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 .
Response to Amendment
Applicant’s amendment and remark filed on 05/18/2026 has been entered. Claims 5-6 are cancelled. New claims 9-14 are added. Claims 1-4 and 7-14 remain pending and examined herein. Applicant’s remark and amendment have overcome each and every objection and rejection under 101 set forth in previous Office Action mailed on 03/06/26.
Status of Rejections
The objection of claims 1 and 2 and specification is withdrawn in light of Applicant’s Amendment.
The rejection of claims 5-6 is obviated by Applicant’s cancellation.
The rejection of claims 1-4 and 7-8 under 101 is withdrawn in view of Applicant’s amendment and remark.
The 103 rejection of claims 1-4 and 7-8 is maintained.
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.
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) 1-4, 8-12, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sakuma (US20090087913A1) in view of Lostia (Measurement of Ethyl Glucoronide, Ethyl Sulphate and Their Ratio in the Urine and Serum of Healthy Volunteers after Two Doses of Alcohol, 2013), Sidqey (Quantitative Determination of Ethyl Glucuronide and Ethyl Sulfate in Postmortem and Antemortem Whole Blood Using Phospholipid Removal 96-Well Plate and UHPLC–MS-MS, 2020), Lee (Presoaking Dried Blood Spot with Water Improves Efficiency for Small-Molecule Analysis, 2019) and Want (Solvent -Dependent Metabolite Distribution, Clustering, and Protein Extraction for Serum Profiling with Mass Spectrometry, 2005), and Steimling (Definitive EtG/EtS LC-MS/MS Analysis, 2019) as cited in previous Office Action.
Regarding claims 1 and 9, Sakuma discloses a method of indication of alcohol consumption by measuring quantity of ethyl glucuronide and ethyl sulfate in the urine (para. [0078]), comprising:
drawing a plurality of urine samples within 0 to 120 h upon start of drinking (Urine samples were collected before and after consumption of alcohol beverage. Para. [0065]; times ranges from 0 to 100 hours after drinking, see para. [0046], [0055], [0068]; Fig. 10-16), testing concentrations of EtG and EtS in the urine sample (The method used for this example detected six chemical species in less than four minutes: (1) ethyl glucuronide and (2) ethyl sulphate…para. [0031]; Figs. 10-16); and obtaining normalized concentrations of EtG and EtS (These metabolite concentrations were normalized to 1 g creatinine/L urine; para. [0031]);
wherein the concentrations of EtG and EtS in the samples are tested by:
S1. Pre-treating the samples (para. [0032]-[0033])
transferring the sample and added into internal standards EtG-D5 and EtS-D5 (According to various embodiments of the applicant's teachings, at least one internal standard can be added to the sample before analysis of the sample. Para. [0024]; The internal standard can comprise a chemical having a chemical structure that mimics that of a component in the sample…. Thus, the internal standards can comprise…deuterated ethyl glucuronide, and/or deuterated ethyl sulphate. Para. [0025]) and adding acetonitrile (Each urine sample (100 μL) was mixed with 200 μL of a solution (80% water+20% acetonitrile) para. [0033]); and
S2. Measuring the concentration of EtG and EtS by liquid chromatography-tandem mass spectrometry for the samples under test in S1 (para. [0034-]-[0035]);
Wherein in S2, a separation condition for liquid chromatography comprises the following parameters:
Chromatographic column: Waters Atlantis ® HILIC, 3.0 x 100 mm, silica 3 micron; and column temperature at 50 DEG C (para. [0040]); and
In an elution system, mobile phase A: a small amount formic acid in water, mobile phase B: a small amount of formic acid in acetonitrile; flow rate 0.35 mL/min (Mobile phases A, B, C, D, and Rinse 3 solution comprised 70% acetonitrile+30% water+10 mM ammonium formate, pH adjusted to 5.0 with a small amount of formic acid at a flow rate of 0.35 mL/min (isocratic). Para. [0040]).
Regarding the slight differences in chromatographic column dimension and operational diameters between Sakuma and claimed invention, the recited ranges are close to values “2.1 mm x 100 mm, column temperature 35 DEG C” and 0.1% of formic acid and flow rate of 0.2 mL/min. It would have been obvious to one of ordinary skill in the art before the effective filing date to have adapted Inertsil ODS-3 column with 2.1 mm x 100 mm, 3 micron and column temperature 35 DEG C instead of Waters Atlantis’s column and a column temperature of 50 DEG C. It is the Examiner’s position that the disclosed values are close enough that one of ordinary skill in the art before the effective filing date of the invention would have expected the same properties. Case law holds that a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Regarding the difference between urine and blood sample, though the Examples provided by Sakuma are for testing in urine, Sakuma explicitly discloses the method can be modified to test for blood (para. [0020] and claim 5). In addition, Sakuma discloses the sample is obtained from human (para. [0020]) but does not explicitly disclose if the subject is alive or deceased. However, the main embodiment/example provided is testing for the metabolites in urine. Generally, urine sample is almost always taken from a live subject. Based on the information and procedure provided by Sakuma, it would have been obvious to one of ordinary skill in the art to have adapt the method of Sakuma for testing blood sample of a live subject.
Regarding the remaining deficiency, with respect to the first deficiency, Sakuma does not disclose utilizing average concentration ratio of CEtG/CEtS of EtG to EtS, obtaining a quadratic regression equation by fitting using the average concentration ratio as an abscissa and sampling time as an ordinate, and measuring the ratio of blood samples under test, obtaining a relationship between the drinking time and the CEtG/CEtS based on the quadratic regression equation, and calculating the drinking time and performing drunk driving identification based on the results and calculations.
Analogous art Lostia discloses a study of measurement of EtG, EtS, and their Ratio in individuals over a period of 12 hours after consumption (Abstract). Losita specifically measure the EtG/EtS ratio over period of consumption time (Fig. 2). Even though the results of the study is limited and preliminary, Losita suggests drinking time can be estimated based on EtG/EtS drinking results (With the data obtained, we postulate that two or three consecutive urine or serum samples with increasing EtG/EtS might indicate recent drinking within the last 6–10 h depending on the biological specimen used for the investigation….In urine samples after 8 units, we found that the EtG/EtS ratio after 24 h returns to the original value after 1 h since alcohol was administered. Because until 6–10 h (depending on the biological specimen: serum or urine) EtG/EtS rises, two or three consecutive decreasing values might suggest drinking before the previous 10 or even more hours. Page 82, left column, para. 2). Losita further suggests refine data collection and further investigation (such as increasing more time-points sampled) allows one to derive a prediction model to determine the time of alcohol intake (Nevertheless, we suggest the monitoring of EtG/EtS in any future drinking experiment to evaluate its possible use in prediction models to determine the time of alcohol intake. Page 82, left column, para. 1).
In addition, the results of Sakuma in Figure 10-13 suggest a parabolic relationship of EtG and EtS concentration and consumption times (initially increasing and decreasing after reaching local max).
Therefore, it would have been obvious to one of ordinary skill in the art to have utilized the suggestions of Lostia and conceive the relationship of CEtG/CEtS and consumption time of data presented by Sakuma, fitting the relationship between the CEtG/CEtS and the time to obtain a regression equation, and when the alcohol drinking time needs to be calculated, first measuring the CEtG/CEtS in a blood sample, and then calculating the alcohol drinking time by means of the equation to derived the claimed invention since it would have been within the ambit of one of ordinary skill in the art to apply routine curve‑fitting and statistical regression techniques (e.g., quadratic regression) for data analysis.
Regarding the second deficiency, neither Sakuma nor Lostia explicitly discloses transferring the sample into centrifuge tubes, adding 80% acetonitrile in methanol, precipitating and centrifuging at 0 DEG C, transferring supernatant, drying, re-dissolving with 5% of acetonitrile in water, centrifuging again and taking the supernatant to obtain the sample under test. However, Sakuma briefly mentions samples can be pre-treated to remove lipid and proteins before being subjected to analysis (para. [0020]).
In an analogous art, Sidqey discloses a sample pretreatment step for analyzing EtG and EtS in blood samples. In addition to mixing the blood samples with internal standards in plastic tubes/centrifuge tubes (The samples were added 50 µL of IS-solution and mixed. Sample Preparation), Sidqey discloses adding acetonitrile, precipitating (four hundred microliters of ice cold ACN was added to precipitate the proteins. Sample Preparation), centrifuging (Following centrifugation at 4,500 x g (4,500 rpm on Heraeus, Multifuge X3R centrifuge, Osterode, Germany) for 5 min. Sample Preparation), transferring supernatant, drying, re-dissolving with 0.2% acetonitrile in water (the supernatants were filtered through a 96-well phospholipid removal Phree plate, 30 mg/well and collected into a 96-well collection plate using AV vacuum manifold all from Phenomenex. The filtered samples were evaporated to dryness under a stream of nitrogen at 65°C using a Zymark TurboVap (Caliper life sciences, Hopkinton, MA, USA). The residue was dissolved in 150 µL water/ACN/FA (100/0.2/0.1, v/v) solution. Sample Preparation), centrifuging again, and taking the supernatant to obtain the blood samples under test (and shaken for 1 min before UHPLC–MS-MS analysis. Sample Preparation).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporate the pretreatment of Sidqey to the method of Sakuma to derive the claimed invention. Doing so remove phospholipid from blood samples which may interfere with the sensitive instrument (Sidqey, Discussion; Sakuma, para. [0020]).
While the proposed combination of Sakuma, Lostia, and Sidqey discloses a method of estimating drinking time with a pre-treatment step comprising: transferring blood samples into centrifuge tubes added with internal standards EtG-D5 and EtS-D5, adding acetonitrile, precipitating and centrifuging, transferring supernatant, drying, re-dissolving with 0.2% acetonitrile in water, centrifuging again, and taking the supernatant to obtain the blood samples under test, the combined method does not disclose using 80% acetonitrile in methanol, centrifuging at 0 Degree C, and re-dissolving/reconstituting with 5% of acetonitrile in water.
Regarding the limitation of “adding 80% acetonitrile in methanol”, Sidqey discloses utilizing an “ice cold acetonitrile” (Sample Preparation), which is presumed to be pure acetonitrile. Even though Sidqey discloses methanol as one of the reagents used in the experiment, the methanol is mainly used as mobile phases or as solution to prepare EtG-d5 and EtS-d5 stock solution (Para. 2, Preparation of Solutions), and there is no disclosure or suggestion of mixture of acetonitrile and methanol being used for preparing the sample. In an analogous art, Want discloses a list of solvent of protein extraction for serum profiling with Mass Spectrometry (Abstract). Furthermore, Want discloses 70:30 ACN/MeOH composition precipitates more protein compared to using pure acetonitrile or methanol (Figure 5). And the addition of methanol to acetonitrile improves detection of metabolites features in LC/MS. (The addition of methanol to acetonitrile increased the number of detected reproducible features by up to 25%...although varying the percentage of methanol between 30 and 70% did not have a significant effect. Number of Reproducible Features, para.2, page 747-748). It would have been obvious to one of ordinary skill in the art before the effective filing date to have experiment with mixing acetonitrile with methanol and optimizing the composition of the solvent of Sidqey to 80:20 ACN/MeOH based on the disclosure of Want. Using a mixture of ACN/MeOH at an optimal composition improves protein precipitation and metabolites detection in LC/MS.
Regarding the limitation of “centrifuging at 0 DEG C”, Sidqey discloses the sample must be prepared with “ice cold acetonitrile” (an indication of low temperature preparation environment) but falls short explicitly stating centrifuging the resulting solution 0 DEG C or a temperature close to 0 DEG C. However, Sidqey discloses the samples, QC, calibrator and stock solutions are stored at 4 DEG C (Collected samples were store at 4 DEG C prior to processing; Biological Samples; IS solution was prepared by dilution…and stored at 4 DEG C; Preparation of Solutions), which is close to the disclosed value of 0 DEG C. Even without explicit disclosure, based on usage of “ice cold” acetonitrile, storing samples and solution at 4 DEG C, and protein’s fundamental property of denature at low temperature, a thermodynamically driven process where proteins lose their native structure and aggregate due to the weakening of the hydrophobic effect and changes in solvent properties at reduced temperatures, it would have been obvious to one of ordinary skill in the art to have kept the temperature of the solution low at 0 DEG C during centrifugation to derive the claimed temperature. Doing so allows proteins to aggregated and precipitated out.
Regarding the limitation of re-dissolving with 5% of acetonitrile in water, Sidqey discloses the sample is re-dissolved/reconstituted in 0.2% of acetonitrile in water. Analogous art Lee discloses for the purpose of analyzing dried blood spots/sample in LC-MS, reconstituting the sample in water improves efficiency (Method Summary, para. 4). Lee reconstitutes such sample in an acetonitrile-water solution (5:95) in HPLC vial (Dried samples were dissolved in 30 μl of acetonitrile-water-formic acid (5:95:0.1, v/v) and transferred into an HPLC vial. Sample preparation). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to reconstituting dried blood sample of Modified Sakuma in solution comprising 5% acetonitrile in water as taught by Lee to derive the claimed invention. While water serves as ideal solvent for the dried blood according to Lee, the addition of small volume of acetonitrile better prepares the mixture for LC-MS analysis, allowing for better resolution.
Overall, it is the Examiner’s position that the disclosed concentration range and temperature are optimum or workable ranges by routine experimentation. Generally, differences in concentration and temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the third and last deficiency, none of the arts cited discloses the claimed gradient time. Analogous art Steimling discloses EtS/EtG analysis by mass spectrometry using following mobile phases and gradient time (Page 5):
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371
832
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Greyscale
Therefore, it would have been obvious to one of ordinary skill in the art to have routinely experiment and optimize elution time and mobile phases volume ratio based on teaching from Steimling to the method of Modified Sakuma to derive the claimed invention. Doing so minimizes the matrix suppression effect (Steimling, Matrix Effect, Page 6).
Regarding claims 2-3 and 10-11, Modified Sakuma discloses the claimed invention as discussed above in claims 1 and 9 respectively. None of the arts cited explicitly discloses the blood alcohol concentration upon drinking is in the range of 0.22 to 0.66 mg/mL or alcohol intake is 0.72 g/kg. Alcohol intake is the amount of pure alcohol consumed per kg of the drinker. Similarly, Blood alcohol concentration is calculated using formula:
B
A
C
=
A
l
c
o
h
o
l
c
o
n
s
u
m
e
d
i
n
g
r
a
m
s
B
o
d
y
w
e
i
g
h
t
i
n
g
r
a
m
s
x
D
i
s
t
r
i
b
u
t
i
o
n
R
a
t
i
o
r
*
100
Where r is 0.68 for men and 0.55 for women.
A BAC of 0.08% means 0.08 g of alcohol per 100 mL or 0.8 mg/mL; the legal limit varies from 0.2 mg/mL (China) to 0.8 mg/mL (most U.S. jurisdiction).
In addition, Sakuma discloses a list of volunteers for the alcohol consumption experiment. Each trial includes the gender of the volunteer, volumes of the alcohol consumed, alcohol content, the country of origin (para. [0048]-[0064]) and the appropriate standard drinks conversion (Fig. 8-9).
For example, male volunteer who consumed 1L of Polish lager (Zywiec, 5.5%) (55 mL of pure alcohol in 1 L of lager) is estimated to have consumed 43 g of alcohol
55
m
L
a
l
c
o
h
o
l
*
10
g
12.7
m
L
=
43
g
a
l
c
o
h
o
l
Sakuma is silent regard providing weight of each volunteer. It is the Examiner’s position that it would have been obvious to one of the ordinary skill in the art before the effective filing date to have derive the disclosed concentration range of blood alcohol concentration and alcohol intakeby routine experimentation based on factors such as type of alcoholic drinks (% alcohol content and the corresponding standard drink conversion), volume consumed, gender of the drinker, and the weight of the drinker. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claims 4 and 12, Modified Sakuma discloses the claimed invention as discussed above in claims 1 and 9 respectively. None of the arts cited discloses the claimed sampling intervals at 0, 0.5, 2, 3, 5, 8, 12, 24, 36, 48, and 120 h; instead, Sakuma discloses taking sampling intervals at 0 hours and multiple smaller sampling intervals between 0 and 5 hours (as low as every 30 minutes to 1 hour), and larger intervals between 5 and 100 hours (in the interval of 10-24 hours)(Fig. 12). It would have been obvious to one of ordinary skill in the art to have modified the sampling intervals of Sakuma (taking samples in the interval of every 30 min to 1 hour for the first few hours after drinking; and 10-24 hours after 8th-12th hour after drinking) to derive the claimed sampling intervals of 0, 0.5, 2, 3, 5, 8, 12, 24, 36, 48, and 120 h. The data of Sakuma suggests the major increase in alcohol metabolites occur between first 5-8 hours after consumption before decreasing over time (Fig. 11-13). Therefore, one of skill in the art is motivated to take more sample within smaller sampling intervals in the first 10 hours similar to Sakuma before taking a longer sampling intervals after alcohol metabolites begin to decrease to better improve the curve fitting and regression models.
Regarding claims 8 and 14, Modified Sakuma discloses the claimed invention as discussed above in claims 1 and 9 respectively. Sakuma discloses the concentration of 1mg/mL is used for internal standard EtG-D5 and EtS-D5 are used (para. [0037]). Furthermore, Sidqey (after incorporation into Sakuma) discloses the internal standard stock solution of EtG-D5 and EtS-D5 at 1 mg/mL (Internal standard (IS) stock solutions of EtG-d5 and EtS-d5 (1 mg/mL) were prepared; Preparation of Solutions) are further diluted to 2.3 and 7.8
μ
g/mL respectively (From the stock solutions, a IS solution was prepared by dilution with Type-1 water to a final concentration of 2.3 mg/L (18 μM) EtS and 7.8 mg/L (35 μM) EtG; Preparation of Solutions), which is close to the claimed range 1
μ
g/mL. The ranges are close enough that one skilled in the art would have reasonable expectations that the compositions would have the same properties. The claimed concentration is 1
μ
g/mL, which is only a 1.3 and 6.8
μ
g/mL difference from the 2.3 and 7.8
μ
g/mL disclosed by Sdiqey. One skilled in the art would reasonably expect that an internal standard solution with concentration of 2.3 and 7.8
μ
g/mL versus 1
μ
g/mL would still allow for proper sample mixing for analyzing the ethanol metabolites. Therefore, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. See Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985). Without showing unexpected results, the claimed range and range disclosed by Sidqey are close enough that one skilled in the art would have a reasonable expectation of success.
Claim(s) 7 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sakuma, Lostia, and Sidqey, Lee, Want, and Steimling as applied to claims 1 and 9 above, and further in view of Sharma (Automated Sample Preparation for the Monitoring of Ethanol Metabolites in Urine by LC-MS/MS, 2015) as cited in previous Office Action.
Regarding claims 7 and 13, Modified Sakuma discloses the claimed invention as discussed above in claims 1 and 9 respectively. Sidqey, (after incorporation with Sakuma) discloses the concentrations were determined using electrospray ionization source using negative mode (Negative ESI-MS-MS-detection in multiple reaction monitoring (MRM) mode with two transitions for EtG and EtS and one transition for the ISs was performed. Ms-MS conditions) at a temperature of 500 DEG C (…delivered at a temperature of 500°C. Ms-Ms conditions). However, Sidqey is silent regarding the voltage of ion spray is at -4000 V. Analogous art Sharma discloses using LC-MS/MS for analyzing EtS and EtG in urine (Abstract). Sharma discloses the LC-MS/MS analysis was performed in negative ionization mode with ion spray voltage at -4500 V (Page 2, right column, para. 3) at a temperature of 600 DEG C (Page 2, right column, para. 1). It would have been obvious to one of ordinary skill in the art before the effective filing date to have use the ion spray parameter of Sharma or a similar value such as -4000 V to the method of Modified Sakuma and have a reasonable expectation of success and achieving similar result since both Sidqey and Sakuma are method of analyzing EtS and EtG metabolites in human fluid using a negative ionization mode at a temperature close to each other (500 DEG C vs 600 DEG C).
Response to Arguments
Applicant’s arguments, see Pages 7-10, filed 05/18/26, with respect to the 101 rejections, have been fully considered and are persuasive. The rejection of claims under 101 has been withdrawn.
Applicant's arguments, see Pages 10-15, filed 05/18/26, with respect to the 103 rejections have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument that none of the cited art either alone or in combination teaches or suggests the claimed technical features, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
For instance, applicant argues that there is no motivation to combine Sakuma’s method with Lostia’s, Sharma’s, or Steimling’s method because the methods are primarily concerned with testing in urine sample (page 12). Examiner respectfully disagrees. First, Lostia reference is primarily used to address the Sakuma’s deficiency of utilizing average concentration ratio of CEtG/CEtS of EtG to EtS, obtaining a quadratic regression equation by fitting using the average concentration ratio as an abscissa and sampling time as an ordinate, and measuring the ratio of blood samples under test, obtaining a relationship between the drinking time and the CEtG/CEtS based on the quadratic regression equation, and calculating the drinking time and performing drunk driving identification based on the results and calculations.
Examiner utilizes the theoretical aspect of Lostia concerning with statistical and mathematical relationship between the concentration of EtG and EtS over time. Losita suggests drinking time can be estimated based on EtG/EtS drinking results. As the aspect of Lostia used in the 103 rejection is theoretical concerning curve-fitting used for predicting/estimating drinking time, the practical effect due to using different sample (such as urine instead of blood) is minimal as one of ordinary skill in the art would have still expected EtG and EtS in a blood sample follows similar quadratic trend as urine sample.
Furthermore, Sakuma discloses blood being used as an alternative as urine, it would have been obvious to one of ordinary skill in the art to have optimize the gradient by routine optimization based on Steimling’s and Sharma’s methods. Applicant’s remark mainly focuses on certain differences in operational parameter but does not argue why such difference cannot be derive from routine optimization based on arts and evidence presented here.
Regarding applicant’s argument regarding Sidqey, Applicant’s argues that Sidqey is more concerned with “postmortem blood samples” rather than “living blood sample” as claimed; as such one of ordinary skill in the art would not have been motivated to utilize or alter Sidqey’s formulation when combined with the method of Sakuma. Applicant argues that while the incorporation of Sidqey cures some deficiency in the pretreatment step of Sakuma, Sidqey does not disclose the limitation of “adding 80% of acetonitrile in methanol, precipitating…” (page 12-13). Furthermore, Applicant argues the Lee and Want do not sufficiently cure the deficiency even though the arts disclose some as pect of adding acetonitrile in methanol and protein precipitation since the arts do not pay attention to EtG or EtS.
The argument is not persuasive. First, Sakuma discloses an optional pretreatment step of removing protein or phospholipids in sample. Sidqey discloses a list of solutions with slight concentration difference from the claimed invention for pretreating/removing residual protein or phospholipids in the sample. As such, the focus now shifts to removing any phospholipids and proteins from the sample in the pretreatment step. Even though neither Lee nor Want pays much attention to EtG or EtS, the arts were, nevertheless, focuses on removing proteins and phospholipids via precipitation. As such, there would have been sufficient motivation for one of ordinary skill in the art to have optimized removal of proteins from sample utilizing procedure from Want and Lee to the pretreatment method of Sidqey.
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 MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
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/M.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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