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 .
DETAILED ACTION
Applicant’s amendments and remarks filed on August 20, 2025 are acknowledged. Claims 1-6 and 8 have been canceled. Claims 7 and 12 were amended. Claims 7 and 9-12 are pending and are examined on the merits herein.
Priority
This application claims priority to PCT/IL2020/050619 filed on June 3, 2020 which claims priority to U.S. provisional application 62/856,332, filed on June 3, 2019.
Withdrawn Objections
In view of Applicant’s amendments and response, the objections to the drawings are withdrawn.
In view of Applicant’s amendments and response, the nucleotide sequence disclosure deficiency is withdrawn.
In view of Applicant’s amendments and response, the objection to claims 7 and 12 is withdrawn. Applicant’s remarks indicate that claim 7 has been amended such that the “bullet points” are presented as “(a)” and “(b)” instead of “a.” and “b.” as previously recited. Although claim 7 now recites “(a)” and “(b)” instead of “a.” and “b.” thus overcoming the objection, it is noted that the claim does not contain any markings to indicate the amendments.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(b) rejections are withdrawn.
Drawings
The drawings were received on August 20, 2025.
The drawings are objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”. In the current case, the view numbers for all of the figures 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.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0104] was amended on August 20, 2025 such that there is a period after the word “small”. It is unclear why Applicant amended paragraph [0104]. Nonetheless, there should not be a period after the word “small”.
Paragraph [0106] is missing a period at the end of the paragraph.
Appropriate correction is required.
Response to Arguments
Applicant's arguments filed August 20, 2025 have been fully considered but they are not persuasive.
Applicant indicates that the specification has been amended as suggested by the Examiner; however, Applicant did not address the objection in reference to paragraph [0106].
Claim Objections
Claim 9 is objected to because of the following informality:
Claim 9 recites “said miR-193a-5a” and should recite “said miR-193a-5p” (emphasis added).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7 and 9-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is
sufficient evidence to support a determination that a disclosure does not satisfy the
enablement requirement and whether any necessary experimentation is "undue".
These factors include, but are not limited to: (A) The breadth of the claims; (B) The
nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary
skill; (E) The level of predictability in the art; (F) The amount of direction provided by the
inventor; (G) The existence of working examples; and (H) The quantity of
experimentation needed to make or use the invention based on the content of the
disclosure.
Breadth of claims and nature of the invention:
Claims 7 and 9-11 are drawn to a pharmaceutical composition and a method of treating or ameliorating a subject afflicted with head and neck squamous cell carcinoma of a hypopharynx squamous cell carcinoma type comprising determining the level of miR-193a-5p in a cancer tissue sample and administering a therapeutically effective amount of miR-193a-5p to a subject determined as having a downregulated expression level of said miR-193a-5p in said cancer tissue sample compared to a control normal adjacent tissue sample.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
At the time of the invention, there was considerable unpredictability in translating the results obtained in cell culture and xenograft models of cancer to treatment of actual disease, as discussed further below.
Mak et al. (Am J Transl Res 2014) taught that although animal models play a large role in the evaluation of efficacy and safety of new cancer interventions, genetic, molecular, and physiological limitations often hinder their utility. Despite successful pre-clinical testing, 85% of early clinical trials for novel drugs fail; of those that survive through to phase III, only half become approved for clinical use. Thus the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Furthermore, fewer than one in five cancer clinical trials find their way to the peer-reviewed literature, generally due to negative findings. See abstract and paragraph bridging columns on page 114.
Morgan (Molecular Therapy 2012) taught that differences in the biology of mice and humans provide restrictions on the utility of tumor xenograft models, e.g. mice are significantly smaller, have a much higher metabolic rate, are inbred, and have a short life span. In addition, whereas most human tumors take years to grow, tumor xenografts are transplantable tumors designed to grow to treatment size in weeks, not years, and so are not representative of the typical disease. Morgan indicated that the tumor line chosen to be transplanted is probably one of the most significant reasons for failure of xenotransplantation data to be translated to human clinical results. Monogenic human tumor cell lines are almost exclusively used, and it is now well established that tumor cell lines can bear little resemblance to primary cancers. For example, in glioblastoma, detailed analysis of genomic stability and gene expression changes revealed considerable differences when primary tumors were compared with established cell lines. See paragraph bridging pages 882 and 883, and first paragraph on page 883.
Similarly, Day et al. (Cell 2015) taught that cancer is typified by enormous disease complexities that challenge clinical success. Such challenges include tumor microenvironment complexities, intra- and inter-tumor molecular and biological heterogeneity, systemic and tumoral immune and metabolic response heterogeneity, and the ability of drug-resistant stem-like cancer-initiating cells to repopulate treated cancers. See first two sentences on page 39. Day indicated that cell line-derived mouse xenograft models are easily established in a wide variety of laboratory settings and have been successfully used to identify an abundance of cytotoxic drugs leading to chemotherapy treatments. However, successful development of effective drugs identified in such models is actually rare, as evidenced by low FDA approval rates of drugs emerging from such studies. The fact that most cancer therapeutics fail in clinical phase II and Ill efficacy assessment indicates that these models inadequately address complex challenges to successful treatment, such as cancer heterogeneity and drug resistance. Consequently, cell line-derived mouse xenograft models cannot be used to optimize a multitude of variables known to influence therapeutic outcomes such as drug delivery methods and variable dosing. As a result, their value lies in identifying non-targeted cytotoxic agents, primary assessment of drug toxicity, analyzing resistance mechanisms, and in triaging potentially effective targeted therapies for evaluation in more representative models. See paragraphs bridging columns on page 41. Therefore, while xenograft models provide a first step in evaluating potential drugs, they do not provide evidence that is reliably predictive of therapeutic success.
Horvath et al. (Nature Reviews Drug Discovery 2016) reviewed the state of the art of cell-based disease models and indicated that "[t]he common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery" (see abstract). Horvath indicated that, in the field of cancer, poor clinical translation can largely be attributed to the failure of disease models to recapitulate key pathophysiological features of the human disease, including complex inter- and intratumor heterogeneity, poor drug penetration through tissue, host-stroma-tumor cell interactions, and the cancer stem cell niche, all of which may have profound effects on the therapeutic response in vivo (page 751, center column). Most cell-based assay screens use transformed or immortalized cell lines that have been cultured for many generations, resulting in a substantial drift in their genetic, epigenetic and physiological characteristics, which means they are not a good model of primary tissue cells. The gross genetic and epigenetic abnormalities (characterized by multiple genetic rearrangements and amplified gene copy numbers) associated with long-term culture confound pharmacogenomic and functional genomic studies. Genetic adaptation resulting from long-term in vitro cultures also contributes to heterogeneity in cultures of the same cell line between passages, batches and laboratories (page 752, second paragraph). In vitro cell culture conditions poorly recapitulate the distinct microenvironments that define normal and diseased tissue phenotypes. This has a profound impact on cell metabolism, reactive oxygen species (ROS) production, mitochondrial functions and, ultimately, the differentiation and function of cells. Conventional tissue culture systems do not readily permit the formation of short-range gradients of nutrients, hormones and oxygen that are often experienced by cells, depending on the distance to the nearest blood vessel (paragraph bridging pages 752 and 753).
Given the state of the art in the use of cancer cell lines and cell line-derived tumor xenograft models, one of skill would recognize that the data provided in such models is usually not predictive of success in treatment, but instead only provides a first step in the evaluation/development process for new drugs.
Amount of direction provided by the inventor and existence of working
examples:
Although the working examples do not explicitly disclose whether miR-193a-5p or miR-193a-3p or both were used, the brief description of the figures section discloses that Figures 2 and 3 are vertical bar graphs of cell viability following miR-193a-5p plasmid transfection. Working examples 1 and 2 show that FaDu cells were highly sensitive to miR-193a transfection where a reduction in cell viability was observed. In working example 5, a xenograft animal model was generated via injection of FaDu cells in mice. The results showed that treatment with miR-193a significantly reduced the weight and tumor volume in mice when compared to the control group. In working example 6, the expression levels of miR-193a in FaDu cells were tested by treating squamous cancer cells with 5-aza-2’-deoxycytidine or transducing squamous cancer cells with AD-miR-193a. The results showed that treatment with 5-aza increased expression levels by 132 fold; whereas, transduction with AD-miR-193a increased expression levels by 4,817 fold. Lastly, HNSCC tissues and normal adjacent tissues were collected to evaluate the expression patterns of miR-193a in the tissues. In this example, miR-193a was consistently downregulated in cancer tissues compared to normal adjacent tissues. Specifically, three out of seven of the cancer tissues did not express miR-193. However, it is unclear from the specification what exactly was measured, miR-193a-5p, miR-193a-3p, or both (i.e. full length miR-193a). The specification indicates that TaqMan primers and probes for miR-193a were used for detection [0105]. These primers and probes are generally specific for -3p and -5p species, and it is unclear which was measured in this case. In this regard, it is noteworthy that Saleh et al. (WO 2017/156015) demonstrated that miRNA-193-3p was downregulated in HNSCC cells whereas miR-193-5p was upregulated. See Table 3 at pages 32-33. Thus it is unclear that the results obtained in the animal model would be broadly applicable to all HNSCC tumors.
Quantity of experimentation:
In view of the state and level of predictability in the art and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Response to Arguments
Applicant's arguments filed August 20, 2025 have been fully considered but they are not persuasive.
Applicant’s remarks reproduced below indicates that claim 1 was amended; however, it appears that this is a typographical error as claim 1 is canceled. Applicant may have intended for the remarks to indicate that claim 7 was amended because in the following paragraph Applicant asserts that the amendment to claim 7 overcomes the enablement rejection.
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Applicant asserts that amending the claim to recite “determining the level of micro-RNA (miR)-193a-5p” and administering “miR-193a-5p” addresses the concern about whether miR-193a-3p or miR-193a-5p or both (miR-193a-3p and miR-193a-5p) are measured and/or administered. Applicant further asserts that the amendment aligns with the working examples which demonstrate efficacy of miR-193a-5p treatment. As discussed in the original 35 U.S.C. 112(a) rejection, it is unclear from the specification what exactly was measured, miR-193a-5p, miR-193a-3p, or both (i.e. full length miR-193a). The brief description of the figures section discloses that Figures 2 and 3 are vertical bar graphs of cell viability following miR-193a-5p plasmid transfection; however, the working examples do not explicitly disclose whether miR-193a-5p or miR-193a-3p or both were used.
Applicant also asserts that claim 7 has been amended to specify comparison “to a normal adjacent tissue sample obtained or derived from said subject” as the control. Applicant further asserts that the amendment is supported by Example 7 which demonstrates downregulation of miR-193a-5p in cancer tissues compared specifically to normal adjacent tissues. Paragraph [0116] of the specification discloses that expression patterns of miR-193a in patient’s tissues were assessed by collecting 7 HNSCC tissues and 7 normal adjacent tissues. miR-193a levels were determined using quantitative RT-PCR and the results showed that miR-193a was consistently downregulated in cancer tissues compared to normal adjacent tissues. Further, three out of seven of the cancer tissues did not express miR-193 at all and the expression levels were zero. However, the specification does not explicitly disclose whether miR-193a-5p, miR-193a-3p, or both miR-193a-5p and miR-193a-3p were measured.
Applicant asserts that the scope of claim 7 is limited to the HNSCC being of “hypopharynx squamous cell carcinoma” type and the working examples demonstrate clear efficacy in FaDu cells which are specifically derived from and used as a model for hypopharynx squamous cell carcinoma. Applicant further asserts that the working examples show reduced cell viability in FaDu hypopharynx squamous cell carcinoma cells treated with miR-193a-5p, reduced tumor growth in xenograft models using FaDu cells, and consistent downregulation of miR-193a-5p in patient cancer tissues versus normal adjacent tissue. However, as discussed in the original 35 U.S.C. 112(a) rejection, it is unclear from the specification what exactly was measured, miR-193a-5p, miR-193a-3p, or both (i.e. full length miR-193a). Furthermore, given the state of the art in the use of cancer cell lines and cell line-derived tumor xenograft models, one of skill would recognize that the data provided in such models is usually not predictive of success in treatment, but instead only provides a first step in the evaluation/development process for new drugs. Therefore, the Examiner is maintaining the 35 U.S.C. 112(a) enablement rejection.
New Matter
Claims 7 and 9-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the amendment filed 8/20/2025, claim 7 part (a) was amended to recite “determining the level of micro RNA (miR)-193a-5p in a cancer tissue sample obtained or derived from said subject”. Claim 7 limits determining the level of miR-193a to miR-193a-5p.
The specification provides support for determining the expression levels of a miR-193a in a sample obtained or derived from the subject [064]. The specification does not provide support for determining the level of micro RNA (miR)-193a-5p.
The specification discloses “miR-193a-5p plasmid transfection” at paragraphs [016] and [017]. Paragraph [038] discloses that an miR-193a-5p sequence is at most 70%, 80%, 90% or 99% identical to SEQ ID NO: 1. Example 5 discloses the effect of overexpression of miR-193a-5p based on injection of cells transfected with plasmid. The specification does not provide literal or inherent support for determining a level of miR-193a-5p in a cancer tissue as claimed.
The original specification, drawings and claims were thoroughly reviewed and no support could be found for the amendment. Accordingly, the amendment is a departure from the disclosure as originally filed, and Applicant has not pointed to a specific portion of the original disclosure that provides support.
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 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, natural phenomenon, or an abstract idea) without significantly more. Claim 12 is drawn to a pharmaceutical composition comprising an effective amount of an expression vector comprising a promoter operably linked to a polynucleotide having a miR-193a precursor sequence and a pharmaceutically acceptable carrier, which is a nature-based product. As outlined below, this judicial exception is not integrated into a practical application, and does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes – Claim 12
Step 1 – Is the claim to a Process, Machine, Manufacture or Composition of Matter? YES.
Claim 12 is directed to a pharmaceutical composition and thus is directed to a statutory category.
Step 2A, Prong One – Does the claim recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES.
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. MPEP 2106.04(c) outlines the markedly different characteristics analysis.
Claim 12 is drawn to a pharmaceutical composition comprising an effective amount of an expression vector comprising a promoter operably linked to a polynucleotide having a miR-193a precursor sequence and a pharmaceutically acceptable carrier. The instant specification discloses on page 7, paragraph [048] that the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. Vectors include, but are not limited to, nucleic acid molecules that are single-stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, no free ends; nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. Although the specification provides a definition for the term “vector”, there is no limiting definition for the term “vector”.
GenBank NCBI Reference Sequence: NC_000017.11 teaches that the human genomic sequence contains the precursor RNA for miR-193a. Further, as evidenced by Lee et al. (The EMBO Journal 2002), Lee et al. teaches that several miRNA genes exist as clusters of 2-7 genes with intervals as short as a few nucleotides long wherein a single promoter drives transcription of the clustered miRNA genes [page 4663, right column, last paragraph]. Thus the sequence encoding the precursor RNA for miR-193a in the chromosome must have a promoter. Given the broadest reasonable interpretation, “expression vector” encompasses a naturally occurring chromosome present in a naturally occurring cell. Furthermore the recitation of “pharmaceutically acceptable carrier” does not provide a markedly different structure relative to the naturally occurring cell comprising the chromosome, where the cell contains naturally occurring salts and buffer compounds, for example. As a whole, the claim is directed to a composition that is not markedly different than its closest nature-based counterpart.
Step 2A, Prong Two – Does the Claim recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
In the instant case, claim 12 does not recite any elements in addition to the judicial exception (i.e., natural product) that would integrate the natural product into a practical application.
Step 2B – Does the Claim recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05).
As stated above, claim 12 does not recite any elements in addition to the judicial exception (i.e., natural product). There are no additional elements to amount to significantly more than the judicial exception.
Thus, claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more.
Response to Arguments
Applicant's arguments filed August 20, 2025 have been fully considered but they are not persuasive.
Applicant asserts that an expression vector including a promoter operably linked to a polynucleotide having a miR-193a precursor sequence and a pharmaceutically acceptable carrier is not a “naturally occurring” product. Paragraph [048] of the specification discloses that vectors include, but are not limited to, nucleic acid molecules that are single-stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, no free ends; nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. Although the specification provides a definition for the term “vector”, there is no limiting definition for the term “vector” and thus still reads on a product of nature (e.g., a chromosome that contains the endogenous locus which would contain a promoter operably linked to a polynucleotide having a miR-193a precursor sequence).
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.
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 12 is rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (US 9,315,809) in view of Croce (US 2010/0249213). This is a new rejection, necessitated by the amendment to the claims in the reply filed on 8/20/2025.
Regarding claim 12, Shi et al. teaches a pharmaceutical composition comprising one or more therapeutic agents which target one or more miRNA molecules that are differentially expressed in cancer stem cells [column 1, Summary] and a pharmaceutically acceptable carrier [column 7, last paragraph]. Shi et al. teaches that therapeutic agents include agents that increase the level of specific miRNA molecules such as an miRNA expression vector that causes a cell to overexpress a downregulated miRNA molecule [column 7, second full paragraph].
However, Shi et al. does not teach an expression vector comprising a promoter operably linked to a polynucleotide having a miR-193a precursor sequence.
Croce teaches that a plasmid expressing the miRs comprises a sequence encoding a miR precursor RNA under the control of the CMV intermediate-early promoter [0111]. Croce teaches that the miRs can also be expressed from recombinant viral vectors [0112] wherein the recombinant viral vectors comprise sequences encoding the miRs and any suitable promoter for expressing the RNA sequences such as the U6 or H1 RNA pol III promoter sequences or the cytomegalovirus promoters [0113]. Paragraph [0219] on page 18 lists hsa-miR-193a-5p (SEQ ID NO: 91; accession number MIMAT0004614) as reproduced below.
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It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the vector of Shi et al. with the expression vector of Croce because Croce teaches vectors comprising a sequence encoding a miR precursor RNA such as hsa-miR-193a-5p. One of skill in the art would have made such a substitution in order to achieve the predictable result of increasing expression in cells.
Conclusion
No claims are allowed.
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 CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637