DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-16, drawn to a method of isolating and/or purifying one or more target analytes in the reply filed on September 9, 2025 is acknowledged.
During a phone interview, Applicant provisionally elected Species A1, vacuum filtration for concentrating the urine sample, without traverse to prosecute the invention of Group I, Species A1, claims 1-2, 6-14, and 16. Affirmation of this election must be made by applicant in replying to this Office action. Claims 3-5, 15, and 17-30 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
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.
Claim(s) 1, 6-14, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foret (F. Foret, Macrofluidic Device for Preparative Concentration Based on Epitachophoresis, Anal. Chem. 2019(91), pp. 7047-52) in view of Visser (N.F.C., Visser, Sample preparation for peptides and proteins in biological matrices prior to liquid chromatography and capillary zone electrophoresis, Anal. Bioanal. Chem. 2005 (382), pp. 535-558).
Regarding claim 1, Foret teaches a method of isolating and/or purifying one or more target analytes from a sample ([Abstract]: to concentrate and collect ions from several milliliter sample volumes to microliter fractions), the method comprising:
adding the sample to a first electrolyte to form a first mixture ([Abstract]: the milliliter volume sample is mixed with the terminating electrolyte);
applying a voltage difference between a first electrode and a second electrode (p. 7049, bridging para. of col. 1-2: power supply was run at a constant power mode for 1 h), wherein:
the first electrode is disposed in the first mixture (Fig. 1A-B; p. 7049, col. 1, para. 4: the stainless steel wire ring electrode was secured on the edge of the circular separation compartment; also see Fig. in [Abstract]: circular electrode in the TE/sample solution),
the second electrode is disposed in a second electrolyte (Fig. 1A-B; p. 7049, col. 1, para. 4: the second Pt-wire electrode placed in the leading electrolyte LE electrode reservoir), and
the first electrolyte is different from the second electrolyte (p. 7049, col. 1, para. 6: the leading electrolyte LE and the terminating electrolyte TE are different);
flowing, using the voltage difference (p. 7049, bridging para. of col. 1-2: power supply was run at a constant power mode for 1 h), the one or more target analytes in one or more focused zones within the second electrolyte to the second electrode ([Abstract]: the sample migrates through the gel toward the center; Fig. 1D: epitachophoretic zone migration); and
collecting the one or more target analytes by collecting a second mixture comprising the one or more focused zones (Fig. 1D; p. 7049, col. 1, para. 5: a mini dialysis cup was used for capture and collection of the analyte zone), wherein the concentration of any of the one or more target analytes in the second mixture is higher than the concentration of the respective target analyte in the sample (p. 7051, col. 1, last para.: the concentration increased approximately 30-fold in the collected fraction).
Foret does not disclose the sample is a urine sample or concentrating the urine sample to form a concentrated urine sample, the concentrated urine sample having a concentration of the one or more target analytes that is at least 10 times higher than an initial concentration of the one or more target analytes in the urine sample;
However, Visser teaches sample preparation of peptides/proteins from biological matrices, e.g., homogenization, centrifugation, precipitation, solid-phase extraction (SPE), etc., before the separation such as liquid chromatography (LC) or capillary zone electrode (CZE) (p. 535, col. 2, para. 2). The main gold of the in-line SPE-CZE system is able to obtain preconcentration and preconcentration factors of several thousands (p. 545, col. 1, last para.), and may be used for urine sample (p. 547, col. 1, last para.). One example of microdialysis before the spPC device would obtain a concentration of 500 (p. 545, col. 2, para. 2). Further, isotachophoresis (ITP) may be used after the elution of the sample components of the SPE device (p. 545, col. 2, para. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Foret by incorporating a step of pre-concentrating the urine sample as taught by Visser before the epitachophoresis because the sample-preparation technique, e.g., SPE, before the separation technique, e.g., CZE, ITP, are known in the art to obtain target analyte for quantitative detection (Visser, p. 535, col. 2, para. 2; p. 542, col. 2, para. 2). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 6, Foret teaches wherein the one or more target analytes comprises DNA ([Abstract]: DNA fragments).
Regarding claim 7, Foret teaches wherein the one or more target analytes comprises cell-free nucleic acids ([Abstract]: DNA fragments; p. 7047, col. 1, last para.).
Regarding claim 8, Foret in view of Visser teaches wherein concentrating the urine sample comprises filtering the urine sample by molecular weight (Visser, p. 537, col. 1, para. 1: using ultrafiltration, in combination with a microconcentrator, a rough protein fractionation or removal of low molecular weight components can be achieved).
Regarding claim 9, Foret in view of Visser teaches wherein filtering the urine sample by molecular weight comprises removing components of the urine sample with a molecular weight above or below a cutoff in a range of 3,000 to 10,000 (Visser, p. 551, col. 1, para. 3: to remove all interfering plasma protein a membrane with a molecular weight cut-off of 5 kDA had to be used).
Regarding claim 10, Foret and Visser disclose all limitations of claim 1. Foret fails to teach wherein the concentration of the one or more target analytes in the concentrated urine sample is at least 40 times higher than the initial concentration.
However, Visser teaches one example of microdialysis before the spPC device would obtain a concentration of 500 (p. 545, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Foret by pre-concentrating the sample by a factor within the claimed range as suggested by Visser because that factor for pre-concentrating sample for subsequent separation is known in the art to obtain target analyte for quantitative detection (Visser, p. 545, col. 2, para. 2; p. 535, col. 2, para. 2; p. 542, col. 2, para. 2). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 11, Foret in view of Visser teaches wherein the concentration of any of the one or more target analytes in the second mixture is at least two times higher than the concentration of the respective target analyte in the concentrated urine sample (p. 7050, col. 1, para. 4: the sample was concentrated 23 times).
Regarding claim 12, Foret in view of Visser teaches wherein the volume of the urine sample is from 10 ml to 50 ml (p. 7048, col. 1, para. 2: 15 mL input).
Regarding claim 13, Foret and Visser disclose all limitations of claim 1, but fail to teach wherein the volume of the urine sample is from 0.5 ml to 2.5 ml.
However, Foret teaches the sample is milliliter volume sample ([Abstract]) in the several ml range (p. 7048, col. 1, para. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Foret and Visser by adjusting the sample volume within the claimed range because in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 14, Foret teaches wherein the second mixture comprises 2 or more focused zones (Fig. 3: focused zones for red dye SPADNS and blue dye Patent Blue V).
Regarding claim 16, Foret teaches the method further comprising sequencing a target analyte of the one or more target analytes in the second mixture (p. 7047, bridging para. of col. 1-2: analysis of ctDNA by next-generation sequencing requires concentration of extracted DNA into small volumes, i.e., the concentrated sample in the second collected mixture of the disclosed epitachophoresis device).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foret in view of Visser, and further in view of Akhavan-Tafti (WO 2006/019388).
Regarding claim 2, Foret and Visser disclose all limitations of claim 1. Visser further discloses some “simple” sample-preparation technique such as centrifugation, filtration and/or precipitation (p. 542, col. 2, para. 1). Foret and Visser fail to teach wherein concentrating the urine sample comprises vacuum filtration
However, Akhavan-Tafti teaches separating the matrix and nucleic acid material bound thereto from the remaining sample components using centrifugation or vacuum filtration (p. 3, ll. 17-21).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Foret and Visser by substituting the sample-preparation, e.g., centrifugation, with vacuum filtration as taught by Akhavan-Tafti because they are alternative approaches for sample preparation and the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795
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