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 .
Summary
Claims 1, 4, 7-9, and 11-23 are pending in this office action. Claims 19-23 are new. Claims 2-3, 5-6, 10, and 19-20 are cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on June 7, 2024 is a 371 of PCT/US2022/081320 filed December 9, 2022, which in turn claims domestic priority to provisional patent application 63/288,537 filed December 11, 2021.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on March 24, 2026 is acknowledged. A signed copy of the document is attached to this office action.
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.
Claims 1, 4, 7-9, and 11-23 are 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.
Claim 1 is amended to read, “…and stored for one month at 6 °C or greater,…” It is not clear whether “or greater” means for a longer time or at a higher temperature.
Dependent claims 4, 7-9, and 11-23 are included in this rejection because they do not cure the defect of claim 1.
Furthermore, claim 20 uses the same indefinite text, “or greater.”
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:
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 non-obviousness.
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, 4, 7-9, and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US6,232,304B1) in view of Devouassoux et al. (US2017/0088333A1), Mendelovici et al. (WO2005/016325A2), and Hong et al. (Journal of Pharmaceutical Sciences, 2011).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Kim et al.
Kim et al. is considered the closest prior art as it teaches inclusion complexes of aryl heterocyclic salts (see title). In addition, Kim et al. disclose compositions of matter comprising a pharmaceutically acceptable salt of an aryl heterocyclic compound, such as ziprasidone, in a cyclodextrin. Preferred cyclodextrins are SBECD and HPBCD. The composition can comprise a dry mixture, a dry inclusion complex or an aqueous solution. The salt/cyclodextrin inclusion complex preferably provides an amount of ziprasidone of at least 2.5 mgA/ml when the complex is dissolved in water at 40% w/v. A variety of ziprasidone salts are preferred, including the mesylate, esylate, besylate, tartrate, napsylate, and tosylate (see abstract).
2. Devouassoux et al.
Devouassoux et al. teach a packaging system for oxygen-sensitive drugs (see title). Furthermore, Devouassoux et al. disclose pharmaceutical packaging systems
which prevent oxidative degradation of oxygen-sensitive drugs, such systems including a primary packaging container with an oxygen permeable component, a secondary packaging with very low permeability to oxygen and an oxygen absorber (see abstract).
3. Mendelovici et al.
Mendelovici et al. teach crystalline ziprasidone HCL and processes for preparation thereof (see title). In addition, Mendelovici et al. disclose crystalline ziprasidone HCl and processes for preparation thereof (see abstract).
4. Hong et al.
Hong et al. teach effect of cyclodextrin derivation and amorphous state of complex on accelerated degradation of ziprasidone (see title). Additionally, Hong et al. disclose inclusion complexes of ziprasidone with several b-cyclodextrins [b-CDs; sulfobutylether-b-cyclodextrins (SBEbCD), hydroxypropyl-b-cyclodextrins (HPbCD), methyl-bcyclodextrins (MbCD), and carboxyethyl-b-cyclodextrins (CEbCD)] were prepared and solution stability was evaluated at elevated temperature. Solid-state stability was assessed by subjecting various CD complexes of ziprasidone, spray-dried dispersion (SDD), partially crystalline ziprasidone-SBEbCD salts, and the physical mixture of ziprasidone-SBEbCD to g-irradiation. Degradant I was formed by oxidation of ziprasidone, which upon aldol condensation with ziprasidone formed degradant II in both solution and solid states. In the solution state, CD complexes with electron-donating side chains, such as SBEbCD and CEbCD, produced the highest oxidative degradation followed by HPbCD with 6, 3, and 4 degrees of substitution. In the solid state, crystalline drug substance and physical mixture of crystalline drug-SBEbCD showed very little to no degradation. In contrast, amorphous bCD, MbCD, CEbCD, and SBEbCD complexes as well as the amorphous SDD exhibited greatest extent of oxidative degradation. Results suggest that electron-donating side chains of the derivatized CD interact with transition state of the oxidation reaction and catalyze drug degradation in solution. However, higher mobility in the amorphous state of CD-drug complexes promoted chemical instability of ziprasidone under accelerated conditions irrespective of the chemical nature of the side chain on CD (see abstract).
Combination of Kim et al. and Mendelovici et al.
Regarding instant claim 1, Kim et al. and Mendelovici et al. teach an aqueous formulation that contains a psychotropic effective amount ziprasidone or a pharmaceutically acceptable salt and/or hydrate thereof. The necessary citations of Kim et al. and Mendelovici et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Kim et al. and Mendelovici et al. Citations
An aqueous formulation that contains a psychotropic effective amount ziprasidone or a pharmaceutically acceptable salt and/or hydrate thereof, being suitable for intramuscular injection, and stored for one month at 6 °C or greater, wherein the aqueous formulation:
Kim et al. teach an aqueous formulation that contains a psychotropic effective amount ziprasidone or a pharmaceutically acceptable salt and/or hydrate thereof (see abstract, Compositions of matter comprising ... ziprasidone ... The composition can comprise an aqueous solution; see col 3, In 11-28, A preferred aryl-heterocyclic is ziprasidone, ... lt is also disclosed in the previously mentioned ... and is thus useful as an antipsychotic; see col 6, In 48-50, The amount of aryl-heterocyclic to be administered to a patient is an effective amount; all within Kim et al.), said aqueous formulation after storage for up to six months at 5 degrees C, being suitable for intramuscular injection (see col 7, In 47-64, An inclusion complex of ziprasidone can be formed ... A product solution made with sterile water can be used as is for administration to patients immediately, no adjustment to isotonicity being required, or stored at 5 degrees C for periods of to two years or longer; see col 8, In 7-10, intramuscular injection is preferred; all within Kim et al.).
Mendelovici et al. disclose crystalline ziprasidone HCl (polymorph A), which does not transform to polymorph M by more than 5% upon storage at a
temperature of between about 25° and 55°C for at least 3 months (see pg 4, ln 17-19 within Mendelovici et al.).
(a) provides greater than 98% purity of the ziprasidone, its pharmaceutically acceptable salt and/or hydrate; and/or (b) has less than 0.5% of USP Related Compound C with respect to ziprasidone itself.
Mendelovici et al. disclose the preparation of substantially pure crystalline ziprasidone HCl (polymorph A) (see pg 13, ln 3-4 within Mendelovici et al.).
The teachings of Mendelovici et al. would allow a skilled artisan (POSITA; person of ordinary skill in the art) to provide greater than 98% purity of the ziprasidone and optimize the psychotropic effectiveness of the aqueous formulation that contains a psychotropic effective amount of ziprasidone.
Kim et al. and Mendelovici et al. do not specifically teach wherein the formulation is stored for one month at 6 °C or greater and wherein the aqueous formulation (a) provides greater than 98% purity of the ziprasidone.
Based on Kim et al.'s and Mendelovici et al.’s teachings, it would have been obvious to one of skilled in the art to adjust the aqueous formulation to be stored for one month at 6 °C or greater and determined its shelf life by routine experimentation.
Optionally, a skilled artisan (POSITA) would select a USP Related Compound C (see PTO-892 NPL V; NF) such that purification would not interfere with the overall purity of ziprasidone (x<0.5%).
Therefore, a skilled artisan (POSITA) would consult the disclosures of Kim et al. and Mendelovici et al. to teach all the elements of instant claim 1 including ziprasidone formulation storage and purity.
The remainder of the instant claims which are either directly or indirectly dependent on claim 1 are taught in full by the combination of Kim et al. and Mendelovici et al.
Regarding instant claim 4, Kim et al. and Mendelovici et al. teach wherein the ziprasidone or a pharmaceutically acceptable salt and/or hydrate thereof is ziprasidone mesylate trihydrate. Kim et al. disclose use of the ziprasidone mesylate trihydrate salt (see col 4, In 60-col 5 In 4, Use of the term "salt" herein, including the appendant claims, shall be understood to refer to pharmaceutically acceptable acid addition salts of aryl-heterocyclics, including ziprasidone ... For example, herein incorporated by reference, discloses the mesylate trihydrate salt of ziprasidone; also see abstract, A variety of ziprasidone salts are preferred, including the mesylate; all within Kim et al.).
Regarding instant claim 7, Kim et al. and Mendelovici et al. teach further comprising b-cyclodextrin sulfobutyl ether sodium (SBECD). Kim et al. disclose the use of SBECD (see abstract; also see col 3, ln 34-35; both within Kim et al.).
Regarding instant claim 8, Kim et al. and Mendelovici et al. teach wherein about 294 mg SBECD is present per 20 mg ziprasidone. Kim et al. disclose the most preferable molar ratio of cyclodextrin:drug between 0.5:1 and 5:1 (2.8:1; see col 7, ln 5-9 within Kim et al.). This molar ratio would include the instant claim 8 limitation.
Regarding instant claim 9, Kim et al. and Mendelovici et al. teach wherein the ziprasidone is present at about 20 mg/mL. Kim et al. disclose the ziprasidone tartrate salt formulation that can be present at about 20 mg/mL (see Example 4 within Kim et al.). A skilled artisan (POSITA) could apply this concentration to the mesylate salt.
Regarding instant claims 11-14, Kim et al. and Mendelovici et al. teach wherein the reduced oxygen headspace container is a vial or ampule with an N2 gas in the headspace and in a container with minimal oxygen headspace. A skilled artisan (POSITA) would commonly “nitrogen or argon blanket” a product to minimize oxygen and moisture exposure, and thus prevent degradation within a laboratory. Furthermore, by minimizing the headspace in a container/vial/or ampule, a skilled artisan (POSITA) would also reduce exposure of the material to both oxygen and moisture. Moreover, a common procedure also includes using a syringe to store a formulation.
Regarding instant claim 15, Kim et al. and Mendelovici et al. teach having a volume of about 0.5 to about 1.5 mL and contains about of about 20 mg of ziprasidone per mL. Kim et al. disclose the ziprasidone tartrate salt formulation that can be present at about 20 mg/mL within the volume range of 0.5 to 1.5 mL(see Example 4 within Kim et al.). A skilled artisan (POSITA) could apply this concentration and volume to the mesylate salt.
Regarding instant claims 19-23, Kim et al. and Mendelovici et al. teach storage of the ziprasidone formulation at the required temperature. Kim et al. disclose an inclusion complex of ziprasidone can be formed ... A product solution made with sterile water can be used as is for administration to patients immediately, no adjustment to isotonicity being required, or stored at 5 degrees C for periods of to two years or longer (see col 7, In 47-64 within Kim et al.). In addition, Mendelovici et al. disclose crystalline ziprasidone HCl (polymorph A), which does not transform to polymorph M by more than 5% upon storage at a temperature of between about 25° and 55°C for at least 3 months (see pg 4, ln 17-19 within Mendelovici et al.). Based on Kim et al.'s and Mendelovici et al.’s teachings, it would have been obvious to one of skilled in the art to adjust the aqueous formulation to be stored at a designated time and temperature while determining its shelf life by routine experimentation.
Combination of Kim et al., Mendelovici et al., and Hong et al.
Regarding instant claim 16, Kim et al., Mendelovici et al., and Hong et al. teach having a pH value of about 2.8 to about 4.0. Hong et al. disclose the pH of the ziprasidone SBECD formulation at 4.02 (see Table 1 within Hong et al.). [This pH value is about 4.0.]
Combination of Kim et al., Mendelovici et al., and Devouassoux et al.
Regarding instant claim 17, Kim et al., Mendelovici et al., and Devouassoux et al. teach in a syringe within secondary packaging that prevents penetration of oxygen through a plunger of the syringe. Ziprasidone (Figure 1) is oxygen sensitive
Figure 1
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due to the two tertiary amines within the piperazine core which either form salts or maintain the free base form (see paragraph [0069] within Devouassoux et al.).
Devouassoux et al. disclose secondary packaging configurations and analytical equipment [syringe] for oxygen-sensitive substrates (see Examples 1-4 within Devouassoux et al.).
Regarding instant claim 18, Kim et al., Mendelovici et al., and Devouassoux et al. teach wherein the secondary packaging is a pouch that comprises an oxygen scavenger. Devouassoux et al. disclose the use of a pouch and oxygen scavenger (see Figure 7 and paragraph [0064] within Devouassoux et al.).
Analogous Art
The Kim et al., Mendelovici et al., Devouassoux et al., and Hong et al. references are directed to the same field of endeavor as the instant claims, that is, an aqueous formulation that contains a psychotropic effective amount ziprasidone or a pharmaceutically acceptable salt and/or hydrate thereof as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the hair care composition disclosed by Kim et al., using the teachings of Devouassoux et al., Mendelovici et al., and Hong et al. in order to arrive at the subject matter of the instant claims.
The Kim et al., Devouassoux et al., Mendelovici et al., and Hong et al. references all have considerable overlap for the development of a drug formulation. In this instance, Kim et al. and Mendelovici et al. supply the preparation of ziprasidone salts and formulations for drug delivery, Devouassoux et al. supplies the oxygen sensitive techniques and equipment, while Hong et al. supplies the pH of the cyclodextrin formulation. All references are directed to the development of a drug formulation and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the four references when seeking to develop a suitable ziprasidone drug formulation.
Starting with Kim et al., the skilled person only had to try the necessary claim limitations disclosed by Devouassoux et al., Mendelovici et al., and Hong et al. The combination of Kim et al., Devouassoux et al., Mendelovici et al., and Hong et al. would allow one to arrive at the present application without employing inventive skill. This combination of the ziprasidone drug formulation taught by Kim et al. along with the use of the necessary claim limitations taught by Devouassoux et al., Mendelovici et al., and Hong et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the ziprasidone drug formulation disclosed by Kim et al. with the use of the necessary claim limitations taught by Devouassoux et al., Mendelovici et al., and Hong et al. Incorporating the disclosure of Kim et al. into the oxygen-sensitive drug techniques, synthesis, and pH of the drug formulation taught by Devouassoux et al., Mendelovici et al., and Hong et al., respectively, represents a predictable use of prior art elements according to their established functions, consistent with MPEP §2143 and KSR.
Furthermore, the additional claim limitations taught by Devouassoux et al., Mendelovici et al., and Hong et al. would have been viewed by a POSITA as routine design optimizations or known modifications for drug delivery formulations. Implementing these features in Kim et al.’s ziprasidone formulations would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Kim et al., supplemented by Devouassoux et al., Mendelovici et al., and Hong et al. provides all the elements of the claimed invention. The ziprasidone drug formulation constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Response to Arguments
Applicant's arguments filed March 24, 2026 have been fully considered but they are not persuasive.
The instant claim amendments were sufficient to address the claim objection. Therefore, the objection is withdrawn from the non-final office action dated March 10, 2026.
The amendments did not necessitate a new ground of rejection.
Applicant Argument: The Applicant argues that none of the references of record support the storage of the ziprasidone formulation at 6 °C or greater for one month.
Examiner’s Rebuttal: The Examiner respectfully disagrees. Yes, none of the references of record disclose a storage temperature of 6 °C or greater for one month while maintaining the required purity.
However, Kim et al. and Mendelovici et al. teach storage of the ziprasidone formulation at temperatures close to the instant claim 1 limitation. This is especially evident with the Kim et al. citation where it discloses an inclusion complex of ziprasidone can be formed ... A product solution made with sterile water can be used as is for administration to patients immediately, no adjustment to isotonicity being required, or stored at 5 degrees C for periods of up to two years or longer (see col 7, In 47-64 within Kim et al.). If a skilled artisan (POSITA) can store the ziprasidone formulation for up to two years without degradation at 5 °C according to Kim et al., then storage for one month at 6 °C becomes obvious. Despite the fact that Kim et al. does not disclose a percent purity for the ziprasidone, a skilled artisan (POSITA) could under routine experimental conditions use HPLC to monitor the formulation purity. This is common within a synthetic organic chemist lab. Also, preparative HPLC and standard column chromatography would be available to the skilled artisan (POSITA).
In addition, Mendelovici et al. disclose crystalline ziprasidone HCl (polymorph A), which does not transform to polymorph M by more than 5% upon storage at a temperature of between about 25° and 55°C for at least 3 months (see pg 4, ln 17-19 within Mendelovici et al.).
Based on Kim et al.'s and Mendelovici et al.’s teachings, it would have been obvious to one of skilled in the art to adjust the aqueous formulation to be stored at 6 °C for one month while maintaining 98% purity.
[Furthermore, Applicant may also argue impermissible hindsight reasoning. However, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight [or piece-meal 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).]
Applicant Argument: The Applicant argues that the storage temperature is an unexpected result.
Examiner’s Rebuttal: The Examiner respectfully disagrees. Kim et al. teach storage of the ziprasidone formulation close to the instant claim 1 limitation (see the discussion above). Additionally, evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (Claims directed to a method of effecting analgesia without producing physical dependence by administering the levo isomer of a compound having a certain chemical structure were rejected as obvious over the prior art. Evidence that the compound was unexpectedly nonaddictive was sufficient to overcome the obviousness rejection. Although the compound also had the expected result of potent analgesia, there was evidence of record showing that the goal of research in this area was to produce an analgesic compound which was nonaddictive, enhancing the evidentiary value of the showing of nonaddictiveness as an indicium of nonobviousness.). [see M.P.E.P. 716.02(c)]. In this instance, the prior art of record is stronger than the unexpected results.
Thus, the 35 U.S.C. §103 rejection for instant claims 1, 4, 7-9, and 11-23 is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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