DETAILED ACTION
This action is in response to papers filed on 02/12/2026. Claims 1-6, 8-14, 17, 19, and 21-26 of A. Lena et al., 17/628,578 (01/20/2022) are pending examination on the merits: claims 1, 17, 19, and 21 are amended, claims 7, 15, 16, 18, and 20 are cancelled, and claims 25-26 are newly added. Claims 1-6, 8-14, 17, 19, and 21-26 are maintained as rejected.
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 is a 371 of PCT/IB2020/057404 filed on 08/05/2020 and claims Foreign Priority to ITALY 10 2019 000014346 filed on 08/08/2019.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/12/2026 has been entered.
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.
Claims 1-6, 8-14, 17, 19, and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Juhasz et al., (2018), WO 2018/165071 A1 (“Juhasz”), in view of:
Karimian et al., US5847118 (“Karimian”)
Cote et al., (US20090111997A1) (“Cote”)
Sanganabhatla et al., (US 2011/0105619 A1) (“Sanganabhatla”)
Regarding claim 1, Juhasz teaches the “solid state forms of Midostaurin, processes of preparation, pharmaceutical compositions thereof, and use thereof in the treatment of Acute Myelogenous Leukemia (AML) and Aggressive Systemic Mastocytosis.” (Abstract).
More specifically, Example 2c of Juhasz teaches limitations of claim 1.
Juhasz Example 2c teaches a process of preparing the amorphous form Midostaurin, following the crude pre-purification of Midostaurin via HPLC on a silica gel column in toluene/methanol. The steps include:
Dissolving the pre-purified product of Midostaurin in Dimethyl-formamide (DMF).
The solution (a) is filtered and the filtrate is added to water.
The solution of (b) is then filtered and a filtered solid is obtained.
The filtered solid of (c) is then stirred in a second amount of water and filtered.
The filtrate of (d) comprised a filtered solid, which is then dried.
The dried solid of (e) is amorphous Midostaurin.
While Juhasz teaches DMF in (a), the claimed invention teaches dimethylsulfoxide (DMSO).
Karimian teaches a process for preparing an amorphous form of a drug comprising the steps of dissolving crystalline form of the drug in a highly polar organic solvent and adding the resulting solution to water (Abstract). For example, in Example 2:
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Karimian Example 2 teaches the use of 15 ml of dimethyl sulfoxide to dissolve the crystalline compound and in Example 1, 12 ml. To one of skill in the art, aprotic solvents such as DMSO and DMF are routine in the art of crystallization.
It would have therefore been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the process as taught by Juhasz which includes the use of DMF and substituting it for another aprotic solvent (i.e., DMSO) in view of Karimian, and arrive at the claimed process using DMSO as the solvent. One would have been motivated to do so, with reasonable expectation of success, because the substituting of one aprotic solvent (DMF) for another (DMSO) is an obvious alternative in the art of forming amorphous compounds. The use of these aprotic solvents is routine in the art and function, not only as solvents, but solvents that are regularly used in the formation of amorphous compounds as taught by Karimian. Moreover, it would be obvious to one of ordinary skill in the art that the product would contain residual amounts of DMSO since it is the solvent used to solubilize the starting material as disclosed above. Regarding the residual amount of DMSO from 100 to 5000 ppm, to one of ordinary skill in the art, this may be optimized through, for example, further washing of the product with water, which is disclosed above by Juhasz in view of Karimian until the acceptable organic solvent levels are obtained. Therefore, "[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). Moreover, said parameters are recognized in the art as a result-effective variables (i.e., a variable which achieves a recognized result), and thus the determination of the optimum or workable ranges of said variables are characterized as routine experimentation. MPEP § 2144.05.
Furthermore, while Juhasz in view of Karimian teaches the process as disclosed above, Juhasz in view of Karimian does not expressly teach wherein said step b) is carried out at a temperature varying from 20 0C to 40 0C.
Sanganabhatla teaches the amorphous preparation of a compound wherein the temperature at which the first amount of water is combined with the initial dissolution mixture ranges from about 0 0C to about 130 0C. Sanganabhatla at page 3, para. [0044]. Sanganabhatla’s disclosed range overlaps the claimed range, establishing a prima facie case of obviousness. Para. [0044] of Sanganabhatla expressly disclosing that “… the dissolution temperature…may range from about 0 ⁰C – 130 ⁰C, or the reflux temperature of solvent used…”, unambiguously encompasses the temperature range recited in the present claims (i.e., 20 ⁰C – 40 ⁰C). Where claimed process parameters overlap or lie within the ranges disclosed in the prior art, a prima facie case of obviousness is established. The burden then shifts to the Applicant to show that the claimed sub-range yields unexpected results. Applicant has not provided any such evidence of criticality or unexpected performance for operating within 20 ⁰C – 40 ⁰C relative to the 0 ⁰C – 130 ⁰C range taught by Sanganabhatla. The recited temperature range represents room to moderate temperatures routinely employed to achieve amorphous precipitates without degradation.
It would have therefore been obvious to one of ordinary skill in the art to carry out the process within the same parameters as disclosed by Sanganabhatla in the preparation of an amorphous form of midostaurin, and arrive at the claimed invention successfully. One would have been motivated to do so, with reasonable expectation of success, because the temperature range is used to prepare stable amorphous compounds, similar to the claimed midostaurin, as disclosed by Sanganabhatla. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Moreover, "[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). Claim 1 is therefore obvious over Juhasz in view of Karimian and Sanganabhatla’s.
Regarding claim 2, Juhasz in view of Karimian teaches the process according to claim 1. As disclosed above, Karimian, in the process steps of preparing a pure amorphous drug, in Example 2 teaches the use of 15 ml of dimethyl sulfoxide to dissolve 5 g of the crystalline compound which is about 3 ml of DMSO per gram of crystalline compound (15 ml of DMSO/5 g of crystalline compound = 3 ml of DMSO per gram of the compound). The claimed range varies from 1 to 30 ml of DMSO per gram of midostaurin. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Claim 2, as is claim 1, is also obvious.
Regarding claim 3, Juhasz in view of Karimian teaches the process according to claim 1. Karimian teaches in Example 2, that 6 ml of first amount of added deionized was used. This is equivalent to 6 ml of deionized water divided by 5 grams of crystalline compound, where the ratio is equivalent to about 1.2 ml of deionized water per gram of crystalline compound. This amount is variable as shown in Example 1 of Karimian where the ratio is about 20 ml of water per gram of crystalline compound. The claimed range varies from 1 to 30 ml of the first amount of water per gram of midostaurin. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Claim 3, as is claim 1, is also obvious.
Regarding claim 4, Juhasz in view of Karimian teaches the process according to claim 1. As applied above to claims 1-3, the ratios are results effective and can be routinely optimized based on desirability.
Nonetheless, while Juhasz in view of Karimian do not expressly teach wherein said first amount of water varies from 0.5 to 1.5 parts in volume per part in volume of DMSO of the solution of step a), Cote Example 1 teaches a method for making an amorphous solid where “the ratio of DMSO to water ratio… ranges from ½ to 1/3…”. Therefore, it would have been obvious to one of ordinary skill in the art, to use similar ratios of DMSO to water in preparation of an amorphous form of midostaurin in view of the cited prior arts, and arrive at the claimed invention successfully. Furthermore,"[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). Claim 4 is also obvious over Juhasz in view of Karimian, and in further view of Cote.
Regarding claim 5, Juhasz in view of Karimian teaches the process according to claim 1. Juhasz in view of Karimian does not expressly teach wherein said step b) is carried out at a temperature varying from 20 0C to 40 0C.
Sanganabhatla teaches the amorphous preparation of a compound wherein the temperature at which the first amount of water is combined with the initial dissolution mixture ranges from about 0 0C to about 130 0C. Sanganabhatla at page 3, para. [0044]. It would have therefore been obvious to one of ordinary skill in the art to carry out the process within the same parameters as disclosed by Sanganabhatla in the preparation of an amorphous form of midostaurin, and arrive at the claimed invention successfully. One would have been motivated to do so, with reasonable expectation of success, because the temperature range is used to prepare stable amorphous compounds, similar to the claimed midostaurin, as disclosed by Sanganabhatla. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Moreover, "[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). Claim 5 is obvious over Juhasz in view of Karimian, and in further view of Sanganabhatla.
Regarding claims 6, the claim is interpreted to depend from claim 1. Juhasz in view of Karimian teaches the process according to claim 1. Juhasz in view of Karimian does not expressly disclose the time range in step b), whereby the first amount of water is added to the solution of step a). However, said time range is recognized in the art as a result-effective variables (i.e., a variable which achieves a recognized result), and thus the determination of the optimum or workable ranges of said variables are characterized as routine experimentation. MPEP § 2144.05. Moreover, "[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). In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). Claims 6-7 are obvious.
Regarding claim 8, Juhasz in view of Karimian teach the process according to claim 1. Karimian, for example, teaches in Example 2 that the precipitate formed was filtered and washed, before being added to a second amount of water. "[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). In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").Claim 8, is also obvious.
Regarding claim 9, Juhasz in view of Karimian teach the process according to claim 1. Karimian teaches in Example 2, that 90 ml of deionized was used. This is equivalent to 90 ml of deionized water divided by 5 grams of crystalline compound, where the ratio is equivalent to about 18 ml of deionized water per gram of crystalline compound. The claimed range varies from 10 to 30 ml per gram of first filtrate of step c). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Claim 9, as is claim 1, is also obvious.
Regarding claim 10, Juhasz in view of Karimian teach the process according to claim 1. As disclosed by Juhasz, “The filtered solid washed two times with 850 ml water by stirring for 30 minutes, and filtered…”. Juhasz at page 26, para. [0134]. Claim 10, as is claim 1, is also obvious.
Regarding claim 11, Juhasz in view of Karimian teach the process according to claim 1. Juhasz at page 26, para. [0134]:
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Karimian also teaches in Example 2: “The damp cake was pulped in ice cold deionized water (30 ml) for 10 minutes, filtered and washed. Pulping was repeated once more. The cake was then dried under a stream of nitrogen for 42 hours and then dried under vacuum at 40° - 45° C. for 48 hours. Karimian at col. 4. Claim 11, is also obvious.
Regarding claim 12, Juhasz in view of Karimian teach the process according to claim 1. As disclosed above, Juhasz in view of Karimian teaches the process of drying is carried out in a vacuum. Juhasz at page 26, para. [0134] and Karimian at col. 4. Claim 12, as is claim 1, is also obvious.
Regarding claim 13, Juhasz in view of Karimian teach the process according to claim 1. Juhasz in view of Karimian teaches an overall range of about 40 °C to about 80 °C for the drying temperature for the amorphous compound, as disclosed above. Moreover, "[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). Claim 13 is also obvious.
Regarding claim 14, Juhasz in view of Karimian teach the process according to claim 1. As disclosed above, both Juhasz and Karimian teach a drying time of about 48 hours, which falls within the claimed range. Moreover, "[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). Claim 14 is also obvious.
Regarding claims 17, Juhasz teaches an amorphous form of midostaurin in Example 2c as disclosed above.
Considering that Juhasz process, as discussed above, uses DMF as an aprotic solvent for step (a), the final product would therefore be essentially free of DMSO, and thus meet the claim limitation of “An amorphous form of midostaurin comprising a residual amount of dimethylsulfoxide, wherein said residual amount is from 100 to 5000 ppm” as per claim 17. Claim 17 is therefore also obvious over Juhasz.
Regarding claim 19, the present claim recites a limitation wherein an amorphous form of midostaurin is claimed as a pharmaceutical composition, and wherein the claimed amorphous form of midostaurin is made by the process recited in claim 1.
As disclosed above, Juhasz teaches the process of preparing an amorphous form of midostaurin in Example 2c and as further disclosed above in claim 17, an amorphous form of midostaurin that is essentially dimethylsulfoxide free.
Juhasz further teaches on p. 3, para [013] and [017] the solid forms of Midostaurin in pharmaceutical compositions, for the treatment of Acute Myelogenous Leukemia (AML) and Aggressive Systemic Mastocytosis, by combining a solid state of midostaurin and at least one pharmaceutically acceptable excipient. Claim 19, is obvious over Juhasz.
Regarding claims 21-24, and as disclosed and applied above, Juhasz teaches an amorphous form of midostaurin, that is essentially free of dimethylsulfoxide (i.e., as per claim 17 above) in a pharmaceutical preparation (i.e., as per claim 19 above) for the treatment of acute Myelogenous Leukemia (AML) and Aggressive Systemic Mastocytosis (p. 3, para [013] and [017]).
Juhasz teaches the limitations of claims 21-24 and as such, the claims are also obvious.
Regarding claims 25-26, Juhasz in view of Karimian teaches the process according to claims 1 and 17. The recitation of wherein said residual amount of DMSO is from 150 to 2500 ppm can be routinely obtained through optimized washes of the product, to obtain the disclosed amounts. As disclosed in MPEP § 2144.05, it is within the skill of an artisan to routinely optimize and formulate the claimed range in order to arrive at the claimed invention with reasonable expectation of success. See In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) which states, "where 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." See MPEP § 2144.05, "II. Optimization of Ranges". Claims 25-26 are also obvious.
Applicant’s Arguments
Applicant argues that Juhasz’s amorphous Midostaurin exceeds the concentration limit of DMF and is not compliant with Federal guidelines. Applicant’s Remarks at page 8. Applicant argues that DMSO’s limit is 5000 ppm and although DMSO has a higher concentration limit than DMF, DMSO is significantly less volatile than DMF. Applicant’s Remarks at page 9. Applicant argues that DMSO has a boiling point of 189 degrees Celsius, while DMF has a boiling point at room temperature and pressure equal to 153 degrees Celsius. Applicant further argues other physical properties of both DMSO and DMF. Applicant’s Remarks at pages 9-10. Applicant argues that Juhasz’s conditions were not capable of removing significant residual amounts of DMF (i.e., 3900 ppm), and that one of ordinary skill in the art would not have been motivated to substitute DMF for DMSO with reasonable expectation of success at obtaining an amorphous Midostaurin comprising residual amount of DMSO from 100 to 5000 ppm because DMSO is significantly less volatile than DMF.
Applicant argues that 48 hours of during at 80 degrees Celsius and 100 mbar were not able to remove significant amounts of DMF, thus one of ordinary skill in the art would not have been motivated to substitute DMF for DMSO – increasing the drying time and/or temperature to facilitate the evaporation of the solvent with reasonable expectation of success of obtaining an amorphous Midostaurin comprising a residual amount of DMSO from 100 to 5000 ppm due to DMSO being significantly less volatile than DMF. Applicant’s Remarks at pages 10-11.
Applicant then argues the terms “solution” and “suspension” in steps (a) and steps (b) and as such, the teachings of Sanganabhatla cannot be construed as directed to step (b) of the present process and only to step (a). Applicant’s Remarks at page 12. Applicant further argues the Sanganabhatla reference, citing that it is incompatible with Juhasz and Karimian, and that none of the references teach the disclosed amounts of DMSO from 100 to 5000 ppm, more preferably 150 to 2500 ppm per newly added claims 25 and 26. In sum, Applicant argues against the prior arts: Juhasz in view of Karimian, Sanganabhatla and/or Cote, as not teaching, suggesting or motivating one of ordinary skill in the art to arrive at the claimed invention.
Examiner’s Response
Applicant’s arguments are acknowledged, but are not found to be persuasive in view of the rejections set forth. Applicant contends that the presently claimed invention is patentably distinct from the cited prior art because Juhasz teaches the use of dimethylformamide (DMF), rather than dimethylsulfoxide (DMSO) as recited in the present claims, and that Karimian fails to cure this alleged deficiency. Regarding the solvent system, while Juhasz specifically exemplifies DMF as a solvent for preparing amorphous midostaurin, the choice of DMF or DMSO represents an obvious substitution of one well-known polar aprotic solvent for another.
Both DMF and DMSO are routinely used interchangeably in pharmaceutical crystallization and amorphization processes due to their similar physiochemical properties. Substituting DMSO for DMF in Juhasz would have been an obvious design choice to one of ordinary skill in the art seeking to achieve equivalent dissolution of midostaurin, as evidenced by the general teachings in Karimian and Cote, which disclose DMSO as a conventional solvent in comparable pharmaceutical contexts. As discussed above, to one of skill in the art, aprotic solvents such as DMSO and DMF are routine in the art of crystallization. Moreover, in order to reduce the amount of DMSO present such that the amounts fall within any guideline, one of skill in the art would be motivated to wash the product with water to further reduce any trace amount of organic solvents such as DMSO. This is routine and considered within the technical grasp of one skill in the art.
Regarding the claimed temperature range (i.e., 20 ⁰C – 40 ⁰C), Juhasz teaches process steps involving dissolution of midostaurin in a solvent (e.g., DMF), followed by addition of water to form an amorphous solid. Applicant argues that Sanganabhatla is completely silent regarding the temperature range for obtaining a first suspension of the active ingredient, and further contends that para. [0044] of Sanganabhatla relates only to dissolution (i.e., step a) and not to suspension (i.e., step b) of the claimed process. Applicant also argues that Sanganabhatla teaches away from the present invention because it allegedly emphasizes precipitation of the active ingredient rather than dissolution.
These arguments are also not found to be persuasive for the following reasons:
Sanganabhatla’s disclosed range overlaps the claimed range, establishing a prima facie case of obviousness. Para. [0044] of Sanganabhatla expressly discloses that “… the dissolution temperature…may range from about 0⁰C–130⁰C, or the reflux temperature of solvent used…”. This disclosure unambiguously encompasses the temperature range recited in the present claims (i.e., 20 ⁰C – 40 ⁰C).
Where claimed process parameters overlap or lie within the ranges disclosed in the prior art, a prima facie case of obviousness is established. The burden then shifts to the Applicant to show that the claimed sub-range yields unexpected results. Applicant has not provided any such evidence of criticality or unexpected performance for operating within 20 ⁰C – 40 ⁰C relative to the 0 ⁰C – 130 ⁰C range taught by Sanganabhatla. The recited temperature range represents room to moderate temperatures routinely employed to achieve amorphous precipitates without degradation.
Accordingly, even if Sanganabhatla’s disclosure were considered to apply to a dissolution step rather than a suspension step, the temperature condition is materially identical to that of the claimed process, and optimization of a known variable within a known range is routine experimentation, which is consistent with In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) which states, "where 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.".
Moreover, the distinction between the term “solution” of step (a), and “suspension” of step (b) is fully addressed by the prior art, and discussed above. Applicants’ argument regarding the terms “solution” and “suspension” in steps (a) and steps (b) and citing such terms as disqualification of Sanganabhatla applicability to step (b) of the present process and only to step (a) is also not persuasive. Sanganabhatla discloses general solvent exchange and precipitation techniques for obtaining amorphous pharmaceutical solids. While it may describe certain embodiments using lower temperatures to achieve precipitation, it does not criticize or dissuade operation at moderate temperatures such as 20 ⁰C – 40 ⁰C, nor does it indicate that such temperatures would be unsuitable. A reference teaches away only when it discourages the combination in such a manner that a person of ordinary skill would be led to a different direction; no such teaching is found here.
Consistent with this reasoning, the combination of the prior art references teaches the overall process that inherently involves dissolution of the drug in a polar aprotic solvent (e.g., DMF or DMSO), followed by the addition of water to yield an amorphous or partially amorphous solid. This process unavoidably passes through a supersaturation to suspension to precipitation continuum. A person of ordinary skill in the art would recognize that the temperature of the dissolution medium and that of the subsequent water-addition step are generally maintained within similar ranges (i.e., ambient to moderately elevated) to ensure homogeneity and reproducibility of the amorphous solid. Sanganabhatla therefore implicitly teaches operation within the claimed temperature range for both dissolution and initial suspension formation.
It would have therefore been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the process of Juhasz by substituting DMSO for DMF (as suggested by Karimian and Cote), and by performing the water-addition step at standard processing temperatures 20⁰C–40⁰C to obtain an amorphous form with acceptable residual solvent levels. The motivation for such modification arises from the desire to optimize solvent selection and processing parameters for solvent removal, stability, and amorphous purity which are well recognized concern in pharmaceutical manufacturing. Accordingly, the Applicant’s arguments are not found to be persuasive. The combination of prior art references continues to render the claimed invention obvious to one of ordinary skill in the art.
What Applicant argues is considered to be within routine experimentation to fine-tune the process of claim 1. Said parameters are recognized in the art as a result-effective variables (i.e., a variable which achieves a recognized result), and thus the determination of the optimum or workable ranges of said variables are characterized as routine experimentation. MPEP § 2144.05. It would be obvious to routinely wash the product for example to further remove any DMSO and to obtain amounts within any defined guideline. The claims are therefore held to be obvious over Juhasz in view of in view of Karimian, Cote, and Sanganabhatla.
Conclusion
No claims are allowed.
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/C A/Examiner, Art Unit 1622 March 18, 2026
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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