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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11 August 2026 has been entered.
Priority
The instant application was filed 30 March 2023 and is the national stage entry of PCT/EP2021/076996 filed 30 September 2021. The Applicant claims priority to provisional application 63/086,691 filed 02 October 2020 and several foreign documents with the earliest priority date of 08 October 2020. The earliest priority date for the limitation including water in claim 21 appears to be 11 January 2021. Claims 1-14, 16-21 have an effective filing date of 08 October 2020.
Examiner’s Note
The Applicant's amendments and arguments filed 11 August 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections not reiterated from previous office actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 11 August 2026, it is noted that claim 1 has been amended for a typographical error and no new claims have been added or canceled. No new matter has been added.
Claim Objections
Claim 1 is objected to because of the following informalities: the Applicant is advised to amend “step b” to “step 4” for consistency reasons. Appropriate correction is required.
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.
Claim(s) 1-14, 16-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bittorf (US 2009/0247468 A1), Friesen (Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview, Molecular Pharmaceutics, 2008), and Schade (Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation, Blood, 2007).
Regarding claim 1, Bittorf teaches methods (step b) of spray drying (entire teaching; abs) dispersions (para. 7) comprising an active ingredient (para. 199), 5-30% (para. 104) HPMCAS (dispersion polymer) (para. 153), water (para. 16), alcohols (para. 141), and acetic acid (para. 16), wherein the amounts of solvents may have a wide range, such as 0.1-15% acetic acid and 40-80% of a volatile solvent, such as an alcohol (paras. 18, 141) (step 1). Bittorf teaches the formation of a solution by solubilizing a polymer (para. 7) (step 1). The preparation to be spray dried includes a therapeutic agent and may form a slurry (para. 115) (step 2). Bittorf does not specify that the solution necessarily becomes a supersaturated solution (component iii). The composition may be a solution, which is interpreted as a single-phase solution (one liquid phase) (para. 8).
Regarding claim 2, the compound of interest possibly becoming supersaturated (para. 165), as well as the use of a non-volatile solvent, such as acetic acid (paras. 140, 142), to increase the solubility of the drug is interpreted as addressing the solubility limitation in claim 2.
Regarding claims 3, 9, and 11, the amount of active ingredient may be about 5-95% (para. 199).
Regarding claim 5, the composition comprises 0.1-15% acetic acid (para. 18).
Regarding claim 7, the composition comprises about 0.1-15% (para. 22) water as a solvent
Regarding claim 10, the composition comprises 5-30% of HPMCAS (para. 104).
Regarding claim 12, the drugs or active agent may be any beneficial therapeutic agent (para. 107), which is interpreted as a biologically active compound
Regarding claim 13, the drugs or active agent may be any beneficial therapeutic agent (para. 107), which is interpreted as a drug compound.
Regarding claims 16-18, the composition comprising HPMCAS (Applicant’s election) is interpreted as addressing the pharmaceutically acceptable dispersion polymer limitation.
Regarding claims 19 and 20, the composition may comprise residual solvents (para. 279), which includes acetic acid, and the residual solvents may be evaporated, which is interpreted as being below 5,000 ppm.
Regarding claim 21, the composition may comprise water and an alcohol as solvents.
Bittorf does not teach Dasitinib (component ii) or a specific alcohol (component i: C1-3 alkanol) in claims 1 and 6. Bittorf does not teach specific molar equivalents of acetic acid in claim 4 or weight ratios of the alcohol to water in claim 8. Bittorf does not specify an active agent with a basic pKa of 4 or 5 or greater in claims 1 and 14.
Friesen teaches that solid dispersions with HPMCAS are very soluble in solvents, such as methanol, and also provides an economical advantage for the spray drying process (pg. 1009).
Schade teaches that Dasatinib is an oral small molecule and tyrosine kinase inhibitor used to treat certain cancers (abs).
In regards to selecting the combination of an active agent, an alcohol, water, HPMCAS, and acetic acid in Bittorf’s teaching in claim 1, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Consistent with this reasoning, it would have been obvious to have selected various combinations of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Since Bittorf does not teach Dasatinib or a specific alcohol in claims 1, 6, and 14, one of ordinary skill in the art would have been led to use Friesen and Schade’s teachings of methanol and Dasatinib, as Friesen teaches that HPMCAS and methanol provide economical and solubility advantages when used together and Bittorf teaches that the drug used in their composition may be a small molecule drug (para. 10). A person of ordinary skill in the art would have been motivated to combine the teachings depending on what the skilled artisan intended to treat, such as certain cancers where a small molecule drug, such as Dasatinib would be desirable to use. Applicant’s election of Dasatinib is interpreted as addressing the pKa, solubility, and Bronstedt base limitations in claims 1 and 14. “Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).”
In regards to the specific molar equivalents of acetic acid in claim 4 or weight ratios of the alcohol to water in claim 8, Bittorf teaches 0.1-15% acetic acid (para. 18), 40-80% of a volatile solvent, such as an alcohol (paras. 18, 141), and 1-15% (para. 22) water. That being said and in lieu of objective evidence of unexpected results, the molar equivalence and weight ratios of solvents can be viewed as a variable that achieves the recognized result of successfully performing the method of spray drying a solid dispersion of an active agent. The optimum or workable range of amounts and ratios can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of solvents as nonobvious.
Response to Arguments
Applicant's arguments filed 11 August 2026 have been fully considered but they are not persuasive.
The Applicant argues that Bittorf does not teach spray drying of a slurry (Remarks, pg. 6).
Applicant’s argument is not found persuasive. Bittorf’s teaching cites that the preparation to be spray dried can be any solution, suspension, coarse suspension, colloidal dispersion, paste, or slurry (para 115).
The Applicant argues that Bittorf teaches away from using C1-3 alkanols (i.e. methanol, ethanol, and/or propanol) (Remarks, pg. 7).
Applicant’s argument is not found persuasive. In response to the Applicant's argument that the references fail to show certain features of applicant’s invention, it is reminded that to properly teach away, the prior art reference must criticize, discredit, or otherwise discourage the solution sought. Merely teaching alternatives does not do this (see MPEP 2145 (X)(D)).
The Applicant argues that VX-950 (Telaprevir) does not have a basic pKa of greater than 4 or 5 (Remarks, pgs. 7-8).
Applicant’s argument is not found persuasive. Since Bittorf does not teach Dasatinib (Applicant’s election), one of ordinary skill in the art would have been led to use Friesen and Schade’s teachings of methanol and Dasatinib, as Friesen teaches that HPMCAS and methanol provide economical and solubility advantages when used together and Bittorf teaches that the drug used in their composition may be a small molecule drug (para. 10). A person of ordinary skill in the art would have been motivated to combine the teachings depending on what the skilled artisan intended to treat, such as certain cancers where a small molecule drug, such as Dasatinib would be desirable to use. Applicant’s election of Dasatinib is interpreted as addressing the pKa, solubility, and Bronstedt base limitations in claims 1 and 14. “Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).”
The Applicant argues that the cited combination of teachings does not teach the sequential process steps of claim 1 (Remarks, pgs. 8).
Applicant’s argument is not found persuasive. Regarding claim 1, Bittorf teaches methods (step b) of spray drying (entire teaching; abs) dispersions (para. 7) comprising an active ingredient (para. 199), 5-30% (para. 104) HPMCAS (dispersion polymer) (para. 153), water (para. 16), alcohols (para. 141), and acetic acid (para. 16), wherein the amounts of solvents may have a wide range, such as 0.1-15% acetic acid and 40-80% of a volatile solvent, such as an alcohol (paras. 18, 141) (step 1). Bittorf teaches the formation of a solution by solubilizing a polymer (para. 7) (step 1). The preparation to be spray dried includes a therapeutic agent and may form a slurry (para. 115) (step 2). Bittorf does not specify that the solution necessarily becomes a supersaturated solution (component iii). The composition may be a solution, which is interpreted as a single-phase solution (one liquid phase) (para. 8).
The Applicant argues that VX-950 (Telaprevir) falls outside the claimed basic pKa range (Remarks, pg. 8).
Applicant’s argument is not found persuasive. As mentioned above, Applicant’s election of Dasatinib is interpreted as addressing the pKa, solubility, and Bronstedt base limitations in claims 1 and 14.
The Applicant argues that Friesen does not provide any teaching related to using acetic acid to solubilize a basic drug in methanol (Remarks, pg. 8).
Applicant’s argument is not found persuasive. Friesen teaches that solid dispersions with HPMCAS are very soluble in solvents, such as methanol, and also provides an economical advantage for the spray drying process (pg. 1009). Therefore, a person of ordinary skill in the art would have been motivated to combine the teachings depending on what the skilled artisan intended to treat, especially with Friesen’s teaching of an economical advantage and good solubility of solid dispersions comprising HPMCAS.
The Applicant argues that Schade does not teach spray drying, solid dispersions, or solvent systems (Remarks, pg. 8).
Applicant’s argument is not found persuasive. Schade teaches that Dasatinib is an oral small molecule and tyrosine kinase inhibitor used to treat certain cancers (abs). Therefore, a person of ordinary skill in the art would have been motivated to combine the teachings depending on what the skilled artisan intended to treat, such as certain cancers where a small molecule drug, such as Dasatinib would be desirable to use.
The Applicant argues the combination of the teachings is an impermissible hindsight combination (Remarks, pg. 8).
Applicant’s argument is not found persuasive. 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).
Conclusion
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
