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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 National Stage application of PCT/US2020/060638 filed 11/15/2020, which claims the benefit of Application Number 62/936,282 filed 11/15/2019. Based on the filing receipt, the effective filing date of this application is November 15, 2019 which is the filing date of Application Number 62/936,282 from which the benefit of priority is claimed.
Information Disclosure Statement
The information disclosure statement (IDS) filed 02/14/2025 has been considered.
Election/Restrictions
Applicant’s election without traverse of E) carboxylate group as the functional group, J) polyethylene glycol as the polymer, and Q) antibody as the probe moiety, in the reply filed on 08/21/2025 is acknowledged.
However, upon examination it has been determined that the species of functional groups of claim 3 do not present an undue search burden. Therefore, the species election of functional groups has been withdrawn.
Status of Claims
Claims 1-22 are pending and examined herein.
Claim Objections
Claim 11 is objected to because of the following informalities: claim 11 recites, "2µm”. The claim should recite “2 µm” to stay consistent with claims 10 and 12. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10-12 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 10-12 recites the limitation "said polystyrene-core" in the “wherein” clauses. There is insufficient antecedent basis for this limitation in the claims. “A polystyrene-core” has not been recited before claims 10-12 recite, “said polystyrene-core”. Due to the insufficient antecedent basis, the metes and bounds of the claims cannot be ascertained.
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.
Claims 1-4 and 9-20 are rejected under 35 U.S.C. 103 as being unpatentable over Janczak (Hybrid Nanoparticles for Enhanced Sensitivity in Biological Labeling and Biomolecular Sensing, published 2011) as evidenced by Sarma, et al. (“Polystyrene Core−Silica Shell Particles with Defined Nanoarchitectures as a Versatile Platform for Suspension Array Technology”, published 2016-03-26).
Janczak teaches a hydrophilic particle scintillator comprising: a polyaromatic-core particle, where the particle is doped with a scintillator material; and a silica-shell portion encapsulates the polyaromatic-core particle, where the silica-shell portion comprises an outer surface, as in claim 1 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”, and p. 158, under “4.2.3 Addition of Silica Shells to PS Core nPs”). Polystyrene (PS) is a polyaromatic, according to claim 15.
Janczak teaches the outer surface of the silica-shell portion comprises a functional group adapted for attaching a probe moiety, specifically an amine group, as in claims 2 and 3 (see, e.g., p. 181: “the PS-core silica-shell nPs are amine-functionalized by including APTES in the shell synthesis”).
Janczak teaches the probe moiety is capable of selectively binding a ligand, as in claim 4 (see, e.g., p. 178, under “4.3.5 Biotin-Streptavidin Binding Model SPA”, para. 1). It is understood that streptavidin is a probe moiety capable of selectively binding the ligand, biotin.
Janczak teaches the probe moiety is an antibody, as in claim 9 (see, e.g., p. 164: “the covalent attachment of receptor molecules such as proteins, antibodies").
Janczak teaches the thickness of the silica-shell portion is 20 nm, as in claims 13 and 14 (see, e.g., p. 166: “Silica shells ca. 20 nm thick were deposited on scintillants-doped PS core nPs”).
Janczak teaches the polyaromatic-core particle is a polystyrene-core particle, as in claim 15 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
Janczak teaches the hydrophilic particle scintillator is at a density of at least about 1.1 g/mL, as in claim 16 (see, e.g., p. 157-157, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs” and “4.2.3 Addition of Silica Shells to PS Core nPs”). Sarma gives evidence that the particles of Janczak have a density of at least about 1.1 g/m (see, e.g., Sarma, p. 3717: “SiO2 particles have higher densities (2 g mL−1)”, and p. 3720: “assuming a density of 1.05 g mL−1 for polystyrene”, and p. 3723: “While a suspension of PS [(a.k.a. polystyrene)] particles remained stable over a period of 360 min, we observed full sedimentation of the SiO2 microparticles. The CS [(a.k.a. core shell)] particles showed intermediate sedimentation behavior with an increasing tendency of sedimentation speed from PS10 to PS360, reflecting well the increasing amount of SiO2 as determined for instance by TGA and a corresponding increase in density”). As evidenced by Sarma above, the particles of Janczak will have a density between 1.05 g/mL (the density of polystyrene particles) and 2 g/mL (the density of silica particles), which meets the limitation of at least about 1.1 g/mL.
Janczak teaches a method for producing a hydrophilic particle scintillator wherein the hydrophilic particle scintillator comprises: a polyaromatic-core particle, wherein the polyaromatic-core particle is doped with at least one scintillator material; and a silica-shell portion encapsulating said polyaromatic-core particle, the method comprising: producing the polyaromatic-core particle that is doped with a scintillator material; and contacting the polyaromatic-core particle with a silica-shell precursor mixture under conditions sufficient to encapsulate the polyaromatic-core particle with a silica-shell portion to produce the hydrophilic particle scintillator, wherein the polyaromatic-core particle is a polystyrene-core particle, as in claim 17 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”, and p. 158, under “4.2.3 Addition of Silica Shells to PS Core nPs”).
Janczak teaches the method of claim 17, wherein the step of producing the polyaromatic-core particle comprises: polymerizing an aromatic vinyl compound under conditions sufficient to produce a polyaromatic particle, wherein the aromatic vinyl compound is styrene, and admixing the polyaromatic particle with the scintillator material under conditions sufficient to produce the polyaromatic-core particle, wherein the polyaromatic-core particle is doped with at least one scintillator material, as in claim 18 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
Janczak teaches the method of claim 18, wherein the step of producing the polyaromatic particle comprises providing a solution of an aromatic vinyl compound and a radical polymer initiator under conditions sufficient to produce the polyaromatic particle, wherein the aromatic vinyl compound is styrene, as in claim 19 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
Janczak teaches the method of claim 19, where the solution further comprises an emulsifier, as in claim 20 (see, e.g., p. 164: “Scintillant-doped PS core nPs were fabricated by entrapping pTP and dimethyl POPOP in the PS matrix using a surfactant-free emulsion polymerization process”).
Janczak fails to teach the particles are microparticles, as in claims 1-4, 9, and 13-20. Janczak fails to teach the polystyrene-core microparticle has mean particle size in the range of from about 1 µm to about 1000 µm, as in claim 10. Janczak fails to teach the D9o particle size of the polystyrene-core microparticle is about 2 µm, as in claim 11. Janczak fails to teach the average particle size of the polystyrene-core microparticle ranges from about 1 µm to about 5 µm, as in claim 12.
However, Janczak teaches, “Polystyrene particles are often fabricated using microemulsion polymerization methods with or without surfactant stabilizers. […] Size, ranging from tens of nanometers to several micrometers in diameter, can be adjusted by changing the monomer and surfactant concentrations and by regulating the rate at which monomer is added to the reaction during polymerization” (see p. 61-62). An artisan would have been motivated to produce hydrophilic microparticle scintillators, wherein the D90 particle size is about 2 µm, as in claims 10-12, because Janczak discloses that larger particles can entrap a greater number of scintillant molecules and may yield a larger signal on a per particle basis (see, e.g., p. 167, para. 1). Therefore, arriving at the claimed invention before the effective filing date of the application would be a matter of routine optimization. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions”). An artisan would have a reasonable expectation of success based on the given disclosure.
Claims 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-20 above, and further in view of Aspinwall (US 20180118916 A1, published 2018-05-03).
Janczak teaches as set forth above, but fails to teach the probe moiety is attached to the silica-shell via a linker, wherein the linker is a hydrophilic polymer, poly(ethylene glycol) (PEG), as in claims 5-8.
However, in a patent application publication on scintillant nanoparticles, Aspinwall rectifies this deficiency. Aspinwall teaches attaching a probe moiety to a scintillant-doped PS particle with a silica-shell via a PEG linker, as in claims 5-8 (see, e.g., para. [0264]).
Janczak and Aspinwall are analogous to the field of the claimed invention because they are both in the field of scintillant-doped particles. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the PEG linker of Aspinwall to the particles of Janczak. An artisan would have been motivated to do so because Aspinwall discloses, “The NHS end of the linker on PS-MPTS-NHS NPs was used to facilitate peptide coupling of SRC kinase substrate through the amine groups on its lysine amino acid residues” (see para. [0264]). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-20 above, and further in view of Ma, et al. (“Preparation of an Immunoaffinity Column with Amino-Silica Gel Microparticles and Its Application in Sample Cleanup for Aflatoxin Detection in Agri-Products”, published 2013-02-11).
Janczak teaches as set forth above, but fails to teach the hydrophilic microparticle scintillators are incorporated into an apparatus, specifically a particle-packed cartridge, as in claims 21 and 22.
However, in a journal article on the preparation of an immunoaffinity column with microparticles, Ma rectifies this deficiency. Ma teaches an apparatus of a particle-packed cartridge, as in claims 21 and 22 (see, e.g., p. 2222, under “Abstract:”).
Janczak and Ma are analogous to the field of the claimed invention because they are both in the field of particle development. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the particle-packed cartridge apparatus of Ma to the particles of Janczak. An artisan would have been motivated to do so because Ma teaches the immunoaffinity column with the particle-packed cartridge is capable of selective extraction of analytes (see, e.g., p. 2222, under “Abstract:”). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4 and 9-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, and 12 of U.S. Patent No. 12,360,107 (referred hereto as ‘107) in view of Janczak (cited above) as evidenced by Sarma (cited above).
‘107 teaches a hydrophilic particle scintillator comprising: a polyaromatic-core particle, where the particle is doped with a scintillator material; and a silica-shell portion encapsulates the polyaromatic-core particle, where the silica-shell portion comprises an outer surface, as in claim 1 (see, e.g., claims 1 and 3 of ‘107).
‘107 teaches the outer surface of the silica-shell portion comprises a functional group adapted for attaching a probe moiety, specifically an amine group, as in claims 2 and 3 (see claim 7 of ‘107: “silica shell precursor […] 3-aminopropyltriethoxysilane”). Janczak discloses that including 3-aminopropyltriethoxysilane (APTES) in shell synthesis leads to amine-functionalized particles (see, e.g., p. 181: “the PS-core silica-shell nPs are amine-functionalized by including APTES in the shell synthesis”).
‘107 teaches the thickness of the silica-shell portion is 50 nm, as in claims 13 and 14 (see claim 12 of ‘107).
‘107 teaches the polyaromatic-core particle is a polystyrene-core particle, as in claim 15 (see, e.g., claim 3 of ‘107).
‘107 teaches a method for producing a hydrophilic particle scintillator wherein the hydrophilic particle scintillator comprises: a polyaromatic-core particle, wherein the polyaromatic-core particle is doped with at least one scintillator material; and a silica-shell portion encapsulating said polyaromatic-core particle, the method comprising: producing the polyaromatic-core particle that is doped with a scintillator material; and contacting the polyaromatic-core particle with a silica-shell precursor mixture under conditions sufficient to encapsulate the polyaromatic-core particle with a silica-shell portion to produce the hydrophilic particle scintillator, wherein the polyaromatic-core particle is a polystyrene-core particle, as in claim 17 (see claims 1 and 3 of ‘107).
‘107 teaches the method of claim 17, wherein the step of producing the polyaromatic-core particle comprises: polymerizing an aromatic vinyl compound under conditions sufficient to produce a polyaromatic particle, wherein the aromatic vinyl compound is styrene, and admixing the polyaromatic particle with the scintillator material under conditions sufficient to produce the polyaromatic-core particle, wherein the polyaromatic-core particle is doped with at least one scintillator material, as in claim 18 (see claims 1 and 3 of ‘107).
‘107 teaches the method of claim 18, wherein the step of producing the polyaromatic particle comprises providing a solution of an aromatic vinyl compound and a radical polymer initiator under conditions sufficient to produce the polyaromatic particle, wherein the aromatic vinyl compound is styrene, as in claim 19 (see claims 1 and 3 of ‘107).
‘107 teaches the method of claim 19, where the solution further comprises an emulsifier, as in claim 20 (see claims 1 and 3 of ‘107).
‘107 fails to teach the particles are microparticles, as in claims 1-4, 9-20. ‘107 fails to teach the probe moiety is capable of selectively binding a ligand, as in claim 4. ‘107 fails to teach the probe moiety is an antibody, as in claim 9. ‘107 fails to teach the polystyrene-core microparticle has mean particle size in the range of from about 1 µm to about 1000 µm, as in claim 10. ‘107 fails to teach the D9o particle size of the polystyrene-core microparticle is about 2 µm, as in claim 11. ’107 fails to teach the average particle size of the polystyrene-core microparticle ranges from about 1 µm to about 5 µm, as in claim 12. ’107 fails to teach the particle density is at least about 1.1 g/mL, as in claim 16.
However, in a dissertation on particles for enhanced sensitivity in biological labeling and biomolecular sensing, Janczak teaches, “Polystyrene particles are often fabricated using microemulsion polymerization methods with or without surfactant stabilizers. […] Size, ranging from tens of nanometers to several micrometers in diameter, can be adjusted by changing the monomer and surfactant concentrations and by regulating the rate at which monomer is added to the reaction during polymerization”, as in claims 1-4 and 9-20 (see p. 61-62).
Janczak teaches the probe moiety is capable of selectively binding a ligand, such as an antibody, as in claim 4 and 9 (see, e.g., p. 164: “the covalent attachment of receptor molecules such as proteins, antibodies").
Janczak teaches the hydrophilic particle scintillator is at a density of at least about 1.1 g/mL, as in claim 16 (see, e.g., p. 157-157, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs” and “4.2.3 Addition of Silica Shells to PS Core nPs”). Sarma gives evidence that the particles of Janczak have a density of at least about 1.1 g/mL, as in claim 16 (see, e.g., Sarma, p. 3717: “SiO2 particles have higher densities (2 g mL−1 )”, and p. 3720: “assuming a density of 1.05 g mL−1 for polystyrene”, and p. 3723: “While a suspension of PS particles remained stable over a period of 360 min, we observed full sedimentation of the SiO2 microparticles. The CS [(a.k.a. core shell)] particles showed intermediate sedimentation behavior with an increasing tendency of sedimentation speed from PS10 to PS360, reflecting well the increasing amount of SiO2 as determined for instance by TGA and a corresponding increase in density”). As evidenced by Sarma above, the particles of Janczak will have a density between 1.05 g/mL (the density of polystyrene particles) and 2 g/mL (the density of silica particles), which meets the limitation of at least about 1.1 g/mL.
‘107 and Janczak are analogous to the field of the claimed invention because they are both in the field of scintillant-doped particles. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to integrate the disclosure of Janczak to the particles of ‘107. An artisan would have been motivated to produce hydrophilic microparticle scintillators, wherein the D90 particle size is about 2 µm, as in claims 1-4 and 9-20, because Janczak discloses that larger particles can entrap a greater number of scintillant molecules and may yield a larger signal on a per particle basis (see, e.g., p. 167, para. 1). Therefore, arriving at the claimed invention before the effective filing date of the application would be a matter of routine optimization. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions”). With respect to the probe moieties, an artisan would have been motivated to add the antibodies of Janczak to the particle of ‘107 because Janczak discloses, “Antibodies, aptamers, or single-stranded DNA could be attached to the scintillant-doped PS-core silica-shell nP surfaces to make more practical SPA probes” (see p. 193). With respect to the density of the particles, an artisan would have been motivated to use the density of particles of Janczak for the particles of ‘107 because Janczak discloses, “it is anticipated that the density of the core-shell nPs will allow the particles to remain dispersed in a sample for a longer period of time than inorganic scintillator particles” (see Janczak, p. 189). An artisan would have a reasonable expectation of success based on the given disclosure.
Claims 5-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, and 12 of ‘107 (cited above) and Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-20 above, and further in view of Aspinwall (cited above).
‘107 and Janczak teach as set forth above, but fail to teach the probe moiety is attached to the silica-shell via a linker, wherein the linker is a hydrophilic polymer, poly(ethylene glycol) (PEG), as in claims 5-8.
However, in a patent application publication on scintillant nanoparticles, Aspinwall rectifies this deficiency. Aspinwall teaches attaching a probe moiety to a scintillant-doped PS particle with a silica-shell via a PEG linker, as in claims 5-8 (see, e.g., para. [0264]).
‘107, Janczak, and Aspinwall are analogous to the field of the claimed invention because they are both in the field of scintillant-doped particles. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the PEG linker of Aspinwall to the particles of ‘107 and Janczak. An artisan would have been motivated to do so because Aspinwall discloses, “The NHS end of the linker on PS-MPTS-NHS NPs was used to facilitate peptide coupling of SRC kinase substrate through the amine groups on its lysine amino acid residues” (see para. [0264]). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
Claims 21 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, and 12 of ‘107 (cited above) and Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-20 above, and further in view of Ma, et al. (cited above).
‘107 and Janczak teach as set forth above, but fail to teach the hydrophilic microparticle scintillators are incorporated into an apparatus, specifically a particle-packed cartridge, as in claims 21 and 22.
However, in a journal article on the preparation of an immunoaffinity column with microparticles, Ma rectifies this deficiency. Ma teaches an apparatus of a particle-packed cartridge, as in claims 21 and 22 (see, e.g., p. 2222, under “Abstract:”).
‘107, Janczak, and Ma are analogous to the field of the claimed invention because they are both in the field of particle development. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the particle-packed cartridge apparatus of Ma to the particles of ‘107 and Janczak. An artisan would have been motivated to do so because Ma teaches the immunoaffinity column with the particle-packed cartridge is capable of selective extraction of analytes (see, e.g., p. 2222, under “Abstract:”). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
Claim 1-4 and 9-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of copending Application No. 17/347,938 (referred hereto as ‘938) in view of Janczak (cited above) as evidenced by Sarma (cited above).
‘938 teaches a hydrophilic particle scintillator comprising: a polymer-core particle, where the particle is doped with a scintillator material; and a silica-shell portion encapsulates the polymer-core particle, where the silica-shell portion comprises an outer surface, as in claim 1 (see claims 1 and 3 of ‘938).
‘938 teaches a method for producing a hydrophilic particle scintillator wherein the hydrophilic particle scintillator comprises: a polymer-core particle, wherein the polymer-core particle is doped with at least one scintillator material; and a silica-shell portion encapsulating said polymer-core particle, the method comprising: producing the polymer-core particle that is doped with a scintillator material; and contacting the polyaromatic-core particle with a silica-shell precursor mixture under conditions sufficient to encapsulate the polyaromatic-core particle with a silica-shell portion to produce the hydrophilic particle scintillator, as in claim 17 (see claims 1 and 3 of ‘938).
‘938 teaches the method of claim 17, wherein the step of producing the polyaromatic-core particle comprises: polymerizing a monomer compound under conditions sufficient to produce a polymer particle and admixing the polymer particle with the scintillator material under conditions sufficient to produce the polymer-core particle, wherein the polymer-core particle is doped with at least one scintillator material, as in claim 18 (see claims 1 and 3 of ‘938).
‘938 fails to teach the particles are microparticles, as in claim 1-4 and 9-19.
‘938 fails to teach the polymer-core is a polyaromatic core, such as polystyrene, as in claims 1-4 and 9-20.
‘938 fails to teach the outer surface of the silica-shell portion comprises a functional group adapted for attaching a probe moiety, specifically an amine group, as in claims 2 and 3.
‘938 fails to teach the probe moiety is capable of selectively binding a ligand, as in claim 4.
‘938 fails to teach the probe moiety is an antibody, as in claim 9.
‘938 fails to teach the polystyrene-core microparticle has mean particle size in the range of from about 1 µm to about 1000 µm, as in claim 10.
‘938 fails to teach the D9o particle size of the polystyrene-core microparticle is about 2 µm, as in claim 11.
‘938 fails to teach the average particle size of the polystyrene-core microparticle ranges from about 1 µm to about 5 µm, as in claim 12.
‘938 fails to teach the thickness of the silica-shell portion is 50 nm, as in claims 13 and 14.
‘938 fails to teach the polyaromatic-core particle is a polystyrene-core particle, as in claim 15.
‘938 fails to teach the hydrophilic particle scintillator is at a density of at least about 1.1 g/mL, as in claim 16.
‘938 fails to teach the method of claim 18, wherein the step of producing the polyaromatic particle comprises providing a solution of an aromatic vinyl compound and a radical polymer initiator under conditions sufficient to produce the polyaromatic particle, wherein the aromatic vinyl compound is styrene, as in claim 19.
However, in a dissertation on particles for enhanced sensitivity in biological labeling and biomolecular sensing, Janczak teaches, “Polystyrene particles are often fabricated using microemulsion polymerization methods with or without surfactant stabilizers. […] Size, ranging from tens of nanometers to several micrometers in diameter, can be adjusted by changing the monomer and surfactant concentrations and by regulating the rate at which monomer is added to the reaction during polymerization”, as in claims 1-4 and 9-19 (see p. 61-62).
Janczak teaches styrene as the monomer for polymerizing the polyaromatic-core particles, as in claims 1-4 and 9-19 (see, e.g., p. 157, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
Janczak teaches the outer surface of the silica-shell portion comprises a functional group adapted for attaching a probe moiety, specifically an amine group, as in claims 2 and 3 (see, e.g., p. 181: “the PS-core silica-shell nPs are amine-functionalized by including APTES in the shell synthesis”).
Janczak teaches the probe moiety is capable of selectively binding a ligand, as in claim 4 (see, e.g., p. 178, under “4.3.5 Biotin-Streptavidin Binding Model SPA”, para. 1). It is understood that streptavidin is a probe moiety capable of selectively binding the ligand, biotin.
Janczak teaches the probe moiety is an antibody, as in claim 9 (see, e.g., p. 164: “the covalent attachment of receptor molecules such as proteins, antibodies").
Janczak teaches the thickness of the silica-shell portion is 20 nm, as in claims 13 and 14 (see, e.g., p. 166: “Silica shells ca. 20 nm thick were deposited on scintillant-doped PS core nPs”).
Janczak teaches the polyaromatic-core particle is a polystyrene-core particle, as in claim 15 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
Janczak teaches the hydrophilic particle scintillator is at a density of at least about 1.1 g/mL, as in claim 16 (see, e.g., p. 157-157, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs” and “4.2.3 Addition of Silica Shells to PS Core nPs”). Sarma gives evidence that the particles of Janczak have a density of at least about 1.1 g/mL, as in claim 16 (see, e.g., Sarma, p. 3717: “SiO2 particles have higher densities (2 g mL−1 )”, and p. 3720: “assuming a density of 1.05 g mL−1 for polystyrene”, and p. 3723: “While a suspension of PS particles remained stable over a period of 360 min, we observed full sedimentation of the SiO2 microparticles. The CS [(a.k.a. core shell)] particles showed intermediate sedimentation behavior with an increasing tendency of sedimentation speed from PS10 to PS360, reflecting well the increasing amount of SiO2 as determined for instance by TGA and a corresponding increase in density”). As evidenced by Sarma above, the particles of Janczak will have a density between 1.05 g/mL (the density of polystyrene particles) and 2 g/mL (the density of silica particles), which meets the limitation of at least about 1.1 g/mL.
Janczak teaches the method of claim 18, wherein the step of producing the polyaromatic particle comprises providing a solution of an aromatic vinyl compound and a radical polymer initiator under conditions sufficient to produce the polyaromatic particle, wherein the aromatic vinyl compound is styrene, as in claim 19 (see, e.g., p. 157-158, under “4.2.2 Fabrication of Scintillant-Doped Polystyrene Core nPs”).
‘938 and Janczak are analogous to the field of the claimed invention because they are both in the field of scintillant-doped particles. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to integrate the disclosure of Janczak to the particles of ‘938. An artisan would have been motivated to produce hydrophilic microparticle scintillators, wherein the D90 particle size is about 2 µm, as in claims 10-12, because Janczak discloses that larger particles can entrap a greater number of scintillant molecules and may yield a larger signal on a per particle basis (see, e.g., p. 167, para. 1). Therefore, arriving at the claimed invention before the effective filing date of the application would be a matter of routine optimization. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions”). As for the polymer-core particles, an artisan would have been motivated to use the styrene of Janczak as the monomer for polymerizing polystyrene as the polyaromatic-core particles in ‘938 because Janczak discloses, “polystyrene has been shown to be a useful material for particle based sensors and markers” (see p. 66). With regards to the probe moieties, an artisan would have been motivated to add the probe moieties, specifically the antibodies, of Janczak to the particle of ‘938 because Janczak discloses, “Antibodies, aptamers, or single-stranded DNA could be attached to the scintillant-doped PS-core silica-shell nP surfaces to make more practical SPA probes” (see p. 193). With regards to the silica-shell thickness, an artisan would have a used the silica-shell thickness of Janczak for the particles of ‘938 because Janczak teaches “For SPA nPs however, thick silica shells increase the distance between the PS core nPs and surface-bound analyte, decreasing the probability that energy from β-particles emitted from the analyte will be absorbed by core nPs. Conversely, silica shells that are too thin may be discontinuous, leaving regions of PS exposed and reducing the number of available binding sites on functionalized scintillant-doped PS-core silica-shell nPs. For these reasons, silica shells ca. 20 nm thick were deposited on scintillant-doped PS core nPs to fabricate core-shell nPs for SPA” (see p. 167-168). With respect to the density of the particles, an artisan would have been motivated to use the density of particles of Janczak for the particles of ‘107 because Janczak discloses, “it is anticipated that the density of the core-shell nPs will allow the particles to remain dispersed in a sample for a longer period of time than inorganic scintillator particles” (see Janczak, p. 189). An artisan would have a reasonable expectation of success based on the given disclosure.
This is a provisional nonstatutory double patenting rejection.
Claims 5-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 ‘938 (cited above) and Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-19 above, and further in view of Aspinwall (cited above).
‘938 and Janczak teach as set forth above, but fail to teach the probe moiety is attached to the silica-shell via a linker, wherein the linker is a hydrophilic polymer, poly(ethylene glycol) (PEG), as in claims 5-8.
However, in a patent application publication on scintillant nanoparticles, Aspinwall rectifies this deficiency. Aspinwall teaches attaching a probe moiety to a scintillant-doped PS particle with a silica-shell via a PEG linker, as in claims 5-8 (see, e.g., para. [0264]).
‘938, Janczak, and Aspinwall are analogous to the field of the claimed invention because they are both in the field of scintillant-doped particles. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the PEG linker of Aspinwall to the particles of ‘938 and Janczak. An artisan would have been motivated to do so because Aspinwall discloses, “The NHS end of the linker on PS-MPTS-NHS NPs was used to facilitate peptide coupling of SRC kinase substrate through the amine groups on its lysine amino acid residues” (see para. [0264]). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
This is a provisional nonstatutory double patenting rejection.
Claims 21 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of ‘938 (cited above) and Janczak (cited above) as evidenced by Sarma (cited above), as applied to claims 1-4 and 9-19 above, and further in view of Ma, et al. (cited above).
‘938 and Janczak teach as set forth above, but fail to teach the hydrophilic microparticle scintillators are incorporated into an apparatus, specifically a particle-packed cartridge, as in claims 21 and 22.
However, in a journal article on the preparation of an immunoaffinity column with microparticles, Ma rectifies this deficiency. Ma teaches an apparatus of a particle-packed cartridge, as in claims 21 and 22 (see, e.g., p. 2222, under “Abstract:”).
‘938, Janczak, and Ma are analogous to the field of the claimed invention because they are both in the field of particle development. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the particle-packed cartridge apparatus of Ma to the particles of ‘938 and Janczak. An artisan would have been motivated to do so because Ma teaches the immunoaffinity column with the particle-packed cartridge is capable of selective extraction of analytes (see, e.g., p. 2222, under “Abstract:”). An artisan would have had a reasonable expectation of success based on the discussed disclosures.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Sarma (cited above) gives evidence of the density of the polystyrene-core silica-shell particles.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678