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 Claims
Pursuant to the Requirement for Restriction/Election, mailed on October 22, 2025, applicant elects without traverse, in a reply received January 22, 2026, methylprednisolone acetate as a corticosteroid, myristyl gamma picolinium chloride as a quaternary ammonium compound, and sodium chloride as a tonicity agent. Applicant states claims 1-10 and 13-24 read on elected species. Accordingly, claims 11-12 are hereby withdrawn.
Claims 1-10 and 13-24 are pending.
Priority
This application, filed on April 19, 2023, is a National Stage entry from the International application PCT/IB2021/059603, filed on October 19, 2021, and claims benefit to US Provisional Application Nos. 63/252,705 and 63/104,143, filed on October 6, 2021 and October 22, 2020, respectively.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on April 19, 2023 has been acknowledged and considered.
Claim Rejections - 35 USC § 103
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 1-10, 13-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014116876 (#1 in Foreign Patent Documents in IDS filed on April 19, 2023) (“Shah”) in view of WO0187262 (#2 in Foreign Patent Documents in IDS filed on April 19, 2023) (“Colombo”).
Shah teaches aqueous pharmaceutical compositions for sustained release delivery of corticosteroid compounds comprising an insoluble and soluble corticoid and a viscosity enhancing agent (Abstract). The soluble corticosteroids include methylprednisolone sodium succinate, dexamethasone sodium phosphate, etc. (¶[0032]). The insoluble corticoids include methylprednisolone acetate, dexamethasone acetate, etc. (¶[0034]). The viscosity agents include sodium hyaluronate, polyvinylpyrrolidone (PVP), etc. Shah states: “The present formulation does not include polyethylene glycol (PEG) due to potential side effects.” (¶[0043]). Shah teaches the pharmaceutical composition comprises insoluble methylprednisolone acetate and soluble methylprednisolone sodium succinate in water and the dose per injection of methylprednisolone is in the range of 20 to 120 mg/dose in 1 to 10 mL of a sterile solution such as water for injection or saline (¶[0058]). Exemplary formulations are described in Table 1 with a total corticosteroid weight of 5 mg, 10 mg 15 mg, 20 mg, 25 mg, 30 mg and are prepared in 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 10 mL unit doses (¶[0067]). The formulations listed in Table 1 can be replaced with methylprednisolone sodium succinate and methylprednisolone acetate (¶[0068]). Shah also teaches the pharmaceutical composition can further include benzalkonium chloride, benzyl alcohol, etc. to increase the shelf life and can be in the range of 0.01-1% (¶[0057]).
Shah does not teach including a tonicity agent like sodium chloride or the quaternary ammonium compound myristyl gamma picolinium chloride (MGPC).
Colombo teaches pharmaceutical aqueous suspension formulation for parenteral administration having stabilized pH, comprising a biologically active compound and PVP to control pH. The biologically active compound is a steroidal compound (Abstract). Examples of the steroidal biologically active compounds taught are medroxyprogesterone acetate, methylprednisolone acetate, etc. and can be in a concentration range from 3-30% w/v (p. 8, lines 14-24). The formulations can include tonicity agents like sodium chloride, sodium sulphate, etc. (p. 7, lines 24-26) and can include cationic surfactants like MGPC (p. 7, lines 1-3). Example A shows a formulation including medroxyprogesterone acetate at 200 mg/mL (20% w/v), MGPC at 0.2 mg/mL (0.2% w/v), sodium sulphate at 11 mg/mL (1.1% w/v), PEG 3350 at 20.3 mg/mL (2.03% w/v), PVP at 20 mg/mL (2.0% w/v), monobasic sodium phosphate hydrate at 0.694 mg/mL (.0694% w/v), and dibasic sodium phosphate hydrate at 0.588 mg/mL (0.0588% w/v) (p. 12, lines 8-26; p. 16, lines 5-18).
Shah and Colombo are considered analogous art to the claimed invention because they are in the same field of optimizing steroidal formulations including methylprednisolone acetate for parenteral administration. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA), before the effective filing date of the claimed invention, to combine the teachings of the prior art elements to arrive at the claimed invention with reasonably predictable results. Based on the teachings of Shah, a PHOSITA would have been motivated to formulate a steroidal solution with methylprednisolone acetate without PEG due to its potential side effects. Shah also teaches a preservative, like benzalkonium chloride can be part of the pharmaceutical composition to increase the shelf life (vide supra). While Shah does not teach a tonicity agent, Colombo rectifies this omission by teaching similar type of formulations can include a tonicity agent like sodium sulphate, sodium chloride, etc. (vide supra). Accordingly, claims 1-2, 6, and 8 are prima facie obvious.
Regarding claims 3-5, Colombo teaches in Example A that MGPC is present in a formulation at 0.2 mg/mL. It would have been prima facie obvious to formulate a steroidal suspension including methylprednisolone acetate and exclude PEG due to its potential side effects, based on the teachings of Shah, and include a tonicity agent like sodium chloride and a preservative like MGPC, based on the teachings of Colombo, wherein MGPC is at 0.2 mg/mL. The amount of MGPC taught by Colombo overlaps with the ranges instantly claimed and therefore would have been prima facie obvious to a PHOSITA (MPEP §2144.05(I)).
Regarding claim 7, Colombo teaches in Example A, a tonicity agent sodium sulphate at 11 mg/mL but states that sodium chloride is also a suitable tonicity agent that may be part of the formulation (vide supra). It would have been prima facie obvious to formulate the suspension instantly claimed as discussed above, and substitute sodium sulphate for sodium chloride (MPEP §2144.06(II)). The amount of 9 mg/mL could have been achieved by a PHOSITA through routine optimization as other examples in Colombo include sodium chloride in the range of 8 mg/mL to 9 mg/mL, namely Examples B-D, identifying it as a result-effective variable (MPEP §2144.05(II)(A)).
Regarding claims 9-10, Colombo teaches the steroidal biologically active compound of the formulation is one known in the art and includes methylprednisolone acetate, medroxyprogesterone acetate, etc. (p. 8, lines 14-19). The teachings state medroxyprogesterone acetate is in a concentration range from 30 mg/mL (3% w/v) to 300 mg/mL (30% w/v), but based on the teachings, this concentration range can be reasonably applied to methylprednisolone acetate as well, as is it is explicitly mentioned as a steroidal biologically active compound from a finite list. Therefore, the range overlaps with the ranges instantly claimed and would have been prima facie obvious to a PHOSITA to prepare the formulate the suspension as discussed above (MPEP §2144.05(I)).
Regarding claim 13, Colombo teaches in Example A that MGPC is present in a formulation at 0.2 mg/mL. It would have been prima facie obvious to formulate a steroidal suspension including methylprednisolone acetate and exclude PEG due to its potential side effects, based on the teachings of Shah, and include a tonicity agent like sodium chloride and a preservative like MGPC, based on the teachings of Colombo, wherein MGPC is at 0.2 mg/mL. With respect to the recitation of “consisting essentially of” in instant claim 13, the exclusion of PEG is rectified by the teachings of Shah, however the claim does not exclude PVP or phosphate buffer, which help maintain the pH of the solution and would not perturb the basic and novel characteristics of the invention claimed. Therefore, the claim is prima facie obvious based on the teachings of Shah and Colombo.
Regarding claim 17, Colombo teaches the formulations have nitrogen blanket overlay on the headspace of the vial (p. 7, lines 27-29).
Regarding claims 14-16, Colombo teaches that both PEGs and polysorbates, when in solution, may undergo degradation and lead to formation of acid species which necessarily reduces the shelf life of the suspension (p. 3, lines 1-8). Colombo further teaches that suitable concentrations of PVP can control the pH of a suspension including a steroidal compound, like methylprednisolone acetate, minimizing its pH decrease (p. 4-6). Table 5 describes the formulation in Example A maintains a 6.19 pH in the presence of PVP and phosphate buffer, at 40°C after 3 months (p. 14). While Example A contains 2.03% PEG, the motivation provided by Shah to exclude PEG in a steroidal formulation, and the motivation to maintain the pH of the formulation through inclusion of PVP, as taught by Colombo, would have led a skilled artisan to arrive at the formulation instantly claimed which maintains a stable pH for 3 months. In other words, the combination of references provides the necessary components to arrive at the formulation instantly claimed, and therefore the stability of the solution is an intended result of the formulation, which would be inherent of the formulation at 40°C for 100, 300, and 500 days. (MPEP §2111.04).
Regarding claims 18-21, Colombo teaches in Example A that medroxyprogesterone acetate is present in a formulation at 200 mg/mL and MGPC is present at 0.2 mg/mL. Colombo teaches methylprednisolone acetate, out of a finite list of other steroidal compounds, can be used in the formulation (vide supra), and therefore can be reasonably interpreted by a PHOSITA to be substituted for medroxyprogesterone in Example A. While the concentration of methyl prednisolone acetate and the relative concentration of MGPC, i.e., 0.1% (
0.2
m
g
/
m
L
200
m
g
/
m
L
*
100
%
)
of the concentration of methyl prednisolone, taught in Colombo is slightly outside of the ranges and amounts instantly claimed, it would have been prima facie obvious to arrive at a concentration within the claimed ranges and amounts through routine optimization (MPEP §2144.05(II)(A)). Colombo also teaches the inclusion of sodium sulphate in Example A, but it would have been prima facie obvious to substitute sodium chloride for sodium sulphate as they are recognized as equivalent tonicity agents by Colombo (§2144.06(II)).
Regarding claims 22- 24, Colombo teaches Example A which is a formulation including medroxyprogesterone acetate at 200 mg/mL, MGPC at 0.2 mg/mL, sodium sulphate 11 mg/mL, PEG 3350 at 20.3 mg/mL, PVP at 20 mg/mL, monobasic sodium phosphate hydrate at 0.694 mg/mL, and dibasic sodium phosphate hydrate at 0.588 mg/mL (vide supra). Methylprednisolone acetate and sodium chloride are taught by Colombo as a suitable steroidal compound and isotonicity agent, respectively, and could have been substituted for medroxyprogesterone acetate sodium sulphate as mentioned earlier. The amount of MGPC taught by Colombo overlaps with instant claim 23 but falls outside claims 22 and 24. The amount of methylprednisolone acetate and sodium chloride falls outside of claims 22-24, but could have been reasonably arrived at through routine optimization by a PHOSITA (MPEP §2144.05(II)(A)).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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