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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/465,425, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicates a lack of support for Formula I in the prior-filed application, Application No. 63/465,425. Thus a date of 05/10/2024 was used for priority.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
The drawings are objected to because Fig. 12D and Fig 37E-F have poor image resolution 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 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 1-20 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 14 recites the limitation "the method of claim 8" in in the first line of claim 14. There is insufficient antecedent basis for this limitation in the claim. The scope of the claim is indefinite because claim 8 is a compound claim and not a method claim and thus there is no method to refer to in claim 8.
Claims 1-20 are indefinite in scope because the scope of the variables of X1 does not allow for a double bond between X1 and X2, which is shown in Formula I and required in claims 6-7 and 14-15. Thus it is unclear what compounds are included in claim 1-20 since it is unclear if a double bond is allowed between X1 and X2. For the purposes of examination the claims were interpreted with the broadest reasonable interpretation to include compounds wherein there is a double bond and X1 can be CH.
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) 1-3, 5-11, 13, 15-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou (Zhou et al., Nature-Inspired Chemical Probes for in-cell Labeling of Lipidized RNA and Identification of New Regulatory Enzymes, bioRxiv 2022, 1-27, IDS).
The reference Zhou teaches geranyl pyrophosphate including Ge6 and Ge5 (Fig. 2, page 4) shown below which are both compounds of formula I. Ge5 is a compound of formula I, wherein X1=CH, X2=C(CH3), m=1, X3=C(CH3), n=1, Y=N3. Ge6 is a compound of formula I, wherein X1=C(=O), X2=NH, m=0, X3=CH2, n=1, Y=N3. For the purposes of examination the claims were interpreted with the broadest reasonable interpretation to include compounds wherein there is a double bond between X1 and X2 and X1 can be CH because otherwise no variables of X1 allow a double bond as show in Formula I.
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This anticipates claims 1-3, 5-7
The reference Zhou teaches “Fig. 5. Fluorescence labeling of E. coli. tRNA-5S in 293T cells. (A) Overall illustrations of the fluorescence labeling g of prenylated RNA in vivo. (B) Top panel: Transfection of fusion plasmid SelU-EGFP with transcript 5S in the e presence of pyrophosphate Ge1 (1 mM), followed by the treatment of PTAD-DBCO-Cy5 probe (50 µM). Bottom m panel: Transfection of fusion plasmid SelU-EGFP without transcript 5S in the presence of pyrophosphate Ge1 (1 1 mM) and PTAD-DBCO-Cy5 treatment. Green fluorescence (left), Cy5 fluorescence (second), merged (third), and d DAPI fluorescence (nuclear staining; right). (C) Transfection of fusion plasmid SelU-pCMV-Myc-EGFP-5s in the presence of pyrophosphate Ge6, followed by the treatment of DBCO-Cy5 probe (5 µM) via click reaction. Imaging g of HEK293T cells harboring the SelU-pCMV-Myc-EGFP-5s plasmid (top line, both red and green fluorescence), SelU-- pCMV-Myc-EGFP plasmid (second line, only green fluorescence in the absence of transcript 5s); pCMV-Myc-EGFP P (bottom line, no green/red fluorescence in the absence of SelU). Green fluorescence (left), Cy5 fluorescence e (second), merged (third), and DAPI fluorescence (nuclear staining; right). DAPI = 4’,6-dianidino-2-phenylindole . Scale bar: 20 µm”(Fig. 5, page 9). This anticipates claim 8.
The reference Zhou also teaches “In conclusion, we report two chemical labeling strategies for the lipid-modified RNAs by taking g advantage of the natural SelU-mediated tRNA geranylation process and the special chemical reactivity of the prenyl-groups. We synthesized a series of ‘clickable’ geranyl pyrophosphate analogs and identified d two candidates Ge5 and Ge6 that are suitable for indirect in-cell RNA labeling through a two-step process, azidation-and-click tagging of fluorescent dye, namely ACT-Flu process. Both fluorescent t microscopy and molecular simulation studies confirmed that the two ligands could serve as ideal SelU U substrates in the tRNA geranylation process, representing a new toolset for detecting and monitoring the 2-thiouridine residue, which is an important biomarker of bacteria infections and cancers”(conclusion). The reference Zhou teaches “RNA modifications play pivotal roles in numerous cellular processes and human diseases. In addition to well-studied methyl-based modifications, hydrophobic prenyl-modifications have also been found in many RNA species. Here we report two chemical labeling strategies for tagging lipid-modified RNAs by taking advantage of a natural SelU-mediated tRNA geranylation process and the special reactivity of prenyl-groups. We synthesized a series of ‘clickable’ geranyl-pyrophosphate analogs and identified two candidates for indirect RNA labeling using a two-step process, azidation-and-click-tagging of fluorescent dyes, namely ACT-Flu. We also developed a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag) method based on the Ene-ligation of prenyl-groups. Both methods have been successfully applied to in-cell RNA labeling and the identification of new proteins associated with the geranylation process through proteomic and bioinformatic studies. These biochemical toolsets enable further in vivo applications to study prenylation pathways and monitor their status in both healthy and diseased cells”(abstract) and “Biochemical tools that enable the labeling of lipidized RNAs will allow for the analysis of hydrophobic modifications during normal and diseased biological processes. In addition, incorporating similar lipid analogs into tRNAs will provide a useful platform for the development of new molecular tools to label, detect, and isolate specific tRNAs 33-34 for in vitro, in situ and in vivo applicaitons. To provide a toolset to fill in these knowledge gaps, we engineered two new methods, including an indirect two-step procedure called azidation-and-click tagging of fluorescent dye (ACT-Flu), and a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag). These tools and methods can be used to analyze and exploit lipid modified RNAs, as well as to identify their interacting enzymes in living cells by taking advantage of the unique chemical reactivity 35-37 of the prenyl groups (overview in Fig. 1)”(page 3). This anticipates claims 9-11, 13 and 15-20.
Claim(s) 1-3 and 6-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN (STN, CAS 856244-51-4 REGISTRY, Entered STN: 20 Jul 2005).
The reference STN teaches the following compound, wherein X1=CH, X2=C(CH3), m=1, X3=C(CH3), n=1, Y=N3. For the purposes of examination the claims were interpreted with the broadest reasonable interpretation to include compounds wherein there is a double bond between X1 and X2 and X1 can be CH because otherwise no variables of X1 allow a double bond as show in Formula I.
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This anticipates claims 1-3 and 6-7.
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, 4, 9 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (Zhou et al., Nature-Inspired Chemical Probes for in-cell Labeling of Lipidized RNA and Identification of New Regulatory Enzymes, bioRxiv 2022, 1-27, IDS).
The reference Zhou teaches geranyl pyrophosphate including Ge6 and Ge5 (Fig. 2, page 4) shown below which are both compounds of formula I. Ge5 is a compound of formula I, wherein X1=CH, X2=C(CH3), m=1, X3=C(CH3), n=1, Y=N3. Ge6 is a compound of formula I, wherein X1=C(=O), X2=NH, m=0, X3=CH2, n=1, Y=N3. For the purposes of examination the claims were interpreted with the broadest reasonable interpretation to include compounds wherein there is a double bond between X1 and X2 and X1 can be CH because otherwise no variables of X1 allow a double bond as show in Formula I.
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The reference Zhou teaches “RNA modifications play pivotal roles in numerous cellular processes and human diseases. In addition to well-studied methyl-based modifications, hydrophobic prenyl-modifications have also been found in many RNA species. Here we report two chemical labeling strategies for tagging lipid-modified RNAs by taking advantage of a natural SelU-mediated tRNA geranylation process and the special reactivity of prenyl-groups. We synthesized a series of ‘clickable’ geranyl-pyrophosphate analogs and identified two candidates for indirect RNA labeling using a two-step process, azidation-and-click-tagging of fluorescent dyes, namely ACT-Flu. We also developed a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag) method based on the Ene-ligation of prenyl-groups. Both methods have been successfully applied to in-cell RNA labeling and the identification of new proteins associated with the geranylation process through proteomic and bioinformatic studies. These biochemical toolsets enable further in vivo applications to study prenylation pathways and monitor their status in both healthy and diseased cells”(abstract) and “Biochemical tools that enable the labeling of lipidized RNAs will allow for the analysis of hydrophobic modifications during normal and diseased biological processes. In addition, incorporating similar lipid analogs into tRNAs will provide a useful platform for the development of new molecular tools to label, detect, and isolate specific tRNAs 33-34 for in vitro, in situ and in vivo applicaitons. To provide a toolset to fill in these knowledge gaps, we engineered two new methods, including an indirect two-step procedure called azidation-and-click tagging of fluorescent dye (ACT-Flu), and a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag). These tools and methods can be used to analyze and exploit lipid modified RNAs, as well as to identify their interacting enzymes in living cells by taking advantage of the unique chemical reactivity 35-37 of the prenyl groups (overview in Fig. 1)”(page 3).
This helps to teach claims 1.
The reference Zhou also teaches “In conclusion, we report two chemical labeling strategies for the lipid-modified RNAs by taking g advantage of the natural SelU-mediated tRNA geranylation process and the special chemical reactivity of the prenyl-groups. We synthesized a series of ‘clickable’ geranyl pyrophosphate analogs and identified d two candidates Ge5 and Ge6 that are suitable for indirect in-cell RNA labeling through a two-step process, azidation-and-click tagging of fluorescent dye, namely ACT-Flu process. Both fluorescent t microscopy and molecular simulation studies confirmed that the two ligands could serve as ideal SelU U substrates in the tRNA geranylation process, representing a new toolset for detecting and monitoring the 2-thiouridine residue, which is an important biomarker of bacteria infections and cancers”(conclusion). The reference Zhou teaches “RNA modifications play pivotal roles in numerous cellular processes and human diseases. In addition to well-studied methyl-based modifications, hydrophobic prenyl-modifications have also been found in many RNA species. Here we report two chemical labeling strategies for tagging lipid-modified RNAs by taking advantage of a natural SelU-mediated tRNA geranylation process and the special reactivity of prenyl-groups. We synthesized a series of ‘clickable’ geranyl-pyrophosphate analogs and identified two candidates for indirect RNA labeling using a two-step process, azidation-and-click-tagging of fluorescent dyes, namely ACT-Flu. We also developed a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag) method based on the Ene-ligation of prenyl-groups. Both methods have been successfully applied to in-cell RNA labeling and the identification of new proteins associated with the geranylation process through proteomic and bioinformatic studies. These biochemical toolsets enable further in vivo applications to study prenylation pathways and monitor their status in both healthy and diseased cells”(abstract) and “Biochemical tools that enable the labeling of lipidized RNAs will allow for the analysis of hydrophobic modifications during normal and diseased biological processes. In addition, incorporating similar lipid analogs into tRNAs will provide a useful platform for the development of new molecular tools to label, detect, and isolate specific tRNAs 33-34 for in vitro, in situ and in vivo applicaitons. To provide a toolset to fill in these knowledge gaps, we engineered two new methods, including an indirect two-step procedure called azidation-and-click tagging of fluorescent dye (ACT-Flu), and a direct metabolic incorporation and biorthogonal tagging (MIBT-Tag). These tools and methods can be used to analyze and exploit lipid modified RNAs, as well as to identify their interacting enzymes in living cells by taking advantage of the unique chemical reactivity 35-37 of the prenyl groups (overview in Fig. 1)”(page 3).
This helps to teach claim 9.
The reference Zhou does not teach wherein m=1 and n=8 (claims 4 and 12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Zhou to produce compounds of the instant claims 4 and 12 because compounds with similar structures generally have similar properties. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.). The only difference between the lead compound Ge6 and the instant compound of claims 4 and 12 is several repeating -CH2- groups. Thus the compounds of instant claims 4 and 12 and Ge6 are homologs. One of ordinary skill in the art would have a reasonable expectation that they would have similar properties and utilities due to their similar structure and one would be motivated to make it to use as a useful platform for the development of new molecular tools to label, detect, and isolate specific tRNAs.
Conclusion
Claims 1-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/ALISON AZAR HASTINGS/Examiner, Art Unit 1627
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