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 .
Status of the Claims
Claims 1-20 are pending in the instant application and subject to examination herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/05/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Interpretation
Claim 7 further limits the method of claim 6, regarding the treatment of an infection caused by a pathogenic organism in a subject in need thereof, to wherein the pathogenic organism is selected from a Markush group that includes bacteria, fungus, and parasite. Claim 8 further limits the Markush group to wherein the bacteria comprise Gram positive bacteria, but crucially does not require that the pathogenic organism causing the infection to be treated is a bacteria. Therefore, any method that meets the limitations of claim 7 in regard to a pathogenic organism that is not a bacteria at all will also meet the limitations of claim 8. Similarly, claims 9-10 and 14 further limit claim 7 to wherein any bacterial infection is further limited to specific bacteria specie(s) but does not require that the infection to be treated is actually caused by any of the named species, and these claims are met by any method that meets the limitations of claim 7 in regard to a pathogenic organism that is not a bacteria at all.
Claim Objections
Claim 17 is objected to because of the following informalities: Claim 17 is an incomplete sentence, as the claim has no verb:
Claim 17: “The method of claim 7, wherein the bacteria Staphylococcus saprophyticus.”
Appropriate correction is required. For purpose of examination, the claim is interpreted as follows:
“The method of claim 7, wherein the bacteria [is] Staphylococcus saprophyticus.”
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 and 5 are anticipated by Zhang.
Claims 1-3 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (CN 107184581 A).
Claim 1 is drawn to a composition comprising N,N-dimethyldithiocarbamate (DMDC) or a derivative thereof. The structure of DMDC, as disclosed in instant claim 1, is shown below:
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102
106
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Zhang discloses a series of “amine-based dithioformate” compounds (i.e., dithiocarbamates) as b-lactamase inhibitors (Abstract), including multiple compounds that derivatives of DMDC, as shown below:
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200
400
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Zhang’s compounds are named herein below:
Zhang compound 1: Piperidine-1-carbodithioic acid, sodium salt
Zhang compound 2: 1-Pyrrolidinecarbodithioic acid, sodium salt
Zhang compound 3: 4-Morpholinecarbodithioic acid, sodium salt
Zhang compound 4: 1,4-Piperazinedicarbodithioic acid, potassium salt
Thus, claim 1 is anticipated by the disclosure of Zhang.
Claim 2 further limits claim 1 to wherein the derivative of DMDC is within the scope of a structural formula wherein the amine nitrogen is substituted with alkyl and/or aryl substituents, as shown in the table below. Zhang’s compounds 1 and 2, shown above, meet this limitation, and Zhang additionally discloses sodium diethyldithiocarbamate as “compound 7”, as shown in the table below:
Claim Number(s) of Instant Application
Instant Application
Zhang
2
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92
124
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wherein:
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118
120
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Claim 3 further limits claim 1 to wherein the derivative of DMDC is within the scope of a structural formula wherein the amine substituents form an aliphatic heterocyclic of ring size 3-8 atoms, and is met by Zhang’s compounds 1 and 2 shown above:
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90
200
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(instant claim 4, DMDC derivative formula)
Claim 5 further limits claim 1 to a Markush group of specific compounds that includes Zhang’s compound 4, shown above.
Thus, claims 2-3 and 5 are anticipated by the disclosure of Zhang.
Claims 1 and 4 are anticipated by Vishnoi .
Claims 1 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vishnoi (Vishnoi, et al.; Asian Journal of Chemistry, v33, pp1133-1136; 2021)1.
The limitations of claim 1 are discussed in the rejection above and hereby incorporated into the instant rejection.
Vishnoi teaches a study in the synthesis and antimicrobial activity of a series of cyclic dithiocarbamates, including multiple compounds that qualify as derivatives of DMDC, including Vishnoi’s compound 12, shown below (page 1135, Table 1):
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160
218
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Thus, claim 1 is anticipated by the teaching of Vishnoi.
Claim 4 further limits claim 1 to wherein the derivative of DMDC is within the scope of a structural formula wherein the amine nitrogen and thiolate sulfur are bound by a joining aliphatic linker of 2-4 carbons, and is met by Vishnoi’s compound 1, shown above.
Thus, claim 4 is anticipated by the teaching of Vishnoi.
Claims 1-2, 6-11 and 14-16 are anticipated by Richter.
Claims 1-2, 6-11 and 14-16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Richter (WO 2021/174284 A1).
The limitations of claims 1 and 2 are discussed in the rejection above and hereby incorporated into the instant rejection.
Richter discloses methods and compositions for treatment of bacterial and fungal infections, including compositions that comprise diethyldithiocarbamate (Abstract). A person of ordinary skill in the art would at once recognize that diethyldithiocarbamate is a derivative of dimethyldithiocarbamate.
Thus, claims 1-2 are anticipated by the disclosure of Richter.
Claim 6 further limits claim 1 to a method of treating an infection caused by a pathogenic organism in a patient in need thereof, the method comprising administering a therapeutic amount of a composition comprising N,N-dimethyldithiocarbamate (DMDC) or derivatives according to claim 1 thereof to said patient.
Claim 7 further limits claim 6 to wherein the pathogenic organism is selected from a Markush group that includes bacteria, a fungus, and a parasite.
Claim 8 further limits claim 7 to wherein the bacteria comprise Gram positive bacteria.
Claim 9 further limits claim 7 to wherein the bacteria selected from a Markush group that includes Staphylococcus aureus.
Claim 14 further limits claim 7 to wherein the bacteria is Methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermis.
Richter provides a method of preventing or treating an infection in a subject, the method comprising providing to the site of infection an effective amount of an antimicrobial composition or an antimicrobial solution as described herein (paragraph [0037]). Richter discloses that in some embodiments of the invention, the antimicrobial composition is composed of diethyldithiocarbamate, or a salt thereof, and copper, or a salt thereof (paragraph [0045]). Richter also discloses that Methicillin-resistant Staphylococcus aureus (MRSA) is a group of genetically distinct gram-positive bacteria that are related to other strains of Staphylococcus aureus (paragraph [0190]). Richter further discloses “Example 3”, wherein strains of Staphylococcus epidermis and Methicillin-resistant Staphylococcus aureus (MRSA) are treated with compositions comprising diethyldithiocarbamate (DDC) and the minimum inhibitory concentration (MIC) of the combination of copper ions with DDC was found to be much lower than the MIC of either copper ions or DDC alone (paragraphs [0259]-[0262] and Figure 3A). Richter additionally discloses “Example 14”, wherein the composition comprising DDC and copper is applied to an artificial model wound to assess its ability to disrupt a MRSA-based biofilm, and showed that DDC alone or copper alone had a negligible effect on MRSA bacterial biofilms, whereas the combination of DDC with copper showed an 82.4% reduction in MRSA biofilms (paragraphs [0344]-[0347]).
Thus, claims 6-9, 11 and 14 are anticipated by the disclosure of Richter.
Claim 10 further limits claim 7 to wherein the Markush group pathogenic organism identified as the cause of the infection to be treated, consisting of bacteria, fungus, and parasite can only include fungus if the fungus is C. posadasii; however, as discussed above in the “Claim Interpretation” section, claim 10 does not require that pathogenic organism is a fungus.
Claim 15 further limits claim 14 to wherein the infection is a skin infection.
Claim 16 further limits claim 6 to wherein the composition is administered topically.
Richter discloses that in some embodiments the invention disclosed therein is for inhibiting the growth of, or killing, a fungus (paragraph [0193]) and also discloses examples of fungal infections suitable to be treated by species (paragraph [0194]) and that the infection may be due to a fungal skin infection (paragraph [0195]) and also discloses means of administration of antimicrobial agents disclosed therein, including “topical administration of antifungals” (paragraph [0217]).
Thus, claims 10 and 15-16 are anticipated by the disclosure of Richter.
Claim 11 further limits claim 6 to wherein the infection to be treated is a respiratory infection. Richter discloses that the method of treating infections disclosed therein can be used for treating infections of the nose or sinuses, for example microbial sinusitis and rhinosinusitis, and that exemplary formulations for treating such sites of infection include drops, emulsions or other solutions which can be squirted into the sinuses including nebulizer or spray-type formulations and sinus irrigation washes (paragraph [0142]).
Thus, claim 11 is anticipated by the disclosure of Richter.
Claims 1-2, 6-10, 13-14, 16 and 19-20 are anticipated by Schlitzer.
Claims 1-2, 6-10, 13-14, 16 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schlitzer (EP 3235815 A1).
The limitations of claims 1-2, 6-7 and 16 are discussed in the rejections above and hereby incorporated into the instant rejection.
Schlitzer discloses novel chemical active ingredients which are effective against parasitic helminths and to a medical agent for the treatment of diseases caused by parasitic helminth-to-forest platter worms, including bilharziosis/schistosomiasis (paragraph [0001]). Included in the active agents disclosed by Schlitzer are many compounds that are derivatives of dimethyldithiocarbamate, for examples diethyldithiocarbamate (paragraph [0054]).
Thus, claims 1-2 are anticipated by the disclosure of Schlitzer.
Regarding claims 6-7, Schlitzer discloses that compounds disclosed therein used as a component of a medical agent for the treatment of diseases which are caused or elicited by parasitic helminths, and that the agent is prepared and administered in any of a Markush group of administration formulations, including, oral spray, nasal spray, inhalation powder, emulsion and capsules, and can be encapsulated in “vesicles” for penetration through the skin (paragraph [0026]).
Thus, claims 6-7 are anticipated by the disclosure of Schlitzer.
As discussed above in the “Claim Interpretation” section, claims 8-10 and 14 further limit the Markush group of pathogenic organisms of claim 7, each with regard to the allowable type(s) of bacteria; however, none of these claims require that the pathogenic organism to be treated is a bacteria, and therefore all of these claims are met by the disclosure of Richter regarding the treatment of fungal infections.
Thus, claims 8-10 and 14 are anticipated by the disclosure of Schlitzer.
Claims 13 and 16 further limits claim 6 to wherein the composition is administered by inhalation, or topically, respectively. As discussed above, Schlitzer provides for a medicament for the treatment of diseases caused by parasitic helminths to be administered in the form of inhalation powder or by penetration of the skin. Schlitzer specifically lists “inhalation” and “topical” as administration routes (paragraph [0026]).
Claim 19 further limits claim 7 to wherein the parasite is a parasitic flatworm that is S. mansoni. Claim 20 further limits claim 19 to wherein the infection is Schistosomiasis. As discussed above, Schlitzer specifically includes schistosomiasis in the definition of diseases to be treated by the invention (paragraph [0001]) and specifically names Schistosoma mansoni as one of the parasitic helminths for which the invention is intended to treat (paragraph [0023]).
Thus, claims 13, 16 and 19-20 are anticipated by the disclosure of Schlitzer.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6-12 and 14-16 are unpatentable over Richter in view of Lewis, Allerberger and Ramani.
Claims 1-2, 6-12 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Richter (WO 2021/174284 A1) in view of Lewis (Lewis, et al.; PLOS Pathogens, v11, issue 5, article e1004762, pp1-7; 2015), Allerberger (Allergerger, et al.; Arzneimittel-Forschung, v41, pp443-448; 1991) and Ramani (Ramani, et al.; Mycopathologia, v163, pp315-319; 2007).
The limitations of claims 1-2, 6-11 and 14-16 and the disclosure of Richter are discussed in the rejection above and hereby incorporated into the instant rejection.
Claim 10 further limits claim 7 to wherein the Markush group of pathogenic organisms identified as the cause of the infection to be treated, consisting of bacteria, fungus, and parasite can only include fungus if the fungus is C. posadasii.
Claim 12 further limits claim 11 to wherein the respiratory infection to be treated is pneumonia or San Joaquin Valley Fever.
As discussed in the rejection above, Richter discloses a method of treating microbial infections disclosed therein, comprising administering an antimicrobial composition or antimicrobial solution as described therein (paragraph [0037). Richter discloses that in some embodiments of the invention, the antimicrobial composition is composed of diethyldithiocarbamate, or a salt thereof, and copper, or a salt thereof (paragraph [0045]). Richter provides a long list of exemplary fungal species for which an infection by any of such fungi would be amenable to treatment by the invention disclosed therein (paragraph [0194]). Richter further discloses “Example 11” wherein the combination of diethyldithiocarbamate and copper consistently shows equal or greater inhibitory action against a variety of fungal species compared to diethyldithiocarbamate alone (paragraphs [0320]-[0331]) and Figure 15).
The list of fungal species provided by Richter does not include C. posadasii, and Richter does not expressly list San Joaquin Valley Fever as an infection to be treated; however, a person of ordinary skill in the art would have a reasonable expectation of success in using the method of treatment of fungal infection provided by Richter to treat C. posadasii, and/or of San Joaquin Valley Fever infections, for the following reasons:
It was known in the art that Valley Fever is caused by Coccidioides fungal species, a genus which includes C. posadasii and C. immitis;
It was known in the art that diethyldithiocarbamate is active in the inhibition of C. immitis, a Coccidioides fungal species, per the teaching of Allerberger;
It was known in the art that antifungal agents active against C. immitis are similarly active against C. posadasii, per the teaching of Ramani.
Lewis teaches a review on Coccidioides immitis and Coccidioides posadasii, including their biology (pp1-2), distribution and ecology (pp2-3) and their role in coccidioidomycosis (pp3-4). Lewis teaches that the inhalation of arthroconidia (mycelial cells) of these fungal species by a potential host “can lead to coccidioidomycosis, commonly known as (San Joaquin) Valley Fever” (page 1). Lewis further teaches that C. immitis is commonly found in the San Joaquin Valley of California, as well as in Utah and eastern Washington, whereas C. posadasii is found from Arizona to Texas and throughout Mexico into Central and South America (page 2).
Allerberger teaches a study on the inhibitory and fungicidal property of sodium diethyldithiocarbamate across 76 fungal strains, finding a broad spectrum of direct antifungal activity (Summary, page 443). Among the many species tested by Allerberger, C. immitis was shown to be susceptible to inhibition by diethyldithiocarbamate, with a minimum inhibitory concentration of 10 mg/mL (Table 3, page 445).
Ramani teaches a study in the comparison of susceptibility of C. immitis and C. posadasii to a variety of antifungal agents (Abstract, page 315). Ramani finds no significant difference in the minimum inhibitor concentration (MIC) and minimum fungicidal concentration (MFC) for C. immitis and C. posadasii isolates, and concludes that Coccidioides species appear to be highly susceptible to most antifungal agents (Abstract, page 315 and Table 2, page 317).
Applicant’s invention is unpatentable over the disclosure of Richter in view of the teachings of Lewis, Allerberger and Ramani, because a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in using the invention of Richter to treat San Joaquin Valley Fever or a respiratory infection wherein the pathogenic organism is C. posadasii, because it was known in the art that (San Joaquin) Valley Fever is caused by C. immitis and/or C. posadasii, depending on geographic location, per the teaching of Lewis, and it was known in the art that diethyldithiocarbamate, an agent in the antimicrobial treatment method of Richter, is an active antifungal agent against C. immitis, per the teaching of Allerberger, and it was known in the art that C. immitis and C. posadasii are broadly susceptible to various antifungals, and show no significant difference in their susceptibility to antifungal agents, per the teaching of Ramani.
Thus, the invention was prima facie obvious at the time of filing.
Claims 1-2, 6-11 and 14-17 are unpatentable over Richter in view of Chen.
Claims 1-2, 6-11 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Richter in view of Chen (Chen, et al.; Journal of Inorganic Biochemistry, v163, pp68-80; 2016).
The limitations of claims 1-2, 6-11 and 14-16 and the disclosure of Richter are discussed in the rejection above and hereby incorporated into the instant rejection.
Claim 17, as interpreted for purpose of examination (see Claim Objections section above), further limits claim 7 to wherein the Markush group of pathogenic organisms identified as the cause of the infection to be treated, consisting of bacteria, fungus, and parasite can only include bacteria if the bacteria is Staphylococcus saprophyticus.
As discussed in the rejection above, Richter discloses a method of treating microbial infections disclosed therein, comprising administering an antimicrobial composition or antimicrobial solution as described therein (paragraph [0037). Richter discloses that in some embodiments of the invention, the antimicrobial composition is composed of diethyldithiocarbamate, or a salt thereof, and copper, or a salt thereof (paragraph [0045]). Richter also discloses that the antibacterial composition and solution of the present invention shows efficacy against a broad range of Gram positive bacteria (paragraph [0181]), and particularly points out the Staphylococcus family among select Gram positive bacteria (paragraph [0182]). Richter further discloses “Example 3”, wherein Richter shows that the combination of diethyldithiocarbamate and copper consistently shows synergistic inhibitory action against Staphylococcus epidermis and Methicillin-resistant Staphylococcus aureus (paragraphs [0258]-[0260] and Figures 3A and 3B). In all examples, the combination of diethyldithiocarbamate and copper was at least as effective as diethyldithiocarbamate alone, and consistently gave lower values of minimum inhibitory concentration (Figures 3A and 3B).
Richter does not specifically name Staphylococcus saprophyticus as a bacteria to be treated, nor provide exemplary data on the inhibition of Staphylococcus saprophyticus; however, a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in using the invention of Richter to treat an infection of Staphylococcus saprophyticus, because it was known in the art that diethydithiocarbamate shows inhibitory action against Staphylococcus saprophyticus, per the teaching of Chen.
Chen teaches a study on the antibacterial properties of a series of metal-ligand complexes and their free ligands, wherein the metal is gold and the ligands are dithiocarbamates, including diethyldithiocarbamate, identified as Chen’s compound 3 (page 68, Abstract). Chen shows that compound 3 (diethyldithiocarbate) inhibits Staphylococcus saprophyticus as well or better than the well known antibiotic tetracycline both in a measurement of growth zone inhibition in agar plate (page 70, Table 1 and page 72, section 2.4.2) and in a broth medium wherein the bacterial persistence/inhibition is measured by colorimetric assay of bacteria action upon a purple dye, p-iodonitrotetrazolium violet (page 70, Table 2, and page 73, section 2.4.3). Thus, Chen shows that diethyldithiocarbamate is an active antibacterial agent against Staphylococcus saprophyticus.
Applicant’s invention is unpatentable over the disclosure of Richter in view of the teaching of Chen, because a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in using the invention of Richter to treat an infection of Staphylococcus saprophyticus with a combination of diethyldithiocarbamate and copper, because Richter discloses that the invention disclosed therein is generally effective against Gram positive bacteria, in particular bacteria of the Staphylococcus genus, and shows examples of synergistic efficacy against multiple Staphylococcus species wherein the combination was never less effective than diethydithiocarbamate alone and often more effective, and because Chen teaches that diethyldithiocarbamate alone is an effective antibacterial agent against Staphylococcus saprophyticus.
Thus, the invention was prima facie obvious at the time of filing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Cited in Applicant’s Information Disclosure Statement dated 04/05/2024.
2 N-Phenyl-2-thiazolidinethione