DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8, 2026 has been entered.
Claims 50-51, 53-69 are pending.
Claims 50-51, 53-69 are herein acted on the merits.
Notice of Pre-AlA 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 .
Application Priority
This application filed 06/15/2023, is a CON of PAT 11717501 filed on 04/24/2019, which claims priority to PRO 62/662,756 filed 04/25/2018.
Response to Arguments
Applicant’s arguments over the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph of claims 70-71 is persuasive in view of cancellation of the claims. The rejection is withdrawn.
Applicant’s arguments over the 35 U.S.C. 103(a) rejection of claims 50-51, 53-71 over Liu et al. (US 20130236542 - IDS) ) in view of Wang et al.( Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations. Acta Pharmacol Sin 32, 1555–1560 (2011). https://doi.org/10.1038/aps.2011.138) is not persuasive. The rejection is maintained. Applicant’s main argument is that the prior art references are silent on the FI of the formulation and further that a FI of less than about 170% results in unexpectedly improved mood and cognition in subjects. In response, the Examiner points out that it is not clear that Liu's formulation teach away from a formulation that reads on the claims. Specifically, Applicant did not make a single formulation of Liu wherein the FI is over the value argued. The arguments are not persuasive.
The ODP rejections depend on the validity of the arguments above, which were not found persuasive. The rejections are herewith maintained.
The following rejections are made:
Claim Rejections - 35 USC § 103
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.
Claim(s) 50-51, 53-69 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 20130236542 - IDS) in view of Wang et al.( Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations. Acta Pharmacol Sin 32, 1555–1560 (2011). https://doi.org/10.1038/aps.2011.138).
Liu et al. teaches extended or modified release oral formulation can be prepared using additional methods known in the art. For example, a suitable extended release form of the magnesium threonate (abstract) compositions provided herein may be a matrix tablet or capsule composition. The magnesium-counter ion composition and/or a method described herein are useful for various purposes, such as maintaining, enhancing, and/or improving health, nutrition, and/or another condition of a subject, and/or cognitive, learning, and/or memory function, for example. Suitable matrix forming materials include, for example, waxes (e.g., carnauba, bees wax, paraffin wax, ceresine, shellac wax, fatty acids, and fatty alcohols), oils, hardened oils or fats (e.g., hardened rapeseed oil, castor oil, beef tallow, palm oil, and soya bean oil), and polymers (e.g., hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, and polyethylene glycol). the formulations described herein, when administered at a substantially constant daily dose, e.g., at a dose ranging between 50 mg and 1000 mg, preferably between 100 mg and 800 mg, and more preferably between 200 mg and 700 mg per day of elemental Mg [0063].The reference teaches supplement has generally been about 200-250 mg per day for adults supplement has generally been about 200-250 mg per day for adults. In some embodiments, the dissolution medium is a saline solution. In some embodiments, the oral dosage form further comprises a polymer binder mixed with the magnesium (Mg) and threonate (T). In some embodiments, the polymer comprises polyvinylpyrrolidone. In some embodiments, the oral dosage form further comprises a pharmaceutically acceptable amount of magnesium stearate. In some embodiments, the oral dosage form further comprises of one or more of polyvinylpyrrolidone, polyvinyl acetate, or propylene glycol. In addition to the active ingredients comprising magnesium and threonate, the oral dosage forms of the present invention can comprise any numbers of physiologically acceptable excipients, depending in part on the controlled release mechanism to be used. “Physiologically Acceptable” includes molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or a human, as appropriate, e.g., those that are pharmaceutically acceptable. “Physiologically Acceptable Carrier” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for physiologically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the magnesium threonate compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. “Physiologically Acceptable Salts” include acid addition salts and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like. General techniques for formulation and administration are found in “Remington: The Science and Practice of Pharmacy, Twentieth Edition,” Lippincott Williams & Wilkins, Philadelphia, Pa. Tablets, capsules, pills, powders, granules, dragees, gels, slurries, ointments, solutions suppositories, injections, inhalants and aerosols are examples of such formulations. Further the composition may contain an insoluble matrix polymer (approximately 15-85% by weight of the coating composition) and a water soluble material (e.g., approximately 15-85% by weight of the coating composition). Optionally an enteric polymer (approximately 1 to 99% by weight of the coating composition) may be used or included. Suitable water soluble materials include polymers such as polyethylene glycol, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, and monomeric materials such as sugars (e.g., lactose, sucrose, fructose, mannitol and the like), salts (e.g., sodium chloride, potassium chloride and the like), organic acids (e.g., fumaric acid, succinic acid, lactic acid, and tartaric acid), and mixtures thereof. Suitable enteric polymers include hydroxypropyl methyl cellulose, acetate succinate, hydroxypropyl methyl cellulose, phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, shellac, zein, and polymethacrylates containing carboxyl groups. Liu et al. teaches the optimal dosage can be dependent on the subject. In some embodiments, the subject is a human. In such embodiment, the dosage can be optimized to treat a condition in a human. [0154] In some embodiments, the oral dosage forms of the present invention is administered to a subject at a dose less than about 2 mg elemental magnesium/kg/day, less than about 4 mg elemental magnesium/kg/day, less than about 6 mg elemental magnesium/kg/day, less than about 8 mg elemental magnesium/kg/day, less than about 10 mg elemental magnesium/kg/day, or less than about 12 mg elemental magnesium/kg/day. In some embodiments, the oral dosage forms of the present invention are administered to a subject at a dose more than about 2 mg elemental magnesium/kg/day, more than about 4 mg elemental magnesium/kg/day, more than about 6 mg elemental magnesium/kg/day, more than about 8 mg elemental magnesium/kg/day, more than about 10 mg elemental magnesium/kg/day, or more than about 12 mg elemental magnesium/kg/day. The optimal dosage can depend on the subject. In some embodiments, the subject is a human. In such an embodiment, the dosage can be optimized to treat a condition in a human.
While Liu et al. does not specify the fluctuation index, the mean AUC, the mean Tmax, a skewness that is less than about 0.2, the mean fluctuation value, the ratio of mean fluctuation value to Cmin, and in vivo plasma profile of threonic acid comprising a mean Cavg of 4.1±0.2, 5.6±0.3, 6.1±0.3, or 8.3±0.4, of the formulation.
Wang et al. teaches monitoring plasma levels of calcium L-threonate. The reference teaches pharmacokinetics of L-threonate was assessed between the fasted and fed subjects. Further, Wang et al. teaches:
Pharmacokinetic analysis was performed with WinNonlin software (Pharsight 4.0.1; NC, USA) utilizing non-compartmental analysis. The maximum plasma drug concentration (Cmax) and time to Cmax (tmax) were directly obtained from the plasma concentration-time curves. The terminal-phase elimination half-life (t1/2) was calculated as 0.693/λz, where λz was the slope of the apparent elimination phase of the natural logarithmic (ln) transformation of the plasma concentration-time curve, which was estimated using liner regression. The area under the plasma concentration-time curve from time zero to t (AUC0–t), where t is the time of last measurable sample, was calculated according to the linear trapezoidal rule. The AUC from time zero to infinity (AUC0–∞) was estimated as AUC0–t+Ct/λz, where Ct was the plasma concentration of the last measurable sample. Apparent total clearance (Cl/F) was calculated as Dose/AUC0–∞ or Dose/AUCss and apparent total volume of distribution (Vz/F) as calculated as CL/λz. Renal clearance was estimated as Au0–t/AUC0–t, where Au0–t was the cumulative amount of drug excreted in urine from time zero to t (24 h). Attainment of steady state by d 7 was evaluated by regressing the natural logarithmic (ln) transformation of trough concentrations on d 3, 4, 5, and 6 over time. Steady-state was attained if the slope was not statistically different from zero. The steady-state AUCs (AUCss) over the dosing interval (τ=12 h) and Cavg (AUCss/τ) were calculated. The degree of fluctuation (DF%) was calculated as (Cmax–Cmin)/Cavg×100%. Accumulation ratios were defined as the steady-state AUC0–τ to the single-dose AUC0–τ ratio or the steady state Cmax to the single-dose Cmax ratio, namely, RAUC= AUC0–τ (steady state)/AUC0–τ (single-dose) (τ=12 h) and RCmax=Cmax (steady state)/Cmax (single-dose), respectively.
The reference teaches “there was a statistically significant difference between the fasted and fed groups using a paired t test (P<0.05); therefore, it was concluded that the absorption of L-threonate was improved by food intake.”
It would have been obvious to one of ordinary skill at the time of filing to test the PK parameters of the L-threonate. The motivation to test a PK parameter is because the assessment of drug behavior allows for drawing conclusions on dosing parameters such as the findings that “L-threonate was absorbed rapidly and exhibited dose-related plasma exposure. After reaching peak exposure, this drug was quickly cleared from the plasma, but renal excretion was not its major elimination route. The absorption of L-threonate was enhanced by food intake, and there was no accumulation after multiple administrations.” Therefore, a skilled artisan would have reasonable expectation of successfully concluding behaviors such as absorption, dose-related plasma exposure, clearance, and excretion for dosing purposes.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 50-51, 53-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. US 9757414 B2, US 9737563 B2, US 9616038 B2, US 9125878 B2, US 8637061 B2, US 8470352 B2, US 8178132 B2, US 8178118 B2, US 8178133 B2, US 8163301 B2, US 8142803 B2, US 8734855 B2 US 8377473 B2, US 9937137 B2, US 10493048 B2, US 10617713 B2, US 11298330, B2, and 11278567. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a formulation or method of administering magnesium threonate to a subject.
Absent evidence to the contrary, the composition would obviously have a similar PK parameters (including the fluctuation index, the mean AUC, the mean Tmax, a skewness that is less than about 0.2, the mean fluctuation value, the ratio of mean fluctuation value to Cmin, and in vivo plasma profile of threonic acid comprising a mean Cavg of 4.1±0.2, 5.6±0.3, 6.1±0.3, or 8.3±0.4) as the compositions set forth in the instant application, as they are sustained release formulations with the identical active.
Claims 50-51, 53-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 17/194,733, 18/077,931, 18/200,410, 18/210,515, 18/226,711, 18/410,786, 18/605,368, 18/673,605 and 18/807,412 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a formulation or method of administering magnesium threonate to a subject.
Absent evidence to the contrary, the composition would obviously have a similar PK parameters (including the fluctuation index, the mean AUC, the mean Tmax, a skewness that is less than about 0.2, the mean fluctuation value, the ratio of mean fluctuation value to Cmin, and in vivo plasma profile of threonic acid comprising a mean Cavg of 4.1±0.2, 5.6±0.3, 6.1±0.3, or 8.3±0.4) as the compositions set forth in the instant application, as they are sustained release formulations with the identical active.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA SOROUSH whose telephone number is (571)272-5008. The examiner can normally be reached on Monday thru Friday; 8:30 AM to 5:00 PM EST.
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622
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