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 .
Election/Restrictions
Applicant’s election of Group I, corresponding to claims 1-5, 7-8, 11-12, 15-18, 22-25 and 28-29 in the reply filed on January 6, 2026 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)).
Claim 41 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected kit, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 6, 2026.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on July 10, 2024 and December 10, 2024 are being considered by the examiner.
Claim Objections
Claim 18 is objected to because of the following informalities: “CXCL1” is repeated in step iv. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11-12, 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 recites “the control” in lines 1 and 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not mention a control. For examination purposes, examiner has interpreted “the control” as “a control”.
Claim 12 recites the limitation “any other acute and/or chronic inflammatory disorder”. The term “any other” renders the scope of the claim unclear because it is indefinite and fails to provide a reasonably certain boundary for the claimed subject matter. One of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the claimed invention because the phrase “any other” could encompass an indeterminate and potentially unlimited range of alternatives. For examination purposes, examiner has interpreted “any other and/or chronic inflammatory disorder” as “any acute or chronic inflammatory disorder”.
Claim 18 recites “the control” in lines 7, 9 and 13. There is insufficient antecedent basis for this limitation in the claim. See supra (Claim 11).
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 8, 11, 15 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 8 depends on claim 1 and recites the method further comprises: (i) determining a ratio of total TF levels to TF activity levels; (ii)obtaining a total TF level and a TF activity level in a sample obtained from a control subject; and/or (iii) measuring a total TF level and a TF activity level in a sample from a control subject.
Step 2A, Prong 1: identify the abstract ideas/law of nature/natural phenomenon.
Regarding claim 8, the claim recites “determining a ratio of total TF levels to TF activity levels” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of total TF levels to TF activity levels. This limitation therefore recites a mathematical calculation. This type of simple arithmetic calculation (division) can be performed in the human mind. The limitation also falls into the “mental process” groupings of abstract ideas. Accordingly, the limitation recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings).
Step 2A, Prong 2: has the abstract ideas/law of nature/natural phenomenon been integrated into a particular practical application?
Neither claim 1 nor claim 8 require any particular application of the recited calculation. Accordingly, the limitation of claim 8 does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Step 2B: does the claim recite any elements which are significantly more than the abstract ideas/law of nature/natural phenomenon?
The claim recites the additional element in limitations “(ii) obtaining a total TF level and a TF activity level in a sample obtained from a control subject and/or (iii) measuring a total TF level and a TF activity level in a sample obtained from a control subject” which do not require any particular application of the recited calculation and is at best the equivalent of data collection/measurement of the judicial exception.
Claim 11 depends on claim 1 and recites that “the TF activity level is elevated in the sample from the subject having an immunothrombotic condition as compared to the TF activity level in the control”.
Claim 18 depends on claim 17, which depends on claim 1, and recites “(ii) Lp(a), and wherein the Lp(a) is elevated in the sample from the subject having an immunothrombotic condition as compared to the Lp(a) in the control; (iii) IL-6, and wherein the IL-6 is elevated in the sample from the subject having an immunothrombotic condition as compared to the IL-6 level in the control; and/or (iv) …and wherein the at least one biomarker is altered in the sample from the subject having an immunothrombotic condition as compared to the level in the control.”
Step 2A, Prong 1: identify the abstract ideas/law of nature/natural phenomenon.
Regarding claim 11 the claim recites “is elevated in the sample from the subject having an immunothrombotic condition”.
Claim 18 recites “at least one biomarker is altered in the sample from the subject having an immunothrombotic condition”.
Both claims recite an evaluation that falls into the “natural phenomenon” groupings of abstract ideas.
Step 2A, Prong 2: has the abstract ideas/law of nature/natural phenomenon been integrated into a particular practical application?
Once the observation of the natural phenomenon is completed there are no process limitations leading to a tangible action. It appears there is no application and by extension, no practical application.
Step 2B: does the claim recite any elements which are significantly more than the abstract ideas/law of nature/natural phenomenon?
The claims as a whole do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4, 7, 8, 11-12, 15, 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Østerud (Increased Tissue Thromboplastin Activity in Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis).
Regarding claim 1, Østerud describes a method comprising obtaining a blood sample comprising a population of peripheral blood mononuclear cells (PBMCs) (monocytes) from a subject having an immunothrombotic condition (meningococcal infection); and measuring a total level of Tissue Factor (TF) (thromboplastin) and a level of TF activity (thromboplastin activity) in the sample obtained from the subject (pg. 5, Summary).
Regarding claim 2, Østerud describes the method further comprises isolating the population of PBMCs from the blood sample (pg. 5, Materials and Methods, Isolation of monocytes).
Regarding claim 3, Østerud describes the method further comprises isolating a population of monocytes and/or macrophages from the PBMCs (pg. 5, Materials and Methods, Isolation of monocytes).
Regarding claim 4, Østerud describes the method comprises measuring the total TF level and the TF activity level from the population of monocytes and/or macrophages (pg. 5, Materials and Methods, Isolation of monocytes).
Regarding claim 7, Østerud describes the method wherein measuring the TF activity level comprises measuring Factor Xa (pg. 5, Materials and Methods, Assay for tissue thromboplastin activity).
Regarding claim 8, Østerud describes (i) determining a ratio of total TF levels to TF activity levels. The ratio is inherently taught because Østerud determines the TF activity increase/activity level compared to a normal TF activity/total TF level (pg. 5, Results).
Regarding claim 11, Østerud describes the method wherein the TF activity level is elevated in the sample from the subject having an immunothrombotic condition as compared to the TF activity level in the control (pg. 5, Results).
Regarding claim 12, Østerud describes the immunothrombotic condition is selected from the group consisting of a virus infection, atherosclerotic cardiovascular disease (ASCVD), coronary heart disease (CHD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic kidney disease, and any other acute and/or chronic inflammatory disorder (meningococcal infection) (pg. 5, Summary).
Regarding claim 15, Østerud describes the immunothrombotic condition is characterized by an altered level of at least one biomarker (thromboplastin activity) (pg. 5, Summary).
Regarding claim 17, Østerud describes the method further comprises measuring a level of at least one biomarker (factor Xa) (pg. 5, Materials and Methods, Assay for tissue thromboplastin activity).
Claim(s) 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Østerud (Increased Tissue Thromboplastin Activity in Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis) as evidenced by Pathan et al. (Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock).
Regarding claim 16, Østerud describes a method for assessing an immunothrombotic condition but does not describe additional biomarkers to further characterize the condition.
Pathan describes the at least one biomarker comprises hyaluronan (Hyal), syndecan-1 (SDC1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa), Lipoprotein(a) (Lp(a)), interleukin 8 (IL-8), P-selectin glycoprotein ligand-1 (PSGL-1), and oncostatin M (OSM), heparan sulfate (HS), high-sensitivity cardiac troponin hs-cTn), high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein (LDL), von Willebrand factor (vWF), and any combinations thereof.
Pathan teaches that interleukin 6/IL-6 is a biomarker of myocardial depression in the immunothrombotic condition, meningococcal disease and that concentrations of interleukin 6 were raised after disease presentation (pg. 208, Discussion, "Interleukin 6 is a pleiotropic cytokine that has been characterised as a biomarker of early inflammatory responses in sepsis. Findings of studies in a few patients with meningococcal disease have established a relation between interleukin 6 and disease severity, which we have confirmed in our cohort of 140 patients. Concentrations of interleukin 6 remain raised…").
Pathan teaches that IL-6 is known to have a relationship with meningococcal infection (Pathan; pg. 203, Interpretation, "Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies."). Hence, it is evident that the infection taught by Østerud is characterized by changes in interleukin.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable by Østerud et al. (Increased Tissue Thromboplastin Activity Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis) in view of Wong et al. (US 2003/0082636A1).
Regarding claim 5, Østerud describes measuring total TF levels (pg. 5, Summary).
Østerud does not describe performing an immunoassay and/or fluorometric assay.
Wong describes the measuring total TF levels comprises performing an immunoassay (paragraph 0024).
Wong teaches that immunoassays can be employed in a competitive or non-competitive format to detect the presence and an amount of native TF in the biological sample. (Wong, paragraph 0024).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure the total TF levels in Østerud using the known alternative immunoassay technique of Wong as such methods were well-known for quantifying protein biomarkers in biological samples and would have predictably provided measurements of TF levels.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable by Østerud et al. (Increased Tissue Thromboplastin Activity in Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis) in view of Pathan et al. (Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock).
Regarding claim 18, Østerud in view of Pathan describes that the at least one biomarker comprises:(i) hyaluronan (Hyal), syndecan-1 (SDC1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa), Lipoprotein(a) (Lp(a)), interleukin 8 (IL-8), P-selectin glycoprotein ligand-1 (PSGL-1), and oncostatin M (OSM), and any combinations thereof (Pathan, pg. 208, Results, “amount of interleukin 6”).
Pathan teaches that interleukin 6/IL-6 is a biomarker of myocardial depression in the immunothrombotic condition, meningococcal disease and that concentrations of interleukin 6 were raised after disease presentation (pg. 208, Discussion, "Interleukin 6 is a pleiotropic cytokine that has been characterised as a biomarker of early inflammatory responses in sepsis. Findings of studies in a few patients with meningococcal disease have established a relation between interleukin 6 and disease severity, which we have confirmed in our cohort of 140 patients. Concentrations of interleukin 6 remain raised…").
Østerud teaches that tissue thrombosis is a direct inducer of DIC in meningococcal infection (Østerud; pg. 5, Summary). Pathan teaches that IL-6 is known to have a relationship with meningococcal infection (Pathan; pg. 203, Interpretation, "Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies."). A person of ordinary skill in the art would be motivated to use the method of claim 1 to measure the tissue factor level of an immunothrombotic condition with an IL-6 biomarker due to Pathan teaching that meningococcal infection is correlated with an elevated IL-6 biomarker.
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to use the relationship between IL-6 and meningococcal infection taught by Pathan with the method of Østerud to determine disease severity (Pathan; pg. 208, Discussion) and that treatment to block or neutralize the myocardial depressant effects of interleukin 6 could be a promising therapeutic direction, not only in septic shock but also in other inflammatory conditions associated with myocardial dysfunction (Pathan; pgs. 208-209, Discussion).
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Østerud et al. (Increased Tissue Thromboplastin Activity Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis).
Regarding claim 22, Østerud teaches that the method further comprises treating the subject based on the TF activity level (pg. 6, Discussion).
Østerud found that the course of the disease was strongly correlated with the concentration of tissue thromboplastin/tissue factor, as all 5 patients dying had superhigh thromboplastin activity/TF activity associated with the monocytes (pg. 6, Discussion). The conclusion was that Østerud found a close relation between the level of tissue thromboplastin activity/TF activity of the monocytes isolated from patients with meningococcal infection on admission to the hospital and the outcome of their disease. As high levels of tissue thromboplastin activity/TF activity were always prevailing in those patients in which the disease had a lethal outcome (pgs. 5-6, Discussion).
One of ordinary skill in the art would come to the conclusion that the patient with high TF activity levels would indicate the severity of the disease and the need for treatment.
Claim(s) 23-24, 28-29 is/are rejected under 35 U.S.C. 103 as being unpatentable by Østerud et al. (Increased Tissue Thromboplastin Activity Monocytes of Patients with Meningococcal Infection: Related to an Unfavourable Prognosis) in view of Levi (Disseminated intravascular coagulation).
Regarding claim 23, Østerud describes elevated TF activity levels in subjects with meningococcal infection/fulminant meningococcal septicemia with disseminated intravascular coagulation/DIC and disease prognosis (pg. 5 Results – pg. 6, Discussion).
Levi describes treating the subject comprises administering anti-thrombotic therapy/heparin (pg. 2194, Management).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date to administer an anti-thrombotic therapy to a subject having elevated TF activity as taught by Østerud. Because Levi teaches that TF mediated coagulation in infectious conditions is treated with anticoagulants in order to reduce pathological coagulation (pg. 2194, Conclusion).
Regarding claim 24, Østerud in view of Levi describes the anti-thrombotic therapy comprises administering a composition comprising heparin. See supra (Claim 23).
Regarding claim 28, modified Østerud describes a method for treating a subject having or suspected of having an immunothrombotic condition, the method comprising: (a) obtaining a blood samples comprising a population of peripheral blood mononuclear cells (PBMCs)/monocytes from a subject having an immunothrombotic condition; (b) measuring a total level of Tissue Factor (TF) and a level of TF activity in the sample obtained from a subject; and (c) administering anti-thrombotic therapy (heparin) and/or an apoptotic modulator to the subject to treat the immunothrombotic condition. See supra (Claim 23).
Regarding claim 29, Østerud describes the method further comprises isolating the population of PBMCs from the blood sample (pg. 5, Materials and Methods, Isolation of monocytes).
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable by Østerud et al. (Increased Tissue Thromboplastin Activity Monocytes of Patients with Meningococcal Infection: Related to an Unfavorable Prognosis) in view of Toltl et al. (Activated protein C modulates inflammation, apoptosis and tissue factor procoagulant activity by regulating endoplasmic reticulum calcium depletion in blood monocytes).
Regarding claim 25, Østerud in view of Levi describes treatment of the subject based on the TF activity level but does not describe treating the subject comprises administering an apoptotic modulator.
Toltl describes the administration of an apoptotic modulator (APC) and its effects on TF activity levels and apoptosis (pg. 582, Summary).
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to try to use the apoptotic modulator (APC) taught by Toltl to treat the subject based on TF activity level in the modified method of Østerud. Toltl taught that rAPC modulates inflammation and apoptotic responses in monocytes (pg. 583) and that it has additional anticoagulant properties via the regulation of monocyte TF expression and activity (TF factor and TF activity) (pg. 588, Effect of rAPC on TF antigen and TF activity in Tg-treated monocytes). A person of ordinary skill in the art would know that TF activity is a key prothrombotic biomarker and would consider administering such modulator after measuring TF activity levels in the Østerud method.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brianna K. Slade whose telephone number is (571)272-8514. The examiner can normally be reached Monday - Friday 8:30 AM - 2:00 PM.
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/B.K.S./Examiner, Art Unit 1796
/PAUL S HYUN/Primary Examiner, Art Unit 1796
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