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 without traverse of Group I and species of gold, calcium phosphate (CaP), and sulforhodamine B (SRB) in the reply filed on February 18, 2026 is acknowledged.
Drawings
The drawings are objected to because:
Regarding FIG. 17A, the brief description of the drawings states that FIG. 17A shows “the green (denoted "(G)") and red (denoted "(R)") plots” (¶ 28 of the specification as filed) but FIG. 17A does not include “(G)” and “(R).”
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.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
The use of the terms NanoSight®, Milli-Q®, SpecVette™, Philips®, JEOL®, Zetasizer®, FluoroMax®, Kevex™, accuSpin™, NanoSight NS300® which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
On page 2, line29, the phrase “the solution comprises and elevated pH” is grammatically incorrect and should be revised. Additionally, the term “pH” is a property or characteristic of the solution rather than a constituent. The solution has a pH range rather than comprising a pH as an ingredient.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 Indefiniteness
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.
Claim 4 recites "the solution comprises a pH” (underlined for emphasis) which is indefinite because the term “pH” is a property or characteristic of the solution rather than a constituent. The solution has a pH range rather than comprising a pH as an ingredient.
Clarification and/or amendment is required.
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.
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.
Claims 1-3, 6, 7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Weidemaier et al. (US 2011 0275061; cited on IDS filed December 15, 2022) in view of Tsien et al. (US 2010 0233726; cited on IDS filed December 15, 2022).
Regarding claim 1, Weidemaier discloses a method for detecting the presence or amount of one or more analytes in a biological sample, the method comprising contacting the sample with a reagent comprising surface enhanced Raman spectroscopy (SERS)-active nanoparticles (NPs) (reads on donor material) and magnetic capture particles associated with at least one reference label capable of generating a detectable signal (reporter molecule, reads on probe); illuminating the localized area; and comparing the detectable signals (claim 1). Weidemaier discloses that the donor materials can be associated with the probe having label (¶ 121; FIG. 2) and the probe can be any molecule that provides a Raman signal upon exposure to appropriate irradiation (¶ 77). Weidemaier discloses that the method can be used for monitoring specific markers or diagnosing abnormal pathology in vivo by introducing the donor materials targeted to a molecule (¶ 282; ¶ 300). Weidemaier discloses that the components can be reversibly bound to a target molecule and the components can be selectively removed by one or more washing steps (¶ 100; ¶ 103). The washing steps would require delivering a solution to dislodge the molecules from the coupling site. Regarding claim 2, Weidemaier discloses that functionalization of the donor material can provide a specific interaction with a target analyte and the probe can be functionalized to be conjugated with the donor material (¶¶ 81-82; ¶ 121; FIG. 2). Regarding claim 3, Weidemaier discloses that the target analyte can be a cancerous cell (¶ 174). Regarding claims 6 and 10, Weidemaier discloses that the donor material can comprise gold (¶ 56). Regarding claim 7, Weidemaier discloses that the donor material can comprise the encapsulated NP with a diameter between about 20 nm and about 200 nm (¶ 68).
Regarding claims 1 and 3, Weidemaier does not disclose the step of extracting the probe from the target in a living organism and extracting the probe comprises a blood draw.
Tsien discloses a recombinant tandem fluorescent protein construct comprising a donor fluorescent protein moiety, an acceptor fluorescent protein moiety, and a peptide linker moiety that couples the donor and acceptor moieties (claim 1). Tsien discloses that the construct can be used for enzymatic assays on living cells or organisms in vivo (¶ 102). Tsien discloses that blood samples containing the construct or cleaved moieties can be extracted from the organism and tested (¶ 107). The blood sample would require drawing the blood from the organism.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Weidemaier to add a step of extracting the probe from the target in a living organism by a blood draw. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Tsien teaches that a blood sample including cleaved moieties such as probe molecule can be extracted from a living organism by a blood draw. Further, a person of ordinary skill in the art would have been motivated to extract the probe from the target in a living organism in order to minimize its residence time in vivo and perform additional analysis. Accordingly, applying the teachings of Tsien to the method of Weidemaier constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claims 1 and 3 obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Weidemaier et al. (US 2011 0275061; cited on IDS filed December 15, 2022) and Tsien et al. (US 2010 0233726; cited on IDS filed December 15, 2022) as applied to instant claims 1-3, 6, 7, and 10 above, and further in view of Baker et al. (US 2008 0261202; cited on IDS filed December 15, 2022).
Weidemaier and Tsien are discussed above.
Neither Weidemaier nor Tsien discloses a solution having a pH within a range of 8.0-8.5.
Baker discloses tagged polyfunctional reagents capable of reversibly binding to target substances in a pH-dependent manner (title). Baker discloses that the binding can be severed at a pH of 8.5 (¶ 51).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Weidemaier and Tsien to include a solution with a pH of 8.5 to sever the coupling between the probe and the donor material. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Baker teaches that a solution with an elevated pH, such as pH 8.5 can be used to sever the coupling between molecules. Further, a person of ordinary skill in the art would have been motivated to use pH-based probe dislodging for specific and efficient extraction of the probe. Accordingly, applying the teachings of Baker to the method of Weidemaier and Tsien constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claim 4 obvious.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Weidemaier et al. (US 2011 0275061; cited on IDS filed December 15, 2022) and Tsien et al. (US 2010 0233726; cited on IDS filed December 15, 2022) as applied to instant claims 1-3, 6, 7, and 10 above, and further in view of Mir (US 2014 0162892; cited on IDS filed December 15, 2022).
In addition to the teachings of Weidemaier discussed above, Weidemaier discloses that the probe can be a dye molecule (¶ 51).
Tsien is discussed above.
Neither Weidemaier nor Tsien discloses that determining the optical change in the probe comprises detecting destruction of the dye molecules.
Mir discloses a method of sequencing a target polynucleotide using a fluorescence tag such as a dye (abstract; ¶ 37). Mir discloses that the detection of signal change can comprise chemically inactivating or photobleaching the fluorescence tag (claim 6; ¶ 44), which reads on the destruction of the dye molecules.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Weidemaier and Tsien to determine the optical change in the probe by detecting destruction of the dye molecules. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mir teaches that determining the optical change can comprise detecting destruction of the dye molecules. Further, a person of ordinary skill in the art would have been motivated to destruct the dye molecule when determine the optical change in order to improve sensitivity. Accordingly, applying the teachings of Mir to the method of Weidemaier and Tsien constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claim 5 obvious.
Claims 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Weidemaier et al. (US 2011 0275061; cited on IDS filed December 15, 2022) and Tsien et al. (US 2010 0233726; cited on IDS filed December 15, 2022) as applied to instant claims 1-3, 6, 7, and 10 above, and further in view of Schmidt and Ostafin (Advanced Materials, 2002; cited on IDS filed December 15, 2022).
Weidemaier and Tsien are discussed above.
Neither Weidemaier nor Tsien discloses that the probe comprises CaP and the probe is characterized by a diameter of between about 5 nm and about 100 nm.
Schmidt discloses nanoscale shells composed of CaP (page 533, col. 1, ¶ 1). Schmidt discloses that the diameter of the shells can be 30-50 nm (page 533, col. 2, ¶ 2). Schmidt discloses that calcium phosphate enclosed liposomes (CaPELs) can be used as sustained delivery vehicles for drugs or fluorescent dyes (page 532, col. 2, ¶3; page 534, col. 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Weidemaier and Tsien to use CaPELs with a diameter of 30-50 nm for the probe. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Schmidt teaches that the CaPELs with a diameter of 30-50 nm can be used as delivery vehicles encapsulating fluorescent dyes. Further, a person of ordinary skill in the art would have been motivated to use CaPELs in order to improve biocompatibility and controlled release. Accordingly, applying the teachings of Schmidt to the method of Weidemaier and Tsien constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claims 8 and 11 obvious.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Weidemaier et al. (US 2011 0275061; cited on IDS filed December 15, 2022) and Tsien et al. (US 2010 0233726; cited on IDS filed December 15, 2022) as applied to instant claims 1-3, 6, 7, and 10 above, and further in view of Vérant et al. (Journal of Biomedical Optics, 2008; cited on PTO-892).
Weidemaier and Tsien are discussed above.
Neither Weidemaier nor Tsien discloses that the probe comprises SRB.
Vérant discloses the use of SRB for in vivo staining and imaging (abstract). Vérant discloses that SRB is an amphiphilic fluorescent dye with notable benefits such as low toxicity, high water solubility, and rapid clearance (page 064028-2, col 1, ¶ 1; page 064028-4, col. 1, ¶ 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Weidemaier and Tsien to use SRB for the probe. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Vérant teaches that the SRB can be an effective dye molecule for in vivo imaging. Further, a person of ordinary skill in the art would have been motivated to use SRB as a highly sensitive, non-destructive, and cost-effective dye. Accordingly, applying the teachings of Vérant to the method of Weidemaier and Tsien constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claim 9 obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 11 of U.S. Patent No. US 11,531,025 (cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, claim 1 of the ‘025 recites a method of confirming a targeting operation, the method comprising: delivering a donor material to a target; delivering a probe to the target, wherein the probe couples with the donor material; irradiating the target; determining an optical change in the probe to confirm the donor material and probe reached the target; delivering a solution to dislodge the probe from the donor material; and extracting the probe from the target, wherein the target is in a living organism.
Regarding claim 2, claim 2 of the ‘025 recites further comprising: functionalizing the donor material to seek the target; and functionalizing the probe to conjugate with the donor material.
Regarding claim 3, claim 3 of the ‘025 recites the target comprises cancerous tissue in the living organism, and wherein extracting the probe comprises a blood draw.
Regarding claim 4, claim 4 of the ‘025 recites the solution comprises a pH of within a range of 8.0-8.5, and wherein the solution severs the coupling between the probe and the donor material.
Regarding claim 5, claim 5 of the ‘025 recites the probe comprises dye molecules, and wherein determining an optical change in the probe comprises detecting destruction of the dye molecules
Regarding claims 6 and 10, claim 6 of the ‘025 recites the donor material comprises at least one material selected from the group consisting of lanthanide oxide, hafnium oxide, tungsten oxide, platinum, gold, bismuth, and uranium-238.
Regarding claim 7, claim 7 of the ‘025 recites the donor material comprises a nanomaterial having a diameter between about 25 nm and about 1,000 nm.
Regarding claim 8, claim 8 of the ‘025 recites the probe comprises at least one material selected from the group consisting of TiO2, ZnO, Al2O3, SiO2, CaP, polystyrene, and poly N-isopropylacrylamide.
Regarding claim 9, claim 9 of the ‘025 recites the probe further comprises at least one material selected from the group consisting of coumarin-3-carboxylic acid, 3′-(p aminophenyl) fluorescein, 2-[6-(4V-amino)phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF), dihydroethidine (DHE), dihydrorhodamine, 4′,5′-diaminofluorescein, sulforhodamine B, calcein, and fluorescein.
Regarding claim 11, claim 11 of the ‘025 recites the probe is characterized by a diameter of between about 5 nm and about 100 nm.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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