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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11, in the reply filed on 03/26/2026 is acknowledged.
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-11 and 16-20 are pending and claims 1-11 are under examination on the merits.
Priority
This application 18/552,397 filed on 09/25/2023 is a 371 national phase of PCT/EP2022/057596 filed on 03/23/2022, and claims the benefit of German Patent Application No. 10 2021 107 508.4, filed on 03/25/2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386 (c) is acknowledged. Receipt of certified copies of papers required by 37 CFR 1.55 is acknowledged. It is noted that foreign priority is not perfected as no English translation was provided for the foreign priority document received on 09/25/2023. In order to perfect the foreign priority claim, please provide a certified English copy.
In the absence of a translated copy, the priority date of claim 1 and its dependents is determined to be 03/23/2022, the filing date of PCT/EP2022/057596.
Drawings
The drawings are objected to because Figures 4 and 5 contain non-English language labels. Replacement Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
(I). Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the filing date of the US application is after 07/01/2022.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
(II). Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Tables 1 and 2 in the specification require additional columns, or changes to the contents of the current columns headed “SEQ ID” such that sequence identifiers are clearly designated in the format “SEQ ID NO:X”.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
(III). Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Figure 1A includes two sequences without sequence identifiers for sequences in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
(IV). Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
The incorporation by reference paragraph (in the amendments to the specification filed 09/25/2023) is defective. The size of the file should be recited in bytes instead of kilobytes (KB).
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 3 of specification). 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:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim recites “nucleic acids --- alter the function of this target RNA”. The claim should be amended to recite “said target RNA” or “the target RNA”. Appropriate correction is required.
Claim Interpretation
Claim 1 step (ii) recites the limitations “esiRNA” and “eRNA”. The instant specification provides no structural limitations beyond those in the claim to define “esiRNA” or “eRNA”. For purposes of examination “esiRNA” and “eRNA” are interpreted as any siRNA or RNA respectively.
Claim 11 recites the limitation “wherein the eNAs are any type of g/crRNAs and the endonuclease is a Cas protein”. It is noted that Claim 1, which claim 11 depends from, does not require g/crRNAs in the presence of a Cas protein due to the and/or phrase between steps (iii) and (iv). Therefore the limitations set forth in claim 11 are not in fact required
Claim Rejections - 35 USC § 112(b)
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 1-11 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.
Claim 1 recites the phrase “complex RNA molecules” in the preamble. It is unclear what defines a complex RNA molecules. Neither the specification nor the claims provides guidance beyond what is in the claim.
Claim 1 recites the limitations “complex RNA molecules (target RNAs)” in the preamble, and “nucleic acids of different types ('eNAs')” in step (v) . It is unclear if the limitations in parentheses is part of the claimed invention. For examination purposes the terms are interpreted as equivalent and not limiting.
Claim 1 recites the limitations ”esiRNA/eRNA” and “g/crRNA” in steps (ii) and (iv). It is unclear if the limitation in after “/” is part of the claimed invention. For examination purposes the terms are interpreted as equivalent and not limiting.
Claim 1 recites the limitation “esiRNAs” and “eRNAs”. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The accepted meaning of “esiRNA” is “endoribonuclease-prepared siRNA”. The accepted meaning of “eRNA” is “enhancer RNA”. The terms are indefinite because the specification does not clearly redefine the term.
Claim 1 recites the limitations “derived antisense DNA oligonucleotides (ASO)” and “g/crRNAs derived therefrom” in steps (iii) and (iv). It is not clear what defines a derived ASO or derived g/crRNAs. The claims provide no structural limitations or other guidance as to what defines a derived ASO or derived g/crRNAs.
Claim 1 includes “and/or” between steps (iii) and (iv). It is unclear if all steps after (iii) are intended to be optional, if all steps, (i)-(v), are optional, or if it is optional to perform step (iii) or step (iv). The claim limitation requirements are made further unclear by inclusion of “and” between steps (iv) and (v). For purposes of examination, the required active steps are interpreted to be (i), (ii), (iii) or (iv), and (v).
Claim 1 step (iv) recites the limitation “to determine whether they can induce a functional change”. There is insufficient antecedent basis for “they” in the claim.
Claim 1 recites the limitation “---identifying the a-sites in the target RNA---” in step (v). It is unclear how this limitation is intended to be achieved. The claim requires “performing an esiRNA/eRNA screen that identifies siRNAs that can reliably induce a functional change in this target RNA”; and “performing a subsequent assay with derived antisense DNA oligonucleotides (ASO) to determine whether they can induce a functional change in the target RNA” or “performing subsequent testing with g/crRNAs derived therefrom to determine whether they can induce a functional change in the target RNA”. “Accessible regions ('a-sites')” are recited only in the preamble and step (v). None of active steps (i) to (iv) require accessible regions or 'a-sites' or recite a relationship between the steps and accessible regions or 'a-sites'. It is unclear what relationship the claimed siRNAs, ASOs, or g/crRNAs have to accessible regions or 'a-sites' or how such sites would be identified by performing the steps of (i) – (iv). The claims do not require identifying accessible regions bound by siRNAs, accessible regions bound by ASOs and/or g/crRNAs, or comparing accessible regions bound by the siRNAs or ASOs and/or g/crRNAs.
Claims 2-11 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 4 recites the limitation “any kind of siRNAs (siRNAs, vsiRNAs, tasiRNAs, hpsiRNAs, natsiRNAs, vasiRNAs, hetsiRNAs, piwi RNAs, easiRNAs, phasiRNAs, endo-siRNAs)”. It is unclear if the limitation in parentheses is part of the claimed invention. For examination purposes the terms are interpreted as equivalent and not limiting. Further, the claim is unclear in stating “any kind of siRNA” followed by a finite list of siRNAs.
Claims 6 and 7 recite the limitation "the alteration in the function of the target RNA". There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites an intended result or property of the claimed method, in particular that the alteration in the function of the target RNA always occurs”. The claim does not recite any additional active method steps. It is unclear what additional step or elements are required, if any, to achieve the recited result or confer the recited property, beyond that specified in independent claim 1.
Claim Rejections - 35 USC § 112(d)
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 5 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 5 recites the limitation “wherein the endonuclease is selected from Argonaute (AGO), RNase H and/or Cas proteins”. Claim 1, which claim 5 depends from, recites the limitations “in complexes with Argonaute (AGO) proteins; --- in the presence or absence of RNase H; and/or --- in the presence of a Cas protein”. Thus claim 5 fails to further limit the claims 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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 1 is directed to a method comprising “identifying the a-sites in the target RNA”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the identifying step encompasses the mental step of looking at data and recognizing accessible sites.
Claims 2-11 depend from claim 1, and require the same step of “ identifying the a-sites”.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites the additional steps of: “(i) provisioning of a target RNA; (ii) performing an esiRNA/eRNA screen ---; (iii) performing a subsequent assay with derived antisense DNA oligonucleotides (ASO) --- ; and/or (iv) performing subsequent testing with g/crRNAs”, these are not integrations of the exception into a practical application. Instead, these steps are data gathering required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to provisioning RNA, performing siRNA/RNA screens, performing assays with ASOs, and testing with g/crRNAs are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Mutso et al. (RNA Interference-Guided Targeting of Hepatitis C Virus Replication with Antisense Locked Nucleic Acid-Based Oligonucleotides Containing 8-oxo-dG Modifications. 2015. PLoSOne. 10(6): e0128686. On IDS dated 09/25/2023) in view of Neumeier et al. (siRNA Specificity: RNAi Mechanisms and Strategies to Reduce Off-Target Effects. 2021.Front. Plant Sci. 11:1-7. Published 01/28/2021).
Regarding claim 1, Mutso teaches a method using RNAi technology to search for highly accessible target sites in the HCV coding region of HCV RNA (p. 9). Regarding steps (i) and (ii), Mutso teaches the method comprises testing a group of siRNAs (i.e. screening) against HCV RNA (p. 9). The method also teaches that, guided by the RNAi screening (p. 9), performing an assay for ASO (antisense oligonucleotide) cleavage (inducing a functional change in the target RNA) of target RNA in the presence of RNase H (p. 6 and 14-15), which reads on step (iii). Mutso teaches the method allows identification of accessible regions for RNA silencing machinery (siRNAs) but also to ASOs, i.e. nucleic acids of different types ('eNAs') (p. 19 and 20).
Mutso does not explicitly teach the siRNAs are in complexes with Argonaute (AGO) proteins.
Neumeier teaches that siRNAs complex with Argonaute to cleave (induce a functional change in) target RNAs by RNAi (p. 1, Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Mutso and Neumeier to arrive at the instantly claimed invention. The modification would have entailed using well-known protocols as taught by Neumeier for use of the siRNAs of Mutso. Complexing of Argonaute proteins with siRNAs for cleavage (functional change in the target RNA) was well-known and conventional at the time of filing as evidenced by the prior art. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 2, Mutso teaches endonucleolytic cleavage (Fig. 6A).
Regarding claim 3, Mutso teaches inhibition of viral target RNA (p. 1, abstract).
Regarding claim 4, Mutso teaches siRNAs and antisense oligonucleotides, i.e. nucleic acids of different types ('eNAs') that target the RNA (p. 4)
Regarding claim 5, Mutso teaches the use of RNase H (p. 6 and 14-15 and Fig. 6).
Regarding claim 6, Mutso teaches RNAi mediated silencing (p. 19).
Regarding claim 7, neither Mutso nor Neumeier specifically teach that the alteration in the function of the target RNA always occurs.
However, Mutso teaches optimizing the method to decrease the uncleaved fraction of a target RNA towards 0% (Fig. 6B), i.e. conditions where cleavage always occurs. Neumeier further teaches differences in cleavage activity of argonaute in different complexes (Fig. 2).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mutso and Neumeier to arrive at the instantly claimed invention. The modification would have entailed requiring conditions in which the alteration in the function of the target RNA always occurs. Both Mutso and Neumeier teach altering the degree of alteration. Determining appropriate conditions would have been merely a matter of judicious selection and routine optimization. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 8, Neumeier teaches perfect complementarity of siRNAs (i.e. having a consensus sequence) that bind in complex with AGO (an endonuclease). Neumeier further teaches miRNAs with only partial complementarity have impaired cleavage activity (Fig. 2 and legend). Thus Neumeier satisfies the requirement of siRNAs with a consensus sequence that increase the affinity of the endonuclease (AGO)
Regarding claim 9, Mutso teaches using siRNAs, but does not explicitly teach the endonuclease is an AGO protein.
Neumeier teaches that siRNAs complex with Argonaute to cleave (induce a functional change in) target RNAs by RNAi (p. 1, Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Mutso and Neumeier to arrive at the instantly claimed invention. The modification would have entailed using well-known protocols as taught by Neumeier for use of the siRNAs of Mutso. Complexing of Argonaute proteins with siRNAs for cleavage (functional change in the target RNA) was well-known and conventional at the time of filing as evidenced by the prior art. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 10, Mutso teaches antisense nucleotides and RNase H (p.1, Abstract).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Mutso et al. (RNA Interference-Guided Targeting of Hepatitis C Virus Replication with Antisense Locked Nucleic Acid-Based Oligonucleotides Containing 8-oxo-dG Modifications. 2015. PLoSOne. 10(6): e0128686. On IDS dated 09/25/2023) in view of Neumeier et al. (siRNA Specificity: RNAi Mechanisms and Strategies to Reduce Off-Target Effects. 2021.Front. Plant Sci. 11:1-7. Published 01/28/2021) as applied to claims 1-10 above, and further in view of Wessels et al. (Massively parallel Cas13 screens reveal principles for guide RNA design. 2020. Nat Biotechnol. 38: 722–727. On IDS dated 09/25/2023).
Regarding claim 11, neither Mutsu nor Neumeier teach the eNAs are any type of g/crRNAs and the endonuclease is a Cas protein.
Wessels teaches guide RNAs (gRNAs) that target RNAs with nuclease activity (p. 722, Abstract) and bind accessible sites with Cas13 (p. 722, col. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Mutso and Neumeier with Wessels to arrive at the instantly claimed invention. The modification would have entailed adding or substituting the gRNAs and Cas protein of Wessels for the antisense oligonucleotides and RNase H of Mutso. Each of these options provide similar target nucleic acids with an exonuclease to cleave a target RNA and require accessibility to the target RNA. The substitution of one well known method pair of reagents with known properties for a second well known pair of reagents with well-known properties would have been prima facie obvious to the ordinary artisan at the time of the invention. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, WINSTON SHEN can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682