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 .
Claim Status
Claims 1-13 are currently pending and under examination herein.
Claims 1-13 are rejected.
Priority
The instant application claims priority as a 371 of PCT/US2022/025440 filed 19 April 2022 and to US Provisional Application 63177216 filed 20 April 2021. In this action, claims 1-13 are examined as though they had an effective filing date of 20 April 2021. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 27 February 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed 20 October 2023 are accepted.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Many instances of links with https:// were found throughout the 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://, www., or other browser-executable code. See MPEP § 608.01. Applicant should review the entire specification to correct any instances of links.
The specification is also objected to because it contains numerous sequences (required for >3 amino acids or >9 nucleic acids) that are not associated with the required sequence IDs or sequence listing (see Nucleotide and/or Amino Acid Sequence Disclosures below). Sequences were found at least in Tables 2 and 4-9 and within the specification. Applicant should review the entire specification to correct any instances of sequences.
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:
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 specification contains numerous sequences that are not associated with Sequence IDs and there is no sequence listing (see objections to the specification above).
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.
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).
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.
Claim Rejections - 35 USC § 112
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.
Claims 4-6 and 10-12 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 4 and 10 recite the limitation "the RNAi". There is insufficient antecedent basis for this limitation in the claim. Claims 4 and 10 depend on claims 1 and 7, which recite “target RNAi transcript hybridization length” but not “an RNAi”. Claims 2 and 8 recite “an RNAi”. Claims 5-6 and 11-12 depend from claims 4 and 10 and this recites the described issues through said dependence.
Claims 4 and 10 recite the limitation "for each of the nucleotide sequences generated". No nucleotide sequences are “generated” in these claims or the claims they depend upon. It is unclear if this limitation is referring to the RNAs selected, the nucleotide sequences determined, or something else. The metes and bounds of the limitations are unclear rendering the claims indefinite. Claims 5-6 and 11-12 depend from claims 4 and 10 and this recites the described issues through said dependence.
Claims 5 and 11 recite “at sites where a given small nucleotide sequence is present”. The term “a given small nucleotide sequence” is considered indefinite because it is unclear if “small nucleotide sequence” is referring to the part of the RNAi system, as in small interfering RNA (siRNA), or if small is describing a separate nucleotide sequence within the set of RNAs, in which case “small” would be indefinite as a relative term. The term “small” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention (MPEP 2173.05(b)). The metes and bounds of the limitations are unclear rendering the claims indefinite.
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 therefore, subject to the conditions and requirements of this title.
Claims 7-13 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to non-statutory subject matter.
Claim 7-12 do not fall within at least one of the four categories of patent eligible subject matter because Claim 7 recites a system with the only structure related limitation being “a computer algorithm”. Products that do not have a physical or tangible form, such as information (often referred to as "data per se") or a computer program per se (often referred to as "software per se") when claimed as a product without any structural recitations are not directed to any of the statutory categories (MPEP 2106.03). Claims 8-12 depend on claims 7 and do not recite any structure.
Claim 13 recites “A computer-readable storage medium” executed by a computer. The claims and specification do not define the computer readable medium as non-transitory. Transitory forms of signal transmission (often referred to as "signals per se") are not directed to any of the statutory categories (MPEP 2106.03). Therefore, the claim is not directed to a statutory category. This rejection can be overcome by specifying that the computer readable medium is non-transitory.
Claims 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. In accordance with MPEP 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea or natural law (Step 2A, Prong 1). Claims 1-6 are directed to a method. Although claims 7-13 are not directed to a statutory category (see above), these claims are included in the subject matter eligibility analysis to facilitate compact prosecution. In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 recites the limitation - selecting an RNA or a set of RNAs. Based on the broadest reasonable interpretation, selecting could practically be done by the human mind. This draws the limitation to a mental process, which classifies the limitation as an abstract idea. The claim also recites defining a minimum and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs; and executing a computer algorithm, wherein the computer algorithm determines either a most abundant nucleotide sequences in the transcript or set of transcripts with a length that matches the minimum target RNAi transcript hybridization length. Based on the broadest reasonable interpretation, defining a minimum and maximum and determining a sequence based on a length determined through an algorithm encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 2 recites the limitation - selecting an RNAi guide sequence based on an index that represents a probability of an RNAi having silencing capabilities against the RNA or set of RNAs. Based on the broadest reasonable interpretation, selecting based on an index/probability encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 3 recites the limitation - wherein only nucleotide sequences with a GC content higher than 35% are considered. This limitation specifies the sequence determined in the judicial exception of claim 1. The refined limitation indicated still represents a judicial expectation.
Claim 4 recites the limitation - for each of the nucleotide sequences generated, a potential reverse complementary guide strand sequence of the RNAi is generated. Based on the broadest reasonable interpretation, the generating could practically be done by the human mind. This draws the limitation to a mental process, which classifies the limitation as an abstract idea.
Claim 5 recites the limitation - wherein the potential reverse complementary guide strand sequence of the RNAi is generated by producing an average nucleotide sequence with the maximum target RNAi transcript hybridization length from the nucleotide sequences of a maximum length at sites where a given small nucleotide sequence is present in the transcript or set of transcripts. Based on the broadest reasonable interpretation, generating based on an average compared to a length encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 6 recites the limitation - each of the potential reverse complementary guide strand sequence of the RNAi is qualified based on certain characteristics, the certain characteristics including: a hit feasibility index; or a custom index, the custom index representing a probability of a given potential hybridization site to have biological significance, or a probability of an RNAi having silencing capabilities against the RNA. Based on the broadest reasonable interpretation, qualifying based on indices/probabilities encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 7 recites the limitation - a computer algorithm, wherein the computer algorithm determines either a most abundant nucleotide sequences in a transcript or set of transcripts with a length that matches a minimum target RNAi transcript hybridization length, and wherein the minimum target RNAi transcript hybridization length and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs are defined from a selected RNA or a set of RNAs. Based on the broadest reasonable interpretation, using an algorithm to determined sequences based on length and defining minimum and maximum lengths encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 8 recites the limitation - the computer algorithm further selects an RNAi guide sequence based on an index that represents a probability of an RNAi having silencing capabilities against the RNA or set of RNAs. Based on the broadest reasonable interpretation, an algorithm selecting based on an index/probability encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 9 recites the limitation - wherein only nucleotide sequences with a GC content higher than 35% are considered. This limitation specifies the sequence determined in the judicial exception of claim 7. The refined limitation indicated still represents a judicial expectation.
Claim 10 recites the limitation - for each of the nucleotide sequences generated, a potential reverse complementary guide strand sequence of the RNAi is generated. Based on the broadest reasonable interpretation, the generating could practically be done by the human mind. This draws the limitation to a mental process, which classifies the limitation as an abstract idea.
Claim 11 recites the limitation - the potential reverse complementary guide strand sequence of the RNAi is generated by producing an average nucleotide sequence with the maximum target RNAi transcript hybridization length from the nucleotide sequences of a maximum length at sites where a given small nucleotide sequence is present in the transcript or set of transcripts. Based on the broadest reasonable interpretation, generating based on an average compared to a length encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 12 recites the limitation - wherein each of the potential reverse complementary guide strand sequence of the RNAi is qualified based on certain characteristics, the certain characteristics including: a hit feasibility index; or a custom index, the custom index representing a probability of a given potential hybridization site to have biological significance, or a probability of an RNAi having silencing capabilities against the RNA. Based on the broadest reasonable interpretation, qualifying based on indices/probabilities encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
Claim 13 recites the limitation - determine either a most abundant nucleotide sequences in a transcript or set of transcripts with a length that matches a minimum target RNAi transcript hybridization length, wherein the minimum target RNAi transcript hybridization length and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs are defined from a selected RNA or a set of RNAs. Based on the broadest reasonable interpretation, determining a sequence based on length and defining the minimum and maximum length of sequences encompasses equations and could practically be done by the human mind. This draws the limitation to a mathematical concept and a mental process, which classifies the limitation as an abstract idea.
These limitations recite concepts of selecting, determining, and comparing information and values and applying algorithms that are so generically recited that they can be practically performed in the human mind as claimed, which falls under the “Mental processes” and “Mathematical concepts” grouping of abstract ideas. A mathematical concept need not be expressed in mathematical symbols, because words used in a claim operating on data to solve a problem can serve the same purpose as a formula (MPEP 2106.04(a)(2)). Additionally, both product claims and process claims may recite mental processes, which can include a claim that requires a computer (MPEP 2106.04(a)(2)). Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. As such, claims 1-13 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). These judicial exceptions are not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology (MPEP § 2106.04(d)(1)). Rather, the claims provide insignificant extra-solution activity (MPEP § 2106.05(g)) and provide mere instructions to apply a judicial exception (MPEP § 2106.05(f)). Specifically, the claims recite the following additional elements:
Claim 13 recites a computer-readable storage medium having data stored therein representing software executable by a computer.
There are no limitations that indicate that the claimed selecting, determining, and comparing information and values and applying algorithms require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible. There is no indication that these steps are affected by the judicial exception in any way and thus do not integrate the recited judicial exception into a practical application. As such, claims 1-13 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite conventional additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
As discussed above, there are no additional limitations to indicate that the claimed selecting, determining, and comparing information and values and applying algorithms require anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea or natural law eligible. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. As specified in MPEP 2106.05(g), extra-solution activities can be understood as incidental to the primary process or product that are merely a nominal or tangential addition to the claim. Insignificant extra-solution activities include mere data gathering, selecting a particular data source or type of data to be manipulated, and displaying information.
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, Claims 1-13 are not patent eligible.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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 1-13 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Cai et al. (US 20170233742 A1).
Regarding Claim 1, 7, and 13, Cai et al. teach selecting an RNA or a set of RNAs (Paragraph 0027: The siRNA molecule of the invention targets and binds to a conserved region of an Ebola virus gene. As used herein, “target” or “targets” means that the molecule binds to mRNA produced by the gene or to viral complementary RNA; Paragraph 0031: the conserved Ebola virus regions are the genes (RNA sequences) for VP24, VP30, VP35, VP40, and L Polymerase or any part thereof). Cai et al. teach defining a minimum and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs (Paragraph 0028: the siRNA molecule is a double-stranded oligonucleotide with a length of 17 to 35 base pairs. In one particular aspect, it has blunt ends at both ends. In one particular aspect, the molecule has a length of 21 base pairs (21 mer)). Cai et al. teach determine either a most abundant nucleotide sequences in the transcript or set of transcripts with a length that matches the minimum target RNAi transcript hybridization length (Paragraph 0052: The software predicts. It determines siRNAs of a given length (21 mer with over hangs, or 25 base blunt ended duplex RNAs) that have identity to a gene that we are aiming to silence). Additionally, Cai et al. teach the methods are executed by a computer, which inherently contains memory and at least one processor (Paragraph 0052: The software predicts).
Regarding Claims 2 and 8, Cai et al. teach selecting an RNAi guide sequence based on an index that represents a probability of an RNAi having silencing capabilities against the RNA or set of RNAs (Paragraph 0052: The software predicts siRNAs with appropriate thermodynamic properties; Paragraph 0059: predict siRNAs de novo against each gene sequence within all sequenced viral strains applying the optimal thermodynamic criteria for siRNA potency).
Regarding Claims 3 and 9, Cai et al. teach only nucleotide sequences with a GC content higher than 35% are considered (Paragraph 0052: The software removes those siRNAs which were not within the appropriate range for GC content (35-65%).
Regarding Claims 4 and 10, Cai et al. teach for each of the nucleotide sequences generated, a potential reverse complementary guide strand sequence of the RNAi is generated (Paragraph 0052: It determines siRNAs of a given length (21 mer with over hangs, or 25 base blunt ended duplex RNAs) that have identity to a gene that we are aiming to silence). To silence the gene, it must act as the guide RNA which binds and is therefore complementary.
Regarding Claim 5 and 11, Cai et al. teach the potential reverse complementary guide strand sequence of the RNAi is generated by producing an average nucleotide sequence with the maximum target RNAi transcript hybridization length from the nucleotide sequences of a maximum length at sites where a given small nucleotide sequence is present in the transcript or set of transcripts (Paragraph 0053: While a region of identity in many siRNAs can include both a T and an A base at the terminus, it is sometimes not feasible to identify an siRNA with absolute identity in this region. Consequently, if the base pairing in the terminal region is not exact, this may help with efficacy of the siRNA (the algorithm accounts for mismatches); Paragraph 0060: We are building tools to allow examination of regions that may not be 100% identical to the siRNA sequence across all bases but which show identity in 19 consecutive bases).
Regarding Claim 6 and 12, Cai et al. teach wherein each of the potential reverse complementary guide strand sequence of the RNAi is qualified based on certain characteristics, the certain characteristics including: a hit feasibility index; or a custom index, the custom index representing a probability of a given potential hybridization site to have biological significance, or a probability of an RNAi having silencing capabilities against the RNA (Paragraph 0052: The software predicts siRNAs with appropriate thermodynamic properties; Paragraph 0059: predict siRNAs de novo against each gene sequence within all sequenced viral strains applying the optimal thermodynamic criteria for siRNA potency). The optimal thermodynamic criteria is interpreted as the custom index.
Claim Rejections - 35 USC § 103
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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Luck et al. (2019, Frontiers in Plant Science, Vol. 10: 1-12), in view of Cai et al. (US 20170233742 A1), as applied to claims 1-13 in the 35 USC 102 rejection above. Italicized text from reference art.
Regarding Claim 1, 7, and 13, Luck et al. teach selecting an RNA or a set of RNAs (Page 3, Column 2, Paragraph 1: probe an mRNA sequence database for matching sequences). Luck et al. teach defining a minimum and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs (Page 3, Column 2, Paragraph 1: where x is the selected length of the siRNA). Luck et al. teach determine either a most abundant nucleotide sequences in the transcript or set of transcripts with a length that matches the minimum target RNAi transcript hybridization length (Page 3, Column 2, Paragraph 1: splitting a long RNAi trigger sequence (the complement to the target sequence of the corresponding RNA) into all possible x-mers). Additionally, Luck et al. teach the methods are executed by a computer, which inherently contains memory and at least on processor (Page 3, Column 1, Paragraph 3: si-Fi has been developed as a Python (v. 2.7) graphical user interface (GUI) for Microsoft Windows-based systems).
Regarding Claims 2 and 8, Luck et al. teach selecting an RNAi guide sequence based on an index that represents a probability of an RNAi having silencing capabilities against the RNA or set of RNAs (Page 3, Column 2, Paragraph 2: a combination of sequence- and thermodynamic-based rules is applied in our approach in order to achieve an acceptable prediction accuracy of the siRNA efficiency).
Regarding Claims 4 and 10, Luck et al. teach for each of the nucleotide sequences generated, a potential reverse complementary guide strand sequence of the RNAi is generated (Page 3, Column 2, Paragraph 1: splitting a long RNAi trigger sequence (the complement to the target sequence of the corresponding RNA)).
Regarding Claim 5 and 11, Luck et al. teach the potential reverse complementary guide strand sequence of the RNAi is generated by producing an average nucleotide sequence with the maximum target RNAi transcript hybridization length from the nucleotide sequences of a maximum length at sites where a given small nucleotide sequence is present in the transcript or set of transcripts (Page 11, Column 2, Paragraph 3: “mismatches” – number of mismatches to the target sequence).
Regarding Claim 6 and 12, Luck et al. teach wherein each of the potential reverse complementary guide strand sequence of the RNAi is qualified based on certain characteristics, the certain characteristics including: a hit feasibility index; or a custom index, the custom index representing a probability of a given potential hybridization site to have biological significance, or a probability of an RNAi having silencing capabilities against the RNA (Page 3, Column 2, Paragraph 2: a combination of sequence- and thermodynamic-based rules is applied in our approach in order to achieve an acceptable prediction accuracy of the siRNA efficiency). This is interpreted as the custom index.
Luck et al. does not explicitly teach a GC content higher than 35% (Claims 3 and 9).
Regarding Claim 1, 7, and 13, Cai et al. teach selecting an RNA or a set of RNAs (Paragraph 0027: The siRNA molecule of the invention targets and binds to a conserved region of an Ebola virus gene. As used herein, “target” or “targets” means that the molecule binds to mRNA produced by the gene or to viral complementary RNA; Paragraph 0031: the conserved Ebola virus regions are the genes (RNA sequences) for VP24, VP30, VP35, VP40, and L Polymerase or any part thereof). Cai et al. teach defining a minimum and a maximum target RNAi transcript hybridization length of the RNA or set of RNAs (Paragraph 0028: the siRNA molecule is a double-stranded oligonucleotide with a length of 17 to 35 base pairs. In one particular aspect, it has blunt ends at both ends. In one particular aspect, the molecule has a length of 21 base pairs (21 mer)). Cai et al. teach determine either a most abundant nucleotide sequences in the transcript or set of transcripts with a length that matches the minimum target RNAi transcript hybridization length (Paragraph 0052: The software predicts. It determines siRNAs of a given length (21 mer with over hangs, or 25 base blunt ended duplex RNAs) that have identity to a gene that we are aiming to silence). Additionally, Cai et al. teach the methods are executed by a computer, which inherently contains memory and at least one processor (Paragraph 0052: The software predicts).
Regarding Claims 2 and 8, Cai et al. teach selecting an RNAi guide sequence based on an index that represents a probability of an RNAi having silencing capabilities against the RNA or set of RNAs (Paragraph 0052: The software predicts siRNAs with appropriate thermodynamic properties; Paragraph 0059: predict siRNAs de novo against each gene sequence within all sequenced viral strains applying the optimal thermodynamic criteria for siRNA potency).
Regarding Claims 3 and 9, Cai et al. teach only nucleotide sequences with a GC content higher than 35% are considered (Paragraph 0052: The software removes those siRNAs which were not within the appropriate range for GC content (35-65%).
Regarding Claims 4 and 10, Cai et al. teach for each of the nucleotide sequences generated, a potential reverse complementary guide strand sequence of the RNAi is generated (Paragraph 0052: It determines siRNAs of a given length (21 mer with over hangs, or 25 base blunt ended duplex RNAs) that have identity to a gene that we are aiming to silence). To silence the gene, it must act as the guide RNA which binds and is therefore complementary.
Regarding Claim 5 and 11, Cai et al. teach the potential reverse complementary guide strand sequence of the RNAi is generated by producing an average nucleotide sequence with the maximum target RNAi transcript hybridization length from the nucleotide sequences of a maximum length at sites where a given small nucleotide sequence is present in the transcript or set of transcripts (Paragraph 0053: While a region of identity in many siRNAs can include both a T and an A base at the terminus, it is sometimes not feasible to identify an siRNA with absolute identity in this region. Consequently, if the base pairing in the terminal region is not exact, this may help with efficacy of the siRNA (the algorithm accounts for mismatches); Paragraph 0060: We are building tools to allow examination of regions that may not be 100% identical to the siRNA sequence across all bases but which show identity in 19 consecutive bases).
Regarding Claim 6 and 12, Cai et al. teach wherein each of the potential reverse complementary guide strand sequence of the RNAi is qualified based on certain characteristics, the certain characteristics including: a hit feasibility index; or a custom index, the custom index representing a probability of a given potential hybridization site to have biological significance, or a probability of an RNAi having silencing capabilities against the RNA (Paragraph 0052: The software predicts siRNAs with appropriate thermodynamic properties; Paragraph 0059: predict siRNAs de novo against each gene sequence within all sequenced viral strains applying the optimal thermodynamic criteria for siRNA potency). The optimal thermodynamic criteria is interpreted as the custom index.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to combine Cai et al. with Luck et al. Luck et al. teach their software excels at designing flexible and versatile RNAi system related to pathogens (Page 9, Column 1, Paragraph 1: The software offers the possibility to create custom sequence databases, allows flexible settings of parameters, and provides easy-to-interpret graphical and tabular outputs), which is a major focus of Cai et al. and in the instant application. Relatedly, Cai et al. teach their methods excel at designing adaptable or specific RNAi systems for medical pathogens (Paragraph 0055: we can identify siRNAs that will be able to a) exhibit a broad strain specificity or b) be selective for a specific gene within a particular viral strain), which is a major focus of Luck et al. and in the instant application. Furthermore, one of ordinary skill in the art would predict that the methods could be readily combined with a reasonable expectation of success because both are within the same technical field - software based methods for designing and optimizing RNAi systems related to pathogens using sequence information.
Double Patenting
No double patenting issues reported.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLAKE H ELKINS whose telephone number is (571)272-2649. The examiner can normally be reached Monday-Thursday 8-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz Skowronek can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.H.E./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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