DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
1. Applicant’s election without traverse of Species B, claims 23 and 25 in the reply filed on October 19, 2025 is acknowledged.
Claims 22, 24, and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Status of the Claims
Claims 21, 23, 25-27, and 29-33 are under examination.
Claim Rejections - 35 USC § 101
2. 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 21, 23, 25-27, and 29-33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
3. Claims 21, 23, 25-27, and 29-31 are directed to method of identifying a somatic mutation. As described in Alice Corp. Pty. Ltd. V. CLS Bank Int’l, 573 U.S._, 134 S. Cr. 2347, 110 U.S.P.Q.2d 1976 (2014), a two-step analysis is required in considering the patent eligibility of the claimed subject matter. The first step requires determining if the claimed subject matter is directed to a judicial exception. Independent claim 21 requires the steps of identifying a variant in a first sequence information, determining a variant in a second sequence information, calculating a likelihood that a variant is present in the second sequence information is due to sequencing error, determining first and second coverage levels of a position corresponding to the variant in the first and second sequence information, and identifying the variant as a somatic mutation when the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold. The steps of identifying a variant in a first sequence information, determining a variant in a second sequence information, determining first and second coverage levels of a position corresponding to the variant in the first and second sequence information, and identifying the variant as a somatic mutation when the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold are drawn to mental steps. The step of calculating a likelihood that a variant is present in the second sequence information is due to sequencing error is drawn to a mathematical algorithm. Dependent claims 23, 25-27, and 29-31 recite additional mathematical or mental steps. Mental steps are a judicial exception. The courts have found mathematical algorithms to be drawn to the judicial exception of an abstract idea (In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)). Thus, the instant claims are drawn to a judicial exception.
This judicial exception is not integrated into a practical application. The instant claims do not recite an element that reflects an improvement in the functioning of a computer or other technology, an element that applies the judicial exception to effect a particular treatment, an element that implements the judicial exception with a particular machine, or an element that effects a transformation of a particular article to a different state or thing. While the instant claims recite the use of a processor, machine readable storage medium, and sequence analysis device, the instant claims do not recite any particular limitations of these elements. Thus, the instant claims do not recite a particular machine, and the judicial exception is not integrated into a practical application. The instant claims also recite a receiving a first and second sequence information. However, receiving information is extra solution activity. Extra solution activity does not provide a practical application that integrates the judicial exception.
The second part of the analysis requires determining if the claims include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant claims recite the additional elements of a processor, machine readable storage medium, and sequence analysis device. However, a processor, machine readable storage medium, and sequence analysis device are a well-understood, routine, and conventional devices for implementing an abstract idea (Specification, pages 7-11). The instant claims also recite receiving a first and second sequence information. However, receiving information is a well-understood, conventional, and routine data gathering step (MPEP §2106.05(d)(II)). Reciting such well-understood, routine, and conventional elements do not transform a judicial exception into patent eligible subject matter. In addition, the recitation of the specific types of data to be used in the judicial exception does not transform the abstract idea into a non-abstract idea. (See buySAFE, Inc. v Google, Inc. 765 F.3d 1350, 112 U.S.P.Q.2d 1093 (Fed.Cir.2014)). Furthermore, the elements taken as a combination are also well-understood, routine, and conventional, since the elements are merely specifying a general device for implementing the judicial exception. Thus, the instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
4. Claims 32 and 33 are directed to method of identifying a somatic mutation. As described in Alice Corp. Pty. Ltd. V. CLS Bank Int’l, 573 U.S._, 134 S. Cr. 2347, 110 U.S.P.Q.2d 1976 (2014), a two-step analysis is required in considering the patent eligibility of the claimed subject matter. The first step requires determining if the claimed subject matter is directed to a judicial exception. The instant claim requires classifying reading corresponding to the first nucleic acid sample as a first sequence information, classifying reads corresponding to the second nucleic acid sample, identifying a variant in the first sequence information, determining the variant is present in the second sequence information, calculating when the variant is present in the second sequence information a likelihood the variant is present in the second sequence information above an expected error rate, identifying the variant as a somatic mutation when the likelihood is below a threshold. However, the steps of classifying and calculating are a mathematical algorithm. The steps of identifying and determining are drawn to mental steps. Mental steps are a judicial exception. The courts have found mathematical algorithms to be drawn to the judicial exception of an abstract idea (In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)). Thus, the instant claims are drawn to a judicial exception.
This judicial exception is not integrated into a practical application. The instant claims do not recite an element that reflects an improvement in the functioning of a computer or other technology, an element that applies the judicial exception to effect a particular treatment, an element that implements the judicial exception with a particular machine, or an element that effects a transformation of a particular article to a different state or thing. The instant claims recite the attaching adapters with barcode sequences to classify the nucleic acid samples and then sequencing the nucleic acid samples. However, this is a step of data gathering which is an extra-solution activity that does not impart a practical application to the judicial exception.
The second part of the analysis requires determining if the claims include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant claims recite the additional element of an adapter including a barcode sequence and sequencing the nucleic acid samples.. However, labeling nucleic acid sequences for the purpose of detecting the nucleic acid sequence and sequencing nucleic acid samples are well-understood, routine, and conventional methods (Specification, pages 12-16 and 19). Reciting such well-understood, routine, and conventional method do not transform a judicial exception into patent eligible subject matter. In addition, the recitation of the specific types of data to be used in the judicial exception does not transform the abstract idea into a non-abstract idea. (See buySAFE, Inc. v Google, Inc. 765 F.3d 1350, 112 U.S.P.Q.2d 1093 (Fed.Cir.2014)). Furthermore, the elements taken as a combination are also well-understood, routine, and conventional, since the elements are a method of detecting the nucleic acid sequences. Thus, the instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 102
5. 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 pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claims 21, 23, 25-27, and 29 are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Li (“A Statistical Framework for SNP Calling, Mutation Discovery, Association Mapping and Population Genetical Parameter Estimation from Sequencing Data” Bioinformatics (2011) volume 27, number 21, pages 2987-2993).
The instant claims include a step of “determining if the variant is present in the second sequence information”. As written, this step is a contingent limitation. According the MPEP §2111.04 (II), “The broadest reasonable interpretation of a system (or apparatus or product) claim having structure that performs a function, which only needs to occur if a condition precedent is met, requires structure for performing the function should the condition occur. The system claim interpretation differs from a method claim interpretation because the claimed structure must be present in the system regardless of whether the condition is met and the function is actually performed.” It is noted that claims 23, 25-27 and 29 are also drawn to contingent limitations.
Li teaches a system that includes receiving a first and second sequence information from a NGS assay (page 2992, under “Comparing sequencing data from the same individual”), identifying a variant in a first sequence information (page 2992, under “3.5 Comparing sequencing data from the same individual”); determining if the variant is present in a second sequence information (i.e. from a normal-tumor pair) (page 2990, under “2.4 Discovering somatic and germline mutations”); calculating a likelihood that the variant is present in the second sequence information and if the variant in the second sequence information is due to error (page 2988, under “Computing genotype likelihoods”; page 2992, under “3.5 Comparing sequencing data from the same individual”); determining first and scone coverage levels corresponding to the variant in the first and second sequence information (page 2991, right column, under “3.3 Inferring the AFS”), and identifying the variant as a somatic mutation (page 2990, under “2.4 Discovering somatic and germline mutations”; and page 2992, under 3.5 “Comparing sequencing data from the same individual”). Furthermore, Li teaches implementing their method using software, which would include computer readable storage medium and a structure that may perform the function should the condition occur. (page 2990, under “3 Results”.)
Claim Rejections - 35 USC § 103
6. 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 30-33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Li (“A Statistical Framework for SNP Calling, Mutation Discovery, Association Mapping and Population Genetical Parameter Estimation from Sequencing Data” Bioinformatics (2011) volume 27, number 21, pages 2987-2993) as applied to claims 21, 23, 25-27, and 29 above, further in view of Xie et al. (US 2014/0155274 A1).
The instant claims 32 and 33 include a step of “determining if the variant is present in the second sequence information”. As written, this step is a contingent limitation. According the MPEP §2111.04 (II), “The broadest reasonable interpretation of a method (or process) having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. In this instance, the instant claims requires attaching an adapter with a barcode sequence to a nucleic acid sample, sequencing the nucleic acid samples, classifying the reads corresponding to the samples, and identifying a variant in the first sequence information.
Li is applied as above.
However, Li does not teach using a barcode.
Regarding claims 30 and 31, Xie et al. teach where the barcode is associated with a first sample and where a barcode is associated with a second sample (paragraph [0088]); and classifying the sequencing reads as corresponding to a first or second sample according to the barcode sequence (paragraph [0088]).
Regarding claims 32 and 33, while Li teaches identifying a variant, where the first nucleic acid sample comprises a tumor sample and the second nucleic acid sample comprises a non-tumor sample (“page 2990, under “2.4 Discovering somatic and germline mutations”).
Li does not teach an adapter with a barcode.
Regarding claims 32 and 33, Xie et al. teach a method that includes attaching a first and second adapter including a barcode to fragments of a first and second nucleic acid sample in a NGS assay (paragraph [0007]; paragraph [0045]), simultaneously generating a plurality of reads (paragraph [0045]; paragraph [0157]); classifying reads as corresponding to a first or second nucleic acid sample based on the barcode sequence (paragraph [0088]).
It would have been obvious for one of ordinary skill in the art, at the time of invention, to combine the references of Xie et al. and Li. Xie et al. teach a method of detecting nucleic acids (paragraph [0006]). One of ordinary skill in the art would have wanted to analyze the data collected from Xie et al.’s method. Li teaches a method of analyzing nucleic acids to discover somatic mutations (abstract). One of ordinary skill in the art, at the time of invention, would have been motivated to use Li’s method of analyzing on the data obtained from Xie et al.’s method of detecting nucleic acids. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success, since one of ordinary skill in the art may readily perform Li’s analysis on the data collected from Xie et al.
Double Patenting
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21, 23, 25-27, and 29-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,468,968. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instants claims 21, 23, 25-27 and 29-33 recite the similar limitations as claims 1-19 the U.S. Patent. The claims differ in that the instant claims recites a non-transitory machine readable storage medium. However, the system in claim 10 of the U.S. Patent would include a machine readable storage medium. Thus, the claims at issue are not patentably distinct from each other.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JERRY LIN whose telephone number is (571)272-2561. The examiner can normally be reached T-F 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JERRY LIN/ Primary Examiner, Art Unit 1685