DETAILED ACTION
Notice of AIA Status
The present application, filed on 1/15/2024, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-23 are pending.
Claims 10-23 are withdrawn.
Claims 1 and 4-9 are rejected.
Claims 2-3 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Election/Restrictions
Applicant’s election of group I, claims 1-9, in the reply filed on 8/17/2026 is acknowledged. Because the applicant did not distinctly and specifically point out supposed errors in the restriction requirement, the election has been treated according to MPEP § 818.01(a)) as an election without traverse. Claims 10-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Weissleder (US20160334398) in view of Kotov (US20160167136).
With respect to Claim 1, Weissleder (US20160334398) teaches a microfluidic device (nano-plasmonic sensor in [0028]) comprising:
a microfluidic channel (microfluidic channel in [0028], which recites “the nano-plasmonic sensor further comprises at least one microfluidic channel”) comprising at least one surface (surface of a glass slide containing nanoaperture arrays, see [0098], which recites “FIG. 4A-FIG. 4C are an illustration and images of a device configuration of a nPLEX sensor integrated with microfluidics. A 12-channel fluidic cell (FIG. 4A) was placed on top of a glass slide containing nanoaperture arrays (FIG. 4B). A total of 36 measurement sites were arranged into a 12×3 array format (FIG. 4C) with each fluidic channel encompassing three measurement sites. Surface functionalization, sample injection, and washing steps were performed through the fluidic system”) having a plurality of nanoparticles (CD63-specific Au nanospheres in [0103]) disposed thereon (see [0103], which recites “FIG. 9C is a set of images and graphs of experimental results that demonstrates signal amplification through secondary labeling. Exosomes captured on the sensor were further targeted with CD63-specific Au nanospheres (arrow) or star-shaped particles to enhance spectral shifts”) wherein the plurality of nanoparticles each comprise an optical material (see [0064], which recites “Surface plasmon resonance,” as used herein, refers to the physical phenomenon in which incident light stimulates collective electron oscillations at the metal surface for planar surfaces. The term “localized surface plasmon resonance (LSPR)” refers to surface plasmon resonance of nanometer-sized structures, such as a metallic nanoparticle”) selected from the group consisting of: gold, silver, copper, nickel, iron, carbon, platinum, silicon, CdTe, CdSe, CdS, HgTe, HgSe, HgS, PbTe, PbSe, PbS, MoS2, FeS2, FeS, FeSe, and combinations thereof (see [0045], which recites “the metallic nanoparticle is a gold sphere”) (see also [0103], which recites “Exosomes captured on the sensor were further targeted with CD63-specific Au nanospheres (arrow)”) (see also [0104], which recites “FIG. 10A-FIG. 10B are SEM images of Au nanoparticles for signal amplification”), and a targeting ligand (antibodies against CD63 in [0192])) associated with the plurality of nanoparticles (see [0096], which recites “FIG. 2A-FIG. 2B indicate that exosomes shed from cancer cells. FIG. 2A is an image of CaOV3 ovarian cancer cells shed nanoscale vesicles as imaged by a scanning electron microscope (SEM). FIG. 2B is a graph of experimental results indicating the size distribution of exosomes, characterized by the nanoparticle tracking analysis”) that is capable of binding to a bioactive target analyte (exosome marker in [0029]) in a biological fluid sample (biological sample in [0071]), wherein the bioactive target analyte (exosome marker) indicates a presence of cancerous cells (see [0241]) or mutated proteins (see [0241]) in the biological fluid sample (see [0004], which recites “most cancers shed large numbers of exosomes that carry molecular information about the parent tumor”) (see [0026], which recites “the exosome marker is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), CD24, cancer antigen 19-9 (CA19-9), Claudin 3, cancer antigen 125 (CA-125), …CD63”).
Weissleder doesn’t teach that the plurality of nanoparticles is chiral.
In the analogous art of providing analytical devices, Kotov (US20160167136) teaches a plurality of chiral nanoparticles each comprise a light- absorbing material (see abstract, which recites “chiral nanoparticles …. the nanoparticles may include a variety of light-absorbing materials (e.g., CdTe, CdS, Au, and the like) (see also claim 6, which recites “the chiral nanoparticle is selected from the group consisting of: gold, silver, copper, nickel, iron, carbon, platinum, silicon, CdTe, CdSe, CdS, HgTe, HgSe, HgS, PbTe, PbSe, PbS, MoS2, FeS2, FeS, FeSe, and combinations thereof”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Weissleder by substituting Weissleder’s nanoparticles with the plurality of chiral nanoparticles disclosed by Kotov, with a reasonable expectation of success, for the benefit of imparting detectable optical activity which is desirable in biosensing applications because Kotov teaches that chiral nanoparticles formed from light absorbing materials possess significant chiroptical activity and are of interest for biosensing applications, thereby providing a known nanoparticle desirable for use in Weissleder’s microfluidic device. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) (see MPEP § 2143, B.).
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Paiva-Marques (“Chiral Plasmonics and Their Potential for Point-of-Care Biosensing Applications”) in view of Frez (US20200277664).
With respect to claim 1, Paiva-Marques (“Chiral Plasmonics and Their Potential for Point-of-Care Biosensing Applications”) teaches a microfluidic device (microfluid system in the legend of Fig. 13) comprising:
a microfluidic channel (plasmonic chamber in the legend of Fig. 13) comprising at least one surface (plasmonic surface on page 5) having a plurality of chiral nanoparticles (plasmonic chiral nanoparticles on page 5) disposed thereon (see page 5, which recites “plasmonic chiral nanoparticles may be used to control circular polarization states of light, which is of practical interest for chemical and biological research owing to the strong optical interaction of molecules/biomolecules near plasmonic surfaces”), wherein the plurality of chiral nanoparticles (plasmonic chiral nanoparticles on page 5) each comprise a light- absorbing material selected from the group consisting of: gold, silver, copper, nickel, iron, carbon, platinum, silicon, CdTe, CdSe, CdS, HgTe, HgSe, HgS, PbTe, PbSe, PbS, MoS2, FeS2, FeS, FeSe, and combinations thereof (gold nanoparticles on page 6), and a targeting ligand (aptamers on page 6) associated with the plurality of chiral nanoparticles (plasmonic chiral nanoparticles) that is capable of binding to a bioactive target analyte (biomolecule of page 6) in a biological fluid sample (samples in the legend of Fig. 3, which recites “Chiral plasmonics for PoC devices integrated with IoT: Biosensing device working as a PoC device that collects samples, e.g., blood, treats them in the microfluidic system (blue way) to reach the plasmonic chamber”) (see also page 6, which recites “plasmonic chiral nanoparticles may be used to control circular polarization states of light, which is of practical interest for chemical and biological research owing to the strong optical interaction of molecules/biomolecules near plasmonic surfaces”).
Paiva-Marques fails to teach that the bioactive target analyte indicates a presence of cancerous cells or mutated proteins in the biological fluid sample.
In the analogous art of analytical fluidic devices, Frez (US20200277664) teaches a bioactive target analyte (see [0909], which recites “the capture probe or plurality of capture probes can be specific for a particular nucleic acid, or detection or expression of a particular set of proteins .., the set of proteins has similar functional domains”) (see [0911], which recites “a capture probe or plurality of capture probes interacts with two or more analytes (e.g., nucleic acids or proteins …sets of nucleic acids or proteins … that are mutated during a pathogenic state … the pathogenic state is cancer) indicates a presence of cancerous cells or mutated proteins in a biological fluid sample (biological sample in [0904], which recites “the biological sample includes an analyte that is or includes a nucleic acid”) (see [0205], which recites “biological samples can include one or more diseased cells … cancer cells”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Paiva-Marques by incorporating the bioactive target analyte indicative of a presence of cancerous cells or mutated proteins in the biological fluid sample as disclosed by Frez, such that the targeting ligand is capable of binding to a bioactive target indicative of a presence of cancerous cells or mutated proteins in a biological fluid sample, with a reasonable expectation of success, for the benefit of effectively detecting the presence and location of analyte of interest indicative of a cancer pathogenic state within a biological sample (see claim 1 of Frez). The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) (see MPEP § 2143, B.).
Claims 4-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Weissleder (US20160334398) in view of Kotov (US20160167136) in view of Shen (US20090051901).
With respect to claim 4, Weissleder in view of Kotov teaches the microfluidic device of claim 1.
Weissleder in view of Kotov fails to teach that the microfluidic channel is formed on a microchip.
In the analogous art of analytical fluidic devices, Shen (US20090051901) teaches a microfluidic channel (microchannel 1118 in [0079]) is formed on a microchip (microchip design in [0079]) (see Fig. 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Weissleder in view of Kotov by incorporating the microchip as disclosed by Shen such that the microfluidic channel is formed on a microchip, with a reasonable expectation of success, for the benefit of providing stable support for the microfluidic channel while permitting optical interrogation (see Fig. 11 of Shen).
With respect to claim 5, Weissleder in view of Kotov teaches the microfluidic device of claim 1, wherein the bioactive target analyte is selected from the group consisting of: phosphatidylserine (PS), tetraspanin proteins, epithelial cancer adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and combinations thereof (see [0026], which recites “the exosome marker is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), … epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)”).
With respect to claim 7, Weissleder in view of Kotov teaches the microfluidic device of claim 1, wherein the targeting ligand (antibodies against CD63 in [0192] of Weissleder) is selected from the group consisting of: Annexin V, anti-CD63, anti-CD81, anti-CD9, anti-CD56, anti-CD-133, anti-EpCAM, anti-EGFR, anti-vimentin, and combinations thereof (see [0192] of Weissleder, which recites “antibodies against CD63”).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Weissleder (US20160334398) in view of Kotov (US20160167136) in view of Di Carlo (WO2020005768).
With respect to claim 6, Weissleder in view of Kotov teaches the microfluidic device of claim 1.
Weissleder in view of Kotov fails to teach the plurality of chiral nanoparticles comprise chiral gold nanoparticles functionalized with mercaptoundecanoic acid (MUA) reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS).
In the analogous art of analytical fluidic devices, Di Carlo (WO2020005768) teaches gold nanoparticles (see [0052], which “conjugation of gold nanoparticles” ) functionalized with mercaptoundecanoic acid (MUA) reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) (see [0053], which recites “Spherical gold nanoparticles 14 (Nanopartz) were centrifuged and resuspended in lmM 1 l-mercaptoundecanoic acid (MU A, 450561, Sigma- Aldrich) for reaction overnight. N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC, E6383, Sigma- Aldrich) and n-hydroxysuccinimide (NHS, 130672, Sigma- Aldrich) solution was mixed in MES buffer at 1 :2 ratio. Gold nanoparticles 14 (also referred to as AuNPs) in MUA solution were centrifuged and resuspended in EDC/NHS (0. l/0.2mM) in lOmM MES buffer and reacted for 30min. The AuNP solution was then centrifuged and resuspended in antigen or antibody solution followed by 2 hours incubation at room temperature. For Anti-BSA detection, 2mM BSA (Sigma) was used for both capture and detector nanoparticles 14”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Weissleder in view of Kotov by functionalizing the chiral gold nanoparticles with mercaptoundecanoic acid (MUA) reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as disclosed by Di Carlo such that the plurality of chiral nanoparticles comprise chiral gold nanoparticles functionalized with mercaptoundecanoic acid (MUA) reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), with a reasonable expectation of success, for the benefit of enabling conjugation of a targeting ligand to the gold nanoparticles for detection of a target analyte, as demonstrated by Di Carlo’s conjugation of antibodies/antigens to MUA/EDC/NHS-functionalized AuNPs on [0053] of Di Carlo.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Weissleder (US20160334398) in view of Kotov (US20160167136) in view of Kraus (US 6,632,599 B1).
With respect to claim 8, Weissleder in view of Kotov teaches the microfluidic device of claim 1.
Weissleder in view of Kotov fails to teach that the bioactive target analyte comprises phosphatidylserine (PS) and the targeting ligand comprises Annexin V.
In the analogous art of analytical devices, Kraus (US 6,632,599 B1) teaches a bioactive target analyte comprises phosphatidylserine (PS) and a targeting ligand comprises Annexin V (see column 1, which recites “labeled reactive ligands, for example annexins, against these surface antigens were added to blood for the detection of phosphatidylserine-containing lipid membranes (Römisch J et al., Anticoagulant properties of placenta protein 4 (annexin V)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Weissleder in view of Kotov such that the bioactive target analyte comprises phosphatidylserine (PS) and the targeting ligand comprises Annexin V as disclosed by Kraus, with a reasonable expectation of success, for the benefit of effectively detecting phosphatidylserine-containing lipid membranes (see column 1 of Kraus, which recites “labeled reactive ligands, for example annexins, against these surface antigens were added to blood for the detection of phosphatidylserine-containing lipid membranes (Römisch J et al., Anticoagulant properties of placenta protein 4 (annexin V)”). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) (see MPEP § 2143, A.).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Weissleder (US20160334398) in view of Kotov (US20160167136) in view Kraus (US 6,632,599 B1) in view of Hollidt (US20210033605).
With respect to claim 9, Weissleder in view of Kotov in view of Kraus teaches the microfluidic device of claim 8, wherein the targeting ligand further comprises avidin associated with biotin that is associated with Annexin V (see column 4, which recites “L, Lx or Ly is bound to particles via a biotin-avidin bridge … L, Lx or Ly … can be …annexin”) (see also column 1, which recites “placenta protein 4 (annexin V)”.
Weissleder in view of Kotov in view of Kraus fails to teach that the avidin is deglycosylated avidin.
In the analogous art of analytical devices, Hollidt (US20210033605) teaches deglycosylated avidin (see [0057], which recites “the “biotin-binding protein” in the context of the present invention may be selected from the group consisting of avidin, streptavidin and deglycosylated avidin. Deglycosylated avidin is known as neutravidin which is also the most suitable biotin-binding protein herein”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device disclosed by Weissleder in view of Kotov in view of Kraus by incorporating deglycosylated avidin as disclosed by Hollidt, with a reasonable expectation of success, for the benefit of providing a highly suitable protein for binding the biotin in the biotin-avidin association (see [0057] of Hollidt). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) (see MPEP § 2143, A.).
Allowable Subject Matter
Claims 2-3 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
With respect to claims 2-3, none of the art available to the public before the effective filing date of the claimed invention teaches or reasonably suggests that the microfluidic channel comprises a multilayered coating wherein an exposed surface defined by the multilayered coating comprises the plurality of chiral nanoparticles having a positive charge, as recited in claim 2.
Citation of Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Hoseon (US2018/0128728) teaches a microfluidic device (microfluidic solenoid array-based device in [0048], illustrated in Fig. 9) comprising: a microfluidic channel (main microfluidic channel in [0102]); and a plurality of chiral nanoparticles (see [0009]) made of a metal (see [0017], which recites “metal nanoparticles tagged to the cells”).
In the analogous art of analytical devices, Liang (Optical anisotropy and sign reversal in layer-by-layer assembled films from chiral nanoparticles) teaches a multilayered coating (LBL coatings from NPs on page 141) formed by a layer-by-layer deposition process (see page 141, which recites “chiral NP films can be made via layer-by-layer assembly (LBL) using negatively charged chiral CdS NPs, stabilized by D- and L-cysteine and positively charged polyelectrolytes”) that comprises a plurality of positive layers interspersed with a plurality of negative layers (see page 143, which recites “the NPs were assembled with cationic poly(diallyldimethylammonium) chloride (PDDA) in a conventional LBL manner … The tests of ellipsometric thickness of the LBL film coatings made after 5, 10, 15, and 20 cycles showed that they increased linearly with the increase of cycles (see ESI†). After one cycle of PDDA/CdS NPs deposition”). Liang employs negatively charged chiral nanoparticles and fails to teach an exposed surface defined by the multilayered coating comprises the plurality of chiral nanoparticles having a positive charge.
Conclusion
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/JONATHAN BORTOLI/Examiner, Art Unit 1797
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