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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/14/2026 has been entered.
Claims 7-9 and 11-12 were previously canceled by the 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Claims 16-28 (non-elected inventions of groups II-IV) remain withdrawn.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 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
1. 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 15 (as presented) 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 15 as presented depends from claim 12, which has been canceled by applicants (i.e. depends from a canceled claim), and therefore metes and bounds of the claimed invention cannot be properly defined.
Appropriate correction is required.
2. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 (as presented) is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 directly depends from claim 1, and recites the limitations “The yeast of claim 1, further comprising downregulated or inactivated DNA-(apurinic or apyrimidinic site) lyase APN1 (APN1),….., or UP Frameshift (UPF3)”, wherein components recited are presented in alternative form. However, the specific component “exosome nuclease subunit RRP6 (RRP6)” is also recited as one of the alternative components that are “downregulated or inactivated”, which fails to further limit the invention of claim 1. Claim 1 as currently presented already recites RRP6 gene as being “downregulated or inactivated”, and therefore instant claim 6 does not seem to further limit the product of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Appropriate correction is required.
NOTE: 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.
1. Claims 1-6, 10 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, 10 and 13-15 as presented (see also 112-b rejections discussed above).
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” (instant claim 1, as amended), or wherein the downregulated or inactivated genes comprise RRP6 and SKI complex subunit tetratricopeptide repeat protein SK13 (SKI3) (see components recited in instant claim 6, 10); 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 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 translated 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 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 yeast cell, as currently amended (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).
Examiner’s Response to Applicant’s Arguments
Applicant's arguments filed on 01/14/2026 (see REM regarding the 103a rejection of record, pages 7-12) have been fully considered but are moot in view of new grounds of objection/rejections made in this office action, as discussed above, and are not deemed persuasive at least for the following reasons of record:
Regarding the 103(a) rejection of record, applicants mainly appear to argue that the yeast cell as claimed is “engineered to provide stability of double stranded RNA”, and that “the double stranded RNA is an RNAi molecule that targets an exogenous organism” (see REM, p. 10-12), which are duly noted and considered. Also, the fact pointed out by the applicants that RRP6 is a component of the nuclear exosome complex (see REM, p. 11, 2nd paragraph) is duly noted and acknowledged. However, it is to be noted that the cited prior art of record (i.e. the teachings and/or suggestions from Kushner et al taken with Hoshino et al, as discussed in the 103a rejection above) discloses the structural features of the claimed yeast cell that can be made in order to downregulate or inactivate the exosome components RRP6 and SKI3 in particular, and therefore, as noted earlier in examiner’s response, the rejection of record already provides the benefits of inactivating exosome components RRP6 or SKI3, or a combination thereof in yeast cells that can help stabilize the transcribed RNAs in the modified yeast cell. Since, the engineered yeast cell as suggested in the cited prior art references has the same inactivated exosome instability genes inactivated (i.e. RRP6 and SKI3; as currently being claimed; see instant claims 1 and 10, in particular), an artisan in the art would normally understand that the intended stabilization of RNA molecules (including newly transcribed as well as double stranded RNAs in the cell) would be intrinsic feature, and that such would be expected from deletion/inactivation of genes that are responsible for RNA instability in the cells. Moreover, instant claim 1 does not require/recite any specific levels and/or degree of increase in “other double stranded RNA (dsRNA), that targets a function in an exogenous organism” per se, as currently being asserted by applicants. Applicants are advised that 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:
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).
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