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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08 April 2026 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant’s arguments, see Remarks page 9, filed 11 March 2026, with respect to the objection to the drawings have been fully considered and are persuasive in light of the amendments. The rejection of the drawings have been withdrawn.
Applicant’s arguments, see Remarks page 9, filed 11 March 2026, with respect to the rejection under 35 USC 112(b) have been fully considered and are persuasive in light of the amendments. The 112(b) rejection of claim 10 has been withdrawn due to the cancellation of the claim.
Applicant's arguments, see Remarks page 9, filed 11 March 2026, with respect to the rejection of the claims under 35 USC 102 and 103 have been fully considered but they are not persuasive.
Applicant’s arguments hinge on the claim that the limitation of “the first reagent is present in the separation membrane at a concentration ranging from about 0.7 milligrams/square centimeter to about 10 milligrams/square centimeter…” is not an optimization within prior art conditions or through routine experimentation. The examiner disagrees, and believes that the applicant’s arguments are not commensurate with the scope of the claimed invention.
The scope of claim 1 encompasses a device with a separation membrane infused with a first reagent, the first reagent comprising a polyanionic non-high density lipoprotein binding reagent. On this basis alone, any argument made by the applicant regarding the relationship between the target protein and the received signal as outlined in the specification is not convincing; the scope of the claims encompasses any polyanionic non-high density lipoprotein binding reagent and any means of detection, not merely the one relied upon in the specification. A device with a means of detection having greater specificity may benefit from a lower concentration of the first reagent.
Likewise, the broad scope of the substances which could potentially serve as the first reagent means that any measurement based on weight would have to be optimized for the weight of the reagent. A molecule which is heavier but less efficient at binding may only work at a higher range of concentrations. A molecule which can bind multiple first protein molecules may require a lower weight. This is to say nothing of, for instance, what counterions might be present in the dry reagent, which greatly affects the dry weight of a reagent but which does not affect the binding efficiency.
Lastly, any consideration of concentration is also a consideration of the sample being assayed. Applicant’s claims rely heavily on functional language, including “for precipitating a first protein contained in the blood fluid sample,” “wherein the separation membrane separates red blood cells from the blood fluid sample,” and “configured to elicit a quantifiable response in the presence of a second protein.” Providing these limitations with the appropriate patentable weight results in a device configured to assay a blood sample containing at least red blood cells and two proteins. A highly concentrated blood sample may require a high concentration of a first reagent. An extremely dilute blood sample may benefit from a lower concentration of a first reagent.
Accordingly, 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 device of Thakore et al with a first reagent present in the separation membrane at a concentration ranging from about 0.7mg/cm2 to about 10mg/cm2 based on a dry weight of the first reagent present on the separation membrane, as optimization of a results-dependent variable. In the case of the instant invention, one of ordinary skill in the art would be motivated by the differing dry weights of possible first reagents, the differing binding efficiencies of possible first reagents, the differing detection efficiencies of possible detection membranes, possible cross-talk between the first reagent and the detection membrane, and different sample concentrations to optimize the concentration of the first reagent based on the result of the detected signal from the detection membrane.
Status of Claims
Applicant's amendments to the claims filed 11 March 2026 have been entered. Applicant's remarks filed 11 March 2026 are acknowledged.
Claims 1, 3, and 7 are in status “Currently Amended.” Claims 2, 5, 8, 9, 11, and 16 are in status “Original” or “Previously Presented.” Claims 4, 6, 10, 12-15, and 17-18 are cancelled. Claims 19 – 27 are withdrawn as due to non-elected subject matter.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1 – 3, 5, 7, 11, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Thakore et al (EP 0408223 A1, cited on the IDS submitted 29 December 2022).
With regards to claim 1, Thakore et al teaches;
The claimed “an assay device for analyzing a blood fluid sample” has been read on the taught (Abstract, “The present invention involves a method and device for obtaining plasma from whole blood and determining one or more analytes contained therein.”);
The claimed “a separation membrane” and “wherein the separation membrane separates red blood cells from the blood fluid sample” have been read on the taught (Column 5, line 57, “…the present invention utilizes tangential flow of blood underneath a suitable microporous plasma separation membrane so that the red cells are retained on the underside but clean plasma is obtained on the top surface of the membrane.”);
The claimed separation membrane “containing a first reagent for precipitating a first protein contained in the blood fluid sample” has been read on the taught (Column 9, line 56, “The precipitants, for example, can be incorporated within the microporous plasma separation membrane…”);
The claimed “wherein the first reagent comprises a polyanionic non-high density lipoprotein binding reagent” has been read on the taught (Column 10, line 11, “…precipitation steps using precipitants such as […] dextran sulfate…”; [0070] of the instant specification teaches that a sulfonated polysaccharide is a polyanionic non-high density lipoprotein binding reagent. Dextran sulfate reads on a sulfonated polysaccharide.).
The claimed “a detection membrane configured to elicit a quantifiable response in the presence of a second protein present in the blood fluid sample” has been read on the taught (Column 4, line 42, “This test membrane is capable of reacting with the plasma (i.e. one of its components) to display at least one analyte characteristic thereof.”);
The claimed detection membrane “wherein the quantifiable response corresponds to an amount of the second protein present in the detection membrane” has been read on the taught (Column 4, line 45, “Preferably, colorimetric reaction takes place and color intensity indicates concentration level of the analyte in the blood.”; Column 9, line 16, “For analyzing analytes such as albumin or other proteins…”);
The claimed “wherein the separation membrane concurrently precipitates the first protein and separates the red blood cells from the blood fluid sample that reaches the detection membrane” has been read on the taught (Column 9, line 56, “The precipitants, for example, can be incorporated within the microporous plasma separation membrane […] so that the precipitation step occurs on-line and the plasma reaching the test membrane is free of the interferent.”).
Thakore et al does not explicitly disclose wherein the first reagent is present in the separation membrane at a concentration ranging from about 0.7 milligrams/square centimeter to about 10 milligrams/square centimeter based on a dry weight of the first reagent present on the separation membrane.
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 device of Thakore et al with a first reagent concentration ranging from about 0.7 milligrams/square centimeter to about 10 milligrams/square centimeter based on a dry weight of the first reagent present on the separation membrane, as optimization of a results-dependent variable. In the case of the instant invention, one of ordinary skill in the art would be motivated by the differing dry weights of possible first reagents, the differing binding efficiencies of possible first reagents, the differing detection efficiencies of possible detection membranes, possible cross-talk between the first reagent and the detection membrane, and different sample concentrations to optimize the concentration of the first reagent based on the result of the detected signal from the detection membrane.
With regards to claim 2, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the first reagent is not immobilized on the separation membrane” has been read on the taught (Column 15, line 50, “…in this case was first soaked in an aqueous 20% by weight solution of PEG 2000 ( a precipitating agent for LDL and VLDL cholesterol) and allowed to dry prior to use.”; A solution soaking and being allowed to dry reads on the reagent not being immobilized on the separation membrane.).
With regards to claim 3, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the first protein comprises a non-high density lipoprotein, wherein the second protein comprises a high density lipoprotein” has been read on the taught (Column 10, line 8, “An application that makes use of the precipitation step is the measurement of high density lipoprotein cholesterol (HDL cholesterol) which typically needs precipitation steps […] to precipitate out cholesterol in low density and very low density lipoproteins (LDL and VLDL), followed by centrifugation. The present invention device achieves this on-line by loading the precipitant into the microporous plasma separation membrane.”; Measurement of high density lipoprotein cholesterol reads on the second protein comprising a high density lipoprotein. Precipitation of LDL and VLDL reads on the first protein comprising a non-high density lipoprotein.).
With regards to claim 5, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the separation membrane includes pores having a pore size ranging from about 0.1 micrometers to about 7.5 micrometers” has been read on the taught (Column 6, line 41, “In general, suitable pore-sizes of such membranes should be between about 0.02 to 10 microns, with the preferred range between 1 to 5 microns.”; The preferred range being between 1 and 5 microns reads on the separation membrane being between 0.1 micrometers to about 7.5 micrometers).
With regards to claim 7, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the first reagent comprises a sulfonated polysaccharide, heparin, or phosphotungstic acid” has been read on the taught (Column 10, line 11, “…precipitation steps using precipitants such as […] dextran sulfate…”; Dextran sulfate reads on a sulfonated polysaccharide.).
With regards to claim 11, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the separation membrane comprises a polysulfone, a polyethersulfone, a polyarylsulfone, a nylon, a nitrocellulose, cellulose filter paper, glass fiber, or a combination thereof” has been read on the taught (Column 6, line 37, “… a 5 micron microporous membrane made from nitrocellulose of Schleicher and Schuell (Keene, New Hampshire) performed optimally in separating plasma from whole blood.”; A microporous membrane made from nitrocellulose reads on the separation membrane comprising a nitrocellulose.).
With regards to claim 16, the device of claim 1 is obvious over Thakore et al.
Thakore et al additionally teaches;
The claimed “wherein the quantifiable response in the presence of a second protein present in the blood fluid sample comprises a color change of at least a portion of the detection membrane” has been read on the taught (Column 5, line 42, “The present invention plasma separation method can be utilized for colorimetric detection of blood analytes.”; Colorimetric detection reads on the response comprising a color change.).
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Thakore et al (EP 0408223 A1) in view of Jones (US 20040235182 A1).
With regards to claim 8, the device of claim 7 is obvious over Thakore et al.
Thakore et al additionally teaches the use of a Group II cation with a precipitant, as read on the taught (Column 10, line 13, “…precipitants such as […] magnesium tungstate…”).
However, Thakore et al does not explicitly teach wherein the first reagent comprising a sulfonated polysaccharide, heparin, or phosphotungstic acid further comprises a Group II cation selected from the group of Mg, Mn, and Ca.
In the analogous art of assay devices for blood analysis, Jones teaches;
The claimed “the first reagent comprising a sulfonated polysaccharide, heparin, or phosphotungstic acid” and “wherein the first reagent further comprises a Group II cation selected from the group of Mg, Mn, and Ca” has been read on the taught ([0032], “The reagent pad […] contains at least one reagent effective to selectively remove LDL and VLDL particles from the fluid sample… Such reagents, which are known in the art, include sulfonated polysaccharides, heparin, and phosphotungstate, in the presence or absence of a group II cation, such as Mg2+, Mn2+, or Ca2+.”).
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 precipitant reagent as taught by Thakore et al with the specific sulfonated polysaccharide in the presence of a group II cation as taught by Jones. Per MPEP 2143(I)(A), combining prior art elements according to known methods to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Thakore et al teaches a device including a precipitating reagent. The prior art of Jones teaches the use of a specific precipitating reagent, and the only different between the claimed invention and the prior art is the lack of the combination. One of ordinary skill in the art could have combined the elements as claimed by the known methods, for the predictable result of removing non-high density lipoproteins from the plasma.
With regards to claim 9, the device of claim 8 is obvious over Thakore et al in view of Jones.
Thakore et al does not explicitly disclose wherein the first reagent comprises phosphotungstic acid and Mg.
Jones additionally teaches;
The claimed “wherein the first reagent comprises phosphotungstic acid and Mg” has been read on the taught ([0032], “The reagent pad […] contains at least one reagent effective to selectively remove LDL and VLDL particles from the fluid sample… Such reagents, which are known in the art, include sulfonated polysaccharides, heparin, and phosphotungstate, in the presence or absence of a group II cation, such as Mg2+, Mn2+, or Ca2+.”).
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 precipitant reagent as taught by Thakore et al with the specific sulfonated polysaccharide in the presence of a group II cation as taught by Jones. Per MPEP 2143(I)(A), combining prior art elements according to known methods to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Thakore et al teaches a device including a precipitating reagent. The prior art of Jones teaches the use of a magnesium phosphotungstate, and the only different between the claimed invention and the prior art is the lack of the combination. One of ordinary skill in the art could have combined the elements as claimed by the known methods, for the predictable result of removing non-high density lipoproteins from the plasma.
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 ALISON CLAIRE GERHARD whose telephone number is (571)270-0945. The examiner can normally be reached M-F, 9:00 - 5:30pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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