DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 06/23/2026 has been entered. Claim 6 is new. Claims 1-6 are pending in this application. Claim 1 is withdrawn. Claims 2-6 are currently under examination.
Priority
This application is a 371 of PCT/CN2022/104400 filed on 07/07/2022 and claims foreign priority of CHINA 202210060838.4 filed on 01/09/2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant's election without traverse of Group II invention (claims 2-6) in the reply filed on 06/23/2026 is acknowledged. Claim 1 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 2-6 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 06/23/2026 has been considered.
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 - 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.
Drawings/Claim Objections
The drawings are objected to because the text and line are barely readable. 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 2 is objected to because of the following informalities: In claim 2, spell out the abbreviated “PSCA” (line 1) to “prostate stem cell antigen (PSCA)”; delete the excessive period “.” Immediately before the recitation “wherein the GGA” (line 6); and replace the incorrect recitation “C6 amino linker” (lines 9 to 10) with “C6NH2 linker” to become proper chemical formula. Appropriate correction is required.
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.
Claim 4 is 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 claim 4, the phrase “i.e.” (line 3, equivalent to "for example") renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Applicant is advised to change the recitation “amino acids, i.e., ALQPGTALLCYSCKA” (lines 3 to 4) to “amino acids (ALQPGTALLCYSCKA).
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.
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.
Claims 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (PLoS ONE 9(6): e100243, p. 1-10, 2014, hereinafter referred to as Wang ‘2014) as evidenced by Tai et al. (The Prostate 71:1668-1679, 2011, hereinafter referred to as Tai ‘2011) in view of Mizrahi et al. (European Journal of Medicinal Chemistry 46, 5175-5183, 2011, hereinafter referred to as Mizrahi ‘2011) and Reed et al. (US 5,512,667, Apr. 30, 1996, hereinafter referred to as Reed ‘667).
With regard to structural limitations “a method comprising contacting prostate stem cell antigen (PSCA) with a near-infrared probe GGa-ICG; and detecting a near-infrared fluorescence signal from the near-infrared probe GGa-ICG (or in prostate cancer; or in vivo imaging); wherein the GGa is an oligonucleotide consisting of the nucleotide sequence of 5'-TGCCACTACAGCTGGTTCGGTTTGGTGACTTCGTTCTTCGTTGTGGTGCTTAGTGGC-3', the ICG is indocyanine green, and the ICG is conjugated to the 3' terminus of the GGa via a C6NH2 amino linker” (claims 2, 5, and 6):
Wang ‘2014 disclosed that in the confocal image of PC-3 cell after incubation with Wy-5a at 37○C for 2 h (Figure 6), strong fluorescence signal was observed on cell membrane and weak fluorescence signal was found in whole cells, suggesting that Wy-5a may be involved in receptor-mediated endocytosis. The aptamer Wy-5a has excellent specificity to PC-3 cells. PC-3 cell line was initiated from a bone metastasis of a grade IV androgen independent prostate cancer (PCa) patient. Therefore the target protein of Wy-5a may have correlation with aggressiveness or metastasis. As shown in Figure 7, after stained by FITC (fluorescein isothiocyanate) labeled aptamer Wy-5a, the cancer tissues exhibited strong fluorescence signal. Sequences of selected aptamers for the PC-3 cells:
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(page 4, right col., para. 1 and 2; Table 1; page 5, left col., para. 1). Comparing to antibodies, aptamers have low-molecular weight, higher stability, rapid tissue penetration, lack of immunogenicity, and especially, aptamers can be chemically synthesized and modified. These advantages make aptamers versatile tools for diagnostics, Image Cytometry (ref. #21, In vivo imaging in experimental preclinical tumor research) and targeted therapeutics (page 2, left col., para. 1; page 10, ref. #21). Tai ‘2011 (cited here as evidence to show stem property of the PC-3 cell) disclosed that CD44 is a putative cancer stem cell-associated marker in various human tumors. PC-3 xenograft tumor cells expressed CD44 strongly and diffusely. Nearly 100% of PC-3 cells express CD44 (page 1672, right col., para. 2; page 1673, left col., para. 1; page 1675, right col., para. 1).
Wang ‘2014 evidenced by Tai ‘2011 did not explicitly disclose the limitations (a) the ICG is indocyanine green, and (b) the ICG is conjugated to the 3' terminus of the GGa via a C6NH2 linker”, required by claims 2-6.
With regard to the limitation (a) above, Mizrahi ‘2011 disclosed a bone-targeting Indocyanine green (ICG) derivative was prepared from Monocarboxy-ICG (
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, Scheme 1, page 5177) conjugated to Alendronate (
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, Scheme 4, page 5178), a bisphosphonate drug. The skeletal fluorescent mark of ICG-Alendronate remained visible for 2 weeks. In the course of the following two weeks, the amide bond of this conjugate undergoes slow hydrolysis, and the fluorescent signal fades. This prolonged fluorescence opens up the possibility for repeated imaging following a single injection. Since the multiple tetrabutylammonium salt is not appropriate for in vivo use, we exchanged the cation back to sodium, before moving on to the animal tests (page 5182, right col., para. 2; page 5179, right col., para. 3). Indocyanine green (ICG), a biocompatible near infrared (NIR) dye, is widely used in the imaging of various organs, such as liver, heart and blood circulation. A preparation and in-vivo testing of a bone-targeting ICG derivative are reported (page 5175, Abstract).
With regard to the limitation (b) above, Reed ‘667 disclosed that various amide linkages can be formed with the terminal amine of the long chain alkylamine on the CPG's for attachment of a growing oligonucleotide during synthesis. Particularly preferred 3'-tailed oligonucleotides would include an oligonucleotide having either cholesterol or acridine joined via a linking molecule to the oligomer's 3' tail. The acridine moiety, preferably 9-ethylacridine, is joined to the oligonucleotide utilizing an amide linkage (page 2/18, col. 2, lines 19-23; page 4/18, col. 5, lines 28-35). Synthesis of a 3' acridine tailed oligonucleotide from acridine-CPG: A quantity of acridine-CPG corresponding to 1 micromole of dimethoxytrityl content was packed into an oligonucleotide synthesis column. An oligonucleotide with the base sequence 5'-CTCTCCATCTTCGTCACA was prepared on a Milligen DNA synthesizer using standard phosphoramidite chemistry. The oligonucleotide was cleaved from the CPG and deprotected by treatment with 2 mL of conc. ammonia at 40° C. for 24 h (page 10/18, col. 17, lines 60-67; col. 18, lines 1-12). The acridine molecule was covalently linked to an oligodeoxynucleotide via a methylene chain of from 3 to 6 carbon atoms connecting the 3'-phosphate of the oligodeoxynucleotide to the 9-amino group of the acridine (page 2/18, col. 1, lines 37-41). CAS deposit, RN 142685-27-6:
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(See the STN search result).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the labeling of fluorescence at 5’-terminal of Wy-5a aptamer as taught by Wang ‘2014 evidenced by Tai ‘2011 with labeling of ICG fluorescence at 3’-terminus via an alkylamine linker, such as C6-NH2, and a formation of amide linkage with carboxyl group of the ICG fluorescence in view of Mizrahi ‘2011 and Reed ‘667 because the ICG is safe for in vivo imaging and 3’-terminal fluorescence labeling is readily produced by a DNA synthesizer using a standard phosphoramidite chemistry, respectively described above. Thus, one of skill in the art would have a reasonable expectation that by substituting the labeling of fluorescence at 5’-terminal of Wy-5a aptamer as taught by Wang ‘2014 evidenced by Tai ‘2011 with labeling of ICG fluorescence at 3’-terminus via an alkylamine linker, such as C6-NH2, and a formation of amide linkage with carboxyl group of the ICG fluorescence in view of Mizrahi ‘2011 and Reed ‘667, one would achieve Applicant’s claims 2-6. "Exemplary rationales that may support a conclusion of obviousness include: (B) Simple substitution of one known element for another to obtain predictable results". See MPEP § 2143 [R-01.2024] [I].
The method of Wang ‘2014 evidenced by Tai ‘2011 in view of Mizrahi ‘2011 and Reed ‘667 meets all structural limitation of claimed method and would achieve the same intended results, including “detecting PSCA“, “the penetration depth… is 6 mm” and “the binding site… to PSCA protein is located in 14-28 amino acids (ALQPGTALLCYSCKA)”, required by claims 2-4.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
