DETAILED ACTION
Claims 1-32 are pending and under consideration on the merits.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/22/2026 has been entered.
Status of the Rejections
The 103 rejections are maintained.
Notice of Subject Matter Free of the Prior Art
Newly added claims 31-32 are free of the prior art. Both of these claims recite “consisting of” language in the preamble, and further include a limitation that the composition contains “water q.s. to 100%,” which implies the presence of an amount of water that is greater than the maximum of 30 wt% which Amith et al. teaches is necessary in order to omit paraben preservatives in the formulation. The prior art does not teach or suggest that a fexofenadine suspension comprising only the preservatives recited by claims 31-32, and omitting paraben preservatives, could be formulated if the amount of water in the formulation exceeds 30 wt%.
Claim Objections
Claims 31-32 are objected to as depending from a rejected base claim, but would be in condition for allowance if rewritten in independent form and incorporating all limitations of base claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 and 6-30 are rejected under 35 U.S.C. 103 as unpatentable over Chrzan et al. (US Pat. Pub. 2008/0299211) in view of Amith et al. (US Pat. Pub. 2016/0184284; of record in IDS).
As to claims 1-2 and 6-30, Chrzan discloses an aqueous pharmaceutical suspension having a pH of about 4.25 to about 9.43 (encompassing the range of claim 1), 0.03-4.80 wt% fexofenadine zwitterionic dihydrate Form 1, 0.01 to 0.20 wt% wetting agent, 0.10 to 0.50 wt% hydrocolloid gum, a sweetener system comprising 5-40 wt% sucrose and 0-40 wt% xylitol wherein the ratio of sucrose to xylitol is equal to or greater than 1:1, a preservative system comprising parabens, 0.06-0.26% edetate disodium, and 0.01 to 0.30% potassium sorbate, a buffer system comprising 0.06 to 1.05% sodium phosphate monobasic and 0.32% to 2.69% sodium phosphate dibasic hydrate, 0.1 to 15% propylene glycol, and 0.20% to 0.70% of a flavoring agent (see claims 1-2, 23, 44-52, 65-67, and 77-79 of Chrzan). The foregoing ranges match or overlap the ranges recited for these ingredients by claims 1-2, 6, 9-11, 15, 17-26, 29, and 31-32. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Chrzan does not disclose the presence of another active in the composition, thereby meeting the “consisting of” language of claim 2
Regarding claims 6-8, Chrzan discloses that at least 90% of the fexofenadine compound has a particle size of less than about 40 microns, which reads on the ranges of these claims (claims 5-7 of Chrzan).
As to claim 16, the hydrocolloid gum may be xanthan gum (claim 14 of Chrzan).
Regarding claims 12-14, the wetting agent may be ionic such as Poloxamer 188 or Poloxamer 407 (claims 54-55 of Chrzan).
As to claims 27-28, the composition further comprises 0.05 to 0.10% of an opacifying agent such as titanium dioxide, which overlaps the range of claim 27 (claims 71-76 of Chrzan).
As to claim 29, Chrzan also teaches that the sodium phosphate dibasic hydrate may be a heptahydrate as recited by this claim (claim 52 of Chrzan).
Regarding claim 30, the flavoring agent may be artificial raspberry cream or orange cream (claims 80-82 of Chrzan).
As to claims 1-2 and 6-30, Chrzan does not further expressly disclose that the composition is free of parabens such that the preservative system consists only of edetate disodium and potassium sorbate as recited by claim 1.
Amith discloses liquid pharmaceutical compositions comprising fexofenadine (paragraph 1). Amith teaches that while prior art fexofenadine formulations comprise parabens as preservatives, parabens have been linked to negative health effects such as drug allergies and negative effects on spermatogenesis (paragraph 10). Amith teaches that its compositions are therefore preferably free of parabens, and that it was found that by keeping the extra water in the composition below a specified range along with the use of a sweetener/stabilizer comprising glycerol or a combination of glycerol with a sugar alcohol , the paraben preservatives could be removed while still maintaining biological stability (paragraphs 38-42 and 64-69).
As to claims 1-2 and 6-30, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the composition of Chrzan by removing all parabens. The skilled artisan would have been motivated to do so because Amith teaches that parabens have been linked to negative health effects such as drug allergies and negative effects on spermatogenesis, and the skilled artisan would have had a reasonable expectation of success in removing the parabens because Amith expressly discloses that preservatives, including parabens, can be removed from aqueous fexofenadine formulations while still maintaining biological stability by controlling the extra water content of the formulation, and additionally because Chrzan itself discloses non-paraben preservatives that can be used in its formulation including edetate sodium and potassium sorbate as discussed above. Thus, the prior art provides evidence of an explicit advantage that would result from modifying the Chrzan disclosure as discussed above. The strongest rationale for combining references is a recognition, as is the case here, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). See also Dystar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick, 464 F.3d 1356, 1368, 80 USPQ2d 1641, 1651 (Fed. Cir. 2006) (“Indeed, we have repeatedly held that an implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the ‘improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal—and even common-sensical—we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves.”).
Claims 3-5 are rejected under 35 U.S.C. 103 as unpatentable over Chrzan et al. (US Pat. Pub. 2008/0299211) in view of Amith et al. (US Pat. Pub. 2016/0184284 as applied to claims 1-2 and 6-30 above, and further in view of Liversidge et al. (US Pat. Pub. 2006/0216353).
The teachings of Chrzan and Amith are relied upon as discussed above, but they do not further expressly disclose that the preservative system comprises domiphen bromide (claims 3, 5) or cetylpyridinium chloride (claim 4).
Liversidge discloses suspensions comprising an antihistamine such as fexofenadine (paragraphs 23, 28, 81-82) along with one or more cationic stabilizers for the poorly soluble fexofenadine such as cetylpyridinium chloride or domiphen bromide (paragraph 19, 86, 103) and which are used in the amount of 0.001 to 99.5 wt% (paragraphs 117 and 119).
As to claims 3-5, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the fexofenadine composition of Chrzan and Amith as combined supra by incorporating cetylpyridinium chloride and domiphen bromide in amounts within the recited ranges, because Liversidge teaches that these compounds are useful in such amounts as stabilizers for poorly soluble antihistamine compounds such as fexofenadine.
Response to Applicant’s Arguments
Applicant argues that Chrzan discloses formulations that require paraben and that further comprise sorbic acid or potassium sorbate or benzyl alcohol as co-preservatives, not as substitutes for parabens. Applicant concludes that the skilled artisan would understand that Chrzan’s antimicrobial performance depends on the combination of preservatives and would not expect equivalent efficacy upon the removal of parabens.
In response, while Applicant argues that Chrzan’s teachings of parabens in combination with additional preservatives implies that the additional preservatives would not be sufficient by themselves, the skilled artisan reading Amit would learn that non-paraben preservatives in fact can be sufficient so long as the water content is controlled, e.g., to below 30%, and it follows that the synergistic effects obtained by combining parabens with other preservatives therefore would not be needed if water content is so controlled.
Applicant argues that Amit provides a different solution for stable fexofenadine compositions by lowering water content, allowing for compositions that are free or substantially free of parabens and other preservatives. Applicant concludes that Amit teaches away from replacing parabens with sorbate and EDTA and instead teaches elimination of preservatives altogether by using 50-90% polyols and maintaining water content below 30%.
In response, and as acknowledged by Applicant, Amith itself suggests that its formulation may still comprise small amounts of preservatives even with control of water content, so the skilled artisan would not have thought it necessary to eliminate all preservatives from the Chrzan composition.
Applicant notes that Amith teaches that preservatives can be omitted if the water content is below 30% and if 35-90% sorbitol is used, and argues that the skilled artisan reading Chrzan in view of Amith would use glycerol and sorbitol and omit sucrose, because it reduces the number of calories and improves the desirability of the formulation. Applicant concludes that the skilled artisan seeking to eliminate the need for preservatives would use a formulation containing less than 30 wt% water and at least 50% glycerol, or a mixture of at least 30% glycerol and at least 20% sorbitol, without further sweeteners, which would lead away from the claimed invention (which requires the presence of sucrose). Applicant also argues that because of the need to avoid a formulation that is too sweet, the skilled artisan combining Amith with Chrzan would likely use the variation of Chrzan’s sweetener system that uses sorbitol (instead of the xylitol recited by the claims), because sorbitol is less sweet than xylitol. Applicant also argues that Chrzan requires a sweetener system of about 5-40% sucrose and 0-40% of other sugar alcohols, and that the skilled artisan would not be motivated to modify the sweetener system by increasing the sweeteners because it may render the formulation too sweet for consumption.
In response, this argument is not persuasive because although Amith teaches that there are advantages to using glycerol and sorbitol instead of sucrose since sucrose is caloric and cariogenic (paragraph 49), the primary reference Chrzan does not teach away from the use of sucrose and in fact expressly teaches that its composition comprises sucrose as discussed in the rejection, and the skilled artisan would not have found it necessary to omit sucrose from the Chrzan composition in those cases where reducing the caloric content of the composition was not a priority. Additionally, the Office does not agree that the skilled artisan incorporating the sweetener system of Amith into the Chrzan formulation would have replaced the xylitol of the Chrzan formulation with sorbitol as taught by Amith. Amith in fact does not require the use of either sorbitol or xylitol. Rather, Amith expressly teaches that the sweetener may comprise glycerol by itself (see, e.g., paragraphs 39-40), and glycerol is also less sweet than xylitol and only slightly sweeter than sorbitol, such that the skilled artisan would have had a motivation to incorporate glycerol in the Chrzan formulation and compensate for the additional sweetness added by the glycerol by using amounts of the other sweeteners in the Chrzan formulation that are near the lower ends of the ranges taught by Chrzan.
Applicant also argues that adding at least 50% glycerol or a mixture of at least 30% glycerol and 25% sorbitol into the Chrzan formulation as taught by Amith is not compatible with the amounts of the ingredients recited by claims 1-2, which Applicant claims would not allow for the addition of at least 50% glycerol.
In response, the Office does not agree with Applicant’s calculations. The use of the lower end of the range for each ingredient recited by claim 1 or claim 2 results in a total amount of slightly more than 19 wt%, which easily allows for the introduction of 50 wt% glycerol.
Applicant also argues that the combination of Chrzan and Amith would require the presence of less than 30 wt% water, but claim 1 is directed to formulations containing more than 30 wt% water.
In response, the Office does not agree that claim 1 is directed to formulations containing more than 30 wt% water. The Office has reviewed the language of claim 1 carefully, but could not locate any limitations that would require the formulation to contain more than 30 wt% water.
Applicant also argues that the claimed invention provides unexpected results by identifying that using potassium sorbate in fexofenadine formulations can result in bioequivalence to paraben containing formulations.
In response, Applicant’s finding is not viewed as unexpected over the prior art, since Amith teaches that fexofenadine formulations that are substantially or even entirely free of preservatives can be substantially equivalent in stability to the paraben-containing Allegra® pediatric fexofenadine suspension (see paragraphs 68-69).
Regarding claims 3 and 5, Applicant argues that Liversidge would not motivate the use of cetylpyridinium chloride or domiphen bromide in a fexofenadine composition as preservatives in place of the synergistic components of Chrzan’s preservative system, because it teaches that these compounds are in fact used as surface stabilizers for corticosteroids, and does not suggest using these compounds in a composition that comprises an antihisitamine alone and omits the corticosteroid.
In response, this is not persuasive because the claims do not exclude the presence of a corticosteroid, and the skilled artisan would have been motivated to not use the synergistic preservative system of Chrzan for the reasons discussed above, i.e., in order to omit undesirable paraben compounds from the formulation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAREN GOTFREDSON whose telephone number is (571)270-3468. The examiner can normally be reached on M-F 9AM-6PM.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
