DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1, 3, 4, and 8-17 are pending and under current examination. Claims 2 and 5-7 are cancelled.
Withdrawn Claim Rejections
All rejections pertaining to claims 2 and 5-7 are moot because the claims are cancelled in the amendments filed 11/2/2025.
All rejections under 35 U.S.C. 102 and 112(b) are withdrawn in view of the amendments filed 11/2/2025.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s amendments to the claims have necessitated the new grounds of rejection of claims 1, 3, 4, and 8-17.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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, 3, 4, 8-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Boyer (WO2018/091473, publication date: 5/24/2018, of record) in view of Maibach (U.S. Patent Application No. 2009/0004254, publication date 1/1/2009, cited in the IDS filed 6/20/2023, of record).
Applicant’s Invention
Applicant’s claim 1 is drawn to an orally dissolving film formulation comprising a) naratriptan or a salt thereof as an active ingredient; and b) a mixture of citric acid and sodium citrate as a buffer, wherein the buffer comprises 0.42 to 1.05% by weight of sodium citrate and 0.015 to 0.038% by weight of citric acid based on the total weight of the film solid.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 1, Boyer teaches an oral dissolvable film suitable for administration to an oral cavity comprising a triptan or pharmaceutically acceptable salt thereof (pg. 3 lines 18-22 and pg. 5 line 15). Boyer teaches that the active pharmaceutical ingredient of the film is a triptan, preferably sumatriptan, zolmitriptan, or naratriptan (pg. 12 line 10). The film includes at least one buffering component (pg. 13 line 15). Boyer teaches that the oral film may comprise any suitable buffering component, including phosphates, citrates, and acetates (pg. 13 line 24 and 31). The film comprises from 0.1-10% by weight of the buffering component (pg. 14 line 3) and may include citric acid at a concentration from 1 to 40mM (pg. 15 line 1).
Regarding claims 3 and 4, Boyer does do not disclose the dissolution properties as recited in claims 3 and 4. However, the invention as claimed is not structurally distinguishable from the disclosure of Boyer and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Regarding claim 8 and 9, Boyer does do not disclose the stability properties as recited in claims 8 and 9. However, the invention as claimed is not structurally distinguishable from the disclosure of Boyer and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Regarding claim 10, Boyer teaches that the film may comprise a film-forming agent (pg. 6 lines 5-6 and pg. 9 line 4).
Regarding claims 11 and 12, Boyer teaches that the film may contain sodium alginate (pg. 8 line 2), pullulan, hydroxypropyl methyl cellulose, and other cellulose-based film-forming agents (pg. 9 line 6).
Regarding claims 13 and 14, Boyer discloses that the oral dissolving films may be prepared by mixing the API and at least one buffering component in water, adjusting the pH of the solution to the desired level by addition of an appropriate acid or base and preferably adjusting the pH of the solution from 3.25 to 12.0, adding further water, plasticizers, and/or fillers under further mixing, adding the alginate salt and mixing until a lump free dispersion is achieved, pouring the cast onto a surface, and drying the cast layer, typically at a temperature of from 45 to 70oC, to form a solid film (pg. 22 lines 10-32). The API and alginate salts may be dissolved together in solution (pg. 23 line 11).
Regarding claim 15, Boyer teaches a method of treating migraine with or without aura comprising administration of at least one orally dissolving film to a human patient (pg. 3 lines 28-31).
Regarding claim 17, Boyer teaches that the film comprises from 0.001% to 75% by weight of the active pharmaceutical ingredient (pg. 12 line 18).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 1, Boyer does not teach that the buffer present in the film may comprise a mixture of citric acid and sodium citrate. However, this deficiency is cured by Maibach.
Maibach discloses an orally-dissolvable film that may contain a citric acid/sodium citrate buffer system that may aid in producing a more palatable product with severely acidic or severely basic active drugs [0129]. The buffering agents present in the film may also provide the ability to place the film comprising active drugs in the mouth in a favorable pH environment for passage across the mucosal tissues of the mouth, pharynx, and esophagus. Buffering agents incorporated within the composition may be used to affect a pH change in the salival environment of the mouth in order to favor the existence of unionized form of the active drug or other active ingredient which more readily moves through the mucosal tissues [0128]. The film disclosed by Maibach may contain naratriptan as the active ingredient [0022].
Regarding claim 17, Boyer does not teach that the orally dissolvable film may contain 2.5mg of naratriptan or disclose the AUC or Cmax in a Beagle dog following administration of the orally dissolving film.
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 1, it would have been prima facie obvious to include a mixture of citric acid and sodium citrate as the buffer system present in the oral dissolving film embraced by Boyer. One would have understood in view of Maibach that a buffering system of citric acid/sodium citrate may be used in oral dissolving films containing severely acidic or severely basic drugs in order to improve the taste or movement through mucosal tissues [0128 and 0129]. It would have been obvious to include a citric acid/sodium citrate buffering system in the oral film disclosed by Boyer. One of ordinary skill in the art of filing would have been motivated to include a citric acid/sodium citrate buffering system in the film disclosed by Boyer in order to improve the taste of the basic active ingredient, naratriptan. The artisan of ordinary skill would have had reasonable expectation of success because Boyer teaches that both citrates and citric acid may be present in the oral dissolving film and Maibach teaches that a film containing sumatriptan may include a citric acid/sodium citrate buffering system.
Regarding the weight percentage ranges of citric acid and sodium citrate as specified in claim 1, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Maibach teaches that a citric acid/sodium citrate buffering system may be used to improve the taste of severely acidic or basic drugs present in oral dissolving films [0129]. The Applicants' specification provides no evidence that the selected weight percentage ranges in claim 1 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to different acidic or basic characteristics and concentrations of the drug present in the oral dissolving film, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the weight percentage ranges of citric acid and sodium citrate. One of ordinary skill in the art would have been motivated to change the weight percentage ranges as this could be expected to be advantageous for altering the taste and transmucosal movement of the drug.
Regarding claim 17, the amount of naratriptan present in the film, the AUC, and the Cmax of the film after administration to a Beagle dog are clearly result effective parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight of naratriptan present in the film in order to best achieve the desired results as such would provide advantageous AUC and Cmax of the drug when administered to a Beagle dog. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Boyer teaches that the active pharmaceutical ingredient may be present at 0.001% to 75% by weight (pg. 12 line 18). The Examiner considers it prima facie obvious to optimize the weight of naratriptan, and therefore the AUC and Cmax of the orally dissolving film, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight of naratriptan present in the film would directly affect the AUC and Cmax of the film and therefore be an optimizable variable.
Claims 16 is rejected under 35 U.S.C. 103 as being unpatentable over Boyer (WO2018/091473, publication date: 5/24/2018, of record), as applied to claims 1-5, 8-15, and 17 above, and further in view of Seeburger et. al. (Headache, pg. 57-67; publication year: 2012, of record).
Applicant’s Invention
Boyer renders obvious the relevant limitations of claims 1 and 15 above. Applicant’s claim 16 further adds the limitation of the method according to claim 15, wherein the orally dissolving film formulation is administered simultaneously with or at a time interval relative to another formulation comprising topiramate as an active ingredient.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Boyer teaches the relevant limitations of claim 1 as described above.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Boyer does not teach that the orally dissolving film may be administered simultaneously or at a time interval with another formulation comprising topiramate as an active ingredient. However, this deficiency is cured by Seeburger.
Seeburger teaches that triptans are prescribed for patients who continue to experience migraine attacks during treatment with prophylactic medications, including topiramate. Seeburger also teaches that topiramate is an anticonvulsant medication approved for reducing the frequency of migraine attacks when taken prophylactically for episodic or chronic migraine (pg. 58 Introduction).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to co-administer the oral dissolving film embraced by Boyer with another formulation comprising topiramate. One would have understood in view of Seeburger that patients experiencing migraines are often prescribed triptans when prophylactic administration of topiramate fails to reduce or eliminate migraine attacks (pg. 58 Introduction). It would have been obvious to one of ordinary skill in the art of filing to administer the oral dissolving film containing sumatriptan embraced by Boyer in conjunction with topiramate. One of ordinary skill would have been motivated to administer the oral dissolving film containing sumatriptan along with topiramate in order to reduce migraines that are unresponsive to prophylactic treatment with topiramate. The artisan of ordinary skill would have had reasonable expectation of success because Seeburger teaches that triptans are commonly prescribed along with prophylactic topiramate. See MPEP 2144.07.
Response to Arguments
Applicant’s arguments, see pg. 6, filed 11/2/2025, with respect to the rejection of claims 1, 3-5, 8-11, and 15 under 35 U.S.C. 102 over Boyer have been fully considered and are persuasive. The rejection of claims 1, 3-5, 8-11, and 15 under 35 U.S.C. 102 over Boyer has been withdrawn.
Applicant's arguments with respect to the claim rejections under 35 U.S.C. 103 filed 11/2/2025 have been fully considered but they are not persuasive.
On pg. 6, applicant argues that Boyer fails to disclose or suggest the claimed structural features of the amended claims. This is not found persuasive. As discussed in the obviousness rejection above, the relevant limitations of claim 1 are obvious over Boyer in view of Maibach. Boyer teaches an orally dissolving film that may contain naratriptan as an active agent. The film includes at least one buffering component (pg. 13 line 15). Boyer teaches that the oral film may comprise any suitable buffering component, including phosphates, citrates, and acetates (pg. 13 line 24 and 31). Maibach discloses an orally-dissolvable film that may contain a citric acid/sodium citrate buffer system that may aid in producing a more palatable product with severely acidic or severely basic active drugs [0129]. The buffering agents present in the film may also provide the ability to place the film comprising active drugs in the mouth in a favorable pH environment for passage across the mucosal tissues of the mouth, pharynx, and esophagus. Buffering agents incorporated within the composition may be used to affect a pH change in the salival environment of the mouth in order to favor the existence of unionized form of the active drug or other active ingredient which more readily moves through the mucosal tissues [0128]. The film disclosed by Maibach may contain naratriptan as the active ingredient [0022]. It would have been prima facie obvious to include a mixture of citric acid and sodium citrate as the buffer system present in the oral dissolving film embraced by Boyer. Therefore, the argument is not persuasive and the rejection is maintained.
On page 6, Applicant argues that Boyer fails to disclose or suggest the unexpected technical effects resulting from the claimed structural features. This is not found persuasive. Please refer to MPEP 716.02 (b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims.
Differences in results are in fact unexpected and unobvious: Applicant argues that a citric acid buffer system within the claimed concentration ranges would simultaneously achieve both superior dissolution and stability characteristics of the claimed invention. However, Borges (U.S. Patent Application No. 2015/0038594, publication year: 2015) teaches that the pH of oral thin films is involved in the dissolution and stability of the components in the formulation [0022], therefore this relationship appears to have been recognized as of the instant effective filing date. The effect of buffers and buffer systems, i.e. to raise or lower pH, is well understood in the art. It would follow that a buffer system, and therefore the weight percentages of citric acid/sodium citrate, would have a direct effect on the dissolution and stability of the components of the formulation. Regarding the weight percentages of citric acid and sodium citrate in the instant claim 1, the Examiner draws attention to MPEP 2144.05, which states: “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. Therefore, the teachings of Boyer and Maibach, as described in the obviousness rejection of claim 1 above, render obvious the claimed weight ranges of citric acid and sodium citrate in the instant claim 1.
Differences are of both practical and statistical significance: The evidence presented in the instant specification amounts to an improved dissolution and stability in naratriptan films, therefore the differences are of practical significance. However, the evidence provided in the examples of the instant specification provide no data demonstrating the criticality of the weight percentages of sodium citrate and citric acid to the demonstrated improved dissolution and stability of naratriptan films and no statistical analysis of the dissolution rates or stability data presented. Therefore, the differences are not of statistical significance.
Evidence of unexpected properties must be in commensurate scope with the claims: The evidence of unexpected properties amounts to the dissolution of the drug from the film and improved stability of the drug in the film, therefore the evidence of unexpected properties is commensurate in scope with the claims.
Additionally, no side-by-side comparison to the closest prior art is provided to establish unexpectedly superior performance. Table 4 of the instant specification details the dissolution of Example 1, a thin film comprising a citric acid/sodium citrate buffer system and Table 5 details the accelerated stability data for Examples 1 and 2 compared to tableted naratriptan. There is no nexus between the purportedly unexpected property and the differences between the instant invention, as claimed, and the closest prior art. Thus, the Applicant’s argument is not persuasive and the rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ANNE MEYERS whose telephone number is (571)272-2271. The examiner can normally be reached Monday-Friday 8am-5pm ET.
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ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617