FINAL ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
This action is in response to papers filed 07/20/2026 in which claims 2-9, 11-15, 33, 35, 37-42, 48, and 54-55 were canceled; and claims 1 and 34 were amended. All the amendments have been thoroughly reviewed and entered.
Claims 1, 10, 16-32, 34, 36, 43-47, 49-53 and 56 are under examination.
Maintained-Modified Rejections
Modification Necessitated by Applicant’s Claim Amendments
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(s) 1, 10, and 16-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dull et al (US 2015/0344456 A1) in view of Keller et al (US 2021/0068446 A1), Duggins et al (US 2013/0209540 A1), and Rubenstein (US 2020/0315241 A1).
Regarding claim 1, Dull teaches a lozenge comprising one or more sugar alcohols such as isomalt and maltitol syrup (sugar substitutes) in the amount of at least about 80% by weight, nicotine (a basic amine), and an organic acid including 2,5-dihydroxybenzoic acid (gentisic acid), wherein nicotine is in association with the organic acid to form a nicotine-organic acid salt (Abstract; [0013]-[0018], [0043], [0045], [0048]-[0049], [0072], [0092]-[0094], [0114]-[0115], [0128]-[0131], [0145]-[0146], [0153], [0170], [0218]; Example 10; claims 1 and 12-16). Dull teaches the lozenge contains water ([0218]).
However, Dull the combination of organic acid and a sodium salt of thereof, wherein the organic acid is decanoic acid, benzoic acid, heptanesulfonic acid, or a combination thereof, and the pH of the oral product of claim 1.
Regarding the combination of organic acid and a sodium salt of thereof and the pH of the oral product of claim 1, Keller teaches an oral product comprising nicotine or salt thereof such as nicotine benzoate, one or more organic acid such as benzoic acid, and water in an amount from about 1% to about 60% by weight, wherein the oral product is formulated to be in the form of a lozenge (Abstract; [0005], [0009], [0011]-[0012], [0014], [0020]-[0021], [0023], [0026], [0041]-[0046], [0051]-[0053], [0055], [0066]-[0072], [0090]-[0100], [0107], [0111]-[0119], [0125]-[0129], [0146], [0155]-[0156]). Keller teaches the organic acid or a portion thereof is added in the form of a salt with an alkali metal such as sodium ([0012] and [0115]), thereby meeting the claimed “a combination of an organic acid and a sodium salt thereof.” Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]).
It would have been obvious to one of ordinary skill in the art to include nicotine salt such as nicotine benzoate, and a sodium salt of benzoic acid in the lozenge of Dull, in which the sodium salt of benzoic acid included in an amount sufficient provide the lozenge of Dull with a pH from about 4.5 to about 6.5, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Keller teaches nicotine benzoate as a suitable form of nicotine salt for use in an oral product such as lozenge, and such oral product can further contain a sodium salt of an organic acid such as a sodium salt of benzoic acid in an amount sufficient to provide the product with a pH of from about 4.5 to about 6.5. Thus, given that Dull and Keller are drawn to commonly drawn to nicotine containing oral products such as lozenges, "[t]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
It would also have been obvious to one of ordinary skill in the art to optimize the content of water in the lozenge of Dull to an amount from 0.1% to 10% by weight, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because as discussed above, Keller teaches that the oral product can be formulated into a lozenge and the content of water can be optimize in amount from about 1% to about 60% by weight, which is a range that overlaps the claimed range of from 0.1% to 10% by weight. Furthermore, it is well-established in the prior art in view of Duggins, water in a low amount (i.e., about 3% by weight) is a typical ingredient generally use in formulating a nicotine lozenge (Duggins: Abstract; [0008]-[0009], [0011]-[0012], [0018]-[0019], [0023]-[0025], [0039], [0041]-[0042], [0044], [0050]-[0051], [0055], [0057]-[0058], [0060], [0066], [0071]; Examples 1, 2, 7-8; claims 1-3 and 7-11). Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of water in an oral product so as to achieve a desired lozenge would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “the ratio of the organic acid to the sodium salt of the organic acid is from about 0.1 to about 10” of claim 1, Keller teaches the oral product contains no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid ([0012] and [0115]). The weight amount range of an alkali metal salt to the weight amount range of organic acid as taught by Keller overlaps the claimed ranges of 0.1 to 10 of an organic acid to the sodium alkali salt thereof. As discussed above, the Courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the molar ratio of the organic acid to the sodium salt of the organic acid would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “the combination of the organic acid and the sodium salt thereof is present in a range from about 2 to about 10 molar equivalents relative to the basic amine, calculated as the amine free base” of claim 1, as discussed above, Keller teaches the oral product in form of a lozenge contains nicotine or salt thereof such as nicotine benzoate, no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid. Furthermore, the prior art per Rubenstein established that molar ratio of nicotine:organic acid (nicotine:benzoic acid) in the lozenge formulation of Dull in view of Keller is preferably 1:2 (Rubenstein: [0039]-[0052]; Table 2), which falls within the claimed feature of “the combination of the organic acid and the sodium salt thereof is present in a range from about 2 to about 10 molar equivalents relative to the basic amine, calculated as the amine free base.” Thus, one of ordinary skill would reasonably conclude that the prior art discloses a molar equivalent of organic acid to basic amine that is in the range of about 2 to about 10 molar equivalents of organic acid and alkali metal salts thereof relative to the basic amine. As discussed above, the Courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of molar ratios of the combination of the organic acid and the sodium salt thereof in relation to nicotine would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” of claim 1, Rubenstein teaches a composition containing nicotine salts such as nicotine benzoate, wherein the composition is suitable for formulating oral lozenges (Abstract; [0002], [0007], [0012], [0020], [0022], [0024], [0031]-[0032], [0036]-[0038], [0041]-[0043], [0052], [0061], [0064]-[0065], [0070], [0079]-[0080], [0099]-[0100], [0106]-[0111], Example II and Table 9). Rubenstein teaches the nicotine benzoate is a nicotine salt complex having nicotine molecules associated with organic acid (benzoic acid) or conjugate base of the benzoic acid (benzoate), in which the organic acid (benzoic acid) or the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) ([0012], [0020], [0022], [0024], [0031]-[0032], [0036]-[0038], [0041]-[0043], [0052], [0061], [0064]-[0065], [0070], [0079]-[0080], [0099]-[0100], [0106]-[0111], Example II and Table 9). Rubenstein teaches the binding action between nicotine and the organic acid has many desirable and beneficial characteristics including nicotine complexed to an organic acid is more stable and resistant to oxidation ([0036]-[0038]). Rubenstein teaches nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen ([0013], [0038], [0048]). Thus, it would have been reasonably obvious that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because the components in the lozenge are mixed and as discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller. As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation.
Regarding claim 10, as discussed above, Keller teaches the organic acid is benzoic acid.
Regarding claim 16, as discussed above, Dull and Keller teaches the oral product contains nicotine (a basic amine).
Regarding claim 17, Dull teaches the lozenge contains about 1% to about 5% by weight of nicotine ([0130]).
Regarding claims 18-19, as discussed above, Dull teaches the lozenge contains isomalt.
Regarding claims 20-21, Dull teaches the lozenge contains at least about 90% by weight of one or more sugar alcohols such as isomalt and maltitol syrup (sugar substitutes) ([0129]).
Regarding claim 22, Dull teaches the lozenge contains at least about 90% by weight of one or more sugar alcohols such as isomalt and maltitol syrup (sugar substitutes) ([0129]). It would have been obvious to one of ordinary skill in the art to optimize the amount of sugar alcohols in the lozenge of Dull to amount of at least about 95% by weight, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because as discussed above, Dull teaches the lozenge con contain sugar alcohols in an amount of at least about 90% by weight, which overlaps the claimed range of at least about 95% by weight. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of weight amount of sugar substitute in the oral product would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
Regarding claims 23-24, as discussed above, Dull teaches the lozenge contains isomalt and maltitol syrup as the one or more sugar alcohols.
Regarding claim 25, Keller teaches and provides guidance including sugar alcohol such as maltitol in the oral product in an amount from about 0.1 to about 1% by weight (Keller: [0119]). Duggins also teach and provide guidance for incorporating maltitol in the oral product in an amount of from about 0.1% to about 2% by weight, as this is an ingredient generally use in formulating a typical nicotine lozenge (Duggins: [0055]; Example 1).
Regarding claim 26, Keller teaches and provides guidance for further including one or more active ingredients in the oral product, wherein the active ingredient is selected from botanicals, stimulants, amino acids, vitamins, and cannabinoids ([0020], [0091] and [0125]).
Regarding claim 27, Dull teaches the lozenge is free of a tobacco material ([0218]).
Regarding claim 28, Dull teaches the lozenge further contains one or more pharmaceutical acceptable components selected from flavorants, sweeteners, fillers, humectants, salts, and mixtures thereof ([0145] and [0218]).
Regarding claim 29 and 30, Keller teaches and provides for adding a salt such as sodium chloride in the oral product in an amount of about 0.5% by weight or more (Keller: [0118]). Duggins also teach and provide guidance for incorporating salt such as sodium chloride in the oral product in an amount of at least about 0.5% by weight, as this is an ingredient generally use in formulating a typical nicotine lozenge (Duggins: [0057]; Example 1).
Regarding claim 31 and 32, Keller teaches and provide guidance for including a sweetener such as sucralose in the oral product in an mount from about 0.1% to about 20% by weight (Keller: [0119]).Duggins also teach and provide guidance for incorporating sweetener such as sucralose in an amount of at least about 0.2%, as this is an ingredient generally use in formulating a typical nicotine lozenge (Duggins: [0051]; Example 1).
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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
Applicant argues that Dull fails to teach or suggest all features of claim 1 as amended. Applicant alleges that “Dull does not disclose a lozenge composition in which a free organic acid and its sodium salt are present in a defined ratio and certainly not such a product having a pH from about 4.5 to about 6.5.” Applicant further alleges “Dull's nicotine salts and co-crystal complexes are not a teaching of the claimed acid/conjugate-base buffer system, in which one of skill in the art would understand that the free acid establishes the recited pH range and the sodium salt of the acid supplies the conjugate base to control extent of ion pairing and nicotine partitioning.” (Remarks, page 7, last paragraph to page 8).
In response, the Examiner disagrees. As discussed above in the standing 103 rejection, the combination of organic acid and a sodium salt of thereof, the “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid,” and the pH of the oral product of claim 1 has been taught and render obvious by Keller and Rubenstein, respectively. See 103 rejection, pages 4-10 of this office action, said pages being incorporated herein its entirety.
Particularly, with respect to the pH of the oral product as amended in claim 1, as discussed in the standing 103 rejection, Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]), which meets the claimed pH of from about 4.5 to about 6.5.
With respect to Applicant’s argument drawn to “one of skill in the art would understand that the free acid establishes the recited pH range and the sodium salt of the acid supplies the conjugate base to control extent of ion pairing and nicotine partitioning,” it is noted that this was also established by the teachings from Rubenstein. As previously discussed, it is reiterated that per page 15 of the specification, ion paring “depends on the electrostatic force of attraction between the positive and negative ions (i.e., a protonated basic amine such as nicotine, and the conjugate base of the organic acid).” Accordingly, as discussed above, Rubenstein teaches the nicotine benzoate is a nicotine salt complex having nicotine molecules associated with organic acid (benzoic acid) or conjugate base of the benzoic acid (benzoate), in which the organic acid (benzoic acid) or the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing). Rubenstein teaches the binding action between nicotine and the organic acid has many desirable and beneficial characteristics including nicotine complexed to an organic acid is more stable and resistant to oxidation.
Furthermore, as discussed above in the standing 103 rejection, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis.
Applicant argues:
“Even if one were motivated to modify Dull, which is certainly not conceded, one would still not arrive at the composition recited in claim 1 as amended. Applicant respectfully submits that the Office's reliance on Keller as allegedly teaching amounts of an alkali metal salt of an organic acid is misplaced. Keller only states that an alkali metal salt may be present in an amount no more than 7.5% by weight; however, this is not an alkali metal salt of an organic acid, this is a different and distinct inorganic salt such as (sodium chloride, potassium chloride, ammonium chloride, or flour salt. See paragraph [0118] of Keller.” (Remarks, page 8, 1st and 2nd paragraphs).
In response, the Examiner disagrees. As least paragraphs [0012] and [0115] from Keller teaches no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid (which benzoic acid was taught as the organic acid). Thus, contrary to Applicant’s allegation, Keller does teach and suggest the claimed combination of organic acid and a sodium salt thereof of claim 1.
Applicant argues:
“the claimed ratio is not simply an amount to be optimized; the specification teaches that the ratio, in view of the composition pH and pKa of the acid, controls the relative amounts of protonated acid and conjugate base, and the sodium salt is added to provide the desired extent of ion pairing. Keller does not recognize this functional relationship and therefore provides no motivation to select the claimed ratio in combination with the pH limitation of claim 1 as amended to achieve the claimed ion-paired nicotine delivery system. Keller is silent with respect to the ratio of free acid to sodium salt providing a desired extent of nicotine ion pairing at a pH from about 4.5 to about 6.5.” (Remarks, page 8, last paragraph to page 9).
In response, the Examiner disagrees. Both Keller and Rubenstein teach the claimed acidic pH from about 4.5 to about 6.5. As discussed above, Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]), which meets the claimed pH of from about 4.5 to about 6.5.
As discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis.
Thus, it is maintained that the claimed ratio is an obvious and optimizable parameter per guidance from Keller to achieve the desired acidic pH of from about 4.5 to about 6.5.
Applicant argues:
“Rubenstein only teaches nicotine salt complexes and solutions
containing said complexes, which are different and distinct from ion pairing. Rubenstein cannot overcome the lack of an inherent presence of ion pairing in the composition of Dull, alone or as modified with Keller as proposed by the Office. Claim 1 as amended is not directed merely to any association between nicotine and an acid or any nicotine salt complex, but requires an oral lozenge having a free organic acid and sodium salt thereof in a defined ratio, a defined molar excess of the acid/salt combination relative to the basic amine, ion pairing with a conjugate base of the organic acid, and a pH from about 4.5 to about 6.5. Rubenstein does not teach this combination nor has the Office established that the specific acid/salt/pH equilibrium recited by amended claim 1 would necessarily and inevitably result from the proposed combination of Dull, Keller, and Rubenstein.”(Remarks, page 9, 1st paragraph).
In response, the Examiner disagrees. As discussed above, Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]), which meets the claimed pH of from about 4.5 to about 6.5.
As discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis.
Applicant argues:
“Duggins does not teach a free organic acid/sodium salt
ratio, does not teach forming a nicotine ion pair with the conjugate base of the organic acid in the claimed acid/salt system, and does not teach a pH from about 4.5 to about 6.5 as part of a coordinated system for enhancing nicotine partitioning while maintaining stability. Duggins therefore cannot supply the missing functional relationship between the claimed free acid/sodium salt ratio, pH, and nicotine ion pairing.” (Remarks, page 9, last paragraph to page 10).
In response, the Examiner disagrees. As discussed above in the standing 103 rejection, the combination of organic acid and a sodium salt of thereof, the “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid,” and the pH of the oral product of claim 1 has been taught and render obvious by Keller and Rubenstein, respectively. See 103 rejection, pages 4-10 of this office action, said pages being incorporated herein its entirety.
Applicant argues:
“one of ordinary skill in the art would not have had a reasonable expectation
that the proposed combination would produce the functional result described in the instant specification. The instant specification discloses that acidic pH conventionally reduces nicotine mucosal availability because nicotine is largely protonated, yet the disclosed ion-pair system surprisingly allows nicotine partitioning consistent with alkaline-pH nicotine behavior. The cited art does not recognize that a free acid/sodium salt ratio in the claimed range, combined with a pH of about 4.5 to about 6.5, can decouple nicotine stability from mucosal availability by forming a lipophilic ion pair in an acidic lozenge system.” (Remarks, page 10, 1st paragraph).
In response, the Examine disagrees. As discussed above, the free acid/sodium salt ratio was taught by Keller. Furthermore, Keller teaches nicotine benzoate as a suitable form of nicotine salt for use in an oral product such as lozenge, and such oral product can further contain a sodium salt of an organic acid such as a sodium salt of benzoic acid in an amount sufficient to provide the product with a pH of from about 4.5 to about 6.5 (Keller: [0113]-[0117]). As discussed above, and in line with Keller, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis. Thus, Applicant’s alleged ion-pair system is not unexpected, but rather expected based on the combined teachings from Keller and Rubenstein.
Applicant argues:
“Claim 1 as amended encompasses an interdependent
compositional system in which the pH, the free acid/sodium salt ratio, the molar amount of acid/salt relative to the basic amine, and the formation of an ion pair together define the operative nicotine delivery mechanism. The specification explains that the relative amounts of organic acid and sodium salt are determined by the desired pH and ionic strength, that the free acid may be added to provide the desired pH, and that the alkali metal salt may be added to provide the desired extent of ion pairing. The specification further explains that the extent of ion pairing varies based on pH, the nature of the organic acid, the concentration of basic amine, the concentration of organic acid or conjugate base, moisture content, and ionic strength. Thus, the claimed acid/salt ratio and pH are not independent variables selected arbitrarily; they are coordinated variables that control the equilibrium population of nicotine ion pairs within the
lozenge system. This coordinated system produces an unexpected result. The specification states that, under acidic conditions, nicotine would be expected to be protonated and therefore to have low mucosal availability. The specification nevertheless reports that nicotine-organic acid ion pairs of moderate lipophilicity provide favorable stability and absorption properties, and that certain such ion pairs allow nicotine partitioning into octanol consistent with what would be predicted for nicotine at pH 8.4. The specification further states that the enhanced nicotine permeation at acidic pH is particularly surprising in view of the predicted decrease in permeability associated with nicotine protonation under acidic conditions. The claimed pH and free acid/sodium salt ratio are therefore tied to a functional and unexpected nicotine-delivery result, not merely a result of routine optimization.” (Remarks, pages 10-11).
In response, the Examiner disagrees. As discussed above and in the 103 rejection, the pH, the free acid/sodium salt ratio, the molar amount of acid/salt relative to the basic amine, and the formation of an ion pair were taught and render obvious by the combined teachings of Keller and Rubenstein. The Examiner maintains the position that the free acid/sodium salt ratio and the molar amount of acid/salt relative to the basic amine are obvious and optimizable parameters per guidance from Keller and Rubenstein in the standing 103 rejection. See 103 rejection, pages 4-10 of this office action, said pages being incorporated herein in its entirety.
Furthermore, Applicant’s alleged unexpected results from the specification drawn to the ion-pair system are not persuasive, and reasonably expected from teachings of Rubenstein. As discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis. Thus, Applicant’s alleged ion-pair system is not unexpected, but rather expected based on the combined teachings from Keller and Rubenstein.
As a result, for at least the reasons discussed above and preponderance of evidence, claims 1, 10, and 16-32 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejection as set forth in this office action.
Claim(s) 34, 36, 43-47, and 49-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boesen et al (US 2021/0106521 A1) in view of Keller et al (US 2021/0068446 A1), Duggins et al (US 2013/0209540 A1), and Rubenstein (US 2020/0315241 A1).
Regarding claim 34, Boesen teaches a compressed nicotine lozenge comprising a first module and a second module, wherein the first module (meets the claimed second discrete portion) comprises a composition containing at least one sugar alcohol (meets the claimed second discrete portion) and the second module comprises a composition containing at least one sugar alcohol and nicotine (meets the claimed first discrete portion) (Abstract; [0006]-[0009], [0018], [0023]-[0025], [0033]-[0035], [0045]-[0046], [0077]-[0081], [0091]-0099], [0106]-[0115], [0141-]-[0155], [0166]-[0174], [0178]-[0183], [0190]-[0191], [0220], [0229], [0240]-[0242], [0250], [0255]; Tables 1-2 and 5; claims 1-2, 8, 36, 47, 51 and 83). Boesen teaches the nicotine is a nicotine salts such as nicotine benzoate ([0034], [0046]). Boesen further teaches nicotine containing module further contains a sugar alcohol such as isomalt and maltitol, in an amount of at least 70% by weight ([0096]-[0098], [0105]-[0110]; Tables 1-2 and 5).
However, Boesen does not teach the combination of organic acid and a sodium salt of thereof, wherein the organic acid is decanoic acid, benzoic acid, heptanesulfonic acid, or a combination thereof, and the pH of the oral product of claim 34.
Regarding the combination of organic acid and a sodium salt of thereof and the pH of the oral product of claim 34, the Keller teaches an oral product comprising nicotine or salt thereof such as nicotine benzoate, one or more organic acid such as benzoic acid, and water in an amount from about 1% to about 60% by weight, wherein the oral product is formulated to be in the form of a lozenge (Abstract; [0005], [0009], [0011]-[0012], [0014], [0020]-[0021], [0023], [0026], [0041]-[0046], [0051]-[0053], [0055], [0066]-[0072], [0090]-[0100], [0107], [0111]-[0119], [0125]-[0129], [0146], [0155]-[0156]). Keller teaches the organic or a portion thereof is added in the form of a salt with an alkali metal such as sodium ([0012] and [0115]), thereby meeting the claimed “a combination of an organic acid and a sodium salt thereof.” Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]).
It would have been obvious to one of ordinary skill in the art to include nicotine salt such as nicotine benzoate, and a sodium salt of benzoic acid in the lozenge of Boesen, in which the sodium salt of benzoic acid included in an amount sufficient provide the lozenge of Boesen with a pH from about 4.5 to about 6.5, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Keller teaches nicotine benzoate as a suitable form of nicotine salt for use in an oral product such as lozenge, and such oral product can further contain a sodium salt of an organic acid such as a sodium salt of benzoic acid in an amount sufficient to provide the product with a pH of from about 4.5 to about 6.5. Thus, given that Boesen and Keller are drawn to commonly drawn to nicotine containing oral products such as lozenges, "[t]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
It would also have been obvious to one of ordinary skill in the art to incorporate and optimize the content of water in the lozenge containing of Boesen to an amount from 0.1% to 10% by weight, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because as discussed above, Keller teaches that the oral product can be formulated into a lozenge and the content of water can be optimize in amount from about 1% to about 60% by weight, which is a range that overlaps the claimed range of from 0.1% to 10% by weight. Furthermore, it is well-established in the prior art in view of Duggins, water in a low amount (i.e., about 3% by weight) is a typical ingredient generally use in formulating a nicotine lozenge (Duggins: Abstract; [0008]-[0009], [0011]-[0012], [0018]-[0019], [0023]-[0025], [0039], [0041]-[0042], [0044], [0050]-[0051], [0055], [0057]-[0058], [0060], [0066], [0071]; Examples 1, 2, 7-8; claims 1-3 and 7-11). Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of water in an oral product so as to achieve a desired lozenge would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “the ratio of the organic acid to the sodium salt of the organic acid is from about 0.1 to about 10” of claim 34, Keller teaches the oral product contains no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid ([0012] and [0115]). The weight amount range of an alkali metal salt to the weight amount range of organic acid as taught by Keller overlaps the claimed ranges of 0.1 to 10 of an organic acid to the sodium alkali salt thereof. As discussed above, the Courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the molar ratio of the organic acid to the sodium salt of the organic acid would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “the combination of the organic acid and the sodium salt thereof is present in a range from about 2 to about 10 molar equivalents relative to the basic amine, calculated as the amine free base” of claim 34, as discussed above, Keller teaches the oral product in form of a lozenge contains nicotine or salt thereof such as nicotine benzoate, no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid. Furthermore, the prior art per Rubenstein established that molar ratio of nicotine:organic acid in the lozenge formulation of Boesen in view of Keller is preferably 1:2 (Rubenstein: [0039]-[0052]; Table 2), which falls within the claimed feature of “the combination of the organic acid and the sodium salt thereof is present in a range from about 2 to about 10 molar equivalents relative to the basic amine, calculated as the amine free base.” Thus, one of ordinary skill would reasonably conclude that the prior art discloses a molar equivalent of organic acid to basic amine that is in the range of about 2 to about 10 molar equivalents of organic acid and alkali metal salts thereof relative to the basic amine. As discussed above, the Courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of molar ratios of the combination of the organic acid and the sodium salt thereof in relation to nicotine would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
With respect to “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” of claim 34, Rubenstein teaches a composition containing nicotine salts such as nicotine benzoate, wherein the composition is suitable for formulating oral lozenges (Abstract; [0002], [0007], [0012], [0020], [0022], [0024], [0031]-[0032], [0036]-[0038], [0041]-[0043], [0052], [0061], [0064]-[0065], [0070], [0079]-[0080], [0099]-[0100], [0106]-[0111], Example II and Table 9). Rubenstein teaches the nicotine benzoate is a nicotine salt complex having nicotine molecules associated with organic acid (benzoic acid) or conjugate base of the benzoic acid (benzoate), in which the organic acid (benzoic acid) or the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) ([0012], [0020], [0022], [0024], [0031]-[0032], [0036]-[0038], [0041]-[0043], [0052], [0061], [0064]-[0065], [0070], [0079]-[0080], [0099]-[0100], [0106]-[0111], Example II and Table 9). Rubenstein teaches the binding action between nicotine and the organic acid has many desirable and beneficial characteristics including nicotine complexed to an organic acid is more stable and resistant to oxidation ([0036]-[0038]). Rubenstein teaches nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen ([0013], [0038], [0048]). Thus, it would have been reasonably obvious that the lozenge of Boesen in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because the components in the lozenge are mixed and as discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Boesen in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Boesen in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller. As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Boesen in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation.
Regarding claim 36, Boesen teaches the lozenge has an exterior outer surface in which the exterior outer surface comprises the module containing nicotine ([0091]-[0095], [0166]-[0174], [0178]-[0183]).
Regarding claim 43, as discussed above, Boesen teaches lozenge containing nicotine.
Regarding claim 44, Boesen teaches nicotine is present in the lozenge in an amount of 0.2% to 5% by weight ([0025]; claim 2), which falls within the claimed range of from about 0.001% to about 10% by weight. Thus, the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of nicotine in the oral product would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
Regarding claim 45, Boesen teaches the sugar alcohol is selected from xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and combinations thereof (0091]-0099], [0106]-[0115]).
Regarding claim 46, Boesen teaches the first module (meets the claimed second discrete portion) contains at least 70% by weight of sugar alcohol and can further contain flavors (Abstract; [0006]-[0009], [0018], [0023]-[0025], [0033]-[0035], [0045]-[0046], [0077]-[0081], [0091]-0099], [0106]-[0115], [0141-]-[0155], [0166]-[0174], [0178]-[0183], [0190]-[0191], [0220], [0229], [0240]-[0242], [0250], [0255]; Tables 1-2 and 5; claims 1-2, 8, 36, 47, 51 and 83). Duggins teaches a lozenge containing nicotine salt, a sugar isomalt, maltitol syrup, a salt such as sodium chloride, a sweetener such as sucralose, and water (Abstract; [0008]-[0009], [0011]-[0012], [0018]-[0019], [0023]-[0025], [0039], [0041]-[0042], [0044], [0050]-[0051], [0055], [0057]-[0058], [0060], [0066], [0071]; Examples 1, 2, 7-8; claims 1-3 and 7-11). Duggins teaches isomalt is present in the lozenge at an amount of at least 80% by weight ([0066]; Example 1). Duggins teaches the salt such as sodium chloride is present in the lozenge at an amount of at least about 0.5% by weight, particularly 1% by weight ([0057]; Example 1). It would have been obvious to one of ordinary skill in the art to optimize and include sugar alcohol in an amount of at least 80% by weight, and salt such as sodium chloride in an amount of at least about 0.5% by weight and particularly 1% by weight, in the first module of the lozenge of Boesen, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Duggins provided the guidance to do so by teaching that the lozenge of Boesen can be formulated such that sugar alcohol in an amount of at least 80% by weight, and salt such as sodium chloride in an amount of at least about 0.5% by weight (and particularly 1% by weight), as these amounts as guided by Duggins are typical amounts generally use in formulating a multilayer nicotine lozenge. Thus, an ordinary artisan would have looked to formulating the lozenge of Boesen such that sugar alcohol is included in an amount of at least 80% by weight, and salt such as sodium chloride is included in an amount of at least about 0.5% by weight such as 1% by weight, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 47, Boesen teaches the first module (meets the claimed second discrete portion) does not contain nicotine ([0190]; Tables 1-2).
Regarding claim 49, Boesen teaches the weight ratio of the first module to the second module is about 2:1 or 3:1 ([0232], [0246], [0250], [0255], [0258]).
Regarding claim 50, Duggins teaches and provide guidance for to the lozenge further contains an outer coating ([0071]). Thus, it would have been obvious to one of ordinary skill in the art to include an outer coating on the lozenge of Boesen, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Duggins provided the guidance to do by teaching that the lozenge of Boesen can further contain an outer coating so as to provide a hard coated lozenge (Duggins: [0071]). Thus, an ordinary artisan seeking to formulate a hard coating-type lozenge would have looked to coating the lozenge of Boesen with an outer coating, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 51, Boesen teaches the first module and the second module is in the form in a core/sheath arrangement or in a layered arrangement ([0091]-[0095], [0166]-[0174], [0178]-[0183]).
Regarding claim 52, Boesen teaches the lozenge further contains menthol and peppermint (a botanical or a terpene) ([0242]).
Regarding claim 53, Boesen teaches the lozenge is free of a tobacco material (Tables 1-2).
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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
Applicant argues:
“Boesen merely discloses that nicotine may be present as the free base or in the form of a salt with certain acids. As with the salts of Dull described herein above, one of skill in the art would understand that the salts of Boesen are not in solution and cannot be ion paired. For at least this reason, Boesen does not inherently comprise nicotine ion paired with an organic acid as the recited association has not been shown to be a necessary outcome of the purported combination of reference teachings. In any event, Boesen also fails to teach or suggest a free acid/sodium salt ratio in a nicotine-containing composition with ion pairing and at a pH from about 4.5 to about 6.5.” (Remarks, page 11, last paragraph to page 12).
In response, the Examiner disagrees. As discussed above in the standing 103 rejection, the combination of organic acid and a sodium salt of thereof, the “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid,” and the pH of the oral product of claim 34 has been taught and render obvious by Keller and Rubenstein, respectively. See 103 rejection, pages 26-31 of this office action, said pages being incorporated herein its entirety.
Particularly, with respect to the pH of the oral product as amended in claim 1, as discussed in the standing 103 rejection, Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]), which meets the claimed pH of from about 4.5 to about 6.5.
With respect to Applicant’s argument drawn to ion pairing,” as previously discussed, it is reiterated that per page 15 of the specification, ion paring “depends on the electrostatic force of attraction between the positive and negative ions (i.e., a protonated basic amine such as nicotine, and the conjugate base of the organic acid).” Accordingly, as discussed above, Rubenstein teaches the nicotine benzoate is a nicotine salt complex having nicotine molecules associated with organic acid (benzoic acid) or conjugate base of the benzoic acid (benzoate), in which the organic acid (benzoic acid) or the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing). Rubenstein teaches the binding action between nicotine and the organic acid has many desirable and beneficial characteristics including nicotine complexed to an organic acid is more stable and resistant to oxidation.
Furthermore, as discussed above in the standing 103 rejection, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Boesen in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Boesen in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller. As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Boesen in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation.
Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis.
Applicant argues:
“Keller is silent with respect to the ratio of free acid to sodium salt and a
pH from about 4.5 to about 6.5, and does not recognize the functional relationship between the acid/salt ratio, the composition pH and pKa of the acid, and the extent of ion pairing, and therefore provides no motivation to select the claimed features in combination to achieve the claimed ion-paired nicotine delivery system.” (Remarks, page 12, 1st paragraph).
In response, the Examiner disagrees. As least paragraphs [0012] and [0115] from Keller teaches no more than about 7.5% of total weight of an alkali metal salt and from about 0.1 to 0.5% of total weight of one or more organic acids, wherein sodium is used as the alkali metal salt to form alkali metal salts of the organic acid (which benzoic acid was taught as the organic acid). Thus, contrary to Applicant’s allegation, Keller does teach and suggest the claimed combination of organic acid and a sodium salt thereof and their ratio of claim 34.
With respect to the claimed pH from about 4.5 to about 6.5, as discussed above and in the 103 rejection, Both Keller and Rubenstein teach the claimed acidic pH from about 4.5 to about 6.5. As discussed above, Keller teaches the organic acid is provided in a quantity sufficient to provide the product with a pH of from about 4.5 to about 6.5 ([0113]-[0117]), which meets the claimed pH of from about 4.5 to about 6.5.
With respect to Applicant’s alleged ion pairing system, as discussed above, Rubenstein established that it is expected that there would be an association between the nicotine and the conjugate base of the benzoate in the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), as the conjugate base of the benzoic acid (benzoate) bonds with the nicotine through hydrogen bonding (ionic interaction or in other words, ionic pairing) to form nicotine salt complex at a pH of from between 4.0 and 6.5, which is the pH of the lozenge product of Dull in view of Keller when sodium salt of benzoic acid (sodium benzoate) is present in an amount sufficient to provide a pH from about 4.5 to about 6.5 per Keller ([0113]-[0117]). As discussed above, Rubenstein established that nicotine complexed to an organic acid at a pH of from between 4.0 and 6.5, particularly when nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, further supporting the obviousness analysis that the lozenge of Dull in view of Keller containing nicotine benzoate and sodium salt of benzoic acid (sodium benzoate), would inherently result in having “at least a portion of the basic amine is associated with at least a portion of the organic acid and the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid” because at a pH from about 4.5 to about 6.5, nicotine molecules are approximately at pH six (6), 99% are protonated at the N-methyl pyrrolidinyl nitrogen, thereby providing nicotine complexed to the organic acid that is more stable and resistant to oxidation. Applicant is noted that the specification discloses: “at acidic pH values (such as from about 6.5 to about 4), certain basic amines, for example nicotine, are largely present in a protonated form, which has relatively high water solubility, and higher stability with respect to evaporation and oxidative decomposition, but low mucosal availability...it has been found that the properties of stability, solubility, and availability of the nicotine in a composition configured for oral use can be mutually enhanced through ion pairing or salt formation of nicotine with appropriate organic acids and/or their conjugate bases.” (Specification: page 16, lines 1-26). These disclosures from the specification are exactly what were taught in Rubenstein supra. This is preponderance of evidence to support the Examiner’s obviousness analysis.
Applicant argues:
“Duggins is relied upon solely for conventional lozenge ingredients and water content, not for the coordinated pH/acid-salt/ion-pairing system. Rubenstein does not teach the claimed multicomponent lozenge composition having both the recited free acid/sodium salt ratio and the amended pH limitation, nor does Rubenstein teach or suggest the existence of ion pairing or the coordinated pH/acid- salt/ion-pairing system of claim 34 as amended.” (Remarks, page 12, 2nd paragraph).
In response, the Examiner disagrees. As discussed above in the standing 103 rejection, the combination of organic acid and a sodium salt of thereof, the “at least a portion of the basic amine is associated with at least a portion of the organic acid and the sodium salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid,” and the pH of the oral product of claim 34 has been taught and render obvious by Keller and Rubenstein, respectively. See 103 rejection, pages 26-31 of this office action, said pages being incorporated herein its entirety.
As a result, for at least the reasons discussed above and preponderance of evidence, claims 34, 36, 43-47, and 49-53 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejection as set forth in this office action.
Claim(s) 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boesen et al (US 2021/0106521 A1) in view of Keller et al (US 2021/0068446 A1), Duggins et al (US 2013/0209540 A1), and Rubenstein (US 2020/0315241 A1), as applied to claim 34 above, and further in view of Kiefer et al (US 2007/0221236 A1).
The multicomponent oral product of claim 34 is discussed above, said discussion being incorporated herein it is entirety.
Regarding claim 56, Kiefer teaches a lozenge formulation containing a menthyl ester selected from monomenthyl succinate and monomenthyl glutarate, wherein the menthyl ester provides a cooling sensation to oral cavity (Abstract; [0023], [0036]-[0037], [0044], [0048], [0050], [0052], [0063], [0068]; Table 1).
It would have been obvious to one of ordinary skill in the art to include monomenthyl succinate or monomenthyl glutarate in the lozenge of Boesen, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Kiefer provided the guidance to do so by teaching that monomenthyl succinate or monomenthyl glutarate can be included in the lozenge formulation so as to provide a cooling sensation to oral cavity. Thus, an ordinary artisan seeking to provide a nicotine lozenge which also have a desired cooling sensation would have looked to including monomenthyl succinate or monomenthyl glutarate in the lozenge, and achieve Applicant’s claimed invention with reasonable expectation of success.
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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
Applicant argues:
“As discussed above, claim 34 is patentable over Boesen, Keller, Duggins, and
Rubenstein. Kiefer cannot remedy any of the aforementioned deficiencies in the teachings of the cited references. Kiefer is relied upon solely with respect to allegedly teaching inclusion of monomenthyl succinate or monomenthyl glutarate. Kiefer does not teach or suggest an oral product having all of the features of claim 34 as amended.
While it is believed that dependent claim 56 recites additional patentable elements, Applicant submits that it is not necessary to further argue these individually due to its reliance on a non-obvious independent claim. This should in no way be interpreted as acquiescence regarding any alleged or obviousness.”
(Remarks, page 13).
In response, the Examiner disagrees. Claim 34 was rendered obvious by the combined teachings of Boesen, Keller, Duggins, and Rubenstein. See 103 rejection, pages 25-31 of the office action. Accordingly, Kiefer was used for teaching dependent claim 56 and remained to render obvious dependent claim 56 for the reason of record.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 10, 16-32, 34, 36, 43-47, 49-53 and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of copending Application No. 17727154 (reference application) in view of Duggins et al (US 2013/0209540 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims in the copending application ‘154 significantly overlap with the subject matter of the instant claims i.e. an oral product, the oral product comprising: at least one sugar substitute; a basic amine (nicotine); and a combination of organic acid and sodium salt thereof, wherein the organic acid has a logP value of from about 1.0 to about 12.0; wherein at least a portion of the basic amine is associated with at least a portion of the organic acid or the alkali metal salt thereof, the association in the form of an ion pair between the basic amine and a conjugate base of the organic acid; wherein the oral product is in the form of a lozenge (pastille); wherein the organic acid is decanoic acid, benzoic acid, heptanesulfonic acid, tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or a combination thereof; wherein a ratio of the organic acid to the sodium salt of the organic acid is from about 0.1 to about 10; wherein the organic acid and the sodium salt thereof is present in a range of from about 2 to about 10 molar equivalents relative to the basic amine, calculated as the amine free base; and wherein the amount of water in the oral products and the pH of the oral products substantially overlaps.
While the oral product in the claims of copending application ‘154 further contains a gum, it would have been obvious to include a gum component in the lozenge of the instant claims, as well as, optimize the amount of sugar substitute and gum in the lozenge to amounts as claimed in the copending application ‘154 in view of the guidance from Duggins (Abstract; [0008]-[0009], [0011]-[0012], [0018]-[0019], [0023]-[0025], [0039], [0041]-[0042], [0044], [0050]-[0051], [0055], [0057]-[0058], [0060], [0066], [0071], [0073]-[0074]; Examples 1, 2, 7-8; claims 1-3, 7-11, and 18-21).
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over copending Application No. 17727154 in view of Duggins.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
Applicant argues that the obviousness type double patenting rejection was provisional and a response was not warranted at the present time. (Remarks, page 13, last paragraph).
In response, the Examiner disagrees. Per MPEP §804(I)(B)(1), provisional double patent rejection should be made and maintained by the Examiner until Applicant overcome the rejection by filing a terminal disclaimer.
Accordingly, the provisional nonstatutory double patenting rejection, as set forth in this office action, is maintained for the reason of record, pending filing of a terminal disclaimer.
Conclusion
No claim is allowed.
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.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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