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
Claims 9, 11-13, 15, 21 and 23 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/24/25.
The non-elected species were cancelled in the amendment filed on 5/6/26.
Drawings
The drawings were received on 5/6/26. These drawings are acceptable.
Specification
The amendment to the specification filed on 5/6/26 has been entered. The sequence listing has been entered.
Claim Objections
Claim 2 is objected to because of the following informalities: Group 2 appears to be recited twice in a row and one of them should be removed.
Response to Arguments
Applicant’s arguments, see page 8, filed 5/6/26, with respect to 103 rejection over Sook et al. (Nature Vol. 584, pages 279-285, pages 1-31, August 2020) taken with Burrows have been fully considered and are persuasive. The rejection of claims 1, 4-5 and 7 has been withdrawn because applicant filed a certified English translation of the priority document of Korean patent application no. 10-2019-0156147 filed 11/28/19 and is now the effective filing date of the present application. However, a new ground(s) of rejection is made in view of new claim 31. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Burrows (WO 2010111290) taken with Duan et al. (Mol. Biosyst, 2014, 10,2775-2782), both cited on an IDS.
Burrows teaches incorporating at least one o8G into one or both strands of a siRNA (also known as double stranded nucleic acid; RNAi) for reduced or complete abrogation of off-target effects (e.g., pages 2-4, 7, 34, 55 and 71-73). Purines in RNAi were switched with N2-alkylated 8-oxoG. Methods of blocking an off-target molecule to an siRNA molecule comprising modifying at least one guanosine base of the siRNA molecule (page 34). The siRNA can comprise at least one modified guanosine where the base opposite is not complementary.
Burrows does not specifically teach incorporating at least one o8G into either strand of a dsRNA comprising a miR-1 sequence.
However, Duan teaches studying miR-1 in heart disease since could be a possible therapeutic target. The nucleotide sequence for miR-1 (miR-1-1 and mir-1-2) taught by Duan reads on an unmodified nucleotide sequence (SEQ ID NOs: 1-3) set forth in instant claim 5 (page 2278, Fig 3, the highlighted nucleotides are the mature miR set forth below).
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It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Burrows taken with Duan to make the claimed product to reduce the off-target effect of the siRNA for targeting miR-1 expression in a cell, namely to arrive at the claimed invention. Duan et al. teach instant SEQ ID NO: 1 is the sequence for a mature miR-1 (Figure 3). The mature miR-1 sequence is UGGAAUGUAAAGAAGUAUGUAU. There are a finite number of guanosines in the dsRNA comprising a miR-1 sequence comprising SEQ ID NO: 1, including at positions 2, 3 and 7, it would have been obvious for one of ordinary skill in the art to try o8G at each guanosine to determine the optimal sequence for reducing the off-target effect of the siRNA in a cell (page 26 of Burrows). See MPEP 2143(I)E. In addition, the sequences in instant claim 5 would be considered obvious variants of the dsRNA having a miR-1 sequence and a sequence complementary thereto; and at least one o8G at the 2nd, 3rd, 7th nucleotide in the 1st to 9th nucleotides from the 5’ end.
The term 'RNA interference inducing nucleic acid' in the pending claims broadly reads on a double stranded RNA comprising a sense and antisense strand, wherein one strand comprises a miR-1 sequence. The new limitation “wherein the RNA interference-inducing nucleic acid induced myocardial hypertrophy when being injected to a cell or an animal” in claim 1 is directed to a ‘wherein’ clause and does not add any patentable weight to the claimed product because it does not add any additional structural limitations to the claim. Also, the limitation could be directed to an intended use of the claimed product. The broadest reasonable interpretation of instant claim 4 embraces either the other strand of the RNA interference nucleic acid having an adenine (A) opposite the o8G (structural limitation) or the target miR-1 sequence in a cell has an A at a position complementary to the position of o8G in the strand of the nucleic acid (functional limitation). The product made obvious by Burrows and Duan would possess the limitation in instant claim 4 because Burrows teaches that at least one o8G can be used to pair with C in a strand and when the siRNA reaches the RISC and is unwound by helicase, the o8G undergoes a conformation change to the syn form, and it now becomes complementary to an A in the RNA sequence (miR-1) in a cell (page 26 of Burrow).
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments
Applicant's arguments filed 5/6/26 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). While it acknowledged that neither Burrow nor Dunn et al. teach the incorporation of at least o8G into the 2nd, 3rd, or 7th nucleotide in the 1st to 9th nucleotide from the 5’ end of the nucleotides of miR-1-1 or miR-1-2, the rejection is under 103 and not 102. Dunn taken with Burrow provide motivation for making a dsRNA comprising the miR-1-1 and miR-1-2, wherein at least one nucleotide is o8G. Duan taught the sequences for the mature miR-1-1 or miR-1-2 recited in instant claim 5 and why one of ordinary skill in the art would have been motivated to study modulating its expression. Burrows provided motivation to try incorporating o8G into a certain positions of either or both strands of a dsRNA.
In response to applicant’s arguments that Burrows teaching incorporation at least one o8G into a siRNA for reduced or complete abrogation of off-target effects, it fails to disclose incorporating at least o8G into the 2nd, 3rd or 7th nucleotide in 1st to 9th nucleotides from the 5’ end of at least one single strand of double stranded RNA, wherein the 1st to 9th nucleotides from the 5’ end comprise a sequence of microRNA wherein the microRNA is miR-1, the argument is not found persuasive because the rejection is under 103 and not 102. Burrow provides motivation for one of ordinary skill in the art to incorporate at least one o8G into a dsRNA and the prior art teaches that there are a finite number of predictable and identified nucleotides in the miR-1 sequence. It would have been obvious for one of ordinary skill in the art to try o8G at each nucleotide to determine the optimal sequence for reducing the off-target effect of the siRNA in a cell. See MPEP 2143(I)E.
In response to applicant’s argument that Burrows fails to disclose or suggest that the RNA-interference-inducing nucleic acid induces myocardial hypertrophy while being injected to a cell or an animal, the argument is not found persuasive because the claims are directed to a product not a method of using the product. The new limitation is a ‘wherein’ clause directed to an intended use of the product. The new limitation does not add any structural limitations that need to be made obvious by the prior art rejection.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Burrows taken with Duan et al. as applied to claims 1 and 4-5 above, and further in view of Agrawal et al. (Pharmacological Research 61, 2010, 269-280, cited on an IDS).
Burrows and Duan do not specifically making a composition comprising the nucleic acid of claim 1 and an antioxidant.
However, Agrawal teaches high doses of vitamin C/superoxide dismutase can be used to treat heart failure in a subject (page 276).
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Burrows and Duan taken with Agrawal to add an antioxidant to a composition comprising the instant nucleic acid, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to combine the agents in a composition to study the potential for an additive effect for treating a cardiac disease in a subject.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). This is the case here because Agrawal was provided to show that there was motivation to combine an antioxidant with a dsRNA comprising a miR-1 sequence made obvious by Burrows and Duan.
New Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Burrows and Duan et al. and Agrawal as applied to claim 7 above, and further in view of Zhang et al. (US 20130155371).
Burrows, Duan and Agrawal do not specifically teach the antioxidant is N-acetylcysteine (NAC) or butylated hydroxyanisole (BHA). The instant specification does not teach an unexpected result or property using the RNA-interference-inducing agent nucleic acid with either NAC or BHA.
The prior art teaches that NAC and BHA were well-known antioxidants. See paragraph 316-317 of Zhang.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Burrows, Duan and Agrawal taken with Zhang as a simple substitution to use any known antioxidant, including NAC or BHA with the dsRNA targeting miR-1 (see MPEP 2143(I)B), namely to arrive at the claimed invention.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Conclusion
See attached PTO-326 for disposition of claims.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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