DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
As detailed on the Filing Receipt filed 1/6/2022, the instant application claims priority to as early as 12/6/2018. At this point in prosecution, all claims are accorded the earliest claimed priority date.
Information Disclosure Statement
The Information Disclosure Statements filed on 1/7/2022 and 10/11/2022 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. Signed copies of the IDS are included with this Office Action.
Claim Status
Claims 1-20 are pending, and under examination.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language, in light of the specification, as it would be understood by one of ordinary skill in the art (MPEP 2111-2111.01). This section documents the Examiner’s interpretation of certain claim elements.
Claims 1-12 and 20 are directed to systems comprising recited components (e.g., a server) “to” practice recited functions (e.g., to communicate with frontend(s) over a network).
The specification states: “the components of [the] system (including any of the frontend, the server, the compute engine, the workflow database, and the reference database(s)) may each be embodied in hardware, software, firmware, or any combination thereof” (para. 0065). Accordingly, each of the recited components is interpreted as encompassing hardware and/or software embodiments capable of practicing the recited functions.
Thus, consistent with the court rulings of In re Translogic Technology, Inc., 504 F.3d 1249, 1258 (Fed. Cir. 2007) and Nazomi Communications, Inc. v. Nokia Corp., 739 F.3d 1339, 1345 (Fed. Cir. 2014), the claimed system having functional limitations is construed as comprising a combination of hardware and/or software components capable of practicing the recited functions.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 USC § 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.
Claims 1-20 are rejected under 35 USC § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor, or a joint inventor, regards as the invention.
With respect to claims 1, 20 and dependents thereof, there is uncertainty regarding the metes and bounds of the claimed systems. Each system comprises a server that is capable of “communicat[ing] with a [number of] remote frontend[s] over a network to receive, from the frontend[s], a [number of] request[s] to screen” (claim 1, lines 3-4; claim 20, lines 3-4) and “report[ing]… to the [respective] frontend… [a result of] screening” (claim 1, lines 19-21; claim 20, line 5). Although referenced therein, the frontends (unlike the server) are not listed as elements of the claimed systems per se.
The specification does mention a frontend among listed “components of [the] system” (para. 0065). However, the courts have warned against importing limitations from the written description to interpret claim language that is broader than the embodiment described (Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875 (Fed. Cir. 2004)). It is unclear whether the referenced frontends are an integral part of, or external to, the systems as claimed. Thus, the scope of each claim is indefinite.
Additionally, a claim to a product (i.e., a device, apparatus, manufacture, or composition of matter) may contain reference to the process in which it is intended to be used, or capabilities of the product, so long as it is clear that the claim is directed to the product and not the process of use. Claims reciting limitations directed to both a product and steps of using the product (i.e., user activity) are indefinite (MPEP 2173.05(p) §§ I-II).
The system claims include the following limitations that appear directed to user activity rather than system capabilities:
the provision of a graphical user interface by each frontend is “to allow a user to input the one or more nucleotide sequences to be screened for hazardous content”, wherein the assigned threat level is displayed “to the user” and pertains to the sequence(s) “input by the user” (claims 9 and 20) wherein:
the provided interface allows a user to input the sequences “by uploading a single file containing the plurality of nucleotide sequences” (claims 10 and 20).
For the above reasons, the claims are indefinite.
Claim Rejections - 35 USC § 101
35 USC § 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 1-20 are rejected under 35 USC § 101 because the claimed invention is directed to an abstract idea without significantly more (i.e., non-statutory subject matter).
"Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I).
Abstract ideas include mathematical concepts (including formulas, equations and calculations), and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea.
Step 1: The Four Categories of Statutory Subject Matter (MPEP 2106.03)
The claims are directed to systems (claims 1-12 and 20) and methods (claims 13-19), which fall under categories of statutory subject matter.
Step 2A, Prong One: Whether the Claims Set Forth or Describe a Judicial Exception (MPEP 2106.04 § II.A.1) ‘Mental processes’ are processes that can be performed in the human mind at least with use of a physical aid, e.g., a slide rule or pen and paper (MPEP 2106.04(a)(2) § III). The claims recite elements that encompass processes that are practicably performable in the human mind, at least under their broadest reasonable interpretation, including:
“compar[ing]… each nucleotide sequence of the [plurality of] nucleotide sequences to each of a plurality of reference sequences” (claims 1, 13 and 20), i.e., comparing sequence strings;
“detect[ing]… whether hazardous content is present in each nucleotide sequence of the plurality of nucleotide sequences based upon the comparison… including performing a sliding window analysis on a composite sequence formed from portions of nucleotide sequences in the plurality of nucleotide sequences” (claims 1, 13 and 20), i.e., identifying presence of particular information in portions of a derived sequence string;
“assign[ing]… one of a plurality of threat levels to each nucleotide sequence based upon the detection” (claims 1, 13 and 20), i.e., annotating a sequence string, wherein:
“the plurality of threat levels includes at least a first level representing a threat, a second level representing a potential threat, a third level representing an unlikely threat, and a fourth level representing a non-threat” (claim 7), i.e., annotations have particular representative significance;
“select[ing]a reference sequence that provided a closest match to that nucleotide sequence during the comparison… wherein the selected reference sequence includes hazardous content ” (claims 2 and 14);
“detect[ing] that hazardous content is present in that nucleotide sequence in response to determining that (i) a matching length between the selected reference sequence and that nucleotide sequence satisfies a threshold length and (ii) a matching percentage between the selected reference sequence and that nucleotide sequence satisfies a threshold percentage” (claims 2 and 14);
“for each reference sequence including hazardous content where (i) a matching length between the selected reference sequence and that nucleotide sequence does not satisfy a threshold length but (ii) a matching percentage between the selected reference sequence and that nucleotide sequence does satisfy a threshold percentage, extending the matching length up to the threshold length” (claims 3 and 15);
“detect[ing] that hazardous content is present in that nucleotide sequence in response to determining that the matching percentage between the extended reference sequence and that nucleotide sequence still satisfies the threshold percentage” (claims 3 and 15);
“for each reference sequence including hazardous content where (i) a matching length between the selected reference sequence and that nucleotide sequence satisfies a threshold length but (ii) a matching percentage between the selected reference sequence and that nucleotide sequence does not satisfy a threshold percentage, apply[ing] a sliding window to analyze a matching percentage between that nucleotide sequence and portions of the reference sequence having the threshold length” (claims 4 and 16);
“detect[ing] that hazardous content is present in that nucleotide sequence in response to determining that the matching percentage between that nucleotide sequence and any portion of the reference sequence having the threshold length satisfies the threshold percentage” (claims 4 and 6);
“detect[ing] that hazardous content is present in the composite nucleotide sequence in response to determining that a matching percentage between any portion of the composite nucleotide sequence having a threshold length and the one of the plurality of reference sequences satisfies a threshold percentage” (claims 5 and 17); and
“determining that a threat level assigned… does not represent a threat” (claim 13).
The recited steps of evaluating information, which are practicably performable in the human mind, constitute mental processes.
‘Mathematical concepts’ are relationships between variables and numbers, numerical formulas or equations, or acts of calculation, which need not be expressed in mathematical symbols (MPEP 2106.04(a)(2) § I). The claims recite the following element which encompasses a mathematical concept, at least under its broadest reasonable interpretation:
“using an alignment algorithm to compare each nucleotide sequence to each of the plurality of reference sequences “ (claims 8 and 19), i.e., evaluating an algorithm.
Algorithms are series of mathematical equations, and evaluating an algorithm is an act of calculation. Evaluation of an alignment algorithm thus constitutes a mathematical concept.
Mental processes and mathematical concepts constitute enumerated categories of abstract ideas (MPEP 2106.04(a)(2) §§ I and III). Hence, the claims recite elements that, individually and in combination, constitute an abstract idea. The claims must therefore be examined further to determine whether they integrate this abstract idea into a practical application (MPEP 2106.04(d)).
Step 2A, Prong Two: Whether the Claims Contain Additional Elements that Integrate the Judicial Exception(s) into a Practical Application (MPEP 2106.04 § II.A.2)
The claims recite the following additional elements that constitute, and/or require practice of claimed functions using, computer hardware and/or software:
“a server” (claims 1 and 20) capable of:
“communicat[ing] with a number of remote frontends over a network to receive, from the frontends, a number of requests to screen… includ[ing]… at least one thousand nucleotide sequences” (claims 1 and 20),
“report[ing] the threat level assigned… to the respective front end that requested screening” (claim 1),
“report[ing] the corresponding metadata… to the respective front end that requested screening” (claim 6),
“writ[ing] each of the plurality of nucleotide sequences received from the frontends to the queue” (claim 12), and
“report[ing], to the frontend, a result of screening… wherein the result reported to the frontend by the server comprises the threat level assigned to… each nucleotide sequence in the plurality” (claim 20);
“[with] a compute engine” (claims 1, 13 and 18) capable of:
“retriev[ing]… the corresponding metadata from the reference database” (claims 6 and 18), and
“read[ing] one nucleotide sequence at a time from the queue in order to compare that nucleotide sequence to each of the plurality of reference sequences” (claim 12);
the reference sequences are “stored in a reference database” (claims 1 and 13), i.e., a digital data structure, wherein:
“the reference database further comprises metadata associated with each reference sequence that describes one or more characteristics of the hazardous content included in that reference sequence” (claims 6 and 18);
“[each] frontend is to provide a graphical user interface… and to display… the [threat level assigned/result of screening]” (claims 9 and 20), wherein:
“[the] graphical user interface is [configured] to allow the user to input [multiple/the plurality of] nucleotide sequences to be screened by uploading a single file containing the… nucleotide sequences” (claims 10 and 20), and
“the graphical user interface is configured to display to the user a progress of the screening of the one or more nucleotide sequences for hazardous content, based upon asynchronous updates received from the server, until the threat level is received from the server” (claim 11);
“a workflow database including a queue of nucleotide sequences to be screened” (claim 12), i.e., a digital data structure; and
“a processor” (claim 20).
The claims do not describe any specific computational steps by which computer hardware and/or software performs or carries out functions drawn to the judicial exceptions, nor do they provide any details of how specific computer structures are used to implement these functions. The claims state nothing more than that systems comprising generic computer hardware and/or software (see ‘Claim Interpretation’ section) perform functions drawn to the abstract idea, and are therefore mere instructions to apply the abstract idea using a computer. As such, the claims do not integrate the abstract idea into a practical application. See MPEP 2106.04(d) § I and 2106.05(f).
The claims further recite the following additional element:
“synthesizing… the nucleotide sequence” (claim 13).
This element indicates a technological environment (i.e., nucleic acid synthesis) in which to apply the result of data analysis steps that constitute the abstract idea. The claims do not recite any particular methods of accomplishing the recited function of synthesis itself, and the addition of the synthesis step does not place meaningful limits on the execution of the prior steps. The synthesis step amounts to post-solutional activity that merely confines the abstract idea to said technological environment. Additional elements drawn to insignificant extra-solution activity, and/or mere instructions to apply the abstract idea in a particular technological environment, are insufficient to integrate the abstract idea into a practical application. See MPEP 2106.05(f-g).
No further additional elements are recited.
When the claims are considered as a whole: they do not improve the functioning of a computer, other technology, or technical field (MPEP 2106.04(d)(1) and 2106.05(a)); they do not apply the abstract idea to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)); they do not implement the abstract idea with, or in conjunction with, a particular machine (MPEP 2106.05(b)); they do not effect a transformation or reduction of a particular article to a different state or thing (MPEP 2106.05(c)); and they do not apply or use the abstract idea in some other meaningful way beyond linking the use of the abstract idea to a particular technological environment (i.e., nucleic acid synthesis; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not integrate the abstract idea into a practical application. See MPEP 2106.04(d) § I.
Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to the abstract idea. Claims that are directed to an abstract idea must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Additional elements besides the abstract idea may constitute inventive concepts that are sufficient to render the claims significantly more (MPEP 2106.05).
Step 2B: Whether the Claims Contain Additional Elements that Amount to an Inventive Concept (MPEP 2106.05)
As noted above, several recited additional elements amount to insignificant extra-solution activity. Mere addition of insignificant extra-solution activity does not amount to an inventive concept that would render the claims significantly more than an abstract idea, particularly when the activities are well-understood or conventional (MPEP 2106.05(g)). The conventionality of recited additional elements that amount to insignificant extra-solution activity must be further considered.
Recited additional elements amounting to insignificant extra-solution activity include the following process, which is indicated as well-understood, routine and conventional by the instant specification (see MPEP 2106.07(a) § III):
synthesizing the nucleotide sequence (pg. 1, para. 3: “Gene synthesis approaches are most often based on a combination of organic chemistry and molecular biology techniques. Gene synthesis is an important tool in many fields”).
Additionally, recited additional elements encompass the following computer-implemented functions, which the courts have held as coextensive with a general-purpose computer and/or well-understood, routine and conventional:
Receiving, storing, and processing data (EON Corp. IP Holdings LLC v. AT&T Mobility LLC, 785 F.3d 616, 622 (Fed. Cir. 2015)), including:
Receiving data over a network (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355 (Fed. Cir. 2014); Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1317 (Fed. Cir. 2016));
Transmitting data over a network (OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015));
Updating a database (Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 715 (Fed. Cir. 2014));
Storing and retrieving information in memory (OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015); Versata Dev. Group, Inc. v. SAP America, Inc., 793 F.3d 1306, 1334 (Fed. Cir. 2015));
Selecting information for display (Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1354-55 (Fed. Cir. 2016));
Displaying the result of data analysis (TLI Communications LLC v. AV Auto. LLC, 823 F.3d 607, 612-13 (Fed. Cir. 2016));
Displaying electronic data (Interval Licensing LLC v. AOL, Inc., 896 F.3d 1335, 1344-45 (Fed. Cir. 2018));
Providing user functionality through a web-based interface (Internet Patent Corp. v. Active Network, Inc., 790 F.3d 1343, 1348 (Fed. Cir. 2015));
Arranging information on a graphical user interface in a manner that assists human activity (Trading Technologies v. IBG LLC, 921 F.3d 1084, 1093-94 (Fed. Cir. 2019)).
Hence, the encompassed activity is considered well-understood, routine and conventional. Well-understood, routine and conventional activity is insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (MPEP 2106.05(d)).
Mere instructions to implement an abstract idea using a computer or in a particular technological environment are, when considered individually, similarly insufficient to constitute an inventive concept that would render the claims significantly more than said abstract idea (MPEP 2106.05(e-h)).
When the claims are considered as a whole: they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a
particular technology; they do not improve a technology by allowing the technology to
perform a function that it previously was not capable of performing; and they do not
provide any limitations beyond generally linking the use of the abstract idea to a particular technological environment (i.e., nucleic acid synthesis). See MPEP 2106.05(h).
Therefore, the claims do not provide an inventive concept and/or significantly more than the abstract idea itself. See MPEP 2106.05.
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11 and 13-20 are rejected under 35 USC § 103 as being unpatentable over Jones (Sequence Screening, In: Working Papers for Synthetic Genomics: Risks and Benefits for Science and Society, pp. 1-16; published 2007), in view of Altschul et al (Nucleic Acids Research 25(17): 3389-3402; published 1997) and Henikoff et al (Protein Science 6(3): 698-705; published March 1997).
Claim 1 recites a system for assessing threat levels associated with synthesizing nucleotide sequences, the system comprising: a server; and a compute engine.
The claim additionally requires that the server possess the capability to: communicate with a number of remote frontends over a network to receive, from the frontends, a number of requests to screen one or more nucleotide sequences for hazardous content, wherein the requests collectively include at least one thousand nucleotide sequences; and report the threat level assigned to synthesizing each nucleotide sequence to the respective front end that requested screening of that nucleotide sequence.
The claim additionally requires that the compute engine possess the capability to: compare each nucleotide sequence to each of a plurality of reference sequences stored in a reference database; detect whether hazardous content is present in each nucleotide sequence based upon the comparison of that nucleotide sequence to each reference sequence, including performing a sliding window analysis on a composite sequence formed from portions of nucleotide sequences in the plurality of nucleotide sequences; and assign one of a plurality of threat levels to each nucleotide sequence based upon the detection of whether hazardous content is present in that nucleotide sequence.
With respect to claim 1, Jones discloses BlackWatch, a software package for sequence screening (pg. 2, para. 6). Jones discusses implementation of BlackWatch on a web server and Linux systems (pg. 12, paras. 1-2), i.e., compute engines.
Jones describes functions of: receiving a request for DNA synthesis including a customer-input sequence (pg. 2, para. 5); comparing input sequences against a database of sequences from known pathogens (pg. 5, para. 3); tagging any request that produces a significant match as being of interest and alerting a site administrator (pg. 5, para. 3), i.e., detecting whether hazardous content is present in each nucleotide sequence based upon the comparison.
Jones discusses commercial oligo synthesis services with high throughput and fast turnaround, exemplifying one company’s daily throughput of 15,000 – 25,000 oligos (pg. 3, paras. 3-4), and discusses application of BlackWatch to screen production databases at synthesis companies (pg. 7, para. 2). In this way, Jones suggests regular receipt of screening requests collectively including at least one thousand nucleotide sequences.
Jones discusses weighted scoring of sequence matches according to biological significance of the match, e.g., interpreting a very strong match to a sequence involved in anthrax toxin as a clear positive match while weighting down a match to a less important region of the B. anthracis genome (pg. 13, para. 3). In this way, Jones suggests assignment of one of a plurality of threat levels based on the comparison.
Jones discloses implementation of sequence comparison via BLAST (pg. 4, para. 4), but does not expressly describe performing sliding window analysis on a composite sequence as claimed.
Altschul discusses BLAST (pg. 3389, Abstract), and describes local alignment functionality of BLAST wherein the program aligns equal-length segments (words) within database and query sequences, scanning the database sequence sequentially and extending alignment windows with two non-overlapping matches (hits) until the running alignment’s score drops below a threshold, to determine high-scoring segment pairs (pg. 3390, l. column – pg. 3391, l. column). Comparing sequences by alignment of subsequence segments within an initially-fixed, extended length is sliding window analysis.
Altschul notes that database searches using position-specific score matrices (PSSMs) often are much better able to detect weak relationships than database searches that use a simple sequence as query, and mentions related work pertaining to construction of a single artificial query sequence that approximates a PSSM (pg. 3394, l. column). However, Altschul does not further discuss construction or evaluation of a composite sequence as claimed.
Henikoff discusses a strategy for utilizing multiple alignment information to detect distant relationships in searches of sequence databases, comprising selection of a single representative query sequence based on multiple alignment of query sequences, replacement of conserved regions of the representative sequence with consensus residues derived from the multiple alignment, and evaluation of the consensus-embedded sequence using single sequence query searching programs such as BLAST (pg. 698, Abstract; pg. 699, r. column; pg. 703, r. column). In this way Henikoff discloses production and evaluation, via BLAST, of a composite sequence formed from portions of nucleotide sequences in a plurality of nucleotide sequences.
Henikoff discloses availability of software programs that implement multiple alignment of a set of unaligned sequences, computation and embedding of consensus residues to produce a consensus-embedded sequence (pg. 705, l. column). Henikoff additionally teaches that construction and evaluation of a consensus-embedded sequence is functionally advantageous to evaluation of a PSSM, albeit less statistically accurate in some circumstances, because a consensus-embedded sequence can be directly utilized as a query for standard searching programs (e.g., BLAST) while evaluation of a PSSM as a query requires modification of such programs (pg. 701, r. column).
With respect to claim 2, Jones discusses assessment of input sequences as short oligos or longer sequences on the basis of length (i.e., length thresholds), and selection of positive sequence matches based on criteria including absolute score and coverage wherein different criteria cutoffs are used for oligos relative to long sequences (pg. 6, paras. 1-2). In this way, Jones discusses determining that hazardous content is present based on threshold lengths and percentages. However, Jones does not specifically describe detection of hazardous content based on satisfaction of a threshold length and a threshold percentage.
Altschul describes BLAST functionality wherein the algorithm locally searches the compared sequences for word pairs meeting an alignment score threshold (T) and extends the search from each ‘hit’ to test whether it is contained in a high-scoring alignment (pg. 3389, r. column). In other words, detection of matches based on satisfaction of a threshold percentage.
Altschul further proposes a ‘two-hit’ technique, requiring the existence of two non-overlapping word matches within a specified distance (A) of each other before further extending the search of a given alignment (pg. 3389, r. column). In other words, additionally requiring satisfaction of a threshold length.
With respect to claim 3, Altschul describes BLAST functionality wherein the algorithm locally searches the compared sequences for word pairs meeting an alignment score threshold (T) and extends the search from each ‘hit’ to test whether it is contained in a high-scoring alignment (pg. 3389, r. column). Altschul further describes extending until the running alignment’s score drops more than a particular value (X) below the maximum score yet attained (pg. 3390, r. column). In other words, determining where a matching sequence percentage satisfies a threshold percentage (a ‘hit’) and assessing alignment score while extending the match length up to a threshold length.
With respect to claim 4, Altschul describes local alignment functionality of BLAST wherein the program aligns equal-length segments (words) within database and query sequences, scanning the database sequence sequentially and extending alignment windows with two non-overlapping matches (hits) until the running alignment’s score drops below a threshold, to determine high-scoring segment pairs (pg. 3390, l. column – pg. 3391, l. column). The described extended alignment process is equivalent to determining where a matching length satisfies a threshold length and performing a sliding window analysis.
With respect to claim 5, the extended alignment process described by Altschul is equivalent to determining where any sequence portion, of a given length, satisfies a threshold percentage and performing a sliding window analysis.
Altschul notes that database searches using position-specific score matrices (PSSMs) often are much better able to detect weak relationships than database searches that use a simple sequence as query, and mentions related work pertaining to construction of a single artificial query sequence that approximates a PSSM (pg. 3394, l. column). However, Altschul does not further discuss construction or evaluation of a composite sequence as claimed.
Henikoff discusses a strategy for utilizing multiple alignment information to detect distant relationships in searches of sequence databases, comprising selection of a single representative query sequence based on multiple alignment of query sequences, replacement of conserved regions of the representative sequence with consensus residues derived from the multiple alignment, and evaluation of the consensus-embedded sequence using single sequence query searching programs such as BLAST (pg. 698, Abstract; pg. 699, r. column; pg. 703, r. column). In this way Henikoff discloses production and evaluation, via BLAST, of a composite sequence formed from portions of nucleotide sequences in a plurality of nucleotide sequences.
Henikoff discloses availability of software programs that implement multiple alignment of a set of unaligned sequences, computation and embedding of consensus residues to produce a consensus-embedded sequence (pg. 705, l. column). Henikoff additionally teaches that construction and evaluation of a consensus-embedded sequence is functionally advantageous to evaluation of a PSSM, albeit less statistically accurate in some circumstances, because a consensus-embedded sequence can be directly utilized as a query for standard searching programs (e.g., BLAST) while evaluation of a PSSM as a query requires modification of such programs (pg. 701, r. column).
With respect to claim 6, Jones discloses comparison of input sequences to a curated database of sequences from known pathogens (‘select agents’) and describes reporting of a “match to a pathogen” (pg. 5, para. 3). This indicates annotation of the database with metadata describing the pathogen with which each reference sequence is associated, and retrieval/reporting of said metadata upon detection of a match.
Jones also includes an exemplary screenshot displaying a positive match, which confirms reporting of metadata describing the associated pathogen (pg. 8, Fig. 3).
With respect to claim 7, Jones discusses weighted scoring of sequence matches according to biological significance of the match, e.g., interpreting a very strong match to a sequence involved in anthrax toxin as a clear positive match while weighting down a match to a less important region of the B. anthracis genome (pg. 13, para. 3). In this way, Jones suggests assignment of one of a plurality of threat levels based on the comparison and exemplifies judgment of a threat (clear positive match) and potential threat (downweighted match).
Jones further discusses an example wherein a query sequence is found to match to two sequences in a pathogen database and one in a non-pathogen database, and judged as more similar to the non-pathogen than to either of the pathogens (pg. 12, para. 5 – pg. 13, para. 2). This is considered equivalent to judgment of an unlikely threat. Jones further discusses discarding of search results for sequences that do not match against the pathogen database (pg. 7, para. 1), which is considered equivalent to judgment of a non-threat.
With respect to claim 8, Jones discloses implementation of sequence comparison via BLAST (pg. 4, para. 4), i.e., an alignment algorithm.
With respect to claim 9, Jones states that the BlackWatch software system includes wrapper scripts for managing the user interface, and can be accessed from a command line, web or custom database interface (pg. 5, paras. 4-5; pg. 6, Fig. 1). Jones further states that input sequences are passed from one of the interfaces (pg. 6, para. 1), and positive results can be reported via email alerts including links to a web interface with details of the match (pg. 7, para. 3).
With respect to claim 10, Jones discloses a web interface showing a query sequence input screen that loads a FASTA format file (pg. 7, para. 5; pg. 8, Fig. 2), i.e., a graphical user interface configured to allow a user to input multiple nucleotide sequences by uploading a single file.
With respect to claim 11, Jones states that searches which do not produce matches are simply acknowledged as having been run, while positive matches and associated information are highlighted (pg. 8, para. 1). Jones also includes an exemplary screenshot displaying a detailed BLAST output for a positive match, which appears to include a search progress bar prior to results (pg. 9, Fig. 4).
Claim 13 recites a method for assessing threat levels associated with synthesizing one or more nucleotide sequences, comprising process limitations of substantive similarity to the functional limitations of claim 1. The teachings of Jones, in view of Altschul, are considered to apply to the substantively similar limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 1.
Claim 13 also uniquely requires determining that a threat level assigned to a nucleotide sequence does not represent a threat; and synthesizing the nucleotide sequence.
With respect to the unique limitations of claim 13, Jones discusses application of BlackWatch to screen production databases at synthesis companies (pg. 7, para. 2). Synthesizing a nucleotide sequence after determining that a corresponding result does not represent a threat is considered an obvious aspect of application in the specified technological environment.
With respect to claim 14, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 2.
With respect to claim 15, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 3.
With respect to claim 16, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 4.
With respect to claim 17, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 5.
With respect to claim 18, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 6.
With respect to claim 19, the teachings of Jones, in view of Altschul, are considered to apply to the process limitations of the claim in the same manner as detailed above regarding the functional limitations of claim 8.
Claim 20 recites a system for assessing threat levels associated with synthesizing nucleotide sequences having structural and functional limitations of substantive similarity to those of claim 1. Claim 20 additionally includes functional limitations of substantive similarity to functional limitations of claims 9-10 and process limitations of claim 13.
With respect to claim 20, the teachings of Jones, in view of Altschul, are considered to apply to the limitations of the claim in the same manner as detailed above regarding limitations of claims 1, 9-10 and 13.
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented search extension and detection of hazardous content (i.e., sliding window analysis) based on threshold lengths and percentages as claimed, to enhance the sequence screening workflow of Jones, because Jones discloses performance of sequence comparison via BLAST (pg. 4, para. 4) while Altschul indicates that BLAST performs sliding window analysis (pg. 3390, l. column – pg. 3391, l. column) and advantageously teaches a ‘two-hit’ BLAST technique (pg. 3390, l. column – pg. 3391, l. column) with combined basis on threshold lengths and percentages as claimed. Said practitioner would have had a reasonable expectation of success because Jones and Altschul both discuss performance of nucleotide sequence comparison via BLAST.
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented formation and analysis of a composite sequence, to enhance the sequence screening workflow of Jones, because Henikoff teaches that a consensus-embedded sequence (i.e., a composite sequence) provides the improved statistical power of a PSSM but, unlike a PSSM, can be directly used as a BLAST query sequence (pg. 701, r. column). Said practitioner would have had a reasonable expectation of success because Jones and Henikoff both discuss performance of nucleotide sequence comparison via BLAST.
In this way the disclosure of Jones, in view of Altschul and Henikoff, makes obvious the limitations of claims 1-11 and 13-20. Thus, the claimed invention is prima facie obvious.
Claim 12 is rejected under 35 USC § 103 as being unpatentable over Jones, in view of Altschul and Henikoff, as applied to claim 1 above, and further in view of Silberschatz et al (Operating System Concepts Essentials, 2nd. Ed., Wiley; published 2014).
Claim 12 is directed to the system of claim 1, and uniquely recites a workflow database including a queue. The claim also uniquely requires that the server is further capable of writing each of the received nucleotide sequences to the queue, and that the compute engine is further capable of reading one nucleotide sequence at a time from the queue in order to compare that nucleotide sequence.
With respect to the unique limitations of claim 12, Jones discusses implementation of BlackWatch on a web server and Linux systems (pg. 12, paras. 1-2), i.e., compute engines. Jones also discloses performance of sequence comparison via BLAST (pg. 4, para. 4). Jones does not describe writing input sequences to, or reading sequences from, a work queue.
Altschul teaches that BLAST scans database sequences sequentially (pg. 3391, l. column). Altschul does not teach writing input sequences to, or reading sequences from, a work queue.
Silberschatz discusses data structuring in computer operating systems, and teaches that CPU tasks are commonly organized into sequentially-ordered queues that use the ‘first in, first out’ principle, i.e., items are removed in the order in which they were inserted (pg. 32, para. 4). In other words, received requests and associated data would be written to the ‘top’ of a queue and read from the ‘bottom’ of the queue. Silberschatz additionally teaches that the Linux kernel uses a first in, first out queue (pg. 35, Linux Kernel Data Structures).
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented the sequence screening workflow of Jones using a ‘first in, first out’ queue, as taught by Silberschatz, because Silberschatz indicates that computer task management based on this queue structure was well-known before the effective filing date of the claimed invention. Said practitioner would have had a reasonable expectation of success because Jones discloses implementation on Linux systems (pg. 12, para. 1) and Silberschatz teaches that the Linux kernel utilizes such a queue by default (pg. 35, Linux Kernel Data Structures).
In this way the disclosure of Jones, in view of Altschul, Henikoff and Silberschatz, makes obvious the limitations of claim 12. Thus, the claimed invention is prima facie obvious.
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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Instant claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 28 of U.S. Patent No. 11,232,852 (hereafter, “‘852”). ‘852 shares joint inventors (Rudraraju, Sachin; Tabbaa, Omar P.) and a common assignee (Battelle Memorial Institute) with the instant application. The instant claims and claims of ‘852 recite limitations that are nonidentical but substantively similar. Significant differences between the instant claim limitations and corresponding limitations of ‘852 are noted below.
With respect to instant claim 1, claim 1 of ‘852 includes limitations of substantive similarity to all limitations of the instant claim. Significant differences in scope pertain to plurality of elements. For example, ‘852 claims “a server to communicate with a remote frontend over a network to receive, from the frontend, a request” (claim 1), where the instant claim recites a server to communicate with a number of remote frontends over a network to receive, from the frontends, a number of requests. Pluralization of elements is not considered to patentably distinguish the instant claim.
With respect to instant claims 2-5, claims 2-5 of ‘852 respectively include limitations of substantive similarity to all limitations of the instant claims.
With respect to instant claim 6, claim 6 of ‘852 includes limitations of substantive similarity to all limitations of the instant claim. Significant differences in scope pertain to plurality of elements. For example, claim 6 of ‘852 requires that the server is capable of reporting metadata “to the frontend” (as the claims of ‘852 involve receipt of a request from a single frontend), where the instant claim requires that the server is capable of reporting metadata to the respective frontend that made the request (as the instant claims involve receipt of a plurality of requests from a plurality of frontends). Pluralization of elements is not considered to patentably distinguish the instant claim.
With respect to instant claims 7-8, claims 7-8 of ‘852 respectively include limitations of substantive similarity to all limitations of the instant claims.
With respect to instant claim 9, claim 9 of ‘852 includes limitations of substantive similarity to all limitations of the instant claim. Significant differences in scope pertain to the nature of displayed data. Claim 9 of ‘852 requires that the graphical user interface is capable of displaying “the result of screening”, where the instant claim requires that the server is capable of graphical user interface is capable of displaying the threat level assigned. Claim 1 of ‘852 requires that “the result reported to the frontend by the server comprises the threat level assigned”, which is considered to read on the noted instant limitation.
With respect to instant claims 10-12, claims 10-12 of ‘852 respectively include limitations of substantive similarity to all limitations of the instant claims.
With respect to instant claim 13, claim 13 of ‘852 includes limitations of substantive similarity to all limitations of the instant claim.
With respect to instant claims 14-19, claims 14-19 of ‘852 respectively include limitations of substantive similarity to all limitations of the instant claims.
With respect to instant claim 20, claim 28 of ‘852 includes limitations of substantive similarity to all limitations of the instant claim, except for the instant limitation of wherein the plurality of nucleotide sequences includes at least one thousand nucleotide sequences. Claim 1 of ‘852 requires that “the compute engine is capable of performing the comparison for thousands of nucleotide sequences”, which is considered to read on the noted instant limitation.
Thus, although the claims at issue are not identical, they are not patentably distinct from each other.
Conclusion
At this point in prosecution, no claim is allowed.
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/T.C.S./Examiner, Art Unit 1685
/JESSE P FRUMKIN/Primary Examiner, Art Unit 1685 January 24, 2026