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 .
Claim Interpretation
Regarding limitations recited in claims 1-13 which are directed to a manner of operating the disclosed system, it is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See MPEP § 2114 and 2115. Further, it has been held that process limitations do not have patentable weight in an apparatus claim. See Ex parte Thibault, 164 USPQ 666, 667 (Bd. App. 1969) that states “Expressions relating the apparatus to contents thereof and to an intended operation are of no significance in determining patentability of the apparatus claim.”
The Applicants are advised, the recited functions (see: “configured to receive one or more chemical reagents…”, etc.) do not require any further elements from the disclosed plurality of inlets/wells in the prior art.
It is the position of the Examiner that the prior art device is fully capable of performing the instantly recited functions.
For purposes of compact prosecution, the functional capabilities recited in the claims have been addressed as if the Applicants positively recited the “one or more chemical reagents”, but the Applicants are advised, the functional limitations recited in the instant claims do not further limit the scope of the instant invention as alleged in the Applicant’s remarks filed 04/13/2026.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rossi (SCALABLE, POINT-OF-CARE, MICROFLUIDIC APPROACH FOR ASSESSING THROMBOSIS AND HEMOSTASIS).
Regarding claim 1, Rossi discloses a system for detecting and quantifying drug and/or chemical interactions within a biological sample, the system comprising:
a detection instrument configured with control functionality (4.2.2. Device preparation and flow control, see: controller (Fluigent) operated via usb communication with a laptop; 4.2.4. Platelet and fibrin detection during clotting, see: LED-based Lumascope 620, an epifluorescence microscope; and ImageJ, an image analysis software platform);
a processing device associated with the detection instrument that includes software, wherein the processing device analyzes multiple independent biological signals associated with clots formed by the biological sample and statistically evaluates one or more of the multiple independent biological signals with a population data set to compute a hemostatic result for the biological sample (4.2.2. Device preparation and flow control, see: controller (Fluigent) operated via usb communication with a laptop; 4.2.4. Platelet and fibrin detection during clotting, see: ImageJ, an image analysis software platform; 4.2.7. Statistical analysis, see: Statistical significance was calculated by two-tailed t-test, using GraphPad Prism (GraphPad Software)); and
an assay device configured to receive physiological flow of the biological sample therethrough, and to effectuate biological processes by which clots accumulate at a discrete reaction zone of the assay device (Figure 2.2, see: 8 by 1 PDMS device channel schematic which includes a reaction zone; Figure 3.1, see: 8-channel device);
wherein the control functionality of the detection instrument varies conditions experienced by the biological sample in the assay device (4.2.2. Device preparation and flow control, see: controller (Fluigent) operated via usb communication with a laptop controls the flow rate);
wherein the assay device is configured to receive one or more chemical reagents compatible with the biological sample and to detect the hemostatic function of the biological sample within the discrete reaction zone (4.2.4. Platelet and fibrin detection during clotting, see: Platelets were labeled in whole blood by the addition of a non-function blocking, AlexaFluor 488-conjugated anti-CD61 molecule (Bio-Rad Laboratories), while fibrin was quantified via addition of AlexaFluor 594-conjugated human fibrinogen (Life Technologies));
wherein the assay device is configured to receive one or more drug reagents compatible with the biological sample to modify the accumulation of the clots within the discrete reaction zone (4.2.5. DOAC reversal and detection, see: Andexanet Alfa (AA, Portola pharmaceuticals) was added to a final concentration of either 50 or 300 nM, in order to assess the impact on blood without inhibitor present, and additional Xa inhibitor, either rivoraxaban or apixaban, to the match the drug already in the patient blood, was added to two of the channels for each patient); and
wherein the statistical evaluation by the processing device of the multiple independent signals associated with the clots with the population data set computes at least one of a drug presence, a drug class, a drug level in relation to a threshold, or a drug concentration, within the biological sample (4.2.6. DOAC concentration prediction, see: the relative fluorescence intensity of the patient’s unmodified blood and the high reversal agent condition were compared. These were then scaled to a previously measured dose response of the fibrin fluorescence intensity to apixaban and rivoraxaban added in vitro to healthy donor whole blood).
Regarding claim 2, Rossi further discloses a fluorescent assembly capable of detection of the biological process by way of fluorescent labeling and detection of a resulting accumulating fluorescent signal (4.2.4. Platelet and fibrin detection during clotting, see: LED-based Lumascope 620, an epifluorescence microscope), and comprising the processing device configured to receive as input a measurement of the fibrin and platelets to determine at least one of the drug presence, the drug class, the drug level in relation to the threshold, or the drug concentration, within the biological sample, and the processing device is configured to correlate a measured fluorescent intensity with accumulation of the fibrin and platelets in flow paths of the assay device (4.2.4. Platelet and fibrin detection during clotting, see: ImageJ, an image analysis software platform; 4.2.7. Statistical analysis, see: Statistical significance was calculated by two-tailed t-test, using GraphPad Prism (GraphPad Software)).
Regarding claim 3, Rossi further discloses the one or more chemical reagents or the one or more drug reagents is a fluorescent reagent capable of labeling fibrin and platelets from the biological sample (4.2.4. Platelet and fibrin detection during clotting, see: Platelets were labeled in whole blood by the addition of a non-function blocking, AlexaFluor 488-conjugated anti-CD61 molecule (Bio-Rad Laboratories), while fibrin was quantified via addition of AlexaFluor 594-conjugated human fibrinogen (Life Technologies)).
Regarding claim 4, Rossi further discloses a light source for monitoring clot development in flow paths of the assay device and for detecting a fluorescent reaction of the one or more chemical reagents or the one or more drug reagents (4.2.4. Platelet and fibrin detection during clotting, see: LED-based Lumascope 620, an epifluorescence microscope).
Regarding claim 5, Rossi further discloses a first inlet port, a second inlet port, a third inlet port, and a fourth inlet port, each configured to receive the biological sample, (Figure 3.1, see: Q1-8 inlet wells which are capable of performing the instantly recited functions); an outlet port (Figure 3.1, see: outlet port); and microfluidic flow paths fluidically connecting each of the first, second, third and fourth inlet ports with the outlet port (Figure 3.1, see: plurality of channels); wherein introduction of the biological sample into the respective first, second, third and fourth inlet ports generates a fibrin signal and a platelet signal (4.2.4. Platelet and fibrin detection during clotting, see: fluorescence images to obtain kinetic data for platelet and fibrin accumulation).
Regarding claim 6, Rossi further discloses at least one of the first, second, third and fourth inlet ports is configured to receive a molar excess of drug to provide a fully attenuated fibrin or platelet signal (4.2.5. DOAC reversal and detection, see: Andexanet Alfa (AA, Portola pharmaceuticals) was added to a final concentration of either 50 or 300 nM, in order to assess the impact on blood without inhibitor present, and additional Xa inhibitor, either rivoraxaban or apixaban, to the match the drug already in the patient blood, was added to two of the channels for each patient).
Regarding claim 7, Rossi further discloses at least one of the first, second, third and fourth inlet ports is configured to receive a first reversal drug to identify a first class of drug present in the biological sample, and wherein at least one of the first, second, third and fourth inlet ports is configured to receive a second reversal drug to identify a second class of drug present in the biological sample (4.2.5. DOAC reversal and detection, see: Andexanet Alfa (AA, Portola pharmaceuticals) was added to a final concentration of either 50 or 300 nM, in order to assess the impact on blood without inhibitor present, and additional Xa inhibitor, either rivoraxaban or apixaban, to the match the drug already in the patient blood, was added to two of the channels for each patient).
Regarding claim 8, Rossi further discloses at least one of the first reversal drug and the second reversal drug inhibits, antagonizes or attenuates an activity of a Xai or DTi class DOAC (4.2.5. DOAC reversal and detection, see: Andexanet Alfa (AA, Portola pharmaceuticals) was added to a final concentration of either 50 or 300 nM, in order to assess the impact on blood without inhibitor present, and additional Xa inhibitor, either rivoraxaban or apixaban, to the match the drug already in the patient blood, was added to two of the channels for each patient).
Regarding claim 9, Rossi further discloses at least one of the first reversal drug and the second reversal drug inhibits, antagonizes or attenuates an activity of the anti-platelet drug (4.2.5. DOAC reversal and detection, see: Andexanet Alfa (AA, Portola pharmaceuticals) was added to a final concentration of either 50 or 300 nM, in order to assess the impact on blood without inhibitor present, and additional Xa inhibitor, either rivoraxaban or apixaban, to the match the drug already in the patient blood, was added to two of the channels for each patient).
Regarding claim 10, Rossi further discloses a processing device is configured to manipulate the biological sample and monitor a direct response of the biological sample to at least one of (i) the first and/or second reversal drug to identify the drug class present in the biological sample, and (ii) a molar excess of the fibrin or platelet attenuating drug to identify a drug or chemical level or concentration present in the biological sample (4.2.6. DOAC concentration prediction, see: the relative fluorescence intensity of the patient’s unmodified blood and the high reversal agent condition were compared. These were then scaled to a previously measured dose response of the fibrin fluorescence intensity to apixaban and rivoraxaban added in vitro to healthy donor whole blood).
Regarding claim 11, Rossi further discloses a processing device is configured to compare a fibrin or platelet signal to a fully recovered fibrin or platelet signal, compare a fibrin or platelet signal to a fully attenuated fibrin or platelet signal, and compare all other coincident signals for all reactions to determine the drug presence, the drug class, the drug level in relation to the threshold, or the drug concentration, in the biological sample (4.2.6. DOAC concentration prediction, see: the relative fluorescence intensity of the patient’s unmodified blood and the high reversal agent condition were compared. These were then scaled to a previously measured dose response of the fibrin fluorescence intensity to apixaban and rivoraxaban added in vitro to healthy donor whole blood).
Regarding claim 12, Rossi further discloses the reaction zone comprises at least one of (i) a single flow path with separate clot sites in a serial configuration having different tissue factor (TF) concentrations (optional limitation), and (ii) two flow paths in parallel along the same plane, each of the flow paths having different tissue factor (TF) concentrations (5.1.2.1 Device Design, Fabrication and Preparation, see: plurality of parallel channels coated with collagen and either tissue factor or vWF, which means some channels have a zero concentration of tissue factor, which is a different concentration from the channels coated with tissue factor).
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(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rossi (SCALABLE, POINT-OF-CARE, MICROFLUIDIC APPROACH FOR ASSESSING THROMBOSIS AND HEMOSTASIS), in view of Hu et al. (US 2002/0074271 A1).
Regarding claim 13, Rossi further discloses the flow paths each having a clot site in a non-overlapping configuration relative to each other having different tissue factor (TF) concentrations (5.1.2.1 Device Design, Fabrication and Preparation, see: plurality of parallel channels coated with collagen and either tissue factor or vWF, which means some channels have a zero concentration of tissue factor, which is a different concentration from the channels coated with tissue factor).
Rossi does not explicitly disclose the flow paths being on separate planes of the assay device.
Hu teaches an plurality of analogous multilevel microfluidic flow structure configurations (Fig. 1C, Fig. 3). It would have been obvious to rearrange the parts of the device disclosed by Rossi, into a multilevel arrangement as taught by Hu, in order to provide for a higher density device in a smaller footprint, thereby providing a reduction in the size of fluid handling and detection devices (Hu: [0006]).
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “a consolidated system for arriving at a clinically useful result” or “a statistical model (regression or CART) that can then determine/report an unknown without the need for a standard curve”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant's argument that the instant invention is capable of “utilizing one model to predict a value for any unknown, regardless of the drug type”, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
The Applicants are advised even if the recited “processing device” were claimed as being “programmed to automatically perform” the instantly recited functions/capabilities, the scope of the recited “statistical evaluation” of “multiple signals associated with the clots with the population data set” to compute “a drug concentration” is broad enough to fully encompass the prior art’s allegedly well known “method for deriving a drug concentration” based on a standard curve.
For the above reasons, the previous grounds of rejection have been maintained with updates to address the claim amendments filed 04/16/2026.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J EOM whose telephone number is (571)270-7075. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at 5712721254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT J EOM/ Primary Examiner, Art Unit 1797
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