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 .
Information Disclosure Statement
The IDS filed 5/25/2023 has been considered by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 62/760,743 filed 11/13/2018 has is acknowledged.
Status of Claims
Amendments to the claims filed 2/03/2026 are acknowledged. Claims 79-90 are new.
Claims 59-62, 64-72 and 79-90 are under consideration.
Claims 1-58, 63 and 73-78 are cancelled.
Claim Objections
The objection to claim 59 is withdrawn in view of Applicant’s amendments filed 5/27/2025.
Claim Rejections - 35 USC § 101
The following rejection is maintained from the Office Action of 11/03/2025 and modified in view of Amendments filed 2/03/2026.
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 59-62, 64-72 and 79-90 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 59-62, 64-72 and 79-90 are drawn to a method, so a process.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. Claim 59 recites sequencing genomic DNA comprising a set of germline heterozygous SNP positions from cells of a tumor sample comprising a somatic allele variant from a subject, wherein each heterozygous SNP has alleles B and A. Claim 79 recites sequencing genomic DNA comprising a set of germline heterozygous SNP positions.
This limitation reads on a process that can be performed by the human mind or mathematics through data analysis of genomic sequencing of DNA. The limitation is drawn to “sequencing” genomic DNA where a set of germline heterozygous SNP position having alleles A and B have been determined. The limitation “sequencing” is therefore analogous to “determining” by the process of sequencing. The instant specification (par. 0044) states that SNP positions can be identified using sequencing data or sequencing reads. The step therefore reads on comparing fragments of sequences to a reference genome. The instant specification (par. 0005, 0006) describes sequencing as needing a reference sequence and a comparator sample for baseline subtraction. The instant specification par. (0016) and Claims 72 and 90 recite that “sequencing comprising fragmentation sequencing that uses a human reference genome.” The step of sequencing reads on nucleic acid data mapping and comparison which is an abstract idea. Claim 79 requires sequencing 5000 germline heterozygous SNP positions which sets forth the quantity of data but does not alter the nature of comparative data analysis performed.
2. Claim 59 recites two germline allele pairings for a SNP position and a variant in a position near the SNP position are sequenced, wherein the two germline allele pairings are (i) allele B and a first variant allele, and (ii) allele A and a second variant allele which maybe the same or different than the first variant allele.
Under Broadest Reasonable Interpretation (BRI) the step reads on determining the sequence of nucleotides corresponding to two germline allele pairings for a SNP position and a variant in a position near the SNP position. The step includes the determination of allele pairings and the position of a variant. The physical aspect of sequencing performed by a sequencer merely reads one base at a time with no means for identifying the structure of the sequence. Therefore sequencing so as to characterize germline allele pairings and a position of a variant is a step of identifying by data analysis and therefore an abstract idea. The process is therefore drawn to organizing and analyzing nucleic acids which can be achieved by the human mind. This limitation reads on a process that can be performed by the human mind through mental analysis of data determined from nucleic acid sequences, and is therefore an abstract idea.
3. Claim 59 recites a third allele pairing which is allele B and a third variant allele that is different from the first variant allele is sequenced. Claim 79 recites that the presence of the third allele pairing is indicative of a somatic allele variant.
This limitation recites a mental process of identifying a third allele pairing which is allele B and a third variant allele that is different from the first variant allele. “Sequencing” involves the mapping of DNA fragments of sample sequences to a reference genome to assemble and identify the sample sequences. The recited wherein clause is essentially intended to set forth a step of determining a third allele pairing of allele B and a third variant step reads on data analysis that can be performed by the human mind and is therefore an abstract idea. Claim 79 further recites that a somatic allele variant is indicated by the presence of the third allele pairing which reads on a the abstract idea of a mental process of correlating the identification of a third allele pairing to the presence of a somatic allele variant.
Claims 60-62, 68-72, 80-82 and 87-90 are drawn to describing the data, quantity of sequence data and analysis which further characterize the abstract idea steps which are judicial exceptions.
Step 2A Prong One: Identification of a Natural Correlation
Claim 79 recites wherein a sequence of a third allele pairing which is allele B and a third variant allele that is different from the first variant allele indicates a somatic allele variant. This is an identification of a natural correlation.
Claim 79 is claiming an identification of a somatic allele variant as being correlated with the existence of an allele pairing which is allele B and a third variant allele that is different from a first variant allele on allele B and a second variant allele on allele A. This is recognition of a natural phenomenon and therefore a judicial exception.
Claims 80-82 and 87-90 are further abstract idea steps which are also judicial exceptions.
Step 2A Prong Two: Consideration of Practical Application
The claims are drawn to “sequencing” (i.e. determining by a process involving sequencing) three allele pairings wherein the third allele pairing is allele B and a third variant allele, thereby identifying a somatic allele variant. The steps is drawn to an abstract idea and recognition of a natural phenomenon. The claims are drawn to nucleic acid sequence analysis by steps that can be performed by the human mind or with math, e.g. sequence alignment. The claims do not recite an additional element that integrates the judicial exception into a practical application.
The judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. sequencing genomic DNA from cells of a tumor sample from the subject, as in claims 59 and 79.
2. wherein the sample is cancer tissue, tumor cells or tumor sample, as in claims 59, 64, 83 and 79.
3. the tumor sample contains non-tumor cells, as in claims 65-66 and 84-85.
4. massively parallel sequencing, hybridization or amplification, as in claims 67 and 86.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because sequencing DNA including heterozygous alleles is well known, routine and conventional. It is also well known to take DNA from mixed tumor sample with non-tumor cells and sequencing that DNA for analysis in cancer treatment. Providing checkpoint inhibitor drug as treatment for cancer is also routine, conventional and well understood. Melendez et al. (Transl. Lung Cancer, vol. 7 (2018) pgs. 551-667) teach sequencing a tumor sample from biopsies (page 662, col. 2, par. 3) which evidences that sequencing tumor cells that contain non-tumor cells is also routine, conventional and well understood.
Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive.
Applicants argue (Remarks, page 6 par. 5-6 to page 7, par. 1-2) limitations that have been deleted and that the rejection over these limitations are now moot.
In response, it is noted that the 35 USC 101 rejection has been modified to address the currently amended claims, as set forth above.
Applicants argue (Remarks, page 7, par. 3-4) that interpreting that the step of “two germline allele pairings for a SNP position … are sequenced,” reads on determining the sequence of nucleotides corresponding to two germline allele pairings is an improper importation of limitations into the claims.
In response, examination using Broadest Reasonable Interpretation (BRI) necessitates interpreting the full breadth of a limitation which may include steps not necessarily explicitly recited. It is well known that “sequencing” is a multistep process of creating sequence fragments and then comparing the fragments in the form of data to a reference genome. It is understood that by “sequencing” two germline allele pairings for a SNP position and a variant position near the SNP position, one of ordinary skill would not be performing said sequencing with prior knowledge of a two germline allele pairings with a SNP position and a variant position near the SNP position. The limitation of “sequencing” therefore reads on and encompasses the process of mapping sequences to a reference sequence to thereby determine the germline allele pairing. This interpretation is made in light of the disclosure (par. 0044) which describes sequencing as a process where SNP positions can be identified using sequencing data or sequencing reads. Therefore sequencing in light of the specification is a process of identifying by sequence data analysis. One of ordinary skill would consider sequencing as a process of comparing fragments of sequences to a reference genome. This is consistent with the instant specification (par. 0005, 0006) which describes sequencing as needing a reference sequence and a comparator sample for baseline subtraction. The instant specification par. (0016) and Claims 72 and 90 recite that “sequencing comprising fragmentation sequencing that uses a human reference genome.”
Applicants argue (Remarks, page 7, par. 5) that the USPTO memorandum on subject matter eligibility distinguishes claims that recite a judicial exception from those that merely “involve” one. Applicants cite Example 39 where reciting “training the neural network” do not recite an abstract idea even though they involve underlying mathematical concepts.
In response, sequencing is a well know process of determining a sequence of nucleic acids which broadly reads on organizing nucleic acid information by comparing sequences to a reference sequence. The instant claims are not specific with respect to which process of “sequencing” is intended. However, one of ordinary skill would understand the sequencing genomic DNA involves creating fragment reads from a sample, translating those fragments into data fragments and then mapping those data fragments or reads to a reference. The step of creating fragment reads from a sample, translating those fragments into data fragments is well known and an extra solution activity of data collection. The process of mapping those data fragments or reads to a reference could involve algorithms or alignment processes which are abstract ideas. Therefore, even though the process of “sequencing” could involve steps that include more than data analysis, these steps are routine extra solution activities for obtaining sequence read data that is then analyzed to determine the sample sequence. Furthermore, In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989) the court stated, “It is of no moment that the algorithm is not expressed in terms of a mathematical formula. Words used in a claim operating on data to solve a problem can serve the same purpose as a formula.”
Furthermore, the instant specification and claims (72 and 90) make clear that “sequencing comprises fragmentation sequencing that uses a human reference genome,” which reads on a process of digitally mapping obtained nucleic acid sequences to a standardized reference genome to reconstruct the original genetic sequence. This is drawn to the abstract idea of organizing information and steps that can be performed by the human mind, irrespective of the amount of data. With respect to large quantities of data, or 5000 germline SNP positions as in claim 79, analyzing a lot of data does not augment the steps being performed to analyze the data, which are abstract ideas. The claims are not specific with respect to algorithms used to “sequence” the genomic DNA. Therefore the claims read on simple mapping and alignment algorithms. Computations on a lot of data performed mentally, or with paper and pencil, would take considerable time and effort, but that is, of course, the singular purpose of computers and computer networks, to perform large numbers of calculations, via algorithms, rapidly, and without error (assuming no error in user input). Although a general purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same, and constitutes an abstract idea. See Bancorp Serves., L.L. C. v. Sun Life Assur. Co. of Canada (U.S.), 687 F.3d 1266,1278 (Fed. Cir. 2012) (holding that “the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter”); see also See SiRF Tech., Inc. v. Int’l Trade Comm ’n, 601 F.3d 1319,1333 (Fed. Cir. 2010) (holding that: In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations).
Claim Rejections - 35 USC § 103
Claim Interpretation
Claim 59 has been amended to recite “wherein the method does not comprise germline subtraction.” In order to interpret the metes and bounds of a negative limitation, the boundaries of the limitation must be clear; it must be clear what process steps the negative limitation excludes. Here one of ordinary skill should exclude “germline subtraction” from being performed within the scope of the claims.
Germline subtraction is interpreted in view of the common definition of the germline subtraction process:
Comparing genetic sequences from a patient’s tumor and normal tissue
Identifying any variants found in both the tumor and normal tissue, as the germline variant.
Subtracting the germline variant from the tumor sequence list.
Resulting in a list of only somatic variants which are the mutations that occurred specifically in the tumor.
The rejection of claims 59-72 under 35 U.S.C. 103(a) as being unpatentable over Chalmers et al. (US 2018/0363066) in view of Sanborn (US 2015/0261912) is withdrawn in view of Applicant’s reciting “wherein the method does not comprise germline subtraction,” wherein germline subtraction is interpreted as its common definition set forth above.
Note Prior Art
Usuyama, Naoto, et al. "HapMuC: somatic mutation calling using heterozygous germ line variants near candidate mutations." BIOINFORMATICS 30.23 (2014): 3302-3309.
E-mail communication 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
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635
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