Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-10 are pending.
Claims 1-10 are rejected.
Priority
The instant application filed 19 January 2023 claims priority to PCT/JP2021/027331 filed 21 July 2-21 and JP2020-125563 filed 22 July 2020. As such, the effective filing date of claims 1-10 is 22 July 2020.
Information Disclosure Statement
All IDS documents were considered by the examiner.
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/PatentLegalFramework), 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 - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Paragraphs [0080] and [0081]include enumerated nucleotide sequences without providing sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Abstract
There are two documents labeled as an abstract in the application contents. One is an abstract and the other appears to be an alternate patent application. The applicant should indicate which was intended as the abstract for the instant application.
Specification
The disclosure is objected to because of the following informalities:
A substitute specification excluding the claims is required pursuant to 37 CFR 1.125(a) because paragraphs [0080] and [0081]include enumerated nucleotide sequences without providing sequence identifiers (see above).
Appropriate correction is required.
A substitute specification must not contain new matter. The substitute specification must be submitted with markings showing all the changes relative to the immediate prior version of the specification of record. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. An accompanying clean version (without markings) and a statement that the substitute specification contains no new matter must also be supplied. Numbering the paragraphs of the specification of record is not considered a change that must be shown.
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” 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 limitation(s) is/are:
acquisition unit: in claims 1, 2, 7, and 8
extraction unit: in claims 1, 2, 7, and 8
separation unit: in claims 1, 2, 7, 8, and 9
learning unit: in claims 1, 2, 3, 4, 7, and 8
prediction unit: in claims 1, 2, 7, and 8
sampling unit: in claim 3
feature value addition and selection unit: in claim 4.
In review of the claims and specification, the functions of these units are not necessarily tied to any specific type of device. The limitations appear to be instructions with no specific guidelines as to how to implement these instructions.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/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 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, 2, 7, 8, 9, and 10 and dependent claims 3-6 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The above-mentioned independent claims include the phrase “extracts contexts in which a mutation…occurs or has occurred.” This language is unclear regarding the status of the mutation. The examiner is interpreting this as “has occurred.”
Claim limitations “acquisition unit,” “extraction unit,” “separation unit,” “learning unit,” “prediction unit,” “sampling unit,” and “feature value and addition unit” invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. These “units” are all part of the claimed device, method, or program for predicting viral mutations. Neither the claims not the specification provide clear structure as to how these units are intended to function. In some cases, there is exemplary language referencing algorithms and generic computing devices. However, the specification lacks any specific instructions as to how to accomplish the tasks through the above listed units. The examiner is interpreting these units as any computing element. “When examining computer-implemented functional claims, examiners should determine whether the specification discloses the computer and the algorithm (e.g., the necessary steps and/or flowcharts) that perform the claimed function in sufficient detail such that one of ordinary skill in the art can reasonably conclude that the inventor possessed the claimed subject matter at the time of filing.” (MPEP 2161.01(I)) Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
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 1-4 and 7-10, and dependent claims 5-6, 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. As indicated above, the claims reference a number of “units” without clear description of how these units function. A review of the specification fails to find explicit instructions or guidelines for these “units.”
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 1-10 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to abstract ideas without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step
1: YES) are then analyzed to determine if the claims recite any concepts that equate to an
abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application,
the claims recite the following limitations that equate to abstract ideas:
Claim 1, and dependent claims 3 - 6, claim 7, and claim 9 recite:
an acquisition unit which acquires a gene sequence,
an extraction unit which extracts cytosine or guanine and extracts contexts with a mutation
a separation unit which checks for an amino acid mutation
a learning unit which learns the sequence data
a prediction unit which predicts a mutation
Claim 2, claim 8, and claim 10 recite:
an acquisition unit which acquires a gene sequence,
an extraction unit which extracts cytosine, guanine, adenine, uracil, or thymine and extracts contexts with a mutation
a separation unit which checks for an amino acid mutation
a learning unit which learns the sequence data
a prediction unit which predicts a mutation
Claim 3 recites:
a sampling unit which selects a predetermined number of synonymous substitutions
the learning unit uses the sequence data of synonymous substitutions
Claim 4 recites:
A feature value addition and selection unit which adds a feature value
The learning unit uses the feature value
The limitations for the listed claims are evaluations or judgements that can be made through mental observations or mathematical calculations which fall under the “mental processes” and “mathematical concepts” groupings of abstract ideas. Under the broadest reasonable interpretation, the abstract ideas recited in the claims are determined to cover performance either in the mind (calculations by hand or pen and paper) or by mathematical operation (calculations/algorithms). See MPEP § 2106.04(a)(2), subsection III. 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."); Synopsys, Inc. V. Mentor Graphics Corp., 839 F.3d 1138, 1139, 120 USPQ2d 1473, 1474 (Fed. Cir. 2016): holding that claims to a mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper"). 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" (see Versata Dev. Group V. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015); Mortgage Grader, Inc. v. First Choice 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").
While claims 9 and 10 recite performing aspects of the methods with a “program”, there are no additional limitations that indicate that this program would require anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation on generic computer components, then it falls into the “mental processes” grouping of abstract ideas. As such, claims 1-20 recite abstract ideas (Step 2A, Prong 1: YES).
Step 2A, Prong 2
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further
analyzed to determine if the claims as a whole integrate the recited judicial exception into a
practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a
practical application because the claims do not recite an additional element that reflects an
improvement to technology or applies or uses the recited judicial exception in some other
meaningful way. Rather, the instant claims recite additional elements that amount to mere
instructions to implement the abstract idea or insignificant extra-solution activity. Specifically,
the claims recite the following additional elements:
Claims 4 recites specific limitations regarding the range of contexts as -3 to +3 or more and -10 to +10 or less
Claim 5 recites a limitation to the virus SARS-CoV-2
Claims 9 and 10 recite a program.
The limitations for defining terms describe mental processes with additional elements. This judicial exception is not integrated into a practical application because these additional
elements do not add any meaningful limitations. The claims do not include additional elements
that are sufficient to amount to significantly more than the judicial exception because they only
describe more specificity to the types of variables. As such, these limitations equate to mere
instructions to implement the abstract ideas.
There are no limitations that indicate that the program would require anything other than a generic computing system. As such, these limitations equate to mere instructions to implement the abstract ideas on a generic computer that the courts have stated do not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
The above recited additional elements do not provide a practical application of the recited
judicial exception. As such, claims 1-20 are directed to an abstract idea (Step 2A, Prong 2:NO).
Step 2B
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere definitions of terms and to mere instructions to apply the recited exception in a generic computing environment.
As discussed above, there are no additional limitations to indicate that the claimed
method requires more than defining terminology. Additionally, there are no additional limitations to indicate that the program requires anything other than generic computer components in order to carry out the recited abstract ideas in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. In addition, mere display of collected and analyzed information that could be performed by the human mind do not render an abstract idea eligible. See Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016)
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-10 are not patent eligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 7, and dependent claims 3-6, are rejected under 35 U.S.C. 103 as being unpatentable over Salama et al. (IDS filed on 1/19/2023, reference NPL No 5) in view of You (TW201741462A, 30 May 2016) and Matyasek and Kovarik (Genes, 7 July 2020, pages 1-13). (Herein referred to as Salama, You, and Matyasek, respectively.)
Salama teaches in “which each iteration the input is an RNA sequence of one generation of the virus.” (Page 2, left column, lines 41-2) Salama further teaches “RNA sequences observed over a period of time… was collected and presented in previous research…preprocessing is started by the alignment of RNA sequence for the purpose of predicting the evolution of the virus based on the gathered sequences. The steps performed are the mining and learning the rules of the virus mutation, in order to predict the mutations.” (Page 4, left column, lines 28-30 and 35-40) Salama discloses “Machine learning techniques help predict the effects of non-synonymous single nucleotide polymorphisms on protein stability, function and drug resistance.” (Page 2, left column, lines 9-11) Salama further discloses “Neural networks technique can be used to predict different mutations in RNA sequences.” (Page 4, right column, lines 23-4) Salama teaches a “proposed a new algorithm for solving the evolution prediction problem that is based on the input time series data set.” (Page 5, left column, lines 16-17)
Salama does not explicitly teach “an extraction unit which extracts C (cytosine) or G (guanine) from the acquired gene sequence data of the genome and extracts contexts in which a mutation from C or G to U (uracil) occurs or has occurred” or “a separation unit which checks whether there is an amino acid mutation when C or G has changed to U and which separates sequences with the amino acid mutation as nonsynonymous substitutions and separates sequences without the amino acid mutation as synonymous substitutions.”
You teaches methods for finding and screening molecular markers, including quantitative molecular markers. [0018] You further teaches using a variety of bioinformatics software to find, extract, and analyze contexts. [0030] You additionally teaches using NGS deep sequencing and cumulative variation analysis tests, which can be used to identify synonymous and nonsynonymous substitutions. [0032]
Matyasek teaches regarding “the frequency of mutations in SARS-CoV-2 (MN908947), using the bat RATG13 (MN996532.1) as a reference…the C>U and reverse U>C transitions were by far the most frequent mutations, accounting for 60% of all SNVs.” (Page 3, Section 3.1, lines 1-2 and 10-11) Matyasek further teaches “Each SNV was further analyzed to see whether it does (nonsynonymous mutation) or does not (synonymous mutation) change the amino acid sequence (Table S5). Out of the 27 C>U substitutions, 14 (52%) were nonsynonymous, 11 (41%) were synonymous, and two (7%) occurred in untranslated regions…[and] [c]ompared to other substitutions, the replacement of C with U nucleotides significantly elevated the frequency of hydrophobic codons.” (Page 5, lines 13-16 and 18-19) Matyasek discloses, regarding spike proteins, “the number of synonymous (silent) and nonsynonymous substitutions was nearly the same, while synonymous substitutions dominated in the rest of the protein. The proportion of C>U and U>C transitions relative to other substitutions was 2:3, reflecting the genome average. Their frequency in nonsynonymous sites was relatively low.” (Page 6, lines 7-11)
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the viral mutation prediction methods of Salama to the methods You and the research of Matyasek. Salama teaches that “[v]iral evolution remains to be a main obstacle in the effectiveness of antiviral treatments. The ability to predict this evolution will help in the early detection of drug-resistant strains and will potentially facilitate the design of more efficient antiviral treatments. Various tools has been utilized in genome studies to achieve this goal. One of these tools is machine learning.” (Abstract, lines 1-4) You teaches “In recent years, due to the frequent influence of globalization and international exchanges, the global public health system is facing the major challenge of the rapid spread and spread of emerging infectious diseases. It is necessary to construct a comprehensive epidemic prevention medical network, including monitoring of epidemic situation, rapid diagnosis methods, introduction of vaccines and drugs, and research and development, etc., through close cooperation between basic academic, clinical research, government policies and the medical biotechnology industry.” [0002] Matyasek teaches “[t]he pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure …[and] [t]he data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus.” (Abstract, lines 1-2 and 11-12) Therefore, one of ordinary skill in the art would have been motivated to combine the virus mutation prediction methods of Salama and You with the specific virus data of Matyasek. It would have been obvious to use the context extraction and analysis methods of Salama and You to look specifically for the mutations identified by Matyasek as being most significant. Additionally, it would have been obvious to incorporate the learning and prediction methods of Salama with the data of Matyasek to address the urgent SARS-CoV-2 pandemic-related needs for treatment and prevention options. The invention is therefore prima facie obvious.
Claims 2 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Salama in view of You and Matyasek. Salama teaches in “which each iteration the input is an RNA sequence of one generation of the virus.” (Page 2, left column, lines 41-2) Salama further teaches “RNA sequences observed over a period of time… was collected and presented in previous research…preprocessing is started by the alignment of RNA sequence for the purpose of predicting the evolution of the virus based on the gathered sequences. The steps performed are the mining and learning the rules of the virus mutation, in order to predict the mutations.” (Page 4, left column, lines 28-30 and 35-40) Salama discloses “Machine learning techniques help predict the effects of non-synonymous single nucleotide polymorphisms on protein stability, function and drug resistance.” (Page 2, left column, lines 9-11) Salama further discloses “Neural networks technique can be used to predict different mutations in RNA sequences.” (Page 4, right column, lines 23-4) Salama teaches a “proposed a new algorithm for solving the evolution prediction problem that is based on the input time series data set.” (Page 5, left column, lines 16-17)
Salama does not explicitly teach “an extraction unit which extracts C (cytosine), G (guanine), A (adenine), U (uracil) or T (thymine) from the acquired gene sequence data of the genome and extracts contexts in which a mutation from G to A, from A to G, from U to C or from T to C occurs or has occurred, a separation unit which checks whether there is an amino acid mutation when the base sequences of the extracted contexts have changed and which separates sequences with the amino acid mutation as nonsynonymous substitutions and separates sequences without the amino acid mutation as synonymous substitutions.”
You teaches methods for finding and screening molecular markers, including quantitative molecular markers. [0018] You further teaches using a variety of bioinformatics software to find, extract, and analyze contexts. [0030] You additionally teaches using NGS deep sequencing and cumulative variation analysis tests, which can be used to identify synonymous and nonsynonymous substitutions. [0032]
Matyasek teaches regarding “the frequency of mutations in SARS-CoV-2 (MN908947), using the bat RATG13 (MN996532.1) as a reference…the C>U and reverse U>C transitions were by far the most frequent mutations, accounting for 60% of all SNVs. The G>A and reverse A>G transitions were the next most abundant, though their frequency was substantially lower (23%).” (Page 3, Section 3.1, lines 1-2 and 10-12) Matyasek further teaches “[e]ach SNV was further analyzed to see whether it does (nonsynonymous mutation) or does not (synonymous mutation) change the amino acid sequence (Table S5).” (Page 5, lines 13-14) Matyasek discloses in Table S5 a list of nucleotide substitutions and their characteristics. This table includes G to A, A to G, U to C, and C to U mutations and indicates whether these are synonymous or nonsynonymous substitutions.
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the viral mutation prediction methods of Salama to the methods of You and the research of Matyasek. Salama teaches that “[v]iral evolution remains to be a main obstacle in the effectiveness of antiviral treatments. The ability to predict this evolution will help in the early detection of drug-resistant strains and will potentially facilitate the design of more efficient antiviral treatments. Various tools has been utilized in genome studies to achieve this goal. One of these tools is machine learning.” (Abstract, lines 1-4) You teaches “In recent years, due to the frequent influence of globalization and international exchanges, the global public health system is facing the major challenge of the rapid spread and spread of emerging infectious diseases. It is necessary to construct a comprehensive epidemic prevention medical network, including monitoring of epidemic situation, rapid diagnosis methods, introduction of vaccines and drugs, and research and development, etc., through close cooperation between basic academic, clinical research, government policies and the medical biotechnology industry.” [0002] Matyasek teaches “[t]he pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure …[and] [t]he data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus.” (Abstract, lines 1-2 and 11-12) Therefore, one of ordinary skill in the art would have been motivated to combine the virus mutation prediction methods of Salama and You with the specific virus data of Matyasek. It would have been obvious to use the context extraction and analysis methods of Salama and You to look specifically for the mutations identified by Matyasek as being most significant. Additionally, it would have been obvious to incorporate the learning and prediction methods of Salama with the data of Matyasek to address the urgent SARS-CoV-2 pandemic-related needs for treatment and prevention options. The invention is therefore prima facie obvious.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Salama, You, and Matyasek as applied to claim 1 above, and further in view of You.
Salama and Matyasek do not explicitly teach “a sampling unit which selects a predetermined number of synonymous substitutions from the synonymous substitutions, wherein the learning unit uses the sequence data of the synonymous substitutions selected by the sampling unit for learning data.”
You teaches tracking specific sites on the HA gene and specifically looking at nucleotide mutations at those sites. [0038-0043]
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the viral mutation prediction methods of Salama and You and the research of Matyasek to the further specific methods of You to sample a subset of contexts with mutations. You teaches that “the method of the present invention can detect early changes in important sites of the virus and potential crises that may increase pathogenicity and spread, and the integration of these quantitative data will establish a rapid screening virus-related variability group for future avian influenza epidemic prevention work. The method of molecular marker change, and other infectious pathogens, such as dengue virus and rabies virus, can also be used to develop digital PCR detection technology to improve the domestic response to infectious diseases.” [0048] Additionally, Matyasek teaches “[p]reviously, six amino acid residues have been identified that appear to be critical for the virus interaction with the ACE2 receptor (boxes in Figure 4b). Out of these, five residues (Leu486Phe, Tyr493Gln, Arg494Ser, Asp501Asn, and His505Tyr) differed between RaTG13 and SARS-CoV-2. In the altered codons, the frequency of nonsynonymous C>U and U>C substitutions was relatively high (Figure 4d).” (Page 6, lines 11-15) Therefore, one of ordinary skill in the art would have been motivated to combine the virus mutation prediction methods of Salama and You and the virus data of Matyasek to focus on specific synonymous substitutions. Given that certain substitutions have potential to have a greater effect on the virus, as described above, it would be obvious to combine these methods to improve the likelihood of identifying significant mutations. The invention is therefore prima facie obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Salama, You, and Matyasek as applied to claim 1 above, and further in view of Salama.
You and Matyasek do not explicitly teach “ a feature value addition and selection unit which adds a feature value that is a value characterized by selecting two bases from the four kinds of RNA bases, A (adenine), U, G and C, and that is used for learning, wherein the learning unit also uses the feature value for learning data.”
Salama teaches “[e]very feature in the input is a nucleotide in the RNA sequence corresponds to a feature in the output. The training of the machine learning technique is fed with aligned RNA sequences of successive generations of the same RNA viruses that exhibited similar environmental conditions. The technique introduced in this paper predicts the last RNA sequence based on the previous RNA generation sequence.” (Page 2, left column, lines 44-50) Salama additionally teaches the “preprocessing step includes the feature selection which is important in decreasing the processing cost by the removal unnecessary nucleotides.” (Page 4, right column, lines 8-10)
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the viral mutation prediction methods of Salama and You and the research of Matyasek to the further specific methods of Salama. As described above, certain nucleotide substitutions are more common and more impactful in the viral genome. Therefore, one of ordinary skill in the art would have been motivated to combine the virus mutation prediction methods of Salama and You and the virus data of Matyasek to focus on specific RNA bases. Given that certain substitutions have potential to have a greater effect on the virus, as described above, it would be obvious to combine these methods to improve the likelihood of identifying significant mutations. The invention is therefore prima facie obvious.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Salama, You, and Matyasek as applied to claim 1 above, and further in view of Salama and Wright et al. (bioRxiv, 26 May 2020, pages 1-17) (Herein referred to as Wright.)
You and Matyasek do not explicitly teach “the range of the contexts is -3 to +3 or more and -10 to +10 or less.”
In Figures 1-3, Salama further teaches ranges of contexts within the limitations indicated in claim 5. (Pages 5 and 6) Wright et al teaches research on the evolution of the SARS-CoV-2 genome, specifically in studying certain nucleotide substitutions. Wright discloses, regarding “two substitutions with more than 30 cases of parallelism across SARS-CoV-2 genomes,” that “[t]he substitution at 11,083 occurred nearby another frequent substitution at position 11,074 that is synonymous. Both substitutions were conversions to uracil at sites adjacent to eight consecutive uracils in the genome The substitution at 11,083 occurred nearby another frequent substitution at position 11,074 that is synonymous. Both substitutions were conversions to uracil at sites adjacent to eight consecutive uracils in the genome (Fig. 3), suggesting they may occur more frequently due to an increased mutation rate at homopolymeric sites. A similar conversion to uracil at position 21,575 is located in the middle of 7 other uracils and results in a non-synonymous change (L5F) to the protein sequence of S (Fig. 3). Three other substitutions were adjacent to at least 3 uracils in the genome: positions 9,474, 26,681, and 28,253.” (Page 7, lines 113-114 and 117-123)
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the viral mutation prediction methods of Salama and You and the research of Matyasek to the further specific methods of Salama and the research of Wright. Regarding the above-described mutation patterns, Wright discloses “[t]he high frequency of substitutions next to poly(U) tracts is likely due to increased mutation rates at these positions, although we cannot rule out that they may also have adaptive significance.” (Page 7, lines 123-125) Given that Wright observed frequent synonymous mutations in contexts within the range of those indicated in the claim, it would have been obvious to apply viral mutation prediction methods on contexts of specific lengths. Therefore, one of ordinary skill in the art would have been motivated to combine the virus mutation prediction methods of Salama and You and the virus data of Matyasek with the teachings of Wright to focus on contexts of a specific range. The invention is therefore prima facie obvious.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Salama in view of Pathan et al. (Chaos, Solitons, and Fractals, 13 June 2020, pages 1-7) (Herein referred to as Pathan.) Salama teaches the acquisition, extraction, separation, learning, and prediction units as indicated above.
Salama does not teach that the virus is SARS-CoV-2.
Pathan teaches “SARS-CoV-2, a novel coronavirus mostly known as COVID-19 has created a global pandemic…[and] [a] recurrent neural network-based Long Short Term Memory (LSTM) model has been applied to predict the future mutation rate of this virus.” (Abstract)
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have applied the method of Salama to predict viral mutations with the method of Pathan. Salama states “[v]iral evolution remains to be a main obstacle in the effectiveness of antiviral treatments. The ability to predict this evolution will help in the early detection of drug-resistant strains and will potentially facilitate the design of more efficient antiviral treatments. Various tools has been utilized in genome studies to achieve this goal. One of these tools is machine learning, which facilitates the study of structure-activity relationships, secondary and tertiary structure evolution prediction, and sequence error correction.” (Abstract) Salama further states their “work paves the way to a new horizon where the prediction of the mutations such as virus evolution, is possible. It can assist the designing of new drugs for possible drug-resistant strains of the virus before a possible outbreak.” (Page 10, Conclusion) Pathan states that at the time of publication, the “whole world is suffering by an ongoing pandemic due to Coronavirus disease brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).” (Page 1, lines 1-3) Pathan further states regarding SARS-CoV-2 at the time of publication that “the mutation power cannot be controlled till now as no reliable vaccine has invented yet.” (Page 7, left column, lines 21-22) Therefore, one of ordinary skill in the art would have been motivated to incorporate the viral mutation prediction methods of Salama with the study of SARS-CoV-2 of Pathan. It would have been obvious to try a prediction method known to work in RNA viruses on another RNA virus. And given the events at the time of the instant application, it would have been obvious to specifically apply a known mutation prediction method to SARS-CoV-2 in an attempt to develop control and treatment options during the pandemic declared in 2020. The invention is therefore prima facie obvious.
Claims 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Salama, You, and Matyasek as applied to claims 1 and 2 above, and further in view of Keskin et al. (US20210382068A1, 2 October 2019) (Herein referred to as Keskin.)
Salama, You, and Matyasek do not explicitly teach a “program that is executed in a viral mutation prediction device that includes: a computing machine.”
Keskin teaches a “computer-implemented method for generating and using a trained prediction model…[and] using one or more computer processors.” (Claims 10, 12, 31, 32, 47, and 51) Keskin further teaches use of genome sequence data, contexts with mutations, determining non-silent somatic mutations, and predictions using machine learning models.(Claims 44 and 10, and Abstract and [0563])
It would have been prima facie obvious to one of ordinary skill in the art at the effective
filing date of the invention to have used the method of Keskin with the nonfunctional parameters as set forth herein. The rationale can further be taken from the case law listed below that reinforces that the claims recite nothing more than a known system and method for displaying the recitation of parameters and/or data that are manipulated in the system and the method provides only non-functional descriptive material such that the claim cannot be distinguished over the systems and methods of the prior art. See In re Gulack (217 USPQ 401 (Fed. Cir. 1983), In re Lowry (32 USPQ2d 1031 (Fed. Cir. 1994), In re Ngai (70 USPQ2d 1862 (Fed. Cir. 2004) and King Pharmaceuticals Inc. v. Eon Labs Inc., 95 USPQ2d 1833 (Fed. Cir. 2010). In the instant claims, the program and computing machine do not impose a change to the system itself. (Note that the claims contain intended use language of "to acquire", "to extract", “to check”, “to learn”, and “to predict”.) When there is no functional relationship between matter and a substrate there is no reason to give patentable weight to the content. (See MPEP § 2111.05.) The invention is therefore prima facie obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Yin et al teaches a method to predict mutations of influenza A viruses. (Bioinformatics, 30 January 2020, pages 2697-2704) Rad and McLellan teach impacts of SARS-CoV-2 mutations on RNA secondary structure. (International Journal of Molecular Sciences, 7 July 2020, 1-18) Butt, et al teaches mutation prediction of Newcastle virus genotypes. (bioRxiv, 17 June 2018, pages 1-32)
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/S.L.G./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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