DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-3 and 6-16 are under examination.
Claim Rejections - 35 USC § 112
2. 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 1-3, 6-11 and 13 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.
Instant claims 1 and 13 recite “Tables 1-4”. The MPEP §21703.05(s) states, “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’ Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)” It is unclear what Tables 1-4 encompass in instant claim 1 and 13. Dependent claims 2, 3, and 6-11 are also rejected for depending from claim 1.
Claim Rejections - 35 USC § 101
3. 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 1-3 and 6-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1-3 and 6-16 are directed to method for detecting circulating tumor DNA. 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 claims require the steps of performing analysis using a classifier or neural network to detect the presence of circulating tumor DNA. However, a classifier and neural network is a mathematical algorithm. Dependent claims 7, 8, and 16 recite additional mathematical steps. 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 elements of obtaining target nucleic acids, performing a targeted methylation assay, performing bisulfite conversion, selecting capturing or amplifying the bisulfite converted target nucleic acids, generating a dataset, performing a hybrid capture, and providing surgical intervention, therapeutic intervention, or lifestyle intervention. However these steps are extra solution data gathering steps or extra solution activity. Extra solution steps do 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 elements of obtaining target nucleic acids, performing a targeted methylation assay, performing bisulfite conversion, selecting capturing or amplifying the bisulfite converted target nucleic acids, generating a dataset, performing a hybrid capture, and providing surgical intervention, therapeutic intervention, or lifestyle intervention. However these steps are well-understood, conventional and routine (Specification, paragraphs [0086], [0096], [0099], [00101]-[00104],[00112], and [00151]). Reciting such well-understood, routine, and conventional steps do not transform a judicial exception into patent eligible subject matter. In addition, the recitation of the specific types of data or source of data, as in instant claims 2, 3, 6, 10, 13 and 14, 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 the types of data for a data gathering step. 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
4. 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.
Claims 1-3, 6, 9, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mueller et al. (U.S. 2019/0256921 A1).
Regarding claim 1, Mueller et al. teach a method that includes obtaining target nucleic acids from a biological sample obtained from the subject (paragraphs [0311], [0052]) who has previously undergone a first cancer test that did not exclude cancer risk for the subject (paragraph [0311]); performing a targeted methylation assay on the sampling comprising performing bisulfite conversion of the target nucleic acids (paragraph [0052]); selectively amplifying from the bisulfite converted target nucleic acids (paragraph [0086]) at least a portion of CpG sites within at least 1000 CPG islands selected from Tables 1-4 (page 15, table 11); generating a dataset comprising methylation information of the at least selectively amplified portion of CpG sites (paragraphs [0121] and [0122]); performing an analysis comprising, using a classifier (i.e. determining if the methylated CpGs meet a predetermined criteria, paragraph [0121]), analyzing the methylation information of at least the portion of CpG sites within the at least 1000 CGIs to detect the presence of circulating tumor DNA in the biological sample (abstract; paragraphs [0052] and [0121]) wherein the analysis achieves at least a positive predictive value of 70% for detecting circulating tumor DNA (paragraph [0003]).
Regarding claim 2, Mueller et al. teach where the biological sample is a blood sample (paragraph [0053]).
Regarding claim 3, Mueller et al. teach where the target nucleic acids comprise cell free DNA (paragraphs [0309] and [0121]).
Regarding claim 6, Mueller et al. teach where amplifying comprises performing hybrid capture (paragraphs [0068]-[0070]).
Regarding claim 9, Mueller et al. teach generating the dataset further comprises accounting for baseline biological signatures of the subject (paragraphs [0121] and [0122]).
Regarding claim 10, Muller et al teach where baseline biological signature is determined from reference nucleic acids derived from the genomic DNA of the subject (paragraph [0122]).
Claim Rejections - 35 USC § 103
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 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.
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 7, 8, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller et al. (U.S. 2019/0256921 A1) as applied to claims 1-3, 6, 9, and 10 above, and further in view of Li et al. (U.S. 2022/0136062 A1).
Mueller et al. is applied as above.
However Mueller et al. does not teach applying a machine learning model.
Regarding claim 7, Li et al. teach applying a machine learning model to analyze the if the sample contains material from a cancer patient (paragraphs [0011]-[0015], [0019]).
Regarding claim 8, Li et al. teach computing a metric for a genomic window of a plurality of genomic windows on a target region and analyzing, using the machine learning model, the metric specific for the window and target region (paragraphs [0250]-[0261]).
Regarding claim 11, Li et al. teach providing surgical intervention or therapeutic intervention (paragraphs [0356] and [0357]).
Regarding claim 12, Mueller et al. teach a method that includes analyzing methylation information of at least a portion of CpG sites within at least 1000 CGIs to detect the presence of circulating tumor DNA in the biological sample (abstract; paragraphs [0052] and [0121]) thereby achieving at least a positive predictive value of 70% for detecting circulating tumor DNA (paragraph [0003]).where the methylation information was obtained by obtaining target nucleic acids from a biological sample obtained from the subject (paragraphs [0311], [0052]); performing bisulfite conversion of the target nucleic acids (paragraph [0052]); selectively amplifying from the bisulfite converted target nucleic acids (paragraph [0086]) at least a portion of CpG sites within at least 1000 CpG islands (page 15, table 11); generating a dataset comprising methylation information of the at least the CpG sites from the target nucleic acids(paragraphs [0121] and [0122]);
However Mueller et al. does not teach using a deep neural network.
Li et al. teach applying a neural network (paragraphs [0270] and [0502]).
Regarding claim 13, Mueller et al. teach wherein the at least 1000 CGIs are selected from CGIs of Tables 1-4 (page 15, table 11).
Regarding claim 14, Mueller et al. teach wherein analyzing the methylation information is performed after performing a screen that determines that the subject is not negative for having cancer (paragraph [0311]).
Regarding claim 15, Mueller et al. teach where amplifying comprises performing hybrid capture (paragraphs [0068]-[0070]).
Regarding claim 16, Li et al. teach computing a metric for a genomic window of a plurality of genomic windows on a target region and analyzing, using the machine learning model, the metric specific for the window and target region (paragraphs [0250]-[0261]).
It would have been obvious for one of ordinary skill in the art, at the time of filing, to combine the references of Li et al. and Mueller et al. Mueller et al. teach a method of detecting the presence of circulating tumor DNA in blood (paragraph [0009]). Li et al. teaches analyzing cell free DNA with protein markers in the plasma to achieve a more sensitive and specific method of cancer detection (paragraph [0007]). One of ordinary skill in the art using the method of Mueller et al. would have been motivated to incorporate the analysis of Li et al. to gain the benefit of a more sensitive and specific method. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success since the data for both Mueller et al. and Li et al. may be obtained from blood.
Double Patenting
6. 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.
7. Claims 1-3 and 6-16 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,788,152 in view of Mueller et al. and Li et al.
The instant claims and the claims of the U.S. Patent recite similar limitations. The claims differ in that the instant claims also recite using a classifier, neural network, or machine learning. However, Mueller et al. teaching using a classifier (paragraph [0121], and Li teaching using a neural network and machine learning (paragraphs [0250]-[0270]). One of ordinary skill in the art, at the time of invention, would have been motivated to incorporate the teachings of Mueller et al. and Li et al. with the U.S. Patent to gain the benefit of increased specificity and sensitivity offered by Mueller et al. and Li et al. (Mueller et al. paragraph [0007]; Li et al. paragraph [0007]).
8. Claims 1-3 and 6-16 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,275,998 in view of Mueller et al. and Li et al.
The instant claims and the claims of the U.S. Patent recite similar limitations. The claims differ in that the instant claims also recite using a classifier, neural network, or machine learning. However, Mueller et al. teaching using a classifier (paragraph [0121], and Li teaching using a neural network and machine learning (paragraphs [0250]-[0270]). One of ordinary skill in the art, at the time of invention, would have been motivated to incorporate the teachings of Mueller et al. and Li et al. with the U.S. Patent to gain the benefit of increased specificity and sensitivity offered by Mueller et al. and Li et al. (Mueller et al. paragraph [0007]; Li et al. paragraph [0007]).
9. Claims 1-3 and 6-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/464,035 in view of Mueller et al. and Li et al.
The instant claims and the claims of the copending application recite similar limitations. The claims differ in that the instant claims also recite using a classifier, neural network, or machine learning. However, Mueller et al. teaching using a classifier (paragraph [0121], and Li teaching using a neural network and machine learning (paragraphs [0250]-[0270]). One of ordinary skill in the art, at the time of invention, would have been motivated to incorporate the teachings of Mueller et al. and Li et al. with the copending application to gain the benefit of increased specificity and sensitivity offered by Mueller et al. and Li et al. (Mueller et al. paragraph [0007]; Li et al. paragraph [0007]).
This is a provisional nonstatutory double patenting rejection.
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.
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/JERRY LIN/ Primary Examiner, Art Unit 1685