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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 January 23, 2026, that includes a response to the Final Office Action mailed July 23, 2025, has been entered. Claims 51 and 53 have been amended; claims 1-50, 52, 55, and 64 have been canceled; and no claims have been newly added. Claims 65-68 have been withdrawn. Claims 51, 53, 54 and 56-63 are currently under examination.
Withdrawal of Prior Objection - Abstract
The abstract has been satisfactorily amended. Therefore, the objection to the abstract presented in the Final Office Action mailed July 23, 2025 is hereby withdrawn.
Withdrawal of Prior Claim Objections
Claims 51 and 53 have been satisfactorily amended. Therefore, the objections to these claims presented in the Final Office Action mailed July 23, 2025 are hereby withdrawn.
Withdrawal of Prior Claim Rejections - 35 USC § 112(b)
Claim 55 has been canceled; and claims 51 and 53 have been satisfactorily amended. Therefore, the 35 USC 112(b) rejection presented in the Final Office Action mailed July 23, 2025 is hereby withdrawn.
Claim Rejections - 35 USC § 103 (I and II)
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 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.
I. Claims 51, 53, 54, and 56-61 are rejected under 35 U.S.C. 103 as being unpatentable over Brittain et al. (U.S. Patent Application Pub. No. 2010/0286099), in view of Wiehl et al. (U.S. Patent Application Pub. No. 2007/0048375), and Amer (U.S. Patent No. 4,866,046).
I. Applicant Claims
Applicant’s elected subject matter is directed to a method of treating acute myocardial infarction in a subject in need thereof comprising administering to the subject an orally disintegrating tablet comprising aspirin, L-theonine, citric acid, and sodium bicarbonate in the amounts of 300-450 mg (20-30 wt%), 300-450 mg (20-30 wt%), 75-200 mg (5-15 wt%), and 200-350 mg (15-25 wt%), respectively; wherein the aspirin, L-theanine, citric acid, and sodium bicarbonate are in the form of a cocrystal.
I. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Brittain et al. disclose a method of treating e.g. myocardial infarction in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising a rapidly water-soluble aspirin (i.e. acetylsalicylic acid)-theanine cocrystal, wherein the amount of aspirin is e.g. 352-435 mg and the amount of theanine is e.g. 340-424 mg; wherein the pharmaceutical composition can be in the form of e.g. an orally-disintegrating tablet for e.g. sublingual administration; wherein the theanine can be e.g. L-theanine; and wherein the composition can further contain e.g. sodium bicarbonate, and can be in the form of e.g. a quick-dissolve effervescent tablet (abstract; paragraphs 0002, 0003, 0021-0023, 0026, 0028, 0037, 0060, 0062, 0084, 0115, 0116-0119, 0121).
Wiehl et al. disclose an effervescent pharmaceutical composition, e.g. tablet, for the treatment of diseases that can comprise e.g. aspirin (i.e. acetylsalicylic acid); wherein the tablet is made effervescent by the combination of a basic component and an acidic component; the basic component is preferably e.g. sodium bicarbonate, and is present in the amount most preferably of 2-10 mmols (i.e. for sodium bicarbonate, with MW 84 g/mol, this is equivalent to 168-840 mg sodium bicarbonate); the acidic component can be e.g. citric acid, and when citric acid is employed with e.g. sodium bicarbonate, the ratio of citric acid to sodium bicarbonate is not more than 1:3. Hence, at a 1:3 ratio of citric acid to sodium bicarbonate (i.e. 168-840 mg), the amount of citric acid would range from about 56-280 mg. (abstract; paragraphs 0014, 0015, 0019-0024, 0027, 0029, 0038, 0042; Example 7).
Amer discloses that an orally-disintegrating tablet containing aspirin is preferably sublingually administered to a patient for the treatment of myocardial infarction since the aspirin is rapidly absorbed from the saliva into the blood system, enabling improved control and suppression of the myocardial infarction by more rapid and efficient inhibition of platelet aggregation, with minimal to no stomach irritation and ulcers (see e.g. abstract; Col. 2, lines 41-67; Col. 4, lines 30-68).
I. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Brittain et al. do not explicitly disclose that an effervescent tablet is made effervescent by the combination of e.g. sodium bicarbonate and citric acid, and that the preferred route of delivery of an aspirin-containing, orally-disintegrating tablet for treatment of myocardial infarction is sublingually. These deficiencies are cured by the teachings of Wiehl et al. and Amer.
I. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Brittain et al., Wiehl et al., and Amer, outlined supra, to devise Applicant’s claimed method.
Brittain et al. disclose a method of treating e.g. myocardial infarction in a subject in need thereof comprising administering to the subject e.g. an orally-disintegrating tablet comprising a rapidly water-soluble aspirin (i.e. acetylsalicylic acid)-L-theanine cocrystal, wherein the amount of aspirin is e.g. 352-435 mg and the amount of theanine is e.g. 340-424 mg; wherein the composition can further contain e.g. sodium bicarbonate for an effervescent tablet. Since Wiehl et al. disclose, regarding an effervescent tablet comprising e.g. acetylsalicylic acid (i.e. aspirin), that the tablet is made effervescent by the combination of a basic component and an acidic component, preferably e.g. sodium bicarbonate present in the amount most preferably of 2-10 mmols (i.e. for sodium bicarbonate, with MW 84 g/mol, this is equivalent to 168-840 mg sodium bicarbonate), and e.g. citric acid, wherein the ratio of citric acid to sodium bicarbonate is not more than 1:3, and thus at a 1:3 ratio of citric acid to sodium bicarbonate (i.e. 168-840 mg), the amount of citric acid would range from about 56-280 mg; one of ordinary skill in the art would thus understand Brittain’s “effervescent tablet”, will contain, in addition to the rapidly water-soluble acetylsalicylic acid-theanine cocrystal, the combination of about 168-840 mg sodium bicarbonate and about 56-280 mg citric acid to thus be effervescent.
Further, since Brittain et al. disclose specifically an aspirin/L-theonine cocrystal, and more broadly that cocrystals can improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties of active agents; since Brittain et al. disclose that any molecule that can participate in hydrogen bonding is predisposed to formation of cocrystals; and since one of ordinary skill in the art would recognize that both citric acid and bicarbonate can participate in hydrogen bonding, one of ordinary skill in the art would thus be motivated to combine all of aspirin, L-theonine, citric acid, and sodium bicarbonate in a cocrystal, with the reasonable expectation that the resulting cocrystal will improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties of the active agent.
Moreover, since Amer discloses that an orally-disintegrating tablet containing aspirin is preferably sublingually administered to a patient for the treatment of myocardial infarction since the aspirin is rapidly absorbed from the saliva into the blood system, enabling improved control and suppression of the myocardial infarction by more rapid and efficient inhibition of platelet aggregation, with minimal to no stomach irritation and ulcers; one of ordinary skill in the art would thus be motivated to sublingually administer the Brittain et al. orally-disintegrating tablet comprising a rapidly water-soluble aspirin, with the reasonable expectation that the resulting method will more rapidly and efficiently treat myocardial infarction, with minimal to no stomach irritation and ulcers.
In Wiehl et al., example 7, the weight percentage amounts of acetylsalicylic acid, citric acid, and sodium bicarbonate are 500 mg/2160 mg, 180 mg/2160 mg, and 450 mg/2160 mg, respectively, or 23 wt%, 8 wt%, and 21 wt%, which fall within the claimed ranges. Further, in view of Brittain et al., one of ordinary skill in the art would understand to employ about the same amounts of acetylsalicylic acid and theanine in the composition (see examples), and thus one of ordinary skill in the art would be motivated to employ about 23 wt% theanine as well.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
II. Claims 62 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Brittain et al. (U.S. Patent Application Pub. No. 2010/0286099), in view of Wiehl et al. (U.S. Patent Application Pub. No. 2007/0048375), Amer (U.S. Patent No. 4,866,046), and Desai et al. (AAPS PharmSciTech. 2014; 15(5): 1093-1104).
II. Applicant Claims
Applicant’s elected subject matter is directed to a method of treating acute myocardial infarction in a subject in need thereof comprising administering to the subject an orally disintegrating tablet comprising aspirin, L-theonine, citric acid, and sodium bicarbonate in the amounts of 20-30 wt%, 20-30 wt%, 5-15 wt%, and 15-25 wt%, respectively; wherein the aspirin, L-theanine, citric acid, and sodium bicarbonate are in the form of a cocrystal.
II. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Brittain et al. disclose a method of treating e.g. myocardial infarction in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising a rapidly water-soluble aspirin (i.e. acetylsalicylic acid)-theanine cocrystal, wherein the amount of aspirin is e.g. 352-435 mg and the amount of theanine is e.g. 340-424 mg; wherein the pharmaceutical composition that can be in the form of e.g. an orally-disintegrating tablet for e.g. sublingual administration; wherein the theanine can be e.g. L-theanine; and wherein the composition can further contain e.g. sodium bicarbonate, and can be in the form of e.g. a quick-dissolve effervescent tablet (abstract; paragraphs 0002, 0003, 0021-0023, 0026, 0028, 0037, 0060, 0062, 0084, 0115, 0116-0119, 0121).
Wiehl et al. disclose an effervescent pharmaceutical composition, e.g. tablet, for the treatment of diseases that can comprise e.g. aspirin (i.e. acetylsalicylic acid); wherein the tablet is made effervescent by the combination of a basic component and an acidic component; the basic component is preferably e.g. sodium bicarbonate, and is present in the amount most preferably of 2-10 mmols (i.e. for sodium bicarbonate, with MW 84 g/mol, this is equivalent to 168-840 mg sodium bicarbonate); the acidic component can be e.g. citric acid, and when citric acid is employed with e.g. sodium bicarbonate, the ratio of citric acid to sodium bicarbonate is not more than 1:3. Hence, at a 1:3 ratio of citric acid to sodium bicarbonate (i.e. 168-840 mg), the amount of citric acid would range from about 56-280 mg. (abstract; paragraphs 0014, 0015, 0019-0024, 0027, 0029, 0038, 0042; Example 7).
Amer discloses that an orally-disintegrating tablet containing aspirin is preferably sublingually administered to a patient for the treatment of myocardial infarction since the aspirin is rapidly absorbed from the saliva into the blood system, enabling improved control and suppression of the myocardial infarction by more rapid and efficient inhibition of platelet aggregation, with minimal to no stomach irritation and ulcers (see e.g. abstract; Col. 2, lines 41-67; Col. 4, lines 30-68).
Desai et al. disclose a pharmaceutical composition that can be in the form of e.g. a fast, orally-disintegrating tablet, comprising aspirin (i.e. acetylsalicylic acid) and a disintegrant; wherein the disintegrant can be crospovidone (i.e. crosslinked polyvinylpyrrolidone) in the amount of up to about 8 wt%, wherein disintegration time decreased when the crospovidone concentration increased up to 8 wt% (beyond which disintegration time increased), but tablet hardness also decreased when the crospovidone concentration increased.
II. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Brittain et al. do not explicitly disclose that an effervescent tablet is made effervescent by the combination of e.g. sodium bicarbonate and citric acid; that the preferred route of delivery of an aspirin-containing, orally-disintegrating tablet for treatment of myocardial infarction is sublingually; and that the tablet further contains crosslinked polyvinylpyrrolidone. These deficiencies are cured by the teachings of Wiehl et al., Amer, and Desai et al.
II. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Brittain et al., Wiehl et al., Amer, and Desai et al., outlined supra, to devise Applicant’s presently claimed method.
Brittain et al. disclose a method of treating e.g. myocardial infarction in a subject in need thereof comprising administering to the subject e.g. an orally-disintegrating tablet comprising a rapidly water-soluble aspirin (i.e. acetylsalicylic acid)-L-theanine cocrystal, wherein the amount of aspirin is e.g. 352-435 mg and the amount of theanine is e.g. 340-424 mg; wherein the composition can further contain e.g. sodium bicarbonate for an effervescent tablet. Since Wiehl et al. disclose, regarding an effervescent tablet comprising e.g. acetylsalicylic acid (i.e. aspirin), that the tablet is made effervescent by the combination of a basic component and an acidic component, preferably e.g. sodium bicarbonate present in the amount most preferably of 2-10 mmols (i.e. for sodium bicarbonate, with MW 84 g/mol, this is equivalent to 168-840 mg sodium bicarbonate), and e.g. citric acid, wherein the ratio of citric acid to sodium bicarbonate is not more than 1:3, and thus at a 1:3 ratio of citric acid to sodium bicarbonate (i.e. 168-840 mg), the amount of citric acid would range from about 56-280 mg; one of ordinary skill in the art would thus understand Brittain’s “effervescent tablet”, will contain, in addition to the rapidly water-soluble acetylsalicylic acid-theanine cocrystal, the combination of about 168-840 mg sodium bicarbonate and about 56-280 mg citric acid to thus be effervescent.
Further, since Brittain et al. disclose specifically an aspirin/L-theonine cocrystal, and more broadly that cocrystals can improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties of active agents; since Brittain et al. disclose that any molecule that can participate in hydrogen bonding is predisposed to formation of cocrystals; and since one of ordinary skill in the art would recognize that both citric acid and bicarbonate can participate in hydrogen bonding, one of ordinary skill in the art would thus be motivated to combine all of aspirin, L-theonine, citric acid, and sodium bicarbonate in a cocrystal, with the reasonable expectation that the resulting cocrystal will improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties of the active agent.
Moreover, since Amer discloses that an orally-disintegrating tablet containing aspirin is preferably sublingually administered to a patient for the treatment of myocardial infarction since the aspirin is rapidly absorbed from the saliva into the blood system, enabling improved control and suppression of the myocardial infarction by more rapid and efficient inhibition of platelet aggregation, with minimal to no stomach irritation and ulcers; one of ordinary skill in the art would thus be motivated to sublingually administer the Brittain et al. orally-disintegrating tablet comprising a rapidly water-soluble aspirin, with the reasonable expectation that the resulting method will more rapidly and efficiently treat myocardial infarction, with minimal to no stomach irritation and ulcers.
Further still, since Desai et al. disclose that crospovidone can be employed in a rapid, orally-disintegrating aspirin tablet up to a concentration of about 8 wt%, wherein increased crospovidone concentration up to this maximum amount provides faster disintegration time but decreased tablet hardness; one of ordinary skill in the art would thus be motivated to employ crospovidone (i.e. crosslinked polyvinylpyrrolidone) at an amount up to about 8 wt% to improve rapid disintegration and also maintain optimal tablet hardness, with the reasonable expectation of success that the resulting tablet will rapidly disintegrate in and deliver a therapeutic amount of acetylsalicylic acid to the oral cavity.
In Wiehl et al., example 7, the weight percentage amounts of acetylsalicylic acid, citric acid, and sodium bicarbonate are 500 mg/2160 mg, 180 mg/2160 mg, and 450 mg/2160 mg, respectively, or 23 wt%, 8 wt%, and 21 wt%. Further, in view of Brittain et al., one of ordinary skill in the art would understand to employ about the same amounts of acetylsalicylic acid and theanine in the composition (see examples), and thus one of ordinary skill in the art would be motivated to employ about 23 wt% theanine as well. Finally, from Desai et al., crospovidone can be employed in a rapid, orally-disintegrating aspirin tablet up to a concentration of about 8 wt%, which would be up to about 173 mg. One of ordinary skill in the art would be able to optimize the dosage within the range of “up to about 173 mg” to achieve the optimal improvement in disintegration time while best maintaining tablet hardness.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed January 23, 2026 have been fully considered but they are not persuasive.
i) Applicant contends that “nowhere do either Brittain, Wiehl, and/or Amer teach or suggest a cocrystal containing aspirin, L-theonine, citric acid, and sodium bicarbonate simultaneously”; that “cocrystal formation is recognized as highly unpredictable” and “cocrystal discovery and optimization remain largely empirical, requiring experimental screening rather than routine prediction or straightforward formulation design”.
The Examiner, however, would like to point out the following:
1. Even assuming, arguendo, that the art of cocrystal formulation generally remains largely empirical for any random set of compounds, requiring experimental screening rather than routine prediction or straightforward formulation design, the issue in this specific case comes down to whether it would have been within the skill of the ordinary mechanic in the art to arrive at a cocrystal containing aspirin, L-theonine, citric acid, and sodium bicarbonate.
2. Brittain, the cited primary reference, discloses a rapidly water-soluble aspirin-L-theanine cocrystal, and further discloses that their composition can also contain e.g. sodium bicarbonate for an effervescent tablet. One of ordinary skill in the art would understand that a tablet is made effervescent by the combination of a basic component and an acidic component, and in this particular case these are sodium bicarbonate and citric acid.
3. Not only does Brittain disclose specifically an aspirin/L-theonine cocrystal, Brittain further teaches more broadly that cocrystals can improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties, of active agents; and that any molecule that can participate in hydrogen bonding is predisposed to formation of cocrystals. One of ordinary skill in the art would recognize that both citric acid and bicarbonate can participate in hydrogen bonding. Certainly, then, there is a motivation for one of ordinary skill in the art to combine all of aspirin, theonine, citric acid, and sodium bicarbonate in a cocrystal to thus improve the solubility, stability, and dissolution rate, and otherwise generally improve the chemical and physical properties of the active agent. The aspirin and theonine are already in the form of a cocrystal, and it would be within the skill of the ordinary mechanic in the art to further include citric acid and bicarbonate based on their ability to form hydrogen bonds. Applicant has provided no evidence to the contrary.
4. According to paragraph [0013] of the present disclosure, cocrystals are mixed crystals where the cocrystal is a structurally homogeneous crystalline material that has been formed from discrete neutral molecular species that are solids at ambient temperature. Cocrystals are characterized by two or more molecules that associate but do not bond on the molecular level.
5. Hence, to the extent that a cocrystal is a mixture of crystals that do not necessarily rely in hydrogen bonds, it is further noted that one of ordinary skill in the art would know that both citric acid and sodium bicarbonate can exist in crystal form, see e.g. Paradkar et al., U.S. Patent Application Pub. No. 2017/0128359; and Gerard et al. Powder Tech. 2014; 255: 134-140. It would be within the skill level of the ordinary mechanic in the art to form a mixture of the aspirin/L-theonine cocrystal, the citric acid cocrystal, and the sodium bicarbonate crystal. Applicant has provided no evidence to the contrary.
For the foregoing reasons, the 35 USC 103 rejections are hereby maintained.
Conclusion
No claims are allowed.
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/DAVID BROWE/Primary Examiner, Art Unit 1617