DETAILED ACTION
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant's election with traverse of Group I and Species A in the reply filed on 10 December 2025 is acknowledged. The traversal is on the ground(s) that there is no undue search burden in examining all of the claimed subject matter. This is not found persuasive because the divergent subject matter of the groups and species result in an undue search burden in examining all of the claimed subject matter.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5 and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group or Species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10 December 2025.
Claims 1-20 are pending in the application.
Claims 1-4 and 6-18 are examined in the instant Office action.
Information Disclosure Statements
The IDSs that have been filed have been considered.
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.
Claim(s) 1-4 and 6-18 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. Claims 1-4 and 6-18 are drawn to methods.
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1 : YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 mathematical manipulations to calculate probabilities of aneuploidy that correspond to the hypotheses.
Claim 1 recites the mental step of selecting a subset of patients that meet a confidence level.
Claim 1 recites the mental step and mathematical manipulation of mathematically normalizing the data to correct for amplification bias.
Claim 1 recites the mental step of determining which hypothesis is the most likely hypothesis.
Claim 1 recites the mental step of adjusting data to correct for amplification bias.
Claim 2 recites the mental steps of calculating a depth of read, a bias parameter, and a goodness of fit value.
Claim 3 recites the mental step of constraining the first plurality of hypotheses to be the same as the second plurality of hypotheses
Claim 4 recites the mental steps of calculating a hypothesis corresponding to quantitative allelic data and mathematically determining a fit between expected and obtained genetic data.
Claim 6 recites the mental steps of constraining the data to comprise a plurality of non-polymorphic loci, that each of the second hypotheses specifies an expected distribution of quantitative data at the plurality of non-polymorphic loci, and determining probability values by calculating a fit between expected genetic data and normalized genetic data.
Claim 9 recites the mental step of constraining the hypothesis to predict a specific chromosome as disomic.
Claim 10 recites the mental step of constraining the type of chromosome in the analysis.
Claim 11 recites the mental step of constraining the type of chromosome segment in the analysis.
Claim 12 recites the mental step of constraining the loci to be present on a selected region of a chromosome.
Claim 13 recites the mental step of performing the method independently for different chromosomes or chromosome segments.
Claim 14 recites the mental step of constraining the set of patients to be at least 24 patients.
Claim 15 recites the mental step of deriving the first probability value form the genetic data obtained from polymorphic loci that comprise alleles present in target cells that are not present in the non-target cells.
Claim 18 recites the mental step of determining an amplification bias by a method comprising presuming that the selected first hypothesis is correct for a subset of patients.
Claim 18 recites the mathematical limitation of requiring the amplification bias, for each locus, to be the difference between the expected genetic data for the selected first hypothesis and the obtained genetic data.
These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1-4 and 6-18 recite(s) an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 1 : YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment.
As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. As such, claims 1-4 and 6-18 is/are directed to an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 2 : NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
The prior art of Benz et al. [WO 2011/051283 A1] teaches analysis of chromosomal data in a mixture of target fetal DNA within non-target maternal DNA is routine and conventional.
The prior art of Lo et al. [US PGPUB 2009/0029377 A1; on IDS] teaches that extracting mixtures of cell-free DNA from target cells, and then amplifying and sequencing this cell-free DNA is routine and conventional in the prior art.
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. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B : No). As such, claims 1-4 and 6-18 is/are not patent eligible.
Claim Rejections - 35 USC § 112(a) - Scope of Enablement
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-4 and 6-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a single chromosome or single chromosome segment, does not reasonably provide enablement for different chromosomes or different copies of a chromosome (i.e. in aneuploidy). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. While amplification bias is correctable within a single chromosome, it is not understood as to how to correct amplification bias amongst different chromosomes.
1. The independent claim recites correcting for amplification bias. Claim 18 recites the mathematical relationship for correcting for amplification bias within a chromosome. Claim 13 recites using a plurality of different chromosomes.
2. The specification describes amplification bias in paragraphs 72, 190, and 327. While paragraphs 233-235 of the specification teach correcting for amplification efficiency, original claim 18 recites that mathematical relationship for correcting for amplification bias in a single chromosome. Paragraph 327 of the specification states, “it is not possible to calibrate out the amplification biases amongst different chromosomes.”
3. The prior art document of Rabinowitz et al. [US PGPUB 2011/0288780 A1] studies methods for non-invasive ploidy calling [title]. Paragraph 317 of Rabinowitz et al. states, “it is not possible to calibrate out the amplification biases amongst different chromosomes.”
4. The claims involve correcting for amplification biases amongst different chromosomes. While possible for a single chromosome, the specification and prior art teach that it is impossible to correct for amplification biases amongst different chromosomes. Consequently, it is unpredictable as to how to correct for amplification biases amongst different chromosomes. Such unpredictability leads to UNDUE EXPERIMENTATION.
In view of the above, it is the Examiner’s position that with the insufficient guidance and working examples and in view of unpredictability and the state of art, one of skill in the art could not make and/or use the invention with the claimed breadth without an undue amount of experimentation.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
No claim is allowed.
The claims are free of the prior art because the prior art does not teach or suggest mathematically normalizing genetic data by correcting for amplification biases within a single chromosome.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/ Primary Examiner, Art Unit 1686 3 March 2026