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 .
Election/Restrictions
Applicant’s election without traverse of Group I, corresponding to claims 90-107, and in the reply filed on 05/06/2026 is acknowledged. Furthermore, applicant’s election of species I, a, and species II, a, is acknowledged.
Claims 95 and 97 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/06/2026. Claims 108 and 109 directed to the non-elected inventions have been canceled by Applicant.
Claims Status
Claims 108 and 109 are canceled.
Claims 90-107 are pending.
Claims 95 and 97 are withdrawn from consideration.
Claims 90-94, 96, and 98-107 are examined on the merits.
Priority
The instant application claims priority to provisional Application No. 63/197,936, filed 06/07/2021. Therefore, the Effective Filing Date (EFD) assigned to each of the claims 90-94, 96, and 98-107 is the provisional filing date of Application No. 63/197,936, filed 06/07/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 10/04/2022, 11/02/2022, 06/26/2023, 11/07/2023, 11/05/2024, 01/31/2025, and 04/09/2025 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
It is noted that certain references lack appropriate page numbers as is required under 37 CFR 1.97. The Examiner has annotated the references herein. Applicant is kindly reminded to provide proper citations in compliance with 37 CFR 1.97 in all future submission to the office.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities:
In paragraph [0037], “pesudogene” should read “pseudogene”
In paragraph [0111], “subjectas a carrier” should read “subject as a carrier”
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 90-94, 96, and 98-107 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to claim 90, the claim recites the limitation of “number of the sequence reads of the second plurality of sequence reads aligned to a unique region between GBA gene and GBAP1 gene in the reference genome sequence”. The claim is indefinite because there is no antecedent basis for “the sequence reads of the second plurality of sequence reads aligned to a unique region”.
With respect to claims 91 and 99, the claims recite the term “about”. The claims are indefinite because “about” is a relative term which renders the claim indefinite. The term 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.
The remaining claims are rejected due to being dependent on indefinite claims without remedying the indefiniteness.
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 90-94, 96, and 98-107 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite a system.
With respect to step (2A)(1): The claims are directed to abstract ideas of mental processes and mathematical concepts, and laws of nature.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 90:
determining a number of the sequence reads of the second plurality of sequence reads aligned to a unique region between GBA gene and GBAP1 gene in the reference genome sequence
phasing one or more haplotypes originated from GBA gene or GBAP1 gene in a region of GBA gene, or a corresponding region of GBAP1 gene, comprising a plurality of GBA/GBAP1 differentiating bases using sequence reads of the second plurality of sequence reads aligned to the region, or the corresponding region, comprising the plurality of GBA/GBAP1 differentiating bases
determining a copy number of each of the one or more haplotypes using the total copy number of GBA gene and GBAP1 gene and a number of sequence reads of the second plurality of sequence reads each comprising one or more of the plurality of GBA/GBAP1 differentiating bases that support the haplotype
determining a GBA status of the subject using the one or more haplotypes originating from GBA gene or GBAP1 gene in the region of the GBA gene, or the corresponding region of GBAP1 gene, and/or the copy number of each of the one or more haplotypes
Mathematical concepts recited in claim 90
determining a normalized number of the sequence reads aligned to the unique region between GBA gene and GBAP1 gene in the reference genome sequence
determining a total copy number of GBA gene and GBAP1 gene using a Gaussian mixture model comprising a plurality of Gaussians each representing a different integer copy number, given the normalized number of the sequence reads aligned to the region between GBA gene and GBAP1 gene
Dependent claims 91-94, 96, and 98-106 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 90, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 91: “wherein the unique region between GBA gene and GBAP1 gene in the reference genome sequence comprises a unique region about 10 kilobases in length, and/or wherein the unique region between GBA gene and GBAP1 gene in the reference genome sequence comprises…”
Claim 92: “determining the normalized number of the sequence reads aligned to the unique region between GBA gene and GBAP1 gene in the reference genome sequence using (1a) a depth of the sequence reads aligned to the unique region between the GBA gene and GBAP1 gene, (1b) a length of the unique region, (2a) a depth of sequence reads of the first plurality of sequence reads aligned to each of a plurality of regions of the reference genome sequence other than a genetic locus comprising GBA gene and GBAP1 gene, and (2b) a length of each of the plurality of regions of the reference genome other than the genetic locus comprising GBA gene and GBAP1 gene”
Claim 93: “determining a normalized, corrected number of the sequence reads aligned to the unique region between GBA gene and GBAP1 gene in the reference genome sequence from the normalized number of the sequence reads aligned to the unique region between GBA gene and GBAP1 gene in the reference genome sequence using (1) a GC content of the unique region between the GBA gene and GBAP1 gene and optionally (2) a GC content of each of one or more regions of the reference genome sequence other than a genetic locus comprising GBA gene and GBAP1 gene, wherein determining the total copy number of GBA gene and GBAP1 gene comprises: determining the total copy number of GBA gene and GBAP1 gene using the Gaussian mixture model, given the normalized, corrected number of the sequence reads aligned to the region between GBA gene and GBAP1 gene”
Claim 94: “determining a copy number of the region between GBA gene and GBAP1 gene using the Gaussian mixture mode, given the normalized number of the sequence reads aligned to the region between GBA gene and GBAP1 gene, and wherein the total copy number of GBA gene and GBAP1 gene is the copy number of the region between GBA gene and GBAP1 gene plus two”
Claim 96: “analyzing linkage information between GBA/GBAP1 differentiating bases of the plurality of GBA/GBAP1 differentiating bases using sequence reads of the second plurality of sequence reads aligned to the region, or the corresponding region, comprising the plurality of GBA/GBAP1 differentiating bases”
Claim 98: “wherein a sequence read of the second plurality of sequence reads is aligned to the region of GBA gene, or the corresponding region of GBAP1 gene, comprising the plurality of GBA/GBAP1 differentiating bases with an alignment quality score of zero or more”
Claim 99: “wherein the region of GBA gene, or the corresponding region of GBAP1 gene, comprising the plurality of GBA/GBAP1 differentiating bases is about 1.1 kilobases in length, wherein the region of GBA gene, or the corresponding region of GBAP1 gene, comprising the plurality of GBA/GBAP1 differentiating bases comprises exons 9-11 of GBA gene, or GBAP1 gene, respectively, and/or wherein the region of GBA gene, or the corresponding region of GBAP1 gene, comprising the plurality of GBA/GBAP1 differentiating bases comprises p.L483P, p.D448H, c.1263del, RecNciI, RecTL, and c.1263del+RecTL”
Claim 100: “wherein the plurality of GBA/GBAP1 differentiating bases comprises 10 GBA/GBAP1 differentiating bases”
Claim 101: “wherein the one or more haplotypes comprises a wildtype GBA haplotype, a wildtype GBAP1 haplotype, and/or a GBA/GBAP1 hybrid haplotype, optionally wherein the GBA/GBAP1 hybrid haplotype comprise a GBA variant haplotype or a GBAP1 variant haplotype”
Claim 102: “determining a likelihood of one copy of a wildtype GBA haplotype is higher than a likelihood of two copies of the wildtype GBA haplotype given the number of sequence reads of the second plurality of sequence reads each comprising one or more of the plurality of GBA/GBAP1 differentiating bases that support the wildtype GBA haplotype; and determining the copy number of the wildtype GBA haplotype is one”
Claim 103: “wherein the copy number of a wildtype GBA haplotype is one, and wherein the GBA status of the subject comprises a carrier of a GBA variant haplotype”
Claim 104: “wherein the one or more haplotypes comprises four haplotypes, wherein the total copy number of GBA gene and GBAP1 gene is four, wherein the copy number of each of the four haplotypes is one, and wherein GBA status of the subject comprises a carrier of a GBA variant haplotype”
Claim 105: “wherein the one or more haplotypes comprises two or more GBA variant haplotypes, wherein none of the two or more GBA variant haplotypes comprises a GBA base at each of the plurality of GBA/GBAP1 differentiating bases, and wherein the GBA status of the subject comprises compound heterozygous of GBA variant haplotypes”
Claim 106: “determining a copy number of a GBA base at each of one or more of the plurality GBA/GBAP1 differentiating bases is zero using sequence reads of the second plurality of sequence reads each comprising a base at the GBA/GBAP1 differentiating base that is not the GBA base, optionally wherein the base at the GBA/GBAP1 differentiating base that is not the GBA base is GBAP1 base, and optionally wherein determining the GBA status comprises: determining the subject is homozygous of each of the one or more of the plurality of GBA/GBAP1 differentiating bases”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes and mathematic concepts because the claims recite no more than performing data analysis on gathered sequence reads in order to determine a status of a subject. Steps of determining and phasing, etc. can be performed mentally and the claims utilize mathematical concepts, through the use of a Gaussian mixture model, to determine a total copy number.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claim 90 recites the following additional elements that are not abstract ideas:
a system comprising non-transitory memory configured to store executable instructions and a hardware processor in communication with the non-transitory memory
receiving a first plurality of sequence reads generated from a sample obtained from a subject
aligning the first plurality of sequence reads to a reference genome sequence to obtain a second plurality of sequence reads aligned to GBA gene or GBAP1 gene in the reference genome
The steps of receiving a first plurality of sequence reads and aligning the first plurality of sequence reads generates the data on which the judicial exceptions are performed and is thus directed to a data gathering step. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). The elements of non-transitory memory and a hardware processor are directed to elements of a generic computer. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc. ... are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(f)).
Dependent claim 107 is directed to an ancillary step that outputs the results of the judicial exceptions and is extra-solution and thus does not integrate the judicial exceptions into a practical application.
None of these dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP at 2106.05(d).I, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claim 1: The additional elements of non-transitory memory configured to store executable instructions, a hardware processor in communication with the non-transitory memory, receiving a first plurality of sequence reads generated from a sample obtained from a subject, and aligning the first plurality of sequence reads do not rise to the level of significantly more than the judicial exception. With respect to the generic computer, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). Furthermore, with regard to receiving the sequence reads, with respect to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, retrieving information in memory is a routine and conventional activity. Furthermore, with respect to buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096, a computer receiving information over a network is a routine and conventional activity. With regard to aligning sequence reads, with respect to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, analyzing DNA to provide sequence information or detect allelic variants is a well-understood, routine, and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 107: The additional element of generating a UI comprising a UI element representing or comprising the GBA status does not rise to the level of significantly more than the judicial exception. A UI is an inherent element of a generic computer. As exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Conclusion
No claims are allowed.
The claims appear to be free from the prior art because while the closest prior art to Maguire et al. (US 2018/0237845 A1, IDS reference) does teach receiving a plurality of sequence reads, aligning sequence reads to a reference genome, determining a normalized number of sequence reads, and determining a total copy number using a Gaussian mixture model, Maguire et al. does not appear to teach or fairly suggest determining a number of the sequence reads of the second plurality of sequence reads aligned to a unique region between GBA gene and GBAP1 gene, phasing one or more haplotype originating from GBA gene or GBAP1 gene in a region of GBA gene, or a corresponding region of GBAP1 gene, comprising a plurality of GBA/GBAP1 differentiating bases, determining a copy number of each of the one or more haplotypes, and determining a GBA status of the subject using the one or more haplotypes originating from GBA gene or GBAP gene. Furthermore, another close prior art, Zampieri et al. (“GBA Analysis in Next-Generation Era: Pitfalls, Challenges, and Possible Solutions”, IDS reference) does teach sequencing and aligned sequence reads to the GBA gene and GBAP 1 pseudogene, and determining GBA variant status based on GBAP1 alignment and variants, Zampieri et al. does not appear to teach or fairly suggest phasing one or more haplotype originating from GBA gene or GBAP1 gene in a region of GBA gene, or a corresponding region of GBAP1 gene, comprising a plurality of GBA/GBAP1 differentiating bases, determining a copy number of each of the one or more haplotypes, and determining a GBA status of the subject using the one or more haplotypes originating from GBA gene or GBAP gene. Thus, a combination of Maguire et al. and Zampieri et al. does not render the claims obvious.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Emilie A Smith whose telephone number is (571)272-7543. The examiner can normally be reached 9am - 5pm.
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, Larry D Riggs can be reached at (571)270-3062. 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.
/E.A.S./Examiner, Art Unit 1686
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
Prosecution Insights