DETAILED ACTION
Applicant's response, filed 3 October 2025, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Claim Status
Claims 1-2 are currently pending and under exam herein.
Specification
Note: All references to the Specification herein pertain to the PG publication: US2022/0093221.
Claim Rejections - 35 USC § 112(b)-Indefiniteness
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.
Claims 1-2 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1, as amended, recites, “administering to the patient the therapeutic agent that the patient is predicted to respond positively to thereby treating the patient’s systemic inflammatory condition” wherein the claim step is unclear with respect to any parameters that would represent “prediction” of a “positive response” because the claim fails to provide any indication of the significance of the comparison of a generically recited SMART profile with historical data beyond the recitation that the two are, in fact, “compared”. What about the comparison yields an indication of a prediction of a positive response to a generically recited agent, for example. This is not clear. Claim 2 fails to remedy the issue. Clarification through clearer claim language is requested.
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 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Any newly recited portions herein are necessitated by claim amendment.
The instant rejection reflects the framework as outlined in the MPEP at 2106.04:
Framework with which to Evaluate Subject Matter Eligibility:
(1) Are the claims directed to a process, machine, manufacture or composition of matter;
(2A) Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
(2B) If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1 Analysis: Are claims directed to process, machine, manufacture/composition of matter
With respect to step (1): yes, the claims are directed to a method for treating a systemic inflammatory condition.
Step 2A, Prong 1 Analysis: Do claims recite abstract idea
With respect to step (2A)(1), the claims recite abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the (2A)(1) evaluation, the claims are found herein to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and in conjunction with mathematical concepts (in particular mathematical relationships and formulas).
The claim steps to abstract ideas are as follows:
Claim 1: “determining whether a patient with a systemic inflammatory condition will respond positively to a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids by… generating from the baseline parameters a systemic mediator-associated response test (SMART) profile comprising independent variables of the systemic inflammatory condition of the patient, wherein the independent variables are selected from the one or more gene expression profiles and one or more demographic variables, physiological variables, and/or results of hospital laboratory tests; (iii) using multivariate regression analysis and stepwise regression analysis, to predict an outcome for treatment of the patient's systemic inflammatory condition with the therapeutic agent based at least on the SMART profile as compared to historical data regarding outcomes of said therapeutic agent administered to a plurality of patients in a phase II or phase III clinical trial”, wherein the abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined herein to each cover performance either in the mind (“determining” and “generating”) and performance by mathematical operation (using multivariate regression analysis and stepwise regression analysis). There are no specifics as to the methodology involved in “determining” beyond making an assessment in a mental fashion given particular data (demographic; physiologic; genetic; laboratory tests) to “generate” a profile based on said data and further, to use “regression analyses” (math) and thus, under the BRI, one could simply, for example, perform said operation with pen and paper, or, alternatively with the aid of a generic computer as a tool to perform said calculations of regression (albeit a computer is not claimed herein). These recitations are similar to the concepts of collecting information, analyzing it and providing certain results from the collection and analysis (Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations (Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in (Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind with pen and paper, and can include mathematical concepts.
Further, see MPEP § 2106.04(a)(2), subsection III. The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation (see, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674: noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1139, 120 USPQ2d 1473, 1474 (Fed. Cir. 2016): holding that claims to a mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper"). Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind" (see Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015); Mortgage Grader, Inc. v. First Choice Loan Servs. Inc., 811 F.3d 1314, 1324, 117 USPQ2d 1693, 1699 (Fed. Cir. 2016): holding that computer-implemented method for "anonymous loan shopping" was an abstract idea because it could be "performed by humans without a computer").
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas.
Step 2A, Prong 2 Analysis: Integration to a Practical Application
Because the claims do recite judicial exceptions, direction under (2A)(2) provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application (MPEP 2106.04(d). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the abstract idea 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 abstract idea, the claim is said to fail to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
With respect to the instant recitations, the claims recite the following additional elements:
Claim 1: receiving data regarding the patient, the data including baseline parameters of the patient, wherein said baseline parameters comprise one or more gene expression profiles and one or more demographic variables, physiologic variables and/or results of hospital laboratory tests, wherein said demographic variables are selected from the group consisting of age, sex, race, comorbidities, and medications; said physiologic variables are selected from the group consisting of height, weight, temperature, MAP, heart rate, diastolic blood pressure, systolic blood pressure, mechanical ventilation, respiratory rate, pressure support, positive end- expiratory pressure, systemic vascular resistance, cardiac index, pulmonary capillary wedge pressure, blood count, prothrombin time, partial thromboplastin time, fibrin degradation products and D-dimer, urine output, chest X-rays, and bacterial cultures; said gene expression profiles consist of upregulation or down regulation of expression of one or more protein kinases, growth factors, hormones, enzymes, chemokines, cytokines, receptors, transcription factors, zinc fingers, structural proteins, inflammatory mediators, cell cycle regulators, immune function genes, antimicrobial genes, extracellular matrix and remodeling genes, carbohydrate metabolism genes, and fatty acid metabolism genes; and said results of hospital laboratory tests are selected from the group consisting of levels of albumin, alkaline phosphatase, ALT, AST, BUN, calcium, cholesterol, creatinine, GGT, glucose, hematocrit, hemoglobin, MCH, MCV, MCHC, phosphorus, platelet count, potassium, total protein, PT, PTT, RBC, sodium, total bilirubin, triglycerides, uric acid, WBCL, base deficit, pH, PaO2, SaO2, FiO2, chloride, and lactic acid… administering the therapeutic agent to the patient the therapeutic agent that the patient is predicted to respond positively thereby treating the patient's systemic inflammatory condition”, wherein the recitations are merely types of data to be collected via routine laboratory testing and further said recitation of administering herein is extra-solution activity.
Dependent claim 2 further limits the data (baseline parameters types) and therefore recite steps that limit the additional elements in independent claim 1 above, for the same reasons.
Further with respect to the additional elements in the instant claims, those steps directed to data gathering perform functions of collecting the data needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract idea, or on 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 courts have recognized the following laboratory techniques as insignificant extra-solution activity. See further, the MPEP at 2106.05(d)II.): determining the level of a biomarker in blood by any means (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)); detecting DNA or enzymes in a sample (Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017)).
Further to administering, the steps herein do not affect a particular treatment or prophylaxis that is particular herein. See Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117, 126 USPQ2d 1266 (Fed. Cir. 2018).
Step 2B Analysis: Do Claims Provide an Inventive Concept
The claims are lastly evaluated using the (2B) analysis, wherein it is determined that because the claims recite abstract ideas, and do not integrate that abstract ideas into a practical application, the claims also lack a specific inventive concept. Applicant is reminded that the judicial exception alone cannot provide the inventive concept or the practical application and that the identification of whether the additional elements 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 directed in the Berkheimer memorandum of 19 April 2018 and set forth in the MPEP, 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) represents 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 instant claims 1-2, the prior art to Slotman (Critical Care (2000) Vol. 4, No. 5:319-326-IDS reference) teach the use of these types of data in a SMART profile. See, as example, Slotman at page 319 at the abstract teaching making predictions that are clinically useful by use of data that includes demographic, physiologic, laboratory testing, and biomarker information data. Further, it is known in the art to use gene espression profiles to predict response to therapies, such as disclosed in Julia et al. (PLoS One (2009) Vol. 4, Issue 10:8 pages-cited herein based on the claim amendments presented) (see abstract). As such, this type of data gathering for prediction purposes is routine, well-understood and conventional in the art. Data gathering steps constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)). The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)II.): determining the level of a biomarker in blood by any means (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)); detecting DNA or enzymes in a sample (Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017)).
The dependent claim has been analyzed with respect to step 2B and none of the elements provide a specific inventive concept, as they fail to rise to the level of significantly more than the identified judicial exception.
For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Applicant’s Arguments
1. Applicant states that, “Applicant disagrees with this rejection. In accordance with the decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceutical, 887 F.3d 1117 (Fed. Cir. 2018) and the USPTO subject matter eligibility guidance” and that “in particular, claim 1 is directed to treating a systemic inflammatory condition by administering a treatment regime (e.g., a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids) to a patient with a systemic inflammatory condition depending on independent variables in the patient's SMART profile that are comparable to historical data regarding positive outcomes of the therapeutic agent when administered to a plurality of patients in a phase II or phase III clinical trial. The administration of different treatment regimes depending on result of SMART profile comparisons is a practical application of the comparison, as found in Vanda, and also in the USPTO subject matter eligibility guidance. Mayo v. Prometheus, 566 US 66 (2012) is distinguished from the present situation, as was in Vanda, in that the claims at issue in Mayo v. Prometheus merely informed the operator of the consequences of the measurement without requiring any specific action integrating the measurements into a practical application.
It is respectfully submitted that this is not persuasive. The claims as present in Vanda recited a method of treating a patient having schizophrenia with iloperidone, a drug known to cause QTc prolongation (a disruption of the heart’s normal rhythm that can lead to serious health problems) in patients having a particular genotype associated with poor drug metabolism. Vanda at 887 F.3d at 1121, 126 USPQ2d at 1269-70. In particular, the claims recited steps of: (1) performing a genotyping assay to determine if a patient has a genotype associated with poor drug metabolism; and (2) administering iloperidone to the patient in a dose range that depends on the patient’s genotype. Id. Although Vanda’s claims recited a law of nature (the naturally occurring relationship between the patient’s genotype and the risk of QTc prolongation) like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 101 USPQ2d 1961 (2012), the Federal Circuit distinguished them from the Mayo claims based on the differences in the administration steps. In particular, the court explained that Mayo’s step of administering a drug to a patient was performed in order to gather data about the recited laws of nature, and this step was thus ancillary to the overall diagnostic focus of the claims. Mayo at 887 F.3d at 1134-35, 126 USPQ2d at 1280. In contrast, Vanda’s claims used the recited law of nature to more safely treat the patients with the drug, thereby reducing the patient’s risk of QTc prolongation. Vanda at 887 F.3d at 1135, 126 USPQ2d at 1280. Accordingly, the court held Vanda’s claims eligible at the first part of the Alice/Mayo test (Step 2A) because the claims were not "directed to" the recited judicial exception. Vanda at 887 F.3d at 1136, 126 USPQ2d at 1281. Because there are no parameters set forth in the instant claims with respect to the particular disease or particular treatment nor are there steps to indicate indications of a positive prediction (see 112b above), the arguments are not deemed persuasive nor are the claims similar to Vanda.
2. Applicant states that, “the step of administering different treatment regimes to a patient depending on assessment of, e.g., particular gene expression profiles and demographics, had not been established at the time of the invention to have been well-understood, routine, and conventional in the field of the invention. For example, while Slotman ((2000) Critical Care 4:319-326; hereinafter "Slotman") is suggested to teach a SMART profile and the making of predictions that are clinically useful, Applicant respectfully submits that Slotman does not support a position that gene expression profile analysis was a well-understood, routine, and conventional activity used in the field of determining a suitable treatment regime for treating a systemic inflammatory condition as required to show lack of patent eligibility under 35 U.S.C. §101”.
It is respectfully submitted that this is not persuasive. As is recited in the above rejection and as is necessitated by claim amendment herein reciting, “wherein baseline parameters comprise one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests” which now requires (i) gene expression profiles and (ii) either demographic variables, physiologic variables and/or laboratory tests, the prior art to at least Julia et al. disclose the assessment of gene expression profiles to predict response to a therapy. As such, said operation is a data gathering operation in addition to those data gathering operations that include other variables. There are no specific gene expression profiles recited that would distinguish the claims herein. As such, gene expression profiling is of routine nature.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
1. Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over 2003/0104453 to Pickar et al. (IDS reference) in view of Slotman (Critical Care (2000) Vol. 4, No. 5:319-326).
Claim 1 is directed to:
A method for treating a systemic inflammatory condition, comprising:
(a) determining whether a patient with a systemic inflammatory condition will respond positively to a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids by
(i) receiving data regarding the patient, the data including one or more baseline parameters of the patient, wherein said baseline parameters comprise demographic variables, physiologic variables, gene expression profiles and results of hospital laboratory tests, wherein
said demographic variables are selected from the group consisting of age, sex, race, comorbidities, and medications;
said physiologic variables are selected from the group consisting of height, weight, temperature, MAP, heart rate, diastolic blood pressure, systolic blood pressure, mechanical ventilation, respiratory rate, pressure support, positive end- expiratory pressure, systemic vascular resistance, cardiac index, pulmonary capillary wedge pressure, blood count, prothrombin time, partial thromboplastin time, fibrin degradation products and D-dimer, urine output, chest X-rays, and bacterial cultures;
said gene expression profiles consist of upregulation or down regulation of expression of one or more protein kinases, growth factors, hormones, enzymes, chemokines, cytokines, receptors, transcription factors, zinc fingers, structural proteins, inflammatory mediators, cell cycle regulators, immune function genes, antimicrobial genes, extracellular matrix and remodeling genes, carbohydrate metabolism genes, and fatty acid metabolism genes; and
said results of hospital laboratory tests are selected from the group consisting of levels of albumin, alkaline phosphatase, ALT, AST, BUN, calcium, cholesterol, creatinine, GGT, glucose, hematocrit, hemoglobin, MCH, MCV, MCHC, phosphorus, platelet count, potassium, total protein, PT, PTT, RBC, sodium, total bilirubin, triglycerides, uric acid, WBCL, base deficit, pH, PaO2, SaO2, FiO2, chloride, and lactic acid;
(ii) generating from the baseline parameters a systemic mediator-associated response test (SMART) profile for the patient;
(iii) using multivariate regression analysis and stepwise regression analysis, to predict an outcome for treatment of the patient's systemic inflammatory condition with the therapeutic agent based at least on the SMART profile and on historical data regarding outcomes of said therapeutic agent administered to a plurality of patients in a phase II or phase III clinical trial; and
(b) administering the therapeutic agent to the patient if the patient is predicted to respond positively to said therapeutic agent.
The prior art to Pickar et al. disclose patient data parameters include gene expression profiles and demographic variables, physiologic variables, and/or results of hospital laboratory tests variables at [Figure 3-52, 70, 76]; [Figure 7C]; [0042]. Pickar et al. further disclose the prediction of outcomes of therapeutic agents for treatment of a disease based on said data [Figure 3-80]; [0035]; [0063]; [0077]. Pickar et al. disclose demographic variables such as age [0042; 0060]; physiological variables, such as patient data related to health history [0060]. Pickar et al. further disclose clinical trial patient data (Pickar at [0014]; [0074]; [0075]. Pickar et al. teach prediction of outcomes using statistical analyses, including regression analysis [0056]; [0072].
With respect to the SMART profile (although not particularly defined by the claims or Specification herein), the prior art Pickar et al. do not specifically teach a profile dedicated by the name SMART. Pickar does not specifically teach hospital specific tests named (although not necessarily limiting herein IF the variable does not include “hospital variables” as now interpreted by the “and/or” in the claim).
However, Slotman teaches methodology that pertains to a Systematic Mediator-Associated Response Test (SMART) to predict a clinical course of septic surgery patients from a database of medical and surgical patients with severe sepsis and/or septic shock (abstract). Said profiles predict outcomes for said set of patients and include information such as demographic, physiologic, hospital laboratory test data as baseline data [p. 320]. Said hospital tests include, for example, alkaline phosphatase and others (see Table 1). Slotman teaches that the data are analyzed using logistical regression in prediction modeling [page 320; page 321; page 322] and that said analysis is useful for treatment protocols (abstract); (page 7, col. 1-SMART models for mediator indications).
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 used the profile information available in the SMART profiles as disclosed in Slotman with the analysis techniques disclosed by Pickar et al. for the prediction of patient specific outcomes. Pickar et al. specifically disclose parameters for such assessment that include those in the named SMART profiles as described by Slotman. As such, Pickar et al. effectively include such profiling in their techniques. In addition, Slotman motivate the use of the SMART profile techniques as a scoring system useful when assessing relationships between standard laboratory tests and other parameters for the prediction of clinical events and providing for improved outcomes (page 324). It is noted that there are no actual
With respect to claim 2, Pickar et al. disclose pre-randomization baseline parameters [0059-teaching that traits of interest can be included from randomly chosen genotypes].
Response to Applicant’s Arguments
1. Applicant states that, “Claim 1 recites a method for treating a systemic inflammatory condition with a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet- activating factor and oxidized phospholipids by using a SMART profile to predict an outcome for treatment of the patient's systemic inflammatory condition with the therapeutic agent and on historical data regarding outcomes of said therapeutic agent administered to a plurality of patients in a phase II or phase III clinical trial. By comparison, Pickar describes a pharmacogenomic system for predicting a risk of adverse events to one or more drugs for a plurality of patients. Pickar does not teach or suggest treatment of a systemic inflammatory condition using such a system. Slotman describes prospectively validated SMART predictions of shock, organ failure and 28-day survival from baseline to improve outcomes. However, this reference also fails to teach or suggest treatment options as presently claimed for subjects with a systemic inflammatory condition”.
This is not persuasive. With respect to prediction of outcomes of therapeutic agents for disease treatment, Pickar et al. disclose association between genotypes and adverse drug events for providing personalized medical advice and pharmacogenomic therapy based on patients personal genetic make-up [abstract]. Pickar et al. further disclose relational database which links individualized genomics information to adverse events of therapeutic agents [0011] and further disclose information regarding a pool of patients (identified anonymously) who have experienced an adverse event to a marketed drug. Such patients may be genotyped for variants of candidate genes relevant to the side effect or class of drug treatment. This may include whole genome-wide SNP data. In this fashion, a unique individualized dataset of clinical populations who have experienced an adverse event can be matched to a corresponding dataset of genetic information [0015] and further disclose relationships between genotype (including low frequency SNP's) and adverse events. The system may include, for example, a genotype database, a clinical database, an analytical computer, an adverse event database, a blood bank, sequencing machines and/or clinical indications for applications of specific drugs [0016]. As such, under the BRI of the instant claims that fil to include details pertaining to any SMART profile or parameters of treatment in clinical trials, the teachings of Pickar et al. reasonable disclose assessment of genotypes and other factors as compared against “historical” (database) information. For example, “clinical databases” may very well include clinical trial historical information. As such, the claims are prima facie obvious.
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.
1. Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 6,190,872 in view of Slotman et al. (Critical Care (2000) Vol. 4, No. 5:319-326) and in further view of Julia et al. (PLoS One (2009) Vol. 4, Issue 10:8 pages).
Instant claim 1 is directed to
A method for treating a systemic inflammatory condition, comprising:
(a) determining whether a patient with a systemic inflammatory condition will respond positively to a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids by
(i) receiving data regarding the patient, the data including baseline parameters of the patient, wherein said baseline parameters comprise one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests, wherein
said demographic variables are selected from the group consisting of age, sex, race, comorbidities, and medications;
said physiologic variables are selected from the group consisting of height, weight, temperature, MAP, heart rate, diastolic blood pressure, systolic blood pressure, mechanical ventilation, respiratory rate, pressure support, positive end- expiratory pressure, systemic vascular resistance, cardiac index, pulmonary capillary wedge pressure, blood count, prothrombin time, partial thromboplastin time, fibrin degradation products and D-dimer, urine output, chest X-rays, and bacterial cultures;
said gene expression profiles consist of upregulation or down regulation of expression of one or more protein kinases, growth factors, hormones, enzymes, chemokines, cytokines, receptors, transcription factors, zinc fingers, structural proteins, inflammatory mediators, cell cycle regulators, immune function genes, antimicrobial genes, extracellular matrix and remodeling genes, carbohydrate metabolism genes, and fatty acid metabolism genes; and
said results of hospital laboratory tests are selected from the group consisting of levels of albumin, alkaline phosphatase, ALT, AST, BUN, calcium, cholesterol, creatinine, GGT, glucose, hematocrit, hemoglobin, MCH, MCV, MCHC, phosphorus, platelet count, potassium, total protein, PT, PTT, RBC, sodium, total bilirubin, triglycerides, uric acid, WBCL, base deficit, pH, PaO2, SaO2, FiO2, chloride, and lactic acid;
(ii) generating from the baseline parameters a systemic mediator-associated response test (SMART) profile comprising independent variables of the systemic inflammatory condition of the patient, wherein the independent variables are selected from the one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests;
(iii) using multivariate regression analysis and stepwise regression analysis, to predict an outcome for treatment of the patient's systemic inflammatory condition with the therapeutic agent based at least on the SMART profile as compared to historical data regarding outcomes of said therapeutic agent administered to a plurality of patients in a phase II or phase III clinical trial; and
(b) administering to the patient the therapeutic agent that the patient is predicted to respond positively to thereby treating the patient's systemic inflammatory condition.
Patent ‘872 claims are directed to:
A method of identifying a patient at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition comprising;
a) measuring selected physiological parameters in the patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6-keto F1α, thromboxane B2, leukotrienes B4, C4, D4 and E4, interleukin 1β, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;
b) producing a systemic mediators-associated response test profile for the patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters set forth in step (a); and
c) comparing said profile with an established control profile to identify the patient as being at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition wherein the systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma.
In view of the teachings in Slotman and Julia, it would have been prima facie obvious to one of ordinary skill in the art to have included multiple data associated with a patient (Slotman at page 2, col. 2; and use regression for assessment of data (Slotman at page 2, col. 2) as combined with gene expression data in Julia et al. for prediction and treatment with specific drugs based on said predictions. As such, said claims are obvious variants ones of the other.
2. Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 6,190,872 in view of Slotman et al. (Critical Care (2000) Vol. 4, No. 5:319-326) and in further view of Julia et al. (PLoS One (2009) Vol. 4, Issue 10:8 pages).
Instant claim 1 is directed to
A method for treating a systemic inflammatory condition, comprising:
(a) determining whether a patient with a systemic inflammatory condition will respond positively to a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids by
(i) receiving data regarding the patient, the data including baseline parameters of the patient, wherein said baseline parameters comprise one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests, wherein
said demographic variables are selected from the group consisting of age, sex, race, comorbidities, and medications;
said physiologic variables are selected from the group consisting of height, weight, temperature, MAP, heart rate, diastolic blood pressure, systolic blood pressure, mechanical ventilation, respiratory rate, pressure support, positive end- expiratory pressure, systemic vascular resistance, cardiac index, pulmonary capillary wedge pressure, blood count, prothrombin time, partial thromboplastin time, fibrin degradation products and D-dimer, urine output, chest X-rays, and bacterial cultures;
said gene expression profiles consist of upregulation or down regulation of expression of one or more protein kinases, growth factors, hormones, enzymes, chemokines, cytokines, receptors, transcription factors, zinc fingers, structural proteins, inflammatory mediators, cell cycle regulators, immune function genes, antimicrobial genes, extracellular matrix and remodeling genes, carbohydrate metabolism genes, and fatty acid metabolism genes; and
said results of hospital laboratory tests are selected from the group consisting of levels of albumin, alkaline phosphatase, ALT, AST, BUN, calcium, cholesterol, creatinine, GGT, glucose, hematocrit, hemoglobin, MCH, MCV, MCHC, phosphorus, platelet count, potassium, total protein, PT, PTT, RBC, sodium, total bilirubin, triglycerides, uric acid, WBCL, base deficit, pH, PaO2, SaO2, FiO2, chloride, and lactic acid;
(ii) generating from the baseline parameters a systemic mediator-associated response test (SMART) profile comprising independent variables of the systemic inflammatory condition of the patient, wherein the independent variables are selected from the one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests;
(iii) using multivariate regression analysis and stepwise regression analysis, to predict an outcome for treatment of the patient's systemic inflammatory condition with the therapeutic agent based at least on the SMART profile as compared to historical data regarding outcomes of said therapeutic agent administered to a plurality of patients in a phase II or phase III clinical trial; and
(b) administering to the patient the therapeutic agent that the patient is predicted to respond positively to thereby treating the patient's systemic inflammatory condition.
The claims of the ‘546 patent are directed to:
A method for identifying a patient who meets clinical entry criteria of a study for a new therapeutic agent for treating sepsis and would respond favorably to the new therapeutic agent said method comprising:
a) measuring physiological, respiratory, metabolic, renal, liver, hematologic and coagulation parameters of patients in clinical trials for a new therapeutic agent for treating sepsis;
b) establishing a systemic mediator-associated response control profile from results of clinical trials in sepsis that identifies patients among whom the new therapeutic agent for sepsis has been shown to have demonstrated efficacy, wherein the control profile comprises one or more of the parameters in step a);
c) measuring physiological, respiratory, metabolic, renal, liver, hematologic and coagulation parameters of a patient with sepsis;
d) generating a systemic mediator-associated response test profile for the patient with sepsis, said test profile comprising one or more of the parameters in step c); and
e) comparing the parameters of the test profile with the same parameters of the control profile, wherein similarities in the parameters of the test profile and the parameters of the established control profile is indicative of a patient that would respond favorably in a clinical trial to the new therapeutic agent for sepsis.
In view of the teachings in Slotman and Julia, it would have been prima facie obvious to one of ordinary skill in the art to have included multiple data associated with a patient (Slotman at page 2, col. 2; and use regression for assessment of data (Slotman at page 2, col. 2) as combined with gene expression data in Julia et al. for prediction and treatment with specific drugs based on said predictions. As such, said claims are obvious variants ones of the other.
3. Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 6,190,872 in view of Slotman et al. (Critical Care (2000) Vol. 4, No. 5:319-326) and in further view of Julia et al. (PLoS One (2009) Vol. 4, Issue 10:8 pages).
Instant claim 1 is directed to
A method for treating a systemic inflammatory condition, comprising:
(a) determining whether a patient with a systemic inflammatory condition will respond positively to a therapeutic agent that inhibits tumor necrosis factor, inhibits endotoxin activity, inhibits interleukin-1 receptor, or degrades platelet-activating factor and oxidized phospholipids by
(i) receiving data regarding the patient, the data including baseline parameters of the patient, wherein said baseline parameters comprise one or more gene expression profiles and one or more demographic variables, physiologic variables, and/or results of hospital laboratory tests, wherein
said demographic variables are selected from the group consisting of age, sex, race, comorbidities, and medications;
said physiologic variables are selected from the group consisting of height, weight, temperature, MAP, heart rate, diastolic blood pressure, systolic blood pressure, mechanical ventilation, respiratory rate, pressure support, positive end- expiratory pressure, systemic vascular resistance, cardiac index, pulmonary capillary wedge pressure, blood count, prothrombin time, partial thromboplastin time, fibrin degradation products and D-dimer, urine output, chest X-rays, and bacterial cultures;
said gene expression profiles consist of upregulation or down regulation of expression of one or more protein kinases, growth factors, hormones, enzymes, chemokines, cytokines, receptors, transcription factors, zinc fingers, structural proteins, inflammatory mediators, cell cycle regulators, immune function genes, antimicrobial genes, extracellular matrix and remodeling genes, carbohydrate metabolism genes, and fatty acid metabolism genes; and
said results of hospital laboratory tests are selected from the group consisting of levels of albumin, alkaline phosphatase, ALT, AST, BUN, calcium, cholesterol, creatinine, GGT, glucose, hematocrit, hemoglobin, MCH, MCV, MCHC, phosphorus, platelet count, potassium, total protein, PT, PTT, RBC, sodium, total bilirubin, triglycerides, uric acid, WBCL, base deficit, pH, PaO2, SaO2, FiO2, chloride, and lactic acid;
(ii) generating from the baseline parameters a systemic mediator-associated respon