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 .
Claim status
Applicants’ preliminary amendment filed 4/18/2022 has been received and entered. Claims 1-78 have been cancelled, claims 79-98 have been added.
Claims 79-98 are pending.
Priority
This application filed 6/18/2025 is a continuation of 15/979973 filed 5/15/2018, now abandoned, which is a continuation of 14/877877 filed 10/7/2015, now abandoned), which is a continuation of PCT/US2015/011465 filed 1/14/2015, which claims benefit to US provisional application 61/927459 filed 1/14/2014; and
is the parent of 19/242500 filed 6/18/2025, RCE filed 7/26/2026.
Information Disclosure Statement
No information disclosure statement has been submitted.
The listing of references in the specification is not a proper information disclosure statement. See citations throughout and specific listing starting on page 51 labelled References. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
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Claims are 79-98 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-11, 14, 16, 17, 19, 22, 26, 27, 31-45 of copending Application No. 19/242500 (RCE filed). Although the claims at issue are not identical, they are not patentably distinct from each other because as amended ‘500 now provides for computer implemented steps consistent with the instant method of associated candidate disease causing genetic variants using ontologies. The method of ‘500 has known conventional steps of obtaining read data to obtain possible variants and appear to be obvious broad means of obtaining genetic variant data about a sample or subject, and are obvious steps of obtaining data for analysis using a computer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
For completeness of record, pending amended claim 1 of ‘500 is provided:
A method comprising:
(a) obtaining a blood sample from a subject;
(b) extracting deoxyribonucleic acid (DNA) molecules from the blood sample;
(c) assaying the DNA molecules or derivatives thereof using a genomic sequencing assay to generate a plurality of sequence reads;
(d) using a computer processor to identify a plurality of genomic variants present in the plurality of sequence reads, wherein the identifying comprises aligning the plurality of sequence reads to a human reference genome;
(e) determining a plurality of variant prioritization scores of the plurality of genomic variants by scoring impacts on gene function of a gene having a genomic variant of the plurality of genomic variants;
(f) receiving a set of disease phenotypes of the subject;
(g) using the computer processor to retrieve, from a Human Phenotype Ontology (HPO) database, a first set of gene ontologies that comprise Human Phenotype Ontology (HPO} terms and a second set of gene ontologies that comprise non-HPO terms;
(h) processing the first set of gene ontologies and the second set of gene ontologies using a cross-ontology linking algorithm, to determine linkages of the set of disease phenotypes to genes as represented in the first set of gene ontologies and the second set of gene ontologies,wherein the cross-ontology linking algorithm comprises
(1) determining a set of genes having common gene annotations to each of two or more different ontologies between the first set of gene ontologies and the second set of gene ontologies, and
(2) constructing ontological relationships between the two or more different ontologies; using the computer processor to automatically prioritize the plurality of genomic variants with respect to relevance to the disease, wherein the prioritizing comprises combining via a computer algorithm the plurality of variant prioritization scores with a likelihood of association of the gene with the disease, as inferred from [[a]] the linkages of the set of disease phenotypes of the subject to the genes as represented in the set of gene ontologies using the computer processor to automatically identify a list of genes harboring at least one of the plurality of genomic variants; and using the computer processor to report, via a user interface of an electronic display, the list of genes prioritized with respect to relevance to the disease.
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 79-98 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because the claimed invention is not directed to patent eligible subject matter.
Claim analysis
The claims are generally directed to a method of producing a computer-generated identification and report of genetic candidate or variant genes associated with disease phenotypes. Specifically, the claim requires three steps of: providing data which prioritized variant information, a description of the phenotype and gene ontologies; prioritizing based on the likelihood and linkage of the phenotype with the identified/exhibited genotype; and reporting a list of genes with identified variants. The steps of the claims appear to be abstract instructional steps of obtaining existing data and analyzing it to provide possible correlations, generically based on an ontology database and other information existing and first received. The claims are broad and generic in what is require foe the ‘prioritizing’ but in light of the specification, this can be accomplished in the analysis where a sequence is identified through alignment and processed by assigning a value to genetic candidate genes or genetic variants based on the association with the disease, algorithmically propagating the value information across or between multiple ontologies, assigning and propagating to assess the priority ranking, which must provide a priority ranking of said first set of phenotype-causing genes or genetic variants. Dependent claims provide a description of possible sequences that may be associated with a condition, and specific programs/protocols for evaluating and/or ranking the association using programs such as VAAST, pVAAST, as well as the source of the information first provided (noting that any organism can be used and compared to others if or when homologues or particular mutant phenotypes have been established). The specification does not provide any specific ontologies or specific rules in prioritizing and appears to rely on the ability of known computer programs to analyze and rank the data, nor does it provide for any known associations between the various gene elements listed/recited. While each step is considered to be implemented on a computer processor that is programmed, accessing a database, assigning values to prioritize sequence information is only generally set forth in the claims, and does not appear to require any specific computer or processor, or specifically rooted to the technology given the guidance of the specification. While there is recitation of ontologies of information required of the claim, it appears to be a static set of information, and to the extent that prioritizing information could be implemented with the use of a database comprising or associated with the ontology, providing values and propagated values appears to be a step wise process and does not require creating a dynamic database that improves the functionality of the computer or processor.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a method.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of accessing sequence data for correlations between sequences and phenotypes based on ‘prioritization’, which is in part based on existing knowledge in ontologies. The claims nor the specification provide for new associations or rules in defining the associations, and appears to rely on the art to provide the data and known associations before generically prioritizing the information by ‘combining’ likelihoods and linkages when known. The judicial exception is a set of instructions for correlating sequence data and phenotype data and appears to fall into the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion). Here, there are no specific rules set forth in the claims nor required of the specification by definition, and prioritization broadly can be evaluation of known information to prioritize it by or to any standard. Using ontologies appears to provide a basis of comparing sequence information to that researched and defined by others to aid in making the correlation(s) between variants that are observed. The breadth of “providing”, “prioritizing”, and “automatically identifying and reporting” encompasses non-transformative visual assessment of sequence and phenotype data for any organism or an individual for given phenotype(s), coupled with prior knowledge of the correlation of said phenotype(s) with the presence of particular genotype(s); for example, seed color, flower color, height, silique size, etc., tolerance to stress for plants or gene variants associated with cancer like BRCA1/2. This breadth does not impose a meaningful limit on the claim scope beyond observing and correlating sequence and phenotype data, such that all others are not precluded from using the natural principle of associating genetic variants with phenotypes. Merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f) is not considered patent eligible since the claims encompass generic instructions to be performed. As the steps of steps required of the claims are very generally recited, the combination of steps is together reasonably interpreted as mere data gathering and analysis. To the extent that the programs recited in the claims can provide prioritization or correlations, computing, constructing datasets and using statistical models was well understood, conventional, and routinely performed in the art at the time the application was filed. For example, dependent claims require the use of VAAST which is named in view of its function for Variant Annotation, Analysis, and Search Tool and is a probabilistic search tool for identifying variants in genes and their disease-causing variants, and appears to fall into the category of Mathematical Concepts to the extent that probabilistic methods are mathematical relationships or mathematical formulas or equations that the program performs in the analysis of the data. The claims appear to fall into the category of Mathematical Concepts, as it applies the use of statistics and mathematical relationships in analyzing probabilities, and also into the category of mental processes, as concepts performed in the human mind (including an observation, evaluation, judgment, opinion) because there is no apparent complexity to or amount of data that is collected and analyzed as presently claimed.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the report is applied. This judicial exception requires steps recited at high level of generality and are not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, the independent claim recites ‘computer implemented’ in the preamble and can be interpreted to be an additional elements, but is found to be a generic computer used for the data analysis. As such, the claims do not provide for any additional element to consider under step 2B which appear as a whole significantly more or provide an improvement to the technical field. It is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process." As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence data. While the instruction can be stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences with possibly associated phenotypes. The judicial exception of the method as claimed can be performed by hand. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis. In the instant case, the claims comprise steps of comparing and correlating sequence/phenotypes and is considered the judicial exception. It is noted that while the claims set forth or imply information about the sequences being analyzed, this is only description of the data being analyzed and context and user defined. As such, the instant claims set forth an inventive concept that are drawn only to an abstract process that only analyzes data and, therefore, are not directed to patent eligible subject matter. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception. Without additional limitations, a process that employs mathematical algorithms (correlating sequences) to manipulate existing information (using existing ontologies) to generate additional information is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract idea (designing probes to a target sequence) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Conclusion
No claim is allowed.
The closest art of record appears to be Blumenfeld et al. (US 6,528,200), Reese et al. (US Patent 8417459 issued 4/9/2013), Yandell et al. (PLoS Comp Biol, Nov 2008), Linghu et al., Frank et al. and Yandell et al. (Genome Res, June 23, 2011) (all of record). Each provide evidence for a general method of correlating information between data bases was known and performed as evidenced by Blumenfeld et al., Reese et al. and Yandell et al. who provide detailed guidance that at the time of filing there were multiple programs that could be used to correlate variant sequences with phenotypes. Linghu et al 2009 and Franke et al 2006 provide evidence for the necessary guidance and success of both using Al to establish correlations with disease causing genes, and the breadth of the claims broadly indicating relationships of nodes are linked/established by the edges it would be obvious to apply know Al methods in a computer environment relative to a patient’s health record and known ontologies of information to explore possible phenotype associations/outcomes associated with identified genes or gene variants. However, none of these teach the steps of prioritizing based on values (of seed nodes) as presently recited in the claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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/Joseph Woitach/ Primary Examiner, Art Unit 1687
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