DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 19-28 are pending and under examination. Claims 1-18 were canceled by preliminary amendment.
This application is a CON of 16/880884, which was a CON of 16/160990, which was a CON of 15/329228. Application 15/329228 was a National Stage application of PCT/US2015/042310, which claimed priority to two US provisional applications. The effective filing date for the examined claims is the earliest provisional application date: 7/25/2014.
The examiner has reviewed the prosecution history of all parent applications, and related 371 paperwork.
This application has published as US PG Pub 2023/0212672 A1.
The petitions for color drawings have been addressed under separate cover.
The preliminary amendment filed 3/10/2023 was entered, however this amendment to the specification no longer applies, as the petition for color drawings was dismissed 4/26/2023. If Applicant has chosen not to proceed with color drawings and the related requirements, this amendment should be deleted.
The preliminary amendment canceling claims 1-18 and providing new claims 19-28, filed 6/28/2023, was entered.
The drawings filed 6/6/2022, and the replacement sheets filed 12/12/2022, are suitable for examination.
The files associated with the Sequence Listing have been entered.
The disclosure is objected to because of the following informalities: At least the first page of the specification has misnumbered paragraphs. The order of numbering on page 1 is: “[0001] … [0002] … [0001] … [0003] ….” Applicant is requested to review the specification for other instances of misnumbering, or other needed corrections. Revising the numbering is likely to require a substitute specification, however the examiner notes: according to Rule 37 CFR 1.125(c): “Numbering the paragraphs of the specification of record is not considered a change that must be shown under 37 CFR 1.125(c). The paragraphs of any substitute specification, other than the claims, should be individually numbered in Arabic numerals (for example [0001]) so that any amendment to the specification may be made by replacement paragraph in accordance with 37 CFR 1.121(b)(1).”
Appropriate correction is required.
Three IDS statements have been entered and considered.
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 19-28 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 steps of claim 19 are not consecutively lettered, as required, making it difficult to know which limitation is being referred to in later steps and dependent claims. Two steps are labeled (a). Re-lettering claim 19 may require amendments within the claim, and to dependent claims to ensure the proper limitations from claim 19 are referenced.
The metes and bounds of claim 19 are unclear with respect to the newly provided preamble of “classifying a test subject as having cancer, or not having cancer” and the steps of the claim. Claim 19 ends with the identification of the presence of tumor related DNA, however that is not necessarily commensurate in scope with a diagnosis of cancer. Amending the final step to indicate a classification of cancer or no cancer in the subject (as opposed to merely the sample) would obviate this rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 19 already states that the reference samples are from people with and without cancer. Thus, claim 20 fails to further limit claim 19. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation (BRI) 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.
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 19-28 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Applicant is directed to MPEP 2106 and the Federal Register notice (FR89, no 137 (7/17/2024) p 58128-58138) for the most current and complete guidelines in the analysis of patent- eligible subject matter. The current MPEP is the primary source for the USPTO’s patent eligibility guidance.
With respect to step (1): YES, the claims are drawn to statutory categories: The claims recite processes.
With respect to step (2A) (1): YES, the claims recite an abstract idea, law of nature and/or natural phenomenon. The claims explicitly recite elements that, individually and in combination, constitute one or more judicial exceptions (JE).
Mathematic concepts, Mental Processes or Elements in Addition (EIA) in the claim(s) include:
19. (New) A method of classifying a test subject as having cancer or not having cancer, the method comprising:
(Preamble, indicating a method, and the goal of the method.)
(a) obtaining a test sample comprising cfDNA from the test subject,
(EIA- a step of data gathering: obtaining a sample, of any type, by any means as long as it comprises cfDNA)
(a) obtaining sequences of at least a portion of cfDNA molecules present in the test sample from the test subject, wherein the sequences have endpoints and the sequences are mappable to genomic locations;
(EIA- a step of data gathering: sequencing the sample, by any means, and a description of the sequences obtained.)
(b) calculating a set of test sample values indicative of the frequency of cfDNA endpoints mapping to single base genomic locations in a defined genome region comprising a plurality of single base genomic locations, wherein the test sample values are calculated using a mathematical transformation of a count of cfDNA endpoints mapping to the single base genomic locations in the genomic region and representing the distribution of the number of cfDNA endpoints occurring at multiple single base locations in the genome region;
(Mathematic Concept: calculating values “indicative of frequency” using a transformation which accounts for counts and a distribution. MPEP 2106.04(a)(2) Section I)
(c) determining a likelihood that the test sample contains tumor DNA by comparing the test sample values calculated from the frequency of cfDNA endpoints in step (b), with a plurality of reference values, wherein the reference values are calculated as in step (b), and the genome region used in the calculation are the same as the genome region in step (a), wherein the reference values are determined from cfDNA in a plurality of reference samples obtained from individuals known to not have cancer or known to have cancer; and
(Mathematic concept of comparing the data values and calculating a likelihood; Alternatively, a mental process of observing the data values, comparing them, and making a judgement as to whether they correlate or not. MPEP 2106.04(a)(2) Sections I and III.)
(d) classifying the sample as (i) containing tumor DNA or (ii) not containing tumor DNA using the likelihood determined in step (c), wherein the classification is dependent upon meeting a classification threshold.
(Mental process of observing a calculated likelihood value, comparing it to a threshold, and making a judgement as to whether the sample contains tumor DNA, or not. Alternatively, a mathematic concept of whether the likelihood value is greater than, or less than, a threshold value. MPEP 2106.04(a)(2) Sections I and III.)
20. (New) The method of claim 19, wherein the plurality of reference samples is obtained from individuals known to not have cancer and from individuals known to have cancer.
(EIA- a step related to data gathering: describing sample data gathered from reference individuals.)
21. (New) The method of claim 19, wherein steps (b) and (c) are performed for a plurality of genome regions.
(Mathematic concepts and mental processes: iterating steps b) and c).)
22. (New) The method of claim 19, wherein at least one genome region comprises a transcription factor binding site.
(Mental Process/ mathematic concept modification: spelling out the type of region to which the sequence reads should map.)
23. (New) The method of claim 19, wherein at least one genome region comprises a CTCF binding site.
(Mental Process/ mathematic concept modification: spelling out the type of region to which the sequence reads should map.)
24. (New) The method of claim 19, wherein the cfDNA sequenced comprises DNA derived from hematopoietic cells and non-hematopoietic cells, and wherein at least a portion of the non-hematopoietic cells are tumor cells.
(EIA- related to data gathering: describing the sample gathered.)
25. (New) The method of claim 19, wherein the test values and reference values are calculated for a plurality of genomic locations.
(Mathematic concepts and mental processes: iterating steps b) and c) at different locations.)
26. (New) The method of claim 19, wherein the cfDNA is sequenced on a massively parallel DNA sequencer.
(EIA- data gathering, specifying a type of sequencer to be utilized in sequencing the sample.)
27. (New) The method of claim 19, wherein the sample is a blood sample.
(EIA- data gathering, describing the type of sample to be gathered.)
28. (New) The method of claim 27 wherein the reference samples are blood samples.
(EIA- data gathering, describing the type of sample to be gathered.)
Natural law embraced by claim(s) 19-28:
The claims embrace the naturally occurring correlation between naturally occurring changes in genetic material, and a naturally occurring phenotype of cancer.
With respect to step 2A (2): NO, the claims do not integrate any JE into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone, or in combination to determine if the JE is integrated into a practical application (MPEP 2106.05(a-c, e, f and h)).
Claim(s) 19-20, 24, 26-28 recite the additional non-abstract element(s) of data gathering, or a description of the data gathered.
Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the JE. The data gathering does not impose any meaningful limitation on the JE, or how the JE is performed. The additional limitation (data gathering) must have more than a nominal or insignificant relationship to the identified judicial exception. (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantec Corp, McRO, TLI communications, OIP Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.).
Dependent claim(s) 21-23, 25 recite(s) an abstract limitation to the JE reciting additional mathematic concepts, or mental processes. Additional abstract limitations cannot provide a practical application of the JE as they are a part of that JE.
In combination, the limitations of data gathering, for the purpose of carrying out the JE, using a general-purpose computer merely provide extra-solution activity, and fail to integrate the JE into a practical application.
With respect to step 2B: NO. The claims recite a JE, do not integrate that JE into a practical application, and thus are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The additional elements were considered individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to claim(s) 19-20, 24, 26-28: The limitation(s) identified above as non-abstract elements (EIA) related to data gathering do not rise to the level of significantly more than the judicial exception.
Chudova (US 2016/0019338 A1) obtains samples comprising cfDNA, and sequences them, providing mappable reads with endpoints.
Lo et al. (US 2013/0040824 A1) obtains samples comprising cfDNA, and sequences them, providing mappable reads, with endpoints.
Song et al. (US 2012/0164646 A1) obtains samples comprising cfDNA, from samples that may contain normal and tumor/ cancer cells, sequences the cfDNA, providing mappable reads with endpoints.
Benz et al. (US 2013/0017958 A1) obtains samples comprising cfDNA, sequences them, providing mappable reads with endpoints.
Quake et al. (US 2012/0295810 A1) obtains samples of plasma comprising cfDNA, sequences them, and provides mappable reads with endpoints.
Schuetz et al. (US 2013/0116127 A1) obtains samples of plasma, blood or serum which comprise cfDNA, sequences the samples, providing mappable reads with endpoints to diagnose cancer.
Rabinowitz et al. (US 2011/0288780) obtain samples of blood or plasma which comprise cfDNA, sequences them to provide mappable reads with endpoints.
Scholl et al. (US 2012/0021919 A1) obtains samples of plasma which comprise cfDNA, sequences them, and provides mappable reads with endpoints which map to genomic regions.
These elements meet the BRI of the identified data gathering limitations. As such, the prior art recognizes that this data gathering element is routine, well understood and conventional in the art (as in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook).
In the specification at [0166-0167] it is disclosed that the steps identified as data gathering can be met using the publicly available sequence read datasets.
Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not effect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).
Dependent claim(s) 21-23, 25 each recite a limitation requiring additional mathematic concepts or mental processes. Additional abstract limitations cannot provide significantly more than the JE as they are a part of that JE (MPEP 2106.05).
In combination, the data gathering steps providing the information required to be acted upon by the JE, performed in a generic computer or generic computing environment fail to rise to the level of significantly more than that JE. The data gathering steps provide the data for the JE, which is carried out by the general-purpose computers. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Double Patenting
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 19-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,352,670. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps representing the invention are the same with the difference being that the application actively obtains a sample, and the preamble indicates the method is intended to diagnose cancer. The differences are shown in BOLD in the table below.
17805656
11352670
19. (New) A method of classifying a test subject as having cancer or not having cancer, the method comprising:
1. A method of classifying a test subject sample as containing tumor DNA, the method comprising:
(a) obtaining a test sample comprising cfDNA from the test subject,
(a) obtaining sequences of at least a portion of cfDNA molecules present in the test sample from the test subject, wherein the sequences have endpoints and the sequences are mappable to genomic locations;
(a) obtaining sequences of at least a portion of cfDNA molecules present in a test sample from the test subject, wherein the sequences have endpoints and the sequences are mappable to genomic locations;
(b) calculating a set of test sample values indicative of the frequency of cfDNA endpoints mapping to single base genomic locations in a defined genome region comprising a plurality of single base genomic locations, wherein the test sample values are calculated using a mathematical transformation of a count of cfDNA endpoints mapping to the single base genomic locations in the genomic region and representing the distribution of the number of cfDNA endpoints occurring at multiple single base locations in the genome region;
(b) calculating a set of test sample values indicative of the frequency of cfDNA endpoints mapping to single base genomic locations in a defined genome region comprising a plurality of single base genomic locations, wherein the test sample values are calculated using a mathematical transformation of a count of cfDNA endpoints mapping to the single base genomic locations in the genomic region and representing the distribution of the number of cfDNA endpoints occurring at multiple single base locations in the genome region;
(c) determining a likelihood that the test sample contains tumor DNA by comparing the test sample values calculated from the frequency of cfDNA endpoints in step (b), with a plurality of reference values, wherein the reference values are calculated as in step (b), and the genome region used in the calculation are the same as the genome region in step (a), wherein the reference values are determined from cfDNA in a plurality of reference samples obtained from individuals known to not have cancer or known to have cancer; and
(c) determining a likelihood that the test sample contains tumor DNA by comparing the test sample values calculated from the frequency of cfDNA endpoints in step (b), with a plurality of reference values, wherein the reference values are calculated as in step (b), and the genome region used in the calculation are the same as the genome region in step (a), wherein the reference values are determined from cfDNA in a plurality of reference samples obtained from individuals known to not have cancer or known to have cancer; and
(d) classifying the sample as (i) containing tumor DNA or (ii) not containing tumor DNA using the likelihood determined in step (c), wherein the classification is dependent upon meeting a classification threshold.
(d) classifying the sample as (i) containing tumor DNA or (ii) not containing tumor DNA using the likelihood determined in step (c), wherein the classification is dependent upon meeting a classification threshold.
20. (New) The method of claim 19, wherein the plurality of reference samples is obtained from individuals known to not have cancer and from individuals known to have cancer.
2. The method of claim 1, wherein the plurality of reference samples is obtained from individuals known to not have cancer and from individuals known to have cancer.
21. (New) The method of claim 19, wherein steps (b) and (c) are performed for a plurality of genome regions.
3. (Previously Presented) The method of claim 1, wherein steps (b) and (c) are performed for a plurality of genome regions.
22. (New) The method of claim 19, wherein at least one genome region comprises a transcription factor binding site.
4. (Previously Presented) The method of claim 1, wherein at least one genome region comprises a transcription factor binding site.
23. (New) The method of claim 19, wherein at least one genome region comprises a CTCF binding site.
5. (Currently Amended) The method of claim 1, wherein [[the]] at least one genome region comprises a CTCF binding site.
24. (New) The method of claim 19, wherein the cfDNA sequenced comprises DNA derived from hematopoietic cells and non-hematopoietic cells, and wherein at least a portion of the non-hematopoietic cells are tumor cells.
6. (Previously Presented) The method of claim 1, wherein the cfDNA sequenced comprises DNA derived from hematopoietic cells and non-hematopoietic cells, and wherein at least a portion of the non-hematopoietic cells are tumor cells.
25. (New) The method of claim 19, wherein the test values and reference values are calculated for a plurality of genomic locations.
7. (Previously Presented) The method of claim 1, wherein test values and reference values are calculated for a plurality of genomic locations.
26. (New) The method of claim 19, wherein the cfDNA is sequenced on a massively parallel DNA sequencer.
8. (Previously Presented) The method of claim 1, wherein the cfDNA is sequenced on a massively parallel DNA sequencer.
27. (New) The method of claim 19, wherein the sample is a blood sample.
9. (Previously Presented) The method of claim 1, wherein the sample is a blood sample.
28. (New) The method of claim 27 wherein the reference samples are blood samples.
10. (Previously Presented) The method of claim 9, wherein the reference samples are blood samples.
Conclusion
The following applications may be subject to a future non-statutory double patenting rejection, depending on the direction of examination:
18/139,231: cfDNA, sequenced, mapped, a second library is generated (reference) sequenced and mapped, and a mathematic transformation is used to identify cancer linked sequences. “sentinel”
16/469132, cfDNA isolated, sequenced, mapped, and transformed mathematically using endpoint data to determine presence or absence of cancer.
16/705,783, cfDNA isolated, sequenced, mapped, transformed into vectors using a mathematic transformation, compared to reference data, and diagnosing a type of cancer.
17/682,759 cfDNA isolated, tagged, sequenced, analyzed, and determined to be from cancer tissue.
18/196,832: endpoint maps, using mathematically transformed sequence location data, for training a model, to identify a disease condition.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY K ZEMAN whose telephone number is 5712720723. The examiner can normally be reached on 8am-2pm M-F. Email may be sent to mary.zeman@uspto.gov if the appropriate permissions have been filed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry Riggs can be reached on 571 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY K ZEMAN/ Primary Examiner, Art Unit 1686
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