DETAILED ACTION
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 .
The Examiner for this Application has changed. Please direct all future
correspondence to Juliana Candelaria, AU 1634. Additional contact information can be
found at the end of this paper.
This action is in response to the papers filed on 06/16/2025. Claims 1-15 are
currently pending as per claims filed on 06/16/2025. Claims 1-10 and 13 have been amended and Claim 15 has been newly added by Applicants’ amendment filed on 06/16/2025.Claims 1, 11 and 13 are independent claims.
Priority
The instant application claims is a 371 of PCT/DE2016/000309 filed on 08/09/2016 which claims benefit of GERMANY 102015012522.2 filed on 09/26/2015. Filing of a certified untranslated copy of the German Application No. 102015012522.2, filed March 26, 2018 is acknowledged. Thus, the earliest possible priority for the instant application is 09/26/2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/16/2025 was filed after the mailing date of the current office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Withdrawn objections/rejection in response to Applicants’ arguments or amendment
Specification Objection
In view of Applicants’ amendment of the abstract, specification objection has been withdrawn.
Claim Rejections - 35 USC § 112(b)
In view of Applicants’ amendment of claims 2-7, 9-10, and 13, the rejection of
claims 2-7, 9-10, and 13 - 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn.
Applicant’s argument with regard to a withdrawn rejection are moot.
Maintained and/or Modified Rejections in response to Applicants’ arguments or amendment
35 USC § 112(a)
This rejection has been modified in consideration of the applicant's amendment.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 1 recites “a guide RNA” that is capable of targeted RNA editing, which encompasses a genus of agents. Claims 2-14 are dependent from Claim 1, do not materially limit the genus of agents, and are therefore included in the rejection. These claims do not require that the genus of the claims possess any particular structure or other distinguishing feature that is characteristic of the genus as a whole. Therefore, the claims are drawn to a genus of “guide RNAs for targeted RNA editing” for which there is inadequate written description.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C).
In the instant case, the only identifying characteristic present in the claim is a recitation of requisite activity “for targeted RNA editing” and “wherein segments H and I are designed such that they pair with an mRNA to be edited”. Regarding the genus of the claims the specification describes 17 species (SEQ ID NOs: 1-7, 24-28, 30, 31, 33, 35, 37) that fall within the genus claimed (pages 4 and 7-8). Between all of these species, the specification describes the following fully defined examples of the claimed guide RNA segments of A-G (see Clustal Omega Multiple Sequence Alignment below):
1 for Segment A: GUGG
3 for Segment B: AAUA, AAGA, and AUA
2 for Segment C: GUAUAACAA and GGAGAACAA
2 for Segment D: SEQ ID NOs 8 and 9
2 for Segment E: UUGUUCUCG and UUGUUAUAG
2 for Segment F: UAUC and UCUC
1 for Segment G: CCAC
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The specification describes 17 fully defined examples for segments H and I (SEQ ID NOs 10-21, 28, 30, 31, 33, 35, and 37). The specification describes 6 fully defined examples of the claimed full length guide RNA including segments A-I (SEQ ID NOs 28, 30, 31, 33, 35, and 37).
From the specification, it is clear that Applicant is in possession of species of the fully defined examples of segments A-I. The claims, however are not limited to those species but also includes RNA segments with multiple variable nucleotides (e.g., see SEQ ID NO: 24), yielding an immense array of possible sequence combinations. This degree of variability could significantly alter the structural and functional properties of the RNA. Consequently, the specification fails to provide a representative number of species within the recited genus.
Stefl, et al. (Cell, 10/15/2010, Vol 143, Issue 2, Pages 225-237, listed on IDS filed 01/25/2021) investigated how the double-stranded RNA-binding motifs (dsRBMs) of ADAR2 recognize the specific RNA sequence of the GluR-2 R/G editing site. By determining the structure of the ADAR2 dsRBMs bound to this RNA, Stefl found that ADAR2 can recognize both the shape and specific sequences of double-stranded RNA via the minor groove. Using mutational studies, Stefl showed that certain bases (e.g., guanine at critical positions) are essential (i.e., necessary) for dsRBM binding. However, Stefl does not show that these bases are sufficient for binding, meaning that simply having the required bases present does not guarantee that binding will occur. This study emphasizes that ADAR2 binding depends not only on specific bases but also on the overall shape of the RNA. The necessary bases may contribute to binding only within the proper structural context, suggesting other sequences or structural features must also be present. The claimed guide RNAs incorporate some of the essential bases identified by Stefl, however the art at the time of filing did not establish whether the bases identified by Stefl are sufficient for binding or what variation in the intervening bases could be tolerated and still maintain binding.
Accordingly, in the absence of sufficient disclosure of distinguishing identifying characteristics of the genus as a whole, or representative number of species within the genus, the specification does not provide adequate written description of the claimed genus.
Response to Applicants’ Arguments as they apply to rejection of claims 1-14 under 35 USC § 112(a)
Applicant's amendments to the claims and arguments filed 06/16/2025 have been fully considered but have not been found persuasive in overcoming the rejection
for reasons of record as discussed in detail below.
On page 8 of the remarks filed on 6/16/2025, Applicants essentially argue that: 1) “claim 1 has been amended to recite that segments H and I are designed such that they pair with an mRNA to be edited”, and 2) “Contrary to the Examiner's assertions, Segments A-I recited in the claims are all structural features of the claimed guide RNAs, including nucleic acids in positions that are likely to preserve the three-dimensional structure of the RNA, which, as the Examiner notes, can be important for ADAR2 binding”. Applicants’ arguments have been respectfully considered but have not been found persuasive.
Regarding argument 1) Applicant amended claim 1 to recite wherein segments H and I are designed such that they pair with an mRNA to be edited” in order to, what appears to be, an amendment to overcome the structure-function issue submitted in office action filed 3/14/2025 page 5. While the recitation “wherein segments H and I are designed such that they pair with an mRNA to be edited”, there remains a lack of function to the structures of segments A-G, more specifically as it relates to the plurality of species that fall under the claimed genus of nucleotide sequences and their combinations recited in segments A-I. In other words, segments A-I still recite broad a range of nucleotides and range of nucleotide sequence lengths for each segment that do not guarantee function. The state of the art, as taught by Stefl, teaches that certain bases (e.g., guanine at critical positions) are essential (i.e., necessary) for dsRBM binding. However, Stefl does not show that these bases are sufficient for binding, meaning that simply having the required bases present does not guarantee that binding will occur. Hence, the assortment of nucleotides that can be substituted at designated positions (i.e the structure of the guide RNA) does not indicate the function is maintained when nucleotides are substituted and segments are different length. Similarly, having segments H-I pairing to mRNA does not indicate that the remainder segment will hybridize to itself and contribute to the structure of the full length guide RNA where the segments are coupled to one another from the 5’ end.
In regards to argument 2) examiner maintains the argument that there is still no clear structure-function correlation disclosed for the claimed variable region. While examiner acknowledges applicant’s assertation that Segments A-I recited in the claims are all structural features of the claimed guide RNAs, the nucleic acids positions being variable do not guarantee the function that the three-dimensional structure of the RNA is preserved and permits dsRBM binding, as evident by Stefl and previously explained in the rebuttal to argument 1 above. While applicant has possession of fully defined examples of segments A-I as a guide RNA (SEQ ID NOs: 28, 30, 31, 33, 35, and 37), the claims remain directed to nucleotide segments of multiple variable nucleotides with an array of combinations. Hence, it would be uncertain how one of ordinary skill in the art would substitute nucleotides and lengths of the segments to preserve the claimed functionality.
Therefore, in view of the lack of structure-function for segments A-I and insufficient working examples for the segments and their vast combinations to elicit their function, the § 112(a) rejection is maintained.
35 USC § 102
This rejection has been modified in consideration of the applicant's amendment.
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)(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 1-9 and 13-14 remain rejected under 35 U.S.C. 102(a)(2) as being anticipated by Fukuda and Umeno (US20180208924A1, published 07/26/2018, effectively filed 07/15/2015) as evidenced by Stefl, et al. (Cell, 10/15/2010, Vol 143, Issue 2, Pages 225-237, listed on IDS filed 01/25/2021).
Regarding claims 1-7, Fukuda teaches a target editing guide RNA for introducing a site-directed RNA mutation at a target editing site of a target RNA (paragraph [0001], page 1), which is a guide RNA for targeted RNA editing. Fukuda further teaches a guide RNA based on the glutamate receptor mRNA precursor (GluR-B pre-mRNA) (paragraph [0176], pages 69 and 70; Fig. 21B, sheet 17) that is divided at a specific position leaving only the ADAR binding region, and which is fused to a complementary region (also called an antisense region) for recognizing the target RNA (paragraphs [0016]-[0018], pages 2-3; Fig. 21A, sheet 17).
Fukuda teaches an ADAR guide RNA with the following nucleotide segments coupled to one another, listed from the 5’ end (Fig. 21B, sheet 7; Fig. 22B, sheet 19; paragraphs [0123]-[0130], pages 13-14):
A) GUGG, which is Segment A of instant claim 1, having the length of four nucleotides of instant claim 2
B) AAUA, which is Segment B of instant claim 1, having the length of four nucleotides of instant claim 3
C) GUAUAACAA, which is Segment C of instant claim 1, having the length of nine nucleotides of instant claim 4
D) UAUGCUAAAUG, which is Segment D (SEQ ID NO:8) of instant claim 1
E) UUGUUAUAG, which is Segment E of instant claim 1, having the length of nine nucleotides of instant claim 5
F) UAUC, which is Segment F of instant claim 1, having the length of four nucleotides of instant claim 6
G) CCAC, which is Segment G of instant claim 1, having the length of four nucleotides of instant claim 7
H) CUAGCC, which is Segment H of instant claim 1
I) CCGUCAGGGUGGUCA, which is Segment I of instant claim 1
Fukuda teaches that A and G, B and F, and C and E pair (Fig. 21B, sheet 7; Fig. 22B, sheet 19) to form “an incomplete double-stranded RNA structure with a stem-loop structure”, and “in the loop structure, the corresponding constituent bases do not form complementary strands to each other” (paragraph [0130], page 13), which is the Segment D hairpin structure of instant claim 1.
Fukuda does not explicitly teach that the segments pair to form a double helix.
Stefl teaches that the segments pair to form a double helix (Figure 1A and 1D, page 227). Therefore, Fukuda inherently teaches that the segments pair to form a double helix.
In the instant case, the “wherein” clause of the segments of the guide RNA provides no patentable weight, as the characteristics (“wherein segments H and I are designed such that they pair with an mRNA to be edited”) are a direct result of the structure of the guide RNA of the independent claim, absent evidence to the contrary. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Regarding claim 8, Fukuda teaches a guide RNA where segments 8 and 9 pair with the mRNA to be edited, such that “the target RNA and the target editing guide RNA complementarily complex to form a target RNA-target editing guide RNA complex” (paragraph [0132], page 13) and this places the base to be edited in an A:C mismatch pair (Fig. 22B, sheet 19; paragraphs [0172]-[0173], pages 63-69; Fig. 11, sheet 11; Fig. 12, sheet 12).
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Regarding claim 9, Fukuda teaches guide RNA sequences ADg-GFP_A200 RNA (SEQ ID NO: 75), ADg-rGFP_A200 RNA (SEQ ID NO: 78), ADg-rGFP_A173 (SEQ ID NO: 89) (Table 6, pages 139-140), and AD-gRNA (Fig. 21B, sheet 17) having the ADAR binding region sequence of the glutamate receptor mRNA precursor (GluR-B pre-mRNA) (paragaraph [0176], pages 69 and 70; Fig. 21B, sheet 17). All of these sequences have 100% identity with SEQ ID NO: 27 of the instant application (see example sequence alignment below: Qy = SEQ ID NO: 27 from instant application, Db= AD-gRNA from Fukuda).
Regarding claims 13-14, Fukuda teaches a method introducing a site-directed RNA mutation at a target editing site of a target RNA using a target editing guide RNA, “including introducing a site-directed RNA mutation by inducing ADAR editing capability at a target editing site of a target RNA having a target base adenosine (A)” (paragraph [0001], page 1). Fukuda further teaches that “an RNA mutation which is a pathogenesis of diseases, can be controlled by converting the target base adenosine into inosine by A-I editing” (paragraph [0066], page 4), which is a method that encompasses instant claims 13 and 14.
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.
Response to Applicants’ Arguments as they apply to rejection of claims 1-9 and 13-14 under 35 USC § 102
At page 9 of the remarks filed on 6/16/2025, Applicants essentially argue that 1) as the examiner alleges that Fukuda teaches a guide RNA where segments 8 and 9 pair with the mRNA to be edited, such that “the target RNA and the target editing guide RNA complementarily complex to form a target RNA-target editing guide RNA complex, the sentences immediately following the quoted portion (the remainder of paragraph [0132]) clarify that the targeting and targeted portions of the complex are a single RNA strand and that Fig 11 and 12 of Fukuda demonstrates that the reference relates to a single artificial RNA strand that self-complexes to achieve editing. Applicant submits that this contrasts to the presently claimed invention as the presently claimed invention relates to a guide RNA that complexes with a separate mRNA to be edited.
Regarding argument 1) The amendments to the claims filed by applicant do not overcome the prior art of Fukuda and Stefl as the added recitation of “wherein segments H and I are designed such that they pair with an mRNA to be edited” are a direct result of the structure of the guide RNA of the independent claim, absent evidence to the contrary. For example, Fukuda teaches guide RNA sequences ADg-GFP_A200 RNA (SEQ ID NO: 75) such that the targeted mRNA is GFP mRNA, demonstrating that it does indeed complex with a separate mRNA to be edited and not with itself as applicant has asserted. This is further shown in Figure 22A (see below).
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Red box = target RNA sequence (GFP mRNA) paired with segment of guide RNA
In regards to recitation of para 0132 of Fukuda, examiner notes that this paragraph discloses the structure of the target RNA-target editing guide RNA complex. In other words, this paragraph describes the structure when the target editing guide RNA (i.e. ADg-GFP_A200 RNA example) binds to the target RNA (i.e. GFP example). This complex is shown in Figure 22A above. Likewise, applicant seems to misinterpret Fig 11 and 12 as it does show the target RNA as a separate RNA and the editing guide RNA which, together, pair and form the target RNA-target editing guide RNA complex. See Figure 11 of Fukuda below:
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Examiner also notes that the variability in nucleotide sequence and length of segment H and I as recited in claim 1 of the instant application permits variability in what mRNA is to be edited since their claimed function is to pair with an mRNA.
Therefore, the teachings of Fukuda anticipate the function of the guide RNA being able to target and pair with an mRNA to be edited. Examiner also notes that, as amendment to claim 1 which recites “wherein segments H and I are designed such that they pair with an mRNA to be edited” which is anticipated by Fukuta as noted above, The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Therefore, in view of the teachings of Fukuda and Stefl, the § 102 rejection is maintained.
Claim Rejections - 35 USC § 103
This rejection has been modified in consideration of the applicant's amendment.
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.
Claims 10-12, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Fukuda and Umeno (US20180208924A1, published 07/26/2018, effectively filed 07/15/2015) as evidenced by Stefl, et al. (Cell, 10/15/2010, Vol 143, Issue 2, Pages 225-237, listed on IDS filed 01/25/2021) as applied to claim 1 above, and further in view of Rosenthal, et al. (US9650627B1, issued 05/16/2017, effectively filed 06/20/2013, listed on IDS filed 01/25/2021) and Montiel-Gonzalez, et al. (PNAS, 11/05/2013, Vol 110 No 45, pages 18285-18290, listed on IDS filed 01/25/2021).
Regarding claims 10-12, and 15, Fukuda, as evidenced by Stefl, teaches all of the elements of the current invention for claim 1 as stated above in the 102 rejection.
Fukuda does not teach a guide RNA, wherein a hairpin structure is appended on the 3' end, a method for directed RNA editing in which the guide RNA is transfected into the cells in which the RNA editing is to be carried out, or a method wherein the transfection occurs by means of a plasmid that codes for the guide RNA and at least one U6 promotor for the transcription of the guide RNA.
Rosenthal teaches an antisense guide RNA oligonucleotide for targeted RNA editing with a Box B RNA hairpin (Abstract; Summary of the Invention, column 1) appended on the 3’ end (Fig. 1, sheet 1; column 2, lines 39-41). Rosenthal provides a teaching, suggestion, or motivation to append a Box B hairpin loop to the 3’ end of a guide RNA, because this allows precise recruitment of ADAR to a desired RNA target, thereby enabling specific and efficient RNA editing. Specifically, Rosenthal teaches that when the bacteriophage λ N-peptide is fused to the (DD) of ADAR, the DD can be targeted to different regions of RNAs for specific editing via the interaction between the λ N-peptide and the Box B RNA hairpin loop of the antisense RNA oligonucleotide, and the Watson-Crick base-pairing interactions between antisense RNA oligonucleotide and its target RNA (Abstract; Summary of the Invention, column 1; Fig. 1, sheet 1). Further, Rosenthal also teaches that full length deaminases could be used, amongst other variations (columns 5-6).
Montiel-Gonzalez teaches an antisense guide RNA oligonucleotide with a Box B RNA hairpin for targeted RNA editing (Results, column 1, paragraph 1, page 18286). Montiel-Gonzalez teaches that when the bacteriophage λ N-peptide is fused to the deaminase domain (DD) of ADAR, the DD can be targeted to different regions of RNAs for specific editing via the interaction between the λ N-peptide and the Box B RNA hairpin loop of the antisense RNA oligonucleotide, and the base pairing interactions between antisense RNA oligonucleotide and its target RNA (Results, column 1, paragraph 1, page 18286; Fig. 2, page 18287). Montiel-Gonzalez teaches a method for directed RNA editing in which the antisense guide RNA is transfected via microinjection into Xenopus oocytes in which the RNA editing is to be carried out (section “Genetically Encoded Site-Directed Editase Can Restore CFTR Function in Xenopus Oocytes”, Fig. 3-4, pages 18287-18287; Method section “Injection of Xenopus Oocytes”, page 18290). Montiel- Montiel-Gonzalez teaches a method for directed RNA editing in which a plasmid that encodes the antisense guide RNA under control of a U6 promoter is transfected into HEK-293T cells in which the editing is to be carried out (column 2, page 18288 and column 1, last paragraph, page 18289; Fig. 5, page 18289). Montiel-Gonzalez further teaches that “both the specificity and catalytic efficiency of our system for site-directed RNA editing can likely be improved by manipulating the guide or the enzyme” (Discussion, paragraph 3, page 18289). Montiel-Gonzalez teaches that these transfections of the guide RNA allow its effectiveness to be tested in living cells (last paragraph, column 2, page 18286).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the guide RNA of Fukuda to include the Box B motif of Rosenthal and to use the guide RNA in the transfection methods of Montiel-Gonzalez. Including the Box B motif with other guide RNA modifications would provide an improvement in the specificity and catalytic efficiency of the system for site-directed editing, as recognized by Montiel-Gonzales, and cellular transfection of the guide RNA would allow for testing of its effectiveness, as recognized by Montiel-Gonzalez. Further, as Rosenthal reports that full length deaminases could be used with the λ N-peptide and the Box B RNA oligo system and Montiel-Gonzales reports that manipulation of the guide RNA is likely to result in improvement of the system, there is a reasonable expectation that the Box B motif and transfection method could be successfully applied to the guide RNA of Fukuda, which also uses guide RNAs for directing deaminases to edit target RNAs.
Response to Applicants’ Arguments as they apply to rejection of claims 10-12 and 15 under 35 USC § 103
Applicant's amendments to the claims and arguments filed 06/16/2025 have been fully considered but have not been found persuasive in overcoming the rejection
for reasons of record as discussed in detail below.
Applicant submits similar argument of defects of Fukuda and Stefl described above and that 1) Rosenthal and Montiel-Gonzalez describe the combination of an antisense RNA oligonucleotide and a deaminase domain of human ADAR2, wherein the oligonucleotide and deaminase are linked by a Box B RNA hairpin on the oligonucleotide and a lambda N peptide on the deaminase domain. Applicant submits that do not remedy the deficiencies of Fukuda.
In regard to argument 1) applicant is directed to argument above for §102 rejection which maintains the § 103 rejection. Furthermore, in regard to what Rosenthal and Montiel-Gonzalez teach, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Therefore, the teachings of a hairpin structure appended on the 3’ end is a BoxB motif as it allows precise recruitment of ADAR to a desired RNA target is taught by Rosenthal and the teachings for methods of transfection is taught by Montiel-Gonzales, and their combination renders claims 10-12 and newly added claim 15 obvious.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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