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 .
Application Status and Election
The amendments and remarks filed 1/20/26 in response to the office action of 10/21/25 are acknowledge and have been entered. Claims 1, 3-5, 7-11 and 15-18 are pending. Claims 1 and 5 are amended. Claims 2, 6 and 12-14 are canceled. Applicant’s election with traverse of group I (claims 1, 2, 5-11, and 13-17) in the reply filed on 8/20/25 remains acknowledged. Claims 3 and 4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Examination on the merits commences on claims 1, 5, 7-11 and 15-18.
Applicants are informed that the rejections and/or objections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant' s arguments and/or amendments. 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 - MODIFIED
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.
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.
Claim(s) 1, 5, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova of record (Khvorova, A., US20070260050A1) in view of Wu (Wu, Haoquan, et al. "Improved siRNA/shRNA functionality by mismatched duplex." PloS one 6.12 (2011): e28580.)
Regarding claim 1 and 18, Khvorova teaches siRNA SEQ ID NO: 577 that targets the MCM7 gene for gene silencing with 100% match for instant SEQ ID NO: 10 and 91.6% match for instant SEQ ID NO: 9 [0482] where the siRNA duplex is comprised of sense and antisense strands and is between 18 and 30 nucleotides in length (claim 1 and [0072]). Khvorova teaches two base 3′ nucleotide overhangs of the sense and antisense strands where the overhangs consist of two nucleotides, often dTdT or UU at the 3′ end of the sense and antisense strand [0416].
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Although Khvorova teaches siRNA SEQ ID NO: 577 that targets the MCM7 gene for gene silencing with 100% match for instant SEQ ID NO: 10 and 91.6% match for instant SEQ ID NO: 9 [0482]. Khvorova does not teach an exact match for instant SEQ ID NO: 9.
However, Wu teaches mismatches in certain positions of siRNA, such as the position 1, seed region (position 4–7), and central region (position 9–12), can increase siRNA functionality (pg 3 col 1 para 1). Wu teaches lowering the thermodynamic stability in the central position (position 9–12) by either introducing mismatches or chemical modifications, could significantly improve the siRNA potency (pg 6 col 2 para 2).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have further modified the overhang modified siRNA duplex of Khvorova targeting MCM7 with only one base mismatch difference at position 9 from instant SEQ ID Nos 9, and modified according to the method of Wu to employ at mismatch at position 9 of the siRNA. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that Khvorova’s siRNA duplex could inhibit expression of MCM7 because Khvorova teaches SEQ ID NO: 577 to target and inhibit expression of MCM7. It would have been predictable that Khvorova’s SEQ ID NO: 577 could be modified at position 9 by a uracil mismatch for enhanced efficacy because Wu teaches effective application of position 9 central mismatch to significantly improve the siRNA potency. The skilled artisan would be motivated to apply Wu’s siRNA composition modifications to Khvorova’s MCM7 targeting siRNA duplex for enhanced ant-tumor therapeutics.
Regarding claims 5, Khvorova teaches the above applied to claim 1, i.e., a composition comprising the siRNA of claim 1. Examiner is interpreting “for preventing or treating a tumor/cancer” as intended use and not a necessary limitation. MPEP 2111.02.II. states, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” However, even if the intended use is recited in the body of a product claim, if the intended use does further limit the structure of the product, it is also not considered a limitation.
Claim(s) 1, 7-11 and 15-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova of record (Khvorova, A., US20070260050A1) in view of Wu (Wu, Haoquan, et al. "Improved siRNA/shRNA functionality by mismatched duplex." PloS one 6.12 (2011): e28580.) as applied to claim 1, in further view of Hamamoto of record (Hamamoto, R., WO2012090479A1).
The teachings of Khvorova and Wu as applied above for claim 1 are incorporated here.
Khvorova does not teach phosphorothioate linkages and 2'-OH modified into 2'-methoxy siRNA compositions within a pharmaceutically acceptable carrier with adjuvant chemotherapeutic agents contained within an aerosol.
However, regarding claims 7 and 8, Hamamoto teaches the anti-cancer compositions within a pharmaceutically acceptable carrier where the pharmaceutically acceptable carrier comprises an excipient [0254].
Regarding claim 9, Hamamoto teaches the compositions co-administered with chemotherapeutic agents [0314].
Regarding claims 10, 15-17, Hamamoto teaches the anti-cancer compositions within an aerosol [0266].
Regarding claim 11, Hamamoto teaches the nucleotides of the invention modified with phosphorothioate linkages (i.e. an oxygen atom of the phosphate is substituted by sulfur) as well as 2'-OH modified into 2'-methoxy [0332].
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to employ the modified siRNA duplex of Khvorova targeting MCM7 with homology to instant SEQ ID Nos 9 and 10, and modified according to the method of Hamamoto to apply to the effective treatment of lung cancer. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that Khvorova’s siRNA duplex could inhibit expression of MCM7 because Khvorova teaches SEQ ID NO: 577 to target and inhibit expression of MCM7. It would have been predictable that Khvorova’s SEQ ID NO: 577 could be modified and applied within Hamamoto’s anti-tumor siRNA/drug delivery system because Hamamoto teaches effective application of chemically modified siRNA/drug compositions delivered to treat tumors. The skilled artisan would be motivated to apply Hamamoto’s siRNA composition modifications to Khvorova’s MCM7 targeting siRNA duplex for enhanced ant-tumor therapeutics.
Response to Arguments
Applicant’s arguments are directed to the withdrawn §102, §112a, and §1112d (Remarks pages 5-9). Therefore, the arguments are moot.
Applicants argue (Remarks pgs 11-13) unexpected results of enhanced effectiveness of MCM7 expression inhibition using the claimed modified SEQ ID NOs 9 with a central base mismatch of SEQ ID NO: 9 at position 9. Applicant’s arguments have been thoroughly reviewed and found unpersuasive. Khvorova differs from the claimed sense strand by only single nucleotide at the 9th position which Applicants argue allows incomplete complementary pairing and the thermodynamic properties of the entire double-stranded RNA changed, which improves the efficiency of the antisense strand to participate in the interference of RNA with a complex protein and thus improves the efficiency of the siRNA-1 to inhibit the target MCM7 gene. This central base mismatch strategy at position 9 is well known in the art and is clearly disclosed by the teachings of Wu, as described above in the modified §103 rejection above. Briefly, Wu teaches mismatches in certain positions of siRNA, such as the position 1, seed region (position 4–7), and central region (position 9–12), can increase siRNA functionality (pg 3 col 1 para 1). Wu teaches lowering the thermodynamic stability in the central position (position 9–12) by either introducing mismatches or chemical modifications, could significantly improve the siRNA potency (pg 6 col 2 para 2). Therefore, it would have been predictable that a base mismatch at position 9 such as in the claimed SEQ ID NO: 9 would lead to enhanced MCM7 expression reduction given Wu teaches this base modification significantly improve the siRNA potency.
Conclusion
No claims are allowable.
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 extension fee 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 date of this final action.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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