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 .
Receipt is acknowledged of Applicant’s Amendment filed on 08/22/2025.
Claims 1, 9-12 have been amended.
Claim 13 has been canceled.
Claims 1-12 are pending in the instant application.
Claim 10 has been previously withdrawn from consideration.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 102/103
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 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.
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.
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) 1-9, 11-13 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over HELLERSTEIN (US 2005/0202406).
HELLERSTEIN teaches a method of screening of compounds in living systems to detect biological actions (see abstract), which reads on “a method of characterizing a mode of action of a test compound”, comprised of: “b) administering an isotope-labeled substrate to said living system for a period of time sufficient for said isotope-labeled substrate to enter into and pass through a metabolic pathway of interest and thereby enter into and label a targeted molecule or molecules of interest within said one or more metabolic pathways in said living system; c) obtaining one or more samples from said living system, wherein said one or more samples comprise one or more isotope-labeled targeted molecules of interest” (see claim 1), wherein groups of living systems, such as plants or animals (see [0094]), such as five rats were given the test compound (see [0275], which reads on (a) the first and second biological samples are isolated from a living system exposed to the test compound; “measuring the molecular flux rates in said one or more metabolic pathways of interest according to steps b) through e) in a living system not administered said one or more compounds” (see claim 1), such as controls (see [0242]), which reads on more than one control and reads on (b) wherein the third and fourth biological samples are isolated from a living system not exposed to the test compound, which appears to be control groups commonly used in research experiments; “d) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said targeted molecule or molecules of interest” (see claim 1), such as using gas chromatography-mass spectrometry (see [0185]-[0186]), which reads on performing chromatograph and mass spectrometry analysis of metabolites extracted from the biological samples to provide mass spectra data; “e) calculating molecular flux rates in said one or more metabolic pathways of interest” (see claim 1), which reads on calculating a mass isotopomer distribution for the metabolites from the mass spectra; “g) comparing said molecular flux rates in said one or more metabolic pathways of interest in said living system administered said one or more compounds to said molecular flux rates in said one or more metabolic pathways in said living system not administered said one or more compounds to screen said compounds for one or more actions on said molecular flux rates” (see claim 1), which reads on identifying metabolites that have a significant different isotopomer distribution when the living system was exposed to the test compound to the isotopomer distribution when the living system was not exposed to the test compound. Note, the steps of “calculating”, “identifying”, “pairing”, “comparison” appears to be mental step and are not active steps (see Applicant’s claim 3).
HELLERSTEIN further teaches: molecular flus rates refers to the rate of synthesis and/or breakdown of molecules within a cell, tissue, or organism (see [0037]-[0039]), which reads on metabolites; living system can be plants or animals (see [0094]); isotope-labeled substrate can be 2H2O, 13CO2, etc. (see [0014]); 2-3 hours after administration to ensure that the mass-isotopically-labeled subunit has decayed substantially from its highest level (see [0212]-[0213]), which reads on exposed to the isotope-labeled substrate for between 10 mins and 48 hours; new compounds, such as biological factors (see [0003]) and new or known chemical entity, such as drugs (see [0010]); a method for “mining” the Physicians Desk Reference or Merck Indexes (see [0033]), which reads on reference library; mass isotopomer distribution analysis (see [0035]); [0056]); "Isotopic pattern" refers to the internal relationships of isotopic labels within a molecule or population of molecules, e.g., the relative proportions of molecular species with different isotopic content, the relative proportions of molecules with isotopic labels in different chemical loci within the molecular structure, or other aspects of the internal pattern rather than absolute content of isotopes in the molecule (see [0059]) and "Mass isotopomer pattern" refers to a histogram of the abundances of the mass isotopomers of a molecule. Traditionally, the pattern is presented as percent relative abundances where all of the abundances are normalized to that of the most abundant mass isotopomer; the most abundant isotopomer is said to be 100%. The preferred form for applications involving probability analysis, such as mass isotopomer distribution analysis (MIDA), however, is proportion or fractional abundance, where the fraction that each species contributes to the total abundance is used. The term "isotope pattern" may be used synonomously with the term "mass isotopomer pattern." (see [0060]), which reads on comparing and analyzing the isotopic difference and different isotopomer distribution.
Response to Arguments
Applicant argues that the '406 publication is directed to determining molecular flux rates within one or more biochemical processes. The cited reference solves the problem of using a high throughput method to determine how a targeted molecule of interest is affected by a test compound. The '406 publication teaches adding an isotope-labeled substrate that, with time, enters one or more metabolic pathways. Molecules of interest then are assessed in samples taken from the treated system. In contrast, the present claims are directed to a completely different method. In particular, the present claims are directed to the problem of determining how a test compound is metabolized, without regard to any particular target or metabolic pathway. In this regard, a metabolite library is created after exposure of a system to an isotopomer. The mass isotopomer distribution for all previously detected metabolites, as well as unknown metabolites, can be calculated. Accordingly, the effect of test compounds on unknown and previously unidentified biochemical pathways can be measured using the method of the present claims. The claimed subject matter clearly differs from the '406 publication in that the reference does not teach or suggest a method of detecting metabolites, known and unknown, in response to a test compound. The technical effect of the difference between
the '406 publication and the present claims is that the method of the present claims can be used to identify the targets of test compounds. A person skilled in the art, after reading the '406 publication, and given the problem solved by the present claims, could not reasonably arrive at the claimed subject matter. The '406 publication provides absolutely no apparent reason or motivation to somehow modify the disclosure of the reference in a way that leads to the claimed invention. The '406 publication does not even remotely suggest how a metabolic profile of known and unknown compounds in response to a test compound could be created. The '406 publication merely addresses targeted molecules. Therefore, it would not have been obvious for a skilled person to measure isotopomer distribution of each metabolite for the population tested based on the '406 publication. In this case, the '406 publication fails to teach or suggest every element recited in the claims and, therefore, cannot render the present claims obvious for this reason alone. In addition, the '406 publication fails to recognize the problem solved by the claimed invention, and, accordingly, the reference provides no incentive or apparent reason for a person skilled in the art to modify the '406 publication in a way that leads to the claimed invention. The '406 publication provides no guidance with respect to such a modification, let alone with a reasonable expectation of determining how a test compound is metabolized. This feature is not remotely considered in the '406 publication.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, the reference teaches Applicant’s active steps. The reference also teaches “d) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said targeted molecule or molecules of interest” (see claim 1), such as using gas chromatography-mass spectrometry (see [0185]-[0186]), which reads on performing chromatograph and mass spectrometry analysis of metabolites extracted from the biological samples to provide mass spectra data.
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.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618