DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3 March 2026 has been entered, and the arguments presented therein have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Note Regarding Class II Compounds
The instant claims require a poorly [water] soluble compound categorized as a Class II compound according to the Biopharmaceutics Classification System. The examiner takes the position that cyclosporine is such a compound. Support for this position is obtained in view of Janssens et al. (US 2011/0018154 A1), paragraph 0164, which is reproduced below with annotation by the examiner.
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As such, the skilled artisan would have understood cyclosporine to have been a BCS class II drug.
Claim Interpretation
Instant claim 1 recites particles having 10% to 40% drug load. For the purposes of examination under prior art, the examiner understands this to mean that 10% to 40% of the particles is made up of drug.
The examiner notes that the phrase “drug load” is understood to differ from the phrase “encapsulation efficiency” or “loading efficiency.” The examiner understands the phrase “encapsulation efficiency” to refer to the percentage of drug used in the beginning of a process of producing nanoparticles that eventually becomes encapsulated in the particles. This differs from “drug load”, which is drawn to the proportion of the particles that comprises the drug.
Instant claim 1 recites an amorphous solid dispersion. This is defined in the specification as of page 4, paragraph 0010, reproduced below.
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See also footnote #8 of the board decision on 22 February 2023, which states the following.
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As best understood by the examiner, a prior art reference teaching polymeric nanoparticle comprising an active agent is understood to be an amorphous solid dispersion if the polymer is solid at room temperature and neither the polymer or the drug is taught to be in crystalline form. The examiner understands such a nanoparticle, in the case wherein it comprises a drug, to be a solid dispersion even if it the nanoparticle itself is dispersed in a liquid such as water. This is because the nanoparticle itself would appear to be a solid dispersion as it comprises the drug dispersed therein, even if the composition as a whole appears to be liquid.
The examiner notes that the claims use the language “such that” at various locations in the claim. The examiner clarifies that “such that” has a different meaning as compared with “such as.” The examiner notes that “such as” may be subject to rejections under 35 U.S.C. 112(b), as per MPEP 2173.05(d). However, the rationale presented in this section does not apply to the claim limitations which recite “such that.” This is because the phrase “such that” has a different meaning as compared with “such as.”
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1-4, 6-9, 14, 16-20, 23, 26, 31-34, 37, 39-41, 43, 52, 54-55, 58-59 and 61-64 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lomuscio et al. (US 2014/0206742 A1) in view of Shen et al. (US 2011/0306539 A1), Panagiotou et al. (US 2009/0269250 A1), and Shen et al. (US 2012/0037232 A1).
Lomuscio et al. (hereafter referred to as Lomuscio) is drawn to a method of producing a drug delivery form with improved bioavailability, as of Lomuscio, title, abstract, and figure on front page, which is reproduced below.
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Lomuscio teaches the following on page 7, wherein relevant text is reproduced below.
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Lomuscio teaches an amorphous MBP (i.e. microprecipitated bulk powder) suspension as of page 7, right column, paragraph 0102 and Table 4, and teaches co-precipitation with Eudragit L100 polymer in paragraph 0103.
Lomuscio does not teach microfluidization or microreaction, and does not teach channels with a diameter of about 10 microns to about 400 microns. Lomuscio also does not teach controlling flow rates.
Shen et al. (hereafter referred to as Shen) is drawn to a process for making drug nanoparticles, as of Shen, title and abstract. Shen teaches combining active agent (in one embodiment fenofibrate) with surfactant (in one embodiment sodium lauryl sulfate) in solvent (ethanol) then combining with antisolvent (water), as of Shen, paragraphs 0290-0291. Shen uses a “micro-mixing” environment, as of Shen, abstract, which is understood to read on the required microreactor. Shen teaches a pipe diameter of 0.01 mm to 5.0 mm (10 µm to 5000 µm), as of Shen, paragraph 0140; this is understood to overlap with the required channel width. Shen teaches flow rates of the solutions in paragraphs 0256 and 0411.
It would have been prima facie obvious for one of ordinary skill in the art to have used the reactor of Shen to have mixed the reactants of Lomuscio. Lomuscio teaches a reaction scheme for making particles for drug delivery, but appears to be silent regarding a reactor to carry out this reaction. As the reactor of Shen appears to be useful for making particles for drug delivery, the skilled artisan would have been motivated to have used the reactor of Shen to have predictably made the particles of Lomuscio with a reasonable expectation of success.
Neither Lomuscio nor Shen teach the required pressure.
Panagiotou et al. (hereafter referred to as Panagiotou) is drawn to apparatus for nanoparticle generation using microreactor technology, having the following structure, as of Panagiotou, title, abstract, and figure in abstract, reproduced below.
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The method of Panagiotou utilizes a solvent and antisolvent stream, and optionally a surfactant, as of Panagiotou, paragraph 0081, reproduced below.
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Panagiotou teaches precipitation in paragraph 0081, reproduced above; this is understood to read on the required formation of amorphous particles, as per the footnote on page 13 of the appeal decision mailed on 22 February 2023. Paragraphs 0109 and 0117 were also cited by the footnote on page 13 of the board decision mailed on 22 February 2023 to teach that the precipitation taught by Panagiotou differs from crystallization and thereby forms amorphous particles. The method of Panagiotou appears to be continuous, as of claim 25 of Panagiotou. The examiner also notes that the maximum pressure of 40,000 psi taught by Panagiotou in the above reproduced figure is understood to be about 2758 bar. Panagiotou teaches controlling the flow rate ratios of the streams in paragraphs 0065, 0071, and elsewhere in the document.
It would have been prima facie obvious for one of ordinary skill in the art to have varied the pressure in Shen to have been in the range taught by Panagiotou. Shen is drawn to a method of mixing ingredients, and appears to teach that the pressure may be varied, as of paragraph 0123 of Shen. Panagiotou teaches pressures that may be used for mixing ingredients, as of Panagiotou, above-reproduced figure, and also teaches precipitation which forms amorphous particles. As such, the skilled artisan would have been motivated to have varied the pressure in the method of Shen in the manner taught by Panagiotou in order to have predictably mixed the ingredients in Shen with a reasonable expectation of success.
Neither Lomuscio, Shen, nor Panagiotou appear to teach the required channel diameter.
Shen et al. (US 2012/0037232 A1) (hereafter referred to as Yun after the second inventor) is drawn to a microchannel double pipe device, as of Yun, title and abstract. Yun teaches preparation of particles with a micron structure, as of Yun, end of abstract, relevant text reproduced below.
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Yun teaches a channel diameter of 0.01 mm to 5 mm as of Yun, paragraphs 0014, 0027, 0048, and elsewhere in the document; this is 10 microns to 5000 microns. This diameter appears to apply to the following portion of the device of Yun, as of Yun, figure on front page, reproduced below with annotation by the examiner.
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The diagram of Yun appears to show that the portions of the channel prior to the nozzle are actually narrower than the portion of the channel at the nozzle, as of the above-reproduced diagram. Yun teaches the use of high pressure, as of at least Yun, paragraphs 0033-0034. The method of Yun appears to be useful for manufacturing a particle comprising an active agent, lactose, and a surfactant, as of Yun, paragraph 0069, reproduced below.
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Yun teaches precipitation, as of at least paragraph 0038, which the examiner understands to refer to formation of an amorphous, non-crystalline particle. The examiner notes that Yun does appear to teach spray drying as a way of purifying the precipitate; however, the inclusion of this spray drying step is not actually excluded by the claimed method.
Yun is silent as to the drug load.
It would have been prima facie obvious for one of ordinary skill in the art to have incorporated the teachings of Yun to improve the process of Lomuscio. Lomuscio is drawn to a process that entails mixing an active agent and a polymer in an organic solvent with an aqueous anti-solvent which is soluble in the organic solvent to produce particles. Yun also teaches mixing an active agent and excipients in an organic solvent (i.e. ethanol) with an aqueous anti-solvent to form particles. As such, the skilled artisan would have looked to the teachings of Yun in order to have predictably improved the process of Lomuscio with a reasonable expectation of success. Use of known technique (e.g. the mixing technique of Yun) to improve similar methods (the method of Lomuscio is similar to Yun in that both entail mixing a water-miscible organic solvent with water in order to produce particles) in the same way is prima facie obvious. See MPEP 2143, Exemplary Rationale C.
As to claim 1, the particle sizes of Lomuscio, paragraph 0081, appear to overlap with the claimed size range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I). Additionally, Lomuscio teaches the following, as of page 2, paragraph 0027, relevant text reproduced below.
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As such, the skilled artisan would have been motivated to have reduced and/or optimized the particle size in the method of Lomuscio. 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)(A). In this case, the general conditions of a method for producing particles via dissolving a drug and polymer in a solvent and adding water as an anti-solvent to produce particles with improved bioavailability has been taught by Lomuscio. As such, it would not have been inventive to have discovered the optimum or workable particle size via routine experimentation. The skilled artisan would have had a reasonable expectation of successfully achieving a narrow particle size, especially since Lomuscio teaches particle size reduction.
As to claim 1, the claims require an amorphous particle with a drug load of between 10% and 40%. Lomuscio teaches this, as of paragraphs 0102 and 0103.
As to claim 1, the claim requires that the first and second streams are delivered, respectively, to a first and second set of one or more channels. Yun appears to teach mixing through channels, as of Yun, figure in abstract. In the case of Yun, there are separate channels, which are referred to as feed pipes for the alcohol phase (which corresponds to the recited first stream) and for the aqueous phase (which corresponds to the recited second stream). Additionally, while Yun teaches a diameter as small as 10 microns (0.01 mm), this appears to be the diameter of a nozzle, and the diameter of the channels appears to be narrower, as of the figure on the front page of Yun. As such, the skilled artisan would have been motivated to have optimized the channels of Yun to have had a diameter smaller than 10 microns for predictable operation to form a nanoparticle with a reasonable expectation of success.
As to claim 1, the claim requires a solid dispersion. Lomuscio teaches this as of the abstract.
As to claim 1, the claim requires particular polymers. HPMCAS (hydroxypropyl methyl cellulose acetate succinate) and Eudragit L100 (a type of poly(methyl methacrylate co methacrylic acid, as of paragraph 0100 of Lomuscio) are understood to read on this claimed requirement.
As to claim 1, the claim recites a BCS class II drug. Shen teaches cyclosporine, as of paragraph 0086, which is understood by the examiner to be a class II drug. Additionally, while Lomuscio is silent as to the BCS class of its active agent, the skilled artisan would have expected the active agent to have been class II because Lomuscio teaches that its active agent has poor bioavailability, and BCS class II drugs have poor bioavailability. Additionally, the examiner understands the fenofibrate of Yun to be a class II drug.
As to claim 1, the claim has been amended to recite the step of feeding the first and second solutions individually at controlled rates. Controlling said flow rates appears to be taught as least as of Panagiotou, paragraphs 0065 and 0071, as well as Shen, paragraphs 0256 and 0411.
As to claim 1, claim 1 recites a maximum flow rate of both the first and second solutions of 50 kg/hour. Shen teaches a flow rate of 100 mL/minute in paragraph 0411; however, this appears to be the flow rate of a single solution. The value of 100 mL/minute would appear to be the following, assuming a density of 1 g/mL which is the density of water.
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While the value of 6 kg/hour appears to apply to only a single stream, the examiner notes that if the second stream were also at 6 kg/hour, then the total flow rate would be 12 kg/hour, which is lower than the recited maximum of 50 kg/hour. As such, the teachings of Shen would appear to have motivated the skilled artisan to have used a flow rate of less than 50 kg/hour.
Additionally, as to this requirement of claim 1, Yun teaches a volume flow rate of 0.01-500 liters per minute, as of paragraph 0028. Assuming a density of 1 g/mL or 1 kg/liter (which is the density of water), this is a flow rate of 0.01-500 kg per minute. This is equivalent to a flow rate of 0.6 kg/hour to 30,000 kg/hour. This range overlaps with the required maximum of 50 kg/hour. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 2, Lomuscio teaches mixing the drug and polymer in the organic solvent (dimethyl-acetamide), as of Lomuscio, paragraph 0102. The skilled artisan would have used this as the first stream, and the aqueous anti-solvent as the second stream.
As to claim 3, the skilled artisan would have expected that the drug of Lomuscio would have been water insoluble, as of Lomuscio, abstract. The skilled artisan would have also expected that the HPMCAS and Eudragit of Lomuscio would have been insoluble, at least in their neutrally charged state. Eudragit L100 comprises carboxyl groups which can be deprotonated and rendered anionic, and the skilled artisan would have expected Eudragit L-100 to have been insoluble when these carboxyl groups would have been protonated.
As to claim 4, the skilled artisan would have been motivated to have combined a first stream of organic solution comprising polymer (which reads on the stabilizing agent) with a second stream of the anti-solvent, based upon the teachings of Lomuscio as combined with other references.
As to claim 6, the pharmaceutical agent in Lomuscio is dissolved in the organic solvent of Lomuscio in paragraph 0102. The organic solvent is understood to read on the first stream, e.g. as in Shen. As such, the skilled artisan would have been motivated to have provided the pharmaceutically active compound in the first stream, as required by claim 6.
As to claim 7, this is an independent claim which differs from claim 1 in that it requires that the stabilizer be added to the second solvent rather (e.g. the antisolvent, which is water) rather than the first solvent (e.g. the organic solvent comprising the drug). Shen appears to teach this in paragraph 0291 in which Shen teaches dissolving lactose, hydroxypropyl methylcellulose, and sodium lauryl sulfate in water.
As to claim 8, Shen teaches a drying step as of part (c) of the abstract and paragraph 0151. Lomuscio also teaches spray drying in the abstract.
As to claim 9, Shen teaches spray drying in paragraph 0163. Lomuscio also teaches spray drying in the abstract.
As to claim 14, Lomuscio teaches the following, as of paragraph 0081, reproduced below.
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In the case wherein the ratio of drug to polymer (which is Copovidone in the above-reproduced paragraph) is 1:1, this results in 1.5-3.5% Copovidone in acetone; this is within the claimed requirement.
As to claims 16, Lomuscio teaches sodium lauryl sulfate and polysorbate 80 in paragraph 0082. These are anionic and non-ionic surfactants.
As to claim 17, Lomuscio teaches sodium lauryl sulfate in paragraph 0104.
As to claim 18, Shen teaches benzalkonium chloride as a cationic surfactant in paragraph 0105.
As to claim 19, Lomuscio’s teaching of polysorbate 80 in paragraph 0082 reads on the required polyoxyethylene sorbitan fatty acid ester.
As to claim 20, in the method of Lomuscio, paragraph 0102, the first solvent is an organic solvent such as dimethyl acetamide, and the second solvent is water; these are different.
As to claim 23, the second solvent in the method of Lomuscio is water, as of paragraph 0102.
As to claim 26, Lomuscio adds dilute hydrochloric acid to the water to adjust its pH in paragraph 0102.
As to claim 31, Lomuscio teaches the following, as of paragraph 0081, reproduced below.
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In the case wherein the ratio of drug to polymer is 1:1, this results in 1.5-3.5% active agent in acetone; this is within the claimed requirement.
As to claim 32, Lomuscio teaches a plasticizer as of page 9, Table 6. While Lomuscio does not appear to teach the reason for adding the plasticizer, this does not distinguish between the prior art and the claimed invention. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See MPEP 2144(IV).
As to claim 33, Shen teaches a microfluid in paragraph 0028. As such, Shen is understood to be drawn to microfluidics.
As to claim 34, Shen teaches a reaction chamber as of paragraph 0127.
As to claim 37, Shen teaches a continuous process in paragraphs 0148 and 0150.
As to claim 39, Shen teaches continuous flow in the mixing zone as of paragraph 0144.
As to claims 40-41, Shen teaches multiple micro-channels impinging stream mixer (MMISM) or a high gravity-controlled precipitation (HGCP) reactor, as of the end of paragraph 0121. The reaction pressure is discussed in paragraphs 0124 and 0131 of Shen. This is understood to read on the additional limitations of claims 40 and 41.
As to claim 43, Panagiotou teaches the following as of paragraph 0022, reproduced below.
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This would appear to have motivated the skilled artisan to have cooled the fluid stream after the reaction.
As to claim 52, the skilled artisan would have been motivated to have provided the anti-solvent in a different stream as compared with the pharmaceutical compound.
As to claim 54, Lomuscio teaches purified water as of page 9, left column, Table 6, footnote #4. The skilled artisan would have expected this purified water to have been deionized.
As to claim 55 Lomuscio adds dilute hydrochloric acid to the water to adjust its pH in paragraph 0102.
As to claims 58-59, Pangiotiou teaches 500-40,000 psi, as of paragraph 0019 of Pangiotiou. This is equivalent to about 35 to 2757 bar, and overlaps with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 61, Yun teaches a 1:1 volumetric flow rate ratio between the solvent and anti-solvent in paragraph 0069. This is not within the claim scope. Nevertheless, 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)(A). In this case, the general conditions of mixing a solvent and anti-solvent are taught by the prior art. As such, it would not have been inventive to have discovered the optimum or workable ranges of flow rate ratio by routine experimentation. The examiner additionally notes that as Yun has taught a numerical value for a flow rate ratio, this would appear to indicate that the flow rate ratio is a result-effective variable. Optimization of a result-effective variable is prima facie obvious; see MPEP 2144.05(II)(B), second paragraph in section.
As to claim 62, Panagiotou teaches that particles of various sizes and densities can be created, as of Panagiotou, paragraphs 0032 and 0046. As such, density, and measurements such as bulk density, would appear to be result-effective variables as Panagiotou teaches optimizing density. The presence of a known result-effective variable is motivation for the skilled artisan to have optimized a parameter; see MPEP 2144.05(II)(B), last paragraph in section. As such, the skilled artisan would have been motivated to have optimized bulk density to have been in the claimed range.
As to claims 63-64, Yun teaches particle sizes from about 50 nm to about 500 nm in paragraph 0119; this is understood to be within the claim scope.
Claim(s) 28, 30, and 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lomuscio et al. (US 2014/0206742 A1) in view of Shen et al. (US 2011/0306539 A1), Panagiotou et al. (US 2009/0269250 A1), and Shen et al. (US 2012/0037232 A1), the combination further in view of Brisander et al. (WO 2013/105895 A1).
Lomuscio is drawn to a process for encapsulating a drug in a particle made from hydroxypropyl methylcellulose acetate succinate or a methacrylate polymer. Shen, Panagiotou, and Yun are drawn to a process for a microreaction. See the rejection above over Lomuscio in view of Shen, Panagiotou, and Yun. While Lomuscio is drawn to only a single drug, Shen teaches a variety of drugs as of at least paragraph 0023, which include fenofibrate, cefuroxime axetil, azithromycin and others.
None of the above references teach nilotinib as the drug.
Brisander et al. (hereafter referred to as Brisander) is drawn to a method of making a nanoparticle of a protein kinase inhibitor, as of Brisander, title and abstract. Brisander teaches nilotinib, as of Brisander, many locations in the reference including but not limited to page 43, table, page 44, Example 1. Brisander teaches that nilotinib is a tyrosine kinase inhibitor, as of page 34, lines 15-20 of Brisander. Brisander teaches that improving the bioavailability of the drugs of Brisander is important, as of Brisander, paragraph 0004.
It would have been prima facie obvious for one of ordinary skill in the art to have conducted the method of Lomuscio in view of Shen using nilotinib to be the drug to be encapsulated. Shen is drawn to a method of encapsulating various drugs in a nanoparticle. This method is useful for improving bioavailability, as of Shen, paragraph 0069 and Lomuscio, title. As such, the skilled artisan would have been motivated to have conducted the process of Lomuscio and Shen on the active agent of Brisander in order to have predictably improved the bioavailability of the active agent of Brisander with a reasonable expectation of success.
As to claims 28, 30, and 56, nilotinib, as of Brisander, is understood to read on the additional requirements of these claims.
Response to Arguments Regarding Obviousness Rejection
Applicant has presented arguments regarding the previously presented rejections, as of applicant’s response on 3 March 2026 (hereafter referred to as applicant’s most recent response). These arguments are addressed below.
In applicant’s response, applicant argues that the particle sizes taught by Lomuscio are for spray-dried particles rather than co-precipitated particles, as of applicant’s response page 17. While the examiner does not disagree with this, the examiner notes that Lomuscio uses the term “microprecipitation” in claims 16-17 of Lomuscio, which indicates that the precipitate has a micron size. The examiner further notes that the process described in claims 16-17 of Lomuscio actually appears to be co-precipitation because the active agent (Compound A) is being co-precipitated with hypromellose acetate succinate.
As such, while Lomuscio teaches spray dried particles, this is a separate embodiment as compared with the precipitated particles also taught by Lomuscio. The prior art’s mere disclosure of more than one alternative (e.g. precipitation and spray drying) does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed. See MPEP 2145(X)(D)(1), second paragraph in section.
Applicant also argues that Lomuscio is drawn to simple addition rather than controlled microfluidization, as of applicant’s response, page 17. In response, the examiner takes the position that the chemistry in Lomuscio appears to be the same as what is claimed. Specifically, Lomuscio, like the instantly claimed invention, is drawn to a method in which a relatively water-insoluble drug is dissolved with an additional agent in a water-miscible organic solvent such as alcohol. An aqueous solution is then added as an anti-solvent, which causes co-precipitation of the water-insoluble drug and additional agent. Where Lomuscio differs from the claimed invention is the engineering aspects of how the water-miscible organic solvent and aqueous anti-solvent are mixed; however, those features are taught by other references relied upon. One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. See MPEP 2145(IV).
Regarding Shen, applicant argues that Shen teaches precipitation rather than co-precipitation, as of applicant’s response, page 17, last paragraph. In response, the examiner agrees that Example 2 of Shen teaches precipitation rather than co-precipitation because the drug is precipitated in the absence of an excipient and an excipient is added later. However, Shen suggests co-precipitation in the broad disclosure of Shen. See Shen, paragraph 0016, relevant text reproduced below.
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Had excipients been present in the precipitant solution (i.e. the solution that reads on the claimed first solution), the result would have been co-precipitation of the excipients and the drug. As such, Shen teaches co-precipitation in the broad disclosure. Patents are relevant for all they contain. See MPEP 2123(I). Additionally, other references relied upon also teach co-precipitation.
Applicant then argues that the method of Shen operates at atmospheric pressure, as of applicant’s response, paragraph bridging pages 17-18. In response, the examiner notes that Shen teaches that the operating pressure may be at atmospheric pressure, as of Shen, paragraph 0131. This indicates that the method of Shen is not limited to atmospheric pressure. Shen appears to teach the use of high pressure in paragraphs 0254 and 0267, wherein the pressure pushes the first and second streams from their storage tanks.
The examiner notes here that Shen does provide teachings regarding undesirable issues relating to the use of high pressures in paragraph 0008 of Shen, which is reproduced below.
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The subject matter in this paragraph is not understood to teach away from the use of high pressure. This is because:
The teachings in the above-reproduced paragraph from Shen appear to be limited to processes involving supercritical fluids. This is not the type of process recited by the instant claims or taught by the other references relied upon in this office action; and
The teachings of Shen would appear to indicate that such high-pressure processes have been used in processes prior to those of Shen, but have their disadvantages. A known or obvious composition (or in this case, method) does not become patentable simply because it has been described as somewhat inferior to some other product for the same use. See MPEP 2145(X)(D)(1).
Regarding Panagiotou, applicant argues that Panagiotou does not teach co-precipitation, as of applicant’s response, page 18. Applicant also argues that Panagiotou does not teach particle size control. The examiner disagrees. In support of this disagreement, the examiner cites paragraph 0178 of Panagiotou, which is reproduced below.
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The examiner takes the position that the above-reproduced text describes co-precipitation of the active agent with the surfactant. The examiner also takes the position that the above-reproduced text is drawn to particle size control because it indicates that the use of a surfactant limits the particle growth and prevents agglomeration.
Applicant makes the following argument, as of page 18 of applicant’s response.
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This is not persuasive because the chemistry of the processes described by Shen, Panagiotou, as well as other references cited is similar to each other. Specifically, the chemical processes of all of the cited prior art references entail dissolving a water-insoluble drug in a water-miscible solvent optionally with excipients, providing an anti-solvent which is water or an aqueous solution with an optional solute dissolved therein, and mixing together to precipitate or co-precipitate the drug. While the engineering aspects of how the mixing occurs differs between references, the purpose of conducting the process is the same in all of the cited references. The teachings of the prior art references taken together indicate that a wide range of process conditions can be used to conduct this type of process. This generally supports the idea that alteration of process conditions in a process of co-precipitation would have been routine optimization since a large variety of processes are known for achieving co-precipitation.
Applicant’s arguments regarding the Jahn reference as of the paragraph bridging pages 18-19 of applicant’s response have not been addressed substantively because Jahn is no longer relied upon in the applied rejection.
In applicant’s response, page 19, bottom paragraph, applicant argues that the cited references are drawn to distinct technologies to achieve distinct objectives. The examiner disagrees that the objectives of the cited references are distinct. In contrast, it is the examiner’s position that the objectives of the cited references are the same. These objectives are to achieve precipitation and/or co-precipitation of a water-insoluble drug by dissolving the drug in a water-miscible organic solvent optionally with an excipient, providing an anti-solvent that is an aqueous solution optionally with an excipient, and mixing these to precipitate and/or co-precipitate the drug. While there are differences in how this method is achieved between the cited references, these differences merely highlight the fact that different modes of achieving this process were known in the art prior to the effective filing date. This would appear to support the idea that the use of different features from different known ways of achieving this method would have been routine optimization.
Applicant then presents arguments regarding an alleged lack of a reasonable expectation of success, as of page 20 of applicant’s response. One argument is that there would have been no expectation that the device of Shen would have had a reasonable expectation of having been capable of successfully operating at the recited pressure range. This is not persuasive because (a) Shen teaches that high pressure has been used to achieve precipitation in references prior to Shen, as of paragraph 0008 of Shen, and (b) Shen teaches high pressure in paragraphs 0254 and 0267, and (c) other cited reference use high pressure to achieve precipitation and co-precipitation. Obviousness requires a reasonable expectation of success, not absolute predictability; see MPEP 2143.02(II).
Applicant then presented arguments regarding claim 43, as of applicant’s response on page 21. These arguments are moot because the examiner has cited a portion of Panagiotou to teach this particular claim element.
Conclusion
No claim is allowed.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
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