DETAILED ACTION
In application filed on 01/02/2024, Claims 1-10 are pending. The claim set submitted on 01/02/2024 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-10 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/02/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
Claims 2 and 6-7 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 2 recites the limitation " the quantity of samples". There is insufficient antecedent basis for this limitation in the claim.
For the purpose of expedited prosecution, the limitation " the quantity of samples" is interpreted by the Examiner as "a quantity of samples".
Claim 6 recites the limitation " the specimen". There is insufficient antecedent basis for this limitation in the claim.
For the purpose of expedited prosecution, the limitation " the specimen" is interpreted by the Examiner as "a specimen".
Moreover, Claims 7 is rejected by virtue of dependency on claim 6.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claims 1-10) (Step 1: YES).
Analysis:
Claim 1: Ineligible.
Step 1:
The claim recites a series of steps or acts, including “content conversion method of free components by transforming ultrafiltration to equilibrium dialysis”. Thus, the claim is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong 1:
Claim 1 recites “a step of establishing a linear equation based on the first concentration and the second concentration (math step)”. Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math process since claim 1 relates to using a math process to “establish a linear equation based on the first concentration and the second concentration” (Step 2A, Prong 1: Patent Ineligible).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the establishment of a linear equation is done, No further action takes place.
Also the steps of “separating the free components from samples by ultrafiltration and measuring concentrations…” and “separating the free components from samples by equilibrium dialysis…” is recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, there are no additional elements which are significantly more than the abstract idea. The steps of steps of “separating the free components from samples by ultrafiltration and measuring concentrations…” and “separating the free components from samples by equilibrium dialysis…” appears to be well-understood, routine, and conventional (WURC) in the field of clinical diagnostics, as evidenced by Soldin (US20060223188A1). (Step 2B: NO).
Therefore, Claim 1 is ineligible.
Moreover, Claims 2-10 are rejected by virtue of their dependency on Claim 1.
Also, each of the dependent claims 2-10 do not solve the issues of claim 1.
Claims 2-9: Ineligible.
Step 2A, Prong One and Prong Two: Claims 2-9 further define the data gathering steps, which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claims 2-9 are ineligible.
Claim 10: Ineligible.
Step 2A, Prong One and Prong Two: Claim 10 further presents an abstract idea “linear equations y = 0.8719x - 0.2116; y = 0.7745x + 0.066 and y = 0.6205x + 0.3418”and further define the data gathering steps which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claim 10 is ineligible.
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 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.
Claims 1 and 3-9 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Soldin (US20060223188A1, submitted in IDS 01/03/2024).
Regarding Claim 1, Soldin teaches a content conversion method of free components by transforming ultrafiltration to equilibrium dialysis, comprising the following steps:
a step of separating (See Para 0045; Claim 43… separating FT4 hormone and FT3 hormone from the sample) the free components (See Para Abstract…analysis of free thyroxine (FT4) hormone and free-triiodothyronine (FT3)) from samples (referred to as Any sample containing or suspected of containing a hormone can be used, including a sample of blood, plasma, serum, urine or saliva. [Para 0094]) by ultrafiltration (See Para 0097…The hormones may also be separated by centrifugation. For example, FT4 may be separated from other compounds, including bound T4 by centrifugation using an ultrafiltration device) and measuring concentrations of free components (‘Serum T4 and T3 concentrations’), to obtain first concentration (See Fig. 8…the T4 concentrations for ultrafiltration; See Para 0126…Serum T4 and T3 concentrations are currently measured by competitive immunoassay methods (IAs) that are mostly non-isotopic and use enzymes, fluorescence or chemiluminescence molecules as signals; See Para 0145…This ultrafiltration plus LC/MS/MS assay is considerably quicker than the time consuming equilibrium dialysis method, thereby teaching “first concentration”);
a step of separating the free components from samples by equilibrium dialysis (See Claim 51…step of separating the FT4 and FT3 hormone from the sample is selected from liquid chromatography, centrifugation using an ultrafiltration device, equilibrium dialysis and combinations of the foregoing.) and measuring concentrations of free components (‘See Para 0064… measurement of free T4’; See Para 0157…FT3 was analyzed by the same method as FT4 (Example 4)), to obtain second concentration (See Fig. 8…the T4 concentrations for equilibrium dialysis; See Para 0064…FIG. 8 is graph showing the comparison of the tandem mass spectrometric method with the equilibrium dialysis method for the measurement of free T4; See Para 0142…Equilibrium Dialysis…The Nichols free T4 kit; See Para 0146…Approximately, 50% of these free T4s run on either the Dade RxL Dimension™ or the DPC Immulite™ give normal results when run by equilibrium dialysis; See Para 0157…FT3 was analyzed by the same method as FT4 (Example 4), except for the analysis of the same transition ions for total T3 and using the API 5000™ mass spectrometer thereby teaching “second concentration”); and
a step of establishing a linear equation (See Fig. 8 for the linear equation for Free T4 …y=0.971 + 0.041) based on the first concentration (See Fig. 8…the concentrations for ultrafiltration) and the second concentration ((See Fig. 8…the concentrations for equilibrium dialysis) (See Para 0115…Standards for the calibration curve in the range of 0.325 to 5 ng/mL for T3 and 12.5 to 200 ng/mL for T4; Under BRI, a calibration curve derives a linear equation used on calculating T3 and T4 concentrations).
Regarding Claim 3, Soldin teaches wherein high-performance liquid chromatography tandem mass spectrometry is used for the step of measuring concentrations (See Para 0098…Optionally, the separation step and step of introducing the hormones into a mass spectrometer can be combined using a combined liquid chromatography spectrometry apparatus (LC/MS); See Para 0104…Kits for use in mass spectrometric analysis of a sample comprising or suspected of comprising FT4, FT3 or both are also provided).
Regarding Claim 4, Soldin teaches wherein the first concentration and the second concentration (See Para 0159… FT4 and FT3 were analyzed simultaneously by a similar method of Example 4 except using the API 5000™ mass spectrometer, thereby teaching “first concentration and the second concentration”; Also see Fig. 8…first concentration…See Fig. 8…the concentrations for ultrafiltration and the second concentration…See Fig. 8…the concentrations for equilibrium dialysis) are measured at different temperatures (See Para 0063… FIG. 7 is a graph showing the effect of temperature on FT4 by tandem mass spectrometry and ultrafiltration.)
Regarding Claim 5, Soldin teaches wherein the first concentration is measured at 4°C to 37°C (See Para 0063… FIG. 7 is a graph showing the effect of temperature on FT4 by tandem mass spectrometry and ultrafiltration); and the second concentration is measured at 4°C to 37°C (See Para 0064…FIG. 8 is graph showing the comparison of the tandem mass spectrometric method with the equilibrium dialysis method for the measurement of free T4; See Para 0145… the results obtained by the tandem mass spectrometric method closely correlate with those obtained by equilibrium dialysis, which employs a temperature of 37° C.).
Examiner further submits that FT3 was analyzed by the same method as FT4 (Example 4) (Para 0157).
Regarding Claim 6, Soldin teaches wherein the specimen is blood, saliva, or urine (See Para 0032… For, example, hormone analysis can be performed on samples of blood, saliva, serum, plasma and urine.).
Regarding Claim 7, Soldin teaches wherein the specimen is serum or plasma (See Para 0032… For, example, hormone analysis can be performed on samples of …serum, plasma…).
Regarding Claim 8, Soldin teaches wherein the free components are free hormones (See Abstract… free thyroxine (FT4) hormone and free-triiodothyronine (FT3); See Para 0002… analyzing free thyroxine (FT4) and free triiodothyronine (FT3) thyroid hormones by mass spectrometry.).
Regarding Claim 9, Soldin teaches wherein the free hormones are free testosterone, free triiodothyronine, or free thyroxine (See Abstract… free thyroxine (FT4) hormone and free-triiodothyronine (FT3); See Para 0002… analyzing free thyroxine (FT4) and free triiodothyronine (FT3) thyroid hormones by mass spectrometry.).
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 2 is rejected under 35 U.S.C. 103 as being unpatentable over Soldin et al. (US20060223188A1, submitted in IDS 01/03/2024) as applied to claim 1 above, and further in view of Jonklaas et al. ("Total and free thyroxine and triiodothyronine: measurement discrepancies, particularly in inpatients." Clinical Biochemistry 47.13-14 (2014): 1272-1278.).
Regarding Claim 2, Soldin teaches wherein there are a plurality of samples, and the quantity of samples (See Standards for the calibration curve in the range of 0.325 to 5 ng/mL for T3 and 12.5 to 200 ng/mL for T4 were prepared, thereby teaching “a plurality of samples, and the quantity of samples”).
Soldin does not teach that there are a plurality of samples, and the quantity of samples is sufficient for a correlation coefficient of the established linear equation to be greater than 0.90.
In the analogous art of total and free thyroxine and triiodothyronine: measurement discrepancies, particularly in inpatients, Jonklass teaches that there are a plurality of samples, and the quantity of samples (See Page 4…concentration
range of 6.5–65.0 pmol/L for FT4 and 1.5–38.0 pmol/L for FT3 (r ≥ 0.995)) is sufficient for a correlation coefficient of the established linear equation to be greater than 0.90 (See Results… for the spearman correlation coefficient of 0.95; 0.91 and linear equation…Slope and Y intercept… y = 1.1249x + 34.13; y = 1.0806x + 1.23; See Page 4…Good linearity was also obtained within the concentration range of 6.5–65.0 pmol/L for FT4 and 1.5–38.0 pmol/L for FT3 (r ≥ 0.995)).
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 the content conversion method of Soldin, to include that there are a plurality of samples, and the quantity of samples is sufficient for a correlation coefficient of the established linear equation to be greater than 0.90, as taught by Jonklass for the benefit of disclosing that good linearity was obtained within the concentration range of 6.5–65.0 pmol/L for FT4 and 1.5–38.0 pmol/L for FT3 (r ≥ 0.995) (Jonklass, Page 4; Assay Performance), allowing for the reliable measurement of free thyroid hormone in any of the conditions that may result in changes in binding protein concentrations (Jonklass, Page 2; Introduction).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Soldin (US20060223188A1, submitted in IDS 01/03/2024) as applied to claim 1 above.
Regarding Claim 10, Soldin teaches wherein when the first concentration (See Para 0126…Serum T4 and T3 concentrations are currently measured by competitive immunoassay methods (IAs) that are mostly non-isotopic and use enzymes, fluorescence or chemiluminescence molecules as signals; See Para 0145…This ultrafiltration plus LC/MS/MS assay is considerably quicker than the time consuming equilibrium dialysis method, thereby teaching “first concentration”) is measured at 25°C (See Para 0063… FIG. 7 is a graph showing the effect of temperature on FT4 by tandem mass spectrometry and ultrafiltration) and the second concentration (See Para 0064…FIG. 8 is graph showing the comparison of the tandem mass spectrometric method with the equilibrium dialysis method for the measurement of free T4; See Para 0142…Equilibrium Dialysis…The Nichols free T4 kit; See Para 0146…Approximately, 50% of these free T4s run on either the Dade RxL Dimension™ or the DPC Immulite™ give normal results when run by equilibrium dialysis; See Para 0157…FT3 was analyzed by the same method as FT4 (Example 4), except for the analysis of the same transition ions for total T3 and using the API 5000™ mass spectrometer thereby teaching “second concentration”) is measured at 37°C (See Para 0064…FIG. 8 is graph showing the comparison of the tandem mass spectrometric method with the equilibrium dialysis method for the measurement of free T4; See Para 0145… the results obtained by the tandem mass spectrometric method closely correlate with those obtained by equilibrium dialysis, which employs a temperature of 37° C.).
Examiner further submits that FT3 was analyzed by the same method as FT4 (Example 4) (Para 0157).
Soldin does not teach that the linear equation is y = 0.8719x - 0.2116 when the free hormone is free testosterone; the linear equation is y = 0.7745x + 0.066 when the free hormone is free triiodothyronine; the linear equation is y = 0.6205x + 0.3418 when the free hormone is free thyroxine; and y represents the first concentration, and x represents the second concentration.
However, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the computation of linear calibration curve in bioanalysis, the selection of optimal experimental conditions including standard purity & preparation, concentration range & standards, curve weighting, intercept treatment and intercept treatment defines the analyte linear equation. Thus, “the linear equation is y = 0.7745x + 0.066 when the free hormone is free triiodothyronine; the linear equation is y = 0.6205x + 0.3418 when the free hormone is free thyroxine; and y represents the first concentration, and x represents the second concentration” are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to derive that the linear equation is y = 0.8719x - 0.2116 when the free hormone is free testosterone; the linear equation is y = 0.7745x + 0.066 when the free hormone is free triiodothyronine; the linear equation is y = 0.6205x + 0.3418 when the free hormone is free thyroxine; and y represents the first concentration, and x represents the second concentration, for the benefit of providing methods and kits for analyzing free thyroxine (FT4) and free triiodothyronine (FT3) thyroid hormones by mass spectrometry (Soldin, Para 0002),which allows for the provision of a fast and accurate method of hormone analysis and quantification using a mass spectrometer. (Soldin, Para 0030).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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