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 Status
Claims 4, 11, 12, 15-19, 22, 24-30, 32, and 35 are canceled.
Claims 36-38 are new.
Claims 1-3, 5-10, 13, 14, 20, 21, 23, 31, 33, 34, and 36-38 are pending.
Claims 1-3, 5-10, 13, 14, 20, 21, 23, 31, 33, 34, and 36-38 are examined.
Priority
The instant application is a national stage application of PCT/US2021/027651, filed 04/16/2021, which claims priority to US provisional application No. 63/012,704, filed 04/20/2020. Therefore, the Effective Filing Date (EFD) assigned to each of the claims 1-3, 5-10, 13, 14, 20, 21, 23, 31, 33, 34, and 36-38 is the provisional filing date of application No. 63/012,704, filed 04/20/2020.
Information Disclosure Statement
The Information Disclosure Statements filed 10/19/2022 is in compliance with the provisions of 37 CFR 1.97 and has therefore been considered. A signed copy of the IDS document is included with this Office Action.
Drawings
The drawings filed 10/19/2022 are accepted.
Claim Objections
Claims 1, 8, 10, 21, and 37 are objected to because of the following informalities:
In claim 1, “calculating the adjusted risk to account for the presence of the CHEK2 DM” should read “calculating the adjusted risk to account for the presence of the CHEK2-DM”
In claim 8, “the presence of the CHEK2 DM” should read “the presence of the CHEK2-DM”
In claim 10, “accounting for the CHEK2 DM” should read “accounting for the CHEK2-DM”
In claim 21, “to account for the presence of the CHEK2 DM” should read “to account for the presence of the CHEK2-DM”
In claim 37, “to account for a presence of the CHEK2 DM” should read “to account for a presence of the CHEK2-DM”
Appropriate correction is required.
Claim Warning
Applicant is advised that should claim 23 be found allowable, claim 33 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 1-3, 5-10, 13, 14, 20, 21, 23, 31, 33, 34, and 36-38 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.
With respect to claims 1, 21, and 34, the claims recite the limitations of “performing […] NGS on a sample”. The claims are indefinite because the acronym “NGS” is not defined.
With respect to claims 1, 21, and 34, the claims recite the limitations of “breast cancer associated SNP markers”. The claims are indefinite because the acronym “SNP” is not defined and the claims must be complete onto themselves.
With respect to claim 1, the claim recites the limitation of “identify a presence of a CHEK2-DM”. The claim is indefinite because the acronym “CHEK2-DM” is not defined.
With respect to claim 2, the claim recites the limitation of “an adjusted TC risk (TC*)”. The claim is indefinite because the acronym “TC” is not defined.
With respect to claim 13, the claim recites the limitation of “coefficient bk is the per-allele log OR for breast cancer association of the kth SNP estimated from meta-analysis of literature and the development cohort; xk is the number of alleles of the kth SNP carried by an individual patient which is 0, 1, or 2; and uk is the average number of alleles of the kth SNP reported for individuals included in large general population studies. The claim is indefinite because there is no antecedent basis for “bk”, “xk”, and “uk”.
With further respect to claim 13, the claim recites the limitation of “the per-allele log OR”. The claim is indefinite because the acronym “OR” is not defined and thus it is unclear what “the per-allele log OR” is.
With respect to claim 21, the claim recites the limitation of “determining […] an adjusted risk in the genotype to account for a presence of the CHEK2 DM”. The claim is indefinite because there is no antecedent basis for “the CHEK2 DM”.
With respect to claim 37, the claim recites the limitation of “the adjusted risk is calculated to account for a presence of the CHEK2 DM”. The claim is indefinite because there is no antecedent basis for “the CHEK2 DM”.
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 38 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 38 recites the limitation that “the system is further configured to output at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen and/or reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk”. However, claim 34, on which the claim depends, already recites the system being configured to “output at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen and/or reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk. 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
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, 2, 5-10, 13, 14, 20, 21, 31, 34, and 36-38 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
Claim 3, 23, and 33 are eligible under 35 U.S.C. 101 because validating the breast cancer risk in a clinical cohort integrates the judicial exceptions into a practical application.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite methods and a system.
With respect to step (2A)(1): The claims are directed to abstract ideas of mathematical concepts and mental processes, and laws of nature.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 1:
determine the subject is negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1
identify a presence of a CHEK2-DM
Mathematical concepts recited in claim 1:
determining a comprehensive breast cancer risk in the subject based on a combination of a polygenic risk score for breast cancer risk for the subject and an adjusted risk, wherein determining the comprehensive breast cancer risk in the subject comprises calculating a polygenic risk score based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject, and calculating the adjusted risk to account for the presence of the CHECK2 DM
Mathematical concepts recited in claim 21:
determining a polygenic risk score for breast cancer risk for the subject based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject
determining an adjusted risk in the genotype to account for a presence of the CHECK2DM
assessing a comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted risk
Mental processes recited in claim 21:
measuring the genotype identifies a subject who tested negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1
identifying based at least on the comprehensive breast cancer risk, the subject having breast cancer who benefits from a treatment for the breast cancer based on the breast cancer risk indicating a need for the treatment
reporting the need for the treat for use in administering to the subject at least one of the treatment or a monitoring period followed by the treatment, wherein the treatment is one or more of surgery, cryoablation, radiation therapy, bone marrow transplant, chemotherapy, immunotherapy, hormone therapy, stem cell therapy, drug therapy, biological therapy, and administration of a pharmaceutical, prophylactic or therapeutic compound
Mental processes recited in claim 34:
identify, based on the genotype, a subject who is negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1
reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk
Mathematical concepts recited in claim 34:
calculate a polygenic risk score for breast cancer risk for the subject based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject
calculate an adjusted risk for the subject
determine a comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted risk
Dependent claims 2, 6-10, 13, 14, 20, 31, 37, and 38 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 1, 21, and 34, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 2: “the adjusted risk is an adjusted TC risk (TC*) for the subject; and the method further comprises assessing comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted TC risk”
Claim 6: “wherein the plurality of breast cancer associated SNP markers is from 10 to 10,000 SNP markers”
Claim 7: “wherein the plurality of breast cancer associated SNP markers is from 50 to 200 SNP markers”
Claim 8: “wherein the adjusted TC risk (TC*) is calculated to account for the presence of the CHEK2DM according to Equation I…”
Claim 9: “wherein the adjusted TC risk includes factors for age, body mass index, age at menarche, obstetric history, age at menopause, history of a benign breast condition that increases breast cancer risk such as hyperplasia, atypical hyperplasia, and/or LCIS, history of ovarian cancer, use of hormone replacement therapy, family history of breast and ovarian cancer, and Ashkenazy inheritance”
Claim 10: “wherein the comprehensive breast cancer risk is a relative risk score (Comprehensive RRS) for breast cancer risk made using an adjusted Tyrer-Cuzick risk and taking into account the presence of a CHEK2-DM according to Equation II…”
Claim 13: “wherein the calculating a polygenic risk score comprises a combination of centered risk alleles according to Equation III…”
Claim 14: “wherein the total number of SNPs is 86”
Claim 20: “recommending a therapy based at least on the comprehensive breast cancer risk, wherein the therapy is one or more of surgery, cryoablation, radiation therapy, bone marrow transplant, chemotherapy, immunotherapy, hormone therapy, stem cell therapy, drug therapy, biological therapy, and administration of a pharmaceutical, prophylactic or therapeutic compound”
Claim 31: “prognosing the subject as having a poor prognosis for the breast cancer based on the comprehensive breast cancer risk”
Claim 37: “wherein the adjusted risk is calculated to account for a presence of the CHEK2 DM”
Claim 38: “reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes and mathematic concepts because the claims recite no more than calculating risk values based on biomarkers. The claims utilize the laws of nature of the correlation between SNP markers and cancer risk to make risk predictions.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claim 1 recites the following additional elements that are not abstract ideas:
a computing system comprising one or more processors
performing NGS on a sample of a subject to measure a genotype of the subject
providing an outputting comprising at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk, wherein providing the output comprises at least one of displaying the output on a display screen or reporting the output to another computing system
Claim 21 recites the following additional elements that are not abstract ideas:
a computing system comprising one or more processors
performing NGS on a sample to measure a genotype
Claim 34 recites the following additional elements that are not abstract ideas:
a system comprising one or more processors
performing NGS on a sample
output at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen
The steps of performing NGS on a sample generate the data on which the judicial exceptions are performed and are thus data gathering steps. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). The element of a computing system comprising one or more processors is directed to a generic computer. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc. ... are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(f)). The steps of outputting at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by either displaying the output or reporting the output to another computing system is an extra-solution step that is ancillary to the judicial exceptions and thus does not integrate them into a judicial exception (see MPEP 2106.05(g)).
Dependent claim 5 is directed to a data gathering step because it limits the way that the data is gathered. Dependent claim 38 is directed to extra-solution steps that are ancillary to the judicial exception and do not integrate the judicial exceptions into a practical application.
Dependent claim 36 is directed to the administration of treatments to the subject based on the output. The additional element does not integrate the judicial exceptions into a practical application because the claim does not recite particular treatments (see MPEP 2106.04(d)(2)).
None of these dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements of data gathering described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP at 2106.05(d).I, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represent well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claim 1: The additional elements of a computing system comprising one or more processors, performing NGS on a sample of a subject to measure a genotype of the subject, and providing, by the computing system, an output comprising at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk, wherein providing the output comprises at least one of displaying the output on a display screen or reporting the output to another computing system do not rise to the level of significantly more than the judicial exception. With respect to the computing system and displaying the output, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). With respect to reporting the output to another computer, as exemplified in the MPEP at 210605(d).II with reference to Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362, utilizing an intermediary computer to forward information is a well-understood, routine, and conventional activity, and with reference to buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014), a computer sending information over a network is a well-understood, routine and convention activity. With respect to performing NGS, as exemplified in the MPEP at 2106.05(d).II with reference to University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), sequencing nucleic acid sequences is a well-understood, routine and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 5: The additional element of the genotype being determined with a sequencing chip does not rise to the level of significantly more than the judicial exception. The prior art Gonsky et al. (US 2019/0300957 A1, published October 2019) discloses that DNA chips are well known in the art and can be purchased in pre-fabricated form with sequences specific to particular species (paragraph [0121]). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 21: The additional elements of a computing system comprising one or more processors, and performing NGS on a sample to measure a genotype do not rise to the level of significantly more than the judicial exception. With respect to the system, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). With respect to performing NGS, as exemplified in the MPEP at 2106.05(d).II with reference to University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), sequencing nucleic acid sequences is a well-understood, routine and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 34: The additional elements of a system comprising one or more processors, performing NGS on a sample to obtain a genotype, and outputting at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen do not rise to the level of significantly more than the judicial exception. With respect to the system and displaying the output, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). With respect to performing NGS, as exemplified in the MPEP at 2106.05(d).II with reference to University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), sequencing nucleic acid sequences is a well-understood, routine and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 36: The additional element of administering at least one of a therapy for breast cancer, a monitoring period followed by the therapy for the breast cancer, or a tapering of the therapy for the breast cancer does not rise to the level of significantly more than the judicial exception. The prior art Stacey et al. (US 2011/0294673 A1, IDS reference) discloses current conventional breast cancer treatments such as surgery, adjuvant chemotherapy, radiotherapy, or long-term hormonal therapy follow up (paragraph [0219]), and that the current clinical preventative options for breast cancer are mainly chemopreventive or prophylactic surgery (paragraph [0283]). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 38: The additional element of the system being configured to output at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen does not rise to the level of significantly more than the judicial exception. This is a function of a generic computer, and, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
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. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 34 and 38 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Black et al. (US 2020/0294618 A1, filed March 12, 2019).
Regarding claim 34, Black et al. teaches performing a method using a generic computing system as evidenced by the use of computational pipelines and tools (paragraphs [0066], [0067], and [0073). Thus, a computer comprising a processor is inherent. Black et al. teaches the method that is performed comprising:
performing NGS on a sample to obtain a genotype (paragraph [0052]) and identify, based on the genotype, a subject who is negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1 (paragraph [0055]);
calculate a polygenic risk score for breast cancer risk for the subject based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject (paragraphs [0046]; [0055]);
calculate an adjusted risk for the subject (paragraph [0047]);
determine a comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted risk (paragraph [0049]); and
output at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen and/or reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk (paragraph [0078]).
Regarding claim 38, the claim is directed to outputting at least one of the polygenic risk score, the adjusted risk, or the comprehensive breast cancer risk by displaying on a display screen and/or reporting the polygenic risk score, the adjusted risk, and/or the comprehensive breast cancer risk. Black et al. teaches the system of claim 34. Black et al. reports the polygenic risk scores (paragraph [0078]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 6, 7, 13, 14, 20, 21, 23, 31, 33, 36 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Black et al. in view of Apostolou et al. (“Current perspectives on CHEK2 mutations in breast cancer”, Breast Cancer: Targets and Therapy, published May 2017).
Regarding claim 1, Black et al. teaches a method comprising:
performing NGS on a sample of a subject to (i) measure a genotype of the subject (paragraph [0052]), (ii) determine the subject is negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1 (paragraph [0055]);
determine a comprehensive breast cancer risk in the subject based on a combination of a polygenic risk score for breast cancer risk for the subject and an adjusted risk, wherein determining the comprehensive breast cancer risk in the subject comprises calculating a polygenic risk score based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject (paragraphs [0046], [0047], [0049]).
Furthermore, although Black et al. does not explicitly recite using a computer system, the method of Black et al. is performed using a generic computing system as evidenced by the use of computational pipelines and tools (paragraphs [0066], [0067], and [0073). Thus, a computer comprising a processor is inherent and a generic computer is configured to display an output or report the output to another computing system.
Black et al. does not teach the claim elements of identifying a presence of a CHEK2-DM and calculating the adjusted risk to account for the presence of the CHEK2DM.
However, Apostolou et al. teaches current perspectives on CHEK2 mutations in breast cancer. Apostolou et al. teaches CHEK2 being a serine/threonine kinase which is activated upon DNA damage and is implicated in pathways that govern DNA repair, cell cycle arrest or apoptosis in response to the initial damage. Apostolou et al. teaches that loss of kinase function has been correlated with different types of cancer, mainly breast cancer and that CHEK2 functionality is affected by different missense or deleterious mutations (Abstract). Apostolou et al. teaches that mutations in CHEK2 have been associated with resistance to anthracycline-based chemotherapy and epirubicin (page 334, column 1, paragraph). Apostolou et al. also teaches that although CHEK2 mutation are rare, the risk of developing breast cancer is higher in carriers of truncating mutations. The risk is correlated with family history and increases when the carriers have first- and second-degree relatives who are affected, and samples with certain variants have a higher risk of breast cancer. Apostolou et al. teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated calculating a breast cancer risk based on the presence of a CHEK2 mutation to the invention of Black et al. because Black et al. is directed to using polygenic risk scores to determine a probability that a patient will develop breast cancer (Abstract) and teaches that BRCA1/2 negative cases have significantly higher polygenic risk score than BRCA1/2 carriers or controls (paragraph [0007]), and that polygenic risk scores may be useful for risk stratification in women with family history of breast cancer who are negative for high-penetrance breast cancer-susceptibility genes (paragraph [0008]). Apostolou et al. is directed to reviewing the advances in research on CHEK2 mutations, focusing on breast cancer (Abstract) and teaches that loss of kinase function has been correlated with different types of cancer, mainly breast cancer and that CHEK2 functionality is affected by different missense or deleterious mutations (Abstract). Apostolou et al. also teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk. Thus, one of ordinary skill in the art would have a reasonable expectation of success of estimating a comprehensive breast cancer risk of a patient with a CHEK2 mutation, but without other high-penetrance breast cancer-susceptibility genes and would be motivated to do so because CHEK2 mutations increase risk of breast cancer but does not affect breast cancer risk in patients with other risk-increasing mutations such as BRCA1 and BRCA2 due to signaling pathway interactions.
Regarding claim 2, the claim is directed to the adjusted risk being an adjusted TC risk (TC*) for the subject; and the method further comprising assessing comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted TC risk. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. also teaches using the Tyer-Cuzick model to calculate a breast cancer risk score that is combined with the polygenic risk score to calculate an absolute risk to the patient of developing cancer (paragraphs [0046] and [0047]).
Regarding claim 3, the claim is directed to validating the comprehensive breast cancer risk in a clinical cohort, wherein the clinical cohort includes women of white/non-hispanic and/or Ashkenazi Jewish ancestry. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. also teaches validating the breast cancer risk calculation in a clinical cohort (paragraphs [0061]-[0063]). Black et al. teaches the women included in the study sample being Caucasian (paragraph [0061], paragraph [0019]).
Regarding claim 6, the claim is directed to the plurality of breast cancer associated SNP markers being from 10 to 10,000 SNP markers. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. teaches 100 breast cancer associated SNP markers (paragraph [0031]), or teaches the minimum number of SNPs being used to calculate the PRS being 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 (paragraph [0034]).
Regarding claim 7, the claim is directed to the plurality of breast cancer associated SNP markers being from 50 to 200 SNP markers. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. teaches 100 breast cancer associated SNP markers (paragraph [0031]), or teaches the minimum number of SNPs being used to calculate the PRS being 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 (paragraph [0034]).
Regarding claim 13, the claim is directed to calculating a polygenic risk score comprising a combination of centered risk alleles according to Equation III. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. also teaches calculating the polygenic risk scores using a combination of centered risk alleles according to Equation III (paragraph [0040]).
Regarding claim 14, the claim is directed to the total number of SNPs being 86. Black et al. teaches the method of claim 13 in view of Apostolou et al. Black et al. also teaches the total number of SNPs being at least 50 (paragraph [0040]) and teaches the total number of SNPs comprising 86 SNPs (paragraph [0034]).
Regarding claim 20, the claim is directed to recommending a therapy based at least on the comprehensive breast cancer risk, wherein the therapy is one or more of surgery, cryoablation, radiation therapy, bone marrow transplant, chemotherapy, immunotherapy, hormone therapy, stem cell therapy, drug therapy, biological therapy, and administration of a pharmaceutical, prophylactic or therapeutic compound. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. also teaches based on the PRS score output, treatment including a physician recommending a drug treatment to the patient (paragraph [0044]).
Regarding claim 21, Black et al. teaches a method comprising:
performing NGS on a sample to measure a genotype (paragraph [0052]), wherein measuring the genotype identifies a subject who tested negative for mutations in breast cancer associated genes comprising BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, ATM, NBN, and BARD1 (paragraph [0055]);
determining a polygenic risk score for breast cancer risk for the subject based on a plurality of breast cancer associated SNP markers of the genotype and additional variables for age, personal cancer history, family cancer history, and ancestry of the subject (paragraphs [0046], [0055]);
determining an adjusted risk in the genotype (paragraph [0047]);
assess a comprehensive breast cancer risk in the subject by combining the polygenic risk score and the adjusted risk (paragraph [0049]);
identifying based at least on the comprehensive breast cancer risk, the subject having the breast cancer who benefits from a treatment for the breast cancer based on the breast cancer risk indicating a need for the treatment (paragraph [0044]); and
reporting the need for the treatment for use in administering to the subject a treatment, wherein the treatment is drug therapy (paragraph [0044]).
Furthermore, although Black et al. does not explicitly recite using a computer system, the method of Black et al. is performed using a generic computing system as evidenced by the use of computational pipelines and tools (paragraphs [0066], [0067], and [0073). Thus, a computer comprising a processor is inherent and a generic computer is configured to display an output or report the output to another computing system.
Black et al. does not teach the claim elements of determining an adjusted risk in the genotype to account for a presence of the CHEK2-DM.
However, Apostolou et al. teaches current perspectives on CHEK2 mutations in breast cancer. Apostolou et al. teaches CHEK2 being a serine/threonine kinase which is activated upon DNA damage and is implicated in pathways that govern DNA repair, cell cycle arrest or apoptosis in response to the initial damage. Apostolou et al. teaches that loss of kinase function has been correlated with different types of cancer, mainly breast cancer and that CHEK2 functionality is affected by different missense or deleterious mutations (Abstract). Apostolou et al. teaches that mutations in CHEK2 have been associated with resistance to anthracycline-based chemotherapy and epirubicin (page 334, column 1, paragraph). Apostolou et al. also teaches that although CHEK2 mutation are rare, the risk of developing breast cancer is higher in carriers of truncating mutations. The risk is correlated with family history and increases when the carriers have first- and second-degree relatives who are affected, and samples with certain variants have a higher risk of breast cancer. Apostolou et al. teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated calculating a breast cancer risk based on the presence of a CHEK2 mutation to the invention of Black et al. because Black et al. is directed to using polygenic risk scores to determine a probability that a patient will develop breast cancer (Abstract) and teaches that BRCA1/2 negative cases have significantly higher polygenic risk score than BRCA1/2 carriers or controls (paragraph [0007]), and that polygenic risk scores may be useful for risk stratification in women with family history of breast cancer who are negative for high-penetrance breast cancer-susceptibility genes (paragraph [0008]). Apostolou et al. is directed to reviewing the advances in research on CHEK2 mutations, focusing on breast cancer (Abstract) and teaches that loss of kinase function has been correlated with different types of cancer, mainly breast cancer and that CHEK2 functionality is affected by different missense or deleterious mutations (Abstract). Apostolou et al. also teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk. Thus, one of ordinary skill in the art would have a reasonable expectation of success of estimating a comprehensive breast cancer risk of a patient with a CHEK2 mutation, but without other high-penetrance breast cancer-susceptibility genes and would be motivated to do so because CHEK2 mutations increase risk of breast cancer but does not affect breast cancer risk in patients with other risk-increasing mutations such as BRCA1 and BRCA2 due to signaling pathway interactions.
Regarding claims 23 and 33, the claims are directed to validating the breast cancer risk in a clinical cohort. Black et al. teaches the method of claim 21 in view of Apostolou et al. Black et al. also teaches validating the breast cancer risk calculation in a clinical cohort (paragraphs [0061]-[0063]).
Regarding claim 31, the claim is directed to prognosing the subject as having a poor prognosis for the breast cancer based on the comprehensive breast cancer risk. Black et al. teaches the method of claim 21 in view of Apostolou et al. Black et al. also teaches using the polygenic risk score to determine that the subject will likely develop breast cancer (paragraphs [0010] and [0011]) and combining the PRS with a score derived from patient history information to calculate an absolute risk to the patient developing cancer (paragraph [0046]).
Regarding claim 36, the claim is directed to administering, based at least on the output, to the subject at least one of: a therapy for breast cancer, a monitoring period followed by the therapy for the breast cancer; or a tapering of the therapy for the breast cancer. Black et al. teaches the method of claim 1 in view of Apostolou et al. Black et al. also teaches the method being useful to treat a human (paragraph [0017]), treating including administering therapeutic agents to a subject in need thereof (paragraph [0028]), and based on the PRS score output, treatment including a physician recommending a drug treatment to the patient (paragraph [0044]).
Regarding claim 37, the claim is directed to the adjusted risk being calculated to account for a presence of the CHEK2-DM. Black et al. teaches the system of claim 34.
Black et al. does not teach the claim element of determining an adjusted risk to account for a presence of the CHEK2-DM and teaches calculating polygenic risk scores for a patient without pathogenic variants or likely pathogenic variants, including CHEK2 (paragraph [0055]).
However, Apostolou et al. teaches that mutations in CHEK2 have been associated with resistance to anthracycline-based chemotherapy and epirubicin (page 334, column 1, paragraph). Apostolou et al. also teaches that although CHEK2 mutation are rare, the risk of developing breast cancer is higher in carriers of truncating mutations. The risk is correlated with family history and increases when the carriers have first- and second-degree relatives who are affected, and samples with certain variants have a higher risk of breast cancer. Apostolou et al. teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated calculating a breast cancer risk based on the presence of a CHEK2 mutation to the invention of Black et al. because Black et al. is directed to using polygenic risk scores to determine a probability that a patient will develop breast cancer (Abstract) and teaches that BRCA1/2 negative cases have significantly higher polygenic risk score than BRCA1/2 carriers or controls (paragraph [0007]), and that polygenic risk scores may be useful for risk stratification in women with family history of breast cancer who are negative for high-penetrance breast cancer-susceptibility genes (paragraph [0008]). Apostolou et al. is directed to reviewing the advances in research on CHEK2 mutations, focusing on breast cancer (Abstract) and teaches that loss of kinase function has been correlated with different types of cancer, mainly breast cancer and that CHEK2 functionality is affected by different missense or deleterious mutations (Abstract). Apostolou et al. also teaches that the prior art discloses that the risk does not alter when the individuals are also carriers of BRCA1 or BRCA2 mutations, which can be caused due to interactions among BRCA1, BRCA2, and CHEK2 because they are involved in the same signaling pathways (page 334, column 1, Section CHEK2 and breast cancer risk. Thus, one of ordinary skill in the art would have a reasonable expectation of success of estimating a comprehensive breast cancer risk of a patient with a CHEK2 mutation, but without other high-penetrance breast cancer-susceptibility genes and would be motivated to do so because CHEK2 mutations increase risk of breast cancer but does not affect breast cancer risk in patients with other risk-increasing mutations such as BRCA1 and BRCA2 due to signaling pathway interactions.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Black et al. in view of Apostolou et al., as applied to claims 1-3, 6, 7, 13, 14, 20, 21, 23, 31, 33, 36 and 37 above, and further in view of Cox et al. (US 2017/0275707 A1, IDS reference).
Regarding claim 5, the claim is directed to the genotype being determined, by the computing system, with a sequencing chip. Black et al. teaches the method of claim 1 in view of Apostolou et al.
Neither Black et al. nor Apostolou et al. teach the claim element of the genotype being determined with a sequencing chip.
However, Cox et al. teaches prognosis breast cancer based on correlations between polymorphisms and breast cancer (Abstract). Cox et al. teaches that a variety of probes have been described in the literature and can be used to detect markers that can be correlated to breast cancer phenotypes, such as DNA probe array chips (paragraph [0088]). Cox et al. also teaches that automated devices that can be incorporated into systems have been used to assess a variety of biological phenomena, like expression levels of genes, using systems such as Microchip Arrays (paragraph [0144]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated the chip of Cox et al. to the method of Black et al. in view of Apostolou et al. because Black et al. is directed to . using SNPs to calculate a polygenic risk score to determine a probability that a patient will develop breast cancer (Abstract). Cox et al. is directed to diagnosing and prognosing breast cancer based on correlations with polymorphisms (Abstract), and teaches that a variety of probe array have been described in the literature for the detection of markers that can be correlated to a breast cancer phenotype, such as DNA probe array chips (paragraph [0088]). Thus, one of ordinary skill in the art would have a reasonable expectation of success of using a sequencing chip to measure the expression levels of genes in correlation to breast cancer by combining prior art elements and it would be obvious to do so because DNA probe array chips are known in the art and thus it would be obvious to try to measure expression levels using the probe array chips.
Conclusion
No claims are allowed.
Claims 8-10 appear to be free from the prior art because the prior art does not seem to teach or fairly suggest calculating an adjusted TC risk to account for the presence of a CHEK2-DM according to Equation I.
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/E.A.S./Examiner, Art Unit 1686
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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