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 .
Applicant’s response
Applicants’ response filed 9/8/2025 did not contain any amendments.
Original claims 1-20 filed 11/29/2020 are pending.
Election/Restriction
Applicant’s election of Group I in the reply filed on 9/8/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon initial search and consideration of the claim limitations of the three groups, it does not appear to be an undue burden to examine the three groups together. Accordingly, the restriction requirement is withdrawn.
Additionally, there was an additional requirement for an election of species, but it does not appear that Applicants replied to this. However, upon review it does not appear that the species of:
Specific diseases (see claims 2-3 for example);
Computational algorithm (see claim 4 for example); and
Specific systems modeled, immune, endocrine, hormone (see list in claim 2).
will require an undue burden, and the species election is also withdrawn.
Claims 1-20, drawn to a method to predict clinical outcome for a complex disease, drawn to a computer system comprising a processor and memory with instructions to accessing a complex disease intervention strategy, and to the program on a medium.
Priority
This application filed 11/29/2021 is a continuation in part of PCT/US2020/035367 filed 5/29/2020 which claims benefit to US Provisional application 62/854196 filed 5/29/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/22/2021 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that several of the cited references are Office actions are from foreign offices, some translated and some providing a summary. In review of these, the pending claims that were reviewed in these actions were not provided, but for completeness and clarity of the record the cited references when provided in this prosecution were not considered in light of the instant claims. The foreign statutes and comments of the reviewers were not clearly in context of the pending claims and were not considered for their logic nor factual accuracy of comments in actions from other foreign offices.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The first inquiry is to determine whether claims are directed to a statutory category of invention. In the instant case, claims 42-61 are directed to a statutory category, i.e. a process (Step 1: Yes).
The second inquiry in the analysis includes the question of whether or not the claims are directed to a judicial exception. The first prong of this analysis is to determine if the claims recite any limitations that are a judicial exception. Claims 42 and 55 recites limitations for identifying coordinated dynamics of identified lymphocyte cell populations, identifying a single consensus immune signaling network for the experiment and control groups, comparing the single consensus immune signaling network for the experimental group with the single consensus immune signaling network for the control group to identify changes in structure and information flow between networks, and identifying the potential therapeutic targets in ME/CFS from changes in structure and information flow identified between the single consensus immune signaling network of the experimental group and the single consensus immune signaling network of the control group. Claim 47 recites further limitations for identifying the coordinated dynamics using a linear rate equation model and projection-based parameter estimation technique. Claim 48 recites further limitations for using complex data sets for identifying coordinated dynamics. Claim 49 recites further limitations for comparing the consensus immune single networks using a graph theoretical analysis. Claims 50-54 and 57-61 recite further limitations on the type of potential therapeutic target identified. The limitations of claims 42, 50-55 and 57-61 under the broadest reasonable interpretation, cover evaluations or judgements performed in the human mind. The limitations of claims 47-49, under the broadest reasonable interpretation, cover utilizing mathematical calculations for identifying coordinated dynamics and comparing networks. Thus, the claims recite a judicial exception that is an abstract idea under Prong One of Step 2A.
The second prong of the analysis under Step 2A is to determine if the claims are directed to a judicial exception by evaluating if the claims integrate the judicial exception into a practical application or not. This judicial exception is not integrated into a practical application because the additional elements of the claims recite mere data gathering activity and do not recite any additional elements that provide a practical application of the recited judicial exceptions in the claim. Specifically, claim 42 recites additional elements of selecting groups of subjects, subjecting the subjects to a graded exercise test, collecting blood samples from the subjects at a more than 3 times before, during and after the exercise challenge, and analyzing the blood samples to identify lymphocyte cell populations and abundance in each blood sample. Claims 43-46 recite further limitations on these additional elements. However, these additional elements are utilized in order to gather data that is then utilized in the abstract idea steps. As such, these limitations equate to mere data gathering steps that do not integrate the claimed judicial exception into a practical application. Therefore, under the second prong of the analysis, the claims are directed to a judicial exception because they recite a judicial exception without integrating the judicial exception into a practical application of the judicial exception (Step 2A: Yes).
Next, the claims as a whole are analyzed to determine whether any additional element or combination of additional elements is/are sufficient to amount to significantly more than the exception. Claims 42 and 45-54 do not include additional elements that amount to significantly more than the judicial exception because they recite additional elements that equate to well-understood, routine and conventional activities known in the art. Claim 44 recites limitations for selecting subjects having myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an experimental group, selecting subjects without ME/CFS as a control group, subjecting both groups to a graded exercise test, collecting blood samples from each subject tests at more than 3 times points before, during and after the exercise challenge and analyzing the blood samples to identify lymphocyte cell populations and abundance in each blood sample. Claims 45-46 recite further limitations on analyzing the lymphocyte cell populations by detecting presence or absence of cluster designation surface markers and limiting the cluster designation markers to specific markers. The instant specification states that the graded exercise test is standard and administered using a commercially available product and the determination of cluster designation markers is determined using a commercially available flow cytometer (pg. 9, paras. 2-4 of the instant specification). Therefore, these elements are well-understood, routine and conventional in accordance with consideration 1 under the Berkheimer memorandum. In addition, the combination of these limitations is conventional as evidenced by LaManca et al. (Journal of Clinical Immunology 1999, vol. 19, no 2, pgs. 135-142), Broderick et al. (Brain, Behavior, and Immunity 2013, vol. 28, pgs. 159-169; IDS document), and Smylie et al. (BMC Immunology 2013, 14:29, pgs. 1-14; IDS Document). LaManca et al. discloses identifying groups of CFS patients and healthy patients, performing a graded exercise test and obtaining blood samples at more than 3 time points before, during and after the test and performing flow cytometry measurements to determine lymphocyte populations, including CD designation markers, in the blood samples (pg. 136, col. 1, para. 1 to pg. 137, col. 2, para. 1). Broderick et al. and Smylie et al. also disclose the combination of a graded exercise test on groups of CFS patients and healthy patients and determining lymphocyte cell populations with flow cell cytometry (pg. 160, col. 2, para. 2 to pg. 161, col. 2, para. 3 of Broderick et al. and pg. 3, col. 1, para. 2 to pg. 4, col. 1, para. 1 of Smylie et al.). The additional elements of claims 42 and 45-54 do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. However, claims 43 and 55 recites limitations for collecting blood samples at 9 predetermined time points across the exercise challenge during a time period of twenty four hours. Claims 45 and 55 also recite the limitations wherein the nine time points are baseline, baseline plus 3 minutes, VO2 max (maximum effort), 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 4 hours after VO2 max, and next day. There is no evidence in accordance with the Berkheimer memorandum dated 19 April that these elements are conventionally performed. Therefore, these elements equate to unconventional additional elements. Therefore, claims 42 and 45-54 do not amount to significantly more than the judicial exception itself (Step 2B: No) but claims 43-44 and 55-62 do amount to significantly more than the judicial exception itself (Step 2B: Yes). As such, claims 42 and 45-54 are directed to non-statutory subject matter and are therefore rejected under 35 U.S.C. 101. However, claims 43-44 and 55-62 are determined to be patent eligible subject matter.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Broderick et al. (Brain, Behavior, and Immunity 2013, vol. 28, pgs. 159-169; IDS document) and LaManca et al. (Journal of Clinical Immunology 1999, vol. 19, no 2, pgs. 135-142).
With respect to claim 1 and claims 2-3 setting forth specific diseases, Broderick et al. discloses selecting a set of ME/CFS subjects and a set of healthy subjects (pg. 160, col. 2, para. 2). Broderick et al. then discloses stimulating immune response with a standard graded exercise test for each subject and collecting blood samples prior to exercise, upon reaching peak effort (VO2 max) and at 4 hours post exercise (pg. 161, col. 1, para. 2). Broderick et al. then discloses performing flow cytometry on each sample to determine lymphocyte subset abundance (pg. 161, col. 2, para. 3). Broderick et al. then discloses determining patterns of pathway-symptom interaction by constructing multi-layer empirical networks that includes changes in immune cell abundance across subject groups and comparing the patterns of pathway-symptom interaction for each subject group to each other to identify immunological targets relevant to disease (pg. 162, col. 2, para. 4 to pg. 163, col. 1, para. 3; pg. 164, col. 1, para. 2 to pg. 167, col. 1, para. 3; Tables S4-S5).
Regarding claims 6-8 and indication that immune cells are analyzed, Broderick et al. discloses that analyzing the lymphocyte cell populations includes determining the abundance of lymphocytes with cluster designation surface markers CD19+, CD3+CD4+, CD3+CD8+, CD3+, CD3-CD56+, CD3-CD16+, CD2+, CD2+CD26+, CD4+CD26+, CD8+CD26+, CD8+CD11a+, and CD3-CD16+CD11a+ (pg. 161, col. 2, para. 3 and Table S3a). Broderick et al. discloses that the method of identifying patterns of pathway-symptom interaction via the construction of multi-layer empirical networks uses partial linear correlation and projection of the values onto minimal pathways using a logical consistency constraint (pg. 162, col. 2, para. 4 to pg. 163, co. 1, para. 3). Further, Broderick et al. discloses comparing graphs of correlation networks between subject groups to identify potential therapeutic targets (pg. 164, col. 1, para. 2 to pg. 167, col. 1, para. 3; Tables S4-S5).
For claim 1, step d) Broderick et al. is silent to the predetermined number of time points being at predetermined time points however, these limitations were known in the prior art at the time of the effective filing date of the invention. LaManca et al. discloses testing immunological response in CFS by having the subjects perform a graded exercise test and collecting blood samples at baseline prior to the exercise challenge, 4 mins after the session exercise, 1 hour after exercise and 24 hours later (pg. 136, col. 1, para. 1 to col. 2, para 4).
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the invention if some teaching or suggestion in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. LaManca et al. discloses obtaining four body samples before, during and after the graded exercise test for analysis of immunological response (pg. 136, col. 1, para. 1 to col. 2, para 4). LaManca et al. further disclose that the data to study changes in immune functioning as a result of chronic fatigue syndrome due to intense exercise and up to 24 hours, which is when feelings of fatigue for CFS patients were significantly increased (pg. 135, co. 2, para. 3; pg. 140, col. 1, para. 1). It would have been obvious to one of ordinary skill in the art to increase the number of blood samples in the method of Broderick et al. taken during the 24 hour period taught by LaManca et al. in order to increase the amount of data for statistical evaluation during the time period of interest for chronic fatigue syndrome. Furthermore, there is a reasonable expectation of success because both LaManca et al. and Broderick et al. disclose utilizing the same graded exercise test and blood sample evaluation for chronic fatigue syndrome. The invention is therefore 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.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,777298 (application 15/028757). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘298 are encompassed by the instant claims. The claims of ‘298 were amended in prosecution to more specifically set forth specific testing and time points and means of assessment of the data, all which are disclosed and encompassed by the instant claims.
A copy of the independent method for both are provided below for comparison and clarity of the pending claims.
Instant method, claim 1:
A method for predicting a clinical intervention strategy to treat a complex disease, the method comprising:
a) accessing a set of predefined conditions that include a number of inhibitors, a number of activators, a healthy control value, and a conditional state of one or more variables;
b) accessing a signaling network that represents a subject across a blood-brain barrier connecting to the subject's central nervous system to a blood-based system of the subject, wherein the signaling network includes the conditional state of one or more variables that produce outputs based on inputs and activations due to external influences on the signaling network, wherein the signaling network includes a set of nodes interconnected by at least one of a static stimulatory edge, a conditional stimulatory edge, an inhibitory edge, or a combination thereof,
c) accessing ternary logic modeling in which signaling molecules and cell types are represented as individual variables, each capable of adopting one of three distinct states;
d) performing computational algorithm that relies on repeated random sampling to obtain numerical results representing of state evolution of the signaling network to identify distinct states as potential stable behaviors compared with a healthy control;
e) topologically compare the model results of the neuroimmune signaling network with and without behavioral disorder to mouse models of a complex disease in blood and use corresponding states in a mouse brain to infer the blood-brain state of the subjects;
f) based on the conditional state of one or more variables equal to a given state, updating at least one of the conditional stimulatory edge to a static stimulatory edge and repeating step b through step e until convergence or for a set number of iterations; and
g) using the inferred blood-brain state of the subject to provide treatment courses thereto.
Claim 1 of ‘298:
A method of analyzing immune signaling networks for identification of potential therapeutic targets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), the method comprising:
selecting a group of subjects having ME/CFS as an experimental group;
selecting a group of healthy subjects not having ME/CFS as a control group;
subjecting both the experimental group and the control group to a graded exercise test (GXT) including an exercise challenge to induce expression of immune signaling networks in the subjects of both the experimental group and the control group in response to exercise;
collecting blood samples from each subject tested at a predetermined number of time points, before, during, and after subjecting the subjects to the exercise challenge, wherein the time points are baseline, baseline plus 3 minutes, V02 max (maximum effort), 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 4 hours after V02 max, and next day; analyzing the blood samples to identify lymphocyte cell populations and abundance in each blood sample at each of the time points;
applying a linear rate equation model and a projection-based parameter estimation technique to the identified lymphocyte cell population at each of the time points;
identifying coordinated dynamics of the identified lymphocyte cell populations identified to determine an immune signaling network, wherein the coordinated dynamics identified include information regarding direction of the immune signaling network, promotion or inhibition of the immune signaling network, and rate at which information is transmitted through the immune signaling network;
identifying a single consensus immune signaling network for the experimental group; 2 identifying a single consensus immune signaling network for the control group;
comparing the single consensus immune signaling network for the experimental group with the single consensus immune signaling network for the control group to identify changes in structure and information flow between the networks; and
identifying the potential therapeutic targets in ME/CFS from the changes in structure and information flow identified between the single consensus immune signaling network of the experimental group and the single consensus immune signaling network of the control group.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R Skowronek can be reached at 571 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Joseph Woitach/Primary Examiner, Art Unit 1687