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 .
Election/Restrictions
Applicant’s election of Invention I (claims 1-13) in the reply filed on 09/22/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant's election with traverse of the species in claim 6 where the first monomer comprises styrene and the second monomer comprises methacrylic acid in the reply filed on 09/22/2026 is acknowledged.
The traversal is on the ground(s) that the options for the two monomers are obvious variants of one another. Particularly, the applicant argues that the first monomer provides a carbon-carbon double bond for polymerization while the second monomer provides functional groups such as carboxyl, amino, and silanol groups for future modifications. Respectfully, this is not found persuasive because a polymer made from styrene is different in packing and is majority unbranched compared to a polymer made from butadiene which does not have aryl rings for pi-pi stacking and is majority branched. As to the second monomer, a polymer made from methacrylic acid is significantly different from a polymer from the ring opening of ethyleneimine in sterics and electronics.
The requirement is still deemed proper and is therefore made FINAL.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Invention II (claims 14-20), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/22/2024.
Status of Application
Applicant’s election of claim(s) 1-13 in the reply filed on 09/22/2026 is acknowledged.
Applicant’s withdrawal of claim(s) 14-20 in the reply filed on 09/22/2026 is acknowledged.
Claims 1-13 are under examination.
Claim Interpretation
Claim 1 recites “a dispersion located between two neighboring magnetic particles” in lines 3-4. The examiner notes that the claim language does not require a dispersion between all magnetic nanoparticles but only between two. Therefore, for the purposes of examination, the examiner interprets any prior art containing a dispersion between two magnetic nanoparticles as reading on this claim limitation.
Claim 1 recites “a material of the dispersion, a material of the main shell body and a material of the modifying layer are the same”. The examiner notes that “a material” is not defined in the claims or in the specification. Therefore, for the purposes of examination, the examiner interprets any prior art containing a polymer microsphere that shares a material in common (e.g. a carbon atom, monomer, magnetic nanoparticle, etc) in the dispersion, shell and modifying layers, as reading on this claim limitation.
Claim 1 recites “the modifying layer is located on one side of the main shell body that is away from the magnetic particles”. The examiner notes that the specification states, “the material of the main shell body and the material of the modifying layer comprises a polymer formed by at least one first monomer and at least one second monomer … and the modifying layer comprises at least one of amino, carboxyl, hydroxyl and silicon hydroxyl.” (pg 1, para [0009]). The examiner notes that the materials of the modifying layer are also present in the other layers, specifically, the two monomers. Therefore, for the purposes of examination, the examiner interprets any prior art containing functional groups on the surface of the magnetic microsphere as reading on this limitation.
Claims 3, 5, and 8-10 recite “molar weight”. The specification defines molar weight as molar mass (pg 10, para [0094]) and the specification further notes, “the mass per mole of a substance is referred to as its “molar mass”” (pg 10, para [0094]). Therefore, for the purposes of examination, the examiner interprets every mention of molar weight in these claims to mean the molar mass or weight per mole of the monomers. For the purposes of examination, the examiner interprets any prior art with two monomers as having a ratio of their molar masses regardless of whether the prior art recites the molar masses of their monomers.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-8 and 12-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu, Z.; et al., CN 1468898 A (as cited in the IDS filed on 10/15/2024).
Liu, Z.; et al., (hereafter referred to as Liu) is drawn to the preparation of super-paramagnetic polymer microspheres (abstract). Liu teaches superparamagnetic polymer microspheres can have various functional groups on the surface by copolymerization and surface modification (pg 2, para 3, lines 1-4) and that there are various ways of synthesizing magnetic polymer composite microspheres such as embedding, chemical conversion and monomer polymerization (pg 2, para 4, lines 1-3) and that thermal initiated polymerization of ethylenic monomers in the presence of a surfactant-stabilized aqueous phase magnetic fluid , and lipophilic alkene can be performed (pg 2, para 5, lines 1-6) and that a microsuspension polymerization method can use a lipophilic coating on the surface of the magnetic nanoparticles dissolved in an oily ethylenic monomer and then polymerizing (pg 3, para 6, lines 1-6). Liu teaches the object of the invention is to provide a preparation method of superparamagnetic polymer microspheres with controllable particle size and distribution, high magnetic content, strong magnetic property, good acid and alkali resistance, and controllable surface functional group content. (pg 3, para 3, lines 1-4). Liu teaches microemulsion polymerization of the coated magnetic ferro/ferric oxide particles comprising lipophilic organic olefin monomer and a functional monomer (pg 3, para 4, lines 1-3) where the copolymer contains nano-magnetic particles and the copolymer is comprised of a lipophilic ethylenic monomer (such as styrene, vinyl chloride, etc) or has a hydrophilic functional group (such as COOH), and a homopolymer or a copolymer from organic monomer of acrylic acid, acrylamide, etc) (pg 3, para 4, lines 1-8). Liu teaches the particle size of the polymer microspheres is between 0.1 and 5 µm (pg 3, para 4, lines 11-12) and the magnetic triiron tetroxide is 0.5-40% of the total mass ratio of the microspheres (pg 3, para 4, lines 12-13). Liu teaches synthesis of the polymer microspheres (pg 4, para 3, lines 1-7).
As to claim 1, Liu teaches a polymer microsphere wherein the polymer microsphere comprises a core and a shell coating the core (pg 8, claim 2, lines 1-6); where the core comprises at least two magnetic particles and a dispersion located between two neighboring magnetic particles (pg 8, claim 2, lines 3-4); where the shell comprises a main shell body and a modifying layer (pg 8, claim 2, lines 1-3; pg 8, claim 4; pg 8, claim 1, pg 3, para 4, lines 1-14), and where the modifying layer is on one side of the main shell body that is away from the magnetic particles (pg 8, claim 4, lines 1-4); and where a material of the dispersion, main shell body, and modifying layer are the same (pg 8, claim 1, lines 1-5).
As to claim 2, Liu teaches the dispersion covers at least part of a surface of the magnetic particles (pg 8, claim 1, lines 4-8).
As to claim 3, Liu teaches the material of the dispersion, main shell body, and modifying layer comprise a polymer formed by at least a first and second monomer (pg 8, claim 1, lines 1-5) and a molar weight ratio range of the first monomer to the second monomer 16:0 and 8:8 (pg 8, claim 3, lines 1-5). This range overlaps with the claimed range of 1:0.1-10. When, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art. See MPEP 2131.03(I).
As to claim 4, Liu teaches the second monomer and the modifying layer comprises at least a carboxyl group (pg 8, claim 1, lines 3-5; pg 8, claim 3, lines 1-5).
As to claim 5, Liu teaches that the second monomer can be methacrylic acid (pg 8, claim 3, lines 4-5). The first monomer can be styrene (pg 8, claim 3, lines 3-5). The molecular weight of methacrylic acid with a molecular weight of 86.09 g/mol, is less than styrene with a molecular weight of 104.15 g/mol.
As to claim 6, Liu teaches the first monomer comprises at least styrene (pg 8, claim 3, lines 3-4) and Liu teaches the second monomer comprises at least methacrylic acid (pg 8, claim 3, lines 3-5).
As to claim 7, Liu teaches a mass ratio of the magnetic particles to a sum of a monomer mass in the range of 0.5-40 wt% (pg 8, claim 1, lines 9-10). The claimed range of 0.5-3 has at least one value in the prior art range of 0.5-40. When, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art. See MPEP 2131.03(I).
As to claim 8, Liu teaches a polymer microsphere wherein the first monomer comprises styrene and the second monomer comprises methacrylic acid (pg 8, claim 3, lines 1-5) and and a molar weight ratio range of the first monomer to the second monomer 16:0 and 8:8 (pg 8, claim 3, lines 1-5). This range overlaps with the claimed range of 1:0.1-10. When, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art. See MPEP 2131.03(I).
As to claim 12, Liu teaches a magnetic particle of 5-20 nm (pg 3, para 5, lines 2-3). The claimed range of 8-15 nm has at least one value inside the prior art range of 5-20 nm. When, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art. See MPEP 2131.03(I).
As to claim 13, Liu teaches the polymer microsphere is 100 nm to 5 µm (pg 8, claim 1, lines 9-10). The claimed range of 100 nm to 5 µm contains at least one value in the prior art range of 100 nm to 5 µm. When, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art. See MPEP 2131.03(I).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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) 9 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu, Z. L.; et al., Preparation and characterization of magnetic P(St-co-MAA-co-AM) microspheres, Journal of Magnetism and Magnetic Materials, 2006, 302, 529-535 and further in view of Digigow, R. G.; et al., Preparation an and characterization of functional silica hybrid magnetic nanoparticles, Journal of Magnetism and Magnetic Materials, 2014, 362, 72-79 and Sawyer, L. H.; et al., US 2011/0155141 A1. The teachings of Liu as applied in the previous rejection are incorporated in this rejection.
Liu, Z.; et al., (hereafter referred to as Liu) is drawn to the preparation of super-paramagnetic polymer microspheres (abstract). Liu teaches superparamagnetic polymer microspheres can have various functional groups on the surface by copolymerization and surface modification (pg 2, para 3, lines 1-4) and that there are various ways of synthesizing magnetic polymer composite microspheres such as embedding, chemical conversion and monomer polymerization (pg 2, para 4, lines 1-3) and that thermal initiated polymerization of ethylenic monomers in the presence of a surfactant-stabilized aqueous phase magnetic fluid , and lipophilic alkene can be performed (pg 2, para 5, lines 1-6) and that a microsuspension polymerization method can use a lipophilic coating on the surface of the magnetic nanoparticles dissolved in an oily ethylenic monomer and then polymerizing (pg 3, para 6, lines 1-6). Liu teaches the object of the invention is to provide a preparation method of superparamagnetic polymer microspheres with controllable particle size and distribution, high magnetic content, strong magnetic property, good acid and alkali resistance, and controllable surface functional group content. (pg 3, para 3, lines 1-4). Liu teaches microemulsion polymerization of the coated magnetic ferro/ferric oxide particles comprising lipophilic organic olefin monomer and a functional monomer (pg 3, para 4, lines 1-3) where the copolymer contains nano-magnetic particles and the copolymer is comprised of a lipophilic ethylenic monomer (such as styrene, vinyl chloride, etc) or has a hydrophilic functional group (such as COOH), and a homopolymer or a copolymer from organic monomer of acrylic acid, acrylamide, etc) (pg 3, para 4, lines 1-8). Liu teaches the particle size of the polymer microspheres is between 0.1 and 5 µm (pg 3, para 4, lines 11-12) and the magnetic triiron tetroxide is 0.5-40% of the total mass ratio of the microspheres (pg 3, para 4, lines 12-13). Liu teaches synthesis of the polymer microspheres (pg 4, para 3, lines 1-7).
As to claim 9, Liu teaches a polymer microsphere wherein the polymer microsphere comprises a core and a shell coating the core (pg 8, claim 2, lines 1-6); where the core comprises at least two magnetic particles and a dispersion located between two neighboring magnetic particles (pg 8, claim 2, lines 3-4); where the shell comprises a main shell body and a modifying layer (pg 8, claim 2, lines 1-3; pg 8, claim 4; pg 8, claim 1, pg 3, para 4, lines 1-14), and where the modifying layer is on one side of the main shell body that is away from the magnetic particles (pg 8, claim 4, lines 1-4); and where a material of the dispersion, main shell body, and modifying layer are the same (pg 8, claim 1, lines 1-5). And Liu teaches the dispersion covers at least part of a surface of the magnetic particles (pg 8, claim 1, lines 4-8). And Liu teaches the material of the dispersion, main shell body, and modifying layer comprise a polymer formed by at least a first and second monomer (pg 8, claim 1, lines 1-5). Liu teaches a molar weight ratio range of the first monomer to the second monomer 16:0 and 8:8 (pg 8, claim 3, lines 1-5). This is equivalent to a molar weight ratio of the first monomer to the total monomer of 16:0 and 8:16 which is equivalent to 1-0.5. This range overlaps with the claimed range of 0.1-0.8. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Liu does not teach the first monomer comprises tetraethyl orthosilicate and the second monomer comprises aminopropyltriethoxysilane and glyoxal.
Liu does not teach a range of a ratio of a molar weight of the aminopropyltriethoxysilane in the second monomer to the molar weight of the total monomer amount is 0.1-0.4.
Liu does not teach a range of a ratio of molar weight of the glyoxal in the second monomer to the molar weight of the total monomer amount is 0.1-0.5.
Digigow, R. G.; et al. (hereafter referred to as Digigow) is drawn to preparation and characterization of magnetic nanoparticles made from APTES and TEOS (title; abstract). Digigow teaches superparamagnetic iron oxide nanoparticles have outstanding magnetic properties (pg 72, col 1, para 1 lines 1-3) and that they are useful as contrast agents in MRI, targeted drug delivery systems (pg 72, col 1, para 1, lines 3-6) and in diagnostics (pg 1, col 1, para 1, lines 6-9). Digigow teaches that synthetic approaches are typically done in aqueous conditions and rely on co-precipitation of ferrous and ferric iron salts (pg 72, col 1, para 2, lines 1-7) and that some magnetic particles are coated with surfactants, polymers, carbohydrates, or proteins (pg 72, col 1, para 2, lines 8-11) and that silica is one of the best inorganic coating materials to prevent agglomeration and improve chemical stability (pg 72, col 1, para 2, lines 10-11; pg 72, col 2, para 1, lines 1-3). Digigow teaches the synthetic route is typically the Stober process or the microemulsion process (pg 72, col 2, para 1, lines 1-3) and that 3-aminopropyltriethoxysilane (APTES) is frequently used to stabilize silica or metal oxide nanoparticles and is used to introduce amine groups for subsequent chemical functionalization (pg 72, col 2, para 2, lines 1-3) and co-condensation with tetraethyl orthosilicate (TEOS) is performed than increased control over the synthesis can be obtained (pg 72, col 2, para 2, lines 9-12; pg 72, col 2, para 3, lines 1-6). Digigow teaches the synthesis (pg 73, col 1, para 3, lines 11) and characterization (pg 73, col 2, para 3-6) and that the amines are available for complexation (pg 74, col 1, para 1, lines 1-4).
Regarding the first monomer comprises tetraethyl orthosilicate and the second monomer comprises aminopropyltriethoxysilane and glyoxal, Digigow teaches a first monomer of tetraethyl orthosilicate and a second monomer of aminopropyltriethoxysilane (abstract; pg 73, col 1, para 5, lines 1-10).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Liu to include monomers as taught by Digigow because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a magnetic microsphere of Liu with a first monomer of TEOS and a second monomer of APTES.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a magnetic microsphere comprising a first monomer of TEOS and a second monomer of APTES because the prior art of Liu disclosed magnetic nanoparticles are susceptible to agglomeration (pg 3, para 2, lines 6-8) that there are various ways of making magnetic microspheres (pg 2, para 4, lines 1-3) and that the magnetic microspheres can be a copolymer such that one of the monomers has functional groups (pg 2, para 3, lines 1-4) known to successfully encapsulate magnetic nanoparticles and reduce agglomeration. Additional prior art of Digigow suggested that the agglomeration issue can be solved with silica-based material which is the best described inorganic coating material to prevent agglomeration (pg 72, col 1, para 2, lines 10-11; pg 72, col 2, para 1, lines 1-2) and that silica-based coated magnetic nanoparticles coated with APTES and TEOS have similar properties of magnetic nanoparticles because of the overlap of the magnetic nanoparticles between them involves known chemistry.
The skilled artisan would have been motivated to modify the magnetic microspheres with APTES and TEOS because possessing an organic coated magnetic microsphere and a silica-based magnetic microsphere improves potential application and provides additional coating chemistries which can provide more options for clinical trials or industrial applications. Therefore, it would have been prima facie obvious to combine the teachings of Liu with Digigow.
The combined teachings of Liu and Digigow do not teach glyoxal.
Sawyer, L. H.; et al. (hereafter referred to as Sawyer) is drawn to a wearable article coated with a composition of aminofunctionalized silane and a dialdehyde (title; abstract). Sawyer teaches a wearable article for prevention of injury or trauma (pg 2, para [0008], lines 1-5) and a coating composition of a aminofunctionalized silane and a dialdehyde (pg 2, para [0009], lines 1-2) and that the aminofunctionalized silane coating the fibers is aminopropyltriethoxysilane (APTES) (pg 2, para [0009], lines 9-11; pg 4, para [0028], lines 6-11) and tetraethoxysilane can also be used as a coating (pg 4, para -0028], lines 1-5). Sawyer teaches a dialdehyde is used to form a matrix among the aminofunctionalized silanes (pg 4, para [0029], lines 1-11) and glyoxal and glutaraldehyde are useful dialdehydes (pg 4, para [0029], lines 1-7). Sawyer teaches adding nanoparticles to the composition (pg 4, para [0030], lines 1-21) and ratios of components in the composition (pg 5, Table 1).
Regarding glyoxal, Sawyer teaches a composition comprising tetraethoxysilane, and 2-aminopropyltriethoxysilane and a dialdehyde (pg 4, para [0027], lines 1-2; pg 4, para [0028], lines 1-11) where the dialdehyde is glyoxal (pg 4, para [0029], lines 1-3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the combined teachings of Liu and Digigow to include glyoxal as taught by Sawyer because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a coating composition containing APTES and TEOS of Digigow with the glyoxal of Sawyer.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a coating composition of a magnetic microsphere of TEOS, APTES and glyoxal because the prior art of Digigow disclosed magnetic microspheres with co-condensation polymer of TEOS and APTES known to successfully encapsulate the magnetic nanoparticles and to show a lower cross-linking density in the gel network (Digigow, pg 75, col 1, para 1, lines 3-6). Additional prior art of Sawyer suggested modifying aminofunctionalized polymers with glycoxal improves the matrix and to have similar ability to form cross-linking in the aminofunctioanlized polymers (Sawyer, pg 4, para [0029], lines 1-11) because of the overlap of the APTES and TEOS between them involves known chemistry.
The skilled artisan would have been motivated to modify the composition of TEOS and APTES of Digigow with the glyoxal of Sawyer because glyoxal helps increase the cross-linking density in the TEOS and APTES co-condensattion polymerization which Digigow identified as a potential issue (pg 75, col 1, para 1, lines 3-6). Therefore, it would have been prima facie obvious to combine the teachings of Digigow with Sawyer.
Regarding a range of a ratio of a molar weight of the aminopropyltriethoxysilane in the second monomer to the molar weight of the total monomer amount is 0.1-0.4, Digigow teaches the molar weight ratio of aminopropyltriethoxysilane to the total weight of the total monomer amount is 0-100 wt% (pg 74, Table 1). The claimed range of 0.1-0.4 lies fully within the prior art range of 0-100 wt%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding a range of a ratio of molar weight of the glyoxal in the second monomer to the molar weight of the total monomer amount is 0.1-0.5, Sawyer teaches a ratio of the glyoxal to other monomers as 8:0.25 to 4:1 (pg 5, Table 1). This is equivalent to a molar weight ratio of the glyoxal to total monomer amount of 8:8.25 to 4:5 which is equivalent to 0.8-0.97. The claimed range of 0.1-0.5 is close to 0.8-0.97. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.
Additionally, Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the concentration range of glyoxal was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
As to claim 11, Liu teaches the magnetic nanoparticles in the core is 5-20 nm (pg 8, claim 2, lines 1-3) and the size of the microspheres containing uniformly dispersed nanoparticles in the core is between 0.1 and 5 µm (pg 8, claim 1, lines 6-10). This is equivalent to a distance from the magnetic nanoparticles to the modifying layer of 0-5 µm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu as applied to claims 1-8 and 12-13 above, and further in view of Yeh, B. M., US 2021/0299284 A1. The teachings of Liu as applied in the previous rejection are incorporated in this rejection.
As to claim 10, Liu teaches polymer microspheres where the first monomer comprises styrene (pg 8, claim 1, lines 1-4) and a second monomer comprises a hydrophilic functional group of amine (pg 8, claim 1, lines 1-5). Liu teaches the ratio of the molar weight of the first monomer to a molar weight of a second monomer is 16:0 and 8:8 (pg 8, claim 3, lines 1-5). This is equivalent to a molar weight ratio of the first monomer to the total monomer of 16:0 and 8:16 which is equivalent to 1-0.5. This range overlaps with the claimed range of 0.1-0.6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And, Liu teaches a range of a ratio of the molar weight of the second monomer to the molar weight of the total monomer of 0:16 and 8:8 (pg 8, claim 3, lines 1-5). This is equivalent to a weight ratio of the second monomer to the total monomer of 0:16 to 8:16 which is equivalent to 0-0.5. The claimed range of 0.4-0.9 overlaps with the prior art range of 0-0.5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Additionally, as to the molar weight ratios of the first and second monomers to the total monomer. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the molar weight ratio, equivalent to the relative concentration of monomers, was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
Liu does not explicitly teach the second monomer is ethyleneimine.
Yeh, B. M. (hereafter referred to as Beh) is drawn to materials to acquires MRIs (title; abstract). Yeh teaches MRI uses enteric contrast media in many clinical scenarios (pg 1, para [0002], lines 1-3) and that native bowel lumen fluid has a low signal on T1 and high signal on T2-weighted images (pg 1, para [0003], lines 1-3). Yeh teaches MRI through administration of a safe and effective low T1 and low T2 signal "dark" oral contrast material suitable for use in humans (pg 1, para [0008], lines 1-7) and that the microbubble contrast agents may be coated with a biocompatible polymer (pg 2, para [0009], lines 6-11). Yeh teaches the polymer that may encapsulate the particle may be a copolymer of styrene and ethyleneimine (pg 7, para [0055], lines 1-2, 5-8, and 17) and that polyethyleneimine is an exemplary material (pg 7, para [0055], col 1, line 27 and col 2, line 1). And, Yeh teaches methods of using the microparticles (pg 11, para [0107], lines 1-14)
Regarding the second monomer is ethyleneimine, Yeh teaches a copolymer of styrene and ethyleneimine as shell for microparticles (pg 7, para [0055], lines 1-2, 5-8, and 17; pg 7, para [0055], col 1, line 27 and col 2, line 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the modify the material of the shell of Liu to include material of the shell as taught by Yeh because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a copolymer of styrene and ethyleneimine in the material around the magnetic nanoparticles.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the amine containing functional monomer of Liu with the ethyleneimine in the copolymer with styrene because the prior art of Liu disclosed a copolymer known to have styrene and a amine containing comonomer for encapsulating magnetic nanoparticles (Liu, pg 8, claim 1, lines 1-4; pg 8, claim 1, lines 1-5). Additional prior art of Yeh suggested polyethyleneimine, which has a terminal amine, to have similar ability to form a shell of a nanoparticle and is capable of copolymerization with styrene (Yeh, pg 7, para [0055], lines 1-2, 5-8, and 17; pg 7, para [0055], col 1, line 27 and col 2, line 1) because of the overlap of structure between them involves known chemistry.
The skilled artisan would have been motivated to modify the amine-containing monomer of the copolymer of Liu with ethyleneimine of Yeh because the ethyleneimine is hydrophilic and when on the surface as part of the modifying layer can help stabilize the magnetic microspheres in aqueous solutions. Therefore, it would have been prima facie obvious to combine the teachings of Liu with Yeh.
Pertinent Art
The prior art of Liu, Z. L.; et al., Preparation and characterization of magnetic P(St-co-MAA-co-AM) microspheres, Journal of Magnetism and Magnetic Materials, 2006, 302, 529-535 is deemed pertinent to the application.
Liu, Z. L.; et al. (hereafter referred to as Liu-2006) is drawn to magnetic polymer-coated microspheres prepared by microemulsion polymerization of styrene methacrylic acid and acrylamide (title; abstract). Liu-2006 teaches magnetic polymer microspheres are used in various aspects of biotechnology and biomedical engineering (pg 529, col 1, para 1, lines 1-6) and that the magnetic microspheres consist of a magnetic core and a polymer shell where the core contains small magnetic nanoparticles typically made of iron or nickel or similar, and the polymer shell around the core enables modification (pg 529, col 1, para 2, lines 1-9). Liu-2006 teaches preparation of microspheres by coating individual magnetic particles with oleic acid, dispersing in styrene and polymerizing at least styrene and methacrylic acid in the presence of emulsifiers (pg 530, col 1, para 2, lines 1-14). Liu teaches magnetic microspheres with a size range of 0.6-1.5 µm (pg 531, col 1, para 1, lines 1-2) and a magnetic core with a size of 5-20 nm (pg 530, col 2, para 5, lines 1-6). Liu-2006 teaches coating the magnetic microspheres with a protein (pg 532, col 1, para 2, lines 12) and with FITC (pg 532, col 2, para 1, lines 1-12).
The examiner considers the magnetic microspheres with a copolymer coating of a core and shell with a modifying layer for attachment to protein or FITC to render this art pertinent to this application.
Conclusion
No claims allowed.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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