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 .
Election/Restrictions
Applicant’s election of Group I in the reply filed on January 5, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 8-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 5, 2026.
Claims 1-7 are pending and will be examined.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
NOTE: If Applicant decides to remove the sequences from Figure 3, then the guidance regarding compliance is moot.
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.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2 and 4-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (Chem Soc Rev, 2018, 47, 3490-3529).
With regard to claim 1, Zhang 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 (Fig 42c, Fig 43, p 3515, “4.3.2 PBNs with self-assembly activated signals” heading; see Table 1, p 3504-05 and p 3515 where various types of organ specific metastases were detectable).
With regard to claim 2, Zhang teaches a molecular beacon nanoprobe of claim 1, wherein the polymer material comprises any one of aptamer conjugated hyaluronic acid, peptide conjugated hyaluronic acid, aptamer conjugated carboxymethyl chitosan, peptide conjugated carboxymethyl chitosan, aptamer conjugated sodium alginate, peptide conjugated sodium alginate, aptamer conjugated heparin sodium, and peptide conjugated heparin sodium (p 3506, where peptide is conjugated to the nanoprobe).
With regard to claim 4, Zhang teaches a molecular beacon nanoprobe of claim 1, wherein the positively charged protein comprises any one of protamine, histone, and lysozyme (p 3498, col. 1, where lysozyme is included).
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).
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) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Chem Soc Rev, 2018, 47, 3490-3529) as applied over claims 1-2 and 4-6 above and further in view of Esposito et al. (PLoS One, 2011, 6(9):e24071, p 1-12).
With regard to claim 3, Esposito teaches a molecular beacon nanoprobe of claim 2, wherein an aptamer comprises at least one of AS1411, SYL3C, MUC1-aptamer, EGFR-aptamer CL4, and ICAM-1-aptamer; and a polypeptide comprises any one of a cell-penetrating peptide TAT, a CXCR4 targeting peptide T22, a VCAM-1 targeting peptide VHPKQ, and a fusion peptide formed by fusion of these peptides (Abstract; p 2 “CL4 aptamer specifically interacts with EGFR” heading; Fig 1).
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 Zhang to include aptamers with different specificities including the aptamer specific for EGFR as taught by Esposito to arrive at the claimed invention with a reasonable expectation for success. Zhang guides that nanoprobes include functional moieties including “small molecules, peptides, proteins, protein scaffolds, antibodies, aptamers, and saccharides. Among various ligands, peptides receive additional interest because of their physiological barrier penetrating and receptor-targeting capabilities with low cost and high biocompatibility” (p 3498, col. 1). Esposito teaches “we have generated a nuclease-resistant RNA-aptamer (named CL4) able to bind at high affinity to EGFR on the surface of different cancer cells and to block EGFR downstream signaling via inhibition of either” (p 2, col. 1) and also “results indicate that the CL4 aptamer recognizes specifically and at high affinity the EGFR in its physiological context on the cell surface as well as the purified extracellular domain of the receptor both as monomer or dimer” (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 Zhang to include aptamers with different specificities including the aptamer specific for EGFR as taught by Esposito 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 Zhang et al. (Chem Soc Rev, 2018, 47, 3490-3529) as applied over claims 1-2 and 4-6 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 Zhang 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. Zhang teaches “[in] addition to their role as probes for endogenous biomolecules, nucleus-targeted nanoprobes have also been used as a tracker for the efficiency of nucleic acid drugs” but does not target tumor specific markers at the mRNA level. 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 Zhang 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.
Conclusion
No claims allowed. All claims stand rejected.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681