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 .
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.
Claim(s) 1, 3, and 6-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tamori (2013/0085199 A1).
With respect to claim 1, Tamori teaches porous polymer particles for affinity chromatography and protein purification (Tamori, [001]).
Claim 1 further requires, “Porous polymer particles comprising: a polymer matrix.” Tamori teaches porous particles formed from a copolymer matrix of methacryloyl-group-containing monomers, including an epoxy-group-containing vinyl monomer and a crosslinkable vinyl monomer (Tamori, [0038]–[0044], [0054]–[0063]).
Claim 1 further requires, “a pore dispersed in the polymer matrix, wherein the pore has a diameter ranging from 50 nm to 500 nm.” Tamori teaches producing its copolymer particles as porous particles by seed or suspension polymerization using monomers, water, and porogens (Tamori, [0071]–[0076]). Tamori teaches a preferred volume-average pore diameter of 55–300 nm and a more preferred range of 60–250 nm for its porous chromatography particles (Tamori, [0157]). Each disclosed range lies within and therefore overlaps the claimed 50–500-nm range. Tamori further teaches that pore volume and related pore properties are controlled by porogen identity, porogen amount, and the monomer-to-porogen relationship (Tamori, [0076], [0085]–[0088], [0096]–[0097]).
Claim 1 further requires, “wherein an epoxy content contained in 1 g of the porous polymer particles measured by the following Equation 1 ranges from 500 μmol to less than 5000 μmol: Epoxy content (μmol/g)=[(V0−V)×Cbase×1000]/W.”
Claim 1 further requires, “wherein in Equation 1, V is an amount (mL) of a base used for the titration of an experimental group sample containing the porous polymer particles, V0 is an amount (mL) of the base used for the titration of a control sample using distilled water instead of the porous polymer particles in the experimental group sample, Cbase is a concentration (M) of the base used for the titration, and W is mass (g) of the porous polymer particles used for the titration.” Tamori teaches that the epoxy-group content of its porous particles before ligand binding is preferably 0.05–2.0 mmol/g, more preferably 0.08–1.5 mmol/g, and most preferably 0.10–1.0 mmol/g (Tamori, [0101]). The portion from 0.500 through 2.0 mmol/g corresponds to 500 through 2000 μmol/g and lies within the claimed range. Tamori’s Example 1 expressly reports an epoxy-group content of 0.55 mmol/g, or 550 μmol/g, for porous particles 1 (Tamori, [0178]). Tamori determines epoxy content by adding acid to open the epoxide, neutralizing with excess base, and titrating the remaining base with acid, normalized to particle mass (Tamori, [0159]–[0160]).
Tamori does not explicitly teach “a pore dispersed in the polymer matrix, wherein the pore has a diameter ranging from 50 nm to 500 nm” together with “an epoxy content contained in 1 g of the porous polymer particles measured by the following Equation 1 ranges from 500 μmol to less than 5000 μmol” for the same precursor particle, and Tamori’s disclosed back-titration is not worded as Equation 1. However, Tamori teaches overlapping working ranges for both properties and identifies the variables that control them (Tamori, [0085]–[0088], [0096]–[0097], [0101], [0157]).
It would have been obvious to a person having ordinary skill in the art before the effective filing date to select Tamori’s epoxy content and pore diameter within the overlapping claimed ranges, calibrate the disclosed porogen and epoxy-monomer variables until the precursor particles possessed both selected properties, and report epoxy content using the claimed control/sample titration calculation. Tamori teaches the selected pore diameter supports dynamic binding capacity, while the selected epoxy content provides adequate ligand-loading capacity and storage stability (Tamori, [0101], [0157]). Applying the claimed titration to Tamori’s particles would be a predictable analytical substitution that reports, rather than changes, their epoxy content. A person having ordinary skill would have had a reasonable expectation of success because Tamori identifies the independent variables controlling pore structure and epoxy content, discloses broad working ranges that encompass the claims, and expressly obtains a precursor epoxy content of 550 μmol/g (Tamori, [0096]–[0097], [0101], [0157], [0178]).
Regarding claim 3, the porous particles of claim 1 has been discussed above.
Claim 3 further requires, “the porous polymer particles have a particle diameter ranging from 10 μm to 150 μm as measured by an optical microscope.” Tamori teaches porous particles having a 35–100-μm particle-size range, preferably 38–75 μm (Tamori, [0153]–[0154]). Those ranges lie inside the claimed 10–150-μm range, but Tamori uses laser diffraction rather than optical microscopy (Tamori, [0161]–[0162]). Tamori therefore does not explicitly teach “the porous polymer particles have a particle diameter ranging from 10 μm to 150 μm as measured by an optical microscope.” It would have been obvious to measure Tamori’s tens-of-micrometers particles by optical microscopy as a direct image-based alternative because such particles are within the ordinary resolving range of an optical microscope, thereby predictably producing individual-particle diameter measurements without modifying the particles. A person having ordinary skill would have had a reasonable expectation of success because Tamori confines the particle population to 35–100 μm, well inside the claim’s broad interval, so ordinary optical measurements of representative particles would remain within 10–150 μm range.
Regarding claim 6, the porous particles of claim 1 has been discussed above.
Claim 6 further requires, “the porous polymer particles are a polymerization reaction product of a dispersive phase solution and a continuous phase aqueous solution, wherein the dispersive phase solution comprises a pore inducing material, a monomer, and a crosslinking agent.” Tamori teaches suspension polymerization of a water-based mixture containing an organic monomer/porogen phase and water as the polymerization solvent (Tamori, [0071]–[0076], [0089]). Example 1 prepares an organic solution containing glycerol monomethacrylate, glycidyl methacrylate, trimethylolpropane trimethacrylate, 2-octanone, and acetophenone; feeds that solution with an aqueous solution to a stirred vessel; and polymerizes the dispersed organic phase to form porous particles (Tamori, [0174]–[0178]). The ketones are pore-inducing materials, glycerol monomethacrylate and glycidyl methacrylate are monomers, and trimethylolpropane trimethacrylate is a crosslinking agent (Tamori, [0062], [0077]–[0084], [0175]).
Regarding claim 7, the porous particles of claim 6 has been discussed above.
Claim 7 further requires, “the pore inducing material comprises an aromatic hydrocarbon-based compound, a ketone-based compound, or an acetate-based compound.” Tamori teaches alkylbenzenes, ketones, and acetate esters as porogens (Tamori, [0075], [0081]–[0084]).
Regarding claim 8, the porous particles of claim 7 has been discussed above.
Claim 8 further requires, “the aromatic hydrocarbon-based compound comprises mesitylene.” The Example 1 embodiment discussed for claim 6 uses ketone porogens rather than mesitylene and therefore does not explicitly teach “the aromatic hydrocarbon-based compound comprises mesitylene.” Tamori nevertheless expressly identifies mesitylene as an alkylbenzene porogen for the same porous-particle process (Tamori, [0083]). It would have been obvious to select Tamori’s expressly listed mesitylene in place of an Example 1 ketone when an aromatic porogen was desired because Tamori presents mesitylene as a functional alternative for forming pores. This substitution predictably provides porous methacrylate particles, and a person having ordinary skill would have had a reasonable expectation of success because Tamori teaches mesitylene for that precise porogen function in the same polymerization system (Tamori, [0075], [0083]–[0085]).
Regarding claim 9, , the porous particles of claim 7 has been discussed above.
Claim 9 further requires, “the ketone-based compound comprises diisobutyl ketone.” Tamori’s Example 1 uses 2-octanone and acetophenone and therefore does not explicitly teach “the ketone-based compound comprises diisobutyl ketone.” Tamori nevertheless expressly identifies 2,6-dimethyl-4-heptanone—the systematic name for diisobutyl ketone—as a ketone porogen (Tamori, [0081]). It would have been obvious to select that expressly listed ketone as an alternative to Example 1’s ketones because Tamori teaches the compounds for the same pore-forming function. The substitution predictably yields porous particles, and a person having ordinary skill would have had a reasonable expectation of success because Tamori teaches ketone porogens as interchangeable members of the disclosed porogen class and identifies the selected species by name (Tamori, [0075], [0081], [0085]).
Regarding claim 10, , the porous particles of claim 7 has been discussed above
Claim 10 further requires, “the acetate-based compound comprises amyl acetate, or hexyl acetate.” Tamori’s Example 1 uses ketone porogens rather than acetate esters and therefore does not explicitly teach “the acetate-based compound comprises amyl acetate, or hexyl acetate.” Tamori nevertheless expressly identifies pentyl acetate and hexyl acetate as ester porogens; pentyl acetate is amyl acetate (Tamori, [0082]). It would have been obvious to select either expressly listed acetate as an alternative porogen because Tamori teaches both for the same pore-forming function. The substitution predictably yields porous particles, and a person having ordinary skill would have had a reasonable expectation of success because the selected species are expressly recommended within Tamori’s porogen system (Tamori, [0075], [0082], [0085]).
Regarding claim 11, the porous particles of claim 6 has been discussed above.
Claim 11 further requires, “the pore inducing material has a viscosity f-ranging from 0.5 cP to 15 cP as measured at 20° C.” Tamori does not explicitly teach “the pore inducing material has a viscosity f-ranging from 0.5 cP to 15 cP as measured at 20° C.,” but it identifies 2,6-dimethyl-4-heptanone (diisobutyl ketone), pentyl acetate (amyl acetate), and hexyl acetate as porogens (Tamori, [0081]–[0082]). Applicant’s own specification teaches at Table 1 that diisobutyl ketone and amyl acetate each have a viscosity of 0.9 cP at 20° C. and hexyl acetate has a viscosity of 1.2 cP at 20° C. These teaching establish that Tamori’s named compounds inherently possess the claimed fixed physical property. It would have been obvious to select any of those Tamori porogens for the reasons stated for claims 9 and 10, predictably supplying a pore-inducing material within the claimed viscosity range. A person having ordinary skill would have had a reasonable expectation of success because viscosity is an inherent property of the selected compound at the stated temperature and applicant confirms the values.
Regarding claim 12, the porous particles of claim 6 has been discussed above.
Claim 12 further requires, “the pore inducing materials comprises a mixture of an alcohol-based compound and an aromatic hydrocarbon-based compound.” Tamori teaches C7–C14 alcohols and C8–C10 alkylbenzenes as porogen classes, teaches that another porogen may be used in combination, identifies 1-heptanol and related alcohols, and identifies xylene and mesitylene as alkylbenzene porogens (Tamori, [0075]–[0078], [0083]). Tamori does not explicitly teach “the pore inducing materials comprises a mixture of an alcohol-based compound and an aromatic hydrocarbon-based compound.” However, Tamori teaches that porogens may be combined and that an additional porogen may be added to regulate pore volume (Tamori, [0076], [0085]).
It would have been obvious to a person having ordinary skill in the art before the effective filing date to use a mixture of one of Tamori’s disclosed alcohol porogens, such as 1-heptanol, and one of Tamori’s disclosed alkylbenzene porogens, such as xylene, because Tamori expressly authorizes combined porogens and teaches adding another porogen to regulate pore volume, thereby predictably providing another composition for controlling the porosity of Tamori’s particles (Tamori, [0076], [0078], [0083], [0085]). A person having ordinary skill would have had a reasonable expectation of success because both selected compounds are taught by Tamori for the same porogen function in the same suspension-polymerization system, and Tamori expressly teaches their use in porogen combinations.
Regarding claim 13, the porous particles of claim 12 has been discussed above.
Claim 13 further requires, “the alcohol-based compound comprises an aliphatic alcohol having 1 to 11 carbon atoms.” Tamori expressly identifies 1-heptanol, a seven-carbon aliphatic alcohol, as a porogen (Tamori, [0078]). No additional modification is required for this added limitation because the alcohol selected in the claim 12 combination is Tamori’s expressly disclosed 1-heptanol (Tamori, [0078]).
Regarding claim 14, the porous particles of claim 12 has been discussed above.
Claim 14 further requires, “the aromatic hydrocarbon-based compound comprises an aromatic hydrocarbon compound having 6 to 8 carbon atoms, wherein some of hydrogens of the aromatic hydrocarbon compound are substituted with an alkyl group having 1 to 3 carbon atoms.” Tamori expressly identifies xylene as an alkylbenzene porogen (Tamori, [0083]). Xylene is an eight-carbon aromatic hydrocarbon having benzene hydrogens substituted by one-carbon methyl groups.
Regarding claim 15, the porous particles of claim 6 has been discussed above.
Claim 15 further requires, “the pore inducing materials in the dispersive phase solution is included in an amount ranging from 10 wt. % to 80 wt. % based on 100 wt. % of the dispersive phase solution.” Tamori’s Example 1 organic/dispersive-phase components include 246 g of 2-octanone and 61.7 g of acetophenone as porogens, 82.4 g of glycerol monomethacrylate, 16.5 g of glycidyl methacrylate, and 65.9 g of trimethylolpropane trimethacrylate (Tamori, [0175]). The porogen content is (246 + 61.7)/(246 + 61.7 + 82.4 + 16.5 + 65.9) × 100 = approximately 65.1 wt. %, within the claimed range. Tamori separately teaches 100–400 parts porogen per 100 parts monomer (Tamori, [0076], [0087]). No additional modification is required because the claim 1 optimization begins with Example 1’s 550-μmol/g precursor and may retain its 65.1-wt.% porogen proportion; any routine pore calibration can be performed by changing porogen identity or conditions while keeping the amount inside the broader 10–80-wt.% interval.
Regarding claim 16, the porous particles of claim 6 has been discussed above.
Claim 16 further requires, “the monomer in the dispersive phase solution is included in an amount ranging from 10 wt. % to 60 wt. % based on 100 wt. % of the dispersive phase solution.” In Tamori’s Example 1, the non-crosslinking monomers total 98.9 g: 82.4 g glycerol monomethacrylate plus 16.5 g glycidyl methacrylate, in 472.5 g of the recited organic/dispersive-phase components (Tamori, [0175]). The monomer content is approximately 20.9 wt. %, which is within the claimed range.
Regarding claim 17, Tamori the porous particles of claim 6 has been discussed above.
Claim 17 further requires, “the crosslinking agent in the dispersive phase solution is included in an amount ranging from 10 wt. % to 60 wt. % based on 100 wt. % of the dispersive phase solution.” Tamori’s Example 1 contains 65.9 g trimethylolpropane trimethacrylate crosslinking agent in 472.5 g of the recited organic/dispersive-phase components (Tamori, [0062], [0175]). The crosslinking-agent content is approximately 13.9 wt. %, within the claimed range.
Regarding claim 18, Tamori teaches the subject matter of claim 1 as discussed above. Claim 18 further requires, “the porous polymer particles are a polymerization reaction product of droplets obtained by passing a dispersive phase solution and a continuous phase aqueous solution through a step emulsification microfluidic device, wherein the dispersive phase solution comprises a pore inducing materials, a monomer, and a crosslinking agent.” The quoted language defines the product by its manufacturing process. Tamori teaches porous, epoxy-functional, crosslinked methacrylate particles having the same claimed polymer matrix, overlapping pore diameter and epoxy content, and the same dispersive-phase categories—porogen, monomer, and crosslinker—polymerized as droplets in a continuous aqueous phase (Tamori, [0054]–[0063], [0071]–[0076], [0089], [0101], [0153]–[0157], [0174]–[0178]). Those matching composition and product-property disclosures provide a sound basis that Tamori’s particles are the same as or substantially identical to the claimed product. Claim 18 recites no resulting structural or performance characteristic attributable to the step-emulsification device. No additional modification is required for this added limitation because, see MPEP § 2113 and *In re Thorpe.*
Regarding claim 19, the porous particles of claim 12 has been discussed above.
Claim 19 further requires, “the step emulsification microfluidic device comprises: a first injection port for injecting the dispersive phase solution; a second injection port for injecting a continuous phase solution; a dispersive phase flow path through which the dispersive phase solution flows; a continuous phase flow path through which the continuous phase solution flows; and a microchannel through which the dispersive phase solution flows out to the continuous phase flow path to form the droplets.” Claim 19 remains a product claim. Its added language describes manufacturing-device components but recites no resulting structural or performance characteristic. The composition-and-property identity findings for claim 18 therefore remain applicable. No additional modification is required for this added limitation because the additional device architecture does not distinguish the product absent evidence that it necessarily imparts a nonobvious structural difference. See MPEP § 2113.
Regarding claim 20, the porous particles of claim 12 has been discussed above.
Claim 20 further requires, “A column for protein purification comprising the porous polymer particles of claim 1.” Tamori teaches packing porous particles bearing a protein-binding ligand into an affinity-chromatography column for protein purification, but its exemplified packed filler has undergone ligand binding and residual-epoxy ring opening (Tamori, [0031], [0136], [0146]–[0150], [0166], [0213]). Tamori therefore does not explicitly teach “A column for protein purification comprising the porous polymer particles of claim 1” while establishing the claimed residual epoxy content in the packed particles. It would have been obvious to begin with Tamori precursor particles toward the upper part of its 0.5–2.0-mmol/g overlapping epoxy range, bind a selected amount of protein-binding ligand through only part of the available epoxy groups, retain at least 0.5 mmol/g residual epoxy, and pack the resulting bifunctional particles into Tamori’s column. Tamori teaches that epoxy content supplies ligand-binding capacity and permits adjustment through monomer amount and processing conditions, and it teaches selecting the ligand-loading amount according to the ligand and target molecule (Tamori, [0101], [0146]–[0148]). A person having ordinary skill would have had a reasonable expectation of success because Tamori provides broad epoxy and ligand-loading ranges and uses the same covalent epoxy chemistry to attach the ligand before packing the column.
Claim(s) 2 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tamori (2013/0085199 A1) as applied to claims 1 and 3 above, and further in view of Steinbach et al., (“Rational Design of Pore Parameters in Monodisperse Porous Poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) Particles Based on Response Surface Methodology,” *Polymers* 2022)
Regarding claim 2, the porous particles of claim 1 has been discussed above.
Claim 2 further requires, “the porous polymer particles have a particle surface pore diameter ranging from 50 nm to 500 nm as measured by SEM.” Tamori teaches porous epoxy-functional methacrylate particles having a preferred 55–300-nm volume-average pore-diameter range and reports a 74-nm pore diameter for Example 1 (Tamori, [0157], [0163]–[0164], [0215]). Tamori does not explicitly teach “the porous polymer particles have a particle surface pore diameter ranging from 50 nm to 500 nm as measured by SEM.” However, Steinbach teaches porous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) particles bearing functional epoxy groups and uses SEM at 10,000× to image and evaluate the particle surfaces and morphology (Steinbach 1-3, Abstract; 2.3; Steinbach 5, 2.6; Steinbach 7, Fig. 2). Steinbach further teaches mean pore sizes of 53.8 nm, 63.1 nm, and 71.5 nm, measured by inverse size-exclusion chromatography, for epoxy-functional GMA/EDMA particle batches (Steinbach 4, Table 2; Steinbach 5, 2.5).
It would have been obvious to use Steinbach’s SEM surface-imaging method to measure surface openings of the Tamori particles selected for claim 1 because Steinbach applies that technique to the surfaces of the same general epoxy-functional, crosslinked methacrylate-particle class, thereby predictably providing direct surface-pore images (Steinbach, p. 5, § 2.6; p. 7, Fig. 2). It also would have been obvious to adjust Tamori’s porogen variables until the SEM-observed surface pores fell within 50–500 nm because Tamori teaches that those variables control pore structure and Steinbach confirms systematic pore design through monomer/porogen composition (Tamori, [0085]–[0088], [0097]; Steinbach, pp. 10–12, § 3.5). A person having ordinary skill would have had a reasonable expectation of success because the claimed interval is broad, Steinbach teaches the required surface-imaging technique, and both references report bulk pore sizes within that interval for porous methacrylate particles.
Regarding claim 4, the porous particles of claim 12 has been discussed above.
Claim 4 further requires, “the porous polymer particles have a particle diameter variation coefficient of 20% or less as measured by an optical microscope.” Tamori teaches controlling particle size in seed polymerization by adjusting seed size and amount, monomer amount, and porogen amount, and controlling particle size in suspension polymerization by adjusting the dispersant, surfactant, stirring speed, blade geometry, and vessel geometry (Tamori, [0096]). Tamori does not explicitly teach “the porous polymer particles have a particle diameter variation coefficient of 20% or less as measured by an optical microscope.”
However, Steinbach teaches that a small particle-size distribution is advantageous, that seeded swelling polymerization provides monodisperse porous microspheres, and that its porous GMA/EDMA particle batches have a maximum coefficient of variation of 15.8% (Steinbach 2, 1; Steinbach 6, 3.1 and Fig. 1). Steinbach determines particle size and dispersity from images of 400–500 particles and reports all batches as monodisperse (Steinbach 5, 2.6; Steinbach 4, Table 2).
It would have been obvious to use Steinbach’s monodisperse seeded-swelling technique when preparing Tamori’s porous epoxy-functional chromatography particles because Steinbach teaches that a small size distribution is advantageous and that seeded swelling controls particle size and dispersity, thereby predictably producing a particle-diameter variation coefficient below 20% (Steinbach2, 1; Steinbach 6, 3.1). It further would have been obvious to determine that same dimensional distribution by optical microscopy: the particles are tens of micrometers in diameter, optical imaging directly resolves individual particles, and changing from SEM to optical imaging measures rather than alters the population. A person having ordinary skill would have had a reasonable expectation of success because Steinbach teaches the same general epoxy-functional, crosslinked methacrylate-particle class, measures 400–500 particles, and reports a maximum coefficient of variation of 15.8%, leaving margin below the claimed 20% ceiling (Steinbach 3–5, 2.3 and 2.6; Steinbach 6, 3.1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STARFARI TESHAWN MCCLAIN whose telephone number is (571)272-0169. The examiner can normally be reached M-F 8 AM- 5 PM.
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/STARFARI TESHAWN MCCLAIN/ Examiner, Art Unit 1736
/DANIEL C. MCCRACKEN/ Primary Examiner, Art Unit 1736
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