jan 15 2026 has been entered.
Status of Claims
Claims 1-19 are pending and under examination.
Response to Arguments
Applicant's arguments filed Dec 16 2025 to rebut the obviousness rejection of claims 1-17 over US 2019/0255085 A1 in view of Sheahan have been fully considered but they are not persuasive for the reasons provided below.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Feb 5 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is 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.
Claim 5 depends from claim 4, where it recites “wherein the simple infection is fever, cough, and/or sore throat.” Claim 4 depends from claim 1, where it recites the disease caused by SARS-CoV-2 is a “simple infection.”
Claim 5 is indefinite as the common usage of “infection” is understood to be the invasion and growth of a pathogen (bacteria, viruses, yeast, fungi, etc.) in an host body. A simple “infection” would not be understood to be as claimed in claim 5, “is fever, cough, and/or sore throat.” Those conditions listed in claim 5 are the consequential symptoms of a “simple infection,” and NOT the actual invasion and growth of a pathogen in a host body. The conditions of claim 5 are the host body’s symptomatic response to a simple infection, not the pathogenic invasion and growth in the host.
This interpretation of “simple infection” is confirmed by the specification, on page 2, middle paragraph, which recites “Patients with simple infection may have non-specific symptoms, such as fever, cough, sore throat, nasal congestion, fatigue, headache, muscle pain or discomfort. . . . .”
Amendment of claim 5 to recite “The method according claim 5, where symptoms of the simple infection. . . . “ will overcome this rejection.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0255085 A1 (published Aug. 22, 2019), (US 085) in view of Sheahan (“Preparing for future pandemics, today with broad-spectrum antivirals”; Nature Portfolio Microbiology Community webpage; published Jan 10, 2020), as evidenced by ECDC webpage “Outbreak of acute respiratory syndrome associated with a novel coronavirus, Wuhan, China; first update,” dated Jan 22, 2020, evidentiary of Jan 9 2020.
Sheahan has been previously cited by the Examiner in earlier office actions and listed on the IDS of Aug. 2, 2021. US 085 was listed by the Examiner in on the PTO-892 form of Dec. 8, 2021. ECDC webpage is listed on the PTO-892 form.
In terms of claim interpretation, the pending claims are directed solely to the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The specification notes the SARS-CoV-2 virus was first identified as 2019-nCoV in 2019, where it states that “[t]he 2019 novel (2019-nCoV) is a new coronavirus strain that has never been found in humans before.” See specification on page 2, first full paragraph.
Amended claim 1 is directed to a method for treating a disease in a mammal in need, the method comprising
administering to the mammal in need
a pharmaceutical composition comprising a therapeutically effective amount of a compound represented by Formula I2, (known compound remdesivir, aka VEKLURY®)3.
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wherein the disease is a disease caused by a SARS-CoV-2, and
wherein the therapeutically effective amount inhibits replication of the SARS-CoV-2 virus genome in a cell of a mammal.
Similar to claim 1, claim 10 is a method of inhibiting replication or reproduction of SARS-Cov-2 virus genome in a cell of a mammal in need comprising the administering to the mammal in a pharmaceutical composition comprising a therapeutically effective amount compound of formula I, aka remdesivir. 4
New claims 18-19 recite the administered drug is remdesivir.
Regarding claims 1, 10 and 18-19, US Pub 085 discloses a method of treating coronavirus (such as SARS-COV) infection, in a human (mammalian subject) via remdesivir administration. See paragraph 316.
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Regarding the treatment of SARS-Cov-2 in a mammalian subject with a remdesivir pharmaceutical composition in instant claim 1 and the method for inhibiting the replication/reproduction of SARS-Cov-2 in mammalian subject in instant claim 10, US Pub 085 discloses a method of treating SARS-COV (different from the recently discovered SARS-COV-2 disease) in a human (mammalian subject), see paragraph 316. This administration of remdesivir will inhibit of replication or reproduction of a coronavirus in a cell of mammalian subject.
Paragraph 316 discloses the administration of remdesivir as the compound used, therein identified as formula I.
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See also claims 59 and 75 disclosing a method administering remdesivir to a human subject in need and claims 65-66 directed to treatment of various Coronaviridae infections including SARS and MERS.
Claim 63 of US Pub 085 discloses administering remdesivir to a subject further comprising a pharmaceutically acceptable carrier/excipient, i.e., a pharmaceutical composition.
In summary, US ‘085 teaches treatment of Coronaviridae infections, including SARS-CoV and MERS, comprising administration of nucleosides and prodrugs thereof, including the claimed compound, remdesivir, as claimed as a pharmaceutical composition. US ‘085 differs from the instant claims in so far as they do not teach the recently discovered Coronaviridae virus, SARS-CoV-2.
Sheahan teaches a new coronavirus is believed to be the cause of an outbreak of viral pneumonia in Wuhan China with potential spread to Hong Kong. See page 1. Sheahan teaches since the initial case reported on December 12th 2019, there have been at least 44 cases 11 of which are severely ill. See page 1.
Regarding claims 1, 10, 18 and 19 Sheahan teaches that the drug [remdesivir] is likely to work against currently emerging [Coronaviridae such as] CoV like MERS and the newly identified virus in Wuhan as well as those of the future. See page 2.
While Sheahan notes the emergence of the newly identified virus in Wuhan in late 2019 and early 2020, it does not explicitly identify the Wuhan virus as SARS-CoV-2.
However one of ordinary skill in the art would predictably arrive at the claimed invention of treating COVID-19 with remdesivir with a reasonable expectation of success, as the prior art suggests that with the emergence of a new Coronaviridae in late 2019, early 2020, broad spectrum antivirals such as remdesivir would be effective.
The genome sequence of SAR-CoV-2 was first released on January 10, 2020. 5 This is evidenced by the European Centre for Disease Prevention and Control (ECDC) website announcing the timeline of the Outbreak of the acute respiratory syndrome caused by the novel coronavirus in Wuhan, China: “On 9 January, 2020, China CDC reported that a novel coronavirus (2019-nCov) had been detected as the causative agent and the genome sequence was made publicly available.” [Emphasis added]
The ECDC web page teaches the Wuhan viral outbreak to be identified as 2019-nCoV by the China CDC, later designated as SARS-CoV-2, and the genome sequence made publicly available. See page 1.
Prior to the filing of the present patent application, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the primary reference, US Pub 085 teaching the claimed compound I, remdesivir, aka VEKLURY known to treat Coronaviridae infections including SARS and MERS modified with the secondary reference Sheahan as evidenced by EDC in order to treat SARS-CoV-2 as presently claimed.
The PHOSITA would have had a reasonable expectation of success because the combination of known prior art elements (use of the anti-viral drug remdesivir to treat the coronavirus outbreak of Dec 2019-Jan 2020 in Wuhan China, as taught by ECDC webpage was identified as 2019-nCoV, the previous name of SARS-CoV-2) according to known methods (US ‘085 teaches treatment of Coronaviridae infections, including SARS and MERS, comprising administration of the claimed compound, remdesivir and pharmaceutical compositions) to predictably arrive at the claimed invention of administering remdesivir to treating SARS-CoV-2 infection, and inhibiting replication and/or reproduction of SARS-CoV-2 virus genome in a mammalian subject. MPEP 2143.
Prior to the priority date of the invention, Jan. 21, 2020, the prior art taught administering remdesivir as claimed to the genus of coronaviruses, inclusive of SAR-CoV, where Sheahan teaches administration of remdesivir to address the 2019 coronavirus viral outbreak in Wuhan, and EDC identified the Wuhan viral outbreak as 2019 nCoV, later identified as SARS-CoV2 as claimed.
Regarding claims 2-5 and 13 and the limitation of a SARS-Cov-2 disease, aka COVID-19, respiratory disease, pneumonia, with infection like symptoms such as fever/cough/sore throat, Sheahan teaches a new coronavirus [evidenced by ECDC website to be SARS-Cov-2] is believed to be the cause of an outbreak of viral pneumonia in Wuhan China with potential spread to Hong Kong. See page 1. Sheahan teaches since the initial case reported on December 12th 2019, there have been at least 44 cases 11 of which are severely ill. See page 1. Sheahan teaches that the drug [remdesivir] is likely to work against currently emerging CoV like MERS and the newly identified virus in Wuhan [evidenced by the EDCD website to be SARS-CoV-2] as well as those of the future. See page 2.
Regarding claims 6-7, 11 and 12 and the limitations of a pharmaceutically acceptable excipient/carrier, which would entail the formulation of pharmaceutical compositions, claim 63 of US Pub 085 discloses the claimed method of administering remdesivir to a subject further comprising a pharmaceutically acceptable carrier or excipient.
Further, US Pub 085 teaches a spray formulation, creams, gels and pastes. See paragraph 413. US Pub 085 further teaches a liquid injectable formulation and a solid tablet formulation. See paragraphs 414-415 and 429, respectively.
Regarding claims 8, 9 and 14-15, and the limitations of primate and/or human subjects, Sheahan, as evidenced by the ECDC website identifies the viral outbreak among the residents of Wuhan China caused by the 2019-nCoV virus, aka SARS-CoV-2. See page 1. Sheahan teaches that the drug [remdesivir] is likely to work against currently emerging CoV like MERS and the newly identified virus in Wuhan [2019-nCoV, aka SARS-CoV-2] as well as those of the future. See page 2. Accordingly, the claimed invention was prima facie obvious in view of the prior art.
Regarding claims 16-17 and the limitation of a therapeutically effective amount of at least 3.7 μM, any amount above the claimed concentration will render the claims obvious. Here US 085 discloses the calculation of effective doses of active ingredient dependent upon the expertise of the skilled artisan and factors such as prophylaxis vs active infection, method of delivery, pharmaceutical formulation etc. See paragraph 422 Such doses that overlap the claimed amounts are from about 0.0001 to about 100 mg/kg body weight per day; typically, from about 0.01 to about 10 mg/kg body weight per day; more typically, from about 0.01 to about 5 mg/kg body weight per day; most typically, from about 0.05 to about 0.5 mg/kg body weight per day. For example, the daily candidate dose for an adult human of approximately 70 kg body weight will range from 1 mg to 1000 mg, preferably between 5 mg and 500 mg, and may take the form of single or multiple doses. Id at paragraph 422.
RESPONSE TO THE ATTORNEY ARGUMENTS:
Throughout the rebuttal of the Attorney response, reference to 2019-nCoV is stated, which is the earlier recognized name of the SARS-CoV-2 virus responsible for COVID-19.
As an introduction discussing uncertainties in the state of the art, the Attorney response discusses parasitic viral life cycle, in its three stages/six steps (Entry, Genome replication and Exit) where a virus commandeers a host cell’s machinery to produce progeny virus, where ssRNA+ CoVs directly translate their genomes into viral proteins by host cells (see Christopher, Cui, Tortura references).
The Attorney response describes the phylogeny viral taxonomy hierarchy6 where the 4 CoV genera are Alpha and Beta CoVs that infect mammals only, Gamma and Delta that infect birds with some mammal crossover. SARS-CoV and MERS-CoV both cause severe acute respiratory disease with a higher than 10% fatality rate.
CoVs (Order of the Nidovirales) rely upon low-fidelity polymerases, allowing them to adapt to different environments like antiviral drug challenges, to synthesize adaptive DNA/RNA, via polymerase RdRp domain (nsp12) (citing to Sola). CoV exhibit an exonuclease proofreading function/activity that protect it from polymerase errors (citing to Ferron). SARS-CoV requires a specific transferase (NiRAN domain of nsp12 protein for viral replication (citing Lehmann).
In rebuttal of the Examiner’s rejection, Attorney response cites to the OSI Pharma case and states the Examiner ignores the PHOSITAs uncertainties and doubts about remdesivir as a potent broad spectrum antiviral (BSA) agent at the priority date.
More specifically at the priority date,
a) the PHOSITA knows the challenges of developing a BSA to treat CoVs (polymerase RdRp allows for CoV/RNA virus to develop resistance and ExoN proofreading of nsp14, citing to Ferron; and challenges of host cell uptake of nucleoside analog drug, citing to various references);
b) not known at the priority date are, remdesivir’s precise mechanism;
remdesivir’s sensitivity to proofreading nsp14-ExoN and its affinity to ATP-binding enzymes of 2019-nCoV (aka the SARS-CoV-2 virus). Also noted is analysis of the 2019-nCoV genome (published Jan 11 2020) that Applicant states raises doubts/questions of the obviousness rejection ((high homology with SARSCoV nsp12 gene; conservation of Orf1b part of genome (replication); and unique amino acid (aa) of Spike protein, where the virus had different cell entry (infectious) capabilities (high efficiency of Furin Cleavage Site (FCS)). See pages 19-34 of the Attorney response.
In response to the statements of regarding the background of the art of SARS-CoV and 2019-nCoV (aka SARS-CoV-2), it is pointed out that teachings from the cited prior art teach the treatment known coronaviruses such as SARS-CoV with remdesivir.
In establishing the prima facie case of obviousness, “Office personnel should weigh all relevant evidence of record in order to determine whether the claims would have been obvious based on a preponderance (more likely than not) standard.” See MPEP 2145 citing to MPEP § 716 - § 716.10 for additional information pertaining to the evaluation of rebuttal evidence submitted under 37 CFR 1.132.
While the general state of the taxonomy art of coronaviruses are relied upon as a way to support arguments of uncertainty and doubt regarding remdesivir and treatment of SARS-CoV2, these initial state of the art statements do not overcome the prima facie case based on a preponderance/more likely than not standard of evidence as detailed in the rejection, especially in light of the explicit teaching/suggestion of Sheahan.
The Attorney response argues claims 1-17 are non-obvious because the Examiner’s reasoning does not allow the PHOSITA to reach the claimed solution as it is based on impermissible hindsight, partial presentation of the facts and ignores the PHOSITA uncertainties and doubts at the priority date, with the rejection hanging on to the Sheahan reference.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The general allegation by Applicant of hindsight reconstruction is rebutted by the teaching and suggestion by Sheahan that remdesivir would be useful to treat the emerging coronavirus infection from Wuhan in late 2019, aka 2019-nCoV, aka SARS-CoV-2.
The Attorney response states the facts of this case are similar to OSI Pharm v. Apotex decision (where the Court noted a lack of disclosure of data in vivo and in vitro AND a finding of Phase II clinical data fact of 99.5% failure for other drugs); the Attorney states “the only reasonable expectation of success at the time of the invention was failure not success.’ See page 20, bottom of page.
The Attorney response opines the Sheahan reference is a promotional publication for the drug [remdesivir] to be taken in account by a PHOSITA to treat the disease later known as COVID-19, where the PHOSITA would have many questions and doubts without experimental data.
In response, it is respectfully submitted that at the priority date of invention, unlike the fact pattern of OSI Pharm, there was not a long established failure of any broad spectrum antiviral drugs against the newly emerging 2019-nCoV outbreak in Wuhan (now known as COVID-19), let alone remdesivir.
Prior to the invention’s filing priority date, a PHOSITA would have relied upon the state of the art suggestion of Sheahan to treat the newly emerging viral outbreak with a known antiviral compound such as remdesivir. While Sheahan’s teaching does not provide either in vitro or in vivo data noted by the Court as per OSI Pharm v. Apotex, based on the statement of Sheahan, a PHOSITA would nonetheless rely upon the statement from Sheahan to treat later identified COVID-19 with remdesivir.
Arguably, even in the absence of the teaching of Sheahan that explicitly teaches treatment of 2019-nCoV infections with remdesivir, as per cited US 085, its prior art teachings (paragraph 316 and claims 59 and 75) that disclose use of remdesivir to treat earlier known SARS-CoV infections would satisfy the preponderance of evidence test to establish a prima facie case of obviousness.
The Attorney response states a PHOSITA would have remaining doubts at the priority date after a comparison of the sequence alignment, where
On pages 35-38 of the Attorney response, the Attorney arguments to rebut obviousness are based on comparison of 2019-nCoV’s genome with those of MERS-CoV and SARS-CoV-1. Comparisons of the NiRAN and RdrP domains were noted to be highlighted in blue and purple boxes, where further comparisons were highlighted in green and yellow, and stars, between 2019-CoV and SARS-CoV-1 . Because the response filed is only in black and white in the PAIR system, the Examiner was not able to note the arguments with regard to blue, purple boxes, and yellow and green highlights.
Applicant states a PHOSITA understands from the sequence comparison that there was no reasonable chance of success to try remdesivir to treat 2019-nCoV (23aa differences in the NiRAN domain (6.25%) and 10 aa differences (1.77%) in the RdRp domain)
Applicant states differences in NiRAN and RdRp (F766 amino acid mutation with conjectured remdesivir but NOT established or proven resistance) subdomain of SARS-CoV2 versus SARS-CoV (see especially page 40 comparison of Motif C and Motif D of various viruses); FCS differences associated with 2019-nCoV spike protein alleged to result in unpredictability;
The Attorney response states the Sheahan reference is merely promotional and speculative, prior to first publication of the first draft genome/phylogenetic analysis; and that Sheahan would only know the emerging outbreak was a corona virus. The Attorney response states a PHOSITA would use great caution, with the implication by the Attorney response the PHOSITA “would thus either dismiss Prof Sheahan' s statements regarding the 2019 Novel Coronavirus as speculative or, at the very least, as lacking any further confirmation.” (Noting reference to the editorial of Exhibit 31, IDS NPL 102 submitted to Nature on Feb 5 2020).
Initially, with respect to bullet point d) regarding Sheahan, these have been addressed above.
With regard to bullet point a), while the Examiner was not able to identify the differed colored boxes and highlights noted by Applicant, even taking Applicant’s statements at face value of the differences between 2019-nCoV genome versus other coronavirus genomes, these statements are what a PHOSITA “would” consider into account based on this genome comparison rather than actual data to consider whether remdesivir was or was not effective against 2019-nCoV prior to the invention’s priority date. While the factual evidence of differences in genome of 2019-nCoV is relevant in the preponderance of the evidence analysis, as not only Sheahan teaches and suggests remdesivir to treat the emerging Wuhan coronavirus epidemic in 2019, US Pub 085 notes the efficacy of known remdesivir to treat other SARS coronavirus infections.
Similarly, with regard to bullet points b) and c), where NiRAN and RdRp subdomain differences are between 2019-nCoV and SARS-CoV are said rebut the finding of obviousness, the Attorney response states “if” some differential nucleoside analog binding activities are mapped to nsp12, “they are more likely” to come from the NIRAN subdomain. See page 39. While the NiRAN/RdRp domain differences are relevant in the preponderance of the evidence analysis, as not only Sheahan teaches and suggests remdesivir to treat the emerging Wuhan coronavirus epidemic in 2019, US Pub 085 notes the efficacy of known remdesivir to treat other SARS coronavirus infections.
Conclusion and Correspondence
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a CON of 17/070,271, which claims earliest priority to CHINA 202010071087.7 filed 01/21/2020.
2 As well as a geometric isomer, a pharmaceutically acceptable salt, a solvate and/or a hydrate thereof
3 Aka GS-441524, or CAS Registry No. 1809249-37-3
4 As well as a geometric isomer, a pharmaceutically acceptable salt, a solvate and/or a hydrate thereof
5 This teaching in the prior art is confirmed by paragraph 5 of the Dr. Luo Declaration submitted with Applicant’s November 2024 response,
6 order, family, subfamily, genus, sub genus, species, type and subtype
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