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 .
Claim Status/Action Summary
This office action is a first action on the merits responsive to the claims filed on September 16, 2024.
Claims 1-10 are currently pending and under examination in the present application. No other claims are currently pending.
Priority
The present application, filed on September 16, 2024 claims foreign priority to CHINA 2023116513069, filed on December 4, 2023.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that no English language translation of the certified priority document has been filed as of the mailing date of this action.
Information Disclosure Statement
No information Disclosure Statement has been filed in this application as of the mailing date of this action.
Drawings
The drawings filed on September 16, 2024 are acceptable.
Specification
The use of the terms “Illumina” and “GeneCards”, which are each a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 4-6 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
Claim 4 is broadly drawn to “the… method… according to claim 3, further comprising constructing mice with conditional knockout or overexpression of the differential gene C10orf10 in adipose tissue and performing related studies comprising…”
Relevant to the lack of particular structural or methodological limitations in the rejected claims drawn to “constructing mice” and “performing related studies”, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
In the case of the instant claims, the functionality of “conditional knockout or overexpression of the differential gene C10orf10 in adipose tissue” is a critical feature of the claimed methods.
The specification mentions “step 6, constructing mice with conditional knockout or overexpression of the differential gene C10ORF10 in adipose tissue and performing related studies” at paragraphs 10, 56, and 82. However, the disclosure does not teach: a) any methods by which such a mouse may be constructed, b) any data collected from said “related studies” performed on said “construct[ed] mice”, or c) any description or support that such mice had actually been constructed at the time the application was filed.
While the skilled artisan may be capable of making mice with the claimed functionality of “conditional knockout or overexpression of the differential gene C10orf10 in adipose tissue”, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of methods comprising a step of “constructing mice” with either of the claimed functionalities, “conditional knockout or overexpression of the differential gene C10orf10 in adipose”. However, the specification fails to teach any methods by which this step is to be accomplished or any data distinguishing even a single species of mice having any of the claimed functionalities.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Even more, regarding the requirements for sufficient description of an original claim, MPEP 2163.03 states:
“An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Thus, considering the breadth of the claimed methods comprising constructing the claimed mice, their specific required functionalities, the teachings in of the instant specification, the lack of support for said “constructing” step in the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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.
Claims 1-10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-10 are indefinite because it is unclear how the preamble is intended to breathe life and meaning into the claims. The preamble of each claim is directed to “A screening method of an autolysosome gene C10ORF10 for regulating a fat function of obese patients”.
However, the claims do not positively recite any particular method steps that clearly identify, define, or determine any “fat function of obese patients” that is regulated by C10ORF10. The only reference in the body of the claims to “a function” is found in claim 7: “conducting database querying and literature research, wherein public databases of systems of Genecards, The Human Protein Atlas and National Center for Biotechnology Information are used to query relevant information about the C10ORF10 gene, and to obtain a mechanism of the gene in a function of the autolysosome.”
This “conducting database querying and literature research” appears to require only looking up that which was already known about C10ORF10 and not any particular manipulative steps that accomplish the goal set forth by the claims.
Claim 1, upon which claims 2-10 depend, requires the following steps: A) “determining autolysosome genes”, B) “collecting subcutaneous and visceral adipose tissues from people with different metabolic conditions and different body mass indexes (BMIs)”, C) “transcriptome sequencing analysis”, Ci) “dividing specimens from people with normal metabolism into two groups of BMI…”, Cii) “comparing the two groups in terms of expression differences of autolysosome-related genes”, Ciii) “screening out differential genes” (i.e. selecting genes that differ in expression between the two groups), Civ) “comparing expressions of the differential genes… in systems of [a set of public databases]”, Cv) “selecting differential genes with high expression for analysis”, D) “analyzing and observing the… adipose tissues, comparing several autolysosome genes in terms of differential expression…”. None of these steps clearly and positively recite any step(s) which mention, much less identify, define, or determine any “fat function of obese patients” that is regulated by C10ORF10.
Claim 1 recites a step of “determining autolysosome genes”. Neither the specification nor the claims define what this term entails. It is unclear whether the claim is intended to encompass a step of “determining” that is simply consulting the prior art (which is not referenced in the application) for gene(s) which were already known to be associated in any way with the subcellular compartment “autolysosome”, or whether the claim is somehow intended to require something more.
Claim 1 recites “collecting… adipose tissues from people with different metabolic conditions and different body mass indexes”. The claims do not define what “metabolic conditions” are intended to be encompassed by the claim and there is no limiting definition in the specification as to what is encompassed by this term. It is unclear whether this claim requires that each person has a “condition” of metabolism that is pathological or variant in some undefined way from an undefined reference condition, or simply that each person has some measurable attribute “condition” associated with metabolism. Furthermore, it is unclear whether “people with different metabolic conditions” requires that each person in has multiple “metabolic conditions”, that each person has a “metabolic condition” that is different from the other people from whom tissues are collected, or something else not defined by the specification.
Claim 1 recites the ordered steps: “determining autolysosome genes firstly… collecting… tissues… followed by transcriptome sequencing analysis”. Claim 1 does not positively recite any step requiring the process user to do anything with the collected tissues to gather transcriptome sequencing data, as “transcriptome sequencing analysis” is analyzing sequencing data, which appears to encompass collecting data from publicly-available databases.
Claim 1 further recites a step of “dividing specimens from people with normal metabolism into two groups” (i.e. people not having “metabolic conditions”). However, the claim previously required “firstly, collecting… tissues from people with different metabolic conditions…”. As described above, it is unclear whether “normal metabolism” is encompassed by “metabolic conditions”, or whether “metabolic conditions” requires “abnormal” metabolism.
Claim 1 recites “comparing the two groups in terms of expression differences…” and “screening out differential genes, followed by comparing expressions of the differential genes in adipose tissues of the two groups in [public databases]”. It is unclear how the steps “comparing the two groups in terms of expression differences” (i.e. identifying genes that are differentially expressed between the two groups) is intended to differ from “screening out (i.e. selecting) differential genes (i.e. “differentially expressed genes”) of the two groups followed by comparing the expressions of the differential genes in [public databases]…”.
Claim 1 recites the claim term “comparing expressions of the differential genes in adipose tissues of the two groups”. It is unclear whether this term requires comparing “expression levels” (i.e. a measure of the amount of steady-state mRNA in the sampled tissue) of the genes already identified as being differentially expressed between the two groups (e.g. expression level of C10ORF10 in the obese group vs. expression level of C10ORF10 in the non-obese group), “differential expression” (i.e. a measure of the difference in “expression level” of a gene between the two groups; e.g. comparing a fold-change in expression of C10ORF10 between the two groups to a fold-change in expression of a second (unspecified) gene between the two groups), or something else entirely.
Claims 1 and 10 recite the term “comparing expressions… in systems of Genecards, The Human Protein Atlas, and the National Center for Biotechnology Information”. It is unclear what “systems” are required by the claim, whether the claim requires comparing expression levels (i.e. a measure of mRNA abundance, e.g. “TPM”, “RPKM”) of genes identified as differentially expressed between the two groups, or among other previously published expression levels in adipose tissue, other tissues, or something else entirely.
The term “selecting differential genes with high expression” in claim 1 is a relative term which renders the claim indefinite. The term “high expression” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear whether the claim requires that the selected genes have “high expression” in one or both of the groups from whom tissues were collected (i.e. a large count of total reads or transcripts relative to other genes in the tissue), or whether the claim requires that the selected genes have “high expression” in the previously published data available from the referenced databases, or something else entirely. Additionally, there is no definition of this relative term or guidance in the specification as to what expression level qualifies as “high expression”, or even whether this term is meant to reference a number of total reads, reads normalized to library size and transcript length (e.g. RPKM, TPM), or some other measure not specified.
Claim 1 recites the steps “selecting differential genes… for analysis” but does not positively recite any step of analyzing the selected genes.
Claim 1 recites a step of analyzing and observing the… tissues (i.e. observing or measuring some unspecified propert(ies) of the tissues, e.g. fat content, density, color, etc.), comparing several autolysosome-related genes in terms of differential expressions existed in the two groups of BMI”.
It is unclear whether the claim requires another analysis and observation of the tissues from which the specimens were collected in addition to the “transcriptome sequencing analysis” and further, what analysis and observation the claim may require (e.g. additional molecular assays? Visual comparison of some property of the tissues? Something else?)
The relative term “several”, which is not defined by the claim or the specification, renders the claim indefinite because it is unclear whether the scope of the claim is meant to require comparing: “two or more…”, “three or more…”, or some other number of genes.
Furthermore, the phrase “differential expressions existed in the two groups” renders the claim indefinite because it is unclear what is meant by this phrase. It is not clear whether applicant intends to recite a step comprising: comparing the [read count? Normalized read count? Fold-change? Something else?] between at least two autolysosome-related genes that were previously identified as differentially expressed between the two groups, or something else.
Claim 3 recites “conducting correlation analysis of differential genes with blood glucose, blood lipids, blood pressure, and blood uric acid in obese patients with different metabolic conditions, comprising high uric acid, high blood lipids, high blood glucose, and high blood pressure; correlations of baseline C10ORF10 mRNA with baseline and post-follow-up reductions in… are observed in patients undergoing bariatric surgery, wherein C10 mRNA levels are observed to be positively correlated with… indicating C10ORF10 mRNA is also involved…”
It is unclear whether the claim is intended to require additional steps required to accomplish “conducting correlation analysis… in obese patients with different metabolic conditions”, as there is no recitation of sampling at any particular time(s) or conducting any treatments or surgeries.
Claim 4 is additionally rendered indefinite by the step “performing related studies comprising…[a non-exclusive list of alternatives]”. The scope of the claimed invention is unclear, as there is no definition of what studies are “related” and no clear reference to which the claimed studies relate (i.e. related to “constructing mice…?”, “transcriptome sequencing analysis [of samples from people (i.e. humans)]? or something else?). Furthermore, it is unclear whether the claim requires performing all of the “related studies”, some unspecified subset thereof, or “comprises” all possible studies that include, for example, at least “overall phenotypic observations” (e.g. visually inspecting the mice).
Claim 5 is also indefinite because the recited steps do not appear to limit the referenced step. Claim 5 recites: “claim 4, wherein determining autolysosome genes comprises: determining autolysosome genes, and identifying a list of autolysosome-related genes through literature research and database querying” Claim 5 further recites steps comprising: “collecting samples… and extracting total RNA…” that appear to be unrelated to the “determining comprising determining and identifying… through literature research and database querying”. It is unclear whether these “collecting samples” and “extracting total RNA” steps are intended to limit some other previously established claim step.
Claim 5 recites “a collection process following ethical regulations and relevant research ethics approvals obtained”. It is unclear what collection processes are intended to be included or excluded by this limitation, as different users will be subject to different regulations and approvals processes and because these regulations and approvals processes are subject to change over time.
Claim 5 recites “extracting total RNA… using a method of RNA extraction kit according to instructions, and high quality of RNA is ensured”.
It is unclear to what “method of RNA extraction kit according to instructions” is meant to encompass, as different RNA extraction kits comprise different sets of instructions depending on the sample type. It appears that the claim as written encompasses embodiments wherein any RNA extraction kit according to any instructions is used (e.g., kits for RNA extraction from plant tissues, fungi, soil or other environmental samples).
It is unclear whether the phrase “high quality of RNA is ensured” is meant to require the process user to “ensure” i.e. verify the quality of RNA obtained by other process steps, or whether this is a statement of an intended/desired result of the claimed method that is not limiting to the claim.
The claim term “high quality of RNA” is a relative term which renders the claim indefinite. The term “high quality” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear whether the claim requires that the RNA is measured by some unspecified quality metric (e.g. RIN, rRNA ratio, or something else) and what value(s) of these metric(s) are required by the claim.
Regarding claim 6, the phrase "typically comprising" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation “an RNA-seq method for transcriptome sequencing”, and the claim also recites “sequencing using an Illumina platform” which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 6 contains the trademark/trade name “Illumina”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the source of a genus of “sequencing platforms” manufactured by a particular company and, accordingly, the identification/description is indefinite.
Regarding claim 8, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 9 recites “statistical methods involving Pearson correlation coefficient and Spearman correlation coefficient are used…” It is unclear what additional steps are required by the method or which “statistical methods” are encompassed by the claim.
Claim 10 recites the phrase “expression differences… are compared based on results of transcriptome sequencing analyses, and a statistical method is available to conduct differential gene analyses”. It is unclear whether the recited statement “a statistical method is available” is intended to limit the claim, or merely state that such statistical methods are known in the art.
The claim term “determining the gene with the greatest expression difference, wherein the gene with a largest expression difference is identified from the differential genes, and the autolysosome-related genes with a most significant expression difference from samples of the two groups are screened out” comprises multiple and conflicting relative terms which renders the claim indefinite. The terms “the gene with the greatest expression difference” (i.e. singular), “the gene with a largest expression difference” (i.e. singular), and “genes with a most significant expression difference” (plural) are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear whether the claim is meant to require selecting one (or more than one) gene from among the genes which were previously determined to be differentially expressed based on any of the criteria: a) the greatest difference in raw (or normalized) expression values, b) the greatest fold-change, c) the gene with a maximal statistical metric (e.g., the smallest p-value), or some combination of these criteria. Furthermore, there is no definition of “significant expression difference” in the claims or the specification. It is unclear whether “significant” is meant to refer to a particular metric produced by a particular statistical test, or simply the gene having the largest difference in expression values, or simply the gene having the largest relative difference in expression values (e.g. fold-change).
Claim 10 recites “conducting database querying and literature search… to obtain a mechanism of the gene in a function of the autolysosome”. It is unclear whether this step requires the process user to do anything in addition to reading that which is already known about the recited gene.
Applicant is reminded that no new matter may be added to the application.
Claim Interpretation
The method claims have been interpreted under the broadest reasonable interpretations based on the positively recited method steps and limitations thereto.
It is noted that the following phrases in the following claims appear to recite non-limiting intended or desired results or outcomes that are inherent to the steps as presently claimed:
Claim 1: “wherein a gene with a greatest expression difference is C10ORF10”
Claim 2: “wherein expression differences… are observed…suggesting a significant correlation with BMI”
Claim 3 “indicating C10ORF10 mRNA is also involved in…”
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 1-3 and 7-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. 35 U.S.C. 101 requires that to be patent-eligible, an in invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. MPEP 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also MPEP 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to a process that involves a natural principle and abstract ideas.
Step 2A Prong I
The claims are taken to be directed to a natural phenomenon and abstract ideas.
Claim 1 is directed to “A screening method of an autolysosome gene C10ORF10 for regulating a fat function of obese patients” comprising steps of: A) “determining autolysosome genes”, B) “collecting… tissues”, C) “transcriptome sequencing analysis”, Ci) “dividing specimens from people with normal metabolism into two groups of BMI”, Cii) “Comparing the two groups in terms of expression differences of autolysosome-related genes”, Ciii) “screening out” (i.e. selecting) “differential[ly expressed] genes”, Civ) comparing expressions of the differential genes in adipose tissues of the two groups in systems of Genecards, The Human Protein Atlas, and the National Center for Biotechnology Information” Cv) “Selecting differential genes with high expression for analysis”, and D) “analyzing and observing the… tissues, comparing… genes in terms of differential [gene] expressions [between the two groups of BMI], wherein a gene with a greatest expression difference is C10ORF10.”
Step A) “determining autolysosome genes” recites an abstract idea (mental process) because it encompasses merely looking at a textbook or pre-existing database and reading the names of genes involved in any way with the subcellular compartment “autolysosome” or processes thereof. Step C) “transcriptome sequencing analysis” recites an abstract idea (mental process/mathematical concepts) because it encompasses simple calculations performed on data downloaded from a pre-existing database. Step C additionally recites the judicial exceptions: “dividing specimens… into two groups of BMI… and comparing the two groups” (abstract idea, comparison to a control) and “comparing expressions of the differential genes… in systems of [pre-existing public databases]” (abstract idea, comparison to a control, and mental process, reading a report). Step D “analyzing and observing the… tissues” recites mental processes (i.e. looking at the tissues, observing any characteristic of the tissues) and “comparing… differential expressions existed in the two groups of BMI<25 kg/m2 and BMI>30 kg/m2, wherein a gene with a greatest expression difference is C10ORF10” (i.e. mental process, comparison to a control, and a natural correlation, the correlation between natural expression levels of C10ORF10 (i.e. abundance of a biomolecule) in human adipose tissues and obesity).
Claim 2 depends from claim 1 and further requires steps of “carrying out correlation analysis”, which is an abstract idea (mental process/mathematical concept) “of a differential gene C10ORF10 with BMI… suggesting a significant correlation… [between C10ORF10 expression and] BMI. The “correlation analysis… suggesting a significant correlation” step amounts to a statement of a pre-existing natural correlation.
Claim 3 depends from claim 2 and further requires a step of “conducting correlation analysis of differential genes with blood glucose, blood lipids, blood pressure, and blood uric acid in obese patients with different metabolic conditions comprising high uric acid, high blood lipids, high blood glucose, and high blood pressure” [wherein] “correlations… are observed in patients… wherein C10ORF10 mRNA levels are observed to be positively correlated with… postprandial glucose and HbA1c… indicating C10ORF10 mRNA is also involved in glucose regulation…”. These “conducting correlation analyses” and “observing correlations” steps amount to a statement of a pre-existing natural correlation.
Claim 7 depends from claim 1 and further requires that “analyzing and observing… the tissues, comparing… genes in terms of differential expression” (i.e. an identified step reciting judicial exceptions in claim 1) further comprises steps of “analyzing differential genes, wherein the expression differences… are compared based on results of transcriptome sequencing analyses”. This step reiterates the comparison to a control and natural correlations identified in claim 1. The claim further recites “a statistical method is available to conduct differential gene analyses”. This claim element recites the mere existence of “a statistical method” and therefore is a recitation of an abstract idea (mathematical concepts).
Claim 7 additionally recites “determining the gene with the greatest expression difference… based on results of statistical analyses”, which is a recitation of a mental process because the “determining… based on results of statistical analyses” encompasses reading a report.
Claim 7 further recites a step of “conducting database querying and literature research”, which is a mental process encompassing reading previously published scientific papers and/or reports.
Claim 8 depends from claim 7 and further requires that the step of “carrying out correlation analysis”, which was identified as reciting judicial exceptions in claim 2, comprises steps of: a) “preparing data… wherein samples selected are collated” which is a mental process encompassing retrieving/reading data from a report, database, or spreadsheet; and, b) “data processing, wherein the samples are divided into different BMI groups based on the BMI data… while the expression data of the C10ORF10 gene is matched with the BMI data”, which also encompasses the mental processes identified in a) and encompasses a statement of observing the natural correlation between C10ORF10 gene expression and BMI.
Claim 9, which depends from claim 8, further requires the “conducting a correlation analysis” step comprises the use of “statistical methods involving Pearson correlation coefficient and Spearman correlation coefficient… wherein a correlation coefficient, strength of correlation, and direction of correlation between expression levels of the C10ORF10 gene and BMI are calculated”. These “correlation analysis” steps further requiring the use of simple statistical calculations to describe the natural correlation between C10ORF10 gene expression and BMI recite general mathematical concepts (Pearson correlation coefficient and Spearman correlation coefficient) and a step of performing a calculation (abstract ideas) recite additional abstract ideas (calculation, mathematical concepts) and reiterate the existence of the natural correlation.
Claim 10, which depends from claim 9, further requires steps of: a) “conducting statistical analyses, wherein results of the correlation analyses are used to conduct statistical tests to determine if a significant correlation exists between the C10ORF10 gene expression and BMI” and b) “[performing] statistical tests using t-tests and analysis of variance”. These “statistical analysis” steps further requiring the use of simple statistical calculations to describe the natural correlation between C10ORF10 gene expression and BMI recite extremely general mathematical concepts (“statistical tests”) and a step of performing a calculation (“using t-tests and analysis of variance) recite additional abstract ideas (calculation, mathematical concepts) and reiterate the existence of the natural correlation.
A comparison to a control is an abstract idea. (See MPEP 2106.04(a)(III)(A); claims to “comparing BRCA sequences and determining the existence of alterations,” wherein the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014).
A correlation that preexists in the human is an unpatentable phenomenon. The association between the expression of “autolysosome-related genes” or “C10ORF10” in adipose tissues and obesity is a law of nature/natural phenomenon. The “analyzing and observing”, “correlation analysis” and “statistical tests” steps recited by the claims amount to no more than an “instruction to apply the natural law”. These steps additionally amount to no more than a mental step, as discussed above. Even if the step(s) requires something more, such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the natural law to a new and useful end. Therefore, these steps fail to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself”.
Step 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claims recite a step of “collecting subcutaneous and visceral adipose tissues from people with different metabolic conditions”, this is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the claimed method. Furthermore, while the recitation in claim 1 of “transcriptome sequencing analysis” does not appear to require the process user do anything to generate the transcriptome sequencing data (e.g. perform mRNA-sequencing), even if the claim did require such a step, this element would not be an integration of the judicial exception into a practical application, but would constitute data gathering necessary to perform the claimed method. Furthermore, while the claims (see claim 3) recite “correlations of baseline and post-follow-up reductions in blood glucose and HbA1c are observed in patients undergoing bariatric surgery”, the claims do not recite any steps of collecting samples for, or measuring, “blood glucose and HbA1c”; additionally, the treatment of a subject prior to data analysis is not an integration of the judicial exception. The claims do not require the process user to do anything in light of the observed correlation(s) and it appears that even if the recitation of “correlations… are observed in patients undergoing bariatric surgery” required the process user to perform any of these physical steps (e.g. performing surgery, collecting samples), these steps would further be extra-solution activities necessary to gather data to perform the claimed method. Furthermore, while the claims (see claim 7) recite “verifying the genes with the greatest expression difference… using a real-time quantitative polymerase chain reaction (qPCR) method, this step is not an integration of the judicial exceptions into a practical application. Rather, this step is extra-solution activity required to gather data necessary to perform the claimed method.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non-patent eligible elements, are sufficient to “transform the nature of the claims into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct at 1297).
The claims are not sufficiently defined to provide a method which is significantly more that a statement of a natural principle for at least these reasons:
The claims do not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to “transcriptome sequencing analysis”, “transcriptome sequencing”, “a real-time quantitative polymerase chain reaction”, and “performing bariatric surgery” are mere data gathering steps that amount to extra solution activity to the judicial exception. Determining the level or amount of mRNAs in adipose tissues was well known in the art at the time the invention was made. The prior art, for example, Mileti et al., “Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State” Diabetes, Volume 70, pg. 1486-1497, July 2021, teaches performing RNA sequencing in obese people, people who are not obese, and the same obese people after bariatric surgery (Mileti et al., page 1486, column 1). Additionally, confirmatory RT-qPCR (Reverse Transcription quantitative PCR) of differentially expressed genes was likewise well known in the art at the time the invention was made. The prior art, for example Dahlman et al., “Changes in adipose tissue gene expression with energy-restricted diets in obese women” Am J Clin Nutr 2005; 81:1275-1285 teach performing RT-qPCR to verify observed differences in gene expression (Dahlman et al., page 1281, column 1, paragraph 2).
Furthermore, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a mere generic manner or as insignificant extra-solution activity:
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 102
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 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mileti et al., “Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State” Diabetes, Volume 70, pg. 1486-1497, July 2021.
Regarding claim 1, Mileti et al. teach methods comprising collecting subcutaneous and visceral adipose tissues from people with different metabolic conditions and different BMI, wherein the samples were split into groups: Obese “Ob” having BMI > 30, Previously Obese “PO” (Ob after bariatric surgery), and Never Obese “NO”, both having BMI <25 (Mileti et al., figure 1C). Mileti et al. further teach sequencing the transcriptomes of the samples from each of the three groups, and identifying differentially expressed genes by transcriptome sequencing analysis (Mileti et al., page 1487, column 2, paragraph 2). While the claim element “wherein a gene with a greatest expression difference is C10ORF10” is an intended result inherent to the preceding method steps, and is thus not limiting to the claim: Even more, Mileti et al. teach C10ORF10 is a gene with a greatest expression difference (Mileti et al., Table_S3_R1, sorted on “logFC” and reproduced in part below for clarity) and page 1489, column 2, paragraph 2).
PNG
media_image1.png
150
854
media_image1.png
Greyscale
Therefore, Mileti et al. teach all of the positively recited method steps required by claim 1 as presently written.
Regarding claim 2, Mileti et al. further teach conducting correlation analysis of C10ORF10 with BMI (Mileti et al., Table_S3_R1 and page 1489, column 2, paragraph 2).
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.
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) 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Mileti et al., “Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State” Diabetes, Volume 70, pg. 1486-1497, July 2021 in view of Gomez-Ambrosi et al., “Gene expression profile of omental adipose tissue in human obesity” , The FASEB Journal express article 10.1096/fj.03-0591fje. Published online November 20, 2003.
Regarding claim 1, Mileti et al. teach methods comprising collecting subcutaneous and visceral adipose tissues from people with different metabolic conditions and different BMI, wherein the samples were split into groups: Obese “Ob” having BMI > 30, Previously Obese “PO” (Ob after bariatric surgery), and Never Obese “NO”, both having BMI <25 (Mileti et al., figure 1C). Mileti et al. further teach sequencing the transcriptomes of the samples from each of the three groups, and identifying differentially expressed genes by transcriptome sequencing analysis (Mileti et al., page 1487, column 2, paragraph 2). While the claim element “wherein a gene with a greatest expression difference is C10ORF10” is an intended result inherent to the preceding method steps, and is thus not limiting to the claim: Even more, Mileti et al. teach C10ORF10 is a gene with a greatest expression difference (Mileti et al., Table_S3_R1, sorted on “logFC” and reproduced in part below for clarity) and page 1489, column 2, paragraph 2).
PNG
media_image1.png
150
854
media_image1.png
Greyscale
Regarding claim 2, Mileti et al. further teach conducting correlation analysis of C10ORF10 with BMI (Mileti et al., Table_S3_R1 and page 1489, column 2, paragraph 2).
Regarding claim 3, Mileti et al. teach correlating differentially expressed genes with blood insulin levels (Mileti et al., page 1491, column 2) that differ between the three groups.
Mileti et al. do not teach further measuring and correlating blood glucose, blood lipids, blood pressure, and blood uric acid with differential gene expression.
However, Gomez-Ambrosi et al. teach measuring clinical characteristics in addition to blood insulin that differ between the two groups (e.g. are correlated with differential gene expression) comprising: blood glucose, blood lipids, and blood uric acid (Gomez-Ambrosi et al., Table 2).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have measured these additional routinely measured clinical characteristics because of the teaching of Gomez-Ambrosi et al. that these characteristics differ between obese and non-obese subjects.
Claims 1-2 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Mileti et al., in view of Dahlman et al., “Changes in adipose tissue gene expression with energy-restricted diets in obese women” Am J Clin Nutr 2005; 81, pg 1275-1285.
Regarding claim 1, from which claim 7 depends, Mileti et al. teach methods comprising collecting subcutaneous and visceral adipose tissues from people with different metabolic conditions and different BMI, wherein the samples were split into groups: Obese “Ob” having BMI > 30, Previously Obese “PO” (Ob after bariatric surgery), and Never Obese “NO”, both having BMI <25 (Mileti et al., figure 1C). Mileti et al. further teach sequencing the transcriptomes of the samples from each of the three groups, and identifying differentially expressed genes by transcriptome sequencing analysis (Mileti et al., page 1487, column 2, paragraph 2). While the claim element “wherein a gene with a greatest expression difference is C10ORF10” is an intended result inherent to the preceding method steps, and is thus not limiting to the claim: Even more, Mileti et al. teach C10ORF10 is a gene with a greatest expression difference (Mileti et al., Table_S3_R1, sorted on “logFC” and reproduced in part below for clarity) and page 1489, column 2, paragraph 2).
PNG
media_image1.png
150
854
media_image1.png
Greyscale
Regarding claim 2, Mileti et al. further teach conducting correlation analysis of C10ORF10 with BMI (Mileti et al., Table_S3_R1 and page 1489, column 2, paragraph 2).
Regarding claim 7, Mileti et al. teach analyzing differential genes between the obese and non-obese groups using statistical methods comprising linear models implemented with edgeR and determined the significance of differentially expressed genes by Benjamini-Hochberg-corrected false discovery rate (Mileti et al., page 1486, column 1, paragraph 2).
While Mileti et al. teach that their RNA-sequencing methodology has higher sensitivity and larger dynamic range compared to microarrays and provides “quantitative data that are reliably mirrored by quantitative polymerase chain reaction” (Mileti et al., page 1487, column 2, paragraph 3), Mileti et al. do not teach performing quantitative polymerase chain reaction to verify the genes with the greatest expression difference between the two groups.
However, Dahlman et al. teach methods comprising measuring gene expression changes associated with diet in obese subjects comprising measuring differentially expressed genes using a microarray (Dahlman et al., page 1276, column 2, paragraph 2) followed by verification of differentially expressed genes by RT-qPCR (Dahlman et al., page 1276, paragraph 3 and page 1280, column 2, paragraph 2). Dahlman et al. teach that one of the genes detected as differentially expressed by microarray analysis was not confirmed by qRT-PCR (Dahlman et al., page 1280-1281 bridging paragraph). Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have modified the methods taught by Mileti et al. by additionally confirming the differentially expressed genes identified by their RNA-sequencing technology by RT-qPCR as taught by Dahlman et al. The ordinary artisan would have been motivated to confirm differentially expressed genes discovered by high-throughput methods such as microarrays or RNA-seq using RT-qPCR because of the teaching of Dahlman et al. that RT-qPCR confirmation allows for identification of false positive results generated by other assays (Dahlman et al., page 1281, paragraph 1, column 1).
Regarding claim 8, Mileti et al. teach differential gene analysis comprises “preparing data” and “data processing comprising matching samples in either BMI group to the expression data (Mileti et al., Table_S3_R1).
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Mileti et al., in view of Dahlman et al. as applied to claims 1-2 and 7 above, and further in view of Siska et al., “Differential correlation for sequencing data” BMC Res Notes (2017) 10:54.
Regarding claim 8, Mileti et al. in view of Dahlman et al. teach identifying differentially expressed genes correlated with BMI using generalized linear models implemented in the edgeR program, wherein statistical significance was determined by Benjamini-Hochberg-corrected false discovery rate (Mileti et al., page 1488, column 1, paragraph 2) . Mileti et al. in view of Dahlman et al. do not teach the statistical methods involve Pearson correlation coefficient and Spearman correlation coefficient. However, Siska et al. teach improved differential correlation methods comprising applying multiple correlation metrics to sequencing data including Pearson and Spearman that output correlation vectors corresponding to biological groups (i.e. a correlation coefficient, strength of correlation, and direction of correlation are calculated) (Siska et al., page 3, column 1). Siska et al. further teach their differential correlation methods were among the first, if not the first, to be validated using negative binomial simulations and sequencing data, and that these methods are essential to analyzing differential correlations in sequencing data (Siska et al., page 9, column 2, paragraph 3).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have combined the methods taught by Mileti et al. in view of Dahlman et al. comprising identifying differentially expressed genes correlated with BMI with the methods for reliable differential correlation for sequencing data taught by Siska et al. The ordinary artisan would have been motivated to combine these methods because of the teaching of Siska et al. that their statistical methods provide greater flexibility relative to other methods with regards to data type and have been validated on simulated and real sequencing data (Siska et al., page 9, column 2, paragraph 3).
Regarding claim 10, Mileti et al. teach conducting statistical test s using t tests and analysis of variance (Mileti et al., page 1488, column 2, paragraph 2).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY MARK TURPIN whose telephone number is (703)756-5917. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights