DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election with traverse of Group I, drawn to a sequencing method, in the reply filed on March 02, 2026 is acknowledged. Applicants arguments are persuasive, therefore the unity of invention objection is withdrawn and all pending claims will be examined together. Applicant cancels claims 10-11, 19-20 and 24-28. Claims 1-9, 12-18, 21-23 and 29 are currently pending and under examination.
Priority
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-
(d) prior to declaration of an interference, a certified English translation of the foreign
application must be submitted in reply to this action. See MPEP 234.01 (c), 37 CFR 41.154(b)
and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the
non-English application.
It is acknowledged that the certified copy for CN 202010362587.6 was received, however there is no certified English translation.
Additionally, no certified copies were received for CN 202010865293.5 or CN202010867569.3.
Information Disclosure Statement
The Information Disclosure Statements filed October 28, 2022; October 04, 2023; and February 28, 2024 have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1),
1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response – Applicant must:
Amend the Sequence Listing Incorporation by Reference paragraph at page 1 of the
specification. It is noted the Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 2 kilobytes, whereas the ASCII text file itself lists the size as 1,312 bytes.
Specification
The use of the term Triton® X-100, (see Page 14, Line 30, Page 15, Line 9, Page 22, Lines 7 and 22, ) which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
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. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to”, “configure for” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitations are: “a first read set determination module configured for constructing a first read set based on the first sequencing data according to the lengths of the reads” in claim 22. Claim 22 additionally recites the limitations “a second and third read set determination module configured for constructing a second read set and a third read set based on the first read set according to the lengths of the corresponding reads”. Claim 22 additionally recites the limitation “a fourth and fifth read set determination module configured for constructing a fourth read set and a fifth read set based on the second read set and the corresponding reads thereof according to the sequencing quality of the reads in the second read set and the corresponding reads thereof”. Claim 22 additionally recites the limitations “a sixth read set determination module configured for filtering the fourth read set according to the sequencing quality so as to construct a sixth read set”. Claim 22 additionally recites the limitations “a seventh read set determination module configured for selecting the reads corresponding to the reads in the sixth read set from the fifth read set according to the sixth read set so as to construct a seventh read set”. Claim 22 additionally recites the limitations “a first difference site determination module configured for aligning the reads in the sixth read set with the reads in the seventh read set, and determining a first difference site on the reads in the sixth read set” as well as “a first sequence information determination module configured for correcting the first difference site using a predetermined sequencing error prediction model so as to determine first sequence information. In addition, claim 23 recites the limitation “an eighth read set determination module configured for filtering the third read set according to the sequencing quality so as to construct an eighth read set”. Additionally, claim 23 recites the limitation “a ninth read set determination module configured for selecting the reads corresponding to the reads in the seventh read set from the second sequencing data according to the eighth read set so as to construct a ninth read set”. Additionally, claim 23 recites the limitation “a second difference site determination module configured for aligning the reads in the eighth read set with the reads in the ninth read set, and determining a second difference site on the reads in the eighth read set”, as well as “a second sequence information determination module configured for correcting the second difference site using the sequencing error prediction model so as to determine second sequence information”. In addition, claim 29 recites the limitation “the instructions cause a computer to execute the method according to claim 1 when the program is executed by the computer”.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 22-23 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As described below, the disclosure does not provide adequate structure to perform the claimed functions of a first read set determination module configured for constructing a first read set based on the first sequencing data according to the lengths of the reads, a second and third read set determination module configured for constructing a second read set and a third read set based on the first read set according to the lengths of the corresponding reads, a fourth and fifth read set determination module configured for constructing a fourth read set and a fifth read set based on the second read set and the corresponding reads thereof according to the sequencing quality of the reads in the second read set and the corresponding reads thereof, a sixth read set determination module configured for filtering the fourth read set according to the sequencing quality so as to construct a sixth read set, a seventh read set determination module configured for selecting the reads corresponding to the reads in the sixth read set from the fifth read set according to the sixth read set so as to construct a seventh read set, a first difference site determination module configured for aligning the reads in the sixth read set with the reads in the seventh read set, and determining a first difference site on the reads in the sixth read set, a first sequence information determination module configured for correcting the first difference site using a predetermined sequencing error prediction model so as to determine first sequence information, an eighth read set determination module configured for filtering the third read set according to the sequencing quality so as to construct an eighth read set, a ninth read set determination module configured for selecting the reads corresponding to the reads in the seventh read set from the second sequencing data according to the eighth read set so as to construct a ninth read set, a second difference site determination module configured for aligning the reads in the eighth read set with the reads in the ninth read set, and determining a second difference site on the reads in the eighth read set and a second sequence information determination module configured for correcting the second difference site using the sequencing error prediction model so as to determine second sequence information. Additionally, in claim 29, a computer program product comprising instructions, wherein the instructions cause a computer to execute the method of claim 1 is described, however the specification does not include said instructions. The specification does not demonstrate that applicant has made an invention that achieves the claimed functions because the invention is not described with sufficient detail that one of the ordinary skill in the art can reasonably conclude that the inventor had possession of the claimed invention.
The following is a quotation of 35 U.S.C. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9, 12-18, 21-23 and 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The following claims limitations invoke 35 U.S.C. § 112(f)/sixth paragraph: “a first read set determination module configured for constructing a first read set based on the first sequencing data according to the lengths of the reads”, “a second and third read set determination module configured for constructing a second read set and a third read set based on the first read set according to the lengths of the corresponding reads”, “a fourth and fifth read set determination module configured for constructing a fourth read set and a fifth read set based on the second read set and the corresponding reads thereof according to the sequencing quality of the reads in the second read set and the corresponding reads thereof”, “a sixth read set determination module configured for filtering the fourth read set according to the sequencing quality so as to construct a sixth read set”, “a seventh read set determination module configured for selecting the reads corresponding to the reads in the sixth read set from the fifth read set according to the sixth read set so as to construct a seventh read set”, “a first difference site determination module configured for aligning the reads in the sixth read set with the reads in the seventh read set, and determining a first difference site on the reads in the sixth read set”, “a first sequence information determination module configured for correcting the first difference site using a predetermined sequencing error prediction model so as to determine first sequence information”, “an eighth read set determination module configured for filtering the third read set according to the sequencing quality so as to construct an eighth read set”, “a ninth read set determination module configured for selecting the reads corresponding to the reads in the seventh read set from the second sequencing data according to the eighth read set so as to construct a ninth read set”, “a second difference site determination module configured for aligning the reads in the eighth read set with the reads in the ninth read set, and determining a second difference site on the reads in the eighth read set” and “a second sequence information determination module configured for correcting the second difference site using the sequencing error prediction model so as to determine second sequence information” as well “the instructions cause a computer to execute the method of claim 1”.
The specification is devoid of adequate structure to perform the claimed function. It is noted that the specification does not explicitly disclose how a first read set determination module constructs a first read set based on the first sequencing data according to the lengths of the reads, how a second and third read set determination module constructs a second read set and a third read set based on the first read set according to the lengths of the corresponding reads, how a fourth and fifth read set determination module constructs a fourth read set and a fifth read set based on the second read set and the corresponding reads thereof according to the sequencing quality of the reads in the second read set and the corresponding reads thereof, how a sixth read set determination module filters the fourth read set according to the sequencing quality so as to construct a sixth read set, how a seventh read set determination module selects the reads corresponding to the reads in the sixth read set from the fifth read set according to the sixth read set so as to construct a seventh read set, how a first difference site determination module aligns the reads in the sixth read set with the reads in the seventh read set, and determining a first difference site on the reads in the sixth read set, how a first sequence information determination module corrects the first difference site using a predetermined sequencing error prediction model so as to determine first sequence information, how an eighth read set determination module filters the third read set according to the sequencing quality so as to construct an eighth read set, how a ninth read set determination module selects the reads corresponding to the reads in the seventh read set from the second sequencing data according to the eighth read set so as to construct a ninth read set, how a second difference site determination module aligns the reads in the eighth read set with the reads in the ninth read set, and determining a second difference site on the reads in the eighth read set and how a second sequence information determination module corrects the second difference site using the sequencing error prediction model so as to determine second sequence information as well as how the instructions cause a computer to execute the method of claim 1 when said instructions are not disclosed. The specification does not provide sufficient details such that one of ordinary skill in the art would understand which structure or structures would perform these claimed functions.
Therefore, claims 22-23 and 29 are indefinite, and are rejected under 35 U.S.C. § 112(b)/second paragraph.
Claim 1 is considered vague and indefinite for the following reasons:
Claim 1 recites the limitation "the 3’ end" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claims 2-9, 12-18, 21-23 and 29 depend from claim 1 and are therefore included in this rejection.
Claim 2 is considered vague and indefinite for the following reasons:
Claim 2 recites the limitation "the 3’ end" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 is considered vague and indefinite for the following reasons:
Claim 3 recites the limitation "the 3’ end" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claims 4-8 depend form claim 3 and are therefore included in this rejection.
Claim 4 is considered vague and indefinite for the following reasons:
Claim 4 recites the limitation "the 3’ end" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 the limitation "the complementary strand extended incompletely" in line 6. There is insufficient antecedent basis for this limitation in the claim.
In claim 4, the terms “extended incompletely” are unclear and confusing. It is unclear as to how many bases must be extended for the extension to be considered complete or incomplete?
Claims 5-8 depend from claim 4 and are therefore included in this rejection.
Claim 5 is considered vague and indefinite for the following reasons:
Claim 5 recites the limitation "the 3’ end" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 6-8 depend from claim 5 and are therefore included in this rejection.
Claim 8 is considered vague and indefinite for the following reasons:
Claim 8 recites the limitation "the 3’ end" in lines 2 and 3-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 is considered vague and indefinite for the following reasons:
Claim 12 recites the limitation "the length" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation "the results" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation "the sequence quality" in line 5. There is insufficient antecedent basis for this limitation in the claim.
In claim 12, lines 4 and 5, the term “the reads” are unclear and confusing. It is unclear if the reads is meant to reference the high-quality reads or corresponding reads or both?
In claim 12, the terms “high-quality”, in lines 3 and 7, are unclear and confusing. It is unclear as to what predetermined quality threshold a sequence must be in order to be considered “high” in quality.
Claim 13 is considered vague and indefinite for the following reasons:
Claim 13 recites the limitation "the lengths" and “ the length” in lines 2-3, 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "the probability" in line 29. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "the sequencing quality" in lines 10, 13-14, 20-21 . There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "the same sequencing quality" in line 17. There is insufficient antecedent basis for this limitation in the claim.
In claim 13, lines 3, 5, 15-16 and 17 the term “the reads” are unclear and confusing. It is unclear which reads “the reads” is meant to be referencing?
In claim 13, lines 17-19, the terms “selecting the reads from the second read set as elements of the fourth read set, and selecting the corresponding reads as elements of the fifth read set” are unclear and confusing. It is unclear what is considered to be an element? Is this an additional sequence quality or something else?
In claim 13, lines 20-21, the terms “filtering the fourth read set according to the sequencing quality so as to construct a sixth read set” are unclear and confusing. It is unclear as to how the fourth read set is to be filtered, or said another way what threshold must be reached in order to be considered part of the sixth read set?
In claim 13, lines 23-24, the terms “selecting the reads corresponding to the reads in the sixth read set from the fifth read set according to the sixth read set so as to construct a seventh read set” are unclear and confusing. It is unclear as to how the read sets are to be selected; what metric is being used to group the read sets here?
Claims 14-17 depend from claim 13 and are therefore included in this rejection.
Claim 14 is considered vague and indefinite for the following reasons:
Claim 14 recites the limitation "the sequencing quality" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
In claim 14, lines 20-21, the terms “filtering the third read set according to the sequencing quality to construct an eighth read set” are unclear and confusing. It is unclear as to how the third read set is to be filtered, or said another way what threshold must be reached in order to be considered part of the eighth read set?
In claim 14, lines 5-6, the terms “selecting the reads corresponding to the reads in the seventh read set from the second sequencing data according to the eighth read set so as to construct a ninth read set” are unclear and confusing. It is unclear as to how the read sets are to be selected; what metric is being used to group the read sets here?
Claim 15 is considered vague and indefinite for the following reasons:
Claim 15 recites the limitation "the results" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 is considered vague and indefinite for the following reasons:
Claim 16 recites the limitation "the probability" in lines 4 and 8. There is insufficient antecedent basis for this limitation in the claim.
In claim 16, lines 3-5, 7-9, and 11-13, the terms “the difference site” is unclear and confusing. It is unclear as to which difference site each “the difference site” is referring; the first difference site, the second difference site, or either or any difference site?
Claim 17 is considered vague and indefinite for the following reasons:
In claim 17, the step indicators (a)-(c) are unclear and confusing. Is this referencing the previous step (a)? If so: the step (a) should include “the” before “first predetermined” in line 2. Is step (b), line 4, referring to “the predetermined length range” from step (a-2)? Is step (c), line 5, “the first predetermined quality threshold” referring to the step (a-4) and “the second predetermined quality threshold” of step (a4-a)?
In claim 17, the terms “or any combination of (a)-(c)” in lines 6-7 are unclear and confusing. It is unclear if any first or second predetermined length may be less than 20 bp; or the predetermined length range is 10-25 bp; or the first predetermined quality threshold and the second predetermined quality threshold are each independently not less than 50?
In claim 17, the terms “quality threshold are each independently not less than 50” in lines 5-6 are unclear and confusing. It is unclear as to what the threshold is less than 50 what; is this a percentage, score, matching base pairs or non-matching pairs or something else?
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 17 recites the broad recitation “[the] first predetermined length and the second predetermined length are each independently not less than 20 bp”, and the claim also recites “preferably not less than 25 bp” which is the narrower statement of the range/limitation. Additionally, claim 17 recites “the first predetermined quality threshold and the second predetermined quality threshold are each independently not less than 50” and also recites “preferably not less than 60” which is the narrower statement of the range/limitation.
Claim 21 is considered vague and indefinite for the following reasons:
Claim 21 recites the limitation "the lengths" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 21 recites the limitation "the results" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 21 recites the limitation "the sequencing quality" in line 5. There is insufficient antecedent basis for this limitation in the claim.
In claim 21, lines 4 and 5 the term “the reads” are unclear and confusing. It is unclear which reads “the reads” is meant to be referencing?
In claim 21, the terms “high-quality”, in lines 3 and 6, are unclear and confusing. It is unclear as to what predetermined quality threshold a sequence must be in order to be considered “high” in quality.
Claim 22 is considered vague and indefinite for the following reasons:
Claim 22 recites the limitation "the probability" in line 35. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "the lengths" and “ the length” in lines 4 and 7-9. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "the sequencing quality" in lines 13, 16-17 and 24. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "the same sequencing quality" in lines 20. There is insufficient antecedent basis for this limitation in the claim.
In claim 22, lines 4 and 5 the term “the reads” are unclear and confusing. It is unclear which reads “the reads” is meant to be referencing?
In claim 22, line 35, the terms “the difference site” is unclear and confusing. It is unclear as to which difference site “the difference site” is referring; the first difference site, the second difference site, or either or any difference site?
Claim 23 depends from claim 22 and is therefore included in this rejection.
Claim 23 is considered vague and indefinite for the following reasons:
Claim 23 recites the limitation "the sequencing quality" twice in line 3. There is insufficient antecedent basis for this limitation in the claim.
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 9, 12-18 and 21-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions (i.e., product of nature, a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Every claimed invention must be examined to determine whether the claimed invention complies with 35 U.S.C. 101, particularly whether the claimed invention falls within a 35 U.S.C. 101 judicial exception of non-patentable subject matter (e.g., an abstract idea, law of nature, natural phenomenon, natural product etc.). Phenomena of nature, though just discovered, natural products, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work. See MPEP 2106. As per the “2019 Revised Subject Matter Eligibility Guidance” (Federal Register Vol. 84, No. 4, available 01-07-2019), claims drawn to a process, machine, manufacture or composition of matter are further analyzed according to a two-part process to determine if A) the claim(s) is/are “directed to” a judicial exception because the claims(s) recite(s) a judicial exception (i.e. prong one) that is not integrated into a practical application (i.e. prong two) and, if so, if B) the claim(s) provide(s) an inventive concept, i.e. recite(s) additional elements that amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES
Claims 9, 12-18 and 21-23 are directed to one of the statutory classes. Claims 9 and 12-17 are directed to a method for analyzing sequencing results (Process). Claims 18 and 21-23 are directed towards a system for analysis of sequencing results, comprising a sequencing device (Machine).
Step 2A, Prong One — Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Claims 9, 12-18 and 21-23 recite the abstract ideas of receiving and processing data using mental steps and mathematical concepts. Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection (see MPEP 2106.04). Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include:
• Analyzing sequencing data; comparing a first and second sequencing data set comprised of sequencing reads (mental process, human mind is capable of receiving/ collecting data, observing/evaluating and organizing information)
• Performing mutual correction: selecting high-quality reads and corresponding reads between two sequencing data sets; aligning high quality reads with the corresponding reads (mental process, human mind is capable of receiving/ collecting data, observing/evaluating/organizing information and mathematical relationships).
• Determining read sets based on comparing sequence quality; selecting reads with higher sequencing quality and selecting reads with lower sequencing quality; selecting reads as elements to be included in a specific read set based on sequencing quality (mental process, human mind is capable of receiving/collecting data, observing/evaluating/organizing information/data and mathematical relationships as well as determining a mathematical quantity).
• Filtering read sets based on comparing sequence quality (mental process, human mind is capable of receiving/collecting data, observing/evaluating/organizing information/data and mathematical relationships as well as determining a mathematical quantity).
• Aligning read sets to determining a difference site (mental process, human mind is capable of receiving/ collecting data, observing/evaluating and organizing information).
• Using an error prediction model to determine sequence information as well as determining the probability of an insertion or deletion (mental process, human mind is capable of receiving/collecting data, observing/evaluating/organizing information/data and mathematical relationships as well as determining a mathematical quantity using mathematical calculations).
• Training a naive Bayes Model based on alignment results (Receiving/collecting data, observing/evaluating/organizing information/data, using mathematical relationships as well as determining a mathematical quantity using mathematical calculations).
Therefore, the claims recite elements that constitute one or more judicial exceptions.
Step 2A, Prong Two — Does the Claim Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. However, absent are any additional elements recited in the claim beyond the judicial exceptions which integrate the exception into a practical application of the exception. The “integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
The claim analysis continues with identifying additional elements beyond the judicial exception(s) that might evidence integration of the judicial exception(s) into a practical application. The steps or elements in addition to the judicial exception(s) are: Providing sets of sequencing data and constructing read sets by quality control.
While the claims recite additional elements related to the use of a determination modules, they do not provide any specific details by which the determination modules or computer system, computer monitor, processors, or storage medium performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of these determination modules elements are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a module/computer (see MPEP 2106.05(f)).
These steps, recited at a high level of generality, comprise routine data gathering, which is considered an insignificant extra-solution activity. This data gathering is required for using the judicial exceptions. Thus, a careful evaluation of the claim as a whole failed to reveal the practical application of the judicial exception to, e.g., effect an improvement to the functioning of a computer or other technology/technical field, effect a particular treatment or prophylaxis for a disease or medical treatment, implement a particular machine that is integral to the claim, or effect a transformation or reduction of a particular article to a different state or thing, or to apply the judicial exception in another meaningful way beyond generally linking its use to a particular technological environment. Accordingly, the claims do not integrate the judicial exception(s) into a practical application and is therefore directed to a judicial exception.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to “significantly more” than the judicial exception(s) itself. The claims as a whole are analyzed to determine whether any additional element/step, or combination of additional elements/steps, in addition to the identified judicial exception(s) is sufficient to ensure that the claim amounts to “significantly more” than the exception(s).
The eligibility analysis proceeds with identifying any additional elements or limitations, separate from the judicial exceptions, that might potentially render the claims directed to a judicial exception patent eligible. To render the claims patent- eligible, these elements must comprise meaningful limitations that add to or transform the judicial exception to the effect that it amounts to significantly more than the natural correlation or abstract idea itself - i.e. provide an “inventive concept’. The elements that are in addition to the judicial exception comprise Providing sets of sequencing data and constructing read sets by quality control. When considered separately and in combination, these elements do not add significantly more to the judicial exception. The steps are well-understood, routine and conventional activities in the field. For example, Haghverdi et al. (“Correcting batch effects in single-cell RNA sequencing data by matching mutual nearest neighbors”. Nat Biotechnol 36, 421–427, published April 02, 2018, discloses providing different sets of sequencing data as well as creating batches according to the sequence quality; Price et al. (United States Patent US 12,188,014 B1, published January 07, 2025, effectively filed June 06, 2019), discloses providing sequencing data using a specific sequencing method; as wells Schirmer et al. (“Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform”. Nucleic Acids Res.;43(6):e37, published January 13, 2015), discloses analyzing sequencing data collected from a sequence template on the surface of a chip using adapters to create newly generated strands. The claims recite an abstract idea with additional elements. Because these elements are not inventive concepts, the claims do not integrate the abstract idea into a practical application. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Furthermore, the additional limitations of a computer, determination module, monitor, storage medium or processors are well-understood, routine, conventional computer elements and functions as recognized by the court decisions listed in MPEP § 2106.05(d). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Accordingly, the claims do not qualify as patent-eligible subject matter.
For further information, please see the latest revision of MPEP 2104-2106 {Patent Subject Matter Eligibility Under 35 U.S.C. 101}, including MPEP 2106.04 {Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception} and 2106.05 {Eligibility Step 2B: Whether a Claim Amounts to Significantly More}, as well as the guidance on Subject Matter Eligibility, including the 2019 Guidance issued Jan. 7, 2019, and the October 2019 Update, provided on the USPTO website at https:/Awww.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter- eligibility.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Price et al. (United States Patent US 12,188,014 B1, published January 07, 2025, effectively filed June 06, 2019).
Regarding claim 1, Price teaches a sequencing method (Abstract and Column 6. Lines 30-52). Price teaches comprising performing first sequencing on a sequencing template on a surface of a chip (flow cell) so as to obtain a first sequencing data by forming a first newly generated sequencing strand (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating first and second sequencing data (Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches the sequencing template is ligated to the surface of the chip through an adapter (Column 6, Lines 26-29, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches performing a first blocking on the 3' end of at least a part of the first newly generated sequencing strand (Column 45, Lines 1-30 and Claims 1, 10-13). Price teaches performing a second sequencing on the sequencing template so as to obtain a second sequencing data by forming a second newly generated sequencing strand (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating sequencing data; Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21).
Regarding claim 2, Price teaches removing the first newly generated sequencing strand on the surface of the chip, and performing the first blocking on the 3' end of the first newly generated sequencing strand remaining on the surface of the chip (Column 49, Lines 14-29 and Lines 40-43, Column 42, Line 60—Column 43, Line 19, Column 45, Lines 1-30, Column 47, Lines 39-59).
Regarding claim 3, Price teaches hybridizing a library molecule in a sequencing library with a probe on the surface of the chip (Column 1, Lines 58—Column 2, Line 3, Column 10, Lines 7-9, Column 19, Lines 42-50, Column 33, Lines 27-42, Column 24, Line 1, Column 51, Lines 41-43, Column 20, Lines 5-26). Price teaches forming the sequencing template by synthesizing a complementary strand with the library molecule as an initial template (Column 31, Lines 4-42, and Column 44, Lines 10-29). Price teaches removing the initial template, and performing second blocking on the 3' end of a nucleic acid molecule on the surface of the chip (Column 49, Lines 14-29 and Lines 40-43, Column 42, Line 60—Column 43, Line 19, Column 45, Lines 1-30, Column 47, Lines 39-59).
Regarding claim 4, Price teaches performing a third blocking on the 3' end of the complementary strand extended incompletely (Column , 45, Lines 1-30, Column 47, Lines 39-54, Column 54, Lines 41-51, Column 44, Lines 10-30 and Claim 1).
Regarding claim 5, Price teaches the first blocking, the second blocking and the third blocking are each independently performed by ligating the 3' end hydroxyl group to an extension reaction blocker (Column 19, Lines 18-20, Column 45, Lines 1-30, Column 43, Line 54—Column 44, Line 9, Column 46, Lines 58-66, Column 9, Lines 37-39, column 54, Lines 48-51).
Regarding claim 29, Price teaches computer program product comprising instructions, wherein the instructions cause a computer to execute the method according to claim 1 when the program is executed by the computer (see Claim 1 above, Column 4, Lines 9-20, Column 5, Lines 6-8, Column 51, Line 60—Column 53, Line 4 and Fig. 9).
Price teaches each and every limitation of claims 1-5 and 29 and therefore Price anticipates claims 1-5 and 29.
Claim Rejections - 35 USC § 103
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 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Price et al. (United States Patent US 12,188,014 B1, published January 07, 2025, effectively filed June 06, 2019), as applied to claims 1-5 and 29 above, in view of Kambara et al. (China Patent Application Publication CN1131157, published September 18, 1996), cited on the IDS filed October 28, 2022.
Regarding claim 6, Price teaches an extension reaction as discussed above.
Regarding claim 7, Price teaches the first blocking, the second blocking and the third blocking are each independently performed using at least one of a DNA polymerase and a terminal transferase (Column 31, Lines 9-24, Column 46, Lines 58-66, Column 45, Lines 1-30, Column 45, Line 57—Column 46, Line 7, column 54, Line 66—Column 55, Line 11).
Regarding claim 8, Price teaches the 3' end hydroxyl group, DNA polymerase and terminal transferase as discussed above.
Price does not teach or suggest the extension reaction blocker is ddntp or a derivative thereof. Price does not teach or suggest the first blocking and the third blocking are each independently performed by connecting the 3' end hydroxyl group to the ddNTP or the derivative thereof using a polymerase, and the second blocking is performed by connecting the 3' end hydroxyl group to the ddNTP or the derivative thereof using the terminal transferase.
Kambara teaches sequencing method, comprising performing first sequencing on a sequencing template so as to obtain a first sequencing data by forming a first newly generated sequencing strand and performing a second sequencing on the sequencing template so as to obtain a second sequencing data by forming a second newly generated sequencing strand (i.e., sequencing template is prepared by means of PCR before sequencing, thereby obtaining a template by extending DNA of a first DNA fragment group to the end belonging to the second DNA fragment group and the sequences of DNA groups belonging to the first fragment group and some of adjacent DNA fragments are identified by means of sequencing reaction with a first primer, such that it is possible to identify each DNA fragment connection region by using overlapping sequences, as well as it is ensured that all sequences are efficiently determined by reading sequence information until an overlap occurs at a sequence close to the end of a shorter DNA fragment; Page 3, [0008]—Page 8, [0029]). Kambara teaches performing a first blocking on the 3' end of at least a part of the first newly generated sequencing strand, the first blocking and the third blocking are each independently performed by connecting the 3' end to the ddNTP or the derivative thereof using a polymerase, and the second blocking is performed by connecting the 3' end to the ddNTP or the derivative thereof using the terminal transferase (Page 14, [0057] and Pages 15-16, [0062]). Kambara teaches using the ddntp method provides higher sequencing efficiency (Page 2, [0005]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Price with the teachings of Kambara to use by connecting the 3' end hydroxyl group to the ddNTP or the derivative thereof using a polymerase, and the second blocking is performed by connecting the 3' end hydroxyl group to the ddNTP or the derivative thereof using the terminal transferase. Using the ddntps would allow for a higher sequencing efficiency as taught by Kambara (Page 2, [0005]).
Claims 9, 12, 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Price et al. (United States Patent US 12,188,014 B1, published January 07, 2025, effectively filed June 06, 2019), as applied to claims 1-5 and 29 above, in view of S. Pfeifer et al. (“From next-generation resequencing reads to a high-quality variant data set”. Heredity (Edinb);118(2):111-124, published October 19, 2016).
Regarding claim 9, Price teaches a method for analyzing sequencing results (Column 43, Lines 14-19 and Column 54, Lines 5-6). Price teaches the sequencing results include a first sequencing data and a second sequencing data, wherein the first sequencing data and the second sequencing data are both composed of a plurality of reads, at least a part of the reads in the first sequencing data have corresponding reads in the second sequencing data (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating first and second sequencing data (Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches the first sequencing data and the second sequencing data are obtained by the method according to claim 1 (see Instant Claim 1 above).
Regarding claim 12, Price teaches the first and second sequencing data as discussed above. Price teaches sequencing nucleic sequences with blockers of a predetermined sequence length (Column 48, Lines 9-19).
Regarding claim 18, Price teaches a system for analysis of sequencing results, comprising a sequencing device suitable for obtaining sequencing results by the method according to claim 1 (see Claim 1 above, Column 43, Lines 14-19, Column 54, Lines 5-6, Column 19, Lines 42-61, Column 49, Lines 57-60 and Column 51, Lines 48-67). Price teaches the sequencing results include a first sequencing data and a second sequencing data, the first sequencing data and the second sequencing data are both composed of a plurality of reads (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating first and second sequencing data (Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches at least a part of the reads in the first sequencing data have corresponding sequencing reads in the second sequencing data (Column 6, Lines 43-52).
Regarding claim 21, Price teaches Price teaches the first and second sequencing data as discussed above.
Price does not teach or suggest performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information. Price does not teach or suggest mutual correction comprises the following steps: selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold. Price does not teach or suggest aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning. Price does not teach an analysis device suitable for performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information. Price does not teach or suggest mutual correction comprises the following steps: selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold. Price does not teach or suggest and aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning.
Pfeifer teaches sequencing method for analyzing sequencing results that comprise of a first and second sequencing data (Abstract, Page 111, Right Column Second Paragraph, Page 121, Right Column, Second Paragraph and Page 122, Left Column, Third Paragraph). Pfeifer teaches performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information (Page 114, Left Column, Last Paragraph—Right Column, Third Paragraph and Figs. 1 and 2). Pfeifer teaches mutual correction comprises the following steps: selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold (Page 114, Left Column, Second Paragraph—Right Column, Second Paragraph, Page 121, Left Column Second Paragraph—Right column, First Paragraph and Figs. 1 and 2). Pfeifer teaches aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning (Page 111, Right Column, Second Paragraph, Page 116, Step 2: Alignment—Page 118, Step 3: Alignment Post Processing and Figs. 1 and 2). Pfeifer teaches the sequencing error prediction model is obtained by training a naive Bayes model based on the results of aligning the first sequencing data and the second sequencing data with a reference genome (Page 120, Left Column, Last Paragraph—Right Column, Second Paragraph, Fig. 1 and Table 4). Pfeifer teaches an analysis device suitable for performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information (Page 112, Left Column, Last Paragraph, Page 114, Left Column Last Paragraph—Right Column, Second Paragraph). Pfeifer teaches aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning (Page 114, Left Column, Second Paragraph—Right Column, Second Paragraph, Page 121, Left Column Second Paragraph—Right column, First Paragraph, Page 111, Right Column, Second Paragraph, Page 116, Step 2: Alignment—Page 118, Step 3: Alignment Post Processing and Figs. 1 and 2).
Pfeifer teaches using the quality score with variant calling and filtering steps disclosed improve calling in low coverage regions and improve specificity (Page 118, Right Column, Third Paragraph, Page 119, Left Column, Left Paragraph and Page 120, Left Column, Second Paragraph). Pfeifer teaches wherein the lengths of the reads are not less than a predetermined length (Page 112, Right Column, Second Paragraph, Fig. 2 and Table 1).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Price with the teachings of Pfeifer, using mutual correction that includes selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and perform sequence correction based on the final aligning results to obtain final sequencing information. Using the high-quality score with variant calling and filtering steps disclosed improve calling in low coverage regions and improve specificity as taught by Pfeifer (Page 118, Right Column, Third Paragraph, Page 119, Left Column, Left Paragraph and Page 120, Left Column, Second Paragraph).
Claims 9-18 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Price et al. (United States Patent US 12,188,014 B1, published January 07, 2025, effectively filed June 06, 2019), as applied to claims 1-5 and 29 above, in view of Schirmer et al. (“Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform”. Nucleic Acids Res.;43(6):e37, published January 13, 2015).
Regarding claim 9, Price teaches a method for analyzing sequencing results (Column 43, Lines 14-19 and Column 54, Lines 5-6). Price teaches the sequencing results include a first sequencing data and a second sequencing data, wherein the first sequencing data and the second sequencing data are both composed of a plurality of reads, at least a part of the reads in the first sequencing data have corresponding reads in the second sequencing data (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating first and second sequencing data (Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches the first sequencing data and the second sequencing data are obtained by the method according to claim 1 (see Instant Claim 1 above).
Regarding claim 12, Price teaches the first and second sequencing data as discussed above. Price teaches sequencing nucleic sequences with blockers of a predetermined sequence length (Column 48, Lines 9-19).
Regarding claim 15, Price teaches the first and second sequencing data as discussed above.
Regarding claim 18, Price teaches a system for analysis of sequencing results, comprising a sequencing device suitable for obtaining sequencing results by the method according to claim 1 (see Claim 1 above, Column 43, Lines 14-19, Column 54, Lines 5-6, Column 19, Lines 42-61, Column 49, Lines 57-60 and Column 51, Lines 48-67). Price teaches the sequencing results include a first sequencing data and a second sequencing data, the first sequencing data and the second sequencing data are both composed of a plurality of reads (i.e., a first and second nucleic acid are used to generate a new third nucleic acid as well as amplification products are a newly generated strands, First and/or second from a nucleic acid template and the strands are sequenced creating first and second sequencing data (Column 1, Line 41—Column 2, Line 2, Column 5, Lines 59-63, Column 6, Lines 26-52, Column 9, Lines 8-36, Column 19, Lines 42-61, Column 10, Line 7-9, Column 21, Lines 15-19, Column 43, Lines 14-19, Column 47, Lines 57-59 and 66-67 and Claim 21). Price teaches at least a part of the reads in the first sequencing data have corresponding sequencing reads in the second sequencing data (Column 6, Lines 43-52).
Regarding claims 21-23, Price teaches the first and second sequencing data as discussed above.
Price does not teach or suggest performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information. Price does not teach or suggest mutual correction comprises the following steps: selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold. Price does not teach or suggest aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning. Price does not teach or suggest constructing read sets based on the length of the read. Price does not teach or suggest constructing read sets according quality of the reads or a quality read threshold. Price does not teach or suggest the sequencing error prediction model is used for determining the probability of an insertion or a deletion occurring at a difference site in a sequencing process or using the sequencing error prediction model so as to determine second sequence information. Price does not teach or suggest the sequencing error prediction model is obtained by training a naive Bayes model based on the results of aligning the first sequencing data and the second sequencing data with a reference genome. Price does not teach an analysis device suitable for performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information. Price does not teach or suggest mutual correction comprises the following steps: selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold. Price does not teach or suggest and aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning. Price does not teach or suggest determining a first and second difference site within multiple reads sets. Price does not teach or suggest the probability of a deletion occurring at the difference site is 50% or more, the probability of an insertion occurring at the difference site is 50% or more. Price does not teach or suggest first predetermined length and the second predetermined length are each independently not less than 25 bp. Price does not teach or suggest a determination module that filtering read sets according to quality score of above a quality threshold to determine a first and second difference site, to be used as sequencing data.
Schirmer teaches a sequencing template and generating new strands (first and second) on the surface of a chip (flow cell) using adapters (Page 1, Right Column, First Paragraph and Page 15, Left Column, Fourth Paragraph). Schirmer teaches performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information. Schirmer teaches using error correction to determine data sets for at least 50 different data sets (Figures S7-S9). Schirmer teaches mutual correction comprises selecting high-quality reads and corresponding reads of the high-quality reads in the first sequencing data and the second sequencing data and the sequencing quality of the reads is not less than a predetermined quality threshold (Page 2, Left Column, Last Paragraph, Page 5, Left Column, Second Paragraph—Right Column, First Paragraph, Page 6, Left Column, Second Paragraph—Right Column, First Paragraph, Page 10, Right Column, Second Paragraph and Figs. 3 and 8). Schirmer teaches aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning (Page 2, Left Column, Last Paragraph and Fig. 10). Schirmer teaches constructing read sets based on the predetermined length of the read (Abstract, Page 1, Right Column, First Paragraph, Page 2, Right Column, Last Paragraph, and Page 3, Left Column, Third Paragraph). Schirmer teaches constructing read sets (at least up 40 different groups/read sets) according quality of the reads or a quality read threshold (Page 2, Left Column, Last Paragraph, Page 10, Right Column, Second Paragraph). Schirmer teaches the sequencing error prediction model is used for determining the probability of an insertion or a deletion occurring at a first and second difference site in a sequencing process and using the sequencing error prediction model so as to determine second sequence information (Page 3, Left Column, Third Paragraph). Schirmer teaches the sequencing error prediction model is obtained by training a naive Bayes model based on the results of aligning the first sequencing data and the second sequencing data with a reference genome (Page 2, Left Column, Second Paragraph and Page 10, Right Column, Third Paragraph). Schirmer teaches an analysis device suitable for performing mutual correction based on at least a part of each of the first sequencing data and the second sequencing data so as to obtain final sequence information (Page 2, Left Column, Last Paragraph—Right Column, Last Paragraph and Page 10, Right Column, Third Paragraph). Schirmer teaches aligning the high-quality reads with the corresponding reads of the high-quality reads, and performing sequence information correction based on the results of the aligning (Page 2, Left Column, Last Paragraph, Page 5, Left Column, Second Paragraph—Right Column, First Paragraph, Page 6, Left Column, Second Paragraph—Right Column, First Paragraph, Page 10, Right Column, Second Paragraph and Figs. 3 and 8). Schirmer teaches the probability of a deletion occurring at the difference site is 50% or more, the probability of an insertion occurring at the difference site is 50% or more (Page 6, Left Column, Second Paragraph—Right Column, First Paragraph and Page 10, Right Column, Second Paragraph). Schirmer teaches first predetermined length and the second predetermined length are each independently not less than 25 bp (Abstract, Page 1, Right Column, First Paragraph, Page 2, Right Column, Last Paragraph, and Page 3, Left Column, Third Paragraph). Schirmer teaches grouping higher quality scores and lover quality scores into different read sets (Page 5, Left Column, Last Paragraph). Schirmer teaches a determination module (program) that filtering read sets according to quality score of above a quality threshold to determine a first and second difference site (Page 3, Left Column, Third Paragraph, Page 6, Left Column, Second Paragraph—Right Column, First Paragraph and Page 10, Right Column, Second Paragraph). Schirmer teaches being able to infer error profiles for individual sequencing runs greatly improves the ability correct errors and thus enhance sequencing analysis (Page 2, Left Column, Second Paragraph).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Price with the teachings of Schirmer, grouping/constructing data sets (for at least a first through ninth reads sets) based on a quality score and a predetermined threshold, as well as according to length of a predetermined length and according a first or second difference site, also using mutual correction and an error prediction models. This would allow one to create predicted error profiles for individual sequencing runs which would greatly improve the ability correct errors and thus enhance sequencing analysis as taught by Schirmer (Page 2, Left Column, Second Paragraph).
Conclusion
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/JESSICA D PARISI/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684
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