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 National Stage application under 35 U.S.C. Q 371 of International Application No. PCT/US2021/025939 having an International Filing Date of April 6, 2021, which claims benefit of priority from U.S. Provisional Application Serial No. 63/010,376, filed on April 15, 2020, and U.S. Provisional Application Serial No. 63/005,937, filed on April 6, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/05/2023, 06/28/2023, 07/26/2023, 07/08/2024, and 12/02/2024 has been considered by the examiner.
Claim status
Claims 27-29, 31-35, 38-39, 42, and 45-53 are pending and under examination. Claims 1-26, 30, 36-37, 40-41, and 43-44 are canceled.
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, 27-29, 31-32, 42, 45, and 50-52 are rejected under 35 U.S.C. 103 as being unpatentable over Jackson et al (British Journal of Pharmacology (2017) 174 4738–475) in view of McGonagle et al (Autoimmunity Reviews 19, April 03, 2020, 102537, pages 1-8) and Li et al (Drug Design, Development and Therapy 2014:8 315–323).
Jackson teaches a method of mitigating pneumonitis/fibrosis in a mammal subject that has been exposed to high dose of radiation, the method comprising administering orally an effective amount of BIO 300 daily in the range of 200 or 400 mg/kg to said mammal subject, the BIO 300 is a nanoparticulate genistein (See Abstract and the second paragraph of the left column of page 4739.) Moreover, Jackson teaches the BIO 300 is provided at a concentration of 325 mg/ml at a total volume not exceed 0.5 ml. (See the second paragraph of the left column of page 4740.) For a 0.5 ml volume and a 325 mg/ml concentration, a 0.650 g (~ 1g) is achieved, meeting the limitations of claims 51 and 52.
Jackson does not teach the subject is a human subject and the subject is identified as being infected or having been infected with a coronavirus in this case SARS-Cov-2.
McGonagle teaches severe Covid-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). Covid-19 infection with MAS (macrophage activation syndrome) typically occurs in human patients with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. (See Abstract.) Moreover, McGonagle teaches cytokine profile, resembling MAS/sHLH has also been noted in COVID-19 patients, notably increased IL-1β, IL-2, IL-6, IL-17, IL-8, TNF and CCL2. The apparent recognition of MAS/sHLH complicating COVID-19 pneumonia forms the backdrop for cytokine suppression strategy. (See first paragraph of the left column of page 2.) McGonagle also teaches pneumonitis and lung injury can occur in Covid-19. (Table 1.)
Li teaches genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNFα-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. (See Abstract.)
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 of use the method of Jackson for treating or reducing pneumonitis and pneumonia in a mammalian subject that can include a human that is identified as being infected of Covid-19 (SARS-CoV-2) by suppressing IL-1β, IL-6, IL-8, TNF-α (cytokine storm) to give Applicant’s claimed invention. One would have been motivated to do so, because not only Jackson teaches genistein is effective for treating pneumonitis, but also because McGonagle teaches cytokine profile, resembling MAS/sHLH has also been noted in COVID-19 patients, notably increased IL-1β, IL-2, IL-6, IL-17, IL-8, TNF and CCL2, and also because Li teaches genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. One would have a reasonable expectation of success of using the BIO 300 formulation comprising nanoparticulated genistein to reduce or treat pneumonitis and pneumonia in a mammalian subject including a human, that is identified as being infected of Covid-19 (SARS-CoV-2), by suppressing IL-1β, IL-6, IL-8, TNF-α (cytokine storm).
Claims 1, 27-29, 31-32, 33-35, 38, 39, 42, 45, and 50-52 are rejected under 35 U.S.C. 103 as being unpatentable over Jackson et al (British Journal of Pharmacology (2017) 174 4738–475) in view of McGonagle et al (Autoimmunity Reviews 19, April 03, 2020, 102537, pages 1-8) and Li et al (Drug Design, Development and Therapy 2014:8 315–323) as applied to claims 1, 27-29, 31-32, 42, 45, and 50-52, in further view of Elder Jr. et al (US9,308,167 B2).
The teachings of Jackson, McGonagle, and Li have been highlighted in the rejection set forth above.
Jackson, McGonagle, and Li collectively do not teach the nanoparticulate genistein has a particle size distribution characterized by a d(0.5) less than or equal to 0.5 µm (claim 33). Moreover, Jackson, McGonagle, and Li do not teach polyvinylpyrrolidone (claim 34), one or more pharmaceutically acceptable excipients that include a nonionic surfactant, a diluent, a preservative, or a buffer (claims 35, 38, and 39).
Elder Jr. teaches genistein has proven difficult to formulate and deliver to subjects in a manner that achieves and maintains therapeutically effective blood plasma levels. (See lines 24-26 of column 1.) Moreover, Elder Jr. teaches the formulations oral or parenteral potentially provide several advantages. For example, because they can be used to achieve therapeutic plasma concentrations of genistein using less amounts of drug Substance and, in Some embodiments, relatively fewer doses, the formulations described herein may reduce the costs of genistein treatments as well as any potential side effects that may be associated with relatively higher doses of the compound. Moreover, because the formulations described herein enable delivery of therapeutic amounts of genistein using relatively smaller administered amounts of formulated drug, they may ease patient compliance and expand the contexts in which administration of genistein may be utilized. (See lines 28-42 of column 2.) Said formulation is a nanoparticulate comprising povidone K 17(polyvinylpyrrolidone), polysorbate 80, genistein, and water) having a particle size distribution d(0.5) of less than 0.2 µm. (See Table 5, and lines 18-20 of column 16.) Elder Jr. teaches a polyvinylpyrrolidone is a water-soluble polymer, polysorbate 80 is a nonionic surfactant, and a preservative. (See lines 2-5 of column 7; line 41 of column 6; and line 58 of column 9.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to formulate the nanoparticulate genistein taught by Jackson by incorporating polyvinylpyrrolidone, a nonionic surfactant, and a preservative in order to give a particle size distribution d(0.5) of less than 0.2 µm. The motivation to do so is to achieve a plasma concentration of genistein using less amounts of drug substance, relatively fewer doses, reduce the costs of genistein treatments as well as any potential side effects that may be associated with relatively higher doses of the compound. One would reasonably expect the obvious method taught by Jackson, McGonagle, and Li to be benefited from said formulation.
Claims 1, 27-29, 31-32, 42, 45, 46-49, 50-52, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Jackson et al (British Journal of Pharmacology (2017) 174 4738–475) in view of McGonagle et al (Autoimmunity Reviews 19, April 03, 2020, 102537, pages 1-8) and Li et al (Drug Design, Development and Therapy 2014:8 315–323) as applied to claims 1, 27-29, 31-32, 42, 45, and 50-52, in further view of McCreary et al (Open Forum Infect Dis. 2020 Mar 23;7(4) pages 1-11) and Pan et al (Radiology. 2020 Feb 13:200370).
The teachings of Jackson, McGonagle, and Li have been highlighted in the rejection set forth above.
Jackson, McGonagle, and Li collectively do not teach administer the composition within about 1 to about 96 hours of diagnosis with a coronavirus infection or within about 1 to 96 hours (claim 46), within about 1 hour to about 72 hours (claim 47), about 4 to 8 weeks (claim 48), and about 8 to 12 weeks (claim 49) after diagnosis with a coronavirus infection or of onset of one or more symptoms of coronavirus infection.
McCreary teaches the authors proposed the importance of early therapy initiation to diminish virus replication and promote pulmonary repair because remdesivir demonstrated less clinical benefit with high-titer virus inoculum. (See first paragraph of the right column of page 2.) Moreover, McCreary teaches given that disease progression can occur rapidly in stable patients and that viral loads are highest early in the infection course, the authors of this review opine that rapid initiation of therapy in high-risk populations. (See last paragraph of the right column of page 8.) Furthermore, McCreary teaches it warrants comment that in the recent randomized controlled trial in COVID-19 pneumonia, the median time from symptom onset to initiation of therapy was 13 days, and in the SARS-CoV-1 experience, therapy appeared effective if started early, but not as rescue and/or salvage. (See second paragraph of the left column of page 6.)
Pan teaches in patients who recovered from COVID-19 pneumonia, initial lung findings on chest CT (computed tomography) were small subpleural ground glass opacities (GGO) that grew larger with crazy-paving pattern and consolidation. Lung involvement increased to consolidation up to two weeks after disease onset. After two weeks, the lesions were gradually absorbed leaving extensive GGO and subpleural parenchymal bands. (Key Results Section.) Moreover, Pan teaches chest CT abnormalities increased in number and severity of lesions in the first 10 weeks (peaking at approximately 10 days). Subsequently, there was a short plateau phase and a gradual decrease in abnormalities. (See first paragraph under Discussion Section.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the obvious method taught by Jackson, McGonagle, and Li at within about 1 to about 96 hours of diagnosis with a coronavirus infection or within about 1 to 96 hours and within about 1 hour to about 72 hours, beginning about 4 to 8 weeks and about 8 to 12 weeks after diagnosis with a coronavirus infection or of onset of one or more symptoms of coronavirus infection that include pneumonia, for treating or reducing pneumonia in a mammalian identified as being infected with Covid-19 (SARS-CoV-2) to give Applicant’s claimed invention. One would have been motivated to do so, because McCreary teaches in the Covid-19 experience group, therapy appeared effective if started early, but not as rescue and/or salvage and also because Pan teaches chest CT abnormalities increased in number and severity of lesions in the first 10 weeks (peaking at approximately 10 days). One would reasonably expect the administration timing to improve patient compliance.
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 27-29, 31-35, 38-39, 42, and 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-33, 36- and 42-47 of copending Application No. 18/271,125 (reference application) in view of McGonagle et al (Autoimmunity Reviews 19, April 03, 2020, 102537, pages 1-8) and Li et al (Drug Design, Development and Therapy 2014:8 315–323). Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending claims teach a method for reducing inflammation and/or an immune response in a mammal identified as having an inflammatory or immunological disorder, the method comprising administering to the mammal a composition comprising genistein in an amount effective to reduce inflammation and/or an immune response in the mammal. (See claim 25.) The copending claims teach the genistein is nanoparticulate genistein and the composition has a nanoparticulate genistein concentration between about 250 mg/mL and about 500 mg/mL. (See claims 26-27.) The subject is human. After all the dependent claims of the copending claims are substantially similar to the instant claims.
The copending claims do not teach treating or reducing pneumonitis and pneumonia in a mammalian subject that can include a human that is identified as being infected
McGonagle teaches severe Covid-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). Covid-19 infection with MAS (macrophage activation syndrome) typically occurs in human patients with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. (See Abstract.) Moreover, McGonagle teaches cytokine profile, resembling MAS/sHLH has also been noted in COVID-19 patients, notably increased IL-1β, IL-2, IL-6, IL-17, IL-8, TNF and CCL2. The apparent recognition of MAS/sHLH complicating COVID-19 pneumonia forms the backdrop for cytokine suppression strategy. (See first paragraph of the left column of page 2.) McGonagle also teaches pneumonitis and lung injury can occur in Covid-19. (Table 1.)
Li teaches genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNFα-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. (See Abstract.)
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 of use the method of the copending claims for treating or reducing pneumonitis and pneumonia in a mammalian subject that can include a human that is identified as being infected of Covid-19 (SARS-CoV-2) by suppressing IL-1β, IL-6, IL-8, TNF-α (cytokine storm) to give Applicant’s claimed invention. One would have been motivated to do so, because McGonagle teaches cytokine profile, resembling MAS/sHLH has also been noted in COVID-19 patients, notably increased IL-1β, IL-2, IL-6, IL-17, IL-8, TNF and CCL2, and also because Li teaches genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. One would have a reasonable expectation of success of using the method of the copending claims to reduce or treat pneumonitis and pneumonia in a mammalian subject including a human, that is identified as being infected of Covid-19 (SARS-CoV-2), by suppressing IL-1β, IL-6, IL-8, TNF-α (cytokine storm).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 27-29, 31-35, 38-39, 42, and 45-53 are not allowed.
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/JEAN P CORNET/ Primary Examiner, Art Unit 1628