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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 06/25/2025, has been entered.
Notice of Non-Compliant Amendment-Withdrawn
The Notice of Non-Compliant Amendment was inadvertently sent in error (see attached interview summary) and is hereby withdrawn.
Objections to the Specification-Withdrawn
The objection to the amendment of ¶ 0024 of the specification filed on 09/20/2021, under 35 U.S.C. 132(a), is overcome by the Applicants’ amendments and is hereby withdrawn. Specifically, Applicants have amended the specification to delete ¶ 0024 in its entirety.
Withdrawn Rejections
The rejection of claims 1-3, 7-8, 10, 22 and 32-37 under 35 U.S.C. 103 as being unpatentable over Collins of record (U.S. Pub. No. 20150071904) in view of: i) Murakami of record (U.S. Pub. No. 20120129905); ii) Edwards of record (British J. Venereal Disease, 1980) and iii) WO2017057919A1 of record (published 04/06/2017, Machine Translation), is overcome by the Applicant’s amendments and is hereby withdrawn. For example, Applicant amended claim 1, so that claim 1 no longer recite “aldaric acid”.
The rejection of claims 1-3, 7-8, 10, 22 and 32-37 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 9-18 of U.S. Application No. 16/258,780 (now U.S. Patent No. 11,684,597), in view of Collins of record (U.S. Pub. No. 20150071904), is overcome by the Applicant’s amendments and is hereby withdrawn. For example, Applicant amended claim 1, so that claim 1 no longer recite “aldaric acid”.
Status of the Claims
Claims 1-2, 7-8, 10, 22-25, 27-30 and 32-38 are pending.
Applicant’s arguments filed on 06/25/2025, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicant’s amendments filed on 06/25/2025, have each been entered into the record. Applicant has amended claims 1 and 32-33. Applicant has cancelled claim 3. Applicant has newly added claim 38. Claims 23-25 and 27-30 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected invention. Therefore, claims 1-2, 7-8, 10, 22 and 32-38 are subject of the Office action below.
Claim Objections
Claim 38 is objected to under 37 CFR 1.71(a) for reciting “an obligate anaerobic will not grow”, instead of reciting “an obligate anaerobic which will not grow”. Appropriate correction is required.
Claim Rejections - 35 USC § 112-2nd Paragraph
Maintained/New grounds of Rejection Necessitated by Applicant’s Amendments
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 32-35 and 37-38 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. Claim 34 depends from claim 33 and is therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth below.
As per MPEP 2173.02, “[d]uring prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude (emphasis added). See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc).”
If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, is appropriate (emphasis added). See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993).
The recited limitation of “an obligate anaerobic microorganism which will not grow in the presence of oxygen” in claims 32 and 38, is superfluous in that a person skilled in the art would have readily understood the term “an obligate anaerobe” as referring to an anaerobe which will not grow in the presence of oxygen. It is recommended that the phrase “which will not grow in the presence of oxygen”, when referring to an obligate anaerobe, be deleted from the claims. Appropriate correction is required.
Claim 33 recites “a lesser dose”, however, a person skilled in the art cannot reasonably determine the meets and bounds of the recited limitation in claim 33. This is because claim 1 from which claim 33 depends, fails recite “a dose” of a nitroimidazole compound administered in combination with a feedstock composition, to a microorganism to achieve minimal inhibitory concentration (MIC) for the microorganism determined via Antimicrobial Susceptibility Testing with a feedstock composition containing an equivalent concentration of glucose as the sugar acid (emphasis added), in which a person skilled in the art can determine “a lesser dose” in claim 33.
The scope of “a lesser dose”, is not defined by the claim or the instant specification to any specific amount of a nitroimidazole compound. The specification does not provide a standard for ascertaining the requisite degree. Thus, one of ordinary skill in the art would not be able to draw a clear boundary between what is and is not covered by the claims. Accordingly, without guidelines in the specification for how the “a lesser dose”, is determined, the skilled artisan cannot reasonably determine what amount of a nitroimidazole compound constitutes as “a lesser dose” from an amount that does not constitutes as “a lesser dose”. Appropriate correction is required.
Claim 33 recites the limitation “administering a laser dose of the nitroimidazole compound with the feed stock composition to the microorganism than would be needed to achieve the same minimal inhibitory concentration (MIC) for the microorganism determined via Antimicrobial Susceptibility Testing with a feedstock composition containing an equivalent concentration of glucose as the sugar acid” (emphasis added). There is insufficient antecedent basis for this limitation in the claim. Claims 33 lacks antecedent basis because claim 1 from which claim 33 depends, fails to recite the limitation of a dose of a nitroimidazole compound needed to achieve MIC for a microorganism. Appropriate correction is required.
The recitation of “wherein no glucose is administered to the microorganism” in claim 35, renders the claim indefinite because it is an attempt to claim the invention by excluding what the Applicant did not invent rather than distinctly and particularly pointing out what the Applicant did invent.
A negative limitation or exclusionary proviso must have basis in the original disclosure (see MPEP § 2173.05(i)). In the instant case, a review of the specification and claims as originally filed, fails to reveal any support for administering a combination of a nitroimidazole, a sugar acid and glucose to a microorganism. Appropriate correction is required.
Claim 37 recites “selecting the sugar acid to decrease or eliminate production of NADH and NADPH in the microorganism”, however, one skilled in the cannot reasonably determine the meets and bounds of the recited limitations. This is because it is not clear from either the specification or the common teachings in the art how this limitation further limits the claims. For example, it is unclear to one skilled in the art as to what sugar acid of claim 32, would “decrease or eliminate production of NADH and NADPH”, and what sugar acid of claim 32, would not “decrease or eliminate production of NADH and NADPH”. The scope of the “decrease or eliminate production of NADH and NADPH”, is not defined by the claims or the instant specification. It is not clear to a person skilled in the art if this limitation is limiting to a certain sugar acid, a certain nitroimidazole compound or a certain microorganism.
The specification does not teach or provide a nexus between the functional result that Applicant claims to achieve by the claimed composition of claim 37, with any particular component of the composition or the manner in which the composition administered to a microorganism. There is no description as to the pharmaceutical approach that makes these results possible, nor does the specification teaches any sugar acid, nitroimidazole compound or microorganism, to avoid. The specification does not provide a standard for ascertaining the requisite degree. Thus, one of ordinary skill in the art would not be able to draw a clear boundary between what is and is not covered by the claims. Accordingly, for the purpose of examination, any administration of a combination of a nitroimidazole compound of claim 32 with a sugar acid of claim 32, to a microorganism, is being included in the interpretation of “selecting the sugar acid to decrease or eliminate production of NADH and NADPH in the microorganism”. Appropriate correction is required.
Claim 37 recites “metabolizing the nitroimidazole compared to glucose”. There is insufficient antecedent basis for this limitation in the claim. Claims 37 lacks antecedent basis because claim 32 from which claim 37 depends, fails to recite “metabolizing a nitroimidazole compared to glucose”. Appropriate correction is required.
This lack of clarity makes it impossible to ascertain with reasonable precision when that claim is infringed and when it is not. Lacking such clarity, the skilled artisan would not be reasonably apprised of the metes and bounds of the subject matter for which Applicants seek patent protection. Rather, a subjective interpretation of the claimed language would be required. However, as such is deemed inconsistent with the tenor and express language of 35 U.S.C. § 112, second paragraph, the claims are deemed properly rejected.
Response to Applicants’ Arguments
Applicant raised several arguments (see pages 8-9 of remarks), alleging that the rejection of claims 33-34 is improper on the grounds that:
1) Applicant has amended claim 33:
2) a person skilled in the art understands that antibiotic dose can be computed from the MIC, which can be experimentally determined via antimicrobial susceptibility testing;
3) the inventor’s experimental data demonstrates that an oxidized sugar acid feedstock yields an increased antibiotic susceptibility of at least two-fold or greater compared to administering the same amount of conventional glucose feedstock
Applicant cites ¶s 0007, 0054, 0059 and Figure 2 of the specification, in support of the Applicant’s position.
Response:
The Applicant has not properly addressed the specific grounds of rejections discussed in the previous Office setting and reiterated above, as it pertains to amended claim 33.
For the reasons above, and those made of record in the previous Office action, the rejections are maintained.
Claim Rejections - 35 USC § 112-New Matter
New grounds of Rejection Necessitated by Applicant’s Amendments
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 32-34 and 36-38 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 Claim 34 depends from claim 33 and is therefore, also under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for the reasons set forth below. Claim 37 depends from claim 32 and is therefore, also under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for the reasons set forth below.
MPEP 2163 states:
“An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention….one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process”.
Applicant’s response filed on 06/25/2025, has introduced new matter.
Each of claims 32 and 38 recites:
“administering an antibiotic comprising a nitroimidazole compound to an obligate anaerobic microorganism which will not grow in the presence of oxygen or a facultative anaerobe growing in an environment devoid of oxygen; and
administering a feedstock composition comprising a sugar acid to the anaerobic microorganism”.
Claim 33 recites:
“administering a lesser dose of the nitroimidazole compound with the feedstock composition to the microorganism than would be needed to achieve the same minimal inhibitory concentration (MIC) for the microorganism determined via Antimicrobial Susceptibility Testing with a feedstock composition containing an equivalent concentration of glucose as the sugar acid”
However, a review of the specification and claims as originally filed, failed to provide adequate support for the particular active step(s) recited in claims 32-33 and 38 and the particular type of anaerobic microorganisms (obligate and facultative) recited in claims 32 and 38, in a method for increasing susceptibility of microorganisms to nitroimidazole antibiotics. The newly introduced particular active step and anaerobic microorganisms (obligate and facultative), are not described in the specification in such a way as to reasonably convey to one skilled in the art that the Applicants, at the time of the instant application, have possession of an active step(s) recited in claims 32-33 and 38 and the particular type of anaerobic microorganisms (obligate and facultative) recited in claims 32 and 38.
Claim 36 recites the limitation of a sugar acid comprising 0.5% (by vol). The specification (see ¶ 0053), only discloses 0.5% D-galacturonate (a sugar acid). However, a review of the specification and claims as originally filed, failed to provide adequate support for the particular sugar acid concentration of 0.5% (by vol), recited in claim 36. The newly introduced particular sugar acid concentration of 0.5% (by vol), recited in claim 36, is not described in the specification in such a way as to reasonably convey to one skilled in the art that the Applicants, at the time of the instant application, have possession of a sugar acid concentration of 0.5% (by vol), recited in claim 36.
New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04(a) to § 608.04(c). Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112(pre-AIA ), first paragraph.
Claim Rejections - 35 USC § 102
New grounds of Rejection Necessitated by Applicant’s Amendments
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.
Claims 1, 7-8, 10 and 33-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ciccarelli et al (hereinafter “Ciccarelli”, Antimicrobial Agents & Chemotherapy, 2012, 10, 5315-5320) as evidenced by: 1) Sohee of record (WO2017057919A1, published 04/06/2017, Machine Translation); and 2) Bonardi et al (hereinafter “Bonardi”, ACS Med. Chem. Lett., 2019, 10, 413-418).
By way of a background, Applicant’s invention (see, e.g., ¶ 0008), is drawn to a method for using a feedstock composition for increasing the susceptibility of a nitroimidazole antibiotic to a microorganism. The specification discloses the term “feedstock”, as referring to glucose, gluconate and galacturonate (see ¶ 0040), and provides working examples of feedstock compositions, each composition comprising glucose, gluconate and galacturonate (see ¶ 0041, Table 1). Accordingly, a composition comprising a sugar acid of the claimed invention, is included in the interpretation of “a feedstock composition”.
Under the broadest reasonable interpretation (BRI), consistent with the specification, independent claim 1 is being interpreted as a method for increasing susceptibility of microorganisms to nitroimidazole antibiotics comprising administering to a microorganism:
a) a nitroimidazole compound; and
b) a sugar acid selected from the group consisting of uronic acid, aldonic acid and ulosonic acid or any salt thereof, with the intended use as energy source.
Regarding claim 1, Ciccarelli teaches a method for increasing susceptibility of Trypanosoma cruzi (a microorganism) to benznidazole (a nitroimidazole, see ¶ 0004 of the specification), comprising administering to the microorganism a) benznidazole; and b) ascorbic acid (vitamin C). The reduction in parasitemia (T. cruzi infection) in benznidazole-treated mice was improved by addition of ascorbic acid. Please see abstract, Materials and Methods section, page 5318, right column ¶ and Figure 7A.
Ascorbic acid is a sugar acid, as evidenced by Sohee, who discloses ascorbic acid as an example of aldonic acid (see page 3).
Therefore, claim 1 is anticipated by Ciccarelli as evidenced by Sohee.
Regarding claims 7-8 and 10, Ciccarelli discloses that benznidazole and/or ascorbic acid were formulated in PBS and administered by intraperitoneal route (see Materials and Methods section).
Regarding claim 33, Ciccarelli (see page 5316, 2nd ¶ on left column), teaches benznidazole’s anti-T. cruzi activity at 0.75-25 µM (i.e., 0.0002-0.007 µg/µL, mw = 260.25), which is less than the MIC of benznidazole against T. cruzi activity (32 µM), as evidenced by Bonardi (see Table 3), who discloses benznidazole’s anti-T. cruzi activity at MIC 32 µM.
Regarding claim 34, Ciccarelli teaches benznidazole at a concentration of less than 1 µg/µL (see discussions above).
Regarding claim 35, Ciccarelli did not teach administering glucose to the microorganism.
Claims 32 and 37-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ciccarelli (Antimicrobial Agents & Chemotherapy, 2012, 10, 5315-5320) as evidenced by: 1) Sohee of record (WO2017057919A1, published 04/06/2017, Machine Translation); and 2) Hall et al (hereinafter “Hall”, Immunology Today, 1991, 12(3), A22-A27).
Regarding claims 32 and 38, Ciccarelli teaches a method for increasing susceptibility of Trypanosoma cruzi (a microorganism) to benznidazole (a nitroimidazole, see ¶ 0004 of the specification), comprising administering to the microorganism a) benznidazole; and b) ascorbic acid (vitamin C). The reduction in parasitemia (T. cruzi infection) in benznidazole-treated mice was improved by addition of ascorbic acid. Please see abstract, Materials and Methods section, page 5318, right column ¶ and Figure 7A.
Ascorbic acid is a sugar acid, as evidenced by Sohee (see page 3), who discloses ascorbic acid as an aldonic acid.
Trypanosoma cruzi is an obligate microorganism, as evidenced by Hall (see abstract), who discloses T. cruzi as an obligate microorganism.
Regarding claim 37, the intended use of a sugar acid to decrease or eliminate NADH and NADPH production in the microorganism, it is noted that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the cited prior art teaches a sugar acid of claim 32 (see discussions above).
Since the prior art teaches the identical chemical structure, the properties Applicants disclose and/or claim are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Applicants are further requested to note that it is well settled that “intended use” of a composition or product, e.g., a sugar acid, will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In re Hack 114, USPQ 161.
Claim Rejections - 35 USC § 103
New grounds of Rejection Necessitated by Applicant’s Amendments
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 7-8, 10 and 32-38 are rejected under 35 U.S.C. 103 as being unpatentable over Knight et al (hereinafter “Knight”, J. Radiation Biology, 1979, 36(4), 367-377) in view of: 1) Sohee of record (WO2017057919A1, published 04/06/2017, Machine Translation); 2) Ciccarelli (Antimicrobial Agents & Chemotherapy, 2012, 10, 5315-5320) as evidenced by Bonardi (ACS Med. Chem. Lett., 2019, 10, 413-418); 3) Josephy et al (hereinafter “Josephy”, Nature, 1978, 271(26), 370-372); and 4) Sagona et al (hereinafter “Sagona”, Bulleting of Insectology, 2015, 68(2), 233-237).
By way of a background, Applicant’s invention (see, e.g., ¶ 0008), is drawn to a method for using a feedstock composition for increasing the susceptibility of a nitroimidazole antibiotic to a microorganism. The specification discloses the term “feedstock”, as referring to glucose, gluconate and galacturonate (see ¶ 0040), and provides working examples of feedstock compositions, each composition comprising glucose, gluconate and galacturonate (see ¶ 0041, Table 1). Accordingly, a composition comprising a sugar acid of the claimed invention, is included in the interpretation of “a feedstock composition”.
Similar to independent claims 1, 32 and 38, Knight discloses that nitroimidazole compounds generally exhibit cytotoxicity towards anaerobes (which necessarily encompass obligate and facultative anaerobes) and hypoxic or anoxic cells (cells deficient in oxygen supply). The basis of the selective toxicity in anaerobes is related to the redox potential of the drugs, the nitro group being reduced by redox mechanisms existing only in anaerobic cells. Please see abstract and page 367.
It is noted that Applicant (see ¶ 0004 of the specification), discloses that at the time of the instant invention, nitroimidazole compounds have been used to combat anaerobic microorganism and parasitic infections. Applicant’s admission constitutes as a prior art (see MPEP § 2129).
Although Knight is not explicit in disclosing use of a sugar acid in improving the toxicity of a nitroimidazole compound, one skilled in the art would have had a reasonable expectation of success in the use of a sugar acid of the claimed invention for improving the toxicity of a nitroimidazole compound. This is because at the time of the instant invention, it was known in the art that:
i) a sugar acid of the claimed invention can be used for improving the toxicity of an antimicrobial composition; and
ii) a sugar acid of the claimed invention, can be used to for improving the toxicity of a nitroimidazole compound.
For example:
i) Sohee teaches a method of using a sugar acid selected from aldonic acid (e.g., glycerin acid, xylonic acid, gluconic acid, and ascorbic acid), uronic acid (e.g., neuramic acid, ketodeoxy oxtuloconic acid, glucuronic acid, galacturonic acid and iduronic acid), ulosonic acid and aldaric acid (see pages 3-4), can be used for improving the toxicity of an antimicrobial composition (see pages 2-3), and the combination can produce a synergistic effect (see page 10).
ii) Ciccarelli teaches a method for increasing susceptibility of Trypanosoma cruzi (a microorganism) to benznidazole (a nitroimidazole, see ¶ 0004 of the specification), comprising administering to the microorganism a) benznidazole; and b) ascorbic acid (a sugar acid, see discussions above). The reduction in parasitemia (T. cruzi infection) in benznidazole-treated mice was improved by addition of ascorbic acid. Please see abstract, Materials and Methods section, page 5318, right column ¶ and Figure 7A.
Furthermore, similar to Sohee (see discussions above), Sagona (see, e.g., abstract and Table 1), teaches gluconic acid’s activity against microorganism.
Therefore, at the time of the instant invention, a person skilled in the art would have found it obvious to administer an antimicrobial compound (e.g., a nitroimidazole compound) and a sugar acid of the claimed invention to a microorganism, with a reasonable expectation of improving the toxicity of the antimicrobial compound and producing a synergistic effect.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
It is therefore reasonable to conclude that the strength of correlation between the antimicrobial activity of: i) a nitroimidazole compound; ii) a sugar acid and iii) the synergistic effect of combining an antimicrobial compound with a sugar acid, gives rise to reasonable expectation of success.
Regarding claims 1, 32 and 38, the intended use of a sugar acid of claims 1, 32 and 38, as an energy source used by the microorganism, is an inherent property of the sugar acid. Any properties exhibited by or benefits provided by the composition are inherent and are not given patentable weight over the prior art. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties Applicants disclose and/or claim are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. In the instant case, the cited references combine to teach a sugar acid of claims 1, 32 and 38 (see discussions above).
Applicants are further requested to note that it is well settled that “intended use” of a composition or product, e.g., a sugar acid, will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In re Hack 114,
Regarding claim 2, Knight discloses metronidazole (see page 367).
Regarding claims 7-8 and 10: i) Sohee discloses that the inventive antimicrobial composition can be formulated as a food composition (see page 6 and reference claim 11); and iii) oral administration, for example, aqueous solution, pills, capsules and tablets. Please see ¶ 0306; and ii) Ciccarelli discloses that benznidazole and/or ascorbic acid were formulated in PBS and administered by intraperitoneal route (see Materials and Methods section).
Regarding claims 33-34, the recitation of the limitation of a lesser amount of a nitroimidazole, is an art-recognized variable. For example, Ciccarelli (see page 5316, 2nd ¶ on left column), teaches benznidazole’s anti-T. cruzi activity at 0.75-25 µM (i.e., 0.0002-0.007 µg/µL, mw = 260.25), which is less than the MIC of benznidazole against T. cruzi activity (32 µM), as evidenced by Bonardi (see Table 3), who discloses benznidazole’s anti-T. cruzi activity at MIC 32 µM.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claim 35, the cited references do not combine to teach administering glucose to the microorganism for the microorganism to metabolize the nitroimidazole.
Regarding claim 36, the recitation of the limitation of a sugar acid in an amount of 0.5% (by vol), is an art-recognized variable. For example, Sohee (see page 5), discloses that the sugar acid may be in an amount of 0.001 to 10.0 wt%, based on the total weight of the composition. It would have been obvious to a person skilled in the art that mass % can be converted to vol %, by employing the appropriate density of the sugar acid.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claim 37, the intended use of a sugar acid to decrease or eliminate NADH and NADPH production in the microorganism, it is noted that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the cited references combine to teach a sugar acid of claim 32 (see discussions above).
Since the prior art teaches the identical chemical structure, the properties Applicants disclose and/or claim are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Applicants are further requested to note that it is well settled that “intended use” of a composition or product, e.g., a sugar acid, will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In re Hack 114, USPQ 161.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1-2, 7-8, 10, 22 and 32-38 are rejected under 35 U.S.C. 103 as being unpatentable over Knight (J. Radiation Biology, 1979, 36(4), 367-377) in view of: 1) Sohee of record (WO2017057919A1, published 04/06/2017, Machine Translation); 2) Ciccarelli (Antimicrobial Agents & Chemotherapy, 2012, 10, 5315-5320) as evidenced by Bonardi (ACS Med. Chem. Lett., 2019, 10, 413-418); 3) Josephy (Nature, 1978, 271(26), 370-372); and 4) Sagona (Bulleting of Insectology, 2015, 68(2), 233-237), as applied to claims 1-2, 7-8, 10 and 32-38 above, and further in view of Heinke et al (hereinafter “Heinke”, EP1138756A2, published 10/04/2001, Machine Translation).
The limitation of claims 1-2, 7-8, 10 and 32-38, as well as the corresponding teachings of Knight, Sohee, Ciccarelli as evidenced by Bonardi, Josephy and Sagona, are described above and are hereby incorporated into the instant rejection.
Claim 22 is similar to claim 1, however, claim 22 differs slightly from claim 1 in that claim 22 requires a sugar acid salt selected from gluconate or galacturonate.
The cited references differ from claim 22 only insofar as the cited references do not combine to explicitly teach the limitation of claim 22.
However, the claimed invention would have been obvious over the cited references, because at the time of instant invention, a sugar acid and salts thereof, are considered as functional equivalents. For example, Heinke (see abstract, ¶s 0020-0021 and 0138), discloses that sugar acids (e.g., galacturonic acid, gluconic acid) and/or salts thereof (e.g., gluconate), as functional equivalents.
Therefore, at the time of the instant invention, one skilled in the art would have found it obvious to substitute a sugar acid (e.g., gluconic acid) for gluconic acid salt (gluconate), with a reasonable expectation of improving the toxicity of the antimicrobial compound and producing a synergistic effect.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Conclusions
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 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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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629