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 .
Priority
This application is a Continuation of PCT Application No.: PCT/US2021/050623 filed September 16, 2021, which claims priority to and the benefit of U.S. Provisional Patent Application Numbers 63/079,746, filed September 17, 2020 and 63/079,742, filed September 17, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/23/2023 has been considered by the examiner.
Status of Claims
Claims 13-15 and 24-25 are canceled by Applicant. Claims 1-12 and 16-23 are pending and under examination.
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.
Claims 9-11 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. The phrase “a second agent (e.g., agent for treating or managing the viral respiratory infection)” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). In the present case, the claim is interpreted to be “...a second agent for treating or managing the viral respiratory infection."
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.
Claims 1-7, 9-12, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Chrusciel et al (US9,499,532 B2) in view of Van de Veerdonk et al (eLife, April 27, 2020;9: e57555), Garvin et al (eLife, July 7, 2020;9: e59177), and Vernuccio et al (Clin Radiol. 2020 Nov;75(11):804-810, Epub 2020 Aug 4).
Chrusciel teaches a method for preventing or treating undesired thrombosis or angioedema (e.g., hereditary angioedema) by administering one or more of compounds of the formula (I) that inhibit Factor XIa or kallikrein alone or in combination with other molecules to a mammal. (See column 2, lines 32-39.) Moreover, Chrusciel teaches the one or more compounds of the formula (I) includes compound 38
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. (See Fig. 1C and claim 11.) Chrusciel teaches the administration of the small molecule Factor XIa inhibitor should have the effect of inhibiting thrombin generation and clot formation with no or substantially no effect on bleeding times and little or no impairment of haemostasis. (See column 179, lines 4-8.) Chrusciel further teaches the method of prophylaxis of pulmonary embolism in a subject that has suffered a pulmonary embolism, comprising administering to the subject an effective amount of a compound of the formula (I)-(VII) or a pharmaceutically acceptable salt thereof. (See column 94, lines 1-5.) Again, the compound of the formula (I) includes the compound 38 with the above structure. Chrusciel teaches the compounds that can inhibit Factor Xia or Kallikrein can be useful to treat or prevent deep vein thrombosis. (See column 178, lines 40-49.) Lastly, Chrusciel teaches the compounds can be administered as a continuous intravenous infusion with a dosage ranging from about 0.5 to about 100 mg/kg of body weight every 4 to 120 hours. (See column 183, lines 1-10.) The 0.5 mg/kg every 4 to 120 hours amount to 0.125 mg/kg/hr to 0.004 mg/kg/hr and the 100 mg/kg every 4 to 120 hours results in 25 mg//kg/hr to 0.8 mg/kg/hr. Said 0.5 mg/kg every 4 to 120 hours touches and renders obvious the claimed 0.6 to 1.0 mg/kg/hr.
Chrusciel does not teach a subject having a viral respiratory infection, in this case Covid-19 which is an infection caused by coronaviruses and covid-19 syndrome.
Van de Veerdonk teaches COVID-19 patients can present with pulmonary edema early in disease is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. Blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS) was proposed. (See Abstract.) Van De Veerdon also teaches Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome. (See Title.)
Garvin a mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. (See Title.) Garvin also teaches the analyses found that SARS-CoV-2 caused the levels of ACE in the lung cells to decrease, while the levels of ACE2 increased. This in turn increased the levels of a molecule known as bradykinin in the cells (referred to as a ‘Bradykinin Storm’). The findings suggest that the Bradykinin Storm may be responsible for the more severe symptoms of COVID-19. (See fourth paragraph of page 2.)
Vernuccio teaches thrombotic complications due to COVID-19 are likely to occur due to a pro-coagulant pattern encountered in some of these patients or to a progressive endothelial thrombo-inflammatory syndrome causing microvascular disease. In the present authors' experience, from five different hospitals in Italy and the UK, imaging has proved its utility in identifying these COVID-19-related thrombotic complications, with translational clinical relevance. The aim of this review is to illustrate thromboembolic complications directly or indirectly related to COVID-19 disease. Specifically, this review will show complications related to thromboembolism due to a pro-coagulant pattern from those likely related to an endothelial thrombo-inflammatory syndrome. (See Abstract.) Moreover, Vernuccio teaches other thromboembolic complications in COVID-19 include catheter-related deep vein thrombosis and disseminated intravascular coagulation. (See last paragraph of the left column of page 809.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Chrusciel by including a patient with a respiratory viral infection in this case covid-19 and a subject at risk of thromboembolic complications such as deep vein thrombosis to give Applicant’s claimed method. One would have been motivated to do, because Chrusciel teaches compound 38 as having kallikrein inhibitory activity and able to reduce deep vein thrombosis and clotting formation and because Van De Veerdon teaches blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome, also because Garvin suggests that the Bradykinin Storm may be responsible for the more severe symptoms of COVID-19, and lastly because Vernuccio teaches other thromboembolic complications in COVID-19 include catheter-related deep vein thrombosis and disseminated intravascular coagulation. . One would reasonably expect the method taught by Chrusciel to effectively reduce the risk of thromboembolic complications such as deep vein thrombosis and blood clot in a subject having Covid-19 with success.
With respect to claims 9-11, Chrusciel, Van de Veerdonk, Garvin, and Vernuccio collectivity do not teach a second agent for treating or managing the viral respiratory infection and the administration sequence.
Vernuccio teaches anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients meeting sepsis-induced coagulopathy criteria or with markedly elevated D-dimer. (See second paragraph of the left column of page 805.)
It would have been prima facie obvious for a person of ordinary skill in the art at the time of the invention was filed to combine the method disclosed by the combination of
Chrusciel, Van de Veerdonk, Garvin, and Vernuccio with that set forth by Vernuccio because each is taught by the prior art to be useful for the same purpose (i.e., treating Covid-19). See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Further, a person of ordinary skill in the art would reasonably have expected to be successful because both compositions were shown to be useful separately for the exact same purpose and thus would be expected to be similarly useful when used together.
With respect to the administration sequence, the instant situation is amenable to the type of analysis set forth in Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) and also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), where the court found that the selection of any order of performing process steps is prima facia obvious in the absence of new or unexpected results. As such, applying the same logic to the instant process claims, one of ordinary skill in the art would have a reasonable expectation that by administering compound 38 prior to, concomitantly with, or following the administration of the low molecular weight heparin taught by Vernuccio, , one would achieve a method to reduce the risk of thromboembolic complications such as deep vein thrombosis and blood clot in a subject having Covid-19 and subject having covid-19 with success.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chrusciel et al (US9,499,532 B2) in view of Van de Veerdonk et al (eLife, April 27, 2020;9: e57555), Garvin et al (eLife, July 7, 2020;9: e59177), and Vernuccio et al (Clin Radiol. 2020 Nov;75(11):804-810, Epub 2020 Aug 4) as applied to claims 1-7, 9-12, and 16-18, in further view of Medina et al (. Nature. 2020; 580:130-135).
The teachings of Chrusciel, Van de Veerdonk, Garvin, and Vernuccio have been highlighted in the above rejection.
Chrusciel, Van de Veerdonk, Garvin, and Vernuccio collectively do not teach covid-19 syndrome.
Medina teaches in these times of a high incidence of post-COVID-19 acute respiratory distress syndrome anticipated to be due to an antiviral or damage-associated cytokine storm, novel therapies that restrict inflammation may be of interest to pursue for both transplanted and non-transplanted patients. (See last paragraph of the right column.) Post-covid-19 is another name for covid-19 syndrome.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Chrusciel, Van de Veerdonk, Garvin, and Vernuccio by including post-covid-19 acute respiratory distress syndrome to give Applicant’s claimed invention. One would have been motivated to do so, because not only the obvious method of Chrusciel, Van de Veerdonk, Garvin, and Vernuccio is known to treat ARSD, but also Medina teaches ARDS can be developed post-Covid-19 (aka covid-19 syndrome). One would reasonably expect the method taught by Chrusciel, Van de Veerdonk, Garvin, and Vernuccio to successfully treat post-COVID-19 acute respiratory distress syndrome.
Claims 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chrusciel et al (US9,499,532 B2) in view of Van de Veerdonk et al (eLife, April 27, 2020;9: e57555), Garvin et al (eLife, July 7, 2020;9: e59177), and Vernuccio et al (Clin Radiol. 2020 Nov;75(11):804-810, Epub 2020 Aug 4.) as applied to claims 1-7, 9-12, and 16-18, in further view of Gawda et al (Anaesthesiol Intensive Ther 03/2020; 52, 3: 253–255).
The teachings of Chrusciel, Van de Veerdonk, Garvin, and Vernuccio have been highlighted in the above rejection.
Chrusciel, Van de Veerdonk, Garvin, and Vernuccio collectively do not teach administration of compound 38 before, during, or after medical procedure where the medical procedure is veno venous ECMO and the subject is being or has been treated with a mechanical ventilation.
Gawda concludes that Veno-venous ECMO can be successfully applied not only in COVID-19 patients at the early stage of the ARDS, but also in COVID-19 convalescents with severely injured lungs. (See Conclusions Section of page 255.) Gawda reported that ECMO is implemented early and such procedure was usually started after 36 hours of mechanical ventilation. (See second paragraph of page 254.)
It would have been prima facie obvious for a person of ordinary skill in the art at the time of the invention was filed to combine the method disclosed by the combination of
Chrusciel, Van de Veerdonk, Garvin, and Vernuccio with method comprising veno venous ECMO after the subject being treated with mechanical ventilation set forth by Gawda because each is taught by the prior art to be useful for the same purpose (i.e., treating Covid-19). See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Further, a person of ordinary skill in the art would reasonably have expected to be successful because both compositions were shown to be useful separately for the exact same purpose and thus would be expected to be similarly useful when used together.
With respect to the administration sequence, the instant situation is amenable to the type of analysis set forth in Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) and also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), where the court found that the selection of any order of performing process steps is prima facia obvious in the absence of new or unexpected results. As such, applying the same logic to the instant process claims, one of ordinary skill in the art would have a reasonable expectation that by administering compound 38 before, during, or after venovenous ECMO taught by Gawda, one would achieve a method to reduce the risk of thromboembolic complications such as deep vein thrombosis and blood clot in a subject having Covid-19 and subject having covid-19 with success.
Conclusion
No claims are allowed.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628