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 .
Information Disclosure Statement
Two information disclosure statements (IDS) submitted: one on 05/27/2025 and one on 05/30/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains several embedded hyperlinks (see page 28, [0138], last 2 lines; also check [0155], [0186], [0202], [0216]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
While the Examiner has made every attempt to check the Specification for hyperlink compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding hyperlink use compliance.
The use of the terms Respimat®, Akita®, Alvesco (see page 107), etc. (many others throughout the spec.) which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
While the Examiner has made every attempt to check the Specification for trade mark compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding trade mark use compliance.
The attempt to incorporate subject matter into this application by reference shown below (see page 30, for example) is ineffective because the root words “incorporate” and/or “reference” have been omitted, see 37 CFR 1.57(c)(1).
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While the Examiner has made every attempt to check the Specification for incorporation by reference language compliance, Applicant is required to carefully check the entire Specification for compliance.
Drawings
The drawings are objected to because:
In Fig. 6E-6H, the “No Hit”/ “Hit” and “No Toxic”/ “Toxic” labels look indistinguishable from each other within the figures and in the legends.
In Fig. 5A-5B and 6E-6K does not show specifically which “compounds” or “selected compounds” correspond to which data point.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 05/08/2026 is acknowledged. Upon election of Group I Applicant was further required to elect:
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Applicant has elected:
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Claims 88 and 94 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/08/2026.
Status of the Claims
Claims 1, 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, 48, 58, 72, 88, and 94 are pending in this application. Claims 2-4, 6-9, 11-13, 15-17, 19, 21, 24-29, 31, 33-37, 42, 44-47, 49-57, 59-71, 73-87, 89-93, and 95-97 have been cancelled by Applicant. Claims 1, 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, 48, 58, and 72 are under examination herein. Claims 88 and 94 have been withdrawn from consideration.
Claim Objections
Claims 18 and 20 are objected to because of the following informalities:
In claims 18 and 20, “single-stranded ssRNA” should read “single-stranded RNA” or simply “ssRNA” to avoid redundance.
Appropriate correction is required.
Examiner Notes
While claims 88 and 94 are not under examination herein, for the purposes of compact prosecution, the Examiner would like to point out that these claims are indefinite due to the reference to tables 2-8 of the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, 48, 58, and 72 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 48, and 58 relate to a method of treatment comprising administration of a compound, an acceptable salt, ester, solvate, stereoisomer, tautomer, or prodrug thereof.
The purpose of the written description requirement is to “ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.” University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920 (Fed. Cir. 2004), (quoting Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345 (Fed. Cir. 2000)). To determine whether there is adequate written description support for the genus of methods and means of achieving the claimed properties, the Specification is reviewed for species that achieve the claimed results. "[T]he specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Ariad, 94 USPQ2d at 1170-1171. See MPEP 2163 (I).
Tables 2-8 contain many different compounds with distinct structures and properties. Specifically for elected compound LXS-196, the specification makes no mention of specific esters or solvates of this compound, other than general statements that these esters or solvates thereof may generally be administered as part of treatment.
In sum, while one of ordinary skill might conclude that Applicant was in possession of LXS-196, pharmaceutically acceptable salts thereof, stereoisomers, tautomers, or prodrugs thereof; one would not conclude that applicant was in possession of esters or solvates thereof.
Claims 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, and 72 are rejected for depending upon the limitations of claim 1.
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 1, 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, 48, 58, and 72 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.
Claims 1, 48, and 58 are rejected because, as stated in MPEP 2173.05(s), claims should be complete to themselves and the reference to tables in the specification renders the claims incomplete. Claims which recite figures or tables are only permitted in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into a claim.
Claims 5, 10, 14, 18, 20, 22-23, 30, 32, 38-41, 43, and 72 are indefinite for depending upon the limitations of claim 1.
Claim 5 recites the limitation "the cell expresses . . .". There is insufficient antecedent basis for this limitation in the claim. For the purposes of applying art, it will be assumed Applicant intended, “wherein the cells of the subject suffering from the infection or disease express angiotensin-converting enzyme 2 (ACE2).”
Claim 10 recites the limitation "the inflammatory effect . . .". There is insufficient antecedent basis for this limitation in the claim. For the purposes of applying art, it will be assumed Applicant intended “wherein the infection or disease leads to inflammatory effects comprising respiratory failure, …”.
Regarding claim 39, it is unclear how Applicant intends to measure “lung bulk virus titer” prior to treatment administration, and still be able to administer treatment as required by the method of claim 1. As an initial matter, the term “lung bulk virus titer” is not defined in the specification. The art (specifically see Flano et al. reference cited herein) seems to require removal/ biopsy of lungs from diseased subject in order to measure the “lung bulk virus titers,” therefore, if “lung bulk virus titer” is measured prior to administration of treatment, the subject will have passed away and will not be able to receive the treatment (?), as required by claim 1. For the purposes of applying art, it will be assumed that lung bulk virus titer was measured after administration of treatment.
Claim Rejections - 35 USC § 103
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, 10, 14, 18, 20, 22-23, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”).
Regarding claim 1, Knox discloses protein kinase C (PKC) inhibitors, including IDE196 (same as elected compound LXS-196) (page 31, Example 3). Knox discloses “PKC inhibitor” refers to a pan inhibitor or selective to one or more PKC isoenzymes, including PKCα and PKCβ [0023].
While Knox does not disclose their PKC inhibitor, IDE196, for the treatment of RNA viruses, such as SARS-CoV-2; the teachings of Ghashghaeinia are relied upon for these disclosures.
Ghashghaeinia discloses that the use of a specific PKCα/ β inhibitor should be a promising approach to treat people infected with SARS-CoV-2 (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Knox’s IDE196 (a known PKC inhibitor) for the treatment of COVID-19. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Knox discloses IDE196 as a safe compound for human administration (see [00105]), which may be a pan PKC inhibitor or selective to one or more isoenzymes, including PKCα and PKCβ; further because Ghashghaeinia suggests the use of a specific PKCα/ β inhibitor should be a promising approach to treat people infected with SARS-CoV-2.
Regarding claims 10, 14, 18, 20, and 22-23, Ghashghaeinia discloses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (abstract); a single-stranded RNA virus (page 3399, col. 2, line 3).
Regarding claim 40, Ghashghaeinia discloses that positive-strand SARS-CoV-2 RNA virus also follows a nuclear replication strategy and that suppression of PKC-α mediated nuclear export of viral RNPs will disrupt the formation of the emerging SARS-CoV-2 virions (page 3400, col. 2, 10 lines from bottom).
Therefore, one having ordinary skill in the art would have expected with a reasonable expectation of success that treated subjects would show reduction of the viral titer of the RNA virus compared to that before administration of treatment, since inhibition of PKC with Knox’s compound will be expected to suppress viral replication and disrupt the formation of the emerging SARS-CoV-2 virions.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Crawford et al. (Viruses, 2020, 12, 513, 15 pages) (“Crawford”).
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach “wherein the cell expresses ACE2” – see 112(b); the teachings of Crawford are relied upon for these disclosures.
Crawford teaches cells expressing ACE2 are efficiently infected by their SARS-CoV-2 Spike-pseudo typed lentiviral particles (abstract; section 2.2, page 4), and suggests that SARS-CoV-2 targets cells that express ACE2.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Knox’s and Ghashghaeinia’s PKC treatment for COVID19 to a subject whose cells express ACE2 (such as a human) in view of Crawford. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Knox and Ghashghaeinia disclose their COVID19 treatment; further because Crawford teaches SARS-CoV-2 targets cells that express ACE2, such as human cells.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Chien et al. (J. Proteome Res., 2020, 19, 4690−4697) (“Chien”).
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach administration of their PKC treatment in combination with a nucleotide analogue reverse transcriptase inhibitor; the teachings of Chien are relied upon for these disclosures.
Chien teaches nucleotide analogue reverse transcriptase inhibitors capable of being incorporated by SARS-CoV-2 RdRp, where they terminate further polymerase extension with varying efficiency (abstract). Chien concludes by stating Sofosbuvir, Tenofovir alafenamide, and Abacavir, the prodrugs of 2’-F,Me-UTP, TFV-DP, and Car-TP, respectively, terminated the RNA synthesis catalyzed by SARS-CoV-2 RdRp and are FDA-approved oral drugs for treatment of other viral infections, and their safety profiles are well established (conclusions).
Therefore, it would have been prima facie obvious to one having ordinary skill prior to the effective filing date of the claimed invention to administer a nucleotide analogue reverse transcriptase inhibitor, such as Sofosbuvir, Tenofovir alafenamide, and Abacavir, in combination with Knox’s and Ghashghaeinia’s PKC treatment (IDE196) for the treatment of COVID19. One having ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in view of Knox and Ghashghaeinia; further in view of Chien’s teaching that nucleotide analogue reverse transcriptase inhibitors Sofosbuvir, Tenofovir alafenamide, and Abacavir (FDA-approved oral drugs for treatment of other viral infections with well-established safety profiles) terminated the RNA synthesis catalyzed by SARS-CoV-2 RdRp.
Applicant is advised, with respect to a mixture of the two claimed reagents, the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Hickey et al. (J. Pharm. Sci., 2013, 102, 1165-1172) (“Hickey”).
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach administration of their PKC treatment by aspiration; the teachings of Hickey are relied upon for these disclosures.
Hickey teaches inhaled therapeutic aerosols continue to be an important treatment for pulmonary diseases and discloses a variety of dosage forms are employed for different indications and demographics including pressurized or propellant-driven metered dose inhalers, dry powder inhalers, and nebulizers/nebules (abstract).
Therefore, regarding claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Knox’s PKC inhibitor compound for the treatment of COVID-19 via aspiration/ inhalation, in view of Ghashghaeinia further in view of Hickey. One having ordinary skill would have been motivated to do so with a reasonable expectation of success because Knox and Ghashghaeinia teach IDE196 for the treatment of COVID19; further because Hickey teaches inhaled therapeutic aerosols continue to be an important treatment for pulmonary diseases and discloses a variety of dosage forms are employed for different indications and demographics including pressurized or propellant-driven metered dose inhalers, dry powder inhalers, and nebulizers/nebules. Therefore, one of ordinary skill would have had a reasonable expectation of success in formulating an “aspirateable”/ inhalable solution for the treatment of COVID19 (a pulmonary condition).
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Mendoza et al. (Current Protocols in Microbiology, 2020, 57, e105, 15 pages) (“Mendoza”).
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach measuring viral titers prior or after administration of treatment, the teachings of Mendoza are relied upon for these disclosures.
Mendoza teaches plaque assays remain the gold standard in quantifying concentrations of replication competent lytic virions, and discloses two plaque assay protocols for quantifying SARS-CoV-2 viral titers (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to measure SARS-CoV-2 viral titers before or after administration of Knox’s in view of Ghashghaeinia’s PKC treatment. One of ordinary skill would have been motivated to do so in order to evaluate the efficacy of treatment, since lower viral titers post-treatment (compared to titers prior to treatment) would indicate that the administered therapeutic is effective in treating the viral infection. One of ordinary skill would have had a reasonable expectation of success in view of Mendoza’s plaque assay protocols for quantifying SARS-CoV-2 titers.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); further in view of Mendoza et al. (Current Protocols in Microbiology, 2020, 57, e105, 15 pages) (“Mendoza”); as applied to claim 38; further in view of Flano et al. (Current Protocols in Cell Biology, 2009, 26.3.1-26.3.28, S43, 28 pages) (“Flano”).
The teachings of Knox, Ghashghaeinia, and Mendoza are disclosed above and incorporated herein.
While Knox in view of Ghashghaeinia further in view of Mendoza do not specifically teach measuring “lung bulk viral titers” after administration of treatment – see 112(b), the teachings of Flano are relied upon for these disclosures.
Flano teaches protocols to study the pathogenesis of respiratory virus infections by sampling tissue of infected animal (in this case, mouse lungs – reading on “bulk lung titers”). Flano uses RSV and influenza (both ssRNA viruses), then infected mice are euthanized and lung tissue is removed for testing (see procedure in first 13 pages).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to measure lung bulk titers of SARS-CoV-2 after administration of Knox’s in view of Ghashghaeinia’s PKC treatment, if the subject dies after treatment. One of ordinary skill would have been motivated to do so in order to evaluate the efficacy of treatment and determine whether death was caused by the treated viral infection or by other causes. One of ordinary skill would have had a reasonable expectation of success in view of Mendoza’s plaque assay protocols for quantifying SARS-CoV-2 titers; and Flano’s detailed protocol for studying pathogenesis of ssRNA viral infections in the lungs of mice. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR,550 U.S. at 421, 82 USPQ2d at 1397.
Claims 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Zeng et al. (The FEBS Journal 288, 2021, 5190–5200 - First published: 24 October 2020) (“Zeng”)
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach measuring protein levels within the lungs of the subject, the teachings of Zeng are relied upon for these disclosures.
Zeng teaches proteomic characteristics in respiratory tract of critical COVID-19 patients still remain to be investigated – reading on measuring total protein level within the lungs of the subject. Zeng performs proteomic analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID-19 and from non-COVID-19 controls. Zeng discloses BALF proteome associated with COVID-19 patients, not present in subjects without COVID-19 (abstract and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to measure the total protein level within the lungs of a subject before and after administration of treatment. One of ordinary skill would have been motivated to do so in order to understand proteomic alterations in the respiratory tract of severe COVID-19 patients and the effects of treatment on these proteomic alterations, which would point to the efficacy of treatment. One of ordinary skill would have had a reasonable expectation of success because Knox and Ghashghaeinia disclose their PKC COVID 19 therapy; and further because Zeng teaches their analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID-19 and their findings of the proteins that are found in COVID19 patients vs non-COVID19 patients. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); as applied to claims 1, 10, 14, 18, 20, 22-23, and 40; further in view of Graninger et al. (Int. J. Antimicrob. Agents, 22, 2003, S73-S78) (“Graninger”); and Reyes et al. (J. Am. Geriatrics Soc., 2020, 68, 1927-1928) (“Reyes”).
The teachings of Knox and Ghashghaeinia are disclosed above and incorporated herein.
While Knox and Ghashghaeinia do not specifically teach coadministration of their PKC with mecillinam; the teachings of Graninger and Reyes are relied upon for these disclosures.
Graninger teaches Pivmecillinam as a prodrug for mecillinam, which is a β-lactam antibiotic with a novel site of action and with specific and high activity against Gram-negative organisms such as Escherichia coli, and has been widely used for the treatment of urinary tract infections (UTI) with low levels of resistance.
Reyes teaches that while treatment with antibiotics in subjects with COVID19 poses risks, if we want to ensure that no patient with COVID-19 dies for lack of antibiotics, then all patients with COVID19 who are seriously ill should be treated with antibiotics (page 1927, col. 2, para. 2). If the patient has urinary tract symptoms as well, antibiotics directed to urinary pathogens should be considered.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Knox’s in view of Ghashghaeinia’s PKC treatment for COVID19, in combination with Pivmecillinam (a prodrug for mecillinam), for the treatment of a UTI in a subject suffering from COVID19 and a UTI infection, in view of Graninger and Reyes. One of ordinary skill would have been motivated to do so because Knox and Ghashghaeinia disclose their PKC treatment for COVID19; Graninger discloses Pivmecillinam as a prodrug for mecillinam, which is an antibiotic for the treatment of UTIs; and further because of Reyes’ teaching that no patient with COVID-19 should die for lack of antibiotics. One of ordinary skill would have had a reasonable expectation of success because Graninger discloses their antibiotic having a novel site of action and with specific and high activity against Gram-negative organisms such as Escherichia coli with low levels of resistance; and because of Reyes’ guidance that prior to antibiotic treatment, subjects afflicted with COVID19 and UTI should be screened for specific infection prior to administering any antibiotic treatment.
Claims 58 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Knox et al. (WO 2020/146355 A1) (“Knox”); in view of Ghashghaeinia et al. (CELL CYCLE, 2020, VOL. 19, NO. 24, 3399–3405 – Pub. Date: 11 Dec 2020) (“Ghashghaeinia”); further in view of Graninger et al. (Int. J. Antimicrob. Agents, 22, 2003, S73-S78) (“Graninger”); and Reyes et al. (J. Am. Geriatrics Soc., 2020, 68, 1927-1928) (“Reyes”); as applied to claim 48; further in view of Zelikowsky et al. (Cell, 2018, 173, 1265–1279) (“Zelikowsky”).
The teachings of Knox, Ghashghaeinia, Graninger, and Reyes are disclosed above and incorporated herein.
Reyes further teaches delirium in elderly subjects with COVID19 and UTI infections could also be explained by the massive social disruption caused by the pandemic that has destroyed comforting routines and group activities, isolated patients, separated close relatives and caregivers, dramatically altered the appearance of all human visitors (para. Bridging col. 1-2, page 1927).
While Knox in view Ghashghaeinia further in view of Graninger and Reyes do not specifically teach coadministration of their PKC and mecillinam with osanetant; the teachings of Zelikowsky are relied upon for these disclosures.
Zelikowsky teaches systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic social isolation stress (SIS) (abstract). Zelikowsky discloses osanetant as a specific Nk3R antagonist that crosses the blood-brain barrier, and that its administration blocked virtually all of the measured behavioral effects of chronic SIS, while leaving non-SIS altered behaviors intact (page 1269, col. 1, last para.).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art prior to the effective filing of the claimed invention to administer osanetant in combination with Knox in view Ghashghaeinia’s PKC COVID19 treatment, and Graninger and Reyes’ UTI therapeutic to elderly COVID19 patients afflicted with a UTI and delirium, which might be due to social isolation. One having ordinary skill would have been motivated to do so because of Knox and Ghashghaeinia’s disclosure of their PKC inhibitor for COVID19 treatment and Graninger and Reyes’ teaching that elderly adults presenting with COVID19, UTI infections, and delirium would benefit from antibiotic treatment with Pivmecillinam. One of ordinary skill would have been further motivated to administer this combination therapy in view of Reyes’ teaching that delirium in elderly subjects with COVID19 and UTI infections could also be explained by the massive social disruption caused by the pandemic that has destroyed comforting routines and group activities, isolated patients, separated close relatives and caregivers, dramatically altered the appearance of all human visitors, which are causes of social isolation stress (SIS); further because Zelikowsky teaches osanetant administration blocked virtually all of the measured behavioral effects of chronic SIS, while leaving non-SIS altered behaviors intact. One of ordinary skill would have had a reasonable expectation of success in therapy administration in view of the disclosures cited herein.
Regarding claim 72, all three compounds are disclosed in individual formulations, therefore, it would have been obvious to one of ordinary skill to administer them in separate compositions.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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