DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendments
2. The amendments filed Feb 13, 2026 have been entered. Claims 23-31 have been withdrawn. Claim 9 is cancelled. Claims 1-8 and 10-22 are under consideration in this Office Action.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on Feb. 13, 2026 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
4. Applicant’s claim for domestic priority under 35 U.S.C. 119(e) is acknowledged. However, provisional application 62/571,009 upon which priority is claimed fails to provide adequate support under 35 U.S.C. 112 for claims 1-8 and 10-22 of this application. The claims all recite methods using a compound or antimicrobials or systems containing chlorate oxyanion having formula ClO3- and a cation counterion, alone or in combination with an antibiotic and/or antimicrobial wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation. There is no teaching of contacting blood, heart, lung, lung sputum and/or urinary tract of an individual with a compound containing chlorate oxyanion having formula ClO3- and a cation counterion having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation. Apparently, the provisional application, for which priority is claimed does not recite any cation counterions which were contacted with a instantly recited medium. There is no teaching of chlorate oxyanion and a cation counterion, alone or in combination with an antibiotic and/or antimicrobial and contacted with a medium. Thus, priority cannot be granted to 62/571,009 since what is now claimed, has not been previously recited in the provisional application. Therefore priority is granted to the filing date of the instant application Oct. 11, 2018.
Response to Arguments
5. Applicant's arguments filed Feb 13, 2026 have been fully considered but they are not persuasive.
Applicants point to Provisional Pages which points to harnessing the ability of the bacterial nitrate reductase to reduce perchlorate or chlorate; and a hypothesize that both chlorite and oxygen generated in this way will potentiate clinically-important antibiotics; sodium chlorate was used in pesticides. Applicants never point to a teaching of contacting blood, heart, lung, lung sputum and/or urinary tract of an individual with a compound containing chlorate oxyanion having formula ClO3- and a cation counterion having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation. The provisional does not exclude a metal cation having +1 charge other than Ag+. Page 5 of the Provisional application in section entitled Differences between proposed research and past or current work; wherein the Provisional states “I have never worked on (per)chlorate reduction, chronic wounds nor animal models.”. Chlorite dismutase (Cld) can readily be expressed and purified (REF), remains stable for several days at 30°C and tolerates > 200mM salt (maximum NaCl concentrations in blood [Evidence of PL Innovativeness]. Applicants point sodium chlorate being used in agricultural and pesticides. Applicants do not point to evidence supporting contacting blood, heart, lung, lung sputum and/or urinary tract of an individual with a compound containing chlorate oxyanion having formula ClO3- and a cation counterion having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation.
Applicants allege that the specific chlorate reactant and the synergistic combination with antibiotics to treat chronic infections in mediums such as the lungs of cystic fibrosis patients; but Applicants do not point to any evidence or support within the Provisional Application. The Provisional does not teach the exclusion of Ag+. The provisional only refers to sodium chlorate, and no other metal cations having charges +2, +3 or +4. There is no teaching of metal cations like, potassium, calcium, magnesium or barium chlorate. There is no exclusion of silver chlorate. Thus Applicants arguments do not take the place of evidence or written description support within the provisional application.
The Office invites Applicants to point to an antimicrobial or a system comprising one or more chlorates compounds containing chlorate oxyanion having formula ClO3- and a cation counterion and in an amount suitable to reduce antibiotic resistance and/or survivability of Nar-containing bacteria and one or more antibiotics wherein the antimicrobial is formulated for administration to blood, lungs, heart or urinary tract of an individual in an effective amount to treat and/or prevent infections of the Nar-containing bacteria in the blood, heart, lungs or urinary tract of the individual, in absence of hypochlorite and chlorite, and wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation.
Therefore Applicants arguments are not found persuasive and the priority is maintained.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on May 19, 2025was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Maintained Grounds of Rejection Necessitated By Applicants Amendments
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.
7. Claims 1-8 and 10-22 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. This is a new matter rejection.
Neither the specification nor originally presented claims provides support for a methods, systems or antimicrobials containing chlorate oxyanion having formula ClO3- and a cation counterion, alone or in combination with an antibiotic and/or antimicrobial wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation. The specification does not support the exclusion of Ag+.
Applicant did not point to support in the specification for methods, systems or antimicrobials containing chlorate oxyanion having formula ClO3- and a cation counterion, alone or in combination with an antibiotic and/or antimicrobial wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation. The specification does not support the exclusion of Ag+. Moreover, applicant failed to specifically point to the identity or provide structural characteristics of an antimicrobial or composition which excludes Ag+.
Paragraph [82] of the instant specification states “Exemplary +1 cation includes Li1+, Na1+, K1+, Cs1+, and Ag1+.”
Paragraph [84] of the instant specification states “Exemplary chlorates include potassium chlorate, sodium chlorate, magnesium chlorate, silver chlorate, or in solution as chloric acid.”
Thus, there appears to be no teaching for any methods, antimicrobial or composition to exclude Ag+. Therefore, it appears that there is no support in the specification. Therefore, applicants must specifically point to page and line number support for the of the exclusion as recited by the newly added amendments. Accordingly, the new claims incorporate new matter and are accordingly rejected.
Response to Arguments
8. Applicant’s arguments with respect to claims 1-8 and 10-22 have been considered but the arguments are not persuasive.
Applicants point to para [0081] "Exemplary +1 cation includes Li¹+, Na¹⁺, K¹+, Cs¹⁺, and Ag¹⁺" where the terms "Exemplary" and "includes" on their face signal a non-exhaustive list. Therefore, Applicants contend that it would be clear from the language of the very same passage mentioned in the Action that the specification identifies common structural features (metal cations with +1 charge) and provides a representative number of species (Li, Na, K, Cs).
Thus Applicants have not pointed to a written description that excludes Ag+. Applicants attention is directed to MPEP 2173.05(i) which states Any claim containing a negative limitation which does not have basis in the original disclosure should be rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. See MPEP § 2163 - § 2163.07(b) for a discussion of the written description requirement of 35 U.S.C. 112(a) and pre-AIA 35 U.S.C. 112, first paragraph. The Examiner is not improperly focused on an illustrative list of five cations while ignoring the broader disclosure that precedes it. The Examiner is not saying only the specifically recited cations have been described. In this case, the Examiner pointed to the list recited by Applicants specification, where Ag+ is among the list of specifically included cations; and then point to the instant claims which exclude Ag+. The Examiner pointed to the lack of support with in the specification for excluding Ag+.
It is unclear why Applicants is arguing the properties and teachings of Lyczak et al. The properties and advantages of Lyczak et al., do not provide Applicant any support for there exclusion. It appears that Applicants want to establish the silver chlorate has different properties; however this is irrelevant to the written description rejection. The rejection is based upon the fact that Applicants specification clearly and specifically includes Ag+ as a named example of +1 cations; yet the instant claims exclude the inclusion of Ag+ without any support within the four corners of the specification to exclude Ag+. Therefore, prior art does not provide support for a negative limitation.
Applicants assert that Ag¹⁺ is not essential of the claimed compositions methods and systems. The Office, points out that the standard is not how essential the cation is. The specification does not differentiate the cations based on essentialness to provide support for the exclusion. Instead, the standard is based upon the written description of the specification. The specification includes the +1 genus Li¹+, Na¹⁺, K¹+, Cs¹⁺, for which they provided identical level of support and this would include Ag+. Again there is no exclusion. Applicants argument is inconsistent with there specification. In this case, Applicants are reminded that their own specification states “.. Exemplary +1 cation includes Li¹+, Na¹⁺, K¹+, Cs¹+, and Ag¹⁺…” and other +1 cations; but yet somehow, does not include Ag+ as now recited by the instant claims. And Applicants can not point to the exclusion of Ag+ within the four corners of the specification.
Applicants response points to numerous times where Ag+ and/or silver chlorate is specifically named as being included with the instantly described methods, antimicrobials and system. As stated numerous times, Applicants are not prevented from claiming +1 genus Li¹+, Na¹⁺, K¹+, Cs¹⁺. The instant claims do not even recite Li¹+, Na¹⁺, K¹+, Cs¹⁺. The issue is that Applicants have not provide support for the exclusion of Ag+ through the negative limitation of “other than Ag+”. Applicant is reminded that description of Ag+ is pointedly and specifically recited as an example of a +1 cation.
Applicants are again invited to specifically point to support with in the instant specification for support to exclude Ag+ from the +1 cations which can be included with the antimicrobial or a system. Therefore the rejection is maintained until Applicants point to support within the instant specification for methods, systems or antimicrobials containing chlorate oxyanion having formula ClO3- and a cation counterion, alone or in combination with an antibiotic and/or antimicrobial wherein the cation counterion is a metal cation having +1 charge other than Ag+. Therefore, none of Applicants augments are found persuasive and the rejection is maintained.
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.
(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.
9. Claims 19-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cha et al., (Korean Journal of Food Hygiene and Safety. 2012. Volume 27 Issue 1. Pages 81-86). For the Cha et al., reference https://doi.org/10.13103/JFHS.2012.27.1.081
The claims are drawn to an antimicrobial or a system comprising one or more chlorates compounds containing chlorate oxyanion having formula ClO3- and a cation counterion and in an amount suitable to reduce antibiotic resistance and/or survivability of Nar-containing bacteria and one or more antibiotics wherein the antimicrobial is formulated for administration to blood, lungs, heart or urinary tract of an individual in an effective amount to treat and/or prevent infections of the Nar-containing bacteria in the blood, heart, lungs or urinary tract of the individual, in absence of hypochlorite and chlorite, and wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation.
Cha et al., describe the antimicrobial activity of sodium chlorate and Korean herbal extracts against mice infected with Escherichia coli O157:H7. Cha et al., describe the antibacterial effect of the combination of Coptidis rhizoma, Glycyrrhiza uralensis Fischet, Schizandra chinensis and Corni Fructus (1:1:1) extracts (CGSC10). Furthermore, the effectiveness of CGSC10, sodium chlorate, and the combination of CGSC10 and sodium chlorate (CGSCS10) against E. coli O157:H7 infection was studied using ICR female mice. During the incubation period, the dose of 5, 10, and 20% CGSC10 inhibited the growth of E. coli O157:H7 by 34.7, 60.2, and 76.4%, respectively. For 7 days after single challenge with E. coli O157:H7, forty female ICR mice were divided into four experimental groups which were administered in drinking water with saline, 10% CGSC10, 15 mM sodium chlorate and CGSCS10, respectively. On the 3rd day, the number of E. coli O157:H7 in mouse feces was significantly decreased by administration of 15 mM sodium chlorate and CGSCS10. On the 7th day-after administration, sodium chlorate and CGSCS10 decreased the number of E. coli O157:H7. According to the results of the present study, administration of CGSCS10 to mice can reduce the severity of E. coli O157:H7 infection. In addition, it is suggested that CGSCS10 represents a good candidate for the treatment of enteric infections in domestic animals.
Therefore Cha et al., teach an antibacterial composition comprising sodium chlorate with a cation other than a metal cation, and an antimicrobial CGSC10 where the combination was in an effective amount to treat E coli infection in the blood, heart, lungs or urinary tract, where E coli is a Nar containing bacteria. Cha et al., teach the antibacterial properties of CGSC10. Cha et al., administered the sodium chlorate and CGSCS10 in drinking water with saline. Thus teaching a system within water, just as recited by claims 20-21.
Response to Arguments
10. Applicant’s arguments with respect to claims 19-21 have been considered but the arguments are not persuasive.
First Applicants point to Cha et al., teaching of administering sodium chlorate in drinking water. Applicant s reminded that the rejected claims are drawn to products, i.e., an antimicrobial or a system. The administration method is irrelevant to the instantly claimed product. Cha et al., an antibacterial composition comprising an effective amount of sodium chlorate with a cation other than a metal cation, and an antimicrobial CGSC10 where the combination.
Applicants assert that the sodium chlorate and CGSC10 of Cha et al., are not one or more compounds containing the chlorate oxyanion having the CIO3 formula. In response, the Office points out that the chemical formula of sodium chlorate is NaCIO3-. Sodium chlorate (NaClO3) is an ionic compound (salt) containing a sodium cation (Na+) and a chlorate anion (ClO-3), whereas the chlorate ion (ClO-3) is the polyatomic anion itself. (NaClO3 -> Na+ + CIO3-). Cha et al., teach the combination of the antibiotic, CGSC10 and sodium chlorate. This argument is not persuasive especially when Applicants previously argued that sodium chlorate is a compound embraced by the instant claims.
Applicants point to Cha et al., drinking water formulation. Applicants is reminded that drinking water is an effective way to "administer" hydration to the urinary tract, acting as a natural flush to remove bacteria from the bladder and urethra. Increasing water intake dilutes urine, reducing irritation and lowering the risk of urinary tract infections.
Drinking water directly "administers" hydration to your cardiovascular system by increasing blood volume, allowing the heart to pump more efficiently with less effort. Proper hydration keeps blood from thickening, reducing strain on the heart, supporting healthy blood pressure, and reducing long-term risks of heart failure.
Drinking 0.9% sodium chloride (normal saline) intended for injection is generally safe and harmless, as it is just salt water. Therefore, the drinking water formulation of Cha et al., which included saline is suitable for administration to the urinary tract, blood, heart and cardiovascular system; contrary to Applicants arguments.
Applicants point to exclusion of hypochlorite and chlorite; yet do not point to a single instance where Cha et al., recites the inclusion of both hypochlorite and chlorite. Applicants fail to provide any evidence showing the Cha et al., included both hypochlorite and chlorite. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references. Therefore this argument is not persuasive.
Finally, Applicants argue about Cha et al., mode of administration. However, the rejected claims are not drawn to a method of administration. In this case the instantly rejected claims are drawn to a product. In response to applicant's argument, there is no structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed product from the prior art product. Here, Cha et al., antibacterial composition comprising sodium chlorate with a cation other than a metal cation, or a +1 which is not Ag+ and an antibacterial compound were formulated in a manner capable of being directly administered to urinary tract of an individual meets the requirements of the instantly rejected claims.
Thus, none of Applicants arguments are found persuasive and the rejection is maintained.
Claim Rejections - 35 USC § 102
11. Claims 1, 3-6, 10-13, 15-16, and 19-22 are rejected under 35 U.S.C. 102(a)(1) and (2) as being anticipated by Martin (US20150216874 published 2015-08-06; priority to 2015-01-07).
Martin disclose an antibiotic composition for killing bacteria comprising: an organic acyl polyoxychlorine coupled to a β-Lactam carrier wherein the polyoxychlorine comprises chlorate having the general formula ClO3 [claims 1 and 3]. The polyoxychlorine comprises a carbon based backbone coupled to an atom directly appending the acyl carbon [para. 17]. The compositions and methods of the invention provide for an antibiotic that is effective against Methicillin-resistant Staphylococcus aureus (MRSA) [abstract]. The β-Lactam carrier is coupled (covalently bonded) to organic acyl polyoxychlorine (OAP) to form the OAP based antibiotic compositions of the invention [para 13]. The β-lactam antibiotics includes penicillins, cephalosporins, and carbapenems. The penicillins consist of penicillins G and V, which are highly active against susceptible gram-positive cocci; penicillinase-resistant penicillins such as nafcillin, which are active against penicillinase-producing Staphylococcus aureus; ampicillin and other agents with an improved gram-negative spectrum, especially when combined with β-lactamase inhibitor; and extended-spectrum penicillins with activity against Pseudomonas aeruginosa, such as piperacillin [para 6]. The polyoxychlorine is selected from at least one chlorate having the general formula ClO3- and perchlorate having the general formula ClO4 and is coupled to the acyl carbon of the organic acyl polyoxychlorine [para 17]. Non-limiting examples of polyoxychlorine donors include: perchloric acid, sodium perchlorate, potassium perchlorate, lithium perchlorate, calcium perchlorate, magnesium perchlorate, sodium chlorate, potassium chlorate, lithium chlorate, calcium chlorate, magnesium chlorate and the like [para 18]. Solvents should be selected to maximize conversion into the organic acyl polyoxychlorine. Non-limiting examples of suitable solvents may include water [para 34].
Martin taught the OAP based antibiotic effectively kills Methicillin-resistant Staphylococcus aureus (MRSA) [para 42]. Martin disclose a method for killing bacteria comprising the steps of: reacting a polyoxychlorine donor with an organic acyl donor to form an OAP leaving group; coupling the OAP leaving group and Beta-lactam carrier to form an OAP based antibiotic; combining an OAP based antibiotic and a pharmaceutically acceptable carrier to form an antibiotic composition; administering said antibiotic composition to a mammal so that at least the OAP based antibiotic is absorbed into the peptidoglycan cell wall of bacteria; enzyme activation of the Beta-Lactam group; release of oxychlorine intermediates, and reduction of the oxychlorine intermediates induces oxidative stress and cell death [para 44].
The OAP based antibiotics of the invention can be formulated to be administered to mammals in a variety of convenient ways. Some non-limiting example of how OAP based antibiotic can be administered include: intravenous, oral, topical, nasal spray, drops, and the like [para 69].
Therefore Martin describe an antimicrobial or a system comprising one or more chlorates compounds containing chlorate oxyanion having formula ClO3- and a cation counterion wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation , as evidenced by teaching sodium chlorate, potassium chlorate, lithium chlorate, calcium chlorate, magnesium chlorate and the like. Martin describe OAP based antibiotic effectively kills MRSA; thus teaching an amount suitable to reduce antibiotic resistance and/or survivability of MRSA, a Nar-containing bacteria. Martin disclosed the chlorate oxyanion in combination with one or more β-lactamase antibiotics. Martin described the antimicrobial is formulated for administration to blood, lungs, heart or urinary tract of an individual via intravenous, oral, nasal spray, drops, and the like all have the ability to travel and interact with blood, lungs, heart and urinary tract; just as instantly claimed.
Response to Arguments
12. Applicant’s arguments with respect to claims 1, 3-6, 10-13, 15-16, and 19-22 have been considered but the arguments are not persuasive.
Applicants point to Martin’s recitation of Chlorite; however Applicants is reminded that the instant claims require the absence of hypochlorite and chlorite. Martin et al., does not recite the inclusion of both hypochlorite or chlorite. At best Martin et al., recites a non-limiting example where chlorite is not included; rather Martin et al., clearly teach when an acyl polyoxychlorine group results from reaction of a chlorate anion with an organic acyl donor undergoes chemical reduction to release a carboxyl group and the oxychlorine intermediate chlorine dioxide, is followed by subsequent oxychlorine species exemplified by chlorite. Therefore, chlorite is absent from the initial compound and Chlorite is not added to the compound. Applicants argument is irrelevant because chlorite was not contacted with the chlorate oxyanion. Martin et al., is merely providing a non-limiting example of a chemical reduction process. Therefore, this argument is not persuasive.
Applicants argue that Martin et al., do not teach each and every instantly claimed limitations. Martin describe an antimicrobial or a system comprising one or more chlorates compounds containing chlorate oxyanion having formula ClO3- and a cation counterion wherein the cation counterion is a metal cation having charges +2, +3, or +4, a metal cation having +1 charge other than Ag+ or a cation other than a metal cation , as evidenced by teaching sodium chlorate, potassium chlorate, lithium chlorate, calcium chlorate, magnesium chlorate and the like. Martin describe OAP based antibiotic effectively kills MRSA; thus teaching an amount suitable to reduce antibiotic resistance and/or survivability of MRSA, a Nar-containing bacteria. Martin disclosed the chlorate oxyanion in combination with one or more β-lactamase antibiotics. Martin described the antimicrobial is formulated for administration to blood, lungs, heart or urinary tract of an individual via intravenous, oral, nasal spray, drops, and the like all have the ability to travel and interact with blood, lungs, heart and urinary tract; just as instantly claimed.
Martin et al., teach administering said antibiotic composition to a mammal so that at least the OAP based antibiotic is absorbed into the peptidoglycan cell wall of bacteria; enzyme activation of the Beta-Lactam group; release of the OAP leaving group, and reduction of the organic acyl polyoxychlorine releases oxychlorine intermediates that induce oxidative stress and cell death in order to kill the bacteria [para 43]. Some non-limiting example of how OAP based antibiotic can be administered include: intravenous, oral, topical, nasal spray, drops, and the like [para 69]. Thus Martin et al., teach the instantly claimed formulations whereby intravenous injection provides for contact with blood and heart; while nasal sprays and drop provide for contact lung. Oral drugs can obviously reach the lungs, heart, bloodstream and urinary tract of an individual. Thus intravenous, oral, nasal spray, drops, are contacted with blood, heart, lung, lung sputum and/or urinary tracts to the contact the biofilm therein. There is not a single sentence or instance where Martin et al., teach hypochlorite and chlorite is administered with the sodium chlorate, potassium chlorate, lithium chlorate, calcium chlorate, and/or magnesium chlorate to allow for contact with the blood, heart, lungs, and/or urinary tract of the individual.
Applicants acknowledge that Martin et al., teach an embodiment where Martin administers chlorate in combination with an antibiotic, where the simple chlorate salt in combination with a separate antibiotic molecule is provided. Thus, Applicants admit Martin et al., teach instant claimed antibiotic and/or system.
Applicants argue that a change to replace Martin’s organic acyl polyoxychlorine coupled to a B-lactam carrier with chlorate oxyanion would be understood to defeat Martin’s intended purpose. However, Applicants is reminded that the Office is arguing about changing anything. This is a 102(a) rejection. Martin et al., is relevant for all that it teaches. In this case Martin et al., disclose a polyoxychlorine comprises chlorate having the general formula ClO3 wherein the polyoxychlorine is coupled to a β-Lactam carrier such as cepholasporin, carbapenem, or beta-lactamase; all of which are antibiotics. Therefore, Applicants argument is not persuasive.
Finally, Applicants argue that intravenous injection is not a sufficient teaching of contacting a medium such as blood, heart, lungs, urinary tract or lung sputum. Applicant is reminded that Applicants own specification at paragraph [116, 153, table 2 and other locations] teach chlorate alone or in combination with the one or more antibiotics or antimicrobial can be provided to an individual intravenously, intramuscularly, or inhaled as an aerosol or via a nebulizer. Furthermore, an intravenous (IV) injection is the delivery of a medication, fluid, or other substance directly into a vein, allowing it to enter the bloodstream immediately. Thus by definition, intravenous injection immediately enters the blood stream, thereby clearly describing contact between blood medium and the chlorate/antibiotic compound. Therefore, this argument is not persuasive.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
13. Claims 1-4, 7-8, 12,14, 17-18 and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Jung et al., (Journal of Food Protection, Vol. 66, No. 4, 2003, Pages 660–663) as evidenced by Wit et al., (Food Microbiology. Volume 7, Issue 2, June 1990, Pages 113-12. See also https://www.sciencedirect.com/science/article/abs/pii/074000209090017C ) in view of Schonewille et al., (FEMS Immunology & Medical Microbio, Vol 65, Issue 2, July 2012, Pages 360-365). For Witt et al. reference https://www.sciencedirect.com/science/article/abs/pii/074000209090017C
The claims are drawn to methods to reduce survivability and/or antibiotic resistance of nitrate reductase (Nar)-and/or periplasmic nitrate reductase (Nap)-containing bacteria in a biofilm. The claims are also drawn to the system.
Jung et al., disclose reduction of Salmonella typhimurium in experimentally challenged broilers by nitrate adaptation and sodium chlorate supplementation in drinking water. Nitrate reductases also convert chlorate (ClO3-) into cytotoxic chlorite (ClO2-), since it mimics the activity of nitrate. A study conducted by Tama´si and Lantos demonstrated that increased death rates for Escherichia coli and Salmonella serotype Enteritidis were due to a reduction in chlorate ions caused by nitrate reductases [page 660, col. 1]. Recently, sodium chlorate has been extensively studied and applied for- the inactivation of foodborne pathogens such as E. coli O157:H7 and Salmonella Typhimurium in vitro and in vivo [page 660, col. 1-2]. Jung et al., teach the third group of broilers were administered experimental sodium chlorate (ECP) at 15mM NaClO3 which contained 15nM chlorate ions and the fourth group was administered ECP in combination with sodium nitrate where the ECP 15mM NaClO3 solution also contained 2.5 mM sodium nitrate and 20 mM sodium lactate [page 660-661, col 2-1]. For the 5 days immediately prior to slaughter, and ECP was provided via ad libitum access to drinking water for the last 2 days before slaughter [page 661, col. 1]. Table 1 shows the bactericidal effects of the chlorate containing treatments against Salmonella relative to those of the non-chlorate-containing groups. In trial 1, concentrations of Salmonella (mean 6 standard deviation) were significantly (P , 0.05) lower for broilers receiving ECP in combination with SN than for untreated control broilers [page 661, col. 2].
In these studies, broilers were challenged with two different levels of inoculum, approximately log 7 CFU/ml for trial 1 and log 9 CFU/ml for trial 2, to determine whether a similar quantitative trend occurred postmortem. Even with the increased inoculum level in trial 2, we observed that the most significant (P , 0.05) reductions (2 log units) occurred for the group receiving SN treatment in combination with ECP treatment [para 661, col. 2].
Wit et al., evidences the antimicrobial activity of sodium lactate. This antimicrobial effect was found to exist towards various lactic acid bacteria Staphylococcus aureus, and Salmonella typhimurium.
While Jung et al., teach an antibacterial composition comprising sodium chlorate with a cation other than a metal cation, alone or in combination with sodium nitrate further comprising water in an effective amount to treat E coli and Salmonella infections and its administration in the blood, heart, lungs or urinary tract, where E coli and Salmonella are Nar containing bacteria; Jung et al., does not state contacting a medium such as blood, heart, lung, lung sputum and/or urinary tract comprising biofilm with an effective amount of the claimed compound.
Schonewille et al., teach the Biofilm (BF) building capacity of different serotypes of Salmonella enterica derived from the poultry farm environment was investigated. Several isolates from different stages of the production cycle were chosen and compared to laboratory grown strains of the same serotype. BF building capacity was analyzed. Results indicated further that certain farm isolates were capable of forming BF under laboratory conditions. The BF building capacity of poultry-derived isolates is a function of adaptation to their host environment. Thus, the control of BF as a reservoir for Salmonella in the farm environment is of crucial importance for the overall improvement of food safety.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Jung et al., method of reducing Salmonella typhimurium in chickens (broilers) by nitrate adaptation and sodium chlorate supplementation in drinking water when Schonewille et al teach Salmonella typhimurium is more than capable of forming biofilms within said chickens. One of ordinary skill in the art would have a reasonable expectation of success by administering sodium chlorate, sodium nitrate and sodium lactate which has antimicrobial activity to chickens to treat their blood, heart, lungs, lung sputum and/or urinary tract with oral administration. Furthermore, no more than routine skill would have been required to orally administer the sodium chlorate antimicrobial combination to reduce Salmonella typhimurium within chickens. Finally it would have been prima facie obvious to combine the knowledge of Witt et al., and Schonewille et al
When Jung et al., advantageously achieves a reduction of Salmonella typhimurium.
Response to Arguments
14. Applicant’s arguments with respect to claims 1-4, 7-8, 12,14, 17-18 and 19-21 have been considered but the arguments are not persuasive.
Applicants argue that Jung et al., is focused on gastrointestinal tract treatment and not administration to blood, heart, lungs, or urinary tract. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Jung et al., method of reducing Salmonella typhimurium in chickens (broilers) by nitrate adaptation and sodium chlorate supplementation in drinking water when Schonewille et al teach Salmonella typhimurium is more than capable of forming biofilms within said chickens. One of ordinary skill in the art would have a reasonable expectation of success by orally administering sodium chlorate, sodium nitrate and sodium lactate which has antimicrobial activity to chickens to treat their blood, heart, lungs, lung sputum and/or urinary tract with oral administration. For decades, orally administered compositions are commonly prescribed to treat and manage heart diseases and infections. Furthermore, oral antibiotics are well known to treat heart, urinary tract and lung infections. Again, Applicant is reminded that drinking water can being safely injected into the urinary tract.
Applicants point to the Oliver reference, which is a reference recited in the pertinent art section and not a reference used within any rejection of record. It is noted, that the references recited within the pertinent art section are merely the Office’s way of alerting Applicants to additional art within a similar scientific area of study. Therefore, the teachings of the Oliver et al., reference are not relevant to the rejection of record.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, the rejection of record only takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made as evidenced by the fact that all the scientific rationale is supported by the prior references. Applicants failed to point to an knowledge gleaned only from the applicant's disclosure; therefore this argument is not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have a reasonable expectation of success by administering sodium chlorate, sodium nitrate and sodium lactate which has antimicrobial activity to chickens to treat their blood, heart, lungs, lung sputum and/or urinary tract with oral administration.
Applicants argue that the proposed modification can not change the principle operation of the primary reference. In this case, neither the antibiotic nor the chlorate composition (or system) of Jung et al., was changed. Additionally the antibiotic compound /composition or system being supplied within the drinking water needs to be changed. It would have been prima facie obvious to combine the knowledge of Witt et al., and Schonewille et al., when Jung et al., advantageously achieves a reduction of Salmonella typhimurium with drinking water when orally administering drinking water is a formulation known to allow the antibiotic to be contacted with blood, heart, lungs and urinary tract. Moreover, drinking water is known to be an efficient and safe composition to be administered into the urinary tract. Applicants have not provided any scientific evidences to the contrary therefore, the rejection is maintained.
Rejoinder
15. The Office Action dated June 1, 2022 contained newly submitted claims and 25-30 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Claims 23 and 25-30 are drawn to additional nonelected methods.
Since applicant has received numerous actions on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 23 and 25-30 were withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Therefore, claims 23 and 25-30 will not be rejoined.
Pertinent Art
16. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of S. aureus resistant to certain antibiotics, making it challenging to treat. The NapABC enzyme is a periplasmic nitrate reductase that supports the growth of certain enteric bacteria like Salmonella enterica serovar Typhimurium in the gut. There's no indication that NapABC is directly involved in MRSA's antibiotic resistance.
NarGHJI (nitrate reductase) and Methicillin-Resistant Staphylococcus aureus (MRSA) lies primarily in the modulation of MRSA's virulence.
The narG gene in Salmonella enterica serovar Typhimurium (S. Typhimurium) encodes the catalytic subunit of the nitrate reductase A (NarG), an enzyme involved in anaerobic respiration. Specifically, narG is part of the narGHJI operon, which is responsible for synthesizing the functional nitrate reductase enzyme complex. This enzyme complex utilizes nitrate as an electron acceptor during anaerobic respiration, a process that can be crucial for bacterial survival and growth in oxygen-limited environments, such as the gut during infection.
In Salmonella Typhimurium, the gene napA encodes for a periplasmic nitrate reductase, a protein that enables the bacteria to utilize nitrate as an electron acceptor under anaerobic conditions. This enzyme is part of the napABC operon, which plays a role in the bacteria's ability to thrive in the inflamed gut environment, particularly during colitis.
The narG gene in E. coli O157:H7 encodes a subunit of the enzyme nitrate reductase.
The NapABC enzyme complex in E. coli O157:H7, a bacterium known for causing severe illness. Specifically, the NapABC complex is a periplasmic nitrate reductase system that allows the bacteria to respire anaerobically using nitrate as an electron acceptor. E. coli O157:H7 is a significant foodborne pathogen, and understanding its metabolic capabilities, like anaerobic respiration, is important for studying its survival and virulence.
Anderson et al., Int J Food Microbiol. 2001 Dec 30;71(2-3):125-30. Oral sodium chlorate administration reduced gut concentrations of E. coli O157:H7 in experimentally infected pigs and wildtype E. coli concentrations in nonchallenged pigs.
Anderson et al., (Vet Res Commun. 2004 Apr;28(3):179-89). Effect of drinking-water administration of experimental chlorate ion preparations on Salmonella enterica serovar Typhimurium colonization in weaned and finished pigs.
Tama´si, G., and Z. Lantos. (Agric. Wastes 6:91– 97. 1983). Influence of nitrate reductases on survival of Escherichia coli and Salmonella enteritidis in liquid manure in the presence and absence of chlorate.
Determination of a Sodium Chlorate Dose that Results in Safe Concentrations of Tissue Residues in Beef Cattle. David Smith. U.S. Department of Agriculture, Agricultural Research Service. May 2005. One steer and one heifer each were randomly selected to receive nominal daily doses of 21, 42, or 63 mg/kg body weight of sodium [36Cl] chlorate. Doses were selected to bracket the preferred use of 42 mg/kg. To prevent the radiochemical contamination of the study facilities, and to ensure quantitative dosing, sodium [36Cl] chlorate was administered through ruminal cannulas.
Effects of repeated-low level sodium chlorate oral gavage administration on ruminal and fecal coliforms in sheep December 2014. Journal of Environmental Science and Health Part B Pesticides Food Contaminants and Agricultural Wastes 49(12).
Pharmacokinetics of ruminally dosed sodium [36Cl]chlorate in beef cattle. C. E. OLIVER et al., published: 29 May 2007. Six Loala cattle were assigned (one heifer and one steer per treatment) to one of three intraruminal doses of radiolabeled sodium [36Cl]chlorate (21, 42, or 63 mg/kg body weight) administered in four equal aliquots over a 24-h period. Blood and serum were collected (29 samples in 48h. Total radioactive residues were measured and the radioactive moieties were speciated. Chlorate appeared rapidly in blood and serum after dosing. For animals administered a dose of 42 or 63 mg/kg, the half-life of absorption was estimated at 0.6–0.9h. Serum chlorate concentrations progressively increased with aliquot administration until peaking at 6–21 parts per million at 26h. Between aliquot administrations, serum chlorate levels typically peaked in 3.5h or less. The half-life of chlorate elimination ranged between 6.9 and 11h, depending on the dose. Ultimately, absorption of chlorate removes it from its desired site of action, the lower gastrointestinal tract, thereby reducing its efficacy. Further research is needed to develop a chlorate formulation that will allow passage to the lower gastrointestinal tract.
Zemke et al., (Free Radic Biol Med. 2014 Sep 16;77:307–316). Nitrite Modulates Bacterial Antibiotic Susceptibility and Biofilm Formation in Association with Airway Epithelial Cells
Conclusion
17. No claims allowed.
18. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645
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