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/Restriction
Applicant's election with traverse of Group II (claims 7-12) in the reply filed on 10/13/2025 is acknowledged. The traversal is on the ground(s) that the statutory language of 35 USC 121 requires that the subject matter of respective claims be both independent and distinct for the election requirement to be proper. Applicant argues that the election restriction requirement fails to show or allege the existence of species that are independent and distinct because group I and group II are related as product and process of use, so it cannot be alleged that “there is no disclosed relationship”.
This is not found persuasive because a proper requirement for restriction between patentably distinct inventions requires the inventions must be either independent or distinct as claimed (see MPEP § 803).
The inventions of group I and group II are related as product and process of use, the inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h).
In the instant case, the process as claimed can be practiced with a precoated microwell plate or a tube and the result is read by a fluorescent reader; and the product of group II can be used in a materially different process such as separation of an analyte from a sample. Therefore, the inventions can be shown to be distinct because they satisfy both the restriction requirements between the product and method of using in MPEP § 806.05(h).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group I, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/13/2025.
Priority
The present application was filed on 11/30/2022. This application is a DIV of 16/689,530 filed 11/20/2019, which claims benefit of U.S. Provisional Patent Application 62/770,056 filed on 11/20/2018.
Status of Claims
Claims 7-12 are currently pending and subject to restriction and/or election requirement.
Drawings/ Specification
The drawings Fig.14B and Fig.15A and disclosure in par.133 and par(s).144-145 are objected to as failing to comply with 37 CFR 1.84(p)(4) because:
“1512” has been used to designate both blank curve in par.133 and Fig.14B, and a capture anybody for procalcitonin in par.144-145 and Fig.15A;
“1514” has been used to designate both PCT curve in par.133 and Fig.14B, and PEG linker in par.144-145 and Fig.15A.
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. 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.
The disclosure (page 28) is objected to because of the following informalities:
Par.4 “Referring specifically now to FIG. 14C, there shown is a plot of time resolved digital immunoassay measurements of PCT at concentration of 31.3 pg/ml, where curve 1522 and curve 1524 are the mean values of three replicates for PCT and blank measurements, respectively.”
Par.5 “Referring specifically now to FIG. 14D, there shown is a plot of time resolved digital immunoassay measurements of PCT at concentration of 12500 pg/ml, where curve 1532 and curve 1534 are the mean values of three replicates for PCT and blank measurements, respectively.”
According to the description above, the curves 1522 and 1532 show the mean values of three replicates for PCT measurements in different concentrations. The curves 1524 and 1534 show the mean values of blank measurements.
However, based on Fig.12A and fig(s).14A-D and disclosure pages 25 and 28, the curves 1524 and 1534 should show the mean values of three replicates for PCT measurements in different concentrations and the curves 1522 and 1532 should show the mean values of blank measurements.
Appropriate correction in the disclosure is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“an automated counter coupled to the image processor and configured to perform real-time particle counting on the plurality of processed images to detect number of single gold nanoparticles immobilized by the tethered antibodies of the plurality of tethered antibodies” in claim 7;
“a delivery device for delivering a sample solution including procalcitonin (PCT) to the sensor” in claim 10.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
Claim limitation “an automated counter” is limited by the description in page 23 line 3 in the specification, which is automated particle counting algorithm; except as otherwise indicated in this Office action.
Claim limitation “a deliver device” is limited by the description in page 10 lines 21-22 in the specification, which can be any device for introducing a fluidic sample to sensor; except as otherwise indicated in an Office action.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 7-12 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 7 recites “an automated counter coupled to the image processor and configured to perform real-time particle counting on the plurality of processed images to detect number of single gold nanoparticles immobilized by the tethered antibodies of the plurality of tethered antibodies.” This limitation in claim 7 is being interpreted under 35 U.S.C. 112(f), it is being interpreted to cover the corresponding structure of the automated counter described in the specification as performing the claimed function. Accordingly, the automated counter in claim 7 is being interpreted as a physical component coupled to the image processor. However, in page 23 line 3 in the specification, the automated counter is defined as an automated particle counting algorithm, which is a software. Therefore, it is not clear if the automated counter is a physical component or a software coupled to the image processor.
All dependent claims are also rejected based on their dependency of the defected parent claims.
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.
Claim(s) 7 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Selvan (US20030129665) in view of Zybin (US20110311962) and Evans (US10571400).
For claim 7, Selvan teaches a system for detection an analyte comprising:
a sensor having a reflective metal surface and a plurality of capture antibodies, each antibody being tethered by a linker, where each tethered antibody is spaced apart from each other tethered antibody by at least one spacer;
(see par(s).182-185, and 285, fig.28A-B: Selvan teaches a reflective disc utilizing the strand of cross-linking agent DCHO (i.e., linker) to immobilize the capture agents within the flow channels 130 of the bio-disc; par.233: Selvan teaches the reflective layer 142 may be formed from a metal such as aluminum or gold; par.284, fig.27A-D: Selvan teaches that antibodies 186, which are bound to a strand of DCHO is spaced apart from each other by at least one DCHO agent);
a light source located at an incident angle with respect to the reflective metal surface;
(see par.85: teaching that “an incident beam of electromagnetic radiation from a radiation source is directed to the disc… A beam of electromagnetic radiation either transmitted through or reflected from the disc is detected”; par.117: Selvan teaches the light source directs light to the disc at the capture zones).
a camera positioned to receive scattered and reflected light from the sensor and configured to produce a plurality of raw images;
(see par.117: Selvan teaches that the photo detector detect light reflected from, or transmitted through the disc and provide an information-carrying signal from an optical disc assembly)
an image processor coupled to the camera and configured to generate a plurality of processed images by removing background noise from the plurality of raw images using differential imaging algorithms executed by a computer, where each processed image of the plurality of processed images is generated from a corresponding unique one raw image of the plurality of raw images; and
(see par.117: Selvan teaches that the processor is coupled to the photo detector circuit to obtain from the information-carrying signal, operational information used to operate the optical disc system and count items in the sample bound to the capture agents; see par.221: teaching the principal steps for data evaluation according to processing methods and computational algorithms related to the system; see par.319: teaching that data is collected and/or processed in a computer; see par.332-335 and fig(s).57A-D: teaching that the detection system provides a plurality of analogue signals (i.e., raw images) which are then directed to processor for transformation to an analogous digital signal (i.e., processed images), thereby encompasses each processed image of the plurality of processed images is generated from a corresponding unique one raw image of the plurality of raw images; see par.344 and fig.58: teaching the system can remove noise)
an automated counter coupled to the image processor.
(see par.117: Selvan teaches that the processor is coupled to the photo detector operating the optical disc system and count items in the sample bound to the capture agents, thus it encompasses a automated counter coupled to the image processor).
Figure 10 shows the system for detection of an analyte comprising a sensor disc 110, a light source 150, a camera or detector 158, an image processor 156, a counter or analyzer 168, which they are communicated to each other and to the computational system.
Selvan does not clearly teach that the camera, the image processor, and the counter are configured to produce plasmonic images; removing background noise from the plurality of raw plasmonic images; perform real-time particle counting on the plurality of processed images to detect number of single gold nanoparticles.
Zybin teaches system and method for high-resolution detection of nanoparticles on two-dimensional detector surfaces comprise: a sensor surface that can be selectively coated with receptors or antibodies selectively binding target analyte (e.g., viruses of a certain kind) thereby selectivity of the detection is ensured; a radiation source ; a detector; an observation optical assembly for imaging the radiation reflected by the sensor surface on the detector (see Title and par(s).2-13).
Particularly, the sensor has a reflective metal surface (see par.2);
the light source (e.g. radiation source) located at an incident angle with respect to the reflective metal surface (see Fig.1, par(s).31 and 44);
the camera positioned to receive scattered and reflected light from the sensor and configured to produce a plurality of raw images (see Fid.1, par(s).27 and 43-47: teaching that the detector is Charge Coupled Device (CCD) camera that can detect a surface plasmon spectrometer);
the image processor (see claim 10 of Zybin: teaching that detector is a Charge Coupled Device for detection of a plurality of time subsequent intensity signals for each pixel and processing means are provided adapted to generate time average values for the reduction of shot noise).
Zybin further teaches the images captured by the system are stored for further image processing (see par.49), for example, removing background noise from the plurality of raw plasmonic images using differential imaging algorithms executed by a computer, where each processed image of the plurality of processed images is generated from a corresponding unique one raw plasmonic image of the plurality of raw plasmonic images (see par(s).25-26: teaching that the method is able to “resolve the signal (particle) from a background signal… In order to avoid a situation where the signal disappears in the noise, preferably the background is corrected applying a reference image. The reference signal can be generated by calculating the average of the images, which are detected before binding a particle at the sensor surface.”)
Zybin also teaches the images of the plasmonic sensor are simultaneously monitored (i.e., real-time analysis), so the system provides the possibility to detect very low particle concentrations (see Fig.5 and par.28).
Zybin does not teach counting number of single gold nanoparticles as recited in claim 7.
Evans teaches a method for detecting a target molecule by using nanoparticles with optical plasmonic resonances, and at least one fluorescent probe (see Abstract, col.2 lines 45-50). The method uses a fluorescence microscope optics in the presence of fluorescent probes, which can be a gold plasmonic particle (see col.2 lines 45-55, col.4 lines 20-24), wherein the punctate light sources of individual plasmonic nanoparticle can be photographed and counted by manual or automated image analysis methods, thus enabling quantification of rare surface antigens (see col.3 lines 40-46). This teaching encompasses the limitation counting number of single gold nanoparticles to detect the target analyte.
Therefore, 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 system of Selvan, using detection system including the light source, a camera, a processor coupled to the camera taught by Zybin and using the automated image analysis algorithm coupled to the image processor taught by Evans for detection of an analyte because the detection system of Zybin and Evans can produce high-resolution images of the number of single gold nanoparticles captured on the sensor, thus provides the possibility to detect very low particle concentrations and quantify rare surface antigens (see Zybin par.28, Evans col.3 lines 40-46). A person of ordinary skill in the art would have been motivated to combine these teachings of Selvan, Zybin and Evans to improve the sensitivity of the detecting system.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Selvan, Zybin and Evans because they are directed to the system of detecting analyte comprising a sensor with a reflective metal surface, a light source, a camera with an image processor. The system of Zybin can be able to detect the signal from the sensor of Selvan because the sensor of Selvan is also a sensor with a reflective metal surface (see Selvan par(s).182-185, and Zybin par.2). The image processor of Zybin and Evans are analogous in terms of detecting and analyzing plasmonic images from the plasmonic nanoparticles on the sensor surface, thus it would be obvious to couple the automated image analysis algorithm into the image processor of Zybin so that the processor can detect and count the number of single gold nanoparticle from the plasmonic images.
For claim 12, Selvan, Zybin, and Evans teach the system of claim 7. Selvan does not teach wherein the light source comprises a super luminescence diode and an oil immersion objective.
Zybin teaches the radiation source is super luminescent diode, and immersion oil is used for fixing and improving the optical contact (see par(s).43-44), thus the teaching encompasses the light source comprising super luminescent diode and oil immersion objective). Zybin teaches that a super luminescent diode has no irregularities on the illuminated surface (speckles) like laser source (see par.44), and the optical microscopy is used to observe small objects and Immersion oil is used for fixing and improving the optical contact (see par.10 and par.43).
Evans also teaches that the method of counting single particle method comprises the use of microscope with oil objective to obtain oil immersion images (see Fig(s).3-4, col.5 lines 25-30, and col.13 lines 15-20).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the super luminescence diode and an oil immersion objective as taught by Zybin and Evans in the system of Selvan, Zybin, and Evans because it reduces irregularities on the illuminated surface and improves the optical contact. A person of ordinary skill in the art would have been motivated to combine these teachings of Selvan, Zybin and Evans to improve the sensitivity of the detecting system.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Selvan, Zybin and Evans because they are directed to the system of detecting analyte comprising a sensor with a reflective metal surface, a light source, a camera with an image processor. The system of Zybin can be able to detect the signal from the sensor of Selvan because the sensor of Selvan is also a sensor with a reflective metal surface (see Zybin par.2). The image processor of Zybin and Evans are analogous in terms of detecting and analyzing plasmonic images from the plasmonic nanoparticles on the sensor surface.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Selvan (US20030129665) in view of Zybin (US 20110311962) and Evans (US10571400), as applied in claim 7 above, and further in view of Worthington (US7200088).
For claim 8, Selvan, Zybin, and Evans teach the system of claim 7. Selvan does not teach wherein the gold nanoparticles comprise streptavidin coated gold nanoparticles.
Worthington teaches a system for detection an analyte that is analogous to the system taught by Selvan comprising a sensor having a reflective metal surface and a plurality of capture agents (see col.3 par.2), a light source (see col.29 par.1), a photo detector (i.e., camera) and a signal processing system (i.e., an image processor coupled to the camera) (see col.6 par.2).
Worthington teaches that the system can detect signal from a complex of antigen-ligand conjugated gold particle wherein the gold nanoparticles comprise streptavidin coated gold nanoparticles (see col.8 lines 56-65: teaching about detecting reporters having an affinity for a respective investigational feature by photo detector wherein the reporter can be gold bead; see col.55 lines 54-64: teaching that a reporter, coated with streptavidin or neutravidin that have an affinity for a biotinylated molecule, may be employed for detection purposes; see Fig.82 showing reporter beads having specific affinity for antigens bound to the surface; Figs. 83A, 83B, 83C, and 83D showing a method of using reporter beads to detect investigational features in a test sample; Fig.84 showing use of reporter beads, capture probes, and signal probes to detect investigational features in a test sample; Fig.85 showing hybridization of the investigational feature to the capture and signal probes). Moreover, the system can process the collected data as it is collected in a real-time manner, or may be stored and post processed by other computers, potentially reducing the complexity of the system (see col.36 par.3).
Therefore, 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 system of Selvan, using nanoparticle coated with streptavidin as a reporter for the detection system as taught by Worthington because Selvan and Worthington teach the analogous analysis systems and Worthington provides an alternative technique to detect an analyte in the test sample that can be applied to the system of detection analyte taught by Selvan.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Selvan (US20030129665) in view of Zybin (US 20110311962), Evans (US10571400) and Worthington (US7200088), as applied in claims 7 and 8 above, and further in view of Zhou et al. (Detection of procalcitonin (PCT) using the double antibody sandwich method based on fluorescence resonance energy transfer between upconversion nanoparticles and quantum dots, Anal. Methods, 2018, 10, 1015–1022).
For claim 9, Selvan, Zybin, Evans, and Worthington teach the system of claim 8. Selvan in view of Worthington teaches the gold nanoparticles comprise streptavidin coated gold nanoparticles (see discussion of Worthington in claim 8 above, see Fig(s).82-85). Selvan does not teach wherein the capture antibodies are configured to bind procalcitonin having a bound detection antibody, and the bound detection antibody is configured to bind the streptavidin coated gold nanoparticles.
Zhou teaches a method of detection procalcitonin (PCT) using nanoparticle based method (see Abstract). Zhou teaches that procalcitonin (PCT) plays a crucial role in providing a promising biomarker for monitoring bacterial infections because the PCT concentration increases to several thousand times higher in the case of severe parasitic, bacterial or fungal infection than normal physiological concentrations (see page 1015 col.1 par.1). The detection of PCT comprises the capture antibody and detection antibody that can bind to PCT (see Schemes 1-2, page 1017 col.1 par.3-4: teaching 3D3-antibody as a capture antibody and 2E6-antibody as a detection antibody, the detection antibody is coated on nanoparticle, the detection is based on the antibody–antigen–antibody “sandwich” immunoassay).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the system of Selvan, Zybin, Evans, and Worthington to detect PCT in the test sample because detecting PCT can help the diagnosis of parasitic, bacterial or fungal infection in a subject as taught by Zhou. Accordingly, it would have been obvious to use the capture antibodies that can bind to PCT to form a complex of antibody-PCT-antibody coupled to gold nanoparticle to detect PCT in the sample as taught by Zhou.
One having an ordinary skill in the art would have had a reasonable expectation of success in detecting PCT using the system of Selvan, Zybin, Evans, and Worthington because Selvan and Worthington teaches that the system can detect signal from a complex of capture antibody-antigen-detection antibody, wherein the detection antibody can be conjugated on gold particle via the link of biotin on the detection antibody and streptavidin on the gold particle (see Worthington col.8 lines 56-65, col.55 lines 54-64, Fig(s).82-85). Zhou specifically teaches the method of detecting PCT using the antibody–antigen–antibody “sandwich” immunoassay, wherein the PCT detection antibody is conjugated on a particle. Therefore the method taught by Zhou can be able to integrate to detection system of Selvan and Worthington.
For claim 10, Selvan, Zybin, Evans, Worthington, and Zhou teach the system of claim 9.
Selvan teaches the system further comprising a delivery device for delivering a sample solution to the sensor (see Selvan at least in fig.28I), wherein the sample can include PCT because the system of Selvan, Zybin, Evans, Worthington, and Zhou can detect PCT by the PCT’s capture antibody as discussed in claim 9 above.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Selvan (US20030129665) in view of Zybin (US20110311962), and Evans (US10571400), as applied in claim 7, and further in view of Kim et al. (Protein immobilization techniques for microfluidic assays, Biomicrofluidics 7, 041501 (2013)).
For claim 11, Selvan, Zybin, and Evans teach the system of claim 7. Selvan teaches that the linker is activated aldehyde dextran (DCHO), but does not teach wherein the linker comprises a polyethylene glycol (PEG) linker.
Kim teaches protein immobilization techniques for microfluidic assays including the use of a spacer or a linker (e.g., PEG) with a surface-attaching head group and a protein-binding tail group (see Fig.2d, and page 9 par.1). This technique has been widely adopted to reduce steric hindrance so that the active sites of an antibody should be accessible to reaction partners (i.e., proteins face away from the immobilization surface to mitigate steric hindrance and are not sterically blocked by neighboring immobilized proteins) (see page 8 par.2). Kim also teaches that dextran, chitosan, and PEG are alternatively used as a spacer for improved assay sensitivity (see page 18 last paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the dextran linker in system of Selvan by the PEG linker as taught by Kim because they are functionally equivalent to be a spacer for immobilizing the protein (e.g., antibody) on the sensor surface as taught by Kim. By using the linker or spacer, the assay sensitivity would be improved because the linker reduces steric hindrance so that the active sites of an antibody should be accessible to reaction partners.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Selvan and Kim because they are directed to a technique to immobilize the protein in microfluidic assay.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached on Mon-Fri 8:30-6:30 CT.
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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 January 7, 2026