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 inventive group I in the reply filed on 09/11/2025 is acknowledged.
Claims 7-8, 12, 13, 15, 17, 19, 21, 25, 26, 30, 31, 33-35, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventive group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/11/2025.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) an RNA that is complementary to a portion of a gene sequence; the noncoding strand of a gene is also a product of nature, even if only a fragment. This judicial exception is not integrated into a practical application because the claim fails to offer significantly more than the natural product. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is not integrated into a practical application and fails to amount to significantly more due to the claim failing to recite any elements other than the natural product.
Claim Interpretation
Paragraph 0065 of the specification defines the term “guide RNA” as “a polynucleotide that cleaves, inserts, or links a target DNA in a cell via RNA editing” and further goes on to list examples of the guide RNA which include a single-chain guide RNA. Therefore, as the conditions of the term “guide RNA” will be satisfied by simply introducing a single guide RNA into a cell, the limitations of claims 1, 3, and 4 are satisfied by reading on a complementary sequence to SEQ ID NOs. 3, 19, or 34.
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.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Shemi et al. (US 8889642 B2) in view of Kelley et al. (Versatility of chemically synthesized guide RNAs for CRISPT-Cas9 genome editing, 2016)
Regarding claims 1, 3, and 4: Shemi teaches compositions and methods for making and using an RNAi to target mutated K-ras. (Col 1, ln 64-66) In an embodiment of the invention, Shemi teaches use of an RNAi which comprises SEQ ID NO. 38, which is 100% complementary to the claimed SEQ ID NO. 19, as shown in the alignment chart below:
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168
734
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Shemi further teaches that the siRNA comprising SEQ ID NO: 38 is a preferred siRNA (see claim 1) that has increased stability and efficacy. Example 5 and the results summarized in figures 5 and 6 demonstrate that siRNA #4 provides lower cell viability (figure 5) and has the highest level of efficacy at 120h (figure 6).
Regarding claim 2: Kelley teaches that both tracrRNA and crRNA molecules are useful as a means of using a synthetic molecule to further control expression level and duration of activity of a target nucleotide sequence. (Pg 79, Methods for enhancing CRISPR-Cas9 specificity) This reads on the use of a non-naturally occurring tracrRNA, and a person of ordinary skill in the art would have been motivated to use a tracrRNA due to Kelley teaching that use of a synthetic guide sequence enhances control over expression level and durability.
Regarding claim 5: Shemi teaches an embodiment of the invention in which the RNAi of the claimed invention is chemically modified, including SEQ ID NO: 38, which when modified is designated as SEQ NO: 40. (Col 9, ln 25)
Regarding claim 6: Per the sequence alignment chart above, Shemi teaches SEQ ID NO. 38 which is 21 nucleotides in length, therefore reading on the claimed guide RNA having a length of no more than about 200 nucleotides.
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 synthetic mutated KRAS sequence (SEQ ID NO 38) as taught by Shemi with the tracrRNA as taught by Kelley to create a non-naturally occurring polynucleotide comprising a guide RNA for targeting a mutated KRAS comprising a crRNA (tracrRNA) comprising a sequence complementary to the claimed SEQ ID NO. 19. One would have been motivated and had a reasonable expectation of success at doing so based on the teachings of Kelley, who states that tracrRNA and crRNA molecules are useful as a means of using a synthetic molecule to further control expression level and duration of activity of a target nucleotide sequence. One of ordinary skill in the art would choose to use the siRNA antisense strand taught by Shemi as the portion of the guide RNA that acts by complementary binding of the target gene because Shemi teaches that an siRNA comprising this complementary portion (SEQ ID NO: 38) is both stable and active, demonstrating this portion of KRAS is a suitable target region for binding of RNAs.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638