DETAILED ACTION
Comments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claims 26 and 29-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 20 May 2025.
Claims 21, 24-26, and 29-33 are pending in the application.
Claims 21, 24-25, and 31-33 are examined in the instant Office action.
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.
The following rejection is reiterated with new prior art:
Claim(s) 21, 24-25, and 31-33 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 21, 24-25, and 31-33 are drawn to processes.
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 21 recites the mental step of estimating the chromosomal dosage of a first fetal chromosome in the maternal sample.
Claim 21 recites the mental step of estimating the chromosome dosage of one or more fetal chromosomes in the maternal sample.
Claim 21 recites the mental step of providing data on prior risk of aneuploidy for at least the first fetal chromosome based on extrinsic characteristics.
Claim 21 recites the mental steps of calculating a value of the likelihood that a first fetal chromosome is either aneuploid or disomic by comparing the chromosome dosage of the first fetal chromosome to the chromosome dosage of one or more fetal chromosomes in view of prior risk of aneuploidy.
Claim 21 recites the mental step of calculating a risk of aneuploidy of the first fetal chromosome based on the calculated values of likelihood.
Claim 21 recites the mental step of determining fetal DNA contribution to the maternal sample.
Claim 25 recites the mental step of constraining data of prior risk to be data on maternal age.
Claim 31 recites the mental step of constraining the value of probability to be an odds ratio.
Claims 32 and 33 recite the mental steps of constraining the value of probability of an aneuploidy for the first fetal chromosome to be based on a value of the likelihood of the chromosome being trisomic or monosomic and the value of the likelihood of the chromosome being disomic.
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) 21, 24-25, and 31-33 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.
There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. 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 21, 24-25, and 31-33 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 document of Lo et al. [US PGPUB 2011/0105353 A1; on attached 892 form] teaches interrogating at least twenty polymorphic loci on a first fetal chromosome in the maternal sample and interrogating at least twenty polymorphic of a second fetal chromosome in the maternal sample are 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 21, 24-25, and 31-33 is/are not patent eligible.
Response to arguments:
Applicant's arguments filed 8 December 2025 have been fully considered but they are not persuasive.
Applicant argues that the claims result in the practical application of an improvement to technology by measuring fetal aneuploidy with increased accuracy than conventional techniques. Applicant argues that the recited computational analysis provides a practical application of a complex math-based process to a real life/practical scenario. This argument is not persuasive because a judicial exception that is an improvement to a judicial exception is still a judicial exception (i.e. and not a practical application).
While applicant cites the Kingsley Declaration in related U.S. application 13/426,157, the Kingsley Declaration was found persuasive in overcoming subject matter eligibility rejections because of the arguments regarding fetal fractions. Fetal fractions are not recited in the instant claims.
Applicant argues that the amendments to the claims overcome the subject matter eligibility rejections. This argument is not persuasive because the prior art document of Lo et al. teaches that the amended limitations are routine and conventional.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The following rejection is newly applied:
Claims 21, 24-25, and 31-33 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fan et al. [US PGPUB 2011/0151442 A1; on IDS] in view of Wong et al. [The American Journal of Human Genetics, volume 80, 2007, pages 91-104] in view of Rabinowitz et al. [WO 2011/146632 A1; on attached 892 form].
Claim 21 is drawn to a computer-implemented process to calculate a risk of a fetal aneuploidy in a maternal sample comprising a fetal source and a maternal source. The maternal source comprises a maternal serum or plasma sample from a pregnant female. The methos comprises interrogating at least twenty polymorphic loci on a first chromosome in the maternal sample and interrogating at least twenty polymorphic loci on a second fetal chromosome in the maternal sample. The method comprises determining fetal DNA contribution to the maternal sample. The method comprises estimating a chromosome dosage of the first fetal chromosome in the maternal sample. The method comprises estimating a chromosome dosage of the second fetal chromosome in the maternal sample. The method comprises calculating a value of the likelihood that the first fetal chromosome is aneuploid by constructing an aneuploid model by comparing the estimated chromosome dosage of the first fetal chromosome to the estimated chromosome dosage of the second fetal chromosome in view of the fetal DNA contribution to the maternal sample. The method comprises calculating a value of the likelihood that the first fetal chromosome is disomic by constructing a disomic model by comparing the estimated chromosome dosage of the first fetal chromosome to the estimated chromosome dosage of the second fetal chromosome. The method comprises providing a calculated risk of aneuploidy of the first fetal chromosome based on the calculated values of likelihood.
Claim 24 is further limiting wherein the maternal sample comprises cells. Claim 25 is further limiting wherein the data on prior risk of aneuploidy comprises information related to maternal age.
Claim 31 is further limiting wherein the probability of aneuploidy is an odds ratio.
Claims 32 and 33 are further limiting wherein the value of probability of an aneuploidy for the first fetal chromosome to be based on a value of the likelihood of the chromosome being trisomic or monosomic and the value of the likelihood of the chromosome being disomic.
The document of Fan et al. studies direct molecular diagnosis of fetal aneuploidy [title]. The abstract of Fan et al. teaches that Fan et al. focuses on determining aneuploidy in chromosomes 1, 13, 18, 21, X and Y. Paragraphs 87-89 of Fan et al. teach a binomial distribution mathematical model by which a target and a reference chromosome are compared. Paragraph 89 of Fan et al. teaches that for the case of disomy, there would be no difference between the target and reference chromosome counts. Paragraph 89 of Fan et al. teaches that for the case of trisomy, the difference between the target chromosome and references chromosome counts would be positive with a ratio of about one-half. Paragraph 89 of Fan et al. teaches that for the case of monosomy, the difference between the target chromosome and references chromosome counts would be negative with a ratio of about one-half. Paragraph 90 of Fan et al. teaches empirical analysis of maternal blood cells to determine aneuploidy.
Fan et al. does not use the exact terminology and odds ratios recited in the claims. Fan et al. does not teach the interrogation of the polymorphic loci and the determination of fetal DNA contribution to the maternal sample.
The document of Wong et al. studies a comprehensive analysis of common copy-number variations in the human gene [title]. The abstract of Wong et al. teaches 3,654 genetic loci. Figure 1 of Wong et al. teaches a plurality of chromosomes for the genetic loci.
The document of Rabinowitz et al. studies methods for non-invasive prenatal ploidy calling [title]. Page 35, line 15 to page 36, line 20 of Rabinowitz et al. teaches interrogating thousands of SNPs on each of multiple fetal chromosomes. Page 66, line 26 to page 67, line 10 of Rabinowitz et al. teaches determining fetal DNA contribution to the maternal sample.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the binomial distribution modeling of Fan et al. to determine the odds and likelihoods recited in the claims because the ratio of the target chromosome distribution to the reference chromosome distribution is an alternative manner of computing an odd or a likelihood that a mathematical model that explicitly calculates an odds/likelihood ratio.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the binomial distribution modeling of Fan et al. by use of the thousands of genetic loci of Wong et al. wherein the motivation would have been that the increased number of genetic loci make the analysis of copy-number variations more comprehensive [title and abstract of Wong et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the binomial distribution modeling of Fan et al. and the thousands of genetic loci of Wong et al. by use of the interrogation of SNPs and determination of fetal DNA contribution to the maternal sample of Rabinowitz et al. wherein the motivation would have been that Rabinowitz et al. gives addition measurements and mathematical tools to facilitate the analysis of aneuploidy in fetal DNA [page 35, line 15 to page 36, line 20 of Rabinowitz et al. and page 66, line 26 to page 67, line 10 of Rabinowitz et al.].
Response to arguments:
Applicant's arguments filed 8 December 2025 have been fully considered but they are not persuasive.
Applicant argues that the prior art does not teach the amended limitations of the claim. The prior art rejection has been modified to address the amended claim limitations, as discussed in the rejection statement above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The following rejection is newly applied:
Double Patenting Rejection #1:
Claims [21, 25, 27, 35, or 36], 24, 28, 31, 32, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 10, 13, 14, and 15, respectively, of U.S. Patent No. 11,031,095 B2 [on IDS].
Both the instant set of claims and the claims of ‘095 use statistical analysis of chromosomal dosages of fetal chromosomes in pregnant maternal samples to determine risks of aneuploidy of the fetus. Since the claims of ‘095 comprise the limitations of the instantly rejected claims, the claims of ‘095 anticipate the instantly rejected claims.
Response to arguments:
Applicant requests the double patenting rejections be held in abeyance.
The following rejection is newly applied:
Double Patenting Rejection #2:
Claim 34 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 11,031,095 B2 [on IDS] in view of Wong et al.
Both the instant claim and the claim of ‘095 use statistical analysis of chromosomal dosages of fetal chromosomes in pregnant maternal samples to determine risks of aneuploidy of the fetus. The claim of ‘095 does not teach sets of at least 20 polymorphic loci on different chromosomes.
The document of Wong et al. studies a comprehensive analysis of common copy-number variations in the human gene [title]. The abstract of Wong et al. teaches 3,654 genetic loci. Figure 1 of Wong et al. teaches a plurality of chromosomes for the genetic loci.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the statistical modeling of aneuploidy of the claims of ‘095 by use of the thousands of genetic loci of Wong et al. wherein the motivation would have been that the increased number of genetic loci make the analysis of copy-number variations more comprehensive [title and abstract of Wong et al.].
Response to arguments:
Applicant requests the double patenting rejections be held in abeyance.
The following rejection is reiterated:
Double Patenting Rejection #3:
Claims 21 and 25 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2, respectively, of U.S. Patent No. 8,700,338 B2 [on IDS]. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are analogously drawn to use statistical analysis of chromosomal dosages of fetal chromosomes in pregnant maternal samples to determine risks of aneuploidy of the fetus. While the claims of ‘338 recite additional limitations relative to the instantly rejected claims, the claims of ‘338 anticipate the instantly rejected claims.
Response to arguments:
Applicant requests the double patenting rejections be held in abeyance.
The following rejection is reiterated:
Double Patenting Rejection #4:
Claim [24, 31-33, 35, or 36] is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, of U.S. Patent No. 8,700,338 B2 [on IDS] in view of Fan et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are analogously drawn to use statistical analysis of chromosomal dosages of fetal chromosomes in pregnant maternal samples to determine risks of aneuploidy of the fetus. The claim of ‘338 does not teach all of the statistical analysis in the instantly rejected claims.
The document of Fan et al. studies direct molecular diagnosis of fetal aneuploidy [title]. The abstract of Fan et al. teaches that Fan et al. focuses on determining an euploidy in chromosomes 1, 13, 18, 21, X and Y. Paragraphs 87-89 of Fan et al. teach a binomial distribution mathematical model by which a target and a reference chromosome are compared. Paragraph 89 of Fan et al. teaches that for the case of disomy, there would be no difference between the target and reference chromosome counts. Paragraph 89 of Fan et al. teaches that for the case of trisomy, the difference between the target chromosome and references chromosome counts would be positive with a ratio of about one-half. Paragraph 89 of Fan et al. teaches that for the case of trisomy, the difference between the target chromosome and references chromosome counts would be negative with a ratio of about one-half. Paragraph 90 of Fan et al. teaches empirical analysis of maternal blood cells to determine aneuploidy.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the statistical modeling of aneuploidy of the claim of ‘338 by use of the statistical analysis of Fan et al. wherein the motivation would have been that Fan et al. gives additional mathematical techniques to analyze risk of fetal aneuploidy that facilitates the fetal aneuploidy statistical analysis of the claim of ‘338 [paragraphs 88-90 of Fan et al.].
Response to arguments:
Applicant requests the double patenting rejections be held in abeyance.
The following rejection is reiterated:
Double Patenting Rejection #5:
Claim [27, 28, or 34] is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, of U.S. Patent No. 8,700,338 B2 [on IDS] in view of Wong et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are analogously drawn to use statistical analysis of chromosomal dosages of fetal chromosomes in pregnant maternal samples to determine risks of aneuploidy of the fetus. The claim of ‘338 does not teach all polymorphic loci and chromosomes of the instantly rejected claims.
The document of Wong et al. studies a comprehensive analysis of common copy-number variations in the human gene [title]. The abstract of Wong et al. teaches 3,654 genetic loci. Figure 1 of Wong et al. teaches a plurality of chromosomes for the genetic loci.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to modify the statistical modeling of aneuploidy of the claim of ‘338 by use of the thousands of genetic loci of Wong et al. wherein the motivation would have been that the increased number of genetic loci make the analysis of copy-number variations more comprehensive [title and abstract of Wong et al.].
Response to arguments:
Applicant requests the double patenting rejections be held in abeyance.
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.
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 27 February 2026