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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-20 and 30 in the reply filed on 01/05/2026 is acknowledged. The traversal is on the ground(s) that (i) multiple groups can be searched and examined together without undue burden and (ii) time and expense will be saved if all claims can be considered at this time. This is not found persuasive because the restriction is based on a lack of unity, and burden is not an element to be considered. The Remarks do not contest the teaching of the reference cited to establish a lack of unity. Additionally, matters of time and expense are not elements to be considered.
Claims 21-25 and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-25 and 30-31 are pending.
Claims 1-20 and 30 are under examination on the merits.
Priority
This application 18/268,893 filed on 06/21/2023 is a 371 national phase of PCT/US21/64613 filed on 12/21/2021, and claims the benefit of provisional U.S. Patent Application No. 63/197,301, filed on 06/04/2021 and provisional U.S. Patent Application No. 63/128,776, filed on 12/21/2020.
The priority date of claim 1 and its dependent claims is determined to be 12/21/2020, the filing date of provisional U.S. Patent Application No. 63/128,776.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 37 and 55). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of terms which are trade names or marks used in commerce (including IIlumina®, Qiagen™, and NEW ENGLAND BIOLABS® among others), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 recites the limitation “extracting cell free (cfDNA) from the subject's biological sample”. The phrasing of this limitation is unclear grammatically. It is suggested to change the language to “extracting cell free (cfDNA) from a biological sample of the subject” or similar.
Claims 12-14 recite range limitations “between about – to less than”. The term “less than” is not necessary and may be removed.
Claim Rejections - 35 USC § 112(b)
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 1-20 and 30 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.
Claim 1 recites the limitation “comparing the subject's cfDNA fragmentation profile and protein biomarkers with normal reference non-cancer subjects”. It is unclear what criteria would identify a “normal reference non-cancer subject” or how or in what combinations the comparison is intended to be made.
Claim 1 is 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. Claim 1 recites the limitation “diagnosing cancer in a subject”. The omitted steps in claim 1 appear to be steps necessary for diagnosing cancer. The claim should clearly delineate all active steps required for performing the claimed methods. The steps of the claim as written do not specifically result in the claimed ability to diagnose cancer.
Claims 2-20 and 30 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 4 recites the limitation “comparing clinical data between the subject diagnosed as having lung cancer and normal non-cancer subjects”. It is unclear what criteria would determine a “normal non-cancer subject” or what clinical data would be compared.
Claim 5 recites the limitation “the cfDNA fragment mean length and profiles are similar among non-cancer individuals”. It is unclear what criteria determine whether lengths or profiles are similar to each other.
Claim 7 recites the limitation “serum levels of or one or more tumor antigens, cytokines or proteins are measured”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation "serum levels of -- proteins", and the claim also recites "serum levels of one or more tumor antigens, cytokines" which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 30, it is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of the claim 30 is directed to “A method of determining recurrence of cancer in a subject”. However, claim 30 only requires the steps of claim 1 “extracting cell free (cfDNA) from the subject's biological sample; generating genomic libraries from the extracted cfDNA and whole genome sequencing of cfDNA fragments; mapping of the cfDNA fragments to a genomic origin and evaluating fragment length and obtaining genome-wide fragmentation profiles for each sample; identifying protein biomarkers of the subject; comparing the subject's cfDNA fragmentation profile and protein biomarkers with normal reference non-cancer subjects; and, diagnosing cancer in a subject.” The claims do not recite process steps that relate to “a method of determining recurrence of cancer in a subject”. Thus, it is unclear if applicant intends to cover any method of performing the active method steps of claim 1, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If the claim requires something more, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of determining recurrence of cancer in a subject as set forth by the preamble of the claim.
Claim 15 recites the limitation “about 0.95 or greater”. The term “greater than” is a relative term which renders the claim indefinite. The term “greater than” does not appear to require an upper bound and encompasses any number above 0.95.
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 1-20 and 30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claims are taken to be directed to a natural phenomenon and abstract ideas, judicial exceptions.
Claim 1 is directed to a method comprising “evaluating fragment length” and “comparing the subject's cfDNA fragmentation profile and protein biomarkers with normal reference non-cancer subjects”. These limitations are an abstract mental processes (see MPEP 2106.04(a)(2)(III)). As written, the evaluating step encompasses the mental step of looking at mapped cfDNA fragments and observing their length. As written, the comparing step encompasses the mental step of looking at two sets of data and making mental judgements.
Claim 1 further sets forth the correlation between cfDNA fragmentation and protein biomarkers and cancer. This relationship is a natural phenomenon that exists apart from any human action and constitutes a law of nature. A correlation that preexists in the human is an unpatentable phenomenon.
Claims 2-20 and 30 depend from claim 1 , and require the same steps of evaluating and comparing in claim 1 and are similarly directed to a natural phenomenon.
Claim 4 is directed to a method comprising “comparing clinical data between the subject diagnosed as having lung cancer and normal non-cancer subjects”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the comparing step encompasses the mental step of looking at multiple sets of clinical data and making mental judgements.
Claim 20 further sets forth the correlation between cfDNA fragmentation and protein biomarkers and recurrence of cancer. This relationship is a natural phenomenon that exists apart from any human action and constitutes a law of nature. A correlation that preexists in the human is an unpatentable phenomenon.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites the additional steps of ” extracting cell free (cfDNA) from the subject's biological sample; generating genomic libraries from the extracted cfDNA and whole genome sequencing of cfDNA fragments; mapping of the cfDNA fragments to a genomic origin and evaluating fragment length and obtaining genome-wide fragmentation profiles for each sample” and “diagnosing cancer in a subject” and claim 3 recites the additional step of “subjecting the subject to a low dose helical computed tomography (LDCT)”. These are not integrations of the exception into a practical application. Instead, these element are data gathering and analysis required to perform the method.
Claim 20 further adds the limitation of “the subject is administered cancer therapies”. This is not an integration of the exception into a practical application. The steps do not recite any particular treatment that integrates the exception into a new and useful end or directed to a particular condition. Instead the claim recites treatment at a high level of generality(See MPEP 2106.04(d)(2)) and does not even limit administering a therapy to a subject with cancer but encompasses any and all potential subjects.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to extracting cfDNA, generating genomic libraries, mapping cfDNA fragments, obtaining genome-wide profiles, diagnosing a subject, and performing low dose helical computed tomography are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
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.
Claims 1-2, 4-20, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Velculescu et al. (WO2019222657) in view of Drake et al. (WO 2019200410 on IDS dated 06/21/2023).
Regarding claim 1, Velculescu teaches methods for identifying a mammal as having cancer (diagnosing), the method comprising: obtaining cfDNA fragments from a sample obtained from the mammal, processing the cfDNA fragments into sequencing libraries, subjecting the libraries to whole genome sequencing, mapping the sequenced fragments to a genome, analyzing to determine cfDNA fragment lengths to determine a cfDNA fragmentation profile (p. 4, lines 11-20). Velculescu further teaches comparing the cfDNA fragmentation profile to a reference cfDNA fragmentation profile that can be a cfDNA fragmentation profile of a healthy mammal (p. 4 line 28 to p. 5 line 4) and identifying a mammal as having cancer (p. 3, lines11-12).
Velculescu teaches that including other characteristic such as biomarkers could improve determining the source of tumor-derived cfDNA and aid in diagnosis (p. 43, lines 28-30) but does not teach specifically identifying protein biomarkers of the subject or comparing the subject's protein biomarkers with normal reference non-cancer subjects.
Drake teaches using multiple analytes, including cell-free DNA and proteins to perform cancer diagnostics, the method comprising: assaying a plurality of classes of molecules in the biological sample (para 10). The classes of molecules can include cfDNA and proteins; i.e. identifying protein biomarkers (para 17). Drake teaches circulating protein biomarker distribution levels versus normal (Fig. 11). Drake further teaches combining features corresponding to properties or the plurality of classes of molecules to generate a classifier (para 10).
Drake states that using multiple assays can increase the sensitivity and specificity of diagnostics (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Velculescu and Drake to arrive at the instantly claimed invention. The modification would have entailed combining the protein biomarkers of Drake with the cfDNA fragmentation diagnosis method of Velculescu. One of ordinary skill in the art would have been motivated to add multiple characteristics or markers, including protein biomarkers, to improve the accuracy of cancer diagnosis, as both Velculescu and Drake acknowledged. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 2, Velculescu teaches the cancer can be lung cancer (p. 6, line 10).
Regarding claim 4, Velculescu teaches comparing clinical data between subjects diagnosed as having lung cancer and healthy subjects (normal non-cancer subjects) (p. 27, line 30 and Table 1, p. 45-46).
Regarding claim 5, Velculescu teaches healthy individuals had very similar fragmentation profiles and cfDNA fragment lengths throughout the genome (p.36 lines 16-17 and Fig. 7 and 8).
Regarding claim 6, Velculescu teaches patients with cancer had multiple distinct genomic differences with increases and decreases in fragment sizes at different regions (p. 36, lines 28-30 and Fig. 7).
Regarding claim 7, Drake teaches detecting the levels of antigens in serum (para 114).
Regarding claim 8, Drake teaches the tumor antigen Carcinoembryonic antigen (CEA) (para 209).
Regarding claim 9, Drake teaches measuring C-reactive protein (CRP) (para 422).
Regarding claim 10, Velculescu teaches DNA Evaluation of Fragments for early Interception (DELFI) (p. 3, lines 27-28) and obtaining a DELFI score (p. 11, line 25).
Regarding claim 11, Velculescu teaches a healthy (non-cancer) DELFI score of 0.1748 (Table 7, p. 77. Patient CGPLH189).
Regarding claim 12, Velculescu teaches a stage I cancer DELFI score of 0.3410 (Table 7, p. 80. Patient CGPLOV47).
Regarding claim 13, Velculescu teaches a stage II cancer DELFI score of 0.7480 (Table 7, p. 76. Patient CGPLBR24).
Regarding claim 14, Velculescu teaches a stage III cancer DELFI score of 0.9082 (Table 7, p. 76. Patient CGCRC308).
Regarding claim 15, Velculescu teaches a stage IV cancer DELFI score of 0.9976 (Table 7, p. 76. Patient CGCRC291).
Regarding claim 16, Velculescu teaches a stage I cancer DELFI score of 0.3410 (Table 7, p. 80. Patient CGPLOV47).
Regarding claim 17, Velculescu teaches a stage II cancer DELFI score of 0.7480 (Table 7, p. 76. Patient CGPLBR24).
Regarding claim 18, Velculescu teaches a stage III cancer DELFI score of 0.9082 (Table 7, p. 76. Patient CGCRC308).
Regarding claim 19, Velculescu teaches a stage IV cancer DELFI score of 0.9976 (Table 7, p. 76. Patient CGCRC291).
Regarding claim 20, Velculescu teaches administering cancer treatments to a mammal identified as having cancer (p. 3, lines 22-23).
Regarding claim 30, Velculescu teaches methods for identifying a mammal as having cancer (diagnosing), the method comprising: obtaining cfDNA fragments from a sample obtained from the mammal, processing the cfDNA fragments into sequencing libraries, subjecting the libraries to whole genome sequencing, mapping the sequenced fragments to a genome, analyzing to determine cfDNA fragment lengths to determine a cfDNA fragmentation profile (p. 4, lines 11-20). Velculescu further teaches comparing the cfDNA fragmentation profile to a reference cfDNA fragmentation profile that can be a cfDNA fragmentation profile of a healthy mammal (p. 4 line 28 to p. 5 line 4) and identifying a mammal as having cancer (p. 3, lines11-12). Velculescu further teaches the cancer can be a recurrence (p. 20, line 30).
Velculescu teaches that including other characteristic such as biomarkers could improve determining the source of tumor-derived cfDNA and aid in diagnosis (p. 43, lines 28-30) but does not teach specifically identifying protein biomarkers of the subject or comparing the subject's protein biomarkers with normal reference non-cancer subjects.
Drake teaches using multiple analytes, including cell-free DNA and proteins to perform cancer diagnostics, the method comprising: assaying a plurality of classes of molecules in the biological sample (para 10). The classes of molecules can include cfDNA and proteins; i.e. identifying protein biomarkers (para 17). Drake teaches circulating protein biomarker distribution levels versus normal (Fig. 11). Drake further teaches combining features corresponding to properties or the plurality of classes of molecules to generate a classifier (para 10).
Drake states that using multiple assays can increase the sensitivity and specificity of diagnostics (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Velculescu and Drake to arrive at the instantly claimed invention. The modification would have entailed combining the protein biomarkers of Drake with the cfDNA fragmentation diagnosis method of Velculescu. One of ordinary skill in the art would have been motivated to add multiple characteristics or markers, including protein biomarkers, to improve the accuracy of cancer diagnosis, as both Velculescu and Drake acknowledged. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Velculescu et al. (WO2019222657) in view of Drake et al. (WO 2019200410 on IDS dated 06/21/2023) as applied to claims 1-2, 4-20 and 30 above, and further in view of Sobue et al. (Screening for Lung Cancer With Low-Dose Helical Computed Tomography: Anti-Lung Cancer Association Project. 2002. J Clin Oncol 20: 911-920).
Regarding claim 3, Velculescu teaches using diagnostic testing including computed tomography (CT) (p. 25, line 5).
Drake also teaches use of computed tomography as a clinical test to confirm a diagnosis (para 284).
However, neither Velculescu nor Drake teach subjecting the subject to a low dose helical computed tomography (LDCT) specifically.
Sobue teaches screening for lung cancer with low dose helical computed tomography and states that screening with low-dose helical CT has potential to improve screening efficacy (p. 911, Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Velculescu and Drake with Sobue to arrive at the instantly claimed invention. The modification would have entailed adding the screening tool of Sobue with the diagnostic methods of Velculescu and Drake. One of ordinary skill in the art would have been motivated to add the low dose helical computed tomography screening tool to improve the accuracy of cancer diagnosis, a stated goal of both Velculescu and Drake. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
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.
(I). Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over, in the alternative claim 1 of U.S. Patent No. 10,982,279, over claim 1 of U.S. Patent No. 10,975,431, in view of Drake et al. (WO 2019200410 on IDS dated 06/21/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application.
The claims of the instant application and the patents cited above are all drawn to methods of detecting cancer comprising determining a cfDNA fragmentation profile, the methods requiring steps which encompass the claims of the instant application.
Regarding instant claim 1, claim 1 of the ‘279 patent requires processing cfDNA fragments obtained from a sample obtained from the mammal into sequencing libraries; subjecting the sequencing libraries to whole genome sequencing to obtain sequenced fragments; mapping the sequenced fragments to a genome to obtain genomic intervals of mapped sequences; analyzing the genomic intervals of mapped sequences to determine cfDNA fragment lengths and determining the cfDNA fragmentation profile; detecting that the cfDNA fragmentation profile that is more variable than a reference cfDNA fragmentation profile from a healthy subject wherein increased variability of the fragmentation profile obtained from the mammal compared to the reference profile is indicative of the mammal as having cancer; and administering to the mammal identified as having cancer, a therapeutic treatment suitable for treatment of the cancer.
Regarding instant claim 1, claim X of the ‘431 patent requires determining a cell free DNA (cfDNA) fragmentation profile of sequenced fragments in a sample obtained from the subject, wherein the sequenced fragments are obtained through whole genome sequencing (WGS); mapping the sequenced fragments to a genome to obtain windows of mapped sequences; analyzing the windows of mapped sequences to determine the cfDNA fragmentation profile;
analyzing the cfDNA fragmentation profile against a reference cfDNA fragmentation profile from a healthy subject; detecting that the cfDNA fragmentation profile obtained from the subject is more variable wherein increased variability of the fragmentation profile obtained from the subject is indicative of the subject as having cancer; and administering to the subject identified as having cancer, a therapeutic treatment suitable for treatment of the cancer.
The claims of the patents do not require identifying protein biomarkers of the subject or comparing the subject's protein biomarkers with normal reference non-cancer subjects.
The teachings of Drake as they relate to claim 1 are given previously in this office action and are fully incorporated here.
(II). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over, in the alternative, claim 1 of copending Application No. 17/056,726, over claim 68 of copending Application 17/204,892, over claims 67 and 71 of copending Application 17/842,893, over claim 1 of copending Application 18/019,448, over claims 1, 8, and 25 of copending Application 18/286,081 in view of Drake et al. (WO 2019200410 on IDS dated 06/21/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application.
The claims of the instant application and the patents cited above are all drawn to methods of detecting cancer comprising determining a cfDNA fragmentation profile, the methods requiring steps which encompass the claims of the instant application.
Regarding instant claim 1, claim 1 of copending application ‘726 requires processing cfDNA fragments obtained from a sample obtained from the mammal into sequencing libraries; subjecting the sequencing libraries to whole genome sequencing to obtain sequenced fragments; mapping the sequenced fragments to a reference genome wherein the windows of mapped sequences comprise positional and size-based data; analyzing the windows of mapped sequences to determine the cfDNA fragment fragmentation profile; wherein variation of the cfDNA fragmentation profile obtained from the mammal is indicative of the mammal as having cancer, administering to the mammal a cancer treatment.
Regarding instant claim 1, claim 68 of copending application ‘892 requires extracting and enriching cfDNA fragments; processing the cfDNA fragments into sequencing libraries; subjecting the sequencing libraries to whole genome sequencing to obtain cfDNA sequenced fragments, wherein genome coverage is from about 0.1 x to 9x;analyzing the cfDNA sequenced fragments to obtain a cfDNA fragmentation profile; executable instructions; and a processor configured to execute the executable instructions to analyze cfDNA sequenced fragments; wherein analyzing the cfDNA sequenced fragments to obtain a cfDNA fragmentation profile comprises: mapping cfDNA sequenced fragments to a human genome; determining cfDNA fragment lengths for the mapped cfDNA; comparing the cfDNA fragmentation profile in the subject to a reference cfDNA fragmentation profile from a subject that does not have cancer; determining, based on the comparison, that the subject has or is at risk of having cancer; administering to the subject identified as having cancer, a therapeutic treatment suitable for treatment of the cancer.
Regarding instant claim 1, claim 67 of copending application ‘893 requires extracting cfDNA fragments; processing the cfDNA fragments into sequencing libraries; subjecting the sequencing libraries to whole genome sequencing to obtain sequenced fragments, mapping the sequenced fragments to a reference genome to generate positional and size-based data; producing a cfDNA fragmentation profile from the mapped sequencing data, wherein the fragmentation profile comprises fragment size distribution, fragment coverage, and positional fragmentation metrics across the whole genome or subgenomic intervals; comparing the cfDNA fragmentation profile to a reference cfDNA fragmentation profile to determine the cancer status of the subject, administering to the subject a cancer treatment. Claim 71 of copending application ‘893 requires the reference cfDNA fragmentation profile is a cfDNA fragmentation profile of at least one mammal without cancer.
Regarding instant claim 1, claim 1 of copending application ‘448 requires processing a sample from the subject comprising cell free DNA (cfDNA) fragments into sequencing libraries; subjecting the sequencing libraries to whole genome sequencing to obtain sequenced fragments; mapping the sequenced fragments to a genome to obtain windows of mapped sequences; analyzing, using a computer, the windows of mapped sequences to determine cfDNA fragment lengths; comparing the shape of the curve of cfDNA fragment size density from the subject to a reference curve shape from a healthy subject; determining that the subject has cancer when the shape of the curve differs from the reference curve shape, and administering a cancer treatment to the subject.
Regarding instant claim 1, claim 1 of copending application ‘081 requires obtaining and isolating cfDNA fragments from the subject, sequencing the cfDNA fragments to obtain sequenced fragments, mapping the sequenced fragments to a genome to obtain windows of mapped sequences, and analyzing the windows of mapped sequences to determine cfDNA fragment lengths and generate the cfDNA fragmentation profile; and classifying the subject as having cancer or not having cancer by calculating a score based on the cfDNA fragmentation profile.
Claim 8 of copending application ‘081 requires wherein sequencing comprises subjecting the cfDNA fragments to low coverage whole-genome sequencing to obtain the sequenced fragments. Claim 25 of copending application ‘081 requires administering a cancer treatment to the subject.
The claims of the copending applications do not require identifying protein biomarkers of the subject or comparing the subject's protein biomarkers with normal reference non-cancer subjects.
The teachings of Drake as they relate to claim 1 are given previously in this office action and are fully incorporated here.
These are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
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, WINSTON SHEN can be reached at (571)272-3157. 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.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682