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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 22, 2025 has been entered.
Claims 1-11 and 13-17 are currently pending and are examined on the merits herein.
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 .
Priority
This application filed 03/07/2024 is a CON of PAT 11957685 filed on 08/10/2023 which is a CON of PAT 11766438 filed on 04/23/2021 which claims foreign priority to INDIA 202041017604 filed 04/24/2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 3/7/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
Response to Arguments
The rejection of claims 1, and 4-5 under 35 U.S.C. 102(a)(1) as being unpatentable over Younis et al. (Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma, AAPS PharmSciTech (2019) 20: 167) is not persuasive. The rejection is herewith maintained. The Applicant argues and provides a Declaration on 7/22/2025, the formulation claimed consisting essentially of the recited limitations, free from precipitation and palatable oral solution. The Applicant argues the continuation was allowed in view of the Dube Declaration filed on 4/28/23.
The Examiner points out that the claims were not allowable due to the drug product being palatable, but due to unexpected results provided in the Application with respect to different claimed limitations. While Applicant contends that Younis et al. does not show a solution that is physically stable and free from ppt, nor the criticality of the pH range, the Examiner points to Younis’ teaching that the tofacitinib solution is soluble at a pH of 3.5, and was so stable that the natural logarithm of the degradation rate constants for pH 2.0 through pH 5.0 could not be calculated due to the samples essentially having zero degradation over the course of the study. (p. 167 left para.). These teachings point to precipitate free and stable formulations. Applicant argues the testing conditions of stability for 40C/75% RH for 3 months is not disclosed in Younis. However, the Examiner points out when the formulation is identical to that claim – that is, consisting of the same active, same carrier, and same pH – the stability would not be different. Lastly, the Examiner points out the Declaration 7/22/2025 argues criticality of limitations not claimed.
The rejection of claims 1, and 4-5 under 35 U.S.C. 102(a)(1) as being unpatentable over Chen (US 2019 / 0231782 A1) is persuasive. The rejection is withdrawn.
The rejection of claims 1-13 under 35 U.S.C. 103 as being unpatentable over Chen (US 2019 / 0231782 A1) is persuasive. The rejection is withdrawn.
The rejection of claims 1-13 under 35 U.S.C. 103 as being unpatentable over Younis et al. (Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma) in view of Xie et al. (CN 109893502 - previously cited) is not persuasive. The rejection is herewith maintained. Applicant argues the Xie reference relates to an oral solution, while the Younis reference is an inhalation delivery. The Examiner points out that Younis et al. is relied on for its preformulation studies on tofacitinib citrate not on an inhalation formulation. The arguments are not persuasive.
Applicant’s state that the provisional ODP rejection be held in abeyance until patentable subject matter is determined. The rejection is herewith maintained.
The following rejections are made:
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Younis et al. (Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma, AAPS PharmSciTech (2019) 20: 167).
The claims read on a stable oral solution of tofacitinib consisting essentially of: tofacitinib at a concentration of about 1 mg/mL; optionally, one or more antioxidants; and a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof: wherein a pH of the solution ranges from 3.5 to 5.0; wherein the solution is free from precipitation when said solution is stored at 40°C/75% RH for 3 months; and wherein said solution is a palatable oral solution.
Younis et al. teaches preformulation studies on tofacitinib citrate, and its free base, to better understand factors that affect its solubility, stability, and solid-state characteristics. (abstract) The reference teaches tofacitinib solution at pH 3.5 having a solubility of 1.8 mg/mL. (p. 166 para. pH Solubility Profile). The aqueous solution includes ethanol. Tofacitinib was so stable that the natural logarithm of the degradation rate constants for pH 2.0 through pH 5.0 could not be calculated due to the samples essentially having zero degradation over the course of the study. (p. 167 left para.)
With respect to the solution is free from ppt when said solution is stored at 40°C/75% RH for a period of 3 months, the level of total impurities in the composition solution is less than 1.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months, and a level of Impurity B in the solution is less than 0.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months recited in the claims, Applicant is informed that a prior art composition that comprise all elemental components of the instantly created composition would meet all functional characteristics of the created composition, because such characteristics are inseparable from the composition. Younis et al. meets all elemental steps of the instant claims and the composition created thereof. Since Younis et al.'s compositions comprise all elemental components of the instantly prepared composition, they would inherently exhibit the same properties as those instantly claimed, because such functional characteristics of the created composition is inseparable from the describe composition of Younis et al. With respect to claim 22, the milligram equivalence of tofacitinib citrate and tofacitinib of 1.62, is inherent as the same tofacitinib is taught.
Claims 1, 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by over Xie et al. (CN 109893502 - previously cited).
Xie et al. teaches 1 mg/mL tofacitinib citrate (claim 1), the pH of the resulting solution to pH of 4.0-5.5 (claim 1), a preservative (claim 2), flavoring agent (claim 2), and water (claim 1).
With respect to the solution is free from ppt when said solution is stored at 40°C/75% RH for a period of 3 months, the level of total impurities in the composition solution is less than 1.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months, and a level of Impurity B in the solution is less than 0.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months recited in the claims, Applicant is informed that a prior art composition that comprise all elemental components of the instantly created composition would meet all functional characteristics of the created composition, because such characteristics are inseparable from the composition.
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 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.
Claims 1-11 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Younis et al. (Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma) in view of Xie et al. (CN 109893502 - previously cited).
Younis et al. teaches preformulation studies on tofacitinib citrate, and its free base, to better understand factors that affect its solubility, stability, and solid-state characteristics. (abstract) The reference teaches tofacitinib solution at pH 3.5 having a solubility of 1.8 mg/mL. (p. 166 para. pH Solubility Profile) Tofacitinib was so stable that the natural logarithm of the degradation rate constants for pH 2.0 through pH 5.0 could not be calculated due to the samples essentially having zero degradation over the course of the study. (p. 167 left para.)
With respect to the respect to the solution is free from ppt when said solution is stored at 40°C/75% RH for a period of 3 months, the level of total impurities in the composition solution is less than 1.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months, and a level of Impurity B in the solution is less than 0.5 % w/w as measured by HPLC, when said composition is stored at 40°C/75% RH for a period of 3 months recited in the claims, Applicant is informed that a prior art composition that comprise all elemental components of the instantly created composition would meet all functional characteristics of the created composition, because such characteristics are inseparable from the composition. Younis et al. meets all elemental steps of the instant claims and the composition created thereof. Since Younis et al.'s compositions comprise all elemental components of the instantly prepared composition, they would inherently exhibit the same properties as those instantly claimed, because such functional characteristics of the created composition is inseparable from the describe composition of Younis et al.
While the reference teach the tofacitinib solution at pH 3.5 having a solubility of 1.8 mg/mL, the reference does not specify a formulation with a pH 3.5- 4.5 containing the specific solvent and antioxidant ingredients.
Xie et al. teaches a tofacitinib citrate oral solution and its preparation method, which has better stability, and is suitable for children and elderly people with dysphagia. The oral solution comprises tofacitinib citrate, pH regulator, preservative and flavoring agent. Water is used as a solvent in the oral solution to bring the composition to 1000mL. In one embodiment, the pH adjuster used in the tofacitib citrate oral solution is selected from: hydrochloric acid, acetic acid, citric acid, phosphoric acid, fumaric acid, tartaric acid(for example, reads on anti-oxidant), lactic acid, succinic acid, sorbic acid, propionic acid, maleic acid, triethylamine, sodium hydroxide, sodium tartrate, arginine, sodium citrate and the like and combinations thereof. The amount of the pH adjusting agent is an amount that enables the pH of the solution to reach the range of 2.5-6.5 , for example, to make the pH value reach 3.0-6.0, or to make the pH value reach the amount of 4.0-5.5. The samples marked as Ex1 and Ex2 were placed at 40 °C, and the RH was 25% + 5% for investigation for 6 months. The embodiments describe the use of purified water.
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate an antioxidant and solvent in a tofacitinib formulation having a pH of 4.5. The motivation comes from the teaching in Younis of solvents and that tofacitinib was so stable that the natural logarithm of the degradation rate constants for pH 2.0 through pH 5.0 could not be calculated, and from Xie’s teaching of the specific solvents and antioxidants in a tofacitinib formulation with overlapping pH. Hence, a skilled artisan would have had reasonable expectation that incorporating an antioxidant and solvent and maintaining the pH of 4.5 would successfully achieve similar efficacy and results.
Claims 1-11 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (CN 109893502 - previously cited).
Xie et al. teaches 1 mg/mL tofacitinib citrate, the pH of the resulting solution to 4.0-5.5, a preservative (claim 2), flavoring agent (claim 2), and water.
While Xie et al. does teach pH adjusting agent selected from tartaric acid, the reference does not specify an amount or ratio as claimed.
It would have been obvious to one of ordinary skill in the art at the time of filing to modify amounts of the actives to anti-oxidants, as claimed. Differences in concentration/ratio will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). Therefore, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
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 1-11 and 13-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. US 11957685 B2. Although the claims at -issue are not identical, they are not patentably distinct from each other because the copending claims recite stable solution of tofacitinib consisting essentially of: tofacitinib at a concentration of about 1 mg/mL;optionally one or more antioxidants; and a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof; wherein a pH of the solution ranges from about 3.7 to 4.5; wherein the solution is free from precipitation when said solution is stored at 25° C./60% RH for at least 6 months; and wherein said solution is a palatable oral solution whereas the claims herein are drawn to a stable solution of tofacitinib comprising: tofacitinib at a concentration of about 1 mg/mL; optionally, one or more antioxidants; and a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof: wherein a pH of the solution ranges from 3.5 to 5.0; wherein the solution is free from precipitation when said solution is stored at 40°C/75% RH for 3 months; and wherein said solution is a palatable oral solution.
Claims 1-11 and 13-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. US 11766438 B2. Although the claims at -issue are not identical, they are not patentably distinct from each other because the copending claims recite stable solution of tofacitinib consisting essentially of: tofacitinib at a concentration of about 1 mg/mL, and optionally one or more antioxidants; and a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof; wherein pH of the solution ranges from 3.7 to 4.5; wherein the solution is free from precipitation when said solution is stored at 25° C./60% RH for at least 6 months; wherein level of total impurities in the solution is less than 1.5% w/w as measured by HPLC, when said solution is stored at 40° C./75% RH for 6 months; wherein said solution is a palatable oral solution whereas the claims herein are drawn to a stable solution of tofacitinib comprising: tofacitinib at a concentration of about 1 mg/mL; optionally, one or more antioxidants; and a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof: wherein a pH of the solution ranges from 3.5 to 5.0; wherein the solution is free from precipitation when said solution is stored at 40°C/75% RH for 3 months; and wherein said solution is a palatable oral solution.
Conclusion
No claims allowed.
Correspondence
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622