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 .
DETAILED ACTION
Claims 1-3, 5-18, and 71-80 were pending, claims 5-18 were withdrawn, claims 1-3 and 71-80 were examined. Applicant has amended claims 1, 75, 77, and 78. Applicant has canceled claims 2-3, 71-74, and 80 per the reply of 8/5/2025. Claims 1, 5-18, and 75-79 are pending.
Claims 1 and 75-79 are present for examination.
Priority
The instant application, filed June 2, 2021 is a Continuation of 15/514,147, filed March 24, 2017, now abandoned and having 1 RCE-type filing therein. 15514147 was filed March 24, 2017 as a national stage entry of PCT/US15/51868, with an International Filing Date of September 24, 2015. PCT/US15/51868 Claims Priority from Provisional Application 62055415, filed September 25, 2014. PCT/US15/51868 Claims Priority from Provisional Application 62083586, filed November 24, 2014.
Claim Rejections - 35 USC § 112
(Maintained)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 75-79 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 75-79 are directed towards specific treatments (bone met prevention, claim 1) of a patient diagnosed with high breast cancer risk. Applicant’s specification does not provide a showing of treating this subgenus of cancer patients with efficacy, Applicant only provides a generic statement of treatment of any cancer given in a generic fashion. At no point in the Specification is there any teaching of treating a breast cancer patient with a specific gene profile with an aggressive treatment or any mTOR inhibitors, PD-1 Inhibitors, or a combination.
Applicant has provided a multivariate diagnostic method. Applicant has not provided a treatment based on the multivariate diagnostic method. PHOSITA would not find the specification provided shows possession of treating a specific subgenus of patients (a score >0.35) with specific drugs (bone metastasis preventative therapies comprise bisphosphonates, anti-RANKL antibody, anti-DKK1 antibody, mTOR inhibitors, and/or PD-1 inhibitors) to treat (provide efficacy) the patient.
Collins makes it clear that a multivariate diagnostic method must be confirmed with external validation, as without external validation they are considered useless. See Collins, Conclusion.
Collins et al. “External validation of multivariable prediction models: a systematic review of methodological conduct and reporting,” BMC Medical Research Methodology 2014, 14:40.
Response to Arguments: Applicant’s argument showing verbatim support for generic language recited does not overcome this rejection. The claims require a “treatment,” an efficacious treatment is not established in the Specification. Applicant argues the specifics of the Collins reference stating that validation is not always needed. While there is some truth to this, that misses the mark, as Applicant has not shown a single example of any treatment method in the Specification. So while Applicant is correct that Collins doesn’t establish a legal standard, it does show the state of the art and what a PHOSITA would know, an oncologist or other medical professional. Therefore, the initial burden of presenting by a preponderance of evidence why a person skilled in the art would not recognize in an applicant’s disclosure a description of the invention defined by the claims is met. Wertheim, 541 F.2d at 263, 191 USPQ at 97. The Applicant has not shown any treatment, of a patient based on the profile claimed. Applicant has only described a post hoc analysis, at most one could use this to show who will or will not have a poor outcome…. Applicant’s Specification has shown NO use of the analysis to guide treatment.
Applicant points to Nuvo Pharm. (Ireland) Designated Activity Co. v. Dr. Reddy's Laboratories Inc., 923 F.3d 1368, 1380 (Fed. Cir. 2019) as stating “[t]he Federal Circuit has held that this level of detail is sufficient to demonstrate possession of the claimed invention.” Pulling the following quote form the case, “[O]ur case law does not require experimental data demonstrating effectiveness.” The problem here is that case is directed to claims drawn to pharmaceutical compositions.” The technology and knowledge of making and using a pharmaceutical composition is quite different from technology directed towards “personalized medicine.” Moreover in those Patents Specifications (US 6,926,907 and 8,557,285) the inventor taught how to make and use the actual formulations. They had detailed description of making the composition. In this instant Application, directed to a nascent technology of personalized medicine, Applicant has no examples of picking a patient based on the profile and treating the patient, let alone with improved efficacy. Therefore this rejection is maintained.
Claim Rejections - 35 USC § 101
(Maintained)
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 and 75-79 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The claims recite “natural principles” as a limiting element or step without reciting additional elements/steps that integrate the natural principles into the claimed inventions such that the natural principles are practically applied, and are sufficient to ensure that the claims amount to significantly more than the natural principles themselves. In the instant case, the “natural principles” include: the expression level of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), at least 5 proliferation signature genes listed in Table 1, and at least 5 immune signature genes listed in Table 2 in a breast cancer biopsy. Table 1 includes: TPX2, CENPA, KIF2C, CCNB2, BUB1, HJURP, CDCA5, PTTG1, CEP55, and SKA1. Table 2 includes: CD3D, CD2, CD3E, ITK, TRBC1, TBC1D10C, ACAP1, CD247, SLAMF6, and IKZF1.
A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966.Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The recent Interim Eligibility Guidance addresses the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception. If yes, Step 2B determines whether the claim “as a whole” amounts to significantly more than the exception.
Claim elements that are not judicial exceptions include the acts of determining, measuring, comparing to other values, a generic quantitative assay, and a generic kit. The latter two are generic since they are not claimed with limitations that specify they use or contain a specific reagent (e.g. a specific antibody). According to the most recent guidance, to be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way (Federal Register, Vol. 79, No. 241,12/16/2014, Pg. 74624, Column 1, Paragraph, final). In other words, does the claim amount to significantly more than the exceptions themselves (Federal Register, Vol. 79, No. 241, 12/16/2014, Pg. 74624, Column 1, Paragraph, final). Limitations that were found not to be significantly more when recited in a claim with a judicial exception include well-understood, routine, and conventional activities previously known to the industry and specified at a high level of generality (Federal Register, Vol. 79, No. 241, 12/16/2014, Pg. 74624, Column 3, Paragraph, first).
Recently, in Univof Utah v Ambry v Myriad (Fed Cir 2014) the court looked to the claims to find any “non-patent-ineligible elements” sufficient to “transform the nature of the claim into a patent-eligible application.” Here, the claims require various physical transformations, including hybridizing the gene probe; amplification of the gene; and sequencing the gene. However, according to the appellate panel, those transformations are insufficient - primarily because those steps “set forth well-understood, routine and conventional activity engaged in by scientists at the time of Myriad’s patent applications” and are the activities that a scientist would have relied upon to achieve the goals of the invention. In the present case, the active method steps set forth well-understood routine and conventional activity engaged in by scientists and are the activities that a scientist would have relied upon to achieve the goals of the invention.
The Court in in Ariosa Diagnositcs vs Sequenom. (2014-1139, 2014-1144) reiterated the two-step analysis required by Mayo and Alice,namely "determin[ing] whether the claims at issue are directed to a patent-ineligible concept" and, if so, "consider[ing] the elements of each claim both individually and ’as an ordered combination' to determine whether additional elements 'transform the nature of the claim' into a patent-eligible application the court went on to point out that the claimed method "begins and ends with a natural phenomenon," i.e., the presence of cffDNA in maternal blood and the diagnostic implications that can be made by correlating that cffDNA with paternally inherited nucleic acid. Thus, the court concluded that the claims of the '540 patent satisfy the first step of the analysis laid out in Alice because they are "directed to matter that is naturally occurring." The Court next evaluated the secondstep of the analysis to determine whether the remaining elements of the claims in the '540 patent "transform" the natural phenomenon into a patent-eligible application. Despite the presence of claims to particular methods for amplifying, detecting, and correlating cffDNA with paternally inherited nucleic acid, the Court concluded that the claims were insufficient to integrate the naturally occurring material into a patent-eligible application. The Court stated that the method steps involving standard PCR amplification and gel electrophoresis are “not new and useful.” Thus, the specific methods recited in the claims were considered "routine and conventional.”
The Federal Circuit also addressed preemption and found that because these method claims were deemed subject matter ineligible, the concern of preemption, i.e., whether the methods preclude alternative methods in the same field but outside the scope of the claims, was moot. The Court further stated that "[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility. The Court further noted that "[w]here a patent's claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are in this case, preemption concerns are fully addressed and made moot."
The Court rejected Sequenom’s arguments that the claimed methods would not preclude alternative methods, and, therefore, would not preempt the field.The Court explained that the questions of preemption are inherent in subject matter eligibility analysis, and when the claims fail the Mayotest, the question of preemption would not arise.
The present claims are directed to a process so Step 1 is satisfied.
The present claims are directed to a judicial exceptions. The claims recite “natural phenomena” as a limiting element, the expression level of genes in breast cancer cells.
The next step, STEP 2B, is to determine whether the claim as a whole recite something significantly different than the judicial exception(s).
The claims are recited at a high level of generality and there are no meaningful limitations here, e.g., the claim merely requires determining the level of expression (intensity) of genes in a biological sample from the breast cancer subject. There are no specific assay steps listed in the claims. The claims are broad enough such that substantially all practical applications for detecting the level of the genes are included in the scope.
In addition, all of the additional claim elements listed are well-understood, routine, and conventional in this art. See Parker et al. “Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes,” Journal of Clinical Oncology 2009, Vol 27, 1160. Parker teaches looking at ER status, HER status, and profiling 50 genes to determine breast cancer risk using a computer algorithm. Thus, the assays steps were well-understood, purely conventional routine procedures.
The implied step (not required by the instant claims) of comparing the level of expression is drawn to an abstract idea. The Federal Circuit in Association for Molecular Pathology v PTO and Myriad) stated the methods of "comparing" or "analyzing" sequences to be patent-ineligible as directed to abstract ideas, (page 56 in Association for Molecular Pathology v PTO and Myriad).
The limitation directed towards calculating a risk score, and the sore being “indicative “of a high risk for bone metastasis does not recite any additional active method steps, but simply states a characterization or conclusion of the results of those steps. Therefore, the “wherein” clause is not considered to further limit the method defined by the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) (“A ‘whereby’ clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim.”). See also Minton v. National Assoc, of Securities Dealers, Inc., 336 F.3d 1373, 1381,67 USPQ2d 1614, 1620 (Fed. Cir. 2003) (“A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.”).
The Court in Diamond v Diehr (450 U. S. 175, 185 (1981)) pointed out that the basic mathematical equation, like a law of nature, was not patentable. But it found the overall process patent eligible because of the way the additional steps of the process integrated the equation into the process as a whole. Those steps included “installing rubber in a press, closing the mold, constantly determining the temperature of the mold, constantly re- calculating the appropriate cure time through the use of the formula and a digital computer, and automatically opening the press at the proper time.” Id., at 187. These other steps apparently added to the formula something that in terms of patent law’s objectives had significance—they transformed the process into an inventive application of the formula.
The process in Parkerv. Flook, (437 U. S. 584, 585-587 (1978)), (held not patentable) provided a method for adjusting “alarm limits” in the catalytic conversion of hydrocarbons. The claimed process amounted to an improved system for updating those alarm limits through the steps of: (1) measuring the current level of the variable, e.g., the temperature; (2) using an apparently novel mathematical algorithm to calculate the current alarm limits; and (3) adjusting the system to reflect the new alarm-limit values. 437 U. S., at 585-587. The Court, as in Diehr, pointed out that the basic mathematical equation, like a law of nature, was not patentable. But it characterized the claimed process as doing nothing other than “provid[ing] a[n unpatentable] formula for computing an updated alarm limit.” Flook, supra, at 586. Unlike the process in Diehr, it [claim] did not contain any disclosure relating to chemical processes at work or the means of setting off an alarm or adjusting the alarm limit.” Diehr, supra, at 192, n. 14; see also Flook, 437 U. S., at 586. And so the other steps in the process did not limit the claim to a particular application. Moreover, “[t]he chemical processes involved in catalytic conversion of hydrocarbons[,] ... the practice of monitoring the chemical process variables, the use of alarm limits to trigger alarms, the notion that alarm limit values must be recomputed and readjusted, and the use of computers for ‘automatic monitoring-alarming’” were all “well known,” to the point where, putting the formula to the side, there was no “inventive concept” in the claimed application of the formula. Id., at 594. “[P]ost-solution activity” that is purely “conventional or obvious,” the Court wrote, “can[not] transform an unpatentable principle into a patentable process.” Id., at 589, 590.
The Court in Alice Corporation Pty. Ltd. v. CLS Bank International, el al. determined that Alice Corp.'s claims to methods were ineligible because "the claims at issue amount to 'nothing significantly more' than an instruction to apply the abstract idea of intermediated settlement using some unspecified, generic computer."
The question then becomes are there other limitations in the claim that show a patent-eligible application of the abstract idea, e.g., more than a mere instruction to apply the abstract idea. If there are no meaningful limitations in the claim that transform the exception into a patent eligible application such that the claim amounts to significantly more than the exception itself, the claim should be rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter.
The Court in Diehr, Flook, and Alice Corporation have pointed out that the basic mathematical equation, like a law of nature, was not patentable. The Court in Diehr, found that there were other steps added to the formula that in terms of patent law had significance—they transformed the process into an inventive application of the formula. In the present claims there are no active method steps that transfer the process into an inventive application of the formula.
The following art: Parker et al. “Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes,” Journal of Clinical Oncology 2009, Vol 27, 1160; Miller et al. US 2006/0074565 A1 published April 6, 2006; Brichard et al. US 2010/0021424 A1 published January 28, 2010; Rakha et al. “Breast cancer prognostic classification in the molecular era: the role of histological grade,” Breast Cancer Research 2010, 12:207; Ligresti et al. “Breast cancer: Molecular basis and therapeutic strategies (Review),” Molecular Medicine Reports 1:451-458, 2008; Zagouri et al. “mTOR inhibitors in breast cancer: A systematic review,” Gynecologic Oncology 127 (2012) 662–672; Suva et al. “Mechanisms of bone metastases of breast cancer,” Endocrine-Related Cancer (2009) 16 703–713; and Collins et al. “External validation of multivariable prediction models: a systematic review of methodological conduct and reporting,” BMC Medical Research Methodology 2014, 14:40; shows the routine and common practice in the art that establishes that the current claims do not have anything more to make them eligible.
Parker teaches looking at ER status, HER status, and profiling 50 genes to determine breast cancer risk using a computer algorithm. Parker used the PAM50 profile which includes the following genes: ACTR3B, ANLN, BAG1, BCL2, BIRC5, BLVRA, CCNB1, CCNE1, CDC20, CDC6, CDH3, CENPF, CEP55, CXXC5, EGFR, ERBB2, ESR1, EXO1, FGFR4, FOXA1, FOXC1, GPR160, GRB7, KIF2C, KRT14, KRT17, KRT5, MAPT, MDM2, MELK, MIA, MKI67, MLPH, MMP11, MYBL2, MYC, NAT1, NDC80, NUF2, ORC6L, PGR, PHGDH, PTTG1, RRM2, SFRP1, SLC39A6, TMEM45B, TYMS, UBE2C, UBE2T.
Miller teaches determining the proliferation genes: TPX2, CENPA, KIF2C, CCNB2, and BUB1 in breast cancer diagnosis and risk assessment. Miller uses a computer algorithm to determine risk.
Brichard teaches determining the immune genes: CD3D, CD2, CD3E, ITK, and TRBC1in breast cancer diagnosis and risk assessment. Brichard uses a computer algorithm to determine risk.
Rakha teaches the role of histological grade for breast cancer prognostic classification. Rakha teaches that the management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to guide patient decision making and the selection of treatment options. In early-stage breast cancer, where the use of systemic therapy has to be determined for every patient, the three main prognostic determinants used in routine practice are lymph node (LN) status, tumor size, and histological grade. The Nottingham (Elston-Ellis) modification of the Scarff -Bloom-Richardson grading system, also known as the Nottingham Grading System (NGS) [1], is the grading system recommended by various professional bodies internationally (World Health Organization [WHO], American Joint Committee on Cancer [AJCC], European Union [EU], and the Royal College of Pathologists (UK RCPath) [2,3]).
Ligresti teaches the treatment of breast cancer which are all routine in the art.
Zagouri teaches the use of mTOR inhibitors in breast cancer and the routine nature of the use of the compounds established as routine practice.
Suva is brought in to show the mechanisms of bone metastases of breast cancer, stating, “In the case of breast cancer, the skeleton is among the most common of metastatic sites.” Suva notes the importance of tumor heterogeneity, tumor-propagating cells, the microenvironment of breast cancer metastasis to bone as well as many current endocrine therapies for the prevention and treatment of metastatic breast cancer is discussed. Suva then discusses the current treatments, all of the instantly claimed are noted.
Lastly, Collins shows the systematic review of “multivariable prediction models” to which instant claims 71-73 are directed towards. The reference itself, and those within show the weighting of different variables towards predicting different outcomes in cancer patients. This is a well-established and routine practice.
In the present claims there are no other active method steps that transform process into an inventive application of detecting the expression level of genes in breast cancer cells and generically treating with any “one or more bone metastasis preventative therapies.” The treatment step is generic and has no correlation to the gene profile. Applicant has not shown any link between the treatment and the profile. Applicant uses the gene markers to note the cancer is aggressive, then the aggressive cancer is treated aggressively to prevent bone mets (the most common mets in breast cancer). Without correlation to a profile showing results in the treatment that is specific to the profile this claim set is clearly ineligible.
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
Response to Arguments: Applicant argues that the instant claims do present something more, showing that a specific score and a specific treatment is required. The problem is that the “specific score” is simply a multivariate model (known modeling practice) of known set of variables (HER, ER, genes, and histology). The specific treatment is known, as showed by the art, and known to be necessary when the cancer is more aggressive as bone metastasis is common in breast cancer. Therefore this argument is not persuasive.
Applicant notes the Vanda Pharma case, in which a specific patient. A patient with schizophrenia is given a different dose based on a specific mutation of CYP2D6, which provides a safe and effective use of iloperidone ( a single drug). This is a very specific example with a very specific patient, with a unknown factor (CYP2D6 metabolism’s effect on safety of one drug). Therefore this comparison is a poor match. As such this case does not provide a compelling argument for eligibility.
Applicant argues that the instant case is similar to USPTO’s May 2016 Life Sciences Examples (specifically, Example 29: Diagnosing and Treating Julitis, hereinafter the “Julitis example”), the claims are patent-eligible. In Example 29 the hypothetical clams are drawn to a method of diagnosing and treating julitis in a patient in which the steps recited for the method include: (a) obtaining a plasma sample from a human patient; (b) detecting whether JUL-1 is present in the plasma sample; (c) diagnosing the patient with julitis when the presence of JUL-1 in the plasma sample is detected; and (d) administering an effective amount of anti-tumor necrosis factor (TNF) antibodies to the diagnosed patient.
The reason Example 29 is distinct from the instant claims is simple, the instant claims do not use a specific treatment prescribed by the diagnostic step. The treatment is not tied to the diagnosis. Applicant has simply appended a conventional step to a prognosis algorithm in an attempt to draft around the 101 rejection. If Applicant had shown just one example of a treatment based on the diagnosis, the 101 would be withdrawn. However, Applicant has not shown a specific treatment.
Claim Rejections - 35 USC § 103
(Maintained)
Claims 1 and 75-79 are rejected under 35 U.S.C. 103 as being unpatentable over Parker et al. “Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes,” Journal of Clinical Oncology 2009, Vol 27, 1160; Miller et al. US 2006/0074565 A1 published April 6, 2006; Brichard et al. US 2010/0021424 A1 published January 28, 2010; Rakha et al. “Breast cancer prognostic classification in the molecular era: the role of histological grade,” Breast Cancer Research 2010, 12:207; Ligresti et al. “Breast cancer: Molecular basis and therapeutic strategies (Review),” Molecular Medicine Reports 1:451-458, 2008; Zagouri et al. “mTOR inhibitors in breast cancer: A systematic review,” Gynecologic Oncology 127 (2012) 662–672; Suva et al. “Mechanisms of bone metastases of breast cancer,” Endocrine-Related Cancer (2009) 16 703–713; and Collins et al. “External validation of multivariable prediction models: a systematic review of methodological conduct and reporting,” BMC Medical Research Methodology 2014, 14:40.
Claim 1 is directed towards a method for predicting prognosis of a patient with breast cancer, comprising: (a) determining from a tumor biopsy sample from the subject gene expression intensities wherein the intensities are determined by quantifying levels of gene transcripts and the intensities are expressed as any quantitative value relative to a control gene or relative to the same gene in another sample, or a log ratio of expression, or any visual representation thereof for each of the following categories of signature genes: (1) estrogen receptor (ER),(2) human epidermal growth factor receptor 2 (HER2),(3) at least 5 proliferation signature genes (Proliferation) listed in Table 1,(4) at least 5 immune signature genes (immune) listed in Table 2;(b) determining from the tumor biopsy sample from the subject a histology score (stage);(c) calculating a breast cancer risk score from the gene expression intensities and the histology score, wherein a high breast cancer risk score is an indication that the subject has a high risk for bone metastasis and death; and (d) treating the subject determined to have a high breast cancer risk score greater than 0.35 with a cancer treatment, wherein the cancer treatment is mTOR inhibitors.PD-1 inhibitors, or any combination thereof.
Parker teaches looking at ER status, HER status, and profiling 50 genes to determine breast cancer risk using a computer algorithm. Parker used the PAM50 profile which includes the following genes: ACTR3B, ANLN, BAG1, BCL2, BIRC5, BLVRA, CCNB1, CCNE1, CDC20, CDC6, CDH3, CENPF, CEP55, CXXC5, EGFR, ERBB2, ESR1, EXO1, FGFR4, FOXA1, FOXC1, GPR160, GRB7, KIF2C, KRT14, KRT17, KRT5, MAPT, MDM2, MELK, MIA, MKI67, MLPH, MMP11, MYBL2, MYC, NAT1, NDC80, NUF2, ORC6L, PGR, PHGDH, PTTG1, RRM2, SFRP1, SLC39A6, TMEM45B, TYMS, UBE2C, UBE2T.
Miller teaches determining the proliferation genes: TPX2, CENPA, KIF2C, CCNB2, and BUB1 in breast cancer diagnosis and risk assessment. Miller uses a computer algorithm to determine risk.
Brichard teaches determining the immune genes: CD3D, CD2, CD3E, ITK, and TRBC1in breast cancer diagnosis and risk assessment. Brichard uses a computer algorithm to determine risk.
Rakha teaches the role of histological grade for breast cancer prognostic classification. Rakha teaches that the management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to guide patient decision making and the selection of treatment options. In early-stage breast cancer, where the use of systemic therapy has to be determined for every patient, the three main prognostic determinants used in routine practice are lymph node (LN) status, tumor size, and histological grade. The Nottingham (Elston-Ellis) modification of the Scarff -Bloom-Richardson grading system, also known as the Nottingham Grading System (NGS) [1], is the grading system recommended by various professional bodies internationally (World Health Organization [WHO], American Joint Committee on Cancer [AJCC], European Union [EU], and the Royal College of Pathologists (UK RCPath) [2,3]).
Ligresti teaches the treatment of breast cancer which are all routine in the art.
Zagouri teaches the use of mTOR inhibitors in breast cancer and the routine nature of the use of the compounds established as routine practice.
Suva is brought in to show the mechanisms of bone metastases of breast cancer, stating, “In the case of breast cancer, the skeleton is among the most common of metastatic sites.” Suva notes the importance of tumor heterogeneity, tumor-propagating cells, the microenvironment of breast cancer metastasis to bone as well as many current endocrine therapies for the prevention and treatment of metastatic breast cancer is discussed. Suva then discusses the current treatments, all of the instantly claimed are noted.
Lastly, Collins shows the systematic review of “multivariable prediction models” to which instant claims 71-73 are directed towards. The reference itself, and those within show the weighting of different variables towards predicting different outcomes in cancer patients. This is a well-established and routine practice.
A person of ordinary skill in the art would have a reasonable expectation of success in combining known diagnostic markers and would be motivated to get a complete picture of the breast cancer treatment and prognosis therefore obtaining the best possible outcome for the patient, then treating a patient with standard of care for the disease at hand which includes preventing bone metastasis. Combining data is completely predictable, treating patients with standard care is predictable. Therefore the instant invention was prima facie obvious at the time of filing.
Response to Arguments: Applicant argues that using 6 references is unreasonable. No limitation exists for the number of references that may be combined when asserting an obviousness rejection. This argument is not persuasive.
Applicant argue that while Collins showing a review of “multivariable prediction models” is not sufficient to render obvious the specific weighting factors of each variable used by Applicant. This is not true, as the method of post hoc analysis, used on the known genes, histology, and HER status will arrive at numbers for weighting. The numbers could all be normalized or all be multiplied by 10, they are simply a weight, and the actual number is not relevant. The obviousness is derived from using a known technique on known data to arrive at a predictable outcome. Therefore this argument is not persuasive.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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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/MICHAEL J SCHMITT/ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629