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 .
Priority
Acknowledgment is made of the present application as a continuation of a proper National Stage (371) entry of PCT Application No. PCT/US2019/021278, filed March 8, 2019, which claims benefit of U.S. Provisional Application No. 62/640,722, filed March 9, 2018.
Information Disclosure Statement
Information Disclosure Statement has not been provided.
Status of claims
Claims 1-40 are pending and examined below.
Drawings
The drawings are objected to because:
Image quality of Fig. 2-6, 8, and 10-12 is low. For example, text in Fig. 6 is not legible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of a poor quality of the claim set and the specification – both are barely legible.
Claim Objections
Claims 10-17 and 27-37 are objected to because of the following informalities:
Claims 10-17 and 27-37 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim 30 recites “claims 18 to 2.”. Should be “claims 18-29”.
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 38 and 40 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 38 recites a method of assessing cardiotoxicity of a test compound as described herein. The claim is indefinite because it fails to recite any method steps.
Additionally, there is insufficient antecedent basis for this limitation in the claim, because claim 38 does not depend on any other claims so there is no “herein” to base it off of.
Claim 40 recites a metabolomic signature for cardiotoxicity as described herein. The claim is indefinite because it fails to recite any specific metabolites of the signature.
Additionally, there is insufficient antecedent basis for this limitation in the claim, because claim 40 does not depend on any other claims so there is no “herein” to base it off of.
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 1-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring correlation between the presence of a cardiotoxic compound and a relative abundance of specific metabolic biomarkers.
Claim 1 is directed to a process, which is one of the four statutory categories.
Claim 1 describes the relationship between cardiotoxicity of a test compound and a relative abundance of specific metabolic biomarkers, which is categorized as a naturally occurring correlation. This judicial exception is not integrated into a practical application.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim recites contacting cells with a test compound, assaying the spent cell culture for two or more metabolites. These limitations do not integrate the judicial exception of the naturally occurring correlation into a practical application, because contacting cells with the test compound, assaying the spent cell culture for two or more metabolites are necessary steps for decision making and their purpose is merely to obtain data. These steps are considered insignificant pre-solution activity, i.e., mere data gathering steps necessarily performed for the judicial exception (see MPEP 2106.05(g)).
Claim 1 and its dependent claims 2-9 fail to recite any practical application for the method.
Furthermore, claim 1 as a whole does not amount to significantly more than the judicial exception of a naturally occurring correlation. The concept of screening cultured cells for toxicity of test compounds is well-understood, routine, and conventional. For examples, see Chaudhari et al. (Amino Acids. 2017 Dec;49(12):1955-1963) and Bitter et al. (PGPub 2011/0287437) screening for cardiotoxicity; Smith et al. (PGPub 2015/0301025) screening for developmental toxicity; Milburn et al. (USP 8,658,351) screening for hepatotoxicity.
Similarly, claims 2-9, which are dependent from claim 1, are rejected as failing to recite significantly more than the judicial exception since each claim specifies steps that do not further integrate the naturally occurring correlation into a practical application beyond generally linking changed metabolite levels with cardiotoxicity. Finally, claims 1-9 fail to recite any method for assaying the metabolites.
Therefore, claims 1-9 are ineligible under 35 U.S.C. 101.
Claims 39-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because a metabolomic signature is not a process, a machine, a manufacture, or a composition of matter - it is information.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 18 are rejected under 35 U.S.C. 102(a)(1) or 35 USC 102 (a)(2) as being anticipated by Bitter et al. (PGPub 2011/0287437).
Regarding claims 1 and 18, Bitter teaches a method of assessing cardiotoxicity of a test compound, the method comprising: contacting an in vitro culture of human cardiomyocyte cells with a test compound and assaying the spent cell culture media for metabolites. Specifically, Bitter teaches “the method for screening candidate compounds for potential cardiotoxicity, comprising providing a plurality of test compounds; treating primary human cardiomyocytes with each compound, performing at least two assays selected from the group consisting … lactate assay” ([0009]).
Regarding claim 1, Bitter teaches wherein a statistically significant abundance difference as compared to cardiomyocyte controls in the one or more of the metabolites indicates cardiotoxicity. Specifically, Bitter teaches “comparing said results with results of the same assays from primary human cardiomyocytes treated with a compound known to demonstrate cardiotoxicity, wherein similar results between the test compound and the known cardiotoxic compound indicates a likelihood that the test compound will demonstrate cardiotoxicity, and rejecting compounds that demonstrate a likelihood of cardiotoxicity” ([0009]) and “Read-outs from 40 in vitro assays and cardiotoxicity labels were acquired for each compound in the training set (N=19). Of the nineteen compounds, ten were assessed as positive for cardiotoxicity and nine were assessed as negative as determined by information available from public literature and from internal data (Table 1)” ([0073]).
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 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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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.
Claims 2-4 are rejected under 35 U.S.C. 103 as being unpatentable over Bitter et al. (PGPub 2011/0287437), as applied to claim 1 above, in view of Smith et al. (PGPub 2015/0301025), Krpo et al. (J Anal Toxicol. 2018 Mar 1;42(2):126-132), and Daykin et al. (Anal Biochem. 2002 May 15;304(2):220-30).
The teachings of Bitter have been set forth above.
Regarding claims 2-4, Bitter fails to teach removing proteins from the sample by precipitation.
Regarding claims 2-4, Smith teaches “Predicting human developmental toxicity of pharmaceuticals using human stem-like cells and metabolomic ratios” (Title) and “rapid, reproducible, biomarker-based screening methods for the developmental toxicity testing of compounds” (Abstract). Smith also teaches removing proteins from the sample by precipitation. Specifically, Smith teaches “the spent media from the final 24-hour treatment period was collected and added to acetonitrile (Sigma-Aldrich, final acetonitrile concentration 40%), to halt metabolic processes and precipitate proteins from solution” ([0121], Col. 2).
Bitter and Smith fail to teach removing proteins using specific methanol/acetonitrile mixture.
Regarding claims 2-4, Krpo teaches determination of acetaminophen, dexchlorpheniramine, caffeine, cotinine, and salicylic acid by UHPLC–MS/MS (Title) and sample preparation for UHPLC-MS/MS analysis using protein precipitation with ice-cold methanol/acetonitrile mixture (Abstract). Krpo also teaches precipitation at about 50% methanol, about 35% acetonitrile, and about 15% sample.
Specifically, Krpo teaches “About 25 µL of internal standard working solution was added to 100 µL whole blood samples. About 500 µL of ice-cold methanol/acetonitrile mixture (85:15, v/v) was added to each tube” (pg. 127, section “Preparation of biological samples”). Sample volume of 100 µL in total mixture volume of 625 µL (25 µL standard + 100 µL sample + 500 µL methanol/acetonitrile) corresponds to 16% of sample, substantially similar to about 15% of claim 4. The exact ratio of methanol to acetonitrile recited by Krpo is different from that of claim 4, but Daykin provides a rational for the difference.
Regarding claims 2-4, Daykin teaches “The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy” (Title). Specifically, Daykin teaches “Different proteins vary greatly in their solubilities under a given set of physicochemical conditions: certain proteins precipitate from solution under conditions in which others remain soluble” and “Likewise, small molecules bound to proteins under physiological conditions may have different binding affinities to the proteins and can therefore be displaced from the proteins in this way” (pg. 221, Col. 1, last paragraph).
Krpo teaches protein precipitation from whole blood samples, while the screening for cardiotoxicity takes place in a cell culture medium. The differences in protein composition of the two sample types make it obvious that some adjustments to methanol/acetonitrile ratio may be necessary to ensure required level of deproteinization and solubilization of the analytes.
Also, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. The specification fails to provide evidence for criticality of the exact claimed methanol to acetonitrile ratio. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the method of assessing cardiotoxicity of Bitter with protein precipitation using methanol/acetonitrile mixture as taught by Smith, Krpo and Daykin in order to provide a method of assessing cardiotoxicity of a test compound with samples free from protein impurities. One having ordinary skill in the art would have been motivated to make such a change because sample deproteinization is a standard technique in metabolite analysis. The use of such combination would have been desirable to those of ordinary skill in the art because deproteinization improves the quality of metabolite assays, such as HPLC and MS/MS.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because sample deproteinization is a standard practice in analysis of metabolites.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Bitter, as applied to claim 1 above, in view of Chaudhari et al. (Amino Acids. 2017 Dec;49(12):1955-1963).
The teachings of Bitter have been set forth above.
Regarding claims 5-6, Bitter fails to teach assaying for two or more, and three or more of the metabolites.
Regarding claims 5-6, Chaudhari teaches “Metabolite signatures of doxorubicin induced toxicity in human induced pluripotent stem cell-derived cardiomyocytes” (Title) and profiling drug-induced cardiotoxicity using extracellular metabolites in culture medium (Abstract). Chaudhari also teaches assaying for two, or three metabolites.
Specifically, Chaudhari teaches measuring levels of alanine, lactate, and pyruvate in the extracellular cell culture media (Table 1) meeting the limitations of claims 5 and 6 reciting assaying two and three metabolites.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the method of assessing cardiotoxicity of Bitter by employing more analytes as taught by Chaudhari, in order to provide a more robust method of assessing cardiotoxicity of test compounds by using more than one or two analytes.
MPEP 2144.06 provides "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because each metabolite quantitation does not affect assaying the other metabolites.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bitter, as applied to claim 1 above, in view of Milburn et al. (USP 8,658,351).
The teachings of Bitter have been set forth above.
Regarding claim 9, Bitter fails to teach assessing the relative abundance of two or more of the metabolites, determining a ratio of two or more of the metabolites, and determining two or more ratios of the metabolites.
Regarding claim 9, Milburn teaches “Determining liver toxicity of an agent using metabolite biomarkers” (Title) and “various biomarkers for hepatotoxicity and various methods of using the biomarkers” (Abstract). Milburn also teaches assessing the relative abundance of two or more of the metabolites, determining a ratio of two or more of the metabolites, and determining two or more ratios of the metabolites.
Specifically, Milburn teaches “A ‘reference level’ of a biomarker may be an absolute or relative amount or concentration of the biomarker … ‘reference levels’ of combinations of biomarkers may also be ratios of absolute or relative amounts or concentrations of two or more biomarkers with respect to each other” (Col. 3, lines 3-12).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the method of assessing cardiotoxicity of Bitter by employing a step of determining a ratio and/or a relative abundance of two or more metabolites as taught by Milburn, in order to provide a method of assessing cardiotoxicity of test compounds by using two or more analytes and being able to compare their relative abundance in different experiments. One having ordinary skill in the art would have been motivated to make such a change because using relative abundance makes data comparable in different experiments and with the reference levels. The use of such combination would have been desirable to those of ordinary skill in the art for the reasons mentioned above.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because using relative abundance or ratios is a standard approach when internal standards are not available.
Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Bitter, as applied to claim 18 above, in view of Smith, Krpo, and Daykin.
The teachings of Bitter have been set forth above.
Regarding claims 19-21, Bitter fails to teach removing proteins from the sample by precipitation.
Regarding claims 19-21, Smith teaches “Predicting human developmental toxicity of pharmaceuticals using human stem-like cells and metabolomic ratios” (Title) and “rapid, reproducible, biomarker-based screening methods for the developmental toxicity testing of compounds” (Abstract). Smith also teaches removing proteins from the sample by precipitation. Specifically, Smith teaches “the spent media from the final 24-hour treatment period was collected and added to acetonitrile (Sigma-Aldrich, final acetonitrile concentration 40%), to halt metabolic processes and precipitate proteins from solution” ([0121], Col. 2).
Bitter and Smith fail to teach removing proteins using specific methanol/acetonitrile mixture.
Regarding claims 19-21, Krpo teaches determination of acetaminophen, dexchlorpheniramine, caffeine, cotinine, and salicylic acid by UHPLC–MS/MS (Title) and sample preparation for UHPLC-MS/MS analysis using protein precipitation with ice-cold methanol/acetonitrile mixture (Abstract). Krpo also teaches precipitation at about 50% methanol, about 35% acetonitrile, and about 15% sample.
Specifically, Krpo teaches “About 25 µL of internal standard working solution was added to 100 µL whole blood samples. About 500 µL of ice-cold methanol/acetonitrile mixture (85:15, v/v) was added to each tube” (pg. 127, section “Preparation of biological samples”). Sample volume of 100 µL in total mixture volume of 625 µL (25 µL standard + 100 µL sample + 500 µL methanol/acetonitrile) corresponds to 16% of sample, substantially similar to about 15% of claim 21. The exact ratio of methanol to acetonitrile recited by Krpo is different from that of claim 21, but Daykin provides a rational for the difference.
Regarding claims 19-21, Daykin teaches “The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy” (Title). Specifically, Daykin teaches “Different proteins vary greatly in their solubilities under a given set of physicochemical conditions: certain proteins precipitate from solution under conditions in which others remain soluble” and “Likewise, small molecules bound to proteins under physiological conditions may have different binding affinities to the proteins and can therefore be displaced from the proteins in this way” (pg. 221, Col. 1, last paragraph).
Krpo teaches protein precipitation from whole blood samples, while the screening for cardiotoxicity takes place in a cell culture medium. The differences in protein composition of the two sample types make it obvious that some adjustments to methanol/acetonitrile ratio may be necessary to ensure required level of deproteinization and solubilization of the analytes.
Also, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. The specification fails to provide evidence for criticality of the exact claimed methanol to acetonitrile ratio. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the method of assessing cardiotoxicity of Bitter with protein precipitation using methanol/acetonitrile mixture as taught by Smith, Krpo and Daykin in order to provide a method of assessing cardiotoxicity of a test compound with samples free from protein impurities. One having ordinary skill in the art would have been motivated to make such a change because sample deproteinization is a standard technique in metabolite analysis. The use of such combination would have been desirable to those of ordinary skill in the art because deproteinization improves the quality of metabolite assays, such as HPLC and MS/MS.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because sample deproteinization is a standard practice in analysis of metabolites.
Claims 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Bitter, as applied to claim 18 above, in view of Chaudhari.
The teachings of Bitter have been set forth above.
Regarding claims 22-23, Bitter fails to teach assaying for two or more, and three or more of the metabolites.
Regarding claims 22-23, Chaudhari teaches “Metabolite signatures of doxorubicin induced toxicity in human induced pluripotent stem cell-derived cardiomyocytes” (Title) and profiling drug-induced cardiotoxicity using extracellular metabolites in culture medium (Abstract). Chaudhari also teaches assaying for three metabolites.
Specifically, Chaudhari teaches measuring levels of alanine, lactate, and pyruvate in the extracellular cell culture media (Table 1) meeting the limitations of claims 22 and 23 reciting assaying two and three metabolites.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the method of assessing cardiotoxicity of Bitter by employing more analytes as taught by Chaudhari, in order to provide a more robust method of assessing cardiotoxicity of test compounds by using more than one or two analytes. MPEP 2144.06 provides "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because each metabolite quantitation does not affect assaying of the other metabolites.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Bitter, as applied to claim 18 above, in view of Milburn.
The teachings of Bitter have been set forth above.
Regarding claim 26, Bitter fails to teach assessing the relative abundance of two or more of the metabolites, determining a ratio of two or more of the metabolites, and determining two or more ratios of the metabolites.
Regarding claim 26, Milburn teaches “Determining liver toxicity of an agent using metabolite biomarkers” (Title) and “various biomarkers for hepatotoxicity and various methods of using the biomarkers” (Abstract). Milburn also teaches assessing the relative abundance of two or more of the metabolites, determining a ratio of two or more of the metabolites, and determining two or more ratios of the metabolites.
Specifically, Milburn teaches “A ‘reference level’ of a biomarker may be an absolute or relative amount or concentration of the biomarker … ‘reference levels’ of combinations of biomarkers may also be ratios of absolute or relative amounts or concentrations of two or more biomarkers with respect to each other” (Col. 3, lines 3-12).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the method of assessing cardiotoxicity of Bitter by employing a step of determining a ratio and/or a relative abundance of two or more metabolites as taught by Milburn, in order to provide a method of assessing cardiotoxicity of test compounds by using two or more analytes and being able to compare their relative abundance in different experiments. One having ordinary skill in the art would have been motivated to make such a change because using relative abundance makes data comparable in different experiments and with the reference levels. The use of such combination would have been desirable to those of ordinary skill in the art for the reasons mentioned above.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because using relative abundance or ratios is a standard approach when internal standards are not available.
Subject Matter Free of the Prior Art
Claims 7-8 and 24-25 are free of the prior art.
Claims 7-8 and 24-25 would be allowable if rewritten to overcome the rejection of the base claim 18 under 35 U.S.C. 102, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Claims 7-8 and 24-25 disclosing a method of assaying cell culture media for: (a) lactic acid, thymidine, arachidonic acid, 2'-deoxycytidine, and N-acetylaspartic acid; (b) alanine, pyruvate, and inosine are free of the prior art.
The prior art neither teaches nor suggests simultaneous assaying for analytes mentioned above. The closest prior art teaches either individual metabolites or limited sets of metabolites:
Bitter et al. (PGPub 2011/0287437) - assay of lactate;
Milburn et al. (USP 8,658,351) - assays of 2'-deoxycytidine and lactate;
Chaudhari et al. (Amino Acids. 2017 Dec;49(12):1955-1963) - assays of alanine, lactate, and pyruvate;
West et al. (USP 8,703,424) - assays of 2’- deoxyuridine;
Zordoky et al. (Toxicol Appl Pharmacol. 2010 Jan 1;242(1):38-46) - assay of arachidonic acid;
Raftery et al. (PGPub 2015/0056605) - assays of alanine and lactate.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
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