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 .
Priority
This application 17/756,610 filed on 05/27/2022 is a 371 national phase of PCT/US2020/062194 filed on 11/25/2020, and claims the benefit of provisional U.S. Patent Application No. 62/941,357, filed on 11/27/2019.
The priority date of claim 1 and its dependent claims 2-6, 9, 12, and 14 is determined to be 11/27/2019, the filing date of provisional U.S. Patent Application No. 62/941,357.
Status of Claims
Applicant’s amendments to claims filed 09/24/2025 in response to the Non-Final Rejection mailed 03/25/2025 are acknowledged.
Claims 1, 5, 9, 12, and 14 are amended.
Claims 7, 8, 10, 11, 13, and 15-18 have been canceled.
Claims 1-6, 9, 12, and 14 are pending and under examination.
Response to Remarks filed 09/24/2025
The amendments and arguments presented in the papers filed 09/24/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 03/25/2025 listed below have been reconsidered as indicated.
a) The objections to the specification regarding informalities; hyperlinks; and the use of trade names or marks are withdrawn in view of the amendments to the specification.
b) The objections to claims 1 and 12 are withdrawn in view of amendments to claim 1 and the cancellation of claim 12.
c) The rejection of claims 1-18 under 35 U.S.C. 112(a) for failing to comply with the enablement requirement are withdrawn in view of the amendments to the claims.
d) The 35 USC 112(a) written description rejection of claim 13 has been withdrawn in view of the cancellation of claim 13.
e) The 35 USC 112(b) indefiniteness rejection of claim 5 have been withdrawn in view of the amendments to claim 5.
f) The 35 USC 112(b) indefiniteness rejections of claims 7 and 11 have been withdrawn in view of the cancellation of claims 7 and 11.
h) The rejection of claims 1 and 4-16 under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bahado-Singh are withdrawn in view of the amendments to the claims and cancellation of claims 7, 8, 10, 11, 13, and 15.
h) The rejection of claims 17 and 18 under 35 U.S.C. 103 as being unpatentable over Bahado-Singh and Sun are withdrawn in view of the cancellation of the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Rejections - 35 USC § 112(b)-Indefiniteness - Updated
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 1-6, 9, 12, and 14 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 following rejections have been maintained and modified as necessitated by amendment.
Regarding claim 1, the claim recites “a subject in need” in line 2. It is unclear what criteria would determine a subject in need, or what category a subject in need would comprise.
Regarding claim 1, the claim recites “altered methylation across one or more loci indicates the subject has CHD” in line 10. It is unclear what criteria is used to determine whether “methylation across one or more loci throughout the genome” is altered by performing the step of “comparing the cytosine methylation level of the cfFDNA sample to the cytosine methylation of a control sample”. This is because the frequency or percentage of cytosine methylation at the one or more loci” from “circulating cell-free fetal DNA (cfFDNA) from a blood sample from the mother of the subject during pregnancy” will certainly be non-identical (i.e. “altered”) as compared to “the cytosine methylation of a control sample”.
Regarding claim 1, the claim is rejected as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the step of determining whether “the frequency or percentage of cytosine methylation” are altered as compared to a control sample. The assaying step of the claim does not specifically result in any defined alteration(s) in methylation as the basis of “predicting or diagnosing congenital heart defect (CHD) in a subject in need thereof”
Claims 2-6, 9, 12, and 14 are rejected due to their dependency on claim 1.
Regarding claim 12, the claim references the loci of Tables 1-6. 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). See MPEP § 2173.05(s).
Response to Arguments against Claim Rejection - 35 U.S. C § 112 (b)
The response asserts that the amendments render the § 112(b) rejections moot (p. 8).
Applicant's arguments have been fully considered but are not persuasive.
As explained above, claims 1 and 12 have not been amended to remedy the indefiniteness rejections as asserted in the applicant's response (p. 8).
Claim Rejections - 35 USC § 112(d) - New
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.
These are new rejections necessitated by amendments to the claims.
Claim 6 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 6 recites the limitation "wherein the biological sample comprises body fluid." Claim 1 recites the limitation “obtaining circulating cell-free fetal DNA (cfFDNA) from a blood sample”. A “blood sample” recited in claim 1 is a species encompassed by the genes of “body fluid” recited in claim 6. Therefore, claim 6 fails to further limit claim 1. 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 12 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 12 recites the limitation "wherein the one or more loci comprise at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 loci from Tables 1-6". Claim 1 recites the limitation “wherein the one or more loci comprise cq04761177, cq21431091, cq01263077, cq09853933, cq27142059, cq16551159, cq14957943, cq06978680, cq12592721, cq06301252, cq02807450, and cq12900404”. Claim 12 fails to further limit the one or more loci claimed in claim 1. 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 Rejections - 35 USC § 101 - Updated
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 1-6, 9, 12 and 14 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
These are modified rejections necessitated by claim amendments
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 claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 1 is directed to a method comprising “comparing the cytosine methylation level of the cfFDNA sample to the cytosine methylation of a control sample”. 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 two set of methylation results and making mental judgements.
Claims 2-6, 9, 12, and 14 depend from claim 1, and require the same step of “comparing the cytosine methylation level of the cfFDNA sample to the cytosine methylation of a control sample”.
Claim 4 is directed to a method further comprising “calculating the subject's risk of developing CHD”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the calculating step encompasses the mental step of looking at the data and evaluating it. The step of calculating risk is also a mathematical concept because it involves making a computation.
The claims further set forth the natural phenomenon that is the naturally occurring association between methylation levels in particular loci and CHD. 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 ”obtaining circulating cell-free fetal DNA (cfFDNA) from a blood sample from the mother of the subject during pregnancy”, and “assaying the cfF DNA to determine the frequency or percentage of cytosine methylation at one or more loci throughout the genome”, these are not integrations of the exception into a practical application. Instead, these elements are mere data gathering required to perform the method.
Claim 1 additionally recites the limitation “treating the subject comprising administering medication and/or performing surgery”, however the treating steps are not to a particular patient identified as having CHD, to a particular type of CHD, or to a particular treatment or surgery. Further, the claims do not require the steps to be performed in particular order, and as written, the treating step may be performed prior to the assaying and comparing steps. Thus, there is no nexus between the above judicial exceptions and the treating step. Additional limitations are merely data gathering steps (see MPEP 2106.05(g)).
Furthermore, while claims 2 and 3 recite steps further comprising using artificial intelligence (Al) techniques, these are not integrations of the exception into a practical application. Rather, these steps are mere data analysis required to perform the method.
Step 2B
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claims do not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to obtaining cfFDNA and assaying cytosine methylation are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below. Further, the claims encompass the use of commercially available arrays that are well-known in the art (examples as described in paragraph 38 of the instant application).
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments against Claim Rejection - 35 U.S. C § 101
The response asserts claim 1 is not directed to a judicial exception because it is directed to an improved method of diagnosing and treating Congenital Heart Defect (CHD). The response asserts that the claimed method is drawn to a non-invasive method of accurately predicting CHD in patients by determining the frequency or percentage of cytosine methylation at one or more specific loci that have been shown to provide an accurate diagnosis of the type of CHD (p. 9). The response further asserts that the claimed method is not a judicial exception as it provides a non-invasive and accurate method of diagnosing and facilitating expeditious or urgent treatment of CHO, which, if delayed or if there is failure to provide needed treatment, can result in severe illness, long-term consequences, or death (p. 9).
Applicant's arguments have been fully considered but are not persuasive.
The claims as amended remain drawn to a natural correlation to a disease state. Further, measuring cytosine methylation percentage at one or more specific loci is considered routine and conventional in the art as explained above and in the 103 rejection below. Arguments regarding the non-invasive nature or accuracy of the assay or the importance of the diagnosis and treatment of CHD are not limitations that appear in the claims and cannot contribute to a consideration of the rejection.
The response asserts that the features of claim 1 amount to "significantly more" than the judicial exception, at least because: the claims recite "a specific limitation other than what is well-understood, routine and conventional in the field, or add[] unconventional steps that confine the claim to a particular useful application." The features recited in claim 1 include features such as measuring cytosine methylation percentage at one or more specific loci for predicting and diagnosing CHD, which is not routine and conventional, and currently never performed in clinical practice for CHD diagnosis and treatment in fetus/embryo in pregnancy. These additional features transform claim 1 into patent eligible subject matter (p. 9-10).
Applicant's arguments have been fully considered but are not persuasive.
The claims as amended remain drawn to a natural correlation to a disease state. Further, measuring cytosine methylation percentage at one or more specific loci is considered routine and conventional in the art as explained above and in the 103 rejection below. Arguments regarding predicting and diagnosing CHD and the use of the method in clinical practice for CHD diagnosis and treatment in fetus/embryo in pregnancy reflect intended use only and do not amount to significantly more than the judicial exception.
The response also asserts that the claims recite a specific treatment step after the subject has been diagnosed with CHD. The response submits that the Federal Circuit has held that claims involving diagnosing whether a patient has a particular genotype associated with poor drug metabolism are patent eligible because they involve an application of a natural relationship by reciting a method of treating a patient having a disease and cites Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018) (p. 10).
Applicant's arguments have been fully considered but are not persuasive.
The response asserts the subject matter is analogous to that claimed in Vanda Pharmaceuticals. However, the instant claims recite a treating step at a high level of generality and do not require a specific treatment in response to a specific genotype, as is the case in Vanda. As such, the claim is directed to the relationship and is not a practical application of the judicial exception.
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, 4-6, 9, 12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Bahado-Singh (US20170166965A1, present on IDS dated 05/27/2022) in view of Sun et al. (Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments. 2015. Cell Biochem Biophys 72: 857–860).
These are new rejections necessitated by claim amendments filed on 09/24/2025..
Regarding claim 1, Bahado-Singh teaches predicting Congenital Heart Defect by assaying a sample from a patient to determine the percentage methylation of cytosine at loci of DNA throughout the genome (para 18 and claim 28).
Bahado-Singh teaches a method comprising obtaining a sample and extracting DNA from blood specimens (i.e., obtaining DNA from a blood sample) (para 18). Bahado-Singh further teaches that the DNA can be cell-free and the DNA of a fetus, which reads on cell free fetal DNA (cfFDNA). The DNA can be obtained from maternal body fluids (para 23 and claim 33), i.e. during pregnancy, and samples used for testing specifically include blood (para 74). Bahado-Singh teaches the method further comprises assaying to determine the percentage methylation of cytosine at loci throughout the genome, and measuring the frequency of cytosine methylation (para 18).
Bahado-Singh teaches using the Illumina Infinium® Human Methylation 450 Beadchip assay for methylation profiling (para 54) that instant application uses. Bahado -Singh also teaches the use of the Illumina document "CpG Loci Identification. A guide to Illumina's method for unambiguous CpG loci identification and tracking for the GoldenGate® and Infinium ™ assays for Methylation" (para 59).Thus, Bahado-Singh teaches cytosine methylation at one or more loci as encompassed by the one or more loci comprising cq04761177, cq21431091, cq01263077, cq09853933, cq27142059, cq16551159, cq14957943, cq06978680, cq12592721, cq06301252, cq02807450, and cq12900404 of claim 1.
Bahado-Singh teaches the method further comprises comparing the cytosine methylation level of the patient to a well characterized population of normal and Congenital Heart Defect groups (para 18 and claim 28) and using the differences in cytosine methylation in CHD and normal groups to predict the likelihood of CHD in an individual (para 12).
Bahado-Singh does not teach treating the subject administering medication and/or performing surgery.
Sun teaches using genomic technology to identify genetic causes of congenital heart disease (p. 858, column 1). Sun also teaches treatment of congenital heart disease with medications or surgeries (abstract and p. 859 col 1 - p. 860 col. 1).
It would have been prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bahado-Singh to predict and diagnose CHD with the treatment of CHD by medication or surgery taught by Sun to arrive at the instantly claimed method with a reasonable expectation of success. The modification would have entailed using the teachings of Sun regarding treating CHD patients with the method of Bahado-Singh to identify CHD patients. The ordinary artisan would have been motivated to make the combination because Bahado-Singh teaches the need for screening to facilitate treatment and identification of individuals with CHD. Sun explicitly teaches treating individuals diagnosed with CHD and presents known treatment options. It would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the treatments described in Sun are known in the art. 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 4, Bahado-Singh teaches calculating the individual risk of Congenital Heart Defect (para 18).
Regarding claim 5, Bahado-Singh teaches that control cases were normal non-CHD and non-anomalous newborns (para 62).
Regarding claim 6, Bahado-Singh teaches that samples can include body fluids (para 74).
Regarding claim 9, Bahado-Singh teaches that the DNA of a fetus can be obtained from maternal body fluids or placental tissue (para 23 and claim 33), i.e. during one of the trimesters of pregnancy as encompassed by the claimed cfF nucleic acids from any trimester of pregnancy.
Regarding claim 12, Bahado-Singh teaches using the Illumina Infinium® Human Methylation 450 Beadchip assay for methylation profiling (para 54) that instant application uses. Bahado-Singh also teaches the use of the Illumina document "CpG Loci Identification. A guide to Illumina's method for unambiguous CpG loci identification and tracking for the GoldenGate® and Infinium ™ assays for Methylation" (para 59).Thus, Bahado-Singh teaches cytosine methylation at one or more loci as encompassed by the one or more loci of claim 12.
Regarding claim 14, Bahado-Singh teaches that the assay is a bisulfite-based methylation assay (para 28).
Claims 2 and 3 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Bahado-Singh (US20170166965A1, present on IDS dated 05/27/2022) in view of Sun et al. (Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments. 2015. Cell Biochem Biophys 72: 857–860) as applied to claims 1, 4-6, 9, 12, and 14 above, and further in view of Drake et al (WO 2019200410).
Regarding claims 2 and 3, Bahado-Singh teaches predicting Congenital Heart Defect by assaying a sample from a patient to determine the percentage methylation of cytosine at loci of DNA throughout the genome and comparing the cytosine methylation level of the patient to a well characterized population of normal and Congenital Heart Defect groups (para 18 and claim 28). Bahado-Singh that the DNA can be cell-free (para 2) and that cfDNA can be tested for cytosine methylation (para 9).
Neither Bahado-Singh nor Sun teach using artificial intelligence (Al), including any of the specific algorithms of claim 3.
Drake teaches prognosing congenital heart disease using machine learning to analyze analytes (including cell-free DNA) to increase the sensitivity and specificity of diagnostics (abstract). Drake teaches assays include methylation analysis (para 19). Drake teaches using artificial intelligence predictors such as machine learning (para 289). Drake further specifically teaches using classifiers that include random forest; support vector machine (SVM); linear discriminant analysis (LDA) (para 20) as well as Prediction Analysis for Microarrays (PAM) (para 278) and deep learning (para 85).
It would therefore have been advantageous and prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bahado-Singh and Drake to arrive at the instantly claimed method with a reasonable expectation of success. Both Drake and Bahado-Singh were interested in using methylation of cell-free DNA to predict disease. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of increased sensitivity and specificity of diagnostics as taught by Drake to classify subjects based on the measured levels of methylation at genomic loci. In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because both relied on known techniques of methylation analysis.
Response to Arguments against Claim Rejection - 35 U.S. C § 102
The response asserts that Bahado-Singh does not anticipate claim 1, and respectfully requests that the Office withdraw the § 102 rejections (p. 12).
Applicant’s arguments, with respect to the rejection(s) of claim(s) 1, 4-6, 9, 12, and 14 under USC 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, new and modified ground(s) of rejection is made and presented in the 103 rejection above.
Applicant's arguments relevant to the new grounds of rejection under 35 U.S.C. 103 documented in this Final Office action have been fully considered but they are not persuasive. It is the Examiner’s position that Bahado-Singh in view of Sun disclose said claim limitations as described in the 103 rejections provided above.
Response to Arguments against Claim Rejection - 35 U.S. C § 103 (Claims 2 and 3)
The response asserts that Bahado-Singh does not disclose the elements of claim 1 and Drake does not remedy the deficiencies of Bahado-Singh for claims 2 and 3. The response further asserts the combination of Bahado-Singh and Drake fails to teach or suggest one or more features of independent claim 1 (p. 13).
Applicant's arguments have been fully considered but are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Drake uses artificial intelligence techniques to analyze assays such as the ones used by Bahado-Singh to improve diagnostics. It would have been obvious to use a proven method to analyze the data of Bahado-Singh with a goal of improving CHD diagnosis. .
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 1, 4-6, 9, 12 and 14 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10745754.
These rejections are modified as necessitated by amendments to the claims of the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1,4-6, 9 and 12-14 of the ‘754 patent require a method of predicting or diagnosing a type of CHD that requires measuring the methylation level of genes in maternal whole blood samples comprising cell free fetal DNA and comparing methylation levels to control samples.
Further, claims 1, 4 and 12 of the ‘754 patent require a biological sample that is blood; claims 5-6 and 12-13 of the ‘754 patent require cell free fetal DNA; claims 4 and 13 of the ‘754 patent require a maternal blood sample comprising cell free fetal DNA (i.e. during pregnancy); claim 9 of the ‘754 patent requires the gene PTPRN2 which is represented in the instant application by the loci identifier cg06301252, as claimed by instant claim 1; claim 1 of the ‘754 patent requires identifying the human patient as being predisposed to having VSD (a type of CHD); and claim 1 of the ‘754 patent requires treating a patient identified as being predisposed to VSD by performing surgery
The species of claims 1,4-6, 9 and 12-14 of the ‘754 patent are encompassed by instant claim 1. Thus, patent claims 1,4-6, 9 and 12-14 anticipate the instant claim 1.
Regarding instant claim 4, claims 1,3,9 and 11 of the ‘754 patent require identifying patients predisposed to having a type of CHD which is encompassed by instant claim 4.
Regarding instant claim 5, claim 1 of the ‘754 patent requires a control blood sample from a human patient without CHD, satisfying the requirements of instant claim 5.
Regarding instant claim 6, claims 1, 4,and 12 of the ‘754 patent require a biological sample that is whole blood, and further maternal whole blood. The elements of claim 1 and the species of claims 4 and 12 are encompassed by the genus of instant claim 6
Regarding instant claim 9, claims 4 and 13 of the ‘754 patent require a maternal blood sample comprising cell free fetal DNA (i.e. during one of the trimesters of pregnancy) as encompassed by the claimed cfF nucleic acids from any trimester of pregnancy In instant claim 9.
Regarding instant claim 12, claim 9 of the ‘754 patent requires genes NSMCE2 & PTPRN2 which are present in Table 1 of the instant application and are thus encompassed by the loci in table 1 of instant claim 12.
Regarding instant Claim 14, claims 7-8 and 15-16 of the ‘754 patent require bisulfite-based methylation assay or whole genome sequencing encompassed by instant claim 14.
Claims 2 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10745754 in view of Drake et al (WO 2019200410).
Regarding instant claims 2 and 3, claims of Patent 10745754 do not require using artificial intelligence (Al), including any of the specific algorithms of claim 3.
The teachings of Drake as they relate to these claims are given previously in this office action and are fully incorporated here.
It would have been obvious to one having ordinary skill in the art before the effective filing date to have modified the method taught in the claims of the ‘754 patent to use the artificial intelligence predictors of Drake in combination with the methylation analysis of patent ‘754. Both Drake and Bahado-Singh were interested in using methylation of cell-free DNA to predict disease. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of increased sensitivity and specificity of diagnostics as taught by Drake to classify subjects based on the measured levels of methylation in DNA. In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because both relied on known techniques of methylation analysis.
Response to Arguments against Double Patenting
The response asserts the claims of the USP'754 and the claims of the present application are directed to patentably distinct subject matter; that the Office has not shown that the claims of USP '754 and the present application are obvious over each other. The response further asserts that the claims of USP '754 and the present application are not directed to methods that use the same reagents and steps for performing the claimed methods. Further, Drake does not remedy
the deficiencies of USP '754. (p. 14)
Applicant’s statements pertaining to the maintained nonstatutory double patenting rejections have been fully considered but are not persuasive because the double patenting rejections have been updated to reflect the amendments to the claims.
Thus, for the reasons stated above, and those already of the record, the rejection
is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682