DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
As detailed on the Filing Receipt filed 7/5/2022, the instant application claims priority to as early as 6/6/2019.
Applicant has not supplied an English translation of the listed foreign priority document (CN 201910491767.1; filed 6/6/2019). All references applied herein stand as prior art with respect to the claimed foreign priority date. However, please note that intervening references may be applied during future prosecution because Applicant has not provided an English translation. Applicant may be required to provide an English translation if an intervening reference is applied. See 37 CFR 1.55(g)(3); MPEP 213.04 and 216.
Information Disclosure Statement
The Information Disclosure Statement filed on 12/6/2021 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of the IDS is included with this Office Action.
Claim Status
Claims 1-19 are pending, and under examination.
Claim Objections
Claims 1, 10 and 13-14 are objected to because of the following informalities:
With respect to claim 1, the recited term “uniparental disomy” (line 1) should read “uniparental disomy (UPD)” to clarify the meaning of the later-recited term “UPD”.
Additionally, the initial instance of the recited term “LOH” (line 5) should read “loss of heterozygosity (LOH)” to clarify the meaning of the term.
With respect to claims 10 and 14, the recited terms “a module of site screening” (claim 10, lines 3 and 6) and “the module of sites screening” (claim 14, line 2) should be brought into grammatical accordance by either amending “site” to “sites” in the former case, or amending “sites” to “site” in the latter case.
With respect to claim 13, the recited term “module of excluding false positive site” (lines 2 and 4) should be brought into grammatical accordance with its recited function (“excluding false positive sites”, recited at line 5) by amending “site” to “sites”.
Appropriate correction is required.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art (MPEP 2111-2111.01). This section documents the Examiner’s interpretation of certain recited claim language.
Claim 1 recites the limitation of: “performing LOH judgement according to the mutations obtained in the step of screening for sites; and a region is judged to be LOH when” (lines 4-5). This limitation is interpreted as “performing LOH judgement according to the mutations obtained in the step of screening for sites, wherein a region is judged to be LOH when”.
Claim 1 additionally recites the limitation of: “judging UPD according to the LOH judgment, wherein when an amount of chromosomes with LOH exceeds 2, a sample is judged as a consanguineous marriage; when there is a single copy of a region with LOH, a sample is judged as a fragment deletion; and other samples are judged as UPD when there are regions with LOH” (lines 8-11).
The specification suggests that the recited sample categories (‘consanguineous marriage’, ‘fragment deletion’ and ‘UPD’) are mutually exclusive: “There are three main conditions resulting in LOH, i.e., fragment deletion, UPD and consanguineous marriage. The LOH caused by these three conditions is different in fragment size, distribution and clinical manifestations such that it is possible to judge whether UPD exists” (pg. 5, paras. 2-3). That is, distinguishing out the ‘consanguineous marriage’ and ‘fragment deletion’ samples allows the remaining samples having regions exhibiting LOH to be judged as ‘UPD’ samples.
However the claim as written does not appear to require exclusivity between at least the ‘consanguineous marriage’ and ‘fragment deletion’ sample categories. In accordance with the claim, a sample comprising >2 chromosomes with regions exhibiting LOH would be judged as a ‘consanguineous marriage’ sample. In accordance with the claim, a sample having a single copy of a region exhibiting LOH would be judged as a ‘fragment deletion’ sample. It follows that a sample meeting both of these criteria (i.e., comprising >2 chromosomes with regions exhibiting LOH and having a single copy of at least one of said regions) would be judged as a ‘consanguineous marriage’ sample and also judged as a ‘fragment deletion’ sample.
Importing claim limitations from the specification is generally improper (MPEP 2111.01 § II), and the recited limitation is not considered to require exclusivity between judgment of a sample as a ‘consanguineous marriage’ sample and judgment of the sample as a ‘fragment deletion’ sample.
Interpretation under 35 USC § 112(f)
The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) is invoked. The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f):
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action.
The following claim limitations are being interpreted under 35 USC § 112(f):
a “module of data acquisition” (claim 10);
a “module of site screening” (claims 10 and 14), also referred to as “the module of screening high-quality mutation sites” (claim 12), which includes:
a “quality control unit” (claim 14);
a “module of LOH judgment” (claims 10 and 15-16);
a “module of UPD judgment” (claim 10) which includes:
a “[unit/module] of judging a pathogenic risk” (claim 17); and
a “module of excluding false positive site[s]” (claim 13).
Because these claim limitation are being interpreted under 35 USC § 112(f), they are being interpreted to cover the corresponding structures described in the specification as performing the claimed functions, and equivalents thereof.
In particular, the specification states that “a stored program… achieves functions of the above-mentioned modules… [and] a processor… is used for running a program that realizes the functions of the above-mentioned modules” (pg. 7, paras. 7-8). The specification thus indicates that computer hardware and software implement the claimed “module” elements. For purposes of prosecution, the claimed “module” elements are interpreted as combinations of computer hardware and software sufficient to implement the recited functions of each element.
If applicant does not intend to have these limitations interpreted under 35 USC § 112(f), applicant may:
(1) amend the claim limitations to avoid them being interpreted under 35 USC § 112(f) (e.g., by reciting sufficient structures to perform the claimed functions); or
(2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed functions so as to avoid them being interpreted under 35 USC § 112(f).
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.
Claims 1-19 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.
With respect to claim 1 and dependents therefrom, there is uncertainty regarding scope of the recited term “other samples” (line 10). Prior claim language requires obtaining whole exome sequencing data, and does not require that said sequencing data corresponds to any particular number of samples (e.g., more than one sample). In the interest of compact prosecution, the term is interpreted as referring to any sample corresponding to the obtained data that is not judged as a ‘consanguineous marriage’ or ‘fragment deletion’ sample.
With respect to claim 6 and dependents thereof, there is uncertainty regarding scope of the recited limitation of “wherein in the step of judging LOH, the amount of contiguous homozygous sites is greater than or equal to 20, and their coverage range is greater than or equal to 3 Mbp” (lines 2-3). It is unclear if the recited limitation indicates a data filtering rule, which is applied in the course of judging LOH, or simply requires performance of the function of judging LOH using data that satisfies the recited criteria. Thus, the scope of the limitation is indefinite. In the interest of compact prosecution, the limitation is interpreted “wherein the step of judging LOH comprises identifying regions having 20 or more contiguous homozygous sites with coverage of 3 Mbp or more” (i.e., as indicating a data filtering rule).
With respect to claim 9, there is uncertainty regarding scope of the claimed method. It is unclear whether the recited clause “comprising applying the method of claim 1” refers to a step of the claimed method of “preparing a device” or merely describes the recited device function of “screening”.
The preamble of claim 1 characterizes its subject matter as a “method of screening a pathogenic uniparental disomy”, which suggests that “applying the method of claim 1 to screen a pathogenic uniparental disomy” would describe the function of a “device for screening a pathogenic uniparental disomy” (i.e., a method of using the device) rather than a process of preparing said device (i.e., a method of making the device). Thus, the scope of the claimed method of preparing (claim 9) is uncertain.
However, under interpretation of the recited clause as merely describing the device function, the claim does not appear to recite any constituent steps of the claimed method. Therefore, in the interest of compact prosecution, the recited limitation of “applying the method of claim 1” is interpreted as a constituent step of the method of preparing the device.
With respect to claim 10 and dependents thereof, there is uncertainty regarding scope of claimed “module” elements. The claims are directed to a device comprising the following components:
a “module of data acquisition” (claim 10, line 2);
a “module of site screening” (claim 10, lines 3 and 6; claim 14, line 2), also referred to as “the module of screening high-quality mutation sites” (claim 12, line 2), which includes:
a “quality control unit” (claim 14, line 2);
a “module of LOH judgment” (claim 10, line 5; claim 16, line 2);
a “module of UPD judgment” (claim 10, line 9) which includes:
a “[unit/module] of judging a pathogenic risk” (claim 17, lines 2 and 3); and
a “module of excluding false positive site[s]” (claim 13, lines 2 and 4).
Claims to a product (e.g., a device) may refer to processes in which it is intended to be used, or capabilities of the product, so long as it is clear that the claim is directed to the product and not the process. Claims reciting limitations directed to both a product and active steps of using the product (i.e., specific actions or functions performed by a user of the product) are indefinite (MPEP 2173.05(p) §§ I-II). The claims further recite the following limitations, which appear to characterize the “module” elements as specific processes rather than device components:
“wherein in the module of screening high-quality mutation sites… the mutation sites passed through a quality control… and having a total coverage range of more than 40X and a mutation frequency of greater than 30%” (claim 12, lines 2-4);
“wherein a module of excluding false positive site is further included between the module of allele frequency screening and the module of mutation frequency screening, wherein the module of excluding false positive site[s] is performed according to the Hardy Weinberg balance, by excluding false positive sites from a frequency database in a regional population to be evaluated” (claim 13, lines 3-6);
“wherein in the module of LOH judgment, when a product of the amount of contiguous homozygous sites and the coverage range thereof is greater than 200 Mbp, a region is judged to be LOH” (claim 16, lines 2-4); and
“wherein in the module of judging a pathogenic risk, the LOH region which is judged to be UPD is further compared with an imprinted gene; and when the LOH region does not cover an imprinted gene or a corresponding band, this region is indicated as a benign UPD; when the LOH region covers the imprint gene or the corresponding band, the region is indicated as being at risk of pathogenic UPD” (claim 17, lines 2-7).
It is unclear if the cited limitations merely describe functional capabilities of the “modules”, or actively require human employment of the device (i.e., the “modules”) in a particular manner. Hence, the cited limitations are indefinite. The Examiner suggests amendment of the above recited dependent limitations to further clarify reference to device component capabilities. For example, amendment to:
“wherein the module of screening high-quality mutation sites is configured to determine… the mutation sites that pass through a quality control… and have a total coverage range of more than 40X and a mutation frequency of greater than 30%” (claim 12);
“wherein the device further includes a module of excluding false positive sites, wherein the module of excluding false positive site[s] is configured to exclude false positive sites, from a frequency database, according to the Hardy Weinberg balance in a regional population to be evaluated” (claim 13, lines 3-6);
“wherein the module of LOH judgment is configured to the amount of contiguous homozygous sites is greater than or equal to 20, and the coverage range is greater than or equal to 3 Mbp” (claim 15);
“wherein the module of LOH judgment is configured to judge a region to be LOH when a product of the amount of contiguous homozygous sites and the coverage range thereof is greater than 200 Mbp” (claim 16); and
“wherein the module of judging a pathogenic risk is configured to further compare the LOH region which is judged to be UPD with an imprinted gene, wherein when the LOH region does not cover an imprinted gene or a corresponding band, this region is indicated as a benign UPD, and when the LOH region covers the imprint gene or the corresponding band, the region is indicated as being at risk of pathogenic UPD” (claim 17).
In the interest of compact prosecution, the cited limitations are interpreted according to the Examiner’s exemplified suggestions.
With respect to claim 11 and dependents thereof, a claim to a product (e.g., a device) may contain a reference to the process in which it is intended to be used, or capabilities of the product, so long as it is clear that the claim is directed to the product and not the process. Claims reciting limitations directed to both a product and active steps of using the product (i.e., specific actions or functions performed by a user of the product) are indefinite (MPEP 2173.05(p) §§ I-II).
Claim 11 is directed to a device. Accordingly, there is uncertainty regarding scope of the recited limitation of “the mutations under pre-determined conditions are screened and obtained through the following approaches” (claim 11, lines 2-3).
It is unclear if the limitation describes device capabilities, or actively require human employment of the device in a particular manner. Hence, the limitation is indefinite. The Examiner suggests amendment of the cited limitation to further clarify reference to device capabilities. For example, amendment to: “the module for site screening is configured to screen and obtain the mutations under pre-determined conditions through the following approaches”.
In the interest of compact prosecution, the cited limitation is interpreted according to the Examiner’s exemplified suggestions.
With respect to claim 15 and dependents thereof, there is uncertainty regarding scope of a claimed “module” element. The claim recites the following limitation, which appears to claim a specific process embodiment of the “module of LOH judgment”: “wherein in the module of LOH judgment, the amount of contiguous homozygous sites is greater than or equal to 20, and the coverage range is greater than or equal to 3 Mbp” (lines 2-3).
Claims reciting limitations directed to both a product (e.g., a device) and active steps of using the product (i.e., specific actions or functions performed by a user of the product) are indefinite (MPEP 2173.05(p) §§ I-II). It is unclear if the cited limitation indicates a data filtering rule that is implemented in the device function of judging LOH, or requires performance of the function of judging LOH using data that satisfies the recited criteria.
Thus, the scope of the limitation is indefinite. In the interest of compact prosecution, the limitation is interpreted “wherein the module of judging LOH is configured to identify regions having 20 or more contiguous homozygous sites with coverage of 3 Mbp or more” (i.e., as indicating an implemented data filtering rule).
For the above reasons, the claims are indefinite.
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 1-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more (i.e., non-statutory subject matter).
"Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea.
Step 1: The Four Categories of Statutory Subject Matter (MPEP 2106.03)
Claims 1-9, 10-17 and 19 are directed to methods (claims 1-9), a device (claims 10-17), and a system (19), which fall under categories of statutory subject matter.
Claim 18 is directed to a computer program product comprising a “computer readable storage medium”. This term, in isolation, encompasses transitory embodiments (e.g., propagating signals) which do not fall under any category of statutory subject matter. See In re Nuijten, 500 F.3d 1346, 84 USPQ2d 1495 (Fed. Cir. 2007). The specification does not reference any non-transitory embodiments of the claimed storage medium.
The Examiner suggests amendment to, e.g., “non-transitory computer readable medium”, which would fall under a category of statutory subject matter, to overcome this
portion of the rejection. However, this amendment alone would likely not overcome rejection
for recitation of an abstract idea without significantly more. In the interest of compact
prosecution, the recited subject matter has been interpreted as limited to non-transitory embodiments for further analysis below regarding recitation of an abstract idea
without significantly more.
Step 2A, Prong One: Whether the Claims Set Forth or Describe a Judicial Exception (MPEP 2106.04 § II.A.1) ‘Mental processes’ are processes that can be performed in the human mind at least with use of a physical aid, e.g., a slide rule or pen and paper (MPEP 2106.04(a)(2) § III). The claims recite elements encompassing processes that are practicably performable in the human mind, at least under their broadest reasonable interpretation, including:
“screening [and obtaining] mutations under pre-determined conditions” (claims 1 and 10), i.e., identifying a subset of data based on a predetermined rule set;
“performing LOH judgement according to the mutations obtained… [wherein] a region is judged to be LOH when a product of an amount of contiguous sites and a coverage range thereof is greater than a pre-set value” (claims 1 and 10), i.e., categorizing data according to derived attributes, wherein:
“the amount of contiguous homozygous sites is greater than or equal to 20, and their coverage range is greater than or equal to 3 Mbp” (claims 6 and 15),
“when the product of the amount of contiguous homozygous sites and their coverage range is greater than 200 Mbp, a region is judged to be LOH” (claims 7 and 16);
“judging UPD according to the LOH judgement, wherein when an amount of chromosomes with LOH exceeds 2, a sample is judged as a consanguineous marriage; when there is a single copy of a region with LOH, a sample is judged as a fragment deletion; and other samples are judged as UPD when there are regions with LOH” (claims 1 and 10), i.e., categorizing data according to attributes;
“screening for high-quality mutation sites from [the] whole exome sequencing data” (claim 2 and 11), wherein:
“the high-quality mutation sites are the mutation sites passed through a quality control of GATK-VQSR, and having a total coverage range of more than 40X and a mutation frequency of greater than 30%” (claims 3 and 12);
“removing Y chromosome mutations from the above mutation sites” (claims 2 and 11), i.e., filtering data based on attributes;
“screening for point mutations from the mutations obtained in the step of removing Y chromosome mutations” (claims 2 and 11), i.e., identifying a subset of data based on attributes;
“screening for sites which are located in the point mutations in the previous step to obtain sites which have a population allele frequency of less than 0.7 in [particular data]” (claims 2 and 11), i.e., identifying a subset of data based on occurrence frequency in a second set of data;
“removing sites which have a mutation frequency of heterozygous sites of higher than 70%” (claims 2 and 11), i.e., filtering data based on an attribute threshold;
“removing sites which have a mutation frequency of homozygous sites of less than 85%” (claims 2 and 11), i.e., filtering data based on attributes;
“excluding false positive sites… according to the Hardy-Weinberg balance… in a regional population to be evaluated” (claims 4 and 13);
“a [step of quality control], wherein the [step of quality control] is used to detect the amount of mutations obtained by the screening; when the amount of mutations is greater than or equal to 10,000, the [step of quality control] indicates PASS; when the amount of mutations is less than 10,000, the [step of quality control] indicates FAIL” (claims 5 and 14); and
identify[ing] regions having 20 or more contiguous homozygous sites with coverage of 3 Mbp or more (claims 5 and 16, see ‘Claim Rejections - 35 USC § 112’ section);
“judging a pathogenic risk… [wherein] the LOH region which is judged to be UPD is further compared with imprinted genes; when the LOH region does not cover an imprinted gene or a corresponding band, a sample is indicated as a benign UPD; when the LOH region covers the imprinted gene or the corresponding band, a sample is indicated as being at risk of pathogenic UPD” (claims 8 and 17).
The recited steps of evaluating information, which are practicably performable in the human mind, constitute mental processes.
Hence, the claims recite elements that, individually and in combination, constitute an abstract idea. The claims must therefore be examined further to determine whether they integrate this abstract idea into a practical application (MPEP 2106.04(d)).
Step 2A, Prong Two: Whether the Claims Contain Additional Elements that Integrate the Judicial Exception(s) into a Practical Application (MPEP 2106.04 § II.A.2)
The claims recite the following additional element, which gathers data necessary for performance of claimed functions: “obtaining whole exome sequencing data” (claims 1 and 10). Necessary data gathering is considered to be insignificant pre-solution activity, and as such insufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)).
The claims further recite additional elements that require performance of claimed functions using a computer, or constitute computer hardware and/or software configured to perform claimed functions, including:
“in each race in a population database” (claims 2 and 11), i.e., in subsets of data within a computer-accessible electronic data structure;
“from a frequency database” (claims 4 and 13), i.e., within a computer-accessible electronic data structure;
a “device… comprising: module[s]” configured to perform claimed functions (claims 10, 12-14 and 16-17), i.e., computer hardware and software (see ‘Claim Interpretation’ section);
a “computer program product, comprising a computer readable storage medium storing a computer readable program code,… comprising an algorithm that when executed by a computer processor… implements” the claimed method (claim 18); and
a “system comprising a processor configured to” perform the claimed method (claim 19).
The claims do not describe any specific computational steps by which computer hardware or software performs or carries out functions drawn to the abstract idea, nor do they provide any details of how specific structures of a computer are used to implement these functions. The claims state nothing more than that computer hardware and software performs functions drawn to the abstract idea, which amounts to mere instructions to apply the abstract idea using a computer. As such, the claims do not integrate the abstract idea into a practical application (see MPEP 2106.04(d) § I and 2106.05(f)).
The claims further recite the following additional element, which applies claimed functions: “applying the method of claim 1 to screen a pathogenic uniparental disomy”
(claim 9). The cited element does not meaningfully limit execution of the claimed functions constituting an abstract idea, and therefore amounts to mere instructions to apply the abstract idea for a particular purpose. Mere instructions to apply an abstract idea, albeit for a particular purpose, are insufficient to integrate an abstract idea into a practical application (MPEP 2106.05(f) and 2106.05(h)).
No further additional elements are recited.
When the claims are considered as a whole: they do not improve the functioning of a computer, other technology, or technical field (MPEP 2106.04(d)(1) and 2106.05(a)); they do not apply the abstract idea to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)); they do not implement the abstract idea with, or in conjunction with, a particular machine (MPEP 2106.05(b)); they do not effect a transformation or reduction of a particular article to a different state or thing (MPEP 2106.05(c)); and they do not apply or use the abstract idea in some other meaningful way beyond linking the use of the abstract idea to a particular technological environment and/or field of use (e.g., computerized screening for pathogenic uniparental disomy; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not integrate the abstract idea into a practical application. See MPEP 2106.04(d) § I.
Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to the abstract idea. Claims that are directed to an abstract idea must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Additional elements besides the abstract idea may constitute inventive concepts that are sufficient to render the claims significantly more (MPEP 2106.05).
Step 2B: Whether the Claims Contain Additional Elements that Amount to an Inventive Concept (MPEP 2106.05)
As noted in Step 2A, several recited additional elements amount to insignificant extra-solution activity. Mere addition of insignificant extra-solution activity does not amount to an inventive concept that would render the claims significantly more than a recited abstract idea, particularly when the activities are well-understood or conventional (MPEP 2106.05(g)). The conventionality of recited additional elements that amount to insignificant extra-solution activity must be further considered.
Recited additional elements amounting to insignificant extra-solution activity encompass the following computer-implemented functions, which the courts have held as coextensive with a general-purpose computer and/or well-understood, routine and conventional:
Receiving, storing, and processing data (In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1316 (Fed. Cir. 2011); EON Corp. IP Holdings LLC v. AT&T Mobility LLC, 785 F.3d 616, 622 (Fed. Cir. 2015)), including by:
receiving or transmitting data over a network (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355 (Fed. Cir. 2014); OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015)), i.e., accessing a remote database.
Hence, the encompassed extra-solution activity is considered well-understood, routine and conventional. Well-understood, routine and conventional activity is insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (MPEP 2106.05(d)).
Mere instructions to apply an abstract idea, either using a computer or in a particular field of use, are similarly insufficient to constitute an inventive concept that would render the claims significantly more than said abstract idea (MPEP 2106.05(f) and 2106.05(h)).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a
particular technology; they do not improve a technology by allowing the technology to
perform a function that it previously was not capable of performing; and they do not
provide any limitations beyond generally linking the use of the abstract idea to a particular technological environment and/or field of use (e.g., computerized screening for pathogenic uniparental disomy; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not provide an inventive concept and/or significantly more than the abstract idea itself. See MPEP 2106.05.
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-19 are rejected under 35 USC § 103 as being unpatentable over Curry et al (US 2011/0301854; published 12/8/2011; on IDS filed 12/6/2021), in view of Bolstad et al (US 2013/0230221; published 9/5/2013), Bonin et al (US 2007/0026443; published 2/1/2007; corresponds to WO 2005/090598 listed on IDS filed 12/6/2021), and Pirooznia et al (Human Genomics 8(1): article no. 14, pp. 1-10; published 7/30/2014).
Claim 1 recites a method of screening a pathogenic uniparental disomy, comprising steps of: obtaining whole exome sequencing data; screening and obtaining mutations under predetermined conditions; performing LOH judgment according to the obtained mutations, wherein a region is judged to be exhibiting LOH when a product of an amount of contiguous sites and a coverage range thereof is greater than a pre-set value; and judging UPD according to the LOH judgment, wherein: 1) when an amount of chromosomes with LOH exceeds 2, a sample is judged as a consanguineous marriage, 2) when there is a single copy of a region with LOH, a sample is judged as a fragment deletion, and 3) other samples are judged as UPD when there are regions with LOH.
With respect to claim 1, Curry discloses a method of estimating the allele-specific copy number of a single-nucleotide polymorphism (SNP) in a test genome, comprising steps of: obtaining a test genome, wherein raw data may be filtered by any suitable method, and calculating a plurality of probability distribution functions that indicate which alleles of a plurality of SNPs are present in diploid regions of the test genome (para. 0071), i.e., obtaining sequencing data and screening and obtaining variants under pre-determined conditions; dividing the genome into regions, determining allele-specific copy numbers thereof (i.e., coverage), and identifying LOH regions based on a statistically significant low incidence of heterozygous SNP calls (paras. 0085-87, 0098-100, 0111 and 0126), i.e., judging LOH according to obtained variants.
Curry further teaches that LOH can result from biological mechanisms including deletion of one copy of a chromosomal region and UPD (para. 0053). In this way Curry suggests judging UPD wherein when there is a single copy of a region with LOH, a sample is judged as a regional deletion.
Curry additionally teaches application of the disclosed methods to identify a copy number neutral LOH event in the genome (para. 0084), wherein copy number neutral LOH can result from biological mechanisms including uniparental contribution of both copies of a genomic region (i.e., UPD), or parental consanguinity (paras. 0053-54).
However, Curry does not teach judgment of LOH when a product of an amount of contiguous sites and a coverage range thereof is greater than a pre-set value, and does not suggest any particular method for judging a sample as associated with consanguineous marriage (as opposed to UPD). Neither does Curry specifically teach obtaining whole exome sequencing data; or screening and obtaining mutations.
Bolstad discusses methods and software for biological data analysis, comprising steps of: obtaining sample data from a microarray (para. 0004); determining which allele or alleles an individual carries for a plurality of SNPs (para. 0069), wherein polymorphisms may comprise insertions, repeats or deletions and particular sequences that differ between alleles can be termed ‘mutations’ (paras. 0063 and 0085), i.e., screening and obtaining mutations.
Bolstad also teaches that long contiguous stretches of homozygosity (LCSH) indicate genomic regions that have a neutral copy number (2 copies) but exhibit loss of heterozygosity for measured SNP alleles (paras. 0096-97), and teaches annotation of genomic segments exhibiting LOH or LCSH, i.e., judging LOH (para. 0149). Bolstad states that LOH may be associated with genetic disorders, and UPD in particular is known to be causatively linked with recessive and developmental disorders (paras. 0093-94).
Bolstad teaches a HMM-based data processing method comprising assigning copy numbers to each marker of a given chromosome, and partitioning the chain of copy number calls (i.e., the chromosome) into contiguous segments of markers having identical copy numbers to judge relative gain and loss (paras. 0100-103). Bolstad further teaches generating confidence parameter values, indicating segment length and number of markers per unit length, which represent likelihood that a given segment represents a real change in genomic sequence (e.g., LOH) relative to a reference (para. 0113).
The disclosed confidence parameter values are considered patentably indistinct from the claimed product of an amount of contiguous sites and a coverage range thereof, and Bolstad is considered to at least suggest judgment of LOH based on the disclosed confidence parameter values.
Bolstad teaches that LOH is associated with consanguinity (para. 0095). However, Bolstad does not suggest any particular method for judging a sample as associated with consanguineous marriage. Neither does Bolstad specifically teach obtaining whole exome sequencing data.
Bonin discusses a method for diagnosing UPD in a human being based on SNP analysis (Abstract), and teaches that clinical consequences of UPD can arise due to LOH (para. 0009, Table A). Bonin further teaches that LOH is also known to be associated with consanguinity and inbreeding, which may result in blocks of LOH across many chromosomes (para. 0095).
Bonin is thus considered to at least suggest judging a sample as associated with consanguineous marriage based on an amount of chromosomes with LOH. The particular claimed threshold (exceeding 2) is a result-effective variable that could be arrived upon by one of ordinary skill in the art through routine experimentation, and is not considered to patentably distinguish from the teachings of Bonin.
Bonin teaches obtaining genotype data from human biological samples (para. 0018), and does not specifically teach obtaining whole exome sequencing data.
Pirooznia discusses variant calling pipeline optimization (pg. 1, Abstract), and teaches that advances in next-generation sequencing technology have provided a cost-effective means for sequencing the whole exome of numerous individuals, allowing researchers to analyze mutations underlying genetic disease at a scale and resolution previously not possible (pg. 1, Background; pg. 5, Conclusions).
With respect to claim 2, Curry discloses determining which alleles of a plurality of SNPs are present in diploid regions of the test genome (para. 0071). Curry further discloses copy number assignment wherein, for a male reference, only autosomes are included (para. 0128). In other words, excluding the Y chromosome.
Curry also discloses analysis of SNPs that are present at an appreciable population allele frequency, often 1% (para. 0048), i.e., 0.01 in a population. Curry does not specifically disclose screening for sites based on allele frequency in each race in a population database. Neither does Curry disclose screening for high-quality mutations or point mutations; or removing sites based on particular mutation frequencies.
Bolstad teaches determining which allele or alleles an individual carries for a plurality of SNPs (para. 0069), wherein polymorphisms may comprise insertions, repeats or deletions and particular sequences that differ between alleles can be termed ‘mutations’ (paras. 0063 and 0085). Bolstad thus teaches screening for single-nucleotide insertions or deletions, which are point mutations.
Bolstad advantageously mentions analysis of samples with good quality control metrics (para. 0230), but does not teach screening for high-quality mutations. Neither does Bolstad teach screening for sites based on allele frequency in each race in a population database; or removing sites based on particular mutation frequencies.
Bonin teaches that an extremely large number of SNPs, distributed over the entire human genome, are known and can be retrieved from databases (para. 0023). Bonin does not teach screening for high-quality mutations; screening for sites based on allele frequency in each race in a database; or removing sites based on particular mutation frequencies.
Pirooznia discusses the necessity of processing the copious data generated by next-generation sequencing techniques to yield high-quality data for downstream analysis (pg. 5, Conclusions), and teaches excluding SNPs based on various filtering rules including quality control measures (e.g., <95% call rates). Pirooznia thus teaches screening for high-quality mutations.
Pirooznia describes additional filtering rules based on statistics derived for control samples within an ancestry group (pg. 8, r. column). As Pirooznia discusses computer-implemented methodology, this rule is implemented with reference to a database. The combined teachings of Curry, Bolstad, Bonin and Pirooznia are thus considered to make obvious the claimed features of screening for sites based on allele frequency in each race in a population database.
Pirooznia also teaches excluding SNPs based on excessively high or low heterozygosity (pg. 8, r. column). The particular claimed zygosity thresholds (>70% heterozygosity and <85% homozygosity) are result-effective variables that could be arrived upon by one of ordinary skill in the art through routine experimentation, and are not considered to patentably distinguish from the teachings of Pirooznia.
With respect to claim 3, Pirooznia teaches that SAMtools and GATK are two of the most widely-used variant calling tools (pg. 3, r. column), and GATK significantly outperforms SAMtools (pg. 1, Abstract; pg. 3, r. column – pg. 4, l. column). Pirooznia further teaches that GATK’s Variant Quality Score Recalibration (VQSR) algorithm significantly outperforms a conventional hard filtering technique (pg. 4, r. column; pg. 7, l. column).
Pirooznia also discusses filtering based on read depth parameters, and teaches that variance of read depth presents a trade-off between increased accuracy and increased missing data (pg. 5, r. column). Pirooznia thus teaches that coverage range is a result-effective variable, and also exemplifies analysis of data of up to 50X read depth (pg. 6, Fig. 4A), i.e., a coverage range of more than 40X.
Additionally, Pirooznia teaches excluding SNPs based on zygosity thresholds (pg. 8, r. columns). The particular claimed threshold (>30% mutation) is a result-effective variable that could be arrived upon by one of ordinary skill in the art through routine experimentation, and is not considered to patentably distinguish from the teachings of Pirooznia.
With respect to claim 4, Pirooznia teaches that a SNP was not analyzed if it violated Hardy-Weinberg equilibrium in control samples within an ancestry group (pg. 8, r. column). As Pirooznia discusses computer-implemented methodology, this rule is implemented with reference to a database.
With respect to claim 5, Pirooznia exemplifies analysis of data including an average of 14,730 single-nucleotide variants (SNVs) per individual (pg. 3, r. column), and discusses exclusion of data based on quality control measures including a call rate of <98.5% (pg. 8, r. column). 14,370*0.985 = ~14,154. Thus, Pirooznia is considered to at least suggest requiring that the number of called variants is greater than 14,154 (i.e., when the amount of mutations obtained is greater than 14,154, the quality control step indicates PASS).
With respect to claim 6, Bolstad teaches that long contiguous stretches of homozygosity (LCSH) indicate genomic regions with a neutral copy number (2 copies) but exhibiting loss of heterozygosity (paras. 0096-97). The particular claimed threshold range (20 or more) is a result-effective variable that could be arrived upon by one of ordinary skill in the art through routine experimentation, and is not considered to patentably distinguish from the teachings of Bolstad.
With respect to claim 7, Bolstad teaches a HMM-based data processing method comprising assigning copy numbers to each marker of a given chromosome, and partitioning the chain of copy number calls (i.e., the chromosome) into contiguous segments of markers having identical copy numbers to judge relative gain and loss (paras. 0100-103). Bolstad further teaches generating confidence parameter values, indicating segment length and number of markers per unit length, which represent likelihood that a given segment represents a real change in genomic sequence (e.g., LOH) relative to a reference (para. 0113).
The disclosed confidence parameter values are considered patentably indistinct from the claimed product of an amount of contiguous sites and a coverage range thereof, and Bolstad is considered to at least suggest judgment of LOH based on the disclosed confidence parameter values.
The claimed threshold range of greater than 200 Mbp is a result-effective variable that could be arrived upon by one of ordinary skill in the art through routine experimentation, and is not considered to patentably distinguish from the teachings of Bolstad.
With respect to claim 8, Bonin teaches that clinical consequences of UPD emerge in cases of homozygosity of autosomal recessive traits, mosaic trisomies or expression changes of imprinted genes, wherein UPD may lead to complete loss of function of imprinted genes in impacted chromosome segments and thus to give rise certain clinical conditions (para. 0007). Bonin discusses many known clinical conditions, such as cystic fibrosis, that can arise from a UPD of an imprinted gene (para. 0012, Table B). Bonin therein teaches that UPD of imprinted genes carries a pathogenic risk, and is considered to at least suggest the claimed process of judging pathogenic risk based on whether a LOH region, judged to be UPD, does not cover or covers an imprinted gene.
With respect to claim 9, Curry discloses implementation of their methods by a computer (i.e., device) and programming (para. 0104). The disclosed implementation is considered equivalent to preparing a device comprising applying the method.
Claims 10-17 are directed to a computer device (see ‘Claim Rejections - 35 USC § 112’ section) having functional limitations of substantive similarity to method limitations respectively recited in claims 1-8. Curry discloses implementation of their methods by a computer and programming (para. 0104). The combined teachings of Curry, Bolstad, Bonin and Pirooznia are considered to apply to the functional limitations of claims 10-17 in the same manner as detailed regarding the process limitations of claims 1-8.
With respect to claim 18, Curry discloses implementation of their methods by a tangibl