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 claims 1-8 in the reply filed on June 15, 2026 is acknowledged.
Claims 9-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1-8 are examined herein.
Claim Objections
Claims 2, 4-6, and 8 are objected to because of the following informalities:
Claim 2 recites “an aspect ratio of 3 to 4”. The recited aspect ratio is used in the art to describe rods with relative dimensions of 3 and 4 (3:4). According to Fig. 2, the nanorods of instant invention are longer than 3:4. Suggested correction is “an aspect ratio from 3 to 4”.
Claims 4-6 contain abbreviation LC3. Abbreviations should be completely spelled out in their first occurrence.
Claim 8 recites “a low limit of detection”. This is not an art recognized terminology because there are no low or high limits of detection. Suggested “the limit of detection”.
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.
Claims 1-8 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 1 recites twice “an autophagy marker”. It is unclear if the claim is referring to one or two autophagy markers.
Claim 5 recites “the LC3 consists of LC3-I and LC3-II”. The language of this limitation implies that LC3-I and LC3-II proteins are constitutive parts of the LC3 protein. In reality, LC3 as a newly synthesized protein is cleaved by a protease generating LC3-I, which in turn is conjugated with phosphatidylethanolamine generating LC3-II. Therefore, it is unclear what Applicant means by adding this limitation. The limitation will be interpreted as LC3 protein is processed after its synthesis and exists as LC3-I and/or LC3-II forms.
Claim 6 recites “the monoclonal antibody is LC3-mAb”. It is unclear what Applicant claims because the name LC3-mAb is not descriptive enough to indicate a specific antibody. The limitation will be interpreted broadly as “the monoclonal antibody is an anti-LC3 monoclonal antibody”.
Claims 2-8 are rejected because they depend from rejected claim 1.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Kimura et al. (IDS; Autophagy. 2007 Sep-Oct;3(5):452-60) in view of Sim et al. (saved as KR-102354345-B1 in PTO-892 and uploaded as KR1020160128654) and Yu et al. (IDS; Mikrochim Acta. 2021 Mar 21;188(4):133), and as evidenced by Wikipedia (MAP1LC3B – Wikipedia, 2026).
Regarding claim 1 and 4, Kimura teaches studying autophagy using fusion protein of monomeric red-fluorescent protein and LC3 (Abstract). Specifically, the reference teaches using a fusion protein between a red-fluorescent protein as a fluorescent label and LC3 protein as an autophagy marker. Fluorescence from LC3 fusion protein was detected using immunofluorescent microscope (pg. 453, col. 2, last par.). LC3 protein is widely used as a marker protein for cellular autophagic process (pg. 452, last par.), meeting claim 4 reciting the autophagy marker is LC3.
Kimura does not teach a nanoplasmonic biosensor, a monoclonal antibody specifically binding to an autophagy marker, immunogold nanorods, and a unit for measuring localized surface plasmon resonance signal.
Regarding claim 1, Sim teaches a nanoplasmonic biosensor for label-free detection of biomarkers (Title). Specifically, the reference teaches a biosensor comprising: a glass slide as a substrate, gold nanoparticles fixed on the surface of the glass slide, and monoclonal antibodies fixed on the surface of the gold nanoparticles. The reference also teaches “gold nanoparticles linked to antibodies that specifically bind to biomarkers (pg. 2, section “The effect of invention”). The biomarkers of Sim are AFP, CEA, and PSA-ACT (pg. 2, section “Solutions to challenges”, par. 4) and the monoclonal antibodies are selected from a group consisting of AFP-mAb, CEA-mAb, and PSA-mAb (pg. 2, section “Solutions to challenges”, par. 7).
Additionally, Sim teaches that plasmonic biosensor detection is based on optical effect of localized surface plasmon resonance (LSPR) (pg. 1, section “Background Description”, par. 3).
Finally, Sim teaches “the step of measuring the Rayleigh scattering spectrum using darkfield microscopy and Rayleigh-scattering spectroscopy” (pg. 2, section “Solutions to challenges”, par. 9). As such, the reference teaches a measurement unit for measuring localized surface plasmon resonance signal from the gold nanoparticles.
Kimura and Sim do not specifically teach gold nanorods.
Regarding claim 1, Yu teaches “Gold nanorods-based lateral flow biosensors for sensitive detection of nucleic acids” (Title). The gold nanorods were synthesized with different aspect ratios “AuNRs-25 (average length, 25 nm), AuNRs-60 (average length, 60 nm), and AuNRs-80 (average length, 80 nm)” (pg. 2, col. 2, section “Preparation of AuNRs”) and detected with a portable test strip reader as a measuring unit (pg. 2, col. 1, last par.).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the detection of autophagy marker LC3 of Kimura by employing the nanoplasmonic biosensor for label-free detection of biomarkers as taught by Sim, in order to simplify LC3 detection process. One having ordinary skill in the art would have been motivated to make such a change because gold nanoparticles can detect LC3 protein without fusing it to the red-fluorescent protein. The use of such combination would have been desirable to those of ordinary skill in the art because the gold nanoparticles improve the biosensor versatility.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the prior art references of Kimura and Sim because both references are similarly drawn to detection of analytes using optical methods, and both fluorescent and gold labels are well-known in the art.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have replaced the monoclonal antibodies of Sim with an anti-LC3 monoclonal antibody specifically binding to an autophagy marker (LC3 protein) of Kimura for using with the biosensor of Sim, as an obvious matter of simple substitution of one known element (an anti-LC3 antibody) for another (AFP-mAb, CEA-mAb, and PSA-mAb of Sim) to obtain predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the prior art references of Kimura and Sim because replacing AFP-mAb, CEA-mAb, and PSA-mAb of Sim with an anti-LC3 antibody to detect LC3 target of Kimura is a routine practice of using an antibody with specificity toward the target molecule.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoplasmonic biosensor of Kimura and Sim by employing gold nanorods as taught by Yu, in order to improve the biosensor performance. One having ordinary skill in the art would have been motivated to make such a change because gold nanorods compared with gold nanoparticles have stronger NIR/Vis absorption and greater enabling cross-sections of surface enhancement Raman spectroscopy (pg. 2, col. 1, par. 2). The use of such combination would have been desirable to those of ordinary skill in the art because the gold nanorods improve the biosensor performance.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the prior art references of Sim and Yu, because both references are similarly drawn to detection of gold nanosized labels and both use surface plasmon resonance for detection.
Regarding claim 2, Kimura, Sim, and Yu teach that gold nanorods can be synthesized with different aspect ratios. AuNRs-25 nanorods had ratio of 3.13 for (Yu, pg. 3, col. 2, last par.), falling within and therefore meeting the limitation of claim 2 reciting an aspect ratio from 3 to 4.
Regarding claim 3, Kimura and Sim teach “a nanoplasmonic biosensor for unlabeled multiple detection is provided featuring the detection of the biomarker by measuring changes in the Rayleigh scattering spectrum that occurs through the specific binding of the biomarker to the monoclonal antibody” (Sim, pg. 2, section “Solutions to challenges”, par. 2).
Regarding claim 5, Wikipedia provides evidence that LC3 protein as a newly synthesized protein is cleaved by a protease generating LC3-I, which in turn is conjugated with a lipid phosphatidylethanolamine generating LC3-II (pg. 2, col. 1, par. 1). After this processing LC3 protein exists as LC3-I and/or LC3-II polypeptides.
Regarding claim 6, Sim teaches using AFP-mAb, CEA-mAb, and PSA-mAb (pg. 2, section “Solutions to challenges”, par. 7) for detection of AFP, CEA, and PSA-ACT targets (pg. 2, section “Solutions to challenges”, par. 4). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have replaced the monoclonal antibodies of Sim with an anti-LC3 monoclonal antibody specifically binding to an autophagy marker (LC3 protein) of Kimura for using with the biosensor of Sim, as an obvious matter of simple substitution of one known element (AFP-mAb, CEA-mAb, and PSA-mAb of Sim) for another (anti-LC3 antibody to detect LC3 target) to obtain predictable results. It is a routine practice of choosing an antibody with specificity toward the target molecule.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kimura, Sim, and Yu, and further in view of Truong et al. (Lab Chip. 2011 Aug 7;11(15):2591-7).
The teachings of Kimura, Sim, and Yu have been set forth above.
Regarding claims 7 and 8, Kimura, Sim, and Yu do not teach a wide detection range and a specific limit of detection.
Regarding claims 7 and 8, Truong teaches “A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor” (Title). Truong also teaches a wide range of femtomolar (fM) to nanomolar (nM) concentrations and a limit of detection in the range of 60 fM to 65 fM.
Specifically, Truong teaches that a gold nanorod immunosensor based on localized surface plasmon resonance achieved detection of a protein biomarker at a concentration as low as 111 aM (Abstract). The concentration of 111 aM corresponds to 0.111 fM, which exceeds sensitivity of 60 fM to 65 fM of the disclosed biosensor.
Additionally, the reference teaches a calibration curve for detection of the PSA–ACT at concentrations ranging from 1.11x102 to 1.11x109 aM using AuNRs (Fig. 4B). The concentration of 1.11x109 aM corresponds to 1.11 nM, meeting the limitation of claim 7 reciting the upper range of detection as nanomolar (nM) concentration.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoplasmonic biosensor of Kimura, Sim, and Yu, by employing gold nanorods as taught by Truong, in order to achieve a wide detection range and a very low limit of detection, as an obvious matter of simple substitution of gold nanorods of Truong for gold nanorods of Yu to obtain predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the prior art references of Truong and Yu, because both references are similarly drawn to detection of protein targets using Rayleigh light scattering on gold nanorods.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 6-8 of copending Application No. 18/095,107.
Although the claims at issue are not identical, they are not patentably distinct from each other because the highly sensitive nanoplasmonic biosensor for detecting an autophagy marker, comprising a substrate, immunogold nanorods immobilized onto the substrate and linked with a monoclonal antibody specifically binding to an autophagy marker, and a measurement unit measuring a localized surface plasmon resonance phenomenon in the immunogold nanorods of instant claim 1 can be used by a method of claim 1 of copending Application No. 18/095,107, and therefore, is anticipated by the claim.
Instant claim 1 is anticipated by claim 1 of ‘107 reciting a method of analyzing expression level of LC3 (microtubule-associated protein 1 Light Chain 3) comprising LC3-I and LC3-II using a nanoplasmonic biosensor for detecting the LC3 with high sensitivity comprising: preparing the nanoplasmonic biosensor comprising a substrate, immunogold nanorods immobilized on the substrate and linked with a monoclonal antibody specifically binding to the LC3, and a measurement unit configured to measure localized surface plasmon resonance in the immunogold nanorods.
Claim 1 of ‘107 does not specifically recite a measurement unit measuring a localized surface plasmon resonance phenomenon, but it does recite measuring Rayleigh scattering spectra, which necessarily means using a measurement unit.
Instant claim 2 is anticipated by claim 1 of ‘107 reciting the immunogold nanorods have an aspect ratio of 3 to 4.
Instant claims 3 and 4 are anticipated by claim 3 of ‘107 reciting the nanoplasmonic biosensor detects the LC3 by measuring a change in Rayleigh scattering spectrum generated by specific binding of the autophagy marker.
Instant claim 5 is anticipated by claim 1 of ‘107 reciting LC3 (microtubule-associated protein 1 Light Chain 3) comprising LC3-I and LC3-II.
Instant claim 6 is anticipated by claim 6 of ‘107 reciting the monoclonal antibody is LC3-mAb.
Instant claim 7 is anticipated by claim 7 of ‘107 reciting the nanoplasmonic biosensor detects the LC3 in a range of femtomolar concentration (fM) to nanomolar concentration (nM).
Instant claim 8 is anticipated by claim 8 of ‘107 reciting the nanoplasmonic biosensor detects the LC3 at a low limit of detection ranging from 102 fM to 106 fM. The limit of detection of instant claim 1 is 60 to 65 fM, which is approximately 102 fM recited by claim 8 of ‘107.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
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