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
Applicant's submission filed on 01/14/2026 has been entered.
Claims 7-9 and 11-12 were previously canceled by the applicants.
Claims 6 and 15 have been amended by applicants.
Claims 1-6, 10 and 13-28 are currently pending in this application.
Claims 16-28 (non-elected inventions of groups II-IV) remain withdrawn.
Claims 1-6, 10 and 13-15 (elected product of Group I, without traverse; drawn to a product in the form of “A yeast cell…”) have been examined on their merits in this action hereinafter.
Priority
This application is a CIP of PCT/CA2019/050610 (filed on 05/08/2019), which claims priority from a provisional application 62/669118 filed on 05/09/2018.
Claim Rejections - 35 USC § 112 - Withdrawn
In view of current amendment to claim 15, the 112b rejection as previously made by the examiner has been withdrawn.
In view of current amendment to claim 6, the 112d rejection as previously made by the examiner has been withdrawn.
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.
Claim Rejections - 35 USC § 103 – Made/Maintained
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 1-6 and 13-15 (as amended/presented) are/remain rejected under 35 U.S.C. 103 as being unpatentable over Kushner et al (2003; NPL cited in applicant’s IDS dated 11/06/2020, citation no. 4) taken with Hoshino et al (JP 2015221026 A; English machine translation, previously made of record by examiner).
Claim 1 (as presented) is directed to “A yeast cell comprising a downregulated or inactivated exosome nuclease subunit ribosomal RNA processing 6 (RRP6) gene in a nuclear exosome and at least one heterologous sequence that encodes an RNA interference (RNAi) effector molecule, wherein the RNAi effector molecule is small interfering RNA (siRNA), long-hairpin (lhRNA), short hairpin RNA (shRNA), or other double stranded RNA (dsRNA), that targets a function in an exogenous organism.”
See dependent claims 2-6 and 13-15 as currently presented.
Kushner et al (2003) reference discloses screening of about 4,500 yeast deletion strains to identify yeast host (saccharomyces cerevisiae BY 4743, WT strain background) genes that function in controlling replication of brome mosaic virus (BMV, a positive-strand RNA virus; see abstract on page 15764). Nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold were identified, including some in RNA modification pathways. Kushner discloses that BMV-directed reporter gene expression (Rluc or Gus) in transformed yeast cells was increased 4- to 6-fold by deleting SKI2, SKI3, SKI7, or SKI8, which encode factors exosome-mediated 3’ to 5’ mRNA decay and inhibit accumulation of non-polyadenylated mRNAs (see Kushner et al, page 15768, right column, 3rd paragraph, for instance). Kushner discloses expression plasmid pB3 with the GALJ promoter expressing BMV 3a protein and the BMV coat protein gene or any gene replacing it, such as Rluc, and a ribozyme (i.e. expressing a heterologous sequence; see Fig. 1 on page 15765). Therefore, Kushner discloses a yeast cell comprising a gene involved in RNA instability that is downregulated or inactivated due to a deletion (see page 15768, left column, 1st and 2nd paragraphs, for instance). Kushner discloses plasmid-based expression and/or reporter system (i.e. a heterologous mRNA), the expression of which may be useful in treatment of a lysosomal diseases, for instance (see reporter system for beta-glucuronidase enzyme, GUS, page 15765 and 15768, left column, 1st paragraphs).
However, Kushner et al do not explicitly disclose the yeast cell - 1) wherein the (RNA instability) gene downregulated or inactivated is exosome nuclease subunit ribosomal RNA processing 6 (RRP6) in a nuclear exosome” (see instant claim 1); and 2) “wherein the RNAi effector molecule is small interfering RNA (siRNA), long-hairpin (lhRNA), short hairpin RNA (shRNA), or other double stranded RNA (dsRNA), that targets a function in an exogenous organism” (see recitations of instant claims 1 and 13-15, as amended/presented).
Hoshino et al (2015; all citations per English translation of record), while teaching a technique for improving translational efficiency of artificial synthetic mRNA in a target eukaryotic cell (see title and Abstract), wherein the method can be used to treat target diseases such as viral disease (see section “Background art” on page 1), disclose the fact that by using a “function-suppressing” substance in combination, an artificially synthesized mRNA can be stabilized in a target cell (any eukaryotic target cell; see translation, page 4, entire 2nd and 3rd paragraphs, in particular), and high expression of the target gene is promoted (see translation, pages 6-7, section “5. Function-suppressing substance”, in particular) by suppressing or inhibiting the degradation of the mRNA by the exosome complex, which comprises known components including RRP6, and cofactor such as SKI3; wherein two or more kinds of function-suppressing substances may be used in combination, which may be same type or different (see translation, page 7, 2nd paragraph); and wherein the function suppressing substances can be “(a) siRNA targeting exosome complex components or cofactors, (b) Nucleic acid constructs that generate siRNAs targeting exosome complex components or cofactors in cells, (c) Antisense nucleic acid targeting exosome complex components or cofactors, and (d) Ribozymes targeting exosome complex components or cofactors” (see translation, page 7, 3rd and 4th paragraphs); wherein above (a) and (b) can be used for expression suppression by RNA interference, RNAi (see also translation, page 8 for dsRNA, shRNA, etc.); wherein the mRNA can be any disease-related target gene, and wherein the target genes can include genes responsible and/or useful for cell survival, maintenance, etc., such as cytokines, hormones, neurotransmitters, etc., for instance interleukins, CRISPER-Cas9 gene, ZFN, TALEN gene, etc. (see translation, page 4, section “3. mRNA of target gene”).
Thus, given the detailed disclosure by Hoshino et al, for stabilization of transcribed mRNA molecules in eukaryotic cells using function suppressing agents, such as by inhibiting the degradation of the mRNA by the major components of the cellular exosome complex, that comprises RRP6, and a cofactor such as SKI3, and using RNAi technique in combination to stabilize the artificially synthesized mRNA, it would have been obvious to an artisan of ordinary skill in the art to prepare combination mutants (i.e. to inactivate both parts of the exosome complex that normally degrades mRNA in cells, as suggested by Hoshino et al, above) in order to stabilize heterologously expressed desired mRNA (as taught by Kushner et al), that can effectuate various functional aspects in terms of treatment of a desired disease, etc., as currently intended by the claims of record (see instant claims 13-15). Since, RNAi methods are already known in the prior art to be effective in suppressing desired genes and/or expression thereof (as shown by Hoshino et al, above), an artisan in the art would have had a reasonable expectation of success in making such yeast cell that comprises downregulated or inactivated “RNA instability” genes such as RRP6 and SKI3, and a heterologous sequence that encodes an RNAi effector molecule construct for a desired target gene for instance, as explicitly suggested by Hoshino et al (see translation, disclosure on pages 10-11). Therefore, the scope of the product invention, in the form of a variant yeast cell, as currently presented (see instant claim 1) fails to structurally distinguish itself over the combined teachings and/or suggestions from the cited prior art references, as discussed above.
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the invention as claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Allowable Subject Matter
Claim 10 is 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.
Examiner’s Response to Applicant’s Arguments
Applicant's arguments filed on 07/28/2026 (see REM regarding the 103a rejection of record, pages 8 and 9) have been fully considered but are not deemed persuasive at least for the reasons discussed by the examiner before (see CTNF dated 01/29/2026, p. 9-10), and additionally for the following reasons of record:
Regarding the 103a rejection of record, applicants mainly appear to argue the intrinsic functionality of the product which has been claimed in the form of a variant yeast cell that has been modified to downregulate or inactivate the RRP6 gene, and that comprises an RNAi effector molecule such as siRNA, shRNA, etc. (see instant claim 1). Applicants argue that “Rrp6 in yeast has never been shown to be able to degrade dsRNA”, “Kushner relates to mRNAs not double stranded RNA”, “Hoshino also relates to mRNA stability (ssRNA)”, and “Yeast exosome components are conserved, but do not necessarily function the same as higher Eukaryotes” (see REM, p. 8-9), which are duly noted and considered (although, applicants have not submitted the NPL references on a proper PTO 1449 form as an IDS, the cited references have been considered to the extent they pertain to the argument proffered by the applicants; see REM, p. 9). In response, however- first, it is to be noted that the claims under examination are drawn to a product, not to a method of use via certain mechanistic underpinning per se. Second, it is known in the prior art that in eukaryotic cells including yeast and human cells, the RRP6 gene is known to be localized mainly in the nucleus, the difference being that in human the RRP6 is also present to lesser extent in cytoplasm (see also the cited pertinent prior art of Dziembowski et al, 2014 WIPO document; see page 4, 1st paragraph). Third, the cited prior art already discloses the inactivation of RRP6 gene and use of RNAi molecules in targeting or gene silencing at a given target cell (see the prior art rejection, above), and therefore the functional features as currently being argued by applicants would be deemed intrinsic to the mutant and/or modified yeast cell, unless evidence/data provided (for the entire scope of the claimed product) on record to the contrary. It is also noted that the fact that the inventors have recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In addition, as pointed out earlier by the examiner, the scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results, for example. In re Dill, 202 USPQ 805 (CCPA, 1979), In re Lindner 173 USPQ 356 (CCPA 1972), In re Hyson, 172 USPQ 399 (CCPA 1972), In re Boesch, 205 USPQ 215, (CCPA 1980), In re Grasselli, 218 USPQ 769 (Fed. Cir. 1983), In re Clemens, 206 USPQ 289 (CCPA 1980). It should be clear that the probative value of the data (see instant specification, p. 40-41, paragraphs [00146]-[00148], for instance) is not commensurate in scope with the degree of protection sought by the claim (see instant claim 1, in particular). Thus, the 103(a) rejection of record is properly made/maintained.
Conclusion
NO claims are currently allowed.
Pertinent Prior Art:
DZIEMBOWSKI et al (WO 2014/188337 A1; FOR cited as ref. [N] on PTO 892 form)- “METHOD FOR SELECTION OF HDIS3 PIN DOMAIN INHIBITORS AND USE OF HDIS3 PIN DOMAIN INHIBITORS FOR CANCER TREATMENT” (discloses the fact that yeast rrp6 is mainly restricted to the nucleus, whereas human rrp6 is also “mainly nuclear and significantly enriched in the nucleoli, with a minor fraction in the cytoplasm”; see page 4, 1st paragraph; and also see double mutants of yeast strains disclosed as “rrp6D dis3-G833R and rrp6D dis3-R847K strains” on page 31, and disclosure on page 33, last paragraph, and Figure 3).
WHYARD et al. (2009; previously made of record by examiner)- “Ingested double stranded RNAs can act as species-specific insecticides”, Insect Biochemistry and Molecular Biology, 2009, vol. 39, pages 824–832 (disclose the fact that RNA interference method using dsRNA can be designed and used for target-specific inactivation of genes and/or gene products in order to kill a desired pathogen with selectivity; see Abstract, in particular).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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