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
Acknowledgement is hereby made of receipt and entry of the communication filed on 6/15/2026. Claims 1-19 are pending. Claims 18-19 are withdrawn. Claims 1-17 are currently examined.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-17), and the required species, a) non-human rotavirus, b) human rotavirus, c) VP7, d) SEQ ID NO: 3, and e) SEQ ID NO: 6 and SEQ ID NO: 7, in the reply filed on 6/15/2026 is acknowledged.
Claims 18 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/15/2026.
Claims 1-17 are under examination on the merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on p. 17. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 10 is objected to because of the following informalities: claim 10 recites “from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5”, but should instead read “from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5”. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: claim 11 recites “the cell line is introduced with a vector containing a double-stranded DNA oligonucleotide encoding a pre-miRNA for the mRNA” on line 2. It should instead recite “a vector containing a double-stranded DNA oligonucleotide encoding a pre-miRNA for the mRNA is introduced into the cell line”. Appropriate correction is required.
Claim Interpretation
The examiner is interpreting the claim limitation “corresponding” in claims 1 and 14 to mean that the step requires addition of the same gene segment from the different rotavirus.
Claims 1 and 17 require a cell that “stably” expresses an inhibitory RNA. The examiner is interpreting “stably” to mean constant, constitutive, or permanent expression of a nucleic acid of interest, as opposed to transient expression, as indicated for “stable expression” on page 16 of the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 6, 11-13, and 17 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.
Claims 3 and 6 recite “rotavirus strain or a progeny thereof”. The term “progeny” is very broad, and is not defined by the specification. As written, the metes and bounds of the term “progeny” are unclear, because it is not apparent what qualifies as a “progeny” for purposes of the claimed invention. For example, is a reassortant rotavirus bearing 10 gene segments from a first rotavirus and 1 gene segment from a second rotavirus considered a “progeny” of the first and/or second rotavirus? Please clarify the meaning of “progeny” for the purposes of the claimed invention.
Claim 11 recites “a vector containing a double-stranded DNA oligonucleotide”. However, the term vector, as used in the disclosure encompasses vectors much larger than oligonucleotides. For instance, Examples 2 and 3 of the specification (pp. 23-25) indicate that some of the vectors for miRNA expression exceed 5.6 kb in length, which is much longer than an oligonucleotide. Accordingly, it is not clear how a vector could contain an oligonucleotide. Claims 12 and 13 have the same issue, and depend from claim 11 but do not resolve this lack of clarity, so are thus also indefinite and rejected.
Claim 12 recites “double-stranded DNA oligonucleotides formed by one or more sequences pairs”. It is unclear if the claim requires the whole sequence of the sequence identifiers (SEQ ID NO: 6 and SEQ ID NO: 7).
Claim 17 depends from claim 1, and recites “further comprising: providing a cell line stably expressing miRNA against a VP7 gene segment of bovine WC3 rotavirus; introducing mRNA of the VP7 gene segment of human rotavirus, or DNA or cDNA encoding the mRNA into the cell line; infecting the cell line with the WC3 rotavirus; and recovering a reassortant rotavirus comprising the VP7 gene segment of human rotavirus.” Due to the language “further comprising “ in line 1, it is unclear if claim 17 requires one to introduce inhibitory RNA to VP7 gene segment and another gene segment from claim 1, or if the claim means that the gene segment of the first rotavirus that the inhibitory RNA is against from claim 1 is the VP7 gene of bovine WC3 rotavirus.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-2, 4-6, 9, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Trask, et al. (Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18652-7. doi: 10.1073/pnas.1011948107. Epub 2010 Oct 11. PMID: 20937889, on IDS).
The claimed invention encompasses a method for producing a reassortant rotavirus, the method comprising: providing a cell line stably expressing an inhibitory RNA against a specific gene segment among 11 gene segments of a first rotavirus; introducing mRNA of a gene segment of a second rotavirus corresponding to said specific gene segment of the first rotavirus, or DNA or cDNA encoding the mRNA, into the cell line; infecting the cell line with the first rotavirus; and recovering a reassortant rotavirus comprising a gene segment of a second rotavirus corresponding to said specific gene segment of a first rotavirus, as represented by claim 1.
The Prior Art
Trask teaches methods for recovering recombinant rotaviruses to engineer single-gene replacements (Abstract). One aspect of Trask’s method is utilizing RNAi-mediated degradation of NSP2 mRNAs to isolate a virus containing a single recombinant gene, with simple and rapid recovery (Abstract). Trask’s methods aim to develop an efficient, broadly applicable method to generate recombinant rotaviruses (p. 18652, col. 1, para. 1). Trask suggests that it is conceivable that other selection mechanisms can be used, and combined, in novel ways to individually manipulate almost every rotavirus gene (p. 18656, col. 2, para. 2). Trask teaches that MA104 cells, which are normally highly permissive for RV infection, were transduced with a lentiviral vector encoding an SA11 gene 8-specific shRNA based on the g8D siRNA (Fig S1A; p. 18653, cols. 1-2, bridging para.), thereby ensuring the entire cell population expresses the shRNA (termed MA104-g8D cells), and the cells are permissive for infection by RV strains encoding gene 8 mRNAs that are not targeted by RNAi but restrict those that are targeted by ~10-fold and significantly reduces plaque size (p. 18653, bridging para.).
Trask’s method utilizes COS-7 cells, which are infected with a T7pol-expressing vaccinia virus and then transfected with an expression plasmid encoding a g8 segment that is resistant to the RNAI-mediated degradation (pBS-SA11g8R), and subsequently infected with a temperature sensitive helper virus (tsE), and allowed to replicate at 30°C (p. 18653, col. 2). And the resulting virus was then passaged in MA104-g8D cells to select for progeny containing the recombinant gene 8 (p. 18653, col. 2). Trask also discloses that its methods were able to replace the SA11 NSP2-coding sequence with that of DC1, DS-1, OSU, or U.K. viruses (Fig. S3, p. 18656, col. 1, para. 3). The instant specification indicates that DS-1 rotavirus is a human rotavirus of G2 serotype (p. 13). Trask refers to Chen, et al. (reference 16), which indicates that SA11 is a simian rotavirus in its title, cited by Trask (Trask, p. 6).
Trask teaches “[T]o develop reverse genetics for RV NSP2, we used a temperature-sensitive (ts) mutant of the SA11 strain, “tsE(1400)” (herein, simply called tsE), which produces a defective NSP2 protein, and RNAi-mediated degradation of tsE NSP2 mRNAs (9) to diminish the expression of parental NSP2. We provided in trans a complete gene 8 cDNA that (i) encodes the wt SA11 NSP2 protein and (ii)
has been engineered at the RNAi target site to avoid degradation. Passage at elevated temperature (39 °C) in a cell line engineered to silence tsE NSP2 expression by RNAi (17) applies two independent selection strategies against tsE and allows rapid isolation of recombinant virus. This method is efficient; after two rounds of selective passage the virus population is almost 100% recombinant and commonly reaches a titer of 104 plaque-forming units(pfu)/mL. Analysis of the selection scheme indicates that tsE is required for rapid isolation of the recombinant, whereas the use of gene 8-specific RNAi is less critical but greatly enhances recovery. We validated this method by generating a panel of engineered single-gene recombinants expressing chimeric NSP2 proteins derived from several group A RVs (those responsible for the majority of human RV disease), including that of a noncultivated, pathogenic isolate.” See p 18652, right column. Also see Fig. 1B shown below:
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The examiner is interpreting the instant claim 1 not to require a specific order of the steps to be formed in producing a reassortant rotavirus, as the claims nor specification indicate that the steps must be performed in a certain order. The MPEP indicates that an examiner should interpret claims ‘in view of the specification’ without unnecessarily importing limitations from the specification into the claims."); Altiris Inc. v. Symantec Corp., 318 F.3d 1363, 1371, 65 USPQ2d 1865, 1869-70 (Fed. Cir. 2003) (Although the specification discussed only a single embodiment, the court held that it was improper to read a specific order of steps into method claims where, as a matter of logic or grammar, the language of the method claims did not impose a specific order on the performance of the method steps, and the specification did not directly or implicitly require a particular order). See MPEP §2111.01(II).
Regarding claim 1, the MA104-g8D cell represents a cell line stably expressing an inhibitory RNA against a specific gene (i.e., gene 8 encoding NSP2) among 11 gene segments of a first rotavirus (i.e., SA11 tsE), while the RV strains encoding gene 8 mRNAs that are not targeted by RNAi can be considered as the second RV. Although Trask does not specifically disclose introducing mRNA of a gene segment of a second rotavirus corresponding to said specific gene segment of the first rotavirus, into the cell line, a person of ordinary skill in the art would immediately envisage that the tsE/SA11g8R rotavirus would, upon entry into the MA104-g8D cell, begin to transcribe mRNAs of the g8R gene segment. The claim limitation of recovering a reassortant rotavirus comprising a gene segment of a second rotavirus corresponding to said specific gene segment of a first rotavirus corresponds to recovering the tsE/SA11g8R reassortant by Trask’s method.
Regarding claim 2, which requires that the first rotavirus is a non-human rotavirus, Trask’s SA11 is a non-human rotavirus, as it is a simian rotavirus strain. Trask refers to Chen, et al. (reference 16), which indicates that SA11 is a simian rotavirus in its title, cited by (Trask, p. 6).
Regarding claims 4-6, wherein the second rotavirus is a human rotavirus, a G2 serotype, or DS-1 specifically, Trask teaches that its methods were able to replace the SA11 NSP2-coding sequence with that of DC1, DS-1, OSU, or U.K. viruses (Fig. S3, p. 18656, col. 1, para. 3). The instant specification indicates that DS-1 rotavirus is a human rotavirus of G2 serotype (p. 13).
Regarding claim 9, which requires the inhibitory RNA is miRNA, siRNA, or shRNA, and claim 16, which requires the cell line is MA-104, Trask teaches that MA104 cells, which are normally highly permissive for RV infection, were transduced with a lentiviral vector encoding an SA11 gene 8-specific shRNA based on the g8D siRNA (Fig S1A; p. 18653, cols. 1-2, bridging para.), thereby ensuring the entire cell population expresses the shRNA (termed MA104-g8D cells), and the cells are permissive for infection by RV strains encoding gene 8 mRNAs that are not targeted by RNAi but restrict those that are targeted by ~10-fold and significantly reduces plaque size (p. 18653, bridging para.).
Accordingly, Trask teaches methods of producing a reassortant rotavirus, a cell line stably expressing an inhibitory RNA against a specific gene segment among 11 gene segments of a first rotavirus, introducing mRNA of a gene segment of a second rotavirus corresponding to said specific gene segment of the first rotavirus, or DNA or cDNA encoding the mRNA into a cell line, infecting a cell line with the first rotavirus, and recovering a reassortant rotavirus comprising a gene segment of a second rotavirus corresponding to said specific gene segment of a first rotavirus. Trask discloses use of shRNA for producing reassortant rotaviruses. Trask teaches production of reassortant rotaviruses bearing a gene from the DS-1 rotavirus, among other strains. Trask discloses SA11, a simian rotavirus, as the backbone strain. Trask also teaches production of rotavirus reassortants in MA-104 cells and COS-7 cells.
Therefore, claims 1-2, 4-6, 9, and 16 are anticipated by Trask.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Trask, et al. (Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18652-7. doi: 10.1073/pnas.1011948107. Epub 2010 Oct 11. PMID: 20937889, on IDS) in view of Trusheim, et al. (PGPub US 20130216573 A1, published 8/22/2013), Heaton, et al. (Clin Infect Dis. 2007 Dec 15;45(12):1618-24. doi: 10.1086/522997. PMID: 18198497), Kanai, et al. (J Virol. 2020 Dec 22;95(2):e01374-20. doi: 10.1128/JVI.01374-20. PMID: 33087468, on IDS), and GenBank: GU565046.1 (5/31/2011), Steel, et al. (PGPub US20110105593A1, published 5/5/2011), Chen, et al. (J Virol. 1994 Nov;68(11):7030-9. doi: 10.1128/JVI.68.11.7030-7039.1994. PMID: 7933085) and Taniguchi, et al. (Curr. Op. Virol. Vol. 2, issue 4, Aug. 2012, pp. 399-407).
The relevance of Trask is set forth in the 102 rejection supra.
Regarding claim 15, Trask does not teach, after infecting the cell line with the first rotavirus, the method further comprises enriching the reassortant rotavirus through subculture.
Trusheim teaches methods for producing reassortant influenza viruses (Abstract; Title). By preferentially reducing the transcription and/or translation of the backbone strain’s HA and/or NA genes during virus production (e.g., by using RNA inhibition), one can greatly increase the speed by which reassortant viruses are produced, and has the advantage that it does not rely on the use of antibodies, and the likelihood of spontaneous mutations is lower as fewer passages are necessary to obtain reassortant viruses (para. [0007]). Over several passages of this treatment one can select for fast-growing reassortant influenza viruses which contain the HA and NA segments from the vaccine strain and the other viral segments from the backbone strain (para. [0004]). Trusheim teaches that suitable inhibitory agents are known to the skilled person and include, but are not limited to, siRNAs, dsRNAs, miRNAs, shRNAs, or siDNAs (para. [0030]). Additionally, Trusheim teaches that where the reassortant viruses are produced in cell culture, it is possible to use cells which have been stably transfected with one or more expression constructs encoding the inhibitory agents, thereby eliminating the need to separately introduce inhibitory agents each time the methods are practiced (para. [0041]). Trusheim also teaches that the inhibitory agent can be introduced into the host cell before, during, or after infection with the virus (para. [0042]).
Trusheim teaches a number of strategies for preparing the reassortant viruses, including the steps of (i) infecting a culture host with a first influenza strain and a second strain, (ii) contacting the culture host of step (i) with an inhibitory agent wherein said inhibitory agent preferentially reduces the transcription and/or translation of the HA or NA genes of at least one of the influenza strains of (i); (iii) culturing the culture host in order to produce reassortant virus; or (i) infecting a culture host with a first influenza virus strain having at least one target segment; (ii) introducing into the culture host one or more expression construct(s) encoding the target segments(s) from a second influenza virus strain; (iii) contacting the culture host with an inhibitory agent which preferentially reduces the transcription and/or translation of the first influenza strain’s target segment(s); and (iv) culturing the culture host in order to produce reassortant virus; and optionally (v) purifying the virus obtained in step (iv). (Trusheim, claims 1-3). Trusheim also discloses the method further comprising the steps of infecting a culture host with the reassortant virus, culturing the host to produce further virus, and purifying the virus (Trusheim, claim 4).
Additionally, Trusheim discloses that in its methods, the steps of (i) infecting the culture host with a virus, (ii) introducing one or more expression constructs into the culture host, and (iii) contacting the culture host with an inhibitory agent, can be performed in any order (para. [0051]).
It would have been obvious to one of ordinary skill in the art to modify Trask’s methods, such that after infecting the cell line with the first rotavirus, the method further comprises enriching the reassortant rotavirus through subculture, because Trusheim discloses infecting a culture host with the reassortant virus, culturing the host to produce further virus, and purifying the virus, which, absent guidance in the specification, the examiner is interpreting to be “subculturing”. There would be a reasonable expectation of success because Trask demonstrates production of reassortant rotaviruses and Trusheim demonstrates that specific strategies, such as those claimed, can be used to generate recombinant segmented viruses. Therefore, claims 1, 2, 4-6, 9, 15, and 16 were prima facie obvious before the priority date of the instant invention.
Regarding claim 3, Trask and Trusheim do not teach the WC3 rotavirus strain, or progeny thereof, as the first rotavirus.
Heaton teaches that the WC3 strain is the parent strain of the pentavalent human-bovine reassortant rotavirus vaccine (PRV) that was discovered in 1981 and licensed in 2006 (Abstract). PRV is orally administered as a liquid vaccine for the prevention of rotavirus gastroenteritis caused by the G serotypes contained in the vaccine, in infants and children, and is recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for administration to all infants in the United States (Abstract). Phase III studies with PRV evaluated serious adverse events in >35,000 infants who received the PRV, and found the vaccine to be well tolerated and not associated with an increase in the frequency of serious or nonserious adverse events (p. 1622, col. 2, para. 2). Heaton discloses that PRV contains 5 reassortant rotaviruses with a WC3 core and a human rotavirus surface protein (G1, G2, G3, G4, or P1A; p. 1619, col. 1, para. 3).
Accordingly, Heaton teaches that the bovine WC3 rotavirus strain is a suitable, safe, and effective backbone strain to use for creating reassortants bearing a single human rotavirus gene segment.
It would have been obvious to one of ordinary skill in the art to modify the method of producing a reassortant rotavirus rendered obvious by Trask and Trusheim to utilize the WC3 strain as the parent strain (akin to first rotavirus in the instant claims). Heaton teaches that other reassortant rotaviruses for use in human vaccines possess a human rotavirus gene in the WC3 strain as the parent strain, and that such viruses are recommended for use and safe. One of ordinary skill in the art would have been motivated to produce safe rotavirus vaccines. There would be a reasonable expectation of success because WC3 has been used as the parent strain for reassortant rotaviruses bearing a human rotavirus gene segment used in vaccines. Therefore, claims 1-6, 9, and 15-16 were prima facie obvious before the priority date of the instant invention.
Regarding claims 7, 8, and 17, Trask, Trusheim, and Heaton do not teach the specific gene segment encodes VP7.
Kanai teaches that reverse genetics is tractable, rapid, and reproducible approach to generating recombinant RV vaccine candidates carrying any VP7 gene that provides selected antigenicity, and developed a vaccine platform by generating recombinant RVs carrying VP7 (G1, G2, G3, G8, and G9) from human rotavirus clinical samples using the simian RV SA11 strain as a backbone (Abstract). Kanai specifically teaches that the multisegmented genome of RVs allows reassortment of VP7 genes from different RV species and strains, thereby controlling viral antigenicity, growth capacity, and pathogenicity (p. 1, importance). Kanai also teaches that VP7 is a glycoprotein and determines the G serotype (p. 2, para. 1).
Accordingly, Kanai teaches reassortment of VP7 genes from different rotavirus species and strains.
It would have been obvious to one of ordinary skill in the art to modify the method of producing a reassortant rotavirus rendered obvious by Trask, Trusheim, and Heaton to produce rotavirus with reassorted VP7 gene segment. Kanai discloses that VP7 is the rotavirus glycoprotein and controls antigenicity. One of ordinary skill in the art would have been motivated to produce vaccine strains for vaccination against a different VP7. There would be a reasonable expectation of success because Kanai discloses reassortment of rotavirus VP7-encoding genes. Therefore, claims 1-9 and 15-17 were prima facie obvious before the priority date of the instant invention.
Regarding claim 10, Trask, Trusheim, Heaton, and Kanai do not teach wherein the inhibitory RNA targets SEQ ID NO: 3.
GenBank: GU565046.1 (5/31/2011) teaches the VP7-encoding gene segment sequence’s DNA equivalent of the WC3 strain used in a pentavalent rotavirus vaccine, which contains a nucleotide sequence that is 100% identical to the instant SEQ ID NO: 3 (pp. 1-2).
Accordingly, GU565046.1 teaches SEQ ID NO: 3.
It would have been obvious to one of ordinary skill in the art to modify the method of producing a reassortant rotavirus rendered obvious by Trask, Trusheim, and Heaton to produce rotavirus with reassorted VP7 gene segment, wherein the inhibitory RNA targets SEQ ID NO: 3. SEQ ID NO: 3 would have been an obvious target to one of ordinary skill in the art wanting to downregulate the gene segment encoding VP7 of WC3, because it is part of the natural sequence (DNA equivalent) of WC3’s VP7-gene encoding segment. One of ordinary skill in the art would have been motivated to produce vaccine strains for vaccination against a different VP7. There would be a reasonable expectation of success because Kanai discloses reassortment of rotavirus VP7-encoding genes. Therefore, claims 1-10 and 15-17 were prima facie obvious before the priority date of the instant invention.
Regarding claims 11 and 13, Trask, Trusheim, Heaton, Kanai, and GU565046.1 do not teach wherein the cell line is introduced with a vector containing a double-stranded DNA oligonucleotide encoding a pre-miRNA for the miRNA, or where the vector is a co-expression vector comprising two or more double-stranded DNA oligonucleotides encoding pre-miRNAs for two or more miRNAs having different target sites.
Steel teaches vectors expressing multiple microRNA from a single transcript, and methods of their use to inhibit expression of one or more target genes (Abstract; Fig. 6; para. [0019]). Steel also discloses that viruses that may be targeted by the vectors of the present invention include but are not limited Reoviridae (e.g., rotaviruses; para. [0042]). Steel also discloses that the vector constructs may be configured to generate the primary miRNA transcript (pri-miRNA), which is then processed into pre-miRNAs, which are then further processed into individual miRNAs (para. [0053]). Steel also specifically discloses nucleic acid vectors wherein at least two miRNA-formatted interfering RNAs are specific for at least one or two pathogen target genes (Steel, claims 43-64). Steel teaches that multiple (two or more) miRNA-formatted interfering RNAs on a single expression construct may be the same miRNA repeated in succession, different miRNAs that are specific for the same target gene, or different miRNAs that are specific for two or more target genes of the same pathogen (para. [0041]). Steel teaches that multiple viral-targeted miRNAs within a single construct significantly decrease the chance of viral escape mutants and broaden the range of genetic viral variants that can be treated (para. [0043]).
Accordingly, Steel teaches an expression vector comprising one, or two or more double-stranded DNA oligonucleotides encoding pre-miRNAs for two or more miRNAs having different target sites.
It would have been obvious to one of ordinary skill in the art to modify the method of producing a reassortant rotavirus rendered obvious by Trask, Trusheim, Heaton, and GU565046.1 to produce rotaviruses with a reassorted gene segment, wherein the inhibitory RNA is miRNA and a vector containing a double-stranded DNA encoding a pre-miRNA for the miRNA (claim 11), or wherein the vector is a co-expression vector comprising two or more double-stranded DNA oligonucleotides encoding pre-miRNAs for two or more miRNAs having different target sites (claim 13). Steel discloses expression constructs that encode multiple miRNAs are specific for the same target gene or different target genes of the same target pathogen. One of ordinary skill in the art would have been motivated to produce reassortant strains of rotavirus. There would be a reasonable expectation of success because Steel contemplates use of multi-expression vectors encoding one or more pre-miRNAs for the miRNAs. Therefore, claims 1-11, 13, and 15-17 were prima facie obvious before the priority date of the instant invention.
Regarding claim 14, Trask, Trusheim, Heaton, Kanai, and Steel do not teach wherein mRNA of the gene segment of the second rotavirus corresponding to the specific gene segment of the first rotavirus is obtained by in vitro transcription.
Taniguchi teaches that transfection of in vitro transcribed RNA from cDNA or of mRNA prepared in vitro from single-shelled core particles into cultured cells yielded infectious viruses for bluetongue virus and African horse sickness virus, which are members in the family Reoviridae (p. 399, col. 2, para. 1).
Accordingly, Taniguchi contemplates use of in vitro transcribed RNAs of Reoviridae genome segments to produce infectious viruses.
Chen teaches in vitro replication of rotavirus RNAs, wherein native rotavirus mRNAs or in vitro transcripts derived from cDNAs were produced (Abstract).
Accordingly, Chen teaches in vitro of rotavirus RNAs.
It would have been obvious to one of ordinary skill in the art to modify the method of producing a reassortant rotavirus rendered obvious by Trask, Trusheim, Heaton, GU565046.1 and Steel to produce rotavirus with reassorted gene segments, such as VP7-encoding genes. Taniguchi discloses that other members of the Reoviridae family may be produced using RNAs transcribed in vitro, and Chen discloses in vitro transcription of rotavirus RNAs. It would have been obvious to use such RNA or mRNA to generate reassortant rotaviruses. One of ordinary skill in the art would have been motivated to produce reassortant strains of rotavirus. There would be a reasonable expectation of success because Taniguchi discloses that other members of the Reoviridae family may be produced using RNAs transcribed in vitro, and Chen discloses in vitro transcription of rotavirus RNAs. Therefore, claims 1-11 and 13-17 were prima facie obvious before the priority date of the instant invention.
Allowable Subject Matter
SEQ ID NOs: 6 and 7 are free of the prior art of record.
Conclusion
No claims are allowed.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671
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