DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application, filed 10/23/2023, is a Continuation of 18/556,705, filed 08/07/2025, and a National Stage entry of PCT/US2022/026143, filed 04/25/2022, which claims domestic priority to U.S. provisional application no. 63/179,855, filed 04/26/2021.
Amendments and Claim Status
The amendment filed on 04/23/2026 is acknowledged and entered.
Claims 1-16 and 18-27 are cancelled;
Claims 28-35 are added
Claims 17 and 28-35 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/23/2023, 01/24/2024, 04/30/2024, 04/30/2024, 08/08/2024, 01/27/25, and 04/28/26 are acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election without traverse of Group III, a method for making compound particles, in the reply filed on 06/22/202 is acknowledged. Furthermore, the species election of a specific surface area between 3.5-18 m2/g is also acknowledged.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species does not make a contribution over the prior art of record.
Status of Claims
Claims 17 and 28-35 are pending in the instant application. Claims drawn to a non-elected invention and species have been canceled. Therefore, claims 17 and 28-35 read on an elected invention and species and are therefore under consideration in the instant application.
Drawings
The drawings filed on 10/23/2023 are objected to under 37 CFR § 1.83(a) for the following reasons:
The different data types are indistinguishable in Figures 15A, 15B, and 16. The original figures rely on color-coding of the data, a feature not available in the black and white drawings. The figures must be remade with shapes or line-types used to describe the different data points.
The different data types are indistinguishable in Figures 16-19. The figures lack a figure key to describe the different data types (e.g., Trial 1, Trial 2). The figures must be remade with a figure key describing the different types of data found in the figures.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 32 and 33 are objected to for the recitation of “super critical,” which should be corrected to “supercritical”.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claims 17 and 28-34 are rejected under 35 U.S.C. § 103 as being unpatentable over Baltezor et al. (US 20190022081 A1, published January 24, 2019, as cited in applicant IDS filed 10/23/2023), hereinafter Baltezor in view of Schmid and Stoeger (J Aeros Sci, Volume 99, pages 133-143, published April 26, 2016)
The instant claims are drawn to a method of making compound particles of cisplatin with a specific surface area of 3.5m2g.
The instant claims are rendered obvious by Baltezor, who teaches the creation of a compound particles by introducing a solution of paclitaxel in acetone into a nozzle inlet (paragraph [0245], see instant claim 17(a)). Baltezor further teaches passing the solution out of the nozzle orifice and into a pressurized chamber, wherein the nozzle orifice is positioned approximately 8 mm apart, which produces sonic energy and 60% of total output power and frequency of 20kHz (paragraph [0245], see instant claim 17 (b)). Baltezor further discloses wherein the atomized droplets contact supercritical carbon dioxide the crystallization chamber at approximately 1200 psi and 38°C, and a flow rate of 24 kg/hour, to produce nanoparticles with a mean particle size of 0.81mm (paragraph [0245], see instant claim 17(c)). Baltezor teaches wherein the sensor carried out under supercritical temperature and pressure for the compressed fluid (paragraph [0245], see instant claim 17(c)).
Baltezor fails to specifically teach cisplatin as the chemotherapeutic compounds used within method of making. However, the specification teaches cisplatin as a suitable chemotherapeutic compound within the scope of the method (paragraph [0164]. Therefore, although the reference does not teach a specific embodiment wherein cisplatin compound particles are created by the cited method, a person of ordinary skill in the art would have found it obvious to substitute cisplatin for paclitaxel in a method of making a compound, as the disclosure is centered on the use of both and they are considered substitutable equivalents, used for a common purpose (i.e., as chemotherapeutic agents). According to MPEP 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. The courts have stated:
(A)n applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
As such, a person of ordinary skill in the art would have found it obvious to use the disclosed method for creating paclitaxel particles to create cisplatin particles, because both cisplatin and paclitaxel are taught for the common purpose as chemotherapeutic agents within the prior art disclosure.
Baltezor fails to teach compounds of the instantly claimed specific surface area. However, Baltezor discloses a large range of specific surface areas, ranging from at least 10 m2/g to at least 35 m2/g. This process is considered a routine optimization of the instantly claimed specific surface area. The courts have found that,
“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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed specific surface area merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Furthermore, the teachings of Schmid and Stoeger remedied the deficiencies of Baltezor, by providing rationale to reduce the specific surface area of the particles. Schmid and Stoeger teach that particle surface area was the strongest predictor of acute nanoparticles induced lung inflammation, explaining approximately 80% of the observed toxicity across multiple the materials (Abstract). The authors propose that service driven interactions, such as reactive oxygen species generation, dissolution, and interaction with biological tissues occur at the particle surface (page 139). The authors therefore conclude that reducing specific surface area may decrease the amount of biologically active surface available, and potentially reduce surface-mediated toxicity (pages 139, 140-142).
Prior to the filing date of the instant claims, a person having ordinary skill in the art would have been motivated to combine the teachings of Baltezor in creating chemotherapeutic particles with the teachings of Schmid and Stoeger in seeking to reduce the specific surface area of the particles created, in order to reduce surface-mediated toxicity of the cisplatin particles, as explicitly taught by Schmid and Stoeger (pages 139, 140-142).
Regarding claim 28, Baltezor teaches that the precipitated nanoparticles are collected from supercritical carbon dioxide (paragraph [046]), thereby demonstrating contacting the compound particles with anti-solvent disease carbon dioxide) to the depletion of the solvent particles. Baltezor teaches that this step is carried out under supercritical temperature, and pressure (1200 psi and 38°C) for the anti-solvent (paragraph [0245 and 0246]), see instant claim 28 (d)).
Regarding claim 29, Baltezor teaches a flow rate of dissolution to the nozzle of 4.5 mL/minute for paclitaxel and 2mL/minute for docetaxel, both of which fell within the claimed range of about 05 – 30 mL/min. It is noted that the courts have stated
where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
Therefore, the claimed ranges merely represent a routine optimization of the values of the cited prior art.
Regarding claim 30, the specification teaches the sonic energy source has a frequency of 20 kHz in both paclitaxel and docetaxel examples (paragraphs [0245] and [0246]), which satisfies the claimed frequency range of between 18-22 kHz. The obviousness rationale MPEP § 2144.05, which addresses overlapping ranges is applied, and included herein in its entirety.
Regarding claim 31, Baltezor discloses that a stainless steel mesh filter with approximately 100 nm holes is attached to the crystallization chamber to collect the precipitated nanoparticles (paragraphs [0245 and 0246]), thereby receiving the plurality particles to the outlet of the pressurized chamber, and collecting the plurality particles in a collection device, as instantly claimed (see instant claims 31(e) and (f)).
Regarding claim 32, Baltezor teaches that the compressed fluid is supercritical carbon dioxide (paragraphs [0245 and 0246]).
Regarding claim 34, Baltezor teaches that the method is carried out at approximately 38°C and 1200 psi, which falls within the instantly claimed ranges of temperature and pressure. The obviousness rationale MPEP § 2144.05, which addresses overlapping ranges is applied, and included herein in its entirety.
The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art (see MPEP § 2143 (I)(A)).
Claim 35 is rejected under 35 U.S.C. § 103 as being unpatentable over Baltezor in view of Schmid and Stoeger (see earlier citations) as applied to claims 17 and 28-34, above, and further in view of Wilson and Lippard (Chem Rev, Volume 114, Issue 8, pages 4470–4495, published November 27, 2013)
The instant claims are further drawn to the use of DMF as a specific solvent to be used in the method of creation of the particles.
The teachings of Baltezor and Schmid and Stoeger are as set forth above.
Neither Baltezor nor Schmid and Stoeger teach the use of DMF as the specific solvent used within method of particle creation.
The deficiencies of Baltezor and Schmid and Stoeger are remedied by Wilson and Lippard, who teach both acetone and DMF as a suitable polar aprotic solvents used in the process of preparing cisplatin anticancer complexes (page 4). More often within the literature, Wilson and Lippard report the use of DMF as a preferred solvent, especially in the purification and recrystallization process (page 4).
Accordingly, prior to the filing date of the instant claims, a person having ordinary skill in the art would have found it obvious to substitute acetone as taught in the process by Baltezor for DMF, as taught by Wilson and Lippard, in order to increase the likelihood of obtaining a purer product. Furthermore, acetone and DMF are both polar aprotic solvents, and are thus considered substitutable equivalents used for a common purpose. According to MPEP 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. The courts have stated:
(A)n applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Therefore, person having ordinary skill in the art would have found it obvious to substitute DMF for acetone in the prior art, as both are recognized as substitutable equivalents used for a common purpose, i.e., as polar aprotic solvents.
Correspondence
No claim is allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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