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 47-63 are under examination.
Claim Interpretation
2. Instant claims 47 and 56 are drawn to a method that include performing a first analysis using a learning machine model to identify whether the subject is at risk of having circulating tumor DNA and then if the biological sample is not identified as not as risk, performing a second analysis or performing an assay. As the claims are written, the performance of the second analysis or assay is contingent on the condition of finding that the biological sample is not at risk of containing circulating tumor DNA. As a contingent limitation, the instant claims do not require the performance of the second analysis (See MPEP §2111.04(II)). Dependent claims 52-55 and 60-63 are also drawn to the second analysis or assay steps. The broadest reasonable interpretation would only require the step of performing the first analysis of claims 47 and 56.
Claim Rejections - 35 USC § 112
3. 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.
4. Claims 47-63 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.
5. Claims 47 and 56 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the steps required for the first analysis and second analysis. The instant claims recite performing a first analysis and second analysis. However, the instant claims do not recite the steps for performing the analysis. Thus, the metes and bounds of the instant claims are unclear and omit essential steps. Clarification via clearer claim language is required. Dependent claims 48-55 and 57-63 are also rejected for depending from claims 47 and 56.
6. Claims 47 and 56 recites Tables 1-4. However, it is unclear to what Tables 1-4 refer. Furthermore, the MPEP 2173.05(s) “Reference to Figures or Tables” 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) (citations omitted).” Thus, the instant claims are indefinite.
Claim Rejections - 35 USC § 101
7. 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.
8. Claims 47-63 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claims 47-63 are directed to method of detecting circulating tumor DNA in a biological sample. 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 recite the steps of performing a first analysis using a machine learning model to identify whether the subject is at risk of having circulating machine learning model it identify whether the subject is at risk of having circulating tumor DNA and performing a second analysis using a machine learning model to analyze methylation information of nucleic acids from a biological sample obtained from the subject. However, performing the first and second analysis using a machine learning model are calculations that may be interpreted as a mathematical algorithm or mental steps. Dependent claims 48-50, 52-55, and 57-63 recite additional calculations that are part of the mathematical algorithm or the data for the 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 performing a bisulfite conversion, providing complementary probes, selectively amplifying nucleic acids, generating a dataset, and a blood sample. However, these steps are extra solutional activity that gather data for the judicial exception. As extra solutional activity, these elements do not integrate the judicial exception into a practical application.
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 performing a bisulfite conversion, providing complementary probes, selectively amplifying nucleic acids, generating a dataset, and a blood sample. However, these elements are well-understood, routine, and conventional data gathering steps (Specification, page 32-34). Reciting such well-understood, routine, and conventional data gathering steps 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 data gathering for the judicial exception. 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 § 103
9. 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.
Claims 47-63 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller et al. (U.S. 2019/0256921 A1) in view of Li et al. (US 2022/0136062 A1).
See claim interpretation above. In addition, claims 52-55 and 60-63 are drawn to the contingent limitation. Thus, claims 52-55 and 60-63 only require the step of performing the first analysis.
Regarding claims 47, 50-56, and 58-63, Mueller et al. disclose a method that includes performing a first analysis to identify whether the subject is at risk of having circulating tumor DNA (abstract; paragraph [0311]); performing bisulfite conversion of nucleic acids from the biological sample (paragraph [0052]); providing probes complementary to sequences within at least 1000 different CpG islands selected from Tables 1-4 and selectively amplifying from bisulfite converted nucleic acids at least the sequences within at least 1000 different CpG islands selected from Tables 1-4 (paragraph [0086]); and performing an analysis to detect circulating tumor DNA in the biological sample (paragraph [0052]) obtained from a subject ([paragraphs [0311], [0052]) where the methylation information is generated by using a sequencer (paragraphs [0121, [0122], [0342]) where the methylation status of genomic sites are within at last 1000 different CpG islands from Tables 1-4 (page 15, Table 11), and where the second analysis of methylation information of the at least 1000 different CGIs to detect the presence of the circulating tumor DNA and where the second analysis is of increased complexity compared to the first analysis (paragraphs [0052], [0311]).
Although Mueller et al. teach analyzing methylation patterns to identify tumors, Mueller et al do not teach using machine learning to analyze their data.
Li et al. teach a method that includes using a machine learning model to analyze nucleic acid data to determine the presence of tumor DNA (paragraph [0196]).
Regarding claims 48 and 57, Mueller et al. disclose where the biological sample is a blood sample (paragraph [0053]).
Regarding claims 49 and 58, Mueller et al. disclose where the nucleic acids comprise cell free DNA (paragraphs [0309] and [0121]).
It would have been obvious to one of ordinary skill in the art, at the time of filing , to combine the teachings of Mueller et al. and Li et al. Both Mueller et al and Li et al. are directed to detecting cell free tumor DNA (Mueller et al., abstract and Li et al., paragraph [0196]). Li et al. teaches that their method offers the benefit of covering a wider genome area of the genome in a more cost-effective manner. (paragraph [0007]). One of ordinary skill in the art would have been motivated to combine the methods of Mueller et al. and Li et al. in order to gain the benefit of wider genome coverage in a more cost effective manner. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success, since the analysis methods a readily combinable.
Double Patenting
10. 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.
11. Claims 47-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No.11,788,152. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the U.S. Patent recite similar limitations. The claims at issue differ in that the claims of the U.S. Patent require additional limitations. Thus, the subject matter of the instant claims encompasses the claims of the U.S. Patent, and the claims at issue are not patentably distinct.
12. Claims 47-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No.12,275,998. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the U.S. Patent recite similar limitations. The claims at issue differ in that the claims of the U.S. Patent require additional limitations. Thus, the subject matter of the instant claims encompasses the claims of the U.S. Patent, and the claims at issue are not patentably distinct.
13. Claims 47-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-11, 13, and 14 of copending Application No. 19/045,446 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the reference application recite similar limitations. The claims at issue differ in that the claims of the reference application require additional limitations. Thus, the subject matter of the instant claims encompasses the claims of the reference application, and the claims at issue are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
14. Claims 47-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 and 26-30 of copending Application No. 18/393,386 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the reference application recite similar limitations. The claims at issue differ in that the claims of the reference application require additional limitations regarding a kit, a reagent set, and computer program instructions. Thus, the subject matter of the instant claims encompasses the claims of the reference application, and the claims at issue are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
15. Claims 47-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-15, and 17-21 of copending Application No. 19/287,202 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the reference application recite similar limitations. The claims at issue differ in that the claims of the reference application require additional limitations that specify that the second analysis is done by classification. Thus, the subject matter of the instant claims encompasses the claims of the reference application, and the claims at issue are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. Claims 47-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/749,399 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims and the claims of the reference application recite similar limitations. The claims at issue differ in that the claims of the reference application require additional limitations. Thus, the subject matter of the instant claims encompasses the claims of the reference application, and the claims at issue are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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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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.
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/JERRY LIN/Primary Examiner, Art Unit 1685
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