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 .
Claims 1-17 are pending in the application.
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 7-9, 13-15 and 17 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.
Regarding claims 7 and 8, they depend on claim 4, which is directed to administering the agent of ii), an agent other than the miRNA-541-3P that inhibits the function or expression of ZNF101. The recitation of “comprising administering the agent of iii) wherein the agent comprises an RNAi agent that inhibits the expression of the CASZ1” renders claim 7 indefinite because it is unclear whether it means ii) and iii) are individually administered, or both administered.
Regarding claim 9, it depends on claim 4, which is directed to administering the agent of ii), an agent other than the miRNA-541-3P that inhibits the function or expression of ZNF101. The recitation of “wherein the miRN-541-3P or the modified version thereof or the agent is administered to liver cells within the individual” renders claim 9 indefinite because it is unclear whether it means i) and ii) are individually administered, or both administered.
Claims 13-15 and 17 are rejected for same reason because they depend on claim 9 but does not remedy the indefiniteness.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1, 7, 11 and 16 is/are rejected under 35 U.S.C. 102(a1) as being anticipated by Ji et al (Genomics and Informatics, 2012, Vol.10, no.1, pages 40-43).
Claim 1 is drawn to a method that comprises a single step of administering i) miRNA-541-3P; or ii) an agent other than miRNA-541-3P that inhibits the function or expression of ZNF101; or iii) an agent other than miRNA541-3P that inhibits the function or expression of CASZ1; or iv) a combination thereof.
Ji et al. teach a method of administering siRNA of CASZ1 to a mice (page 42, 2nd col., 3rd paragraph). Therefore, the claimed invention of claims 1 and 7 is anticipated by the teaching of Ji et al.
Regarding claims 11 and 16, the wherein clause is not given patentable weight because it simply recites the intended result of a process step positively recited.
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.
Claim(s) 1, 2 and 9-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lv et al (Molecular Medicine Reports, 2021, Vol.23, no. 312, pages 1-8).
Lv teaches bioinformatic analysis predicted that STIM1, a potent target for the prevention and treatment of atherosclerosis, is a target of miR-541-3P (abstract). Lv teaches Ox-LDL treatment downregulates the expression level of miR-541-3P and upregulates STIM1 expression levels (page 3, 2nd col., last paragraph), and overexpression of miR-541-3P inhibits the viability and migration of VSMC (page 4, Figure 2 and legend). Lv teaches that knockdown of miR-541-3P promotes ox-LDL-induced VSMC viability and migration by targeting STIM1 (page 6, 1st col., 2nd paragraph, Figure 4 and legend). Lv also teaches that one of the main limitation of study is miR-541-3P/STIM1 axis was only investigated in vitro for the atherosclerosis model, thus in vivo experiments should be performed in future studies to determine the role of the miR-541-3P/STIM1 axis in the pathogenesis of atherosclerosis (page 6-7, bridging paragraph). Lv teaches the finding of the study suggested that miR-541-3P may efficiently suppress ox-LDL-induced increase in VSMS viability and migration (page 7, 1st col., last paragraph).
The only difference between the claimed invention of claim 1 and the teaching from Lv is that the miR-541-3P is administered in an in vitro cell model of atherosclerosis rather than in vivo in a subject.
It would have been obvious to an ordinary skilled in the art reading Lv to recognize that the next step would be to test miR-541-3P in an in vivo setting to verify whether the observed suppression of ox-LDL-induced increase in VSMS viability and migration also occurs in vivo because Lv teaches in fact suggested such experiment is needed. Therefore, the claimed invention of claim 1 and claim 2 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 9, this claim is interpreted as administering the miRNA-541-3P individually. It would have been obvious to an ordinary skilled in the art that liver is responsible for regulating LDL metabolism and atherosclerosis risk by eliminating ox-LDL, which is highly atherogenic, triggering inflammation and foam cell formation in arterial walls. It would have been obvious to administer miRNA-541-3P to the liver in an in vivo model of atherosclerosis to further the finding from in vitro data obtained by Lv. Therefore, the claimed invention of claim 9 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claims 10, 12, 13, 15, it would have been obvious from the teaching from Lv that in vivo model of treatment or prophylaxis atherosclerosis, reduction of LDL or increase of HDL needs to be tested for observed effect of miRNA-541-3P to determine its role in the pathogenesis of atherosclerosis. Such model would meet the limitation of a subject in need of treatment or prophylaxis atherosclerosis, reduction of LDL or increase of HDL.
Regarding claims 11, 14, 16 and 17, the wherein clause is not given patentable weight because it simply recites the intended result of a process step positively recited. As such, the claims would have obvious in view of teaching from Lv for same reason as applied to claims 1 and 9 set forth above.
Claim(s) 1, 4 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Balashanmugam et al (Biomolecules, 2020, Vol.10, no.35, pages 1-22).
Balashanmugam teaches coronary artery disease (CAD) is a major cause of end stage cardiac disease (abstract). Balashanmugam teaches target gene-miRNA regulatory network were constructed and analyzed, and differentially expressed genes were identified (abstract). Balashanmugam teaches in target gene-miRNA network, upregulated genes includes ZNF101, which is predicted as novel prognostic or diagnostic biomarkers and new therapeutic target in CAD (page 15, 1st paragraph).
However, Balashanmugam does not specially teach inhibiting ZNF101 in an individual.
It would have been obvious to an ordinary skilled in the art that ZNF101 is a predicted prognostic or diagnostic marker and therapeutic target in CAD according to the teaching from Balashanmugam. The ordinary skilled in the art would thus be motivated to inhibit the expression and/or function of this gene in an individual to further validate this hypothesis. Using miRNA targeting ZNF101 would have been a common practice in the art for inhibiting the expression of ZNF101. Therefore, the claimed invention of claims 1, 4 and 5 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 6 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ji and Balashanmugam, in view of Shalem et al (Science, 2014, Vol. 343, page 84-87).
The teaching from Ji and Balashanmugam has been discussed above.
However, neither reference teaches reducing the expression of CASZ1 or ZN101 using CRISPR system.
Shalem teaches RNAi is limited to transcripts, whereas Cas9:sgRNA can target elements across the entire genome, the efficiency of complete knockout is also high (page 87, 1st and 2nd col., bridging paragraph).
It would have been obvious to an ordinary skilled in the art that using CRISPR system to knockout CASZ1 and ZNF101 would have been an alternative method to inhibit CASZ1 and ZNF101 based the knowledge in prior art. The ordinary skilled in the art would have been motivated to use CRISPR system to accomplish expression inhibition of said genes, especially in situation when complete knockout is required according to the teaching from Shalem. Therefore, the claimed invention of claims 6 and 8 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 1 and 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lv, in view of Foster (Molecular Therapy, 2018, vol.26, No.3, pages 708-717).
The teaching from Lv has been discussed above. However, Lv does not teach miR-541-3P is modified by ribosugar, ribonucleotide, internucleoside linkage or a combination thereof.
Foster teaches modification of siRNA chemistry for in vivo therapy including 2-deoxy-2-fluoro and 2-methyl ribosugar increases both stability and efficacy (page 714, 1st col., 1st and 3rd paragraph).
It would have been obvious to an ordinary skilled in the art that modification to RNAi molecules with 2-deoxy-2-fluoro and 2-methyl ribosugar specific position for in vivo delivery increases RNAi stability and efficacy based on teaching from Foster. The ordinary skilled in the art would have been motivated to do so because Foster has demonstrated the success of such modification. The ordinary skilled in the art would have reasonable expectation of success to make such modification to miRNA-541-3P following combined teaching from Lv and Foster. Therefore, the claimed invention of claims 1 and 3 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637
