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
Claims 1 – 21 are pending in this application. Applicant’s amendment, submitted October 21, 2025, is entered, wherein claims 4, 6, 8 – 9, 12, 14 – 15, 18, and 20 – 21 are amended.
Priority
This application is a national stage application of PCT/IB2021/057356, filed August 10, 2021, which claims benefit of foreign priority document IN202021034475, filed August 11, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. IN202021034475, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The foreign priority IN202021034475 does not provide support for the limitation of “non-aqueous vehicle is in range from 200 – 1000 mg/mL” recited in claim 7, “Propylene glycol and polyethylene glycol is in range from 0.1 to 15 mL” recited in claims 8, 15, and 21. Thus, the priority date of claims 7 – 8, 15, and 21 is August 10, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/21/2025 was filed after the mailing date of the previous Office Action on July 22, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
5. The objections of claims 4, 6, 8 – 9, 12, 14 – 15, 18, and 20 – 21 in the previous Office Action, mailed July 22, 2025, are withdrawn in view of the amended claims.
Withdrawn Rejections
6. The rejection of claims 1 – 6 and 9 – 14 in the previous Office Action, mailed July 22, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Joshi-Hangal et al. has been considered and is withdrawn because Joshi-Hangal et al. do not teach a suspension formulation.
The rejection of claims 1 – 15 in the previous Office Action, mailed July 22, 2025, under 35 U.S.C. 103 as being unpatentable over Joshi-Hangal et al. in view of Chemical Book has been considered and is withdrawn because Joshi-Hangal et al. do not teach a suspension formulation.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
a. Claim 9 recites the limitation "the process" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 9 depends from claim 1 and recites “the process”, however, claim 1 never recites “process”. It is unclear which process the claim is referring to.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 – 7 and 10 – 14 are rejected under 35 U.S.C. 103 as being unpatentable over Joshi-Hangal et al. (US2004/0259820A1, cited in the previous Office Action) in view of Kumar (Journal of Drug Delivery and Therapeutics, 2019, Vol. 9, Issue 4-A, page 803 – 805, Reference included with PTO-892).
Regarding claims 1 – 7 and 10 – 14, Joshi-Hangal et al. teach pharmaceutical formulations, kits, and vessels for delivering decitabine to a patient suffering from a disease in need of treatment with decitabine. The pharmaceutical formulation comprises decitabine solvated in a non-aqueous solvent that comprises glycerin, propylene glycol, polyethylene glycol, or combinations (Abstract), wherein decitabine is in a range between 0.1 and 200 mg/mL (para. [0040]). The pharmaceutical formulation may further comprise an acidifying agent, wherein the acidifying agent is citric acid (para. [0020 – 0021]), wherein the acidifying agent is at a concentration of 0.01 – 0.2 mg/mL (para. [0022]). Joshi-Hangal et al. teach that the formulation is prepared by dissolving crystalline powder of ascorbic acid in glycerin, mixing thoroughly, and dissolving micronized decitabine (para. [0153]). Joshi-Hangal et al. further teach an example that glycerin is in 980 mg with the specific gravity of glycerin and the formulation of 1.25 (para. [0152]). Moreover, Joshi-Hangal et al. discloses that decitabine is commonly formulated together with buffering salt, such as potassium dihydrogen phosphate, The example further discloses that amount of KH2PO4 used is 6.8 mg (para. [0008]).
However, Joshi-Hangal et al. do not teach a suspension formulation.
Kumar teaches parenteral suspensions as a stability enhancing liquid dosage forms (Title). The advantages of parenteral suspensions include increasing the resistance of the suspensions to hydrolysis and oxidation, which are present in the form of solids, eliminating hepatic first pass effect, and formulating controlled release drug (page 803, Right Col., para. 2). Typical excipients used in parenteral suspensions include wetting agents and buffering agents. The wetting agents may be non-aqueous solvents, such as propylene glycol and glycerin, whereas buffering agent is citric acid. Buffering agents are added to minimize pH-sensitive degradation reactions, therefore, improving product stability (page 804, Right Col., para. 4; page 805, Left Col., para. 7 – 8). Suspension is a better choice of drug dosage form due to its fast onset of action and its bioavailability over the other dosage forms. As the other dosages forms facing the problem of first pass metabolism and other drug stabilities, in respect to above qualities suspension is a good choice of drug (page 805, Right Col., para. 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the pharmaceutical formulation comprising decitabine, glycerin, and citric acid as taught by Joshi-Hangal et al. into an injectable non-aqueous suspension in view of Kumar because Kumar teaches that suspension has a higher stability and better bioavailability. One would have been motivated to modify the pharmaceutical formulation comprising decitabine, propylene glycol, and citric acid as taught by Joshi-Hangal et al. into an injectable non-aqueous suspension in view of Kumar because of the advantages of parenteral suspension disclosed in Kumar. For the non-aqueous vehicle, the calculated amount based on the example is 1225 mg/mL of glycerin. One would have performed routine experimentation to discover the best amount of non-aqueous vehicle and stabilizing agent for the optimal formulation characteristics. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify the pharmaceutical formulation comprising decitabine, glycerin, and citric acid as taught by Joshi-Hangal et al. into an injectable non-aqueous suspension in view of Kumar because the modification is known in the art to enhance stability and bioavailability of drug, thereby, yielding an improved drug formulation.
Claims 8 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Joshi-Hangal et al. (US2004/0259820A1, cited in the previous Office Action) in view of Kumar (Journal of Drug Delivery and Therapeutics, 2019, Vol. 9, Issue 4-A, page 803 – 805, Reference included with PTO-892) as applied to claims 1 – 7 and 10 – 14 above, and further in view of Walker (Organic Analytical Services, 2008, Reference included with PTO-892) and Chemical Book (Chemicalbook.com, July 2020, cited in the previous Office Action).
b. Regarding claims 8 and 15, the references teach the limitations discussed above.
However, these references do not teach the formulation comprises triethanolamine together with potassium dihydrogen phosphate in a range of 0.01 to 50 mg/mL.
Walker teaches that triethanolamine is used as dispersion agent (page 2, 1.1.3 Workplace exposure).
Chemical Book teaches that triethanolamine (TEA) has been used in salt formation for injectable solutions (page 3, para. 6). The lethal human oral dose of TEA is estimated to be 5 – 15 g/kg body weight (page 4, para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date to combine the injectable pharmaceutical suspension comprising decitabine, potassium dihydrogen phosphate, propylene glycol, polyethylene glycol, and citric acid as taught by Joshi-Hangal et al. and Kumar with TEA in view of Walker and Chemical Book because Walker teaches the function of TEA as a dispersion agent and Chemical Book suggests that TEA is one of the components used in injectable solutions. The combination will yield predictable results for an injectable non-aqueous suspension. For the non-aqueous vehicle, the calculated amount based on the example is 1225 mg/mL of glycerin. One would have performed routine experimentation to discover the best amount of non-aqueous vehicle and stabilizing agent for the optimal formulation characteristics. One would also have performed routine experimentation to discover the best non-aqueous vehicle, whether alone or in combination, used in the suspension for the optimal formulation characteristics. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the injectable pharmaceutical suspension comprising decitabine, potassium dihydrogen phosphate, propylene glycol, polyethylene glycol, and citric acid as taught by Joshi-Hangal et al. and Kumar with TEA in view of Walker and Chemical Book because it is known in the art that TEA is used in injectable pharmaceuticals and it acts as a dispersion agent.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Joshi-Hangal et al. (US2004/0259820A1, cited in the previous Office Action) in view of Kumar (Journal of Drug Delivery and Therapeutics, 2019, Vol. 9, Issue 4-A, page 803 – 805, Reference included with PTO-892) as applied to claims 1 – 7 and 10 – 14 above, and further in view of MacLeod et al. (US2010/0247666A1).
c. Regarding claim 9, the references teach the limitation discussed above.
However, these references do not teach the process for preparing the non-aqueous injectable suspension of anti-cancer agent.
MacLeod et al. teach the method for preparing a suspension, wherein the method comprises (a) adding a predetermined amount of a solvent into a vessel; (b) sequentially adding predetermined amount of one or more other desired ingredients other than the API into the vessel while mixing continues; (c) adding a desired amount of a carboxy-containing vinyl polymer into the vessel while mixing continues until the polymer is completely dissolved to produce a first solution; (d) adjusting pH of the first solution to a predetermined pH value; and (e) adding a predetermined amount of API into the first solution while mixing continues under conditions of high-shear mixing to produce the suspension (para. [0057]).
It would have been prima facie obvious to combine the pharmaceutical formulation comprising decitabine, glycerin, and citric acid in the form of suspension as taught by Joshi-Hangal et al. and Kumar with the method of preparing suspension in view of MacLeod et al. to achieve the claimed process because MacLeod et al. explicitly teach the steps of preparing a suspension. One would have been motivated to apply and modify the process for preparing a suspension because MacLeod et al. teach a known technique, which would yield predictable results. In this case, a suspension formulation is yielded. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the pharmaceutical formulation comprising decitabine, glycerin, and citric acid in the form of suspension as taught by Joshi-Hangal et al. and Kumar with the method of preparing suspension in view of MacLeod et al. to achieve the claimed process because the process for preparing a suspension formulation is known in the art and modifying such process to cater the need of the current invention is within the skill of the artisan.
Claims 16 – 21 are rejected under 35 U.S.C. 103 as being unpatentable over Joshi-Hangal et al. (US2004/0259820A1, cited in the previous Office Action), Kumar (Journal of Drug Delivery and Therapeutics, 2019, Vol. 9, Issue 4-A, page 803 – 805, Reference included with PTO-892), Walker (Organic Analytical Services, 2008, Reference included with PTO-892), and Chemical Book (Chemicalbook.com, July 2020, cited in the previous Office Action) as applied to claims 1 – 8 and 10 – 15 above, and further in view of Leung (US2017/0252409A1, cited in the previous Office Action).
Regarding claims 16 – 21, the references teach the limitations discussed above.
However, these references do not teach that the anticancer agent is azacitidine.
Leung teaches the use of GLP-1 receptor agonists for the treatment of cancer with additional beneficial agents, such as anticancer agent (Abstract). In an embodiment, the suspension formulation comprises a particle formulation comprising a GLP-1 receptor agonist and/or beneficial agent, a disaccharide, methionine, and a buffer, and a non-aqueous, single-phase suspension vehicle (para. [0016]). In another embodiment, the suspension formulation may further comprises one or more stabilizers (para. [0015]), wherein the stabilizer is citric acid (para. [0020]). In one embodiment, the anticancer agent is a chemotherapeutic agent, wherein the chemotherapeutic agent is an antimetabolites, wherein the antimetabolite is azacitidine or decitabine (para. [0143]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute decitabine in the suspension formulation as taught by Joshi-Hangal et al. and Kumar with azacitidine in view of Leung because Leung also teaches a suspension formulation comprising azacitidine and Leung discloses that the anticancer agent may be either azacitidine or decitabine. It would also have been obvious to do this because both drugs are known separately in the prior art for the purpose of treating cancer, and it would have been obvious to substitute equivalent drug known to treat the same disease. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to substitute decitabine in the suspension formulation as taught by Joshi-Hangal et al. with azacitidine in view of Leung because it is well known to substitute drug to treat the same disease and Leung explicitly teaches that decitabine may be replaced by azacitidine.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date to combine the injectable pharmaceutical suspension comprising azacitidine, potassium dihydrogen phosphate, propylene glycol, polyethylene glycol, and citric acid as taught by Joshi-Hangal et al., Kumar, and Leung with TEA in view of Walker and Chemical Book because Walker teaches the function of TEA as a dispersion agent and Chemical Book suggests that TEA is one of the components used in injectable solutions. The combination will yield predictable results for an injectable non-aqueous suspension. For the non-aqueous vehicle, the calculated amount based on the example is 1225 mg/mL of glycerin. One would have performed routine experimentation to discover the best amount of non-aqueous vehicle and stabilizing agent for the optimal formulation characteristics. One would also have performed routine experimentation to discover the best non-aqueous vehicle, whether alone or in combination, used in the suspension for the optimal formulation characteristics. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the injectable pharmaceutical suspension comprising azacitidine, potassium dihydrogen phosphate, propylene glycol, polyethylene glycol, and citric acid as taught by Joshi-Hangal et al., Kumar, and Leung with TEA in view of Walker and Chemical Book because it is known in the art that TEA is used in injectable pharmaceuticals and it acts as a dispersion agent.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed October 21, 2025, have been fully considered and are found to be not persuasive.
Regarding Joshi-Hangal et al., Applicant argues that Joshi-Hangal et al. teach a solution/solvate system instead of a non-aqueous suspension. The examiner acknowledges Applicant’s argument. However, the new 103 rejection is based on Joshi-Hangal et al. in view of Kumar for achieving the claimed composition. Joshi-Hangal et al. teach the claimed components of the non-aqueous injectable formulation and Kumar teaches the benefits of formulating a injectable suspension, providing a motivation for one skilled in the art to modify the non-aqueous injectable formulation disclosed by Joshi-Hangal et al.
Regarding TEA, Applicant argues that Chemical Book merely discloses TEA as an injectable excipient and does not teach or suggest the claimed stabilizing function within a non-aqueous suspension system. However, Walker, as an additional reference, supports and provides motivation to incorporate TEA in the suspension formulation because Walker explicitly teaches that TEA is a dispersion agent, which would enhance stability of the formulation. Applicant further argues that Chemical Book does not teach the use of TEA together with a phosphate buffer to stabilize a water-soluble anticancer drug in a non-aqueous suspension. This argument is not persuasive because it is not commensurate in scope with the claims. The current scope of the claims do not require any specific synergistic or stabilizing interaction between TEA and the phosphate buffer system. Therefore, Applicant’s argument concerning the lack of a TEA-phosphate buffer combination is not persuasive because such a limitation is not recited in the claims.
Regarding Chemical Book contains no teaching on non-aqueous particulate suspension behavior, PSD stabilization, or hydrolytic protection under low moisture conditions, Applicant argues that the examiner’s assumption relies on hindsight reconstruction. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Also, Walker provides motivation to incorporate TEA in the suspension formulation because Walker explicitly teaches that TEA is a dispersion agent, which would enhance stability of the formulation.
Regarding Leung, Applicant argues that Leung relates to GLP-1 receptor agonist formulations , not nucleoside analog suspension mechanics, implying that Leung are not applicable to formulations involving azacitidine. However, this argument is not persuasive because it is not commensurate in scope with the claims. The claims do not require any particular stabilization mechanism specific to nucleoside analogs or exclude peptide-related formulations.
Applicant contends that substituting decitabine with azacitidine is not a simple equivalent swap due to formulation differences and unpredictability in non-aqueous systems. However, Leung provides a clear teaching and motivation to use azacitidine as a substitute. Applicant further argues that Leung does not teach switching active agents under a dual-buffer non-aqueous suspension framework, nor does it suggest stability equivalence in such an environment. The argument is not persuasive because it is not commensurate in scope with the claims. Applicant tries to frame the invention narrowly, such as dual-buffer, cytidine-specific suspension framework, but the claims do not reflect that. Claim 16 recites any non-aqueous injectable azacitidine suspension with a stabilizer. There is no limitation requiring a unique or complex buffer system. Furthermore, Applicant has not provided objective evidence showing that substituting azacitidine in a known suspension context or using the claimed stabilizers yields unexpected properties. Therefore, the rejection is maintained.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647