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
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP21305619.5, filed on 5/12/2021.
Information Disclosure Statement
The information disclosure statement filed 11/07/2023 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the fifth reference is not in English. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The disclosure is objected to because it contains an embedded hyperlink ((page 5) see, e.g., http://www.genet.sickkids.on.ca/cftr) and/or other form of browser-executable code. 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.
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 1-4, 6-11, 14 and 16-19 and rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while likely being enabling for pulmonary inflammation caused by SARS-CoV-2, LPS or bacteria, does not reasonably provide enablement for all inflammation including but not limited to myocarditis, irritable bowel syndrome, skin inflammation, sepsis or multisystem inflammatory syndrome with severe myocarditis, or inflammation caused by influenza virus, respiratory syncytial virus, adenovirus, metapneumovirus, cytomegalovirus, parainfluenza virus and smallpox. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).[1]
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill level
The invention relates to a method of a method of treating inflammation or preventing inflammation-induced fibrosis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of clofoctol. The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites the fact that while Applicant demonstrated the use of clofoctol in treating pulmonary inflammation caused by SARS-CoV-2 or LPS, nowhere in the specification did applicant demonstrate the use of clofoctol in treating myocarditis, irritable bowel syndrome, skin inflammation, sepsis or multisystem inflammatory syndrome or inflammation caused by influenza virus, respiratory syncytial virus, adenovirus, metapneumovirus, cytomegalovirus, parainfluenza virus and smallpox. Further, the predictability of treating inflammation of all types is relatively low given that the various types of inflammation have different causative agents (e.g. viruses, bacteria, chemicals, food, stress, injuries) and thus involve different cellular mechanisms, and consequently, differ in treatment protocol(Cleveland Clinic, Inflammation, 03/22/2024). For example, clofoctol is very hydrophobic (e.g., 2 benzene rings, tetramethylbutyl group, etc.) and thus works best in hydrophobic environments (e.g., interacts with pulmonary surfactants in lungs such as oily DPPC), would not be expected to work as well (or even be soluble) in aqueous environments (e.g., aqueous humor of eye) and thus not work for uveitis (eye inflammation), etc.
2. The breadth of the claims
The claims are thus very broad insofar as they recite the treating inflammation or preventing inflammation-induced fibrosis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of clofoctol. While such “treatment” might theoretically be possible for treating pulmonary inflammation utilizing clofoctol, as a practical matter it is nearly impossible to achieve a treatment for all possible inflammation with the same compound.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for the use of clofoctol for all inflammations and disease subtypes. No reasonably specific guidance is provided concerning useful therapeutic protocols for all inflammations and disease subtypes, other than treating pulmonary inflammation caused by SARS-CoV-2 or LPS. The latter is corroborated by the working examples on pages 14-23.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion clofoctol could be predictably used for the treatment of every single inflammation as inferred by the claims and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
[1] As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.
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 20-21 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 20 recites the limitation "the coronavirus " in claim 14. There is insufficient antecedent basis for this limitation in the claim. Claim 14 has deleted the limitation the coronavirus and thus the scope of claim 20 is unclear because the coronavirus lacks antecedent basis.
Claims 21 recites the limitation "the SARS-coronavirus " in claim 14. There is insufficient antecedent basis for this limitation in the claim. Claim 14 has deleted the limitation the SARS-coronavirus and thus the scope of claim 21 is unclear because the SARS-coronavirus lacks antecedent basis.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 20-21 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 20-21 improperly broaden claim 14 from which they dependent because claim 14 does not include coronavirus. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1-2, 5-6, 8, 12-13, 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by D'ANGELO (D'ANGELO ET AL: "Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 62, no. 11, 2018-11-01, IDS).
The reference D'ANGELO teaches “Here, we describe the identification of new inhibitors of the pqs QS system of the human pathogen Pseudomonas aeruginosa by screening a library of 1,600 U.S. Food and Drug Administration-approved drugs. Phenotypic characterization of ad hoc engineered strains and in silico molecular docking demonstrated that the antifungal drugs clotrimazole and miconazole, as well as an antibacterial compound active against Gram-positive pathogens, clofoctol, inhibit the pqs system, probably by targeting the transcriptional regulator PqsR. The most active inhibitor, clofoctol, specifically inhibited the expression of pqs-controlled virulence traits in P. aeruginosa, such as pyocyanin production, swarming motility, biofilm formation, and expression of genes involved in siderophore production. Moreover, clofoctol protected Galleria mellonella larvae from P. aeruginosa infection and inhibited the pqs QS system in P. aeruginosa isolates from cystic fibrosis patients. Notably, clofoctol is already approved for clinical treatment of pulmonary infections caused by Gram-positive bacterial pathogens; hence, this drug has considerable clinical potential as an antivirulence agent for the treatment of P. aeruginosa lung infections”(abstract). This anticipates claims 1, 2, 5, 6, 8, 12-13, and 18.
The instant specification defines inflammation as: “As used herein, the term "inflammation" is used to describe the fundamental pathological process consisting of a dynamic complex of cytologic and histologic reactions that occur in tissues in response to an injury or abnormal stimulation caused by a physical, chemical or biologic agent (e.g. bacterium, virus...) including the local reactions and resulting morphologic changes, the destruction or removal of the injurious material, and the responses that lead to repair and healing”(page 2) and “The method of the present invention is thus particularly suitable for the treatment of 5 inflammatory diseases. As used herein, "inflammatory disease" means a clinical disorder in which inflammation is a prominent contributor to the clinical condition. Typically, the inflammatory disease is selected from the group consisting of asthma, chronic obstructive lung disease, pulmonary fibrosis, pneumonitis (including hypersensitivity pneumonitis and radiation pneumonitis), pneumonia, cystic fibrosis... bacterial-induced inflammation, and viral induced inflammation”(page 3). Clofoctol is commonly known as an antibiotic (D'ANGELO) and has been used in the treatment of infectious respiratory diseases(D'ANGELO). Respiratory diseases are inflammatory diseases (instant specification). Additionally, as defined by the instant specification (pages 2-3), inflammation can be defined as a fundamental pathological processes that occur in tissues in response biologic agent (e.g. bacterium, virus...). Thus treating a bacterial infection or virus would reduce these processes and thus reduce inflammation as defined herein. Thus, any prior art relating to the antimicrobial activities of clofoctol regarding microbiota causing diseases in the respiratory tract renders the subject-matter of at least present claims 1, 2, 5-6, 8, 12-13, 18 anticipated.
Claim(s) 1, 2, 5-6, 8-10, 12-13 and 20-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BAILLY (BAILLY ET AL: "A new horizon for the old antibacterial drug clofoctol", DRUG DISCOVERY TODAY, vol. 26, no. 5, p. 1302-1310, 2021-02-10, IDS).
The reference BAILLY teaches “The synthetic antibacterial drug clofoctol (CFT) has long been used to treat respiratory tract infections in Europe. In recent years, the drug was found to target two biologically important proteins, the Cdc7/Dbf4 protein kinase complex and the mRNA-binding protein cold shock domain containing E1 (CSDE1), also known as upstream-of-N-Ras protein (UNR). These interactions are at the origin of the antitumor activity of CFT, recently evidenced in prostate cancer and neuroglioma. Drug–protein binding models provide a structural basis to guide the design of more potent anticancer compounds. A renewed interest in CFT can be anticipated for the treatment of cancers, and possibly Coronavirus 2019 (COVID-19)”(abstract) and “CFT (Fig. 1) is an old antibacterial drug, active essentially on Gram-positive bacteria, such as Streptococcus pyogenes and Streptococcus pneumoniae, common pathogens of upper and lower respiratory tract infections. CFT was developed during the late 1970s and marketed in France (trade name Octofene1) until January 2005 and in Italy (Gramplus1), where it is still prescribed. CFT inhibits cell wall synthesis in bacteria and induces membrane permeabilization, which is at the origin of the bactericidal activity [1–3]. The drug is active against clinical isolates of penicillin-susceptible and penicillin-resistant S. pneumoniae, and against methicillin-susceptible and methicillin-resistant Staphylococcus aureus [4]. It was a useful antibacterial drug to treat ear, nose, and throat infections, providing an alternative to antibiotic therapy for the treatment of bronchopulmonary diseases [5,6]. The drug does not induce antibacterial drug resistance, thus permitting complete eradication of the pathogen [7]. CFT can be administered by the oral or rectal route, the latter producing a more rapid absorption and elimination compared with oral treatment. By both routes, the drug circulates well in the body and can easily accumulate in tissues, reaching concentrations higher than in the plasma [8]. Interestingly, the drug accumulates in the lung. Ninety minutes after injection of a rectal suppository containing 1.5 g CFT, the lung tissue: plasma ratio was 6.2, illustrating the rapid and time-dependent delivery of the drug into the lung and its storage in this compartment. This property might explain its efficacy against bacterial respiratory infections [9,10] and could be useful to combat other lung diseases (see later)”(page 1302). This anticipates claims 1, 2, 5, 8, and 12-13.
The instant specification defines inflammation as: “As used herein, the term "inflammation" is used to describe the fundamental pathological process consisting of a dynamic complex of cytologic and histologic reactions that occur in tissues in response to an injury or abnormal stimulation caused by a physical, chemical or biologic agent (e.g. bacterium, virus...) including the local reactions and resulting morphologic changes, the destruction or removal of the injurious material, and the responses that lead to repair and healing”(page 2) and “The method of the present invention is thus particularly suitable for the treatment of 5 inflammatory diseases. As used herein, "inflammatory disease" means a clinical disorder in which inflammation is a prominent contributor to the clinical condition. Typically, the inflammatory disease is selected from the group consisting of asthma, chronic obstructive lung disease, pulmonary fibrosis, pneumonitis (including hypersensitivity pneumonitis and radiation pneumonitis), pneumonia, cystic fibrosis... bacterial-induced inflammation, and viral induced inflammation”(page 3). Clofoctol is commonly known as an antibiotic (BAILLY) and has been used in the treatment of infectious respiratory diseases(BAILLY). Respiratory diseases are inflammatory diseases (instant specification). Additionally, as defined by the instant specification (pages 2-3), inflammation can be defined as a fundamental pathological processes that occur in tissues in response biologic agent (e.g. bacterium, virus...). Thus treating a bacterial infection or virus would reduce these processes and thus reduce inflammation as defined herein. Thus, any prior art relating to the antimicrobial activities of clofoctol regarding microbiota causing diseases in the respiratory tract renders the subject-matter of at least present claims 1, 2, 5, 8, 12 anticipated.
The reference BAILLY teaches “As a regulator of UPR, different applications beyond cancer can be envisioned for CFT. Recently, the hypothesis was formulated that a mild UPR induction is associated with protective effects in the vascular endothelium against inflammation [64]. In particular, UPR is triggered in the airway of patients with different respiratory diseases, including obstructive lung diseases (such as asthma), lung cancer and some pulmonary viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [65–68]. Therefore, the use of small molecules targeting the UPR, or distinct components of this complex machinery, is envisioned for the treatment of various human diseases [69]. In particular, the pharmacological modulation of the UPR is viewed as a new strategy to control respiratory virus replication, notably rhinovirus infections [70]” (page 1308). This anticipated claims 6, 9, 10, 12 and 20-21.
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.
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) 1-3 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over D'ANGELO (D'ANGELO ET AL: "Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 62, no. 11, 2018-11-01, IDS) in view of AZIMI (AZIMI et al., The role of bacteria in the inflammatory bowel disease development: a narrative review, APMIS 126: 275–283, 2018).
The D'ANGELO has been discussed supra and does not disclose inflammatory bowel disease (claims 3).
The reference AZIMI teaches “Inflammatory bowel disease (IBD) is a general term used for the ulcerative colitis (UC) and Crohn’s disease (CD); in addition, IBD principally refers to a chronic disease of the gastrointestinal tract in which mediated by immune system”(abstract) and “Clostridium difficile is a Gram positive, anaerobe, spore-forming bacteria that primarily affect the colon and can produce toxins type A and B (50). It was reported that IBD patients with C. difficile infections (CDI), manifest severe clinical symptoms; including, abdominal pain, diarrhea, bloody stools, and leukocytosis (51). According to the reports, high prevalence of CDI in patients with IBD was revealed (52–55). Evidently, the toxins produced by this bacteria, inactivate the Rho family proteins which are involved in intracellular signaling pathways (56, 57). The inactivation of these proteins, impairs the integrity of the membrane cytoskeleton and the barrier function of epithelial cells (56, 57). Type A and B toxins in C. difficile, could also activate the productions of multiple inflammatory cytokines; for instance, Interleukin8 (IL8), IL1, IL6, and Tumor necrosis factor (TNF-a) which could damage the intestinal epithelial cells (57). Thus, the malfunction of immune system in patients with CDI may trigger IBD. Change in bile salt in the intestines of patients with IBD may affect the proliferation of C. difficile. In the order word, reduction in bile salt that occurs in the Colon of patients with IBD provides a desirable condition for growth and spore germination of C. difficile (58–60)”(page 279).This helps to teach claims 3 and 19.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified D'ANGELO with AZIMI because D'ANGELO teaches an antibacterial compound active against Gram-positive pathogens, clofoctol, and AZIMI teaches Gram-positive pathogens may trigger IBD. One would be motivated to combine the references to treat IBD and one would have a reasonable expectation of success because clofoctol is a well-known antibacterial.
Claim(s) 1 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over D'ANGELO (D'ANGELO ET AL: "Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 62, no. 11, 2018-11-01, IDS) in view of Sriskandan (Sriskandan et al., GRAM-POSITIVE SEPSIS: Mechanisms and Differences from Gram-Negative Sepsis, Infectious Disease Clinics of North America Volume 13, Issue 2, 1 June 1999, Pages 397-412).
The D'ANGELO has been discussed supra and does not disclose sepsis (claims 11).
The reference Sriskandan teaches “In modern intensive care settings, gram-positive bacteria account for up to 50% of severe sepsis or septic shock cases, yet the pathogenesis of gram-positive shock is poorly understood”(abstract). This helps to teach claim 11.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified D'ANGELO with Sriskandan because D'ANGELO teaches an antibacterial compound active against Gram-positive pathogens, clofoctol, and Sriskandan teaches Gram-positive pathogens may trigger sepsis. One would be motivated to combine the references to treat sepsis and one would have a reasonable expectation of success because clofoctol is a well-known antibacterial.
Claim(s) 1 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over D'ANGELO (D'ANGELO ET AL: "Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 62, no. 11, 2018-11-01, IDS) in view of Martin (Martin et al., Gram-Negative Sepsis and the Adult Respiratory Distress Syndrome, Clinical Infectious Diseases 1992;14:1213-28).
The D'ANGELO has been discussed supra and does not disclose respiratory distress syndrome (claims 15).
The reference Martin teaches “Gram-negative sepsis has dramatically increased in frequency throughout the twentieth century in the United States. Currently, —200,000 patients develop gram-negative sepsis each year in this country. Of these, about one-quarter develop the adult respiratory distress syndrome (ARDS). Among these critically ill patients, mortality is estimated at 60%-90%. In the complex series of events leading to acute lung injury in gram-negative sepsis, endotoxin is the proximal mediator. Although endotoxin may be capable of causing direct injury to the pulmonary endothelium, its primary role is as a trigger activating inflammatory agents, including complement, neutrophils, and platelets, and inducing the production of cytokines and arachidonic acid metabolites. The end results are impairment of the endothelial barrier, diffusely increased capillary permeability, and adherence of neutrophils to the endothelium with subsequent migration into the tissues. The consequent clinical syndrome is one of acute respiratory distress with pulmonary edema, poorly compliant lungs, and refractory hypoxemia”(abstract) and “Although our review focuses on acute lung injury occurring during the course of gram-negative sepsis, ARDS can also develop as a consequence of sepsis caused by gram-positive bacteria or even fungi”(page 1214).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified D'ANGELO with Martin because D'ANGELO teaches an antibacterial compound active against Gram-positive pathogens, clofoctol, and Martin teaches Gram-positive pathogens may trigger ARDS. One would be motivated to combine the references to treat ARDS and one would have a reasonable expectation of success because clofoctol is a well-known antibacterial.
Claim(s) 1, 7, and 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over BAILLY (BAILLY ET AL: "A new horizon for the old antibacterial drug clofoctol", DRUG DISCOVERY TODAY, vol. 26, no. 5, p. 1302-1310, 2021-02-10, IDS) in view of Grimaud (Grimaud et al., Acute myocarditis and multisystem inflammatory emerging disease following SARS‑CoV‑2 infection in critically ill children, Ann. Intensive Care (2020) 10:69).
The BAILLY has been discussed supra and does not disclose myocarditis (claims 7), multisystem inflammatory syndrome(claim 16) or multisystem inflammatory syndrome (MIS-C) with severe myocarditis (claim 17).
The reference Grimaud teaches “Acute myocarditis and multisystem inflammatory emerging disease following SARS‑CoV‑2 infection in critically ill children” (title). This helps to teach claims 7 and 16-17.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified BAILLY with Grimaud because BAILLY teaches clofoctol for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , and Grimaud teaches acute myocarditis and multisystem inflammatory maybe caused by SARS‑CoV‑2 infection. One would be motivated to combine the references to treat acute myocarditis and multisystem inflammatory caused by SARS‑CoV‑2 infection and one would have a reasonable expectation of success because clofoctol is proposed to treat SARS‑CoV‑2 infection.
Claim(s) 1 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over D'ANGELO (D'ANGELO ET AL: "Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 62, no. 11, 2018-11-01, IDS) in view of STULBERG (STULBERG et al., Common Bacterial Skin Infections, Am Fam Physician. 2002;66(1):119-125).
The D'ANGELO has been discussed supra and does not disclose skin inflammation (claims 4).
The reference STULBERG teaches “Family physicians frequently treat bacterial skin infections in the office and in the hospital. Common skin infections include cellulitis, erysipelas, impetigo, folliculitis, and furuncles and carbuncles. Cellulitis is an infection of the dermis and subcutaneous tissue that has poorly demarcated borders and is usually caused by Streptococcus or Staphylococcus species. Erysipelas is a superficial form of cellulitis with sharply demarcated borders and is caused almost exclusively by Streptococcus. Impetigo is also caused by Streptococcus or Staphylococcus and can lead to lifting of the stratum corneum resulting in the commonly seen bullous effect. Folliculitis is an inflammation of the hair follicles. When the infection is bacterial rather than mechanical in nature, it is most commonly caused by Staphylococcus. If the infection of the follicle is deeper and involves more follicles, it moves into the furuncle and carbuncle stages and usually requires incision and drainage. All of these infections are typically diagnosed by clinical presentation and treated empirically. If antibiotics are required, one that is active against gram-positive organisms such as penicillinase-resistant penicillins, cephalosporins, macrolides, or fluoroquinolones should be chosen”(abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified D'ANGELO with STULBERG because D'ANGELO teaches an antibacterial compound active against Gram-positive pathogens, clofoctol, and STULBERG teaches Gram-positive pathogens may cause skin inflammation. One would be motivated to combine the references to treat skin inflammation and one would have a reasonable expectation of success because clofoctol is a well-known antibacterial.
Conclusion
Claims 1-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.S./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627