DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 18 JUNE 2026 has been entered.
Status of Claims
The claim set filed on 18 JUNE 2026 submitted with the RCE is considered. In the claim set, Claims 1, 6 and 8 are ‘Currently Amended’; Claims 2-5 and 9 are ‘Previously presented’; Claims 14-15 are marked as ‘New’, however, these claim were submitted in the previous claim set and are considered to be ‘Previously presented’; and Claims 7 and 10-13 are ‘Cancel’.
Current pending claims are Claims 1-6, 8, 9, and 14-15 and are considered on the merits below.
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 6 and 8 are rejected under 35 U.S.C. 101 because the claimed invention, Claim 6 is directed to an abstract idea without significantly more; and Claim 8 is directed to an abstract idea without significantly more. The claim recites a method for identifying a subject as having or that will develop Post-Traumatic Stress Disorder (PTSD) and treating the subject, said method comprising measuring a level of Plasminogen activator inhibitor-1 (PAI-1) protein in a body fluid sample obtained from said subject, determining that the subject has a higher level of PAI-1 protein compared to a control reference value, and treating the subject determined to have a higher level of PAI-1 protein compared to the control reference value by administering a PAI-1 antagonist to prevent or treat PTSD in the subject. in Claim 6; and similarly in Claim 8 method for monitoring a therapy for treating Post- Traumatic Stress Disorder (PTSD) in a subject and treating the subject comprising measuring a level of Plasminogen activator inhibitor-1 (PAI-1) in a first body fluid sample obtained from said subject at tl, wherein tl is prior to or during therapy for PTSD, measuring a level of PAI-1 in a second body fluid sample obtained from said subject at t2, wherein t2 is during or following therapy, and when tl is during therapy, t2 is later during therapy or following therapy for PTSD, and either determining that the level of PAI-1 in the sample measured at t2 is decreased compared to the level of PAI-1 in the sample measured at tl, and treating the subject determined to have a decreased level of PAI-1 by maintaining a dosage of a PAI-1 antagonist, or determining that the level of PAI-1 in the sample measured at t2 is increased compared to the level of PAI-1 in the sample measured at t1, and treating the subject determined to have an increased level of PAI-1 by increasing a dosage of the PAI-1 antagonist, which are all considered to be an abstract idea and can be performed with the human mind and is considered a mental analysis step.
The limitation of Claim 6 of ‘measuring the level of PAI-1 in a subject…determining the subject has a high level of PAI-1 compared to a control reference value and ….treating…’ is a measuring step and is therefore data gathering and comparing can be done mentally is an abstract idea. In addition, the treating step is not particular and is merely instructions to “apply” the exception in a generic way. Thus the treating step does not integrate the mental analysis step into a practical application. “The claims teach treating the subject and this treatment is not specifically detailed so there is no particular application claimed and is therefore not significantly more than an abstract idea.” The treatment of PAI-1 must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). Furthermore, although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. The treatment limitation must have more than a nominal or insignificant relationship to the exception(s).
The limitation in Claim 8 of measuring the levels of PAI-1 in a first sample and in a second sample, and determining the different levels and comparing and treating, as drafted measuring step is therefore data gathering and determining/comparing can be done mentally and is an abstract idea. While in the instant claim measuring level during or following therapy this is necessary for all uses of the recited exception thus it is an extra-solution activity , and does not integrate the judicial exception into a practical application. In addition, the treating step is not particular and is merely instructions to “apply” the exception in a generic way. Thus the treating step does not integrate the mental analysis step into a practical application. “The claims teach treating the subject and this treatment is not specifically detailed so there is no particular application claimed and is therefore not significantly more than an abstract idea.” The treatment of PAI-1 must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). Furthermore, although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. Thus the treating step does not integrate the mental analysis step into a practical application.
If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental Processes” grouping of abstract ideas. Accordingly, the claim recites an abstract idea.
This judicial exception is not integrated into a practical application. In each of Claims 6 and 8, the method as claim is recited at a high-level of generality and the claims as a whole does not integrate the judicial exception into a practical exception. In the claims, after the comparison step and generic treatment step; nothing else is done. As mentioned above, the treating step is not particular and is merely instructions to “apply” the exception in a generic way. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. There are no additional steps which are significantly more than the abstract idea.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, the additional element of ‘treating’ is not particular and is merely instructions to “apply” the exception in a generic way. Mere instructions for treating cannot provide an inventive concept. Each of the claims do not include limitations which are more than well understood routine and conventional.
The claims are not patent eligible.
Claim 9 merely recites where the sample is to be obtained from which is does not make the method have a practical application nor is it significantly more than the abstract idea.
Claim 14 attempts to further define what the PAI-1 antagonist does. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. MPEP 2106.040 (a)(2)(III).
Claim 15 just further defines the PAI-1 antagonist to not be EGCG, which does not make the invention practical nor significantly more.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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.
Claims 1-5 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BOMBI, submitted on the Information Disclosure Statement on 23 DECEMBER 2022, Non-Patent Literature Documents, Cite No. 1.
Applicant’s invention is directed towards a method.
Regarding Claim 1, the reference BOMBI discloses a method of preventing or treating Post-Traumatic Stress Disorder (PTSD) in a patient in need thereof, page 979, chronic treatment of EGCG…effective in modulating stress stimulated behavioral alternations such as PTSD, comprising : administering to a patient identified has having or that will have PTSD the patient a therapeutically effective amount of a Plasminogen activator inhibitor-1 (PAI-1) antagonist sufficient to reverse, alleviate, or inhibit one or more symptoms of PTSD, title , abstract, page 979, chronic treatment of EGCG…effective in modulating stress stimulated behavioral alternations such as PTSD, page 980: Materials and Methods, Epigallocatechin gallate administration.
Additional Disclosures Included are: Claim 2: wherein the method according to claim 1, wherein said PAI-1 antagonist directly binds to PAI-1 protein or to a-nucleic sequence encoding PAI-1 and promotes tPA/plasmin activity to mediate the proteolytic processing of pro-Brain derived neurotrophic factor (pro-BDNF) to mature BDNF, Materials and Methods, Epigallocatechin gallate administration. Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”) ; Claim 3: wherein the method according to claim 1 wherein said PAI-I antagonist is 1) an inhibitor of PAI-1 activity and/or 2) an inhibitor of PAI-1 gene expression, page 980: Materials and Methods, Epigallocatechin gallate administration, It is known in the art that Epigallocatechin-3-gallate (EGCG) Serves as a Novel Scaffold for Designing an Inhibitor of Plasminogen Activator Inhibitor-1 (PAI-1). ; Claim 4: wherein the method according to claim 3 wherein said inhibitor of PAI-I activity is selected from the group consisting of a small organic molecule, an anti-PAI-1 neutralizing antibody, a polypeptide and an aptamer, page 979-980: abstract, Introduction EGCG, Materials and Methods, Epigallocatechin gallate administration. ; Claim 5: wherein the method according to claim 3 wherein the inhibitor of PAI-1 gene expression is selected from the group consisting of an antisense oligonucleotide, a nuclease, siRNA, shRNA and a ribozyme nucleic acid sequence, page 979-980: abstract, Introduction EGCG, Materials and Methods, Epigallocatechin gallate administration. ; and Claim 14: wherein the method according to claim 1, wherein the PAI-1 antagonist reduces a number of pathological memories in the patient, page 979, 984 abstract, Discussion.
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) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over BOMBI in view of CHAN, 2018. Inhibition of PAI (plasminogen activator inhibitor)-1 improves brain collateral perfusion and injury after acute ischemic stroke in aged hypertensive rats. Stroke, 49(8), pp.1969-1976.
Regarding Claim 15, the BOMBI reference discloses the claimed invention , but is silent in regards to wherein the PAI-1 antagonist is not epigallocatechin gallate (EGCG).
The CHAN reference discloses a method of treating a patient with a brain injury, abstract, page 1969, the method comprising : administering to a patient identified has having a brain injury, page 1970, Stroke Outcome Determinations, the patient a therapeutically effective amount of a Plasminogen activator inhibitor-1 (PAI-1) antagonist sufficient to reverse, alleviate, or inhibit one or more symptoms, page 1974, Discussion, TM5441 administration, abstract, Methods, Results.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the type of PAI-1 antagonist to not be epigallocatechin gallate (EGCG) as suggested by CHAN because the administration of TM5441 significantly increased collateral perfusion and dilated leptomeningeal anastomotic arterioles by 44±10%, abstract, ‘Results’; page 1974 Discussion.
Claim(s) 6, 8 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over CHAN, 2018. Inhibition of PAI (plasminogen activator inhibitor)-1 improves brain collateral perfusion and injury after acute ischemic stroke in aged hypertensive rats. Stroke, 49(8), pp.1969-1976 and further in view of BOMBI.
Applicant’s method is directed towards a method.
Regarding Claim 6, the reference CHAN discloses a method for identifying a subject as assessing a subject's risk of having or that will develop a brain injury and treating the subject, page 1969, abstract, said method comprising measuring a level of Plasminogen activator inhibitor-1 (PAI-1) protein in a body fluid sample obtained from said subject, abstract, page 1969, page 1970, Determination of Circulating Oxidative Stress and Inflammation Markers, determining that the subject has a higher level of PAI-1 protein compared to a control reference value, page 1970, Data Calculations and …, page 1972, Inhibition of PAI-1 During MCA…; and treating the subject determined to have a higher level of PAI-1 protein compared to the control reference value by administering a PAI-1 antagonist , page 1972, Inhibition of PAI-1 During MCA…, page 1969, abstract, page 1974 Discussion.
The CHAN reference discloses a method of identifying and treating a patient with a brain injury with the use of a PAI-1 inhibitor/antagonist, however it is silent in the preamble language of patient that is ‘having or will develop Post-Traumatic Stress Disorder’ and using the PAI-1 antagonist to prevent or treat PTSD in the subject.
BOMBI discloses a method of preventing or treating Post-Traumatic Stress Disorder (PTSD) in a patient in need thereof, comprising : administering to a patient identified has having or that will have PTSD the patient a therapeutically effective amount of a Plasminogen activator inhibitor-1 (PAI-1) antagonist sufficient to reverse, alleviate, or inhibit one or more symptoms of PTSD, title , abstract, Materials and Methods, Epigallocatechin gallate administration.
It would be obvious to one having ordinary skill in the art to modify the method of diagnosis and treatment in CHAN such that the traumatic event in the brain is / can be linked and diagnosed / accompanied with post-traumatic stress disorder as they both can have overlapping symptoms such as memory problems, irritability, anxiety and mood changes as well as sleep disturbance and negative thoughts and feelings. While CHAN teaches the use of a PAI-1 inhibitor “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999), so it would be obvious to use the PAI-1 taught in CHAN to be used to identify and treat a patient with PTSD.
See also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”)
Applicant’s invention is directed towards a method.
Regarding Claim 8, the reference CHAN discloses a method for monitoring a therapy for treating a brain injury in a subject and treating the subject comprising :
measuring a level of Plasminogen activator inhibitor-1 (PAI-1) in a first body fluid sample obtained from said subject at tl, abstract: Methods, wherein tl is prior to or during therapy for a brain injury , abstract: Methods, without treatment of PAI-1 inhibitor, page 1970, Model of Transient Focal Ischemia and Treatment, measuring a level of PAI-1 in a second body fluid sample obtained from said subject at t2, abstract, Methods, with treatment of PAI-inhibitor, page 1970, Model of Transient Focal Ischemia and Treatment, wherein t2 is during or following therapy, page 1970, Model of Transient Focal Ischemia and Treatment, and when tl is during therapy, t2 is later during therapy or following therapy for the brain injury, page 1970, Determination of Circulating Oxidative Stress and Inflammatory Markers , and either determining that the level of PAI-1 in the sample measured at t2 is decreased compared to the level of PAI-1 in the sample measured at tl, and treating the subject determined to have a decreased level of PAI-1 by maintaining a dosage of a PAI-1 antagonist, or determining that the level of PAI-1 in the sample measured at t2 is increased compared to the level of PAI-1 in the sample measured at t1, and treating the subject determined to have an increased level of PAI-1 by increasing a dosage of the PAI-1 antagonist, , page 1970, Determination of Circulating Oxidative Stress and Inflammatory Markers, Data Calculations and Statistical Analysis.
The CHAN reference discloses a method of identifying and treating a patient with a brain injury with the use of a PAI-1 inhibitor/antagonist, however it is silent in the preamble language of patient that is ‘monitoring a therapy for treating Post-Traumatic Stress Disorder’.
BOMBI discloses a method of monitoring a therapy for treating Post-Traumatic Stress Disorder (PTSD) in a subject and treating the subject comprising: administering to a patient identified has having or that will have PTSD the patient a therapeutically effective amount of a Plasminogen activator inhibitor-1 (PAI-1) antagonist sufficient to reverse, alleviate, or inhibit one or more symptoms of PTSD, title , abstract, Materials and Methods, Epigallocatechin gallate administration.
It would be obvious to one having ordinary skill in the art to modify the method of diagnosis and treatment in CHAN such that the traumatic event in the brain is / can be linked and diagnosed / accompanied with post-traumatic stress disorder as they both can have overlapping symptoms such as memory problems, irritability, anxiety and mood changes as well as sleep disturbance and negative thoughts and feelings. While CHAN teaches the use of a PAI-1 inhibitor “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999), so it would be obvious to use the PAI-1 taught in CHAN to be used to identify and treat a patient with PTSD.
See also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”)
Additional Disclosures Included is: Claim 9: wherein the method according to claim 6, wherein the body fluid sample is blood sample and/or urine sample, CHAN, page 1970, Determination of Circulating Oxidative Stress and Inflammatory Markers.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 EST.
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CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797
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