DETAILED ACTION
This is the first action in response to US Patent Application No. 18/270,508, filed 30 June, 2023, as the National Stage Entry of International Application PCT/IB2022/050962, filed 03 February, 2022, and with priority to provisional application 63/133,440, filed 04 January, 2021.
The preliminary amendments filed 04 January, 2024, have been entered. Claims 11-12 have been amended to remove multiple dependencies. Claims 21-31 are cancelled. Claims 1-20 are pending and have been fully considered.
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 .
Claim Interpretation
Claim 4 recites “the composition comprises an α-glucoheptonic acid concentration, based on total isomers of glucoheptonic acid, of about 90% or greater”. In other words, this limitation requires that at least about 90% of the glucoheptonic acid present in the aqueous solution is α-glucoheptonic acid. Similarly phrased limitations in claims 8-9, and 17-18 are interpreted in a corresponding manner.
Claim 6 further recites the limitation “β73-glucoheptonate”. The instant specification at [0041] indicates that “sodium β73-glucoheptonate is a solution of sodium glucoheptonate comprising from about 60% to about 75% β-isomer…or from about 69% to about 71% of the β-isomer”, and further indicates that “In another embodiment, the sodium β73-glucoheptonate solution comprises about 61-73.5% β-isomer”. From the written description, it is thus understood that the notation “β73” refers to the percentage of the glucoheptonate species present in the beta isomer form. The term is interpreted in view of [0041] as encompassing embodiments wherein the beta isomer is present at a percentage within a range of about 60% to about 75%, which is the broadest range recited in [0041].
Claim 7 recites the limitation “β81-glucoheptonate”. The instant specification at [0096] indicates that the term “β81-glucoheptonate” refers to a glucoheptonate salt having a β-isomer content of 81%. The claim has been interpreted accordingly.
Claim 19 recites various ranges from the molar ratio of glucoheptonic acid to chlorhexidine, including broader ranges and narrower ranges which fall within the broader range. The claim recites the ranges with the conjunction “or”, and the broadest recited range of “about 1.5:1 to about 3:1” (claim 19, line 2) encompasses all of the other recited ranges (i.e., all the other recited ranges lay within the range of about 1.5:1 to about 3:1). Accordingly, the scope of the claim is interpreted as encompassing any molar ratio within the range of “about 1.5:1 to about 3:1”. While the claim language is not indefinite (because the conjunction “or” establishes that any of the recited ranges are within the scope of the claim), the clarity of the claim could be improved by reciting a single range.
Claim 13 similarly recites a plurality of ranges connected with the conjunction “or”, wherein the broadest recited range of “about 99% or greater” (lines 5-6) encompasses all other ranges and establishes the broadest scope of the claim limitation.
Claim Rejections - 35 USC § 112
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.
Claims 2-10 and 20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 recites the limitation “the Log Reduction” (claim 2, line 2) without proper antecedent basis. It is suggested claim 2 be adjusted to recite “The method of claim 1, wherein a Log Reduction of the microbial population is about 3 or greater, 30 seconds after application.”
Claim 3 depends from claim 1 and recites that “the microbial population is contacted with an aqueous composition comprising glucoheptonic acid”. It is ambiguous if claim 3 is referring to the “aqueous composition” recited in claim 1 and further limiting said aqueous composition by requiring the component be/include glucoheptonic acid, or if the claim 3 is suggesting an additional step of contacting the microbial composition with an additional aqueous composition that is distinct from the aqueous composition of claim 1.
Claims 4-10, similarly to claim 3, refer to “an aqueous composition” limited to include a particular component, and it is ambiguous if the recitations necessarily refer to the aqueous composition of claim 1 or if they may refer to distinct aqueous compositions.
With respect to claim 3, it is suggested the claim be adjusted to read “wherein the component includes glucoheptonic acid”. The stated suggestion assumes claim 3 is intended to further limit the aqueous composition recited in claim 1. If the aqueous composition of claim 3 is meant to be distinct from that of claim 1, claim 3 could instead be adjusted to read “wherein the microbial population is contacted with a[[n]] second aqueous composition comprising glucoheptonic acid”
Claims 4-10 should be similarly adjusted to clarify the relationship between the recitations of “an aqueous composition” in each of claims 4-10 and the recitation of “an aqueous composition” in claim 1. For example, claim 5 could be adjusted to read: “wherein the es
Claim 20 is rejected by virtue of dependency on claim 10
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 and 3 are rejected under 35 U.S.C. 102(a)(1&2) as being anticipated by Rees et al. (US 2002/0155969 A1, cited in the IDS filed 20 September, 2023).
Regarding claim 1, Rees teaches an antimicrobial cleaner (acidic hard-surface antimicrobial cleaner—title) comprising an aqueous solution (aqueous liquid cleaning and antimicrobial compositions—[0003]; aqueous solutions are most preferred—[0051]) including an organocarboxylic acid (abstract: antimicrobial solution containing about 0.2% by weight of an acid selected from a group consisting of organocarboxylic acids), wherein glucoheptonic acid is disclosed as an exemplary organocarboxylic acid (exemplary organocarboxylic acids include…glucoheptonic acid—[0028]; also claims 2 and 36). Rees further teaches a method of using the composition to reduce microbial contamination present on a surface by application of the composition to a substrate ([0053]).
Accordingly, Rees teaches a method of disinfecting or sanitizing, wherein the method comprises: contacting an aqueous composition comprising glucoheptonic acid with a microbial population (method of reducing microbial contamination present on a surface by the application of the composition to the substrate—[0053]; composition is an aqueous solution—[0003], [0051]—comprising glucoheptonic acid— [0028], claims 2 and 36).
It is noted that although glucoheptonic acid is disclosed by Rees as one of many suitable organocarboxylic acids, Rees is nonetheless anticipatory of the claim because MPEP 2131.02(II.) establishes that a reference that clearly names the claimed species anticipates the claim no matter how many other species are named.
Regarding claim 3, Rees discloses the method of claim 1, and further teaches that the aqueous composition comprises glucoheptonic acid ([0028], claims 2 and 36).
Claims 1 is rejected under 35 U.S.C. 102(a)(1&2) as being anticipated by Gluck (US 4,919,837, cited in IDS filed 20 September, 2023).
Regarding claim 1, Gluck teaches antiseptic compositions comprising salts of chlorhexidine (abstract), wherein embodiments thereof define an aqueous composition (composition comprising salt of chlorhexidine, nonionic surfactant, and an inert diluent or carrier—column 2, lines 28-31;diluents or carriers include water—column 3, lines 37-39) including chlorhexidine diglucoheptonate (column 2, lines 44-64, especially lines 62-63: compositions of the invention…can be used for cleaning and sterilizing surgical and other instruments…[and comprise] suitable concentrations of water soluble chlorhexidine salt…[wherein] examples of such suitable salts are…glucoheptonate; also see claim 3; it is noted that the chlorhexidine salt of glucoheptonate is chlorhexidine diglucoheptonate). Gluck indicates that the composition is to be used for the disinfection and cleansing of inanimate surfaces, especially surgical instruments, or the hands and skin (column 2, lines 23-27 and 44-48); while not explicitly stated by Gluck, such use of the composition necessarily implies a least a step of contacting a surface contaminated with microorganisms with the composition.
Therefore, Gluck fairly teaches a method of disinfecting or sanitizing (column 2, lines 23-27 and 44-48), wherein the method comprises: contacting an aqueous composition comprising chlorhexidine diglucoheptonate (column 2, lines 44-64, especially lines 62-63, and claim 3) with a microbial population.
As similarly noted in the rejection of claim 1 over Rees above, the fact that Gluck discloses the chlorhexidine diglucoheptonate salt as one of a plurality of disclosed species does not discredit the anticipation of the claimed invention by Gluck, as per MPEP 2131.02(II.).
Claims 1, 10, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Evans et al. (WO 2018/033718 A1).
Regarding claim 1, Evans teaches an antimicrobial composition which includes a component (ii) comprising an anti-microbial quaternary ammonium compound and a chlorhexidine salt (abstract; also page 8, lines 19-23), the composition comprising a polar solvent such as water (page 12, lines 23-24, 31-32 and 34-37). Evans discloses benzalkonium chloride as an exemplary anti-microbial quaternary ammonium compound (page 6, lines 15-21; page 8, lines 5-9) and discloses chlorhexidine diglucoheptonate as an exemplary chlorhexidine salt (page 5, lines 7-9 and 19). Evans indicates the composition is intended to be used on skin (page 1, lines 4-5) or other surfaces (page 17, lines 4-6 ) to control, reduce, or prevent the formation of new microbial colonies (page 16, liens 29-34), such use involving the direct application of the composition of the surface to be treated (compositions of the invention are used for direct application on skin or hair—page 17, lines 33-36; also see page 18, lines 6-14 and 19-31).
Accordingly, Evans fairly teaches a method of disinfecting or sanitizing comprising contacting an aqueous (page 12, lines 31-37) composition (abstract) comprising chlorhexidine diglucoheptonate (page 5, lines 7-9 and 19) and benzalkonium chloride (page 6, lines 15-21; page 8, lines 5-9) with a microbial population (compositions of the invention can be applied to materials such as surfaces which come into contact with animals and to which microorganisms may be transferred from the animal, the benefit of which is to eradicate or inhibit micro-organisms which otherwise may be transferred to another animal or human—page 18, lines 6-17).
Regarding claim 10, Evans teaches the method of claim 1. The method of Evans identified with respect to claim 1 above includes contacting a surface contaminated by a microbial population with an aqueous solution that includes chlorhexidine diglucoheptonate and benzalkonium chloride (see rejection of claim 1 above). Evans indicates that all components of the composition have good water solubility (page 5, lines 30-31; page 11, lines 22-23). Accordingly, it is understood that disassociated benzalkonium ions and glucoheptonate ions freely exist in the aqueous solution of Evans, such that the solution of Evans is compositionally indistinguishable from (i.e., patentably identical to) an aqueous solution comprising benzalkonium glucoheptonate.
Regarding claim 20, Evans teaches the method of claim 10. As discussed with respect to claim 10 above, the composition of Evans includes a glucoheptonate salt (chlorhexidine diglucoheptonate—page 5, line 19) and a benzalkonium salt (benzalkonium chloride—page 8, lines 5-9) which are combined to yield an aqueous solution that is patentably indistinguishable from a benzalkonium glucoheptonate solution. Evans further teaches combining the components and stirring (page 22, lines 19-21), which implies the use of a container in which the components are combined and stirred. Thus, Evans fairly teaches the benzalkonium glucoheptonate is prepared by a method comprising: combining a benzalkonium salt and a glucoheptonate salt in a container and stirring the combination.
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.
Claim 2 is rejected under 35 U.S.C. 102(a)(1&2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Rees et al. (US 2002/0155969 A1).
Regarding claim 2, Rees discloses the method of claim 1. Claim 2 is recognized as reciting a result of method claim 1, without providing any further limitation of the manipulative steps, structures, or compositions required by the claimed process in order to yield the recited result. Accordingly, the result recited in claim 2—which is a Log Reduction of about 3 or greater of the microbial population 30 seconds after application of the composition—is presumed to be an inherent result of the method of claim 1. MPEP 2112(III.) indicates that a rejection under 35 U.S.C. 102 and 103 is proper when a prior art invention appears to be identical except that the prior art is silent as to an inherent characteristic:
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims. (from MPEP 2112(III.), emphasis added)
Accordingly, Rees anticipates claim 2 because Rees discloses a method which is indistinguishable from (i.e., identical to) an embodiment of the claimed method (see rejection of claim 1 above), such that the method of Rees must have the inherent characteristic of achieving a Log reduction of about 3 or greater of the microbial population 30 seconds after application of the composition. Furthermore, to the extent that achieving the result of claim 2 would require a modification of the method of claim 1 which is not explicitly recited in claim 2 (e.g., a minimum concentration of the component, a particular application technique, or a particular target strain of microbes), it would be obvious to a person having ordinary skill in the art to make such adjustments to the method of Rees and arrive at a Log Reduction of about 3 or greater, 30 seconds application by way of routine optimization for the benefit of improving the removal of potentially harmful microbes from an environment. As further evidence, it is noted that Rees discloses related embodiments of aqueous compositions achieving microbial log reductions of at least 3 within a short time (1 minute) (see Table 2, [0059]), which supports the finding that the embodiments of Rees which include glucoheptonic acid would achieve similarly high microbial Log Reductions on a surface within a relatively short time.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Rees et al. (US 20020155969 A1) in view of Zak (US 3,679,659 A, cited in IDS filed 20 September, 2023).
Regarding claim 4, Rees teaches the method of claim 3 wherein the microbial population is contacted with an aqueous composition comprising glucoheptonic acid, but Rees does not specify which isomers of glucoheptonic acid are present or in which proportion they are present. Thus, Rees does not teach that both α-glucoheptonic acid and β-glucoheptonic acid are present in the solution, with about 90% or greater of the glucoheptonic acid being the alpha isomer.
However, in the analogous art of preparing glucoheptonate compounds, Zak teaches a process for the preparation of sodium glucoheptonate (title) which produces both alpha and beta glucoheptonates (column 2, lines 18-20). Both the alpha and beta glucoheptonates can be converted to glucoheptonic acid by ion exchange techniques (column 5, lines 3-9). The process of Zak yields the alpha isomer at 60-100%, with no more than 40% of the beta form (column 3, lines 24-29). The process of Zak minimizes the formation of color bodies (column 3, lines 2-4) and yields light colored alpha glucoheptonate salts (column 2, lines 43-45) and a light straw colored liquor containing the beta isomer (column 2, lines 49-54) which can be spray dried to produce dry glucoheptonate powder (column 3, lines 19-23) having between 60 and 100% alpha isomer (column 3, liens 24-29).
Therefore, it would be obvious to a person having ordinary skill in the art to produce the glucoheptonic acid utilized in the method of Rees from the techniques disclosed by Zak in order to yield glucoheptonic acid that is at least 60% alpha isomer—which overlaps with the claimed range of at least 90% alpha isomer—for the benefit of providing glucoheptonic acid which is relatively free of contaminants which could alter the color of the solution. Furthermore, it would be obvious to select the overlapping portion of the claimed (at least 60%) and prior art (at least 90%) range for the benefit of promoting desired crystallization properties (Zak indicates the beta isomer does not crystallize—column 4, lines 73-74—while the alpha isomer does—see column 2, lines 40-48).
Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Werle (US 2002/0018814 A1, cited in the IDS filed 20 September, 2023).
Regarding claim 1, Werle teaches the use of chlorhexidine salts as disinfectants (title, abstract), including formulations comprising chlorhexidine heptagluconate ([0027]) salts, which is recognized as synonymous with the claimed chlorhexidine diglucoheptonate. Werle suggests that the liquid formulations of the salt are suitable for use to disinfect skin, wounds, and other surfaces ([0003]; [0020]). Thus, Werle fairly teaches a method of disinfecting or sanitizing comprising the use of an aqueous composition comprising chlorhexidine diglucoheptonate to disinfect ([0023], in combination with [0010], sets forth an embodiment wherein an aqueous solution comprising chlorhexidine heptagluconate salt is formed from chlorhexidine base and heptagluconic acid; abstract, [0003], and [0020] fairly suggest the use of said salt solution as a disinfectant). Werle is not explicitly clear in teaching that the use of the disinfectant necessarily includes contacting the aqueous composition with a microbial population, but it would be obvious to a person having ordinary skill in the art to apply the composition of Werle so that it contacts a surface contaminated with a microbial population for the evident benefit of reducing, eliminating, or suppressing the microbial population in order to impede the spread of pathogenic microbes from the surface to humans.
Regarding claim 5, Werle teaches the method of claim 1, wherein the microbial population is contacted with an aqueous composition comprising chlorhexidine di-α-glucoheptonate (Werle forms the chlorhexidine heptagluconate with alpha-D-heptagluconic acid—[0010], [0023]—and it is presumed that the stereochemistry is preserved so that all or most of the heptagluconate in the formed chlorhexidine di-heptagluconate of the method comprises the alpha isomer).
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Werle et al. (US 2002/0018814 A1), in view of Zak (US 3,679,659 A).
Regarding claim 8, Werle teaches the method of claim 1. As discussed with respect to claim 5 above, Werle fairly suggests that all or most of the chlorhexidine di-glucoheptonate comprises the alpha isomer (Werle forms the chlorhexidine heptagluconate with alpha-D-heptagluconic acid—[0010], [0023]—and it is presumed that the stereochemistry is preserved to yield chlorhexidine-di-heptagluconate that is almost entirely of the alpha isomer). Werle does not clearly suggest that both the alpha and beta isomers of the glucoheptonate are present, with the alpha isomer accounting for 90% or more of the glucoheptonate.
However, in the analogous art of processes for preparing glucoheptonate compounds (title), Zak indicates that glucoheptonic acid can be obtained from a solution of sodium glucoheptonate which includes both the alpha and beta glucoheptonate isomers (column 5, lines 3-9: glucoheptonic acid obtained from beta isomer solution…by cation exchange according to conventional techniques; glucoheptonate content of solutions is 60 to 100% alpha glucoheptonate and not more than 40% beta glucoheptonate —column 3, lines 24-29). The glucoheptonic acid of Zak is presumed to preserve the ratio of alpha to beta isomers from the sodium glucoheptonate form which it was converted. Zak further indicates that the method for producing the sodium glucoheptonate advantageously yields lightly colored materials (column 2, lines 3-6; column 5, lines 1-2).
Therefore, it would be obvious to a person having ordinary skill in the art to use the glucoheptonic acid of Zak to form the chlorhexidine diglucoheptonate of Werle (process of Werle at [0010], [0023] combines glucoheptonic acid with chlorhexidine base to form chlorhexidine diglucoheptonate) for the benefit of providing a glucoheptonic acid that has minimal color contamination (Zak at column 2, lines 3-6, and column 5, lines 1-2, indicates the glucoheptonate compounds of Zak have a much lighter color relative to prior art). Assuming that the stereochemistry of the glucoheptonate of Zak is unchanged when forming the chlorhexidine glucoheptonate of Werle, the proposed modification yields chlorhexidine glucoheptonate which is 0-40% beta isomer and 60-100% alpha isomer (see Zak at column 3, lines 24-29). Accordingly, it would be obvious to a person having ordinary skill in the art to select the overlapping portion of the claimed (90%-100%) and prior art (60-100%) ranges of alpha isomer prevalence for the benefit of achieving a chlorhexidine salt solution suitable for disinfection (consider Werle at [0010], [0020], and [0023]).
Regarding claim 9¸ Werle teaches the method of claim 1. It would be obvious to modify the method of Werle in view of Zak as set forth with respect to claim 8 above, which would yield an aqueous solution comprising both the alpha and beta isomer of chlorhexidine diglucoheptonate, with the beta isomer accounting for 0 to 40% of the glucoheptonate (see rejection of claim 8 above and Zak at column 3, lines 24-29). Furthermore, it would be obvious to a person having ordinary skill in the art to select the overlapping portion (25-40%) of the claimed (25-100%) and prior art (0-40%) ranges of beta isomer prevalence for the benefit of achieving a chlorhexidine salt solution suitable for disinfection.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Rees et al. (US 2002/0155969 A1).
Regarding claim 11, Rees teaches the method of claim 1. Rees teaches the use of related embodiments of an antimicrobial aqueous solution against test microorganisms including S. aureus, (test solutions were evaluated versus staphylococcus aureus—[0058]), and identifies S. aureus as a pathogenic micro-organism which all embodiments of the antimicrobial aqueous solution should be effective against (retaining efficacy against pathogenic micro-organisms such as staphylococcus aureus—[0016]). Although Rees does not explicitly discuss the application of the embodiments of the antimicrobial aqueous solution which contain glucoheptonic acid to a surface contaminated with S. aureus, it is evident that Rees recognized S. aureus is a pathogenic microorganism which should be removed from surfaces persons may be exposed to ([0016]) and that aqueous solutions containing glucoheptonic acid have antimicrobial properties ([0028], claim 2, claim 36; [0021]). Therefore, it would be obvious to a person having ordinary skill in the art to apply the aqueous glucoheptonic acid solution of Rees to a surface contaminated with S. aureus for the benefit of suppressing the spread of S. aureus, which is a pathogenic microorganism (see Rees at [0016], [0021], [0028], [0053], and [0058]).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Evans (WO 2018/033718 A1).
Regarding claim 12, Evans discloses the method of claim 1. Evans indicates that the composition is capable of inhibiting or eradicating viruses such as norovirus, polio virus, or adenovirus (page 18, lines 26-27; also see page 20, lines 3-8), which suggests application of the composition of Evans discussed with respect to claim 1 above to a microbial population comprising a virus. Evans does not explicitly suggest application of the composition to SARS-CoV-2. However, it was well known by the spring of 2020 that the coronavirus SARS-CoV-2 posed a significant risk to public health and that measures should be taken to suppress its spread. Therefore, it would have been obvious to person having ordinary skill in the art to try applying the method of Evans [as identified with respect to claim 1 above] to a microbial population including SARS-CoV-2 for the expected benefit of suppressing the spread of the virus to protect public health (Evans indicates that the composition is anti-viral, being capable of inhibiting or eradication common pathogenic viruses including norovirus, polio virus, and adenovirus—page 18, lines 26-27, and page 20, lines 3-8—and thus would be reasonably expect to have a similarly anti-viral effect against SARS-CoV-2).
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Zak (US 3,679,659 A) in view of Cavanaugh et al. (US 2007/0282044 A1) and Gerberding et al. (US 2012/0289742 A1).
Regarding claim 13, Zak teaches a method of preparing glucoheptonic acid by cation exchange from alpha or beta sodium glucoheptonate using conventional techniques (column 5, lines 3-9). Zak does not specify if such techniques necessarily include: dissolving a glucoheptonate salt in water to form a solution, combining the solution with an acidic ion exchange resin to form a slurry; filtering the slurry to remove the ion exchange resin to form glucoheptonic acid, wherein the conversion of the glucoheptonate salt to glucoheptonic acid is about 99% or greater.
However, the claimed steps of dissolving a salt of organic acid in water, combining the solution with an ion exchange resin, and removing the ion exchange resin to form an organic acid are recognized as defining a conventional technique for using an ion exchange resin.
For example, Cavanaugh discloses a technique for bringing a liquid mixture in contact with an ion exchange resin by adding beads of the ion exchange resin to a stirred tank containing the liquid to form a slurry, followed by separation of the liquid mixture from the ion exchange beads by filtration ([0045]); such a technique is an alternative to passing the liquid mixture over a fixed bed of ion exchange resin ([0045]). It is thus evident that it is conventional to perform an ion exchange process by combining a liquid with the exchange resin to form and slurry, and subsequently filtering the resin from the slurry.
Furthermore, Gerberding teaches a process for recovering carboxylic acid from a solution (fermentation broth) by providing a solution containing a salt of a carboxylic acid and passing the solution through a column filled with an acidic ion exchange resin in order to yield an aqueous solution of carboxylic acid that results from the exchange of the cation of the salt with a proton from the ion exchange resin (claim 13). Gerberding further discloses various examples of suitable acidic cation exchange resins, including DOWEX Marathon C ([0089]) and Lanxess Lewit MonoPlus S 100H ([0100]). This further evidences that the conversion of a carboxylate salt to a carboxylic acid through the use of an acidic cation exchange resin is a conventional technique. In combination with the teaching of Cavanaugh ([0045]) above, it is evident that combining the solution and ion exchange resin of Gerberding in a stirred tank and subsequently filtering out the resin is a suitable alternative to passing the solution over a the column (i.e., fixed bed) of the resin.
From the suggestion of Zak to convert sodium glucoheptonate salt to glucoheptonic acid through a conventional cation exchange technique, and from the teachings of Cavanaugh and Gerberding with respect to conventional techniques of using ion exchange resins, it would be obvious to a person having ordinary skill in the art to arrive at a method comprising dissolving the glucoheptonate salt of Zak in water to form a solution, combining the solution with an acidic ion exchange resin to form a slurry; filtering the slurry to remove the ion exchange resin (consider technique suggested by Cavanaugh at [0045]) to form glucoheptonic acid (consider process of claim 13 of Gerberding and suggestion of Zak at column 5, lines 3-9). Such a modification amounts to applying a known technique (combining a solution with an ion exchange resin to form a slurry and subsequently filtering out the resin; see Cavanaugh at [0045]; Gerberding at claim 13 guides the selection of a cationic ion exchange resin for forming a carboxylic acid from a salt of carboxylic acid) to a known product (glucoheptonate salt of Zak) to yield the predictable result of producing glucoheptonic acid, wherein the resulting method would fairly be expected to provide the benefit of good product purity (as a result of removing sodium or other cations from the solution by ion exchange and removal of the resin material by filtration, leaving glucoheptonic acid as the most prevalent non-solvent component in the solution). See MPEP 2143(I.)(D.).
With respect to the claim language indicating that the conversion of glucoheptonate salt to glucoheptonic acid is about 99% or more, it is noted the claim does not recite any further particular manipulative steps or limitations thereof (e.g., ratio of components, resin type/structure, contact time, etc.) which produce the result of a conversion of at least 99%. Accordingly, the prior art method arrived at through the combination of Zak, Cavanaugh, and Gerberding, is presumed to have the characteristic of achieving a conversion of 99% or more, and it would otherwise be obvious to a person having ordinary skill in the art to optimize the process (e.g., by adjusting the ratio of salt to resin, or selecting a particular type of resin) and arrive at a conversion of 99% of greater for the benefit of maximizing the yield of the desired product (glucoheptonic acid).
Regarding claim 14, the combination of Zak, Cavanaugh, and Gerberding teaches the method of claim 13. Zak does not explicitly suggest a step wherein the slurry is dried to form the glucoheptonic acid.
However, Gerberding teaches the process for converting a carboxylic acid salt into carboxylic acid (claim 13), and further suggests a step of crystallization subsequent to recovering the aqueous carboxylic acid solution (claim 18), the crystallization step understood to comprise evaporating water out of the solution ([0026], [0134]-[0137]). Such a step fairly constitutes a drying step which serves to concentrate, and in some instance assist in purifying, a carboxylic acid ([0134] suggests evaporating aqueous succinic acid recovered from an ion exchange process to achieve a high concentration of succinic acid and to remove some more volatile components from the solution). Therefore, it would be obvious to a person having ordinary skill in the art to further modify the method of Zak to include a step of evaporating (i.e. drying) the glucoheptonic acid recovered from filtering the slurry for the benefit of increasing the concentration of the glucoheptonic acid and driving off more volatile impurities (consider Gerberding at [0134]).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Zak (US 3,679,659 A) in view of Cavanaugh et al. (US 2007/0282044 A1) and Gerberding et al. (US 2012/0289742 A1), as applied to claim 13 above, and further in view of Dow (Product Sheet, Dow, “Dowex Marathon MSC”, cited in IDS filed 20 September, 2023).
Regarding claim 15, the combination of Zak, Cavanaugh, and Gerberding teaches the method of claim 13. Zak and Cavanaugh do not teach that the acidic ion exchange resin comprises a DOWEX MARATHON MSC and/or LEWATIT MONOPLUS SP 112 H ion exchange resin.
As discussed with respect to claim 13 above, Gerberding does suggest the use of strongly acidic ion exchange resin, and discloses particular examples including Dowex Marathon C ([0089]). Nonetheless, Gerberding does not explicitly indicate that the resin is a DOWEX MARATHON MSC and/or LEWATIT MONOPLUS SP 112 H ion exchange resin.
However, Dow—the product data sheet cited in the IDS filed 20 September 2023—discloses that DOWEX MARATHON MSC is a strong acid cation exchange resin (see product data sheet uploaded to the file wrapper 20 September, 2023) suitable for water softening and demineralization. Therefore, it would be obvious to a person having ordinary skill in the art to further modify the method of Zak such that the DOWEX MARATHON MSC ion exchange resin is selected as the ion exchange resin of the method because Gerberding indicates that strongly acidic ion exchange resins are suitable for converting salts of carboxylic acids to carboxylic acids (see Gerberding at [0089], claim 13) and the DOWEX MARATHON MSC is a strongly acidic cationic exchange resin. Such modification amounts to the substation of one known ion exchange resin for another to maintain the predictable result of converting a carboxylic acid salt (glucoheptonate salt) to a carboxylic acid (glucoheptonic acid).
Claims 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zak (US 3,679,659 A) in view of Cavanaugh et al. (US 2007/0282044 A1) and Gerberding et al. (US 2012/0289742 A1), as applied to claim 13 above, and further in view of Werle et al. (US 2002/0018814 A1, cited in the IDS filed 20 September, 2023).
Regarding claim 16, the combination of Zak, Cavanaugh, and Gerberding teaches a method of preparing glucoheptonic acid consistent with claim 13. Zak, Cavanaugh, and Gerberding do not suggest using the prepared glucoheptonic acid to prepare chlorhexidine diglucoheptonate by: combining chlorhexidine and water to form a slurry; and adding the glucoheptonic acid of claim 13 to the slurry and mixing the combination.
However, in the analogous art of chlorhexidine formulations, Werle teaches formulations of chlorhexidine salts (title, abstract), including salts comprising a chlorhexidine cation and the acid anion of α-D-heptagluconic acid ([0010]; note that heptagluconic acid is understood to be synonymous with glucoheptonic acid). Werle further teaches preparing chlorhexidine heptagluconate (i.e., chlorhexidine glucoheptonate) salt solutions by adding 25.0 g of chlorhexidine base and 21 g of heptagluconic acid ([0010], [0022]) to water to form a milky suspension and stirring for 10-15 minutes ([0023]). These steps clearly constitute combining chlorhexidine and water to form a slurry, adding glucoheptonic acid to the slurry, and mixing the combination. Werle further indicates that the solution is useful as a disinfectant and/or to prepare disinfectants (abstract, [0020]).
Therefore, it would be obvious to a person having ordinary skill in the art to combine the glucoheptonic acid from the method of modified Zak (see rejection of claim 13 above) with chlorhexidine by mixing both components together in water (as see in Werle, [0023]) for the benefit of forming a chlorhexidine heptagluconate salt solution which is useful as a disinfectant or for preparing a disinfectant (see Werle at abstract, [0020]).
Regarding claim 17, the combination of Zak, Cavanaugh, Gerberding, and Werle teaches the method of claim 16. Zak teaches producing sodium glucoheptonate that is 60-100% alpha isomer (column 3, lines 24-29), and Zak teaches converting the salt to glucoheptonic acid (column 5, lines 3-9). As modified in view of Cavanaugh, Gerberding, and Werle with respect to claims 13 and 16 above, the glucoheptonic acid of Zak is mixed with chlorhexidine to form chlorhexidine diglucoheptonate. The glucoheptonate of the chlorhexidine salt is presumed to retain its stereochemistry from the original sodium salt of Zak; accordingly, the chlorhexidine diglucoheptonate of the modified method of the prior art presented with respect to claim 16 yields chlorhexidine diglucoheptonate with 60-100% of the alpha isomer, which overlaps with the claimed range of about 90% or greater. Accordingly, it would be obvious to a person having ordinary skill in the art to select the overlapping portion of the claimed (90-100%) and prior art (60-100%) range, for the benefit of providing the glucoheptonate as an isomer suitable for disinfecting compositions (Werle prepares the chlorhexidine heptagluconate salt solutions using the alpha heptagluconate isomer, the salt solution being used as or as part of a disinfectant—see [0008], [0020]-[0023]).
Regarding claim 18, the combination of Zak, Cavanaugh, Gerberding, and Werle teaches the method of claim 16. As outlined with respect to claim 17 above, the modified method of Zak presented with respect to claim 16 above is understood to yield chlorhexidine glucoheptonate salt wherein the stereochemistry of the glucoheptonate is preserved from the sodium glucoheptonate first introduced into the modified prior art process. Zak indicates that the initial sodium glucoheptonate is 60-100% alpha isomer and no more than 40% beta isomer (column 3, lines 24-29), such that the final chlorhexidine glucoheptonate salt of the modified process is up to 40% beta isomer. Therefore, it would be obvious to a person having ordinary skill in the art to select the overlapping portion (25%-40%) of the claimed (25%-100%) and prior art (0%-40%) ranges of beta isomer prevalence for the benefit of providing an effective disinfecting solution (Werle indicates chlorhexidine heptagluconate salt solutions are useful as disinfectants—[0020]).
Regarding claim 19, the combination of Zak, Cavanaugh, Gerberding, and Werle teaches the method of claim 16. The method of Zak as modified with respect to claim 16 above incorporates the chlorhexidine diglucoheptonate preparation step of Werle, wherein Werle discloses combining 25.0 g of chlorhexidine base and 21 g of heptagluconic acid ([0023]); based on respective approximate molar masses of 505 g/mol and 226 g/mol, the step of Werle yields roughly 0.05 mol of chlorhexidine and 0.09 mol of heptagluconic acid. Thus, Werle teaches a ratio of glucoheptonic acid to chlorhexidine between 1.5:1 and 2:1, which lays within the effectively claimed range of 1.5:1 to 3:1.
Allowable Subject Matter
Claims 6-7—as best understood—would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Regarding claim 6, the claim has been interpreted in view of the instant specification as requiring that an aqueous composition be brought into contact with a microbial population, wherein the aqueous composition comprises chlorhexidine di-glucoheptonate, and wherein between 60% and 75% of the glucoheptonate is of the β-isomer form (see claim interpretation section above). Gluck (US 4,919,837) teaches the method of claim 1, but does not provide an indication that the chlorhexidine di-glucoheptonate includes the beta isomer at a percentage of 60-75%. Werle et al. (US 2002/0018814 A1) also teaches the method of claim 1, but only teaches use of the alpha heptagluconate isomer (alpha-D-heptagluconic acid—[0010]—which is combined with chlorhexidine base to form a chlorhexidine salt solution—[0023]).
Zak (US 3,679,659 A), discussed with respect to claim 13 above, teaches a method of producing sodium glucoheptonate (title) which yields glucoheptonate that is from 60-100% alpha isomer and no more than 40% beta isomer (column 3, lines 24-29). The disclosure of Zak indicates that the alpha isomer readily crystallizes, while the beta isomer does not (column 3, lines 45-47 describes crystallization of the alpha form; column 4, line 73-37 recites “the non-crystallizable beta isomer”). These teachings suggest that the relative proportion of the glucoheptonate isomers would be expected to yield different properties, especially with respect to crystallization. Nonetheless, Zak does not clearly teach a proportion of the beta isomer within the claimed range of 60-75%, and instead sets an upper limit of 40%. Also, the teachings of Zak are with respect to sodium glucoheptonate, such that not all teachings of Zak are directly applicable to the claimed chlorhexidine di-glucoheptonate component.
Villa (US 5435845 A), in the art of cement compositions (abstract), discusses glucoheptonate compositions (title), indicating that sodium glucoheptonate has known applications in germicidal compositions (column 1, lines 46-52) and that both a crystalline dihydrate alpha isomer of glucoheptonate and an aqueous solution predominantly of the beta isomer are commercially available (column 2, lines 3-13). Villa also indicates the alpha isomer is preferred for cementitious compositions (abstract). Nonetheless, Villa does not clearly disclose a beta isomer proportion of 60-75%. Also, the teachings of Villa are with respect to sodium glucoheptonate, not the claimed chlorhexidine diglucoheptonate.
Although the teachings of Zak and Villa do suggest that the relative amount of each glucoheptonate isomer in a composition will have an impact on the properties of a solution, Zak and Villa provide insufficient evidence to guide a person of ordinary skill in the art to modify the composition of Gluck or Werle and arrive at a method of disinfecting using an aqueous solution comprising chlorhexidine di-glucoheptonates, wherein 60-75% of the glucoheptonate is of the beta isomer. No further prior art was found which teaches or fairly suggest all elements of the claimed method. Accordingly, the subject matter of claim 6 (as interpreted) is novel and non-obvious over the prior art.
Claim 7 is interpreted in a similar manner as claim 6, with claim 7 requiring an aqueous solution comprising chlorhexidine di-glucoheptonate, wherein 81% of the glucoheptonate is of the β-isomer form (see claim interpretation section above). For substantially the same reasons as set forth with respect to claim 6 above, the subject matter of claim 7 [as interpreted] is novel and non-obvious over the prior art. That is, the prior art does not suggest the use of chlorhexidine di-glucoheptonate with a beta isomer content as high as 81% for disinfection. Instead, the prior art typically favors lower amounts of the beta isomer (Zack at column 3, lines 24-29, discusses sodium glucoheptonate having no more than 40% of the beta isomer; Villa indicates the alpha isomer is preferred for certain use cases—see abstract; Werle only discuses use of the alpha isomer), does not explicitly discuss the beta isomer in the context of chlorhexidine diglucoheptonate (instead discussing the isomer with respect to sodium glucoheptonate), and provides insufficient evidence to suggest that a beta-isomer proportion of 81% would provide a predictable result with respect to the effect on the claimed method.
Conclusion
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/BRADY C PILSBURY/Examiner, Art Unit 1799
/JENNIFER WECKER/Primary Examiner, Art Unit 1797