DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s amendment and response filed 10/01/2025 have been entered, and carefully considered, but are not completely persuasive.
Claims 41, 43-59 are pending and under examination. Claim 42 has been canceled, and claim 59 is newly added. The examiner acknowledges the election of dPTP, as opposed to dTTP.
Replacement figures 4A and 4B have been entered.
The amendment to the specification related to the description of figures 4A and 4B has been entered.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation (BRI) 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.
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 41, 43-59 is/ are/ remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
The claims have been significantly amended.
Applicant is directed to MPEP 2106 and the Federal Register notice (FR89, no 137 (7/17/2024) p 58128-58138) for the most current and complete guidelines in the analysis of patent- eligible subject matter. The current MPEP is the primary source for the USPTO’s patent eligibility guidance.
With respect to step (1): YES. The claims are drawn to statutory categories: Processes.
With respect to step (2A) (1): YES. The claims recite an abstract idea, law of nature and/or natural phenomenon. The claims explicitly recite elements that, individually and in combination, constitute one or more judicial exceptions (JE).
Mathematic concepts, Mental Processes or Elements in Addition (EIA) in the claim(s) include:
41. A method for characterizing tandem repeats in a region of a genome, comprising:
(EIA- preamble setting forth the method, and the goal of the method.)
(i) producing a plurality of amplified and modified nucleic acid molecules by:
(a) modifying a plurality of nucleotides in a plurality of repeated regions of nucleic acid molecules from a genome to form modified nucleic acid molecules comprising a pattern of synthetic polymorphisms;
(b) amplifying the modified nucleic acid molecules to form amplified and modified nucleic acid molecules;
(EIA- data gathering step, performing routine, generically stated, modification and amplification of nucleic acid molecules. The source of the NA is not set forth. The modification and amplification are carried out using routine prior art methods as set forth in [0033-0039] of the specification.)
(ii) sequencing the amplified and modified nucleic acid molecules;
(EIA- data gathering step, performing routine, generally stated sequencing of the product of the previous step. Sequencing used routine processes, as set forth in [0042-0046].)
(iii) aligning sequence reads of the amplified and modified nucleic acid molecules with one another by reference to the pattern of synthetic polymorphisms in regions of sequence overlap of the sequence reads, thereby obtaining a sequence alignment and
(Mental process, using a computer as a tool, or in a computing environment, of observing the pattern, comparing the patterns to one another, and making a judgement as to whether they represent overlapping, or the same sequence. [0016, Fig 4, Fig 5, 0044] “In some instances, the synthetic polymorphism alignment comprises matching (i.e. by a computer implemented method) a pattern of synthetic polymorphisms in a first nucleic add fragment sequence ...”)
(iv) determining a characteristic of tandem repeats in the sequence alignment, wherein the characteristic of the tandem repeats is a length, number, sequence, or type.
(Mathematic concept of counting the length of the repeat, or the number of tandem repeats; and a mental process in a computing environment, or using a computer as a tool, of observation of the sequence or type of the tandem repeat, and making a judgement. [0017, Fig 5, 0075] “It is contemplated that one or more software programs for use with methods and compositions disclosed herein will have the capacity to recognize the incorporated synthetic polymorphism patterns present in the fragment sequence data, align the polymorphisms identified in the fragment sequence data and output a sequence based on that alignment... In other embodiments, output may comprise forensic nucleotide repeat information, such a type (i.e., sequence of repeat, location of repeat, number of short or intermediate tandem repeats, etc.”)
42. (CANCELED)
43. (CURRENTLY AMENDED) The method of claim 41, wherein step (iii) comprises:
matching a pattern of synthetic polymorphisms in a first sequence read with a like pattern of synthetic polymorphisms in a second sequence read, and
repeating said matching with a plurality of sequence reads, thereby creating the sequence alignment based on the pattern of synthetic polymorphisms.
(Mental Process in a computing environment: modification of step (iii) by observing and matching similar patterns, and repeating the matching and alignment with the plurality of modified sequences. [0017, Fig 5, 0075])
44. (CURRENTLY AMENDED) The method of claim 41, wherein step (iii) further comprises aligning sequence reads against a reference genome.
(Mental process of matching, in a computing environment, between sequence reads and a reference genome, by any alignment method, with any reference genome. [0049, 0075-0076, 0078-0079])
45. (CURRENTLY AMENDED) The method of claim 41, wherein step (iii) comprises identifying patterns of synthetic polymorphisms in regions of sequence overlap of the sequence reads that are unique to two sequence reads of the sequence reads of the plurality of amplified and modified nucleic acid molecules.
(Mental process step added to step iii) in a computing environment, of observing unique patterns. [0008, 0017, 0043, 0078))
46. (CURRENTLY AMENDED) The method of claim 41, wherein the tandem repeats comprise short tandem repeats (STRs).
(Mental process modification specifying the type of repeat to be characterized.)
47. (Previously Presented) The method of claim 41, wherein modifying a plurality of nucleotides comprises chemical mutagenesis.
(EIA- modification of step i), a data gathering step modification, by prior art processes. [0051, 0061])
48. (Previously Presented) The method of claim 47, wherein the chemical mutagenesis comprises cytosine deamination.
(EIA- modification of step i) a data gathering step modification by prior art processes [0051, 0061]).
49. (Previously Presented) The method of claim 48, wherein the cytosine deamination comprises partial and incomplete bisulfite conversion of cytosine to uracil or thymine.
(EIA- modification of step i) a data gathering step modification by prior art processes [0051, 0061]).
50. (Previously Presented) The method of claim 41, wherein the nucleic acid molecules are extracted from a cell.
(EIA- modification of step i) a data gathering step modification, specifying a routine source of nucleic acid molecules. [0054-0056])
51. (Previously Presented) The method of claim 41, further comprising fragmenting the nucleic acid molecules.
(EIA- modification of step i) a data gathering step modification, specifying a routine source of nucleic acid molecules. [0011, 0030-0031])
52. (Previously Presented) The method of claim 41, further comprising fragmenting the amplified and modified nucleic acid molecules.
(EIA- modification of step i) a data gathering step modification, specifying a routine source of nucleic acid molecules. [0011, 0030-0031])
53. (Previously Presented) The method of claim 41, further comprising tagging the nucleic acid molecules with an adaptor sequence.
(EIA- modification of step i), a data gathering step modification, specifying use of a routine tag in the amplification. [0030-0031, 0037, 0040, 0068]
54. (Previously Presented) The method of claim 53, wherein the adaptor sequence lacks a nucleotide that may be modified in step i) a).
(EIA- modification of step i), a data gathering step modification, specifying use of a routine tag in the amplification. [0030-0031, 0037, 0040, 0068]
55. (Previously Presented) The method of claim 54, wherein modifying a plurality of nucleotides comprises cytosine deamination, and wherein the adaptor sequence lacks a cytosine nucleotide.
(EIA- modification of step i), a data gathering step modification, specifying a type of modification and the use of a type of routine tag in the amplification. [0010, 0028, 0030-0031, 0037, 0040, 0068]
56. (Previously Presented) The method of claim 53, wherein the adaptor sequence is unique for each nucleic acid molecule.
(EIA- modification of step i), a data gathering step modification, specifying use of a routine tag in the amplification. [0030-0031, 0037, 0040, 0068]
57. (Previously Presented) The method of claim 53, wherein the adaptor sequence comprises a primer sequence.
(EIA- modification of step i), a data gathering step modification, specifying use of a routine tag and primer in the amplification. [0030-0031, 0037, 0040, 0068]
58. (Previously Presented) The method of claim 57, wherein modifying a plurality of nucleotides comprises cytosine deamination, and wherein the primer sequence lacks a cytosine nucleotide.
(EIA- modification of step i), a data gathering step modification, specifying use of a routine tag and primer in the amplification. [0030-0031, 0037, 0040, 0068]
59. (NEW) The method of claim 41, wherein step (a) comprises performing a partial modification of nucleotides of the plurality of nucleotides selected from (i) partial bisulfite conversion of cytosine to uracil or thymine; (ii) incorporation of 80xodGTP in the presence of at least one of dGTP and dTTP; or (iii) incorporation of dPTP in the presence of at least one of dCTP and dTTP.
(EIA modification of the data gathering steps of elements (i)(a).)
Broadest Reasonable Interpretation:
In claim 41, the method for characterization of tandem repeats in a region of a genome comprises both abstract ideas, and additional elements of data gathering, as set forth above. The claim is not limited to a computer-implemented process nor are any computer processor limitations present.
The BRI of the claim is determined in light of the specification (MPEP 2106.03/ .04). With respect to the limitations determined to recite abstract ideas, the Examiner reviewed the specification for how the “aligning” and “determining a characteristic” were to be carried out (steps (iii) and (iv) of claim 41).
The processes related to “aligning” as disclosed meet the requirements for falling within the abstract idea grouping of mental processes, as the processes performed require data observation, comparison of data, and making a judgement as to whether the sequences are “in alignment” (MPEP 2106.04(a)(2)). These steps do not require any element for which the human mind is not equipped (SRI Int’l, CyberSource, SiRF Tech Inc., Electric Power Group, Ambry Genetics, Classen Immunotherapies Inc. et al.). The Examiner noted that computer-implemented processes were a preferred embodiment. “In some instances, the synthetic polymorphism alignment comprises matching (i.e. by a computer implemented method) a pattern of synthetic polymorphisms in a first nucleic add fragment sequence ...”).
With respect to “determining a characteristic”, the abstract idea is identified on the basis of what characteristic is to be determined and the characteristics fall into two categories of abstract ideas set forth in MPEP 2106.04(a)(2): mathematic concepts and mental processes.
For the characteristics related to length and number of repeats, this is a mathematic concept of counting elements meeting the condition. (MPEP 2106.04(a)(2), “For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation.”)
The plain meaning of the term “length” is the measurement of something from end to end. Sequence read length is the number of consecutive nucleotide calls for a particular sequence read. The specification sets forth lengths of sequence reads between 250 and 6000bp long (p25).
The plain meaning of “number” is an arithmetical value representing a quantity, used in counting and making calculations. Determining the number of repeat units present at a location is the mathematic concept of counting.
For the characteristics related to sequence or type, this is a mental process of observing the sequence, or observing the repeat and making a judgement as to the type of repeat present. These elements meet the requirements for mental processes as defined in MPEP 2106.04(a).) This process does not require any elements for which the human mind is not equipped (SRI Int’l, CyberSource, SiRF Tech Inc., Electric Power Group, Ambry Genetics, Classen Immunotherapies Inc. et al.). The Examiner noted that a preferred embodiment carries out these steps using computer-implemented software. “It is contemplated that one or more software programs for use with methods and compositions disclosed herein will have the capacity to recognize the incorporated synthetic polymorphism patterns present in the fragment sequence data, align the polymorphisms identified in the fragment sequence data and output a sequence based on that alignment... In other embodiments, output may comprise forensic nucleotide repeat information, such a type (i.e., sequence of repeat, location of repeat, number of short or intermediate tandem repeats, etc.” [0075])
Therefor, the claims recite abstract elements which alone, and in combination represent a Judicial Exception.
With respect to step 2A (2): NO the identified JE are not integrated into a practical application. The claims were examined further to determine whether they integrated any JE into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone, or in combination to determine if the JE is integrated into a practical application (MPEP 2106.04(d) and 2106.05).
Claim(s) 41, 47-59 recite the additional non-abstract element(s) of data gathering, or a description of the data gathered.
MPEP 2106.04(d): “Limitations the courts have found indicative that an additional element (or combination of elements) may have integrated the exception into a practical application include:
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• An improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
• Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
• Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
• Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
• Applying or using 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, as discussed in MPEP § 2106.05(e).
The courts have also identified limitations that did not integrate a judicial exception into a practical application:
• Merely reciting the words "apply it" (or an equivalent) with the judicial exception, or 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);
• Adding insignificant extra-solution activity to the judicial exception, as discussed in MPEP § 2106.05(g); and
• Generally linking the use of a judicial exception to a particular technological environment or field of use, as discussed in MPEP § 2106.05(h).”
The claims do not provide an improvement in the functioning of the computer itself.
The claims do not provide an improvement to technology or to a technical field. The steps of modifying, amplifying and sequencing are carried out without any particular non-routine or non-conventional elements. The technology of modifying nucleic acids is not improved. The technology of amplifying modified nucleic acids is not improved. The technology of sequencing the amplified modified nucleic acids is not improved. The improvement is in the analysis of the information provided by the sequence reads generated by the sequencing process.
The claims do not provide a particular treatment or prophylaxis for a disease or medical condition.
The claims do no require a particular machine or manufacture integral to the claim.
The claims do not effect a transformation or reduction of a particular article to a different state or thing.
The claims do not go beyond generally linking the JE to the technology of analysis of sequence read data.
The data gathering steps are generically recited, and represent insignificant extra-solution activity, and generally link the JE to the field of use of the analysis of sequence read data.
Dependent claim(s) 43-46 recite(s) an abstract limitation to the JE reciting additional mathematic concepts, or mental processes. Additional abstract limitations cannot provide a practical application of the JE as they are a part of that JE. (MPEP 2106.05)
In combination, the limitations of data gathering, for the purpose of carrying out the JE, merely provide extra-solution activity, and fail to integrate the JE into a practical application.
With respect to step 2B: NO the claims do not provide a specific inventive concept. The claims recite a JE, do not integrate that JE into a practical application, and thus are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The additional elements were considered individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to claim(s) 41, 47-59: The limitation(s) identified above as non-abstract elements (EIA) related to data gathering do not rise to the level of significantly more than the judicial exception.
With respect to i) a) modifying a plurality of polynucleotides in a repeat region:
Clark (Clark et al 1994 NAR 22:2990-2997; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Lyko (Lyko et al 2000 Nature 408: 538-540; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Ramsahoye (Ramsahoye et al (2000) PNAS 97:5237-5242; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Cantor (US 2011/0124518 A1; of record) provided modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
With respect to i) b) amplifying the modified polynucleotides:
WO2011/106368 performs biased amplification of modified polynucleotides.
Dressman (Dressman (2003) PNAS 100:8817-8822; of record) provides emulsion amplification of modified polynucleotides.
Cantor (US 2011/0124518 A1) provided amplification of modified polynucleotides.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided amplification of modified polynucleotides.
With respect to step ii) performing sequencing of modified, amplified polynucleotides:
Puchkarev (Puchkarev et al. 2009) Nature Biotechnology 27:847-852; of record) provides single molecule sequencing of modified, amplified polynucleotides.
US 2009/0247414 A1; 2010/0111768 A1 (of record) describe routine high throughput sequencing of modified polynucleotides.
Cantor (US 2011/0124518 A1) provided sequencing of amplified modified polynucleotides.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided sequencing of amplified modified polynucleotides.
These elements meet the BRI of the identified data gathering limitations. As such, the prior art recognizes that this data gathering element is routine, well understood and conventional in the art (as in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook).
In the specification at [0034, 0036, 0047-0048, 0057, 0072-0073] it is disclosed that the steps identified as data gathering can be met using the commercially available products of Roche Applied Sciences, Zymo Research, Bioline, Pacific Biosciences, Applied Biosciences Life Technologies, Illumina, Oxford Nanopore and others.
In the specification at [0057] it states “Methods and systems disclosed herein are not necessarily limited to any particular library preparation or technology.”
Repeating the analysis of elements MPEP 2106.05 a-c and e-h: The claims do not provide an improvement in the functioning of the computer itself.
The claims do not provide an improvement to technology or to a technical field. The steps of modifying, amplifying and sequencing are carried out without any particular non-routine or non-conventional elements. The technology of modifying nucleic acids is not improved. The technology of amplifying modified nucleic acids is not improved. The technology of sequencing the amplified modified nucleic acids is not improved. The improvement is in the analysis of the information provided by the sequence reads generated by the sequencing process.
The claims do not provide a particular treatment or prophylaxis for a disease or medical condition.
The claims do not require a particular machine or manufacture integral to the claim.
The claims do not effect a transformation or reduction of a particular article to a different state or thing.
The claims do not go beyond generally linking the JE to the technology of analysis of sequence read data.
The data gathering steps are generically recited, and represent insignificant extra-solution activity, and generally link the JE to the field of use of the analysis of sequence read data.
Dependent claim(s) 43-46 each recite a limitation requiring additional mathematic concepts or mental processes. Additional abstract limitations cannot provide significantly more than the JE as they are a part of that JE (MPEP 2106.05).
In combination, the data gathering steps providing the information required to be acted upon by the JE, in combination with the JE, fail to rise to the level of significantly more than that JE. The data gathering steps provide the data for the JE. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Applicant’s arguments:
Applicant’s arguments have been considered but are not persuasive.
Applicant argues the categorization or identification of abstract ideas in the claims. The Examiner has specifically identified each limitation in each claim, and what category of judicial exception is encompassed. The abstract ideas identified in the independent claims are the same as those identified as mathematic concepts: mathematic correlations, mathematic calculations, and mathematical relationships, or as mental processes: concepts performed in the human mind including observations, evaluations, judgements and opinions; MPEP 2106.04.
With respect to whether the claim recites mental processes, and the notation by the Examiner that the mental processes identified can be carried out using a pen and paper, in a computing environment, or using a computer as a tool, the Examiner notes that the claim is NOT computer-implemented, nor does it recite carrying out any particular step “in a processor.”
Even if the claim were to be amended to be computer-implemented, MPEP 2106.04 clearly sets forth “the courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation. See, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (noting that the claimed "conversion of binary- coded decimal numerals to pure binary numerals can be done mentally,” i.e., "as a person would do it by head and hand").” MPEP 2106.04
“Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent ineligible invention could be performed via pen and paper or in a person’s mind." Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681,1702 (Fed. Cir. 2015). See also Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307,1318, 120 USPQ2d 1353, 1360 (Fed. Cir. 2016) (‘‘[W]ith the exception of generic computer-implemented steps, there is nothing in the claims themselves that foreclose them from being performed by a human, mentally or with pen and paper.’’); Mortgage Grader, Inc. v. FirstChoice Loan Servs. Inc., 811 F.3d 1314, 1324, 117 USPQ2d 1693, 1699 (Fed. Cir. 2016) (holding that computer-implemented method for "anonymous loan shopping” was an abstract idea because it could be "performed by humans without a computer").
With respect to the identification of certain steps as mental processes, and whether the human mind is equipped to perform the steps classified as mental processes: there is no step identified as a mental process in the claim which requires an element which cannot practically be performed in the human mind, because there are no limitations requiring an element for which the human brain is not equipped. The MPEP sets forth a discussion of such elements including a GPS receiver, specific computer-integrated elements such as network monitors or network packets, and limitations to a multistep encryption of data for computer communication. No modified computer structures, such as self-referential tables, neural networks, artificial intelligence are present in the claims. (See SRI Int’l, Inc. v. Cisco Systems, Inc., (declining to identify the claimed collection and analysis of network data as abstract because "the human mind is not equipped to detect suspicious activity by using network monitors and analyzing network packets as recited by the claims"); CyberSource, (as directed to inventions that ‘‘could not, as a practical matter, be performed entirely in a human’s mind’’). MPEP 2106.04)
Applicant’s arguments in this aspect appear to be directed to either the data gathering processes which is the incorrect application, or refer to an amount of information required to be processed in the steps. The data gathering steps were NOT identified as reciting mental processes, they were labeled additional elements, or elements in addition to the JE (EIA).
The amount of information generated at each step does not represent an element for which the human mind is not equipped: the process may be long and tedious but there are no limitations requiring a particular amount of data in each step, or a particular manipulation of the data in any way that cannot be performed by mental processes as identified by the Courts. It is the process performed on that data which is the mental step, and mental steps identified in the claims do not have to be fastest, most efficient, or require specialized computing elements. Data recognition, data comparison, and making judgements about the compared data all can be performed in the human mind, albeit slowly, using pen and pencil, and slightly faster using the general-purpose computer as a tool or in a computing environment. Computations on large amounts of data performed mentally, or with paper and pencil, would take considerable time and effort, 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.) (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, (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).
The newly added limitation of “aligning sequence reads… by reference to the pattern of synthetic polymorphisms…obtaining a sequence alignment” does not require processes for which the human mind is not equipped. Aligning two patterns is a matching step, requiring observing a pattern, comparing patterns, and making a judgement as to when two patterns represent the same sequence, each of which can be done in the human mind or using the computer as a tool, without any specialized computer elements required. Each pattern can be compared, one-by-one to each other, or the reference genome, to determine an alignment.
With respect to the argument that “it would be practically impossible for a human mind to align sequence reads by aligning patterns of synthetic polymorphisms from the sequence data obtained in step (ii) and determine characteristics of tandem repeats from that alignment,” Applicant is encouraged to provide proof of this assertion, and to point out particular structures, steps or requirements of the claims that would make such pattern assessment “practically impossible.” The patterns themselves have no particular structure or number of synthetic polymorphisms, or particular complexity. The examiner reviewed the specification for basis for this assertion, and did not find such support. While computer software could be used, the steps performed still fall within the category of mental processes.
“[0075] … It is contemplated that one or more software programs for use with methods and compositions disclosed herein will have the capacity to recognize the incorporated synthetic polymorphism patterns present in the fragment sequence data, align the polymorphisms identified in the fragment sequence data and output a sequence based on that alignment. In some embodiments, the output may comprise a haplotype (e.g. haplotype content or phase) for the target sample. In other embodiments, the output may comprise de novo sequence information for the target sample. In other embodiments, output may comprise forensic nucleotide repeat information, such a type (i.e., sequence of repeat, location of repeat, number of short or intermediate tandem repeats, etc.”
Figure 1, sheet 2/19 is an illustration, using the equivalent of pen and paper, of aligning sequence reads based on the pattern of artificial SNP. This step does not require any specific type of alignment, or any type of analysis, comparison, manipulation for which the human mind is not equipped.
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With respect to “determining a characteristic of tandem repeats… sequence or type” this limitation does not require processes for which the human mind is not equipped. Determining a sequence characteristic is the observation of the sequence of consecutive nucleotide calls for the sequence read, and is performed on each amplified sequence, one at a time. Determining a type of repeat is the observation of the structure of the repeated unit, and making a judgement as to the type of tandem repeat described. This determination is performed on the sequence reads, one at a time. These are all steps which can be performed in the human mind, using an aid such as pen and paper, in a generic computing environment, or using the computer as a tool.
With respect to the argument that the claims do not recite data gathering, these arguments are not persuasive. Steps (i) and (ii) as set forth above, recite steps which generate the data which is to be acted upon by the abstract ideas identified in steps (iii) and (iv). Steps (iii) and (iv) were not identified as data gathering steps.
Steps (i) and (ii) perform routine, well understood and conventional laboratory processes for a) modifying polynucleotides, 2) amplifying polynucleotides and 3) sequencing polynucleotides. These steps do not represent “innovative steps to create and sequence a library of nucleic acid molecules modified with a pattern of synthetic polymorphisms” as demonstrated by the multiple citations to prior art publications describing the same processes for the same purposes. Each of the limitations within steps (i) and (ii) were analyzed alone and in combination, to determine whether they provide integration into a practical application, or a specific inventive concept.
With respect to i) a) modifying a plurality of polynucleotides in a repeat region:
Clark (Clark et al 1994 NAR 22:2990-2997; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Lyko (Lyko et al 2000 Nature 408: 538-540; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Ramsahoye (Ramsahoye et al (2000) PNAS 97:5237-5242; of record) provides modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Cantor (US 2011/0124518 A1; of record) provided modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided modification of a plurality of polynucleotides including incorporation of synthetic nucleic acid residues.
With respect to i) b) amplifying the modified polynucleotides:
WO2011/106368 performs biased amplification of modified polynucleotides.
Dressman (Dressman (2003) PNAS 100:8817-8822; of record) provides emulsion amplification of modified polynucleotides.
Cantor (US 2011/0124518 A1) provided amplification of modified polynucleotides.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided amplification of modified polynucleotides.
With respect to step ii) performing sequencing of modified, amplified polynucleotides:
Puchkarev (Puchkarev et al. 2009) Nature Biotechnology 27:847-852; of record) provides single molecule sequencing of modified, amplified polynucleotides.
US 2009/0247414 A1; 2010/0111768 A1 (of record) describe routine high throughput sequencing of modified polynucleotides.
Cantor (US 2011/0124518 A1) provided sequencing of amplified modified polynucleotides.
Seligson (US 2015/0211070 A1, having priority to 3/8/2012; of record) provided sequencing of amplified modified polynucleotides.
At least two of the cited references perform all three steps for the same purposes: Cantor and Seligson.
Additionally, the specification itself sets forth that these three steps are all generically described and can be met by a plethora of prior art processes. In the specification at [0034, 0036, 0047-0048, 0057, 0072-0073] it is disclosed that the steps identified as data gathering can be met using the commercially available products of Roche Applied Sciences, Zymo Research, Bioline, Pacific Biosciences, Applied Biosciences Life Technologies, Illumina, Oxford Nanopore and others.
In the specification at [0057] it states “Methods and systems disclosed herein are not necessarily limited to any particular library preparation or technology.”
This is not the recitation of “innovative steps to create and sequence a library…” as asserted. This is the recitation of routine modification of polynucleotides, routine amplification of modified polynucleotides, and routine sequencing of the amplified, modified polynucleotides. Even the ordered combination of the three was shown to be routine, well understood and conventional. One modifies prior to amplification. One amplifies prior to sequencing. No aspect of these limitations as present in the rejected claims represents innovative or non-routine elements, in combination.
Further, with respect to the arguments regarding the alleged improvement, it is unclear that the independent claims recite all the necessary and sufficient steps required to achieve that improvement. MPEP 2106.05(a): “An important consideration in determining whether a claim improves technology is the extent to which the claim covers a particular solution to a problem or a particular way to achieve a desired outcome, as opposed to merely claiming the idea of a solution or outcome. McRO, 837 F.3d at 1314-15, 120 USPQ2d at 1102- 03; DDR Holdings, 773F.3d at 1259, 113 USPQ2d at 1107.”
The MPEP sets forth that “if the examiner concludes the disclosed invention does not improve technology, the burden shifts to applicant to provide persuasive arguments supported by any necessary evidence to demonstrate that one of ordinary skill in the art would understand that the disclosed invention improves technology. Any such evidence submitted under 37 CFR 1.132 must establish what the specification would convey to one of ordinary skill in the art and cannot be used to supplement the specification.” Applicant’s arguments cannot take the place of evidence.
An indication that the claimed invention provides an improvement can include a discussion in the specification that identifies a technical problem and explains the details of an unconventional technical solution expressed in the claim, or identifies technical improvements realized by the claim over the prior art.
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.
Claims 41, 43-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,605,446. Although the claims at issue are not identical, they are not patentably distinct from each other because the application steps of modifying the polynucleotides encompasses the fragmentation steps of the patent, both require amplification and sequencing of the modified polynucleotides, both observe patterns of synthetic nucleotides in the sequence reads, align them with one another, and determine a characteristic of the tandem repeat. This application is generic, with respect to the patent. This rejection is newly applied in light of the amendments made.
Claims 41, 43-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2o of U.S. Patent No. 9,977,861. Although the claims at issue are not identical, they are not patentably distinct from each other because the application steps of modifying the polynucleotides encompasses the fragmentation steps of the patent, both require amplification and sequencing of the modified polynucleotides, both observe patterns of synthetic nucleotides in the sequence reads, align them with one another, and determine a characteristic of the tandem repeat. This application is generic, with respect to the patent. This rejection is newly applied in light of the amendments made.
Claims 41, 43-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,257,568. Although the claims at issue are not identical, they are not patentably distinct from each other because the application steps of modifying the polynucleotides encompasses the fragmentation steps of the patent, both require amplification and sequencing of the modified polynucleotides, both observe patterns of synthetic nucleotides in the sequence reads, align them with one another, and determine a characteristic of the tandem repeat. This application is generic, with respect to the patent. The patent is directed to systems for carrying out the encompassed methods. This rejection is newly applied in light of the amendments made.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY K ZEMAN whose telephone number is 5712720723. The examiner can normally be reached on 8am-2pm M-F. Email may be sent to mary.zeman@uspto.gov if the appropriate permissions have been filed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry Riggs can be reached on 571 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY K ZEMAN/ Primary Examiner, Art Unit 1686