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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a PCT application filed as PCT/EP2022/072484 on 08/10/2022.
Should applicant desire to obtain the benefit of foreign priority of the foreign application filed as Italy 102021000021779 on 08/11/2021 under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
All claims are given the priority date of 08/10/2022.
Application Status
Receipt is acknowledged of amendment, filed 02/05/2024. Claims 1-9 are currently pending.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 02/05/2024 have been received and all references have been considered.
Drawings
The drawings are objected to for the following reasons: 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view numbers for Figures 1-3 are preceded by the word "Figure" instead of the abbreviation "FIG.".
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.
Claim Objections
Claims 2 and 9 are objected to because of the following informalities:
Claims 2 and 9 recites the term “tumour” in the second line of both of the claims which is misspelled and should recite “tumor”.
Appropriate correction is required.
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.
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 1-9 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 is vague and indefinite in that the metes and bounds of the phrase “A method of treating KRASG12D-expressing tumor, with a therapeutic composition…” are unclear. The phrase is unclear in that the term “with” does not positively recite the physical action occurring within the steps of the method being claimed. It would be remedial to replace the phrase “A method of treating KRASG12D-expressing tumor, with a therapeutic composition…” with “A method of treating KRASG12D-expressing tumor, comprising administering a therapeutic composition…”.
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.
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.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over in Shemi et al (WO 2020/234868 A1) view of Gresele et al (WO 2014/118817 A2).
Regarding claim 1, Shemi teaches Hepal-6 cells were transfected with three siRNAs of interest (targeting KRAS WT, KRAS G12D, and F-Luc) (Page 30, Lines 19-20). Shemi teaches the use of siRNA targeting KRASG12D which has a sense strand set forth herein as SEQ ID NO: 10 (5'-GUUGGAGCUGAUGGCGUAGTT-3'), and an antisense strand set forth herein as SEQ ID NO: 11 (5'-CUACGCCAUCAGCUCCAACTT-3') (Page 26, Lines 1-5) wherein SEQ ID NO: 10 is 100% identical to instant SEQ ID NO: 1 and SEQ ID NO: 11 is 100% identical to instant SEQ ID NO: 2 (Appendices I and II, respectively). Shemi teaches siG12D can effectively target expression of the assayed KRAS mutant alleles to varying extents from 63.8% (G12S) to 95.8% (Gl2D) (Page 30, Lines 25-26 and Page 31, Table 2).
Shemi does not teach the siRNA is comprised within a platelet.
Gresele teaches siRNAs usable against common oncogenes and transfectable in mature platelets specifically a KRAS oncogene which permits to obtain high percentages of transfection (Page 1, lines 5-16; Page 10, lines 13-24 and Page 12, Table 1). Gresele teaches the practice used in transfusion medicine of separating platelets and plasma, collect platelets, transfect them, resuspend them into plasma and reinfusing them (Page 8, Lines 15-20).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Shemi to include the platelets comprising a siRNA for targeting KRAS mRNA in cancer as taught by Gresele because Shemi teaches it is within the ordinary skill in the art to use siRNA targeting KRASG12D which has a sense strand set forth herein as SEQ ID NO: 10 (5'-GUUGGAGCUGAUGGCGUAGTT-3'), and an antisense strand set forth herein as SEQ ID NO: 11 (5'-CUACGCCAUCAGCUCCAACTT-3') to effectively target the mutated KRAS mRNA for treatment and Gresele teaches siRNAs usable against common oncogenes and transfectable in mature platelets specifically a mutated KRAS oncogene which permits to obtain high percentages of transfection.
One would have been motivated to make such a modification in order to receive the expected benefit of high percentages of transfection of mature platelets comprising siRNAs for targeting the mutated KRAS oncogene as taught by Gresele.
Regarding claims 2, 3 and 9, Shemi teaches the KRASG12D mutation is the most abundant mutation in pancreatic ductal adenocarcinoma (PDAC) patients (Page 29, Lines 1-2). Shemi teaches transfection of MIA PaCa-2 cells in triplicate with siRNA directed against the
KRASG12D gene (siG12D) (SEQ ID NOs 10 and 11) and found the maximal decrease of 60% in KRAS transcript level was achieved with a concentration of 1 nM siRNA (Page 27, lines 20-30).
Regarding claims 4 and 5, Shemi teaches the siRNA targeting KRASG12D has a sense strand set forth herein as SEQ ID NO: 10 (5'-GUUGGAGCUGAUGGCGUAGTT-3'), and an antisense strand set forth herein as SEQ ID NO: 11 (5'-CUACGCCAUCAGCUCCAACTT-3') (Page 26, Lines 1-5) wherein SEQ ID NO: 10 is 100% identical to instant SEQ ID NO: 1 and SEQ ID NO: 11 is 100% identical to instant SEQ ID NO: 2 (Appendices I and II, respectively).
Regarding claims 6-8, Shemi teaches Hepal-6 cells were transfected with three siRNAs of interest (targeting KRAS WT, KRAS G12D, and F-Luc) (Page 30, Lines 19-20). Shemi teaches the siRNA targeting KRASG12D has a sense strand set forth herein as SEQ ID NO: 10 (5'-GUUGGAGCUGAUGGCGUAGTT-3'), and an antisense strand set forth herein as SEQ ID NO: 11 (5'-CUACGCCAUCAGCUCCAACTT-3') (Page 26, Lines 1-5) wherein SEQ ID NO: 10 is 100% identical to instant SEQ ID NO: 1 and SEQ ID NO: 11 is 100% identical to instant SEQ ID NO: 2 (Appendices I and II, respectively). Shemi teaches siG12D can effectively target expression of the assayed KRAS mutant alleles to varying extents from 63.8% (G12S) to 95.8% (Gl2D) (Page 30, Lines 25-26 and Page 31, Table 2).
Shemi does not teach the siRNA is comprised within a platelet.
Gresele teaches siRNAs usable against common oncogenes and transfectable in mature platelets specifically a KRAS oncogene (Page 10, lines 13-24 and Page 12, Table 1). Gresele teaches the practice used in transfusion medicine of separating platelets and plasma, collect platelets, transfect them, resuspend them into plasma and reinfusing them (Page 8, Lines 15-20). Gresele teaches the following steps: venous peripheral blood was harvested and collected in tubes containing 3.8% of sodium citrate as anticoagulant (1:9 citrate-blood v/v), the sample was centrifuged at 120 g for 10 minutes in order to obtain PRP (platelet-rich plasma), the isolation of plasma platelets, the transfection medium is prepared, inserting 32.4 microliter of
absolute ethyl alcohol, 120 microliters of a polyethylammine solution (0.1% in water) and 47.6 microliters of RPM1 1640 medium, after waiting for 5 minutes, the siRNA of interest was added to the above-mentioned mixture of the siRNA of interest to the maximum concentration of 200 nM and after 15 minutes of incubation at room temperature, the solution was transferred into the well in which 1 ml of platelet suspension had previously been placed (Page 29-30, Example 5). Gresele teaches that following steps 1-5, platelet microparticles containing the siRNA
previously transfected into platelets are obtained by incubating platelet suspension, centrifuging platelets at 3,000 g for 10 minutes, recovering supernatant and further centrifuging it at 12,000
g for 1 o minutes in order to remove possible remained platelets, centrifuging supernatant at 160,000 g for 1 hour at 4°C and removing supernatant and resuspending microparticle pellet in 1 milliliter of RPMI 1640 (Page 30, Lines 16-31).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Shemi to include the mature platelets comprising a siRNA for targeting KRAS mRNA, specifically the steps for the process of harvesting, transfecting and transducing the mature platelets for treatment as taught by Gresele because Shemi teaches it is within the ordinary skill in the art to use siRNA targeting KRASG12D which has a sense strand set forth herein as SEQ ID NO: 10 (5'-GUUGGAGCUGAUGGCGUAGTT-3'), and an antisense strand set forth herein as SEQ ID NO: 11 (5'-CUACGCCAUCAGCUCCAACTT-3') to effectively target the mutated KRAS mRNA for treatment and Gresele teaches siRNAs usable against common oncogenes and transfectable in mature platelets specifically a mutated KRAS oncogene which permits to obtain high percentages of transfection.
One would have been motivated to make such a modification in order to receive the expected benefit of high percentages of transfection of mature platelets comprising siRNAs for targeting the mutated KRAS oncogene as taught by Gresele.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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