Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I, claims 32-48, in the reply filed on 12 May 2025 is acknowledged.
Claim Rejections - 35 USC § 103
3. 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.
4. 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.
5. Claims 32-33, 36-38, and 40-42, 44, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Blower et al (Combining Different mRNA Capture Methods to Analyze the Transcriptome: Analysis of the Xenopus laevis Transcriptome, PLoS ONE 8(10): e77700, published 15 October 2013) in view of Abbas et al (Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2’-O methylations, PNAS, 114(11), E2106-E2115, published 01 March 2017) and Daugherty et al (Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals, eLIFE, e14228, published 31 May 2016).
Blower teaches a method of RNA capture (i.e., selection and/or enrichment; abstract) comprising: expressing and purifying eIF4E (i.e., preparing an RNA binding protein; pg. 11, column 2, ¶ 5 and pg. 12, column 1, ¶ 1), binding GFP-Trap beads (i.e., a bed) to RNA via rEIF4E (i.e., an RNA binding protein; pg. 12, column 1, ¶ 4), washing the beads (this would inherently wash away unbound RNA molecules; pg. 12, column 1, ¶ 4), and detecting the selected RNA molecules by sequencing (pg. 12, column 1, ¶ 4 and pg. 13, column 1 ¶ 1).
Blower does not teach that a protein of the IFIT protein family or its functional variants, homologues or mutants are used as the RNA binding protein.
However, Abbas teaches that various IFIT proteins are alternatives to eIF4E for RNA binding (E2106, column 1, ¶ 1 and E2107, column 1, ¶ 1).
It would have been obvious to one having ordinary skill in the art to have substituted eIF4E in the RNA purification method taught by Blower with IFIT1 as taught by Abbas to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this substitution because Abbas specifically teaches IFIT1 as a competitive alternative to eIF4E (pg. E2112, column 2, ¶ 3). In addition, one having ordinary skill in the art would have recognized that the known techniques of the cited references could have been combined with a predictable results because the known techniques of the cited references predictably result in the binding and capture of RNA molecules.
Abbas teaches that human IFIT1 can target Cap0 mRNAs when overexpressed in a yeast system (pg. E2113, column 1 ¶ 2), but neither Blower nor Abbas specifically teach that the mRNA targets are “RNA molecules selected from fungi” (e.g., yeast).
However, Daugherty teaches that IFIT1 proteins overexpressed in budding yeast inhibit the growth of yeast wherein the Cap0 mRNA expressed by budding yeast is targeted by IFIT1 (i.e., bound by IFIT1; pg. 3 ¶ 3, FIG 4 and associated caption, pg. 11 ¶ 1).
It would have been obvious to one having ordinary skill in the art to have substituted the viral RNA taught by the combination of Blower and Abbas with yeast RNA as taught by Daugherty to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this substitution because Abbas suggests that IFIT proteins bind yeast mRNA (E2113 column 1 ¶ 2) and Daugherty specifically teaches that proteins in the IFIT1 family bind Cap0 mRNA from yeast as discussed fully above and incorporated here. In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictably results because the known techniques in the cited references predictably result in the study of IFIT family proteins and their interaction with mRNA cap structures.
Regarding claim 33, Abbas teaches producing IFIT1 (i.e., the RNA binding protein) in a bacterial protein expression system and purifying IFIT1 (pg. E2114, column 2, ¶ 3 and Supporting information pg. 1, column 1, ¶ 1).
Regarding claims 36 and 37, Blower teaches that binding the RNA to the GFP-Trap beads (i.e., the bed) comprises first forming RNA-RNA binding protein complexes and then binding the bed (pg. 12, column 1, ¶ 4) as described in instant claim 37. However, MPEP 2144(IV)(C) states that the order of performing steps is prima facie obvious in the absence of new or unexpected results. Therefore claim 36 is an obvious variant of claim 37.
Regarding claim 38, Blower teaches that RNA molecules are released from the RNA-RNA binding protein complexes before sequencing (i.e., detection; pg. 12, column 1, ¶ 4).
Regarding claims 40 and 41, Abbas teaches that IFIT proteins bind mRNAs with an m7Gppp cap (i.e., a cap 0 structure; E2108, column 1, ¶ 1).
Regarding claim 42, Abbas teaches that IFIT only binds structured RNAs if they have a sufficiently single-stranded region at the Cap site (a 4 nucleotide overhang at the 5' end; E2108, column 1, ¶ 2 and Supplemental FIG 7).
Regarding claim 44, Abbas teaches that the RNA binding IFIT protein comprises a tetratricopeptide repeat region and a structural motif with an amino acid sequence CHFxW (abstract and FIG S2).
Regarding claims 47 and 48, Abbas teaches an IFIT1 protein cloned into an expression vector and expressed in BL21 cells. Abbas additionally teaches the recombinant IFIT1 protein comprises a cleavable 6xHis-Sumo tag (i.e., a recombinant protein; Supporting information pg. 1, column 1, ¶ 1).
6. Claims 34-35 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Blower et al (Combining Different mRNA Capture Methods to Analyze the Transcriptome: Analysis of the Xenopus laevis Transcriptome, PLoS ONE 8(10): e77700, published 15 October 2013) in view of Abbas et al (Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2’-O methylations, PNAS, 114(11), E2106-E2115, published 01 March 2017) and Daugherty et al (Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals, eLIFE, e14228, published 31 May 2016) as applied to claim 32 above, and further in view of Katibah et al (tRNA Binding, Structure, and Localization of the Human Interferon-Induced Protein IFIT5, Molecular Cell, 49, 743-750, published 21 February 2013).
Regarding claim 34, the method of claim 32 is discussed fully above and incorporated here. The combination of Blower and Abbas does not teach an RNA binding protein used in step (a) is in a form bound to a reporter molecule.
However, Katibah teaches an RNA binding protein, IFIT5, bound to a radiolabeled RNA (i.e., a reporter molecule; FIG S4).
It would have been obvious to one having ordinary skill in the art to have modified the RNA pulldown assay taught by the combination of Blower and Abbas to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this combination because Katibah specifically teaches that binding of the IFIT protein to the reporter RNA is out-competed by the addition of other RNA targets with preferential 5' RNA motifs and Katibah uses this approach to screen RNAs that bind to the IFIT protein (FIG S4). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results, because the known techniques in the cited references predictably result in the analysis of RNA binding to IFIT proteins.
Regarding claim 35, Katibah teaches an IFIT protein bound to a reporter complex, but teaches that the binding of the radiolabeled reporter molecule is blocked from binding to the IFIT protein is blocked when the IFIT protein is bound to a preferred target (FIG S4). However, MPEP 2144(IV)(C) states that the order of performing steps is prima facie obvious in the absence of new or unexpected results, therefore it would have been obvious to one having ordinary skill in the art to have had the reporter molecule bound to the IFIT protein prior to the addition of the RNA desired for selection or enrichment. This reporter molecule would be displaced by the stronger RNA binders, and the reporter molecule would inherently be washed away in step (c) taught by the combination of Blower and Abbas.
Regarding claim 39, Katibah teaches the detection of the radiolabeled reporter molecules (FIG S4). Detection of the released radiolabeled reporter molecule inherently detects the binding of preferred RNA molecules bound to the IFIT protein.
Response to Arguments
7. Previous rejections under U.S.C. 112(a) and 112(b) have been overcome by amendment and/or cancellation of the rejected claims
Applicant's arguments filed 14 October 2025 have been fully considered but they are not persuasive.
Applicant argues on pg. 9 ¶ 3 of their remarks that differences in mRNA binding between eIF4E and IFIT are sufficient that one having ordinary skill in the art would not recognize these proteins as 1:1 substitutes. This argument is not persuasive, however, because as discussed in the Office Action dated 15 July 2025 Abbas specifically teaches that IFIT family proteins compete with eIF4F to selectively bind and capture Cap0-mRNA. Therefore these proteins are substitutes regarding the binding of certain families of RNA and claim 32 does not specify or provide additional limitations regarding the nature of RNA binding. Additionally, the only claimed cap structure in the instant claims is Cap0 (see claims 40 and 41), which Abbas specifically states is bound by both eIF4F and IFIT. Therefore these arguments are not persuasive.
Applicant’s amendment to claim 32 of “whereby the selected RNA molecules are selected from the group consisting of: mRNA molecules of bacteria, fungi, protozoa, and/or plants; mtRNA molecules of vertebrates; or RNA molecules being an intermediate in the RNA maturation process” necessitated the use of Daugherty as an additional reference, as discussed fully above in this Office Action.
8. 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.
Conclusion
9. No claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN ELLIS YOUNG whose telephone number is (703)756-5397. The examiner can normally be reached M-F 0730 - 1700.
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/BRIAN ELLIS YOUNG/Examiner, Art Unit 1684
/JULIET C SWITZER/Primary Examiner, Art Unit 1682