DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-13 are canceled.
Claims 14-26 are pending and examined on the merits.
Claim Objections
Claims 17, 21, and 24 are objected to because of the following informalities:
Claim 17 is objected to because a comma or semi-colon is missing at the end of line 3. Also, “, and” or “; and” is missing at the end of line 4. These are missing in order to separate i), ii), and iii) in the claim.
Also, claim 17 is objected to because it recites “comprises the step of:” in line 2 but then recites multiples steps (steps i) to iii)). The recitation “step” in line 2 should be amended to “steps.”
Since claim 17 is objected to, then its dependent claim, claim 24, is also objected to.
Claim 21 is objected to because the full name for the abbreviation “CSF” should be recited. According to the specification, the abbreviation corresponds to “cerebrospinal fluid” (page 8, second paragraph of substitute specification filed March 8, 2024).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 19, 20, and 24 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 19 is rendered indefinite by the recitation “performing the ionic chromatography.” It is unclear that ionic chromatography is performed since step b) of parent claim 14 recites using an “assay based on ionic chromatography.” Using an “assay based on ionic chromatography” does not require that ionic chromatography is performed. Since claim 19 is indefinite, then its dependent claim 20 is rendered indefinite. Thus, claims 19 and 20 are rejected under 35 U.S.C. 112(b).
Claim 24 recites the limitation "the bioluminescence measured by adding ATP sulfurylase" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Parent claim 17 does not recite adding ATP sulfurylase to produce bioluminescence, or that the bioluminescence that is measured is from adding ATP sulfurylase. Instead, parent claim 17 recites step iii) of detecting the bioluminescence produced after using luciferase in the presence of luciferin in step ii). Though step i) of parent claim 17 involves ATP sulfurylase, there is no recitation that ATP sulfurylase is added to any material (e.g., the biological sample, or the first fraction of the biological sample). For the purpose of applying prior art, the recitation “the bioluminescence measured by adding ATP sulfurylase” in claim 24 is being interpreted as the bioluminescence detected in step iii).
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 14-26 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 a statutory category, i.e. a process (Step 1: YES).
Claim 14: The claim recites step c) of comparing two values (each value is a concentration of PPi), and assessing if the difference is above a pre-determined threshold. This comparison and assessment is a mental process because it can be performed in the human mind. They are directed to an evaluation which is an example of a mental process. Thus, step c) is a ‘Mental process’ which is an abstract idea grouping. See MPEP 2106.04(a)(2)(III).
Claim 14 also recites step d) which includes two embodiments, according to the difference determined in step c). In a first embodiment, if the difference between the two values is lower than or equal to the pre-determined threshold, the concentration of PPi in the biological sample is determined as the mean of the two values. This first embodiment sets forth a mathematical calculation. Thus, step d) is a ‘Mathematical concept’ which is an abstract idea grouping. See MPEP 2106.04(a)(2)(I), particularly MPEP 2106.04(a)(2)(I)(C).
Accordingly, claim 14 recites abstract ideas (Step 2A, Prong One: YES).
The judicial exceptions are not integrated into a practical application. Claim 14 recites two initial steps, steps a) and b), in which the concentration of PPi is measured in two fractions of the biological sample using two assays Steps a) and b) are ‘additional elements’ other than the abstract ideas. These additional elements are mere data gathering to obtain the two values needed in steps c) and d) (the first embodiment discussed above). Mere data gathering is extra-solution activity, specifically pre-solution activity, which is recognized as failing to integrate a judicial exception into a practical application. See MPEP 2106.04(d)(I), as well as MPEP 2106.05(g). As such, the ‘additional elements’ of claim 14 do not integrate the abstract ideas into a practical application (Step 2A, Prong Two: NO). Accordingly, claim 14 is directed to judicial exceptions, specifically abstract ideas (Step 2A: YES).
Claim 14 does not include additional elements that are sufficient to amount to significantly more than the judicial exception. As pointed out in the preceding paragraph, the ‘additional elements’ other than the recited abstract ideas are steps a) and b). The courts have found that limitations adding insignificant extra-solution 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 MPEP 2106.05(I)(A).
Additionally, steps a) and b) are well-understood, routine, conventional activity in the field of assaying inorganic pyrophosphate (PPi). In particular, the measurement of the concentration of PPi in a sample using an assay based on enzymatic reaction is well known in the art, dating back at least the 1980s as evidenced by Nyren (Analytical Biochemistry. 1985. 151: 504-509). Nyren, published in 1985, discloses a method for analyzing inorganic pyrophosphate which utilizes the enzymes ATP sulfurylase and firefly luciferase (abstract). Nyren also points out that most of the methods for determining PPi, which include enzymatic methods, had been developed with the aim of measuring the intracellular concentrations of PPi in biological material (page 504, left column, second paragraph). Also, Silcox (The Journal of Clinical Investigation. 1973. 52(7): 1595-1600. Listed on IDS filed 3/8/24) demonstrates that measurement of the concentration of PPi in a biological sample using an assay based on enzymatic reaction, and also using an assay based on ionic chromatography, is well-understood, routine, conventional activity in the field of assaying PPi. Silcox, which dates back to 1973, teaches performing two enzymatic methods and one method based on anion exchange chromatography (directed to ‘ionic chromatography’) for measuring PPi in platelets (abstract; page 1597, right column, last paragraph; Table II on page 1598). The three methods were previously published. See page 1596, right column, last two paragraphs; page 1597, left column, third paragraph; and Table II on page 1598.
Since steps a) and b) of claim 14 have been well known since as early as the 1970s and 1980s as evidenced by Nyren and Silcox (as well as being previously published, as pointed out by Silcox), then these steps, directed to ‘additional elements’ other than the abstract ideas, are well-understood, routine, conventional activity. Well-understood, routine, conventional activity do not qualify as ‘significantly more’ when recited in a claim with a judicial exception. See MPEP 2106.05(I)(A). Therefore, steps a) and b) of claim 14 do not add ‘significantly more’ than the recited judicial exceptions (Step 2B: NO). As such, claim 14 is eligible subject matter under 35 U.S.C. 101.
Claims 15-16: Claims 15 and 16 further limit the pre-determined threshold that is used for assessing the difference between the two values. Therefore, claims 15 and 16 further limit the judicial exceptions (steps c) and d), for the first embodiment in which the difference between the values is lower than or equal to the pre-determined threshold). Therefore, claims 15 and 16 are rejected on the same basis as claim 14.
Claim 17: Claim 17 further limits step a) which is an ‘additional element’ other than the judicial exceptions. Nyren, discussed above, meets the limitations of claim 17 since Nyren discloses a rapid, enzymatic method utilizing enzyme ATP sulfurylase and firefly luciferase according to two reactions in which ATP sulfurylase catalyzes the conversion of PPi to ATP, and luciferase catalyzes the conversion of ATP to light (hv) in the presence of luciferin (page 504, right column, second paragraph). In the assay of PPi, the luminescence was measured and calibrated by addition of a known amount of ATP or PPi (page 505, right column, first paragraph). See also page 505, left column, first paragraph. Nyren, dating back to the 1980s, demonstrates that the limitation of claim 17 (directed to an ‘additional element’ other than the judicial exceptions) is well-understood, routine, conventional activity, thus not adding ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 17. As such, claim 17 is not eligible subject matter under 35 U.S.C. 101.
Claim 18: Claim 18 further limits step a) which is an ‘additional element’ other than the judicial exceptions. Nyren also discloses that the luminescence was calibrated by the addition of a known amount of PPi (page 505, right column, first paragraph). Figure 3 on page 507 shows the influence of PPi concentration on intensity and decay rate of bioluminescence, providing multiple data points. Figure 3 is directed to a calibration curve established by adding increasing concentrations of exogenous PPi to fractions of a sample, and performing the enzymatic method on those fractions. Based on that teaching in Nyren, then the limitation of claim 18 (directed to an ‘additional element’ other than the judicial exceptions) is well-understood, routine, conventional activity, thus not adding ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 18. As such, claim 18 is not eligible subject matter under 35 U.S.C. 101.
Claim 19: Claim 19 further limits step b) which is an ‘additional element’ other than the judicial exceptions. Silcox, discussed above, meets the limitation of claim 19. In particular, Silcox discloses that the platelets were suspended in a solution comprising EDTA (page 1596, left column, second paragraph). Furthermore, Silcox discloses that the column chromatographic method (directed to ionic chromatography due to the anion exchange resin) used for measuring PPi was previously described in Russell (page 1597, left column, last full paragraph; Russell is cited as reference number 7 in Silcox). Russell (J. Clin. Invest. 1971. 50(5): 961-969. Listed on IDS filed 3/8/24) discloses the measurement of PPi in human plasma, pointing out that after collection of blood, EDTA was added (page 962, left column, fourth paragraph). This addition of EDTA reduced the rate of hydrolysis of PPi in the blood (page 962, left column, fourth paragraph). EDTA is directed to a ‘calcium chelating agent.’ Based on Silcox and Russell which date back to the 1970s, then the limitation of claim 19 is well-understood, routine, conventional activity, thus not adding ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 19. As such, claim 19 is not eligible subject matter under 35 U.S.C. 101.
Claim 20: Claim 20 further limits the calcium chelating agent of claim 19 to EGTA. The claim further limits the pre-solution activity of data gathering. The courts have found that limitations adding insignificant extra-solution 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 MPEP 2106.05(I)(A). Therefore, the limitation of claim 20 does not add ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 20. As such, claim 20 is not eligible subject matter under 35 U.S.C. 101.
Claim 21: Claim 21 further limits the biological sample. As discussed above, Silcox demonstrates that steps a) and b) (the additional elements) were performed on platelets. Also, Silcox discloses measuring PPi in plasma using a yeast PPiase method (paragraph bridging pages 1595 and 1596), wherein the yeast PPiase method is directed to an assay based on enzymatic reaction. Furthermore, Silcox discloses that the column chromatographic method (directed to ionic chromatography due to the anion exchange resin) used for measuring PPi was previously described in Russell (page 1597, left column, last full paragraph; Russell is cited as reference number 7 in Silcox). Russell (J. Clin. Invest. 1971. 50(5): 961-969. Listed on IDS filed 3/8/24) discloses the measurement of PPi in human plasma (page 962, left column, fourth paragraph). Therefore, Silcox and Russell demonstrate that the limitation of claim 21 (plasma) is well-understood, routine, conventional activity. As such, the limitation of claim 21 does not add ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 21. As such, claim 21 is not eligible subject matter under 35 U.S.C. 101.
Claims 22-23: Claims 22 and 23 are ‘additional elements’ to the judicial exceptions. The limitations of claims 22 and 23 affect the data gathering of steps a) and b) (also ‘additional elements’) since they affect the biological sample. The limitations of claims 22 and 23 are directed to pre-solution activity, which is recognized as failing to integrate a judicial exception into a practical application. As such, the ‘additional elements’ of claim 22 and 23 do not integrate the abstract ideas into a practical application (Step 2A, Prong Two: NO). Accordingly, claim 22 and 23 are directed to judicial exceptions, specifically abstract ideas (Step 2A: YES).
As discussed above regarding claim 21, Silcox discloses measuring PPi in plasma using an assay based on enzymatic reaction. Also, Russell discloses the measurement of PPi in human plasma by a column chromatographic method that is directed to ionic chromatography. Russell teaches that the plasma was separated from blood by centrifugation (page 962, left column, second-to-last paragraph). The separation of plasma from blood is directed to removing or reducing the presence of contaminants (cells of the blood). Therefore, steps a) and b) are well-understood, routine, conventional activity (as demonstrated by Silcox) which are preceded by the well-understood, routine, conventional activity of the pre-treatment of the biological sample to remove or reduce the presence of contaminants (cells), wherein the pre-treatment is centrifugation. Therefore, claims 22 (at least cells as the contaminants) and 23 (centrifugation) do not add ‘significantly more’ than the recited judicial exceptions (Step 2B: NO). In combination with the analysis as performed with claim 14, then claims 22 and 23 are not eligible subject matter under 35 U.S.C. 101.
Claim 24: Claim 24 further limits step a) which is an additional element other than the judicial exceptions. The claim further limits the pre-solution activity of data gathering. The courts have found that limitations adding insignificant extra-solution 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 MPEP 2106.05(I)(A). Therefore, the limitation of claim 24 does not add ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claims 14 and 17 applies to claim 24. As such, claim 24 is not eligible subject matter under 35 U.S.C. 101.
Claim 25: Claim 25 further limits step a) which is an ‘additional element’ other than the judicial exceptions. Nyren, discussed above, meets the limitations of claim 25 since Nyren discloses an assay of PPi using luciferase, wherein the luminescence was measured (page 504, right column, second paragraph; page 505, right column, first paragraph). Burkhardt (US 2010/0092966) discloses methods for detecting pyrophosphate by means of bioluminescence detection (abstract) that includes the embodiment of using luciferase (paragraph [0034]). The luciferase can be recombinant (paragraph [0039]). Pyrophosphate is also referred to as PPi (paragraph [0003]). Burkhardt is evidence that the use of recombinant luciferase in detecting pyrophosphate (e.g. PPi) is well-understood, routine, conventional activity, thus not adding ‘significantly more’ than the judicial exceptions (Step 2B: NO). The analysis as performed on claim 14 applies to claim 25. As such, claim 25 is not eligible subject matter under 35 U.S.C. 101.
Claim 26: Claim 26 incorporates claim 14 and includes the additional element of detecting a condition associated with deregulated inorganic pyrophosphate level in an individual using a biological sample from the individual in the method of claim 14. The additional element of claim 26 fails to integrate the judicial exceptions into a practical application since the determination of the level of PPi is then not applied in any manner (e.g., specific treatment of the condition) (Step 2A, Prong Two: NO). Accordingly, claim 26 is directed to judicial exceptions, specifically abstract ideas (Step 2A: YES).
Russell teaches measuring PPi in human plasma (abstract), including in plasma of persons with various bone diseases including hypophosphatasia (page 961, right column, second paragraph). Plasma PPi was raised in hypophosphatasia (abstract). Therefore, Russell demonstrates that the additional element of claim 26 was well-understood, routine, conventional activity, thus not adding ‘significantly more’ than the judicial exceptions (Step 2B: NO). In combination with the analysis as performed with claim 14, then claim 26 is not eligible subject matter under 35 U.S.C. 101.
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Silcox (The Journal of Clinical Investigation. 1973. 52(7): 1595-1600. Listed on IDS filed 3/8/24) discloses steps a) and b) of claim 14. In particular, Silcox teaches performing two enzymatic methods and one method based on anion exchange chromatography (directed to ‘ionic chromatography’) for measuring inorganic pyrophosphate (PPi) in platelets (abstract; page 1597, right column, last paragraph; Table II on page 1598). See page 1596, right column, last two paragraphs; page 1597, left column, third paragraph; and Table II on page 1598. Platelets are directed to a biological sample. Performing either of the two enzymatic methods on platelets is directed to step a) of claim 14. Performing the column chromatographic method using anion exchange resin on platelets is directed to step b) of claim 14. In providing the PPi levels from the three tested methods in Table II, then Silcox suggests the limitation of step c) of claim 14 of comparing the value measured in step a) and the value measured in step b). However, Silcox differs from the claimed method in that Silcox does not disclose the limitation of step c) of claim 14 of assessing if the difference is above a pre-determined threshold, followed by step d) of claim 14 of, if the difference between the values is lower than or equal to the pre-determined threshold, the concentration of PPi in the biological sample is determined as the mean of said values, and if the difference between the values is greater than the pre-determined threshold, steps a) to c) are repeated on new fractions of the biological sample.
Conclusion
No claims are allowed.
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Sef
/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
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