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 .
DETAILED ACTION
Priority
This application is a 371 of PCT/US2021/064392 filed December 20, 2021, which claims priority to US Provisional Application No. 63/128,451, filed on December 21, 2020 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 06/21/2023 is acknowledged. Claims 1-20 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/21/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Claim Objections
Claims 2, 9 and 15 are objected to for the following informalities:
Claim 2, 9 and 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-8 and 10-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. “Li” (PLoS ONE, 2011, 6(10):1-9, IDS of record dated 06/21/2023).
The claims are directed to a method of detecting severe disease-associated mutations in an enterovirus 71 (EV-A71), comprising: performing an assay on a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof to detect one or more severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 protein or fragment thereof, wherein the one or more mutations are selected from mutations at positions corresponding to 5’ UTR nucleotide positions C580, A707, and C709 in an EV-A71 5’ UTR nucleic acid sequence and at residues corresponding to A280 and E145 in an EV-A71 VP1 protein sequence.
Regarding claims 1, 3, 8 and 10, Li discloses a method of detecting severe disease-associated mutations in an enterovirus 71 (EV71= EV-A71) comprises (a) obtaining a sample containing an EV71 VP1 protein from a subject; (b) detecting the presence of one or more severe disease-associated mutations/mutation at E145 residue; 145G, 145Q, 145R in the EV71 VP1 protein, wherein the mutation 145G, 145Q, 145R in the EV71 VP1 protein are associated with EV71 virulent phenotype, and wherein EV71 with the mutations can cause severe clinical outcomes (Abstract, pages 2, 7-8; figure 2) (instant claims 1, 3, 8 and 10).
Regarding claims 4 and 11, Li discloses the assay is a PCR amplification followed by sequencing (page 8 last para.).
Regarding claims 5-7 and 12-13, Li discloses biological samples from a subject (skin vesicles and stool samples (page 8 first column first full para. and fourth full para.).
Therefore, the cited prior art anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
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. Applicant is 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 14 and 16-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al. “Li” (PLoS ONE, 2011, 6(10):1-9, IDS of record dated 06/21/2023) as applied to claims 1, 3-8 and 10-13, in view of Chua (WO2016122403, IDS of record dated 06/21/2023). The teachings of Li are outlined above and incorporated herein.
The claims are directed to a method of treating a subject infected with an enterovirus 71 (EV-A71), comprising: obtaining a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof, wherein the test sample is prepared from a biological sample from a subject infected with the EV-A71; and detecting in the test sample the presence of one or more of severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 VP1 protein or fragment thereof, wherein the mutations are selected from mutations at positions corresponding to 5’ UTR nucleotide positions C580, A707, and C709 in an EV-A71 5’ UTR nucleic acid sequence and at residues corresponding to A280 and E145 in an EV-A71 VP1 protein sequence; and administering a treatment or treatment regimen for decreasing risk of development of a severe disease in the subject.
Regarding claims 14 and 16, Li discloses a method of detecting severe disease-associated mutations in an enterovirus 71 (EV71= EV-A71) comprises (a) obtaining a sample containing an EV71 VP1 protein from a subject; (b) detecting the presence of one or more severe disease-associated mutations/mutation at E145 residue; 145G, 145Q, 145R in the EV71 VP1 protein, wherein the mutation 145G, 145Q, 145R in the EV71 VP1 protein are associated with EV71 virulent phenotype, and wherein EV71 with the mutations can cause severe clinical outcomes (Abstract, pages 2, 7-8; figure 2) (instant claims 1, 3, 8 and 10).
Li does not explicitly disclose a method of treating a subject.
Chua, however, discloses the development of an animal model as it pertains to EV-71; and screening of candidate anti-EV71 compounds the development of an animal model and screening of candidate anti-EV71 compounds (Abstract). Chua states “ the present invention provides a method to screen antiviral drugs. In accordance with this aspect, the method comprises the following steps: providing a test group of animals and a control group of animals in which the animals of each group are animals of the animal model described herein; administering to the test group an antiviral drag candidate; monitoring disease progression in the test group and the control group; comparing the disease progression in the test group to the disease progression in the control group; and selecting the antiviral drug candidate that reduces disease progression in the test group relative to the control group. In one embodiment, the antiviral drug is first screened in a test rodent cell line infected with a rodent cell line adapted Enterovirus 71 before screening in the animals. In another embodiment, the antiviral drug is first screened in a test rodent cell line infected with a clone derived virus (CDV) containing mutations in VP1 before screening in the animals (paragraph [0016]). Chua also discloses “the present invention provides a method to screen effective antiviral vaccines. According to this aspect, the method comprises the following steps: providing a test group of animals and a control group of animals in which the animals of each group are animals of the animal model described herein; administering to the test group an antiviral vaccine candidate; monitoring disease progression in the test group and the control group; comparing the disease progression in the test group to disease progression in the control group; and selecting the antiviral vaccine candidate that reduces disease progression in the test group relative to the control group. In one embodiment, the antiviral vaccine candidate is first screened in a test rodent cell line infected with a rodent cell line adapted Enterovirus 71 before screening in the animals. In another embodiment, the antiviral vaccine candidate is first screened in a test rodent cell line infected with clone derived vims (CDV) containing mutations in VP1 before screening in the animals (paragraph [0017]).
It would have been obvious to one of ordinary skill in the art to generate a method of detecting severe disease-associated mutations in an EV-A71 as disclosed by Li whereby the method can be utilized in treating a subject infected with an enterovirus 71 and administering a treatment or treatment regimen for decreasing risk of development of a severe disease in the subject as taught by Chua. One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success given the knowledge that the severity of disease based on EV-A71 mutations are known as disclosed by Li and given the fact that Chua demonstrates that antiviral drug are first screened in a test rodent cell line infected with a clone derived virus (CDV) containing mutations in VP1 before screening in the animals (paragraph [0016]); and “the present invention provides a method to screen effective antiviral vaccines. According to this aspect, the method comprises the following steps: providing a test group of animals and a control group of animals in which the animals of each group are animals of the animal model described herein; administering to the test group an antiviral vaccine candidate; monitoring disease progression in the test group and the control group; comparing the disease progression in the test group to disease progression in the control group; and selecting the antiviral vaccine candidate that reduces disease progression in the test group relative to the control group (paragraph [0017]). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 17, Li discloses the assay is a PCR amplification followed by sequencing (page 8 last para.).
Regarding claims 18 and 19, Li discloses biological samples from a subject (skin vesicles and stool samples (page 8 first column first full para. and fourth full para.).
Regarding claim 20, Li discloses “EV71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. To identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 59-NTR and 39-NTR in 25 SC-EV71 strains (strains from severe cases) and 31 MC-EV71 strains (strains from mild cases) were analyzed” (Abstract).
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672