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 .
Applicant’s response filed on April 15, 2026 is acknowledged and has been entered. Claim 1 and 10 are amended. Claims 2-3 are canceled. Claims 8-10 are withdrawn. Claims 1-8 are pending and will be examined.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL.
Prior Grounds of Rejection
Priority
Should applicant desire to obtain the benefit of foreign priority 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.
Nucleotide and/or Amino Acid Sequence Disclosures
The prior objection to the specification and figures is withdrawn in view of the amendment to Figure 3.
New Grounds of Rejection
Claim Rejections - 35 USC § 103
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 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Anal Chem, 2022, 94:10610-10616) in view of Sener et al. (Anal Biochem, 2021, 628:114262, p 1-9).
With regard to claim 1, Xu teaches a molecular beacon nanoprobe for directly detecting organ-specific metastasis related genes of tumor cells in peripheral blood,
wherein the molecular beacon nanoprobe is a nanoparticle formed by self-assembly of a polymer material, a positively charged protein, a functional polypeptide, and a molecular beacon of organ-specific metastasis related RNA biomarkers of tumor cells,
wherein the polymer material is conjugated with at least two different aptamers for targeting epithelial and mesenchymal tumor cells simultaneously, wherein the polymer material comprises an SYL-3C conjugated hyaluronic acid, and wherein the positively charged protein, the functional polypeptide, and the molecular beacon of organ-specific metastasis related RNA biomarkers of tumor cells are encapsulated within the polymer material. (Scheme 1, where there are three aptamers that target epithelial CTC, mesenchymal CTC and stem CTC and two molecular beacons specific to tumor specific targets: E-cad and RPL15; also note the molecular beacons are encapsulated; also note p 10611 where the positively charged protein is included).
With regard to claim 4, Xu teaches a molecular beacon nanoprobe of claim 1, wherein the positively charged protein comprises any one of protamine, histone, and lysozyme (p 10611, col 2, bottom of page, where protamine sulfate is included within the nanoprobe).
Regarding claim 1, while Xu teaches dual targeting aptamers, Xu does not teach ICAM specifically.
With regard to claim 1, Sener teaches an ICAM-1 aptamer conjugated hyaluronic acid (Abstract, Fig 1 and legend; p 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Xu to include an ICAM aptamer as described by Sener to arrive at the claimed invention with a reasonable expectation for success. Xu teaches “we show direct detection of two metastasis-related mRNAs of diverse CTCs in whole blood by a triple-targeting nanoprobe. In the nanoprobe, two kinds of molecular beacons, MB1 to detect RPL15 mRNA and MB2 to detect Ecadherin (E-cad) mRNA, are loaded in a highly efficient delivery vector decorated with EpCAM-targeted SYL3C, EGFR-targeted CL4, and CD44-targeted hyaluronic acid chains to specifically deliver MB1/MB2 into epithelial, mesenchymal, and stem CTCs in unprocessed peripheral blood” (abstract). Sener teaches “results suggested that these aptamers have potential to detect specifically ICAM-1 expressing tumor cells and inhibit migration and invasion by blocking ICAM-1 related interactions of circulating tumor cells” (Abstract). Sener also teaches “In the present study, the selection of DNA aptamers to ICAM-1 using both cell-SELEX and protein SELEX was described and their inhibitory effects on metastatic features; migration and invasion of ICAM-1(+) cells were demonstrated for the first time” (p 2, col. 2). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Xu to include an ICAM aptamer as described by Sener to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Anal Chem, 2022, 94:10610-10616) in view of Sener et al. (Anal Biochem, 2021, 628:114262, p 1-9) as applied over claims 1 and 4 above and further in view of Zhang et al. (Chem Soc Rev, 2018, 47, 3490-3529).
With regard to claim 5, Zhang teaches a molecular beacon nanoprobe of claim 1, wherein the molecular beacon of organ-specific metastasis related genes of tumor cells comprises at least one of a tumor marker molecular beacon, a tumor brain metastasis marker molecular beacon, a tumor lung metastasis marker molecular beacon, a tumor bone metastasis marker molecular beacon, and a tumor liver metastasis marker molecular beacon (see Table 1, p 3504-05 and p 3515 where various types of organ specific metastases were detectable);
and the tumor marker molecular beacon comprises a 5' end labeled with a fluorescence group and a 3' end labeled with a fluorescence quenching group (p 3513 “4.2.2 nanoparticles as a component of the peptide based beacon” heading, where quenchers or quenching are a key component to the function of nanoparticles and beacons).
With regard to claim 6, Zhang teaches a molecular beacon nanoprobe of claim 1, wherein the functional polypeptide comprises any one of a KALA peptide, other penetrating peptides, a targeting peptide, and a fusion peptide (p. 3499, “3.1.3 cell penetrating peptides heading; p 3492, col. 2 describes an imaging probe that uses an activatable cell penentrating peptide).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Xu and Sener to include the organ specific targets as described by Zhang to arrive at the claimed invention with a reasonable expectation for success. Zhang teaches “Many probes for molecular imaging are being tested in preclinical and clinical studies with the aim to accurately probe the metabolism, angiogenesis, gene expression, enzyme expression, and hypoxia of diseased sites.” (p 3492, col. 2). Zhang also teaches “Other peptide based probes designed for the imaging of the somatostatin receptor (68Ga-DOTA-NOC,43 and 68Ga-DOTATOC44), cyclophilin A (ASYNYDAGGGSK-FITC45), colonic dysplasia related receptor (VRPMPLQ-FITC46), Annexin A2 (BLZ-10047), tyrosine kinase c-Met (GE-13748), and cathepsin (LUM01549) have been or are currently being tested in the clinic, as detailed in Table 1” (p. 3492, col. 2). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Xu and Sener to include the organ specific targets as described by Zhang to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Anal Chem, 2022, 94:10610-10616) in view of Sener et al. (Anal Biochem, 2021, 628:114262, p 1-9) as applied over claims 1 and 4 above and further in view of Hwang et al. (ACS Sens, 2018, 3, 2651-2659).
With regard to claim 7, Hwang teaches a molecular beacon nanoprobe of claim 1, wherein a nucleic acid capable of being detected by the molecular beacon nanoprobe comprises any one of miR-21, miR-221, CXCR4 mRNA, CTSC mRNA, Jagged1 mRNA, Ki67 mRNA, and EGFR mRNA (Abstract; p 2652, col. 2 and Fig 1, for example where tumor markers are detected using molecular beacons).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Xu and Sener to include the ability to detect specific tumor markers as described by Hwang to arrive at the claimed invention with a reasonable expectation for success. Hwang teaches “CTC derived microRNAs (miRs) in blood and tissues have been proposed as the novel noninvasive biomarkers for monitoring tumor progression, especially at the early stages. To monitor circulating miRs, a tool should have high sensitivity, be a simple procedure, and allow detection in very small volumes. Thus, we designed a sensing tool for sensitive monitoring of blood or tissue miRs using a fluorophore-quencher probe-based molecular beacon (MB)” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Xu and Sener to include the ability to detect specific tumor markers as described by Hwang to arrive at the claimed invention with a reasonable expectation for success.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-8 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed. All claims stand rejected.
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 STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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