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 Objections
Claim 32 is objected to because of the following informalities: The claim recites a ‘ “one-pot three-stage” continuous process, which process comprises:’. This phrase, including quotation marks, appears to be a typographical error. This phrase is treated as a ‘ one-pot three-stage continuous process comprising: ‘without quotation marks.
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.
Claim 9 is 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. The claim recites conditions “(a)…; and/or (b)…;(c)…”, which renders the claim indefinite. It is not clear whether the condition is limited to one of (a), (b), or (c) or some combination of the three is required.
While not a suggestion of claim language, in the interest of compact prosecution, the conditions will be treated as ‘(a)…; and/or (b)…; and/or (c)…’.
Appropriate correction is required.
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 instant claims contain the transitional phrase “comprising”. Per MPEP 2111.03 ‘The transitional term “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps'. This open-ended definition has been taken into consideration in the following rejections.
Claims 1-4, 6-14, 16, 21, 22, 29, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over JP 2006-265290 A to Ichiro et al. (hereinafter Ichiro), provided in the IDS filed 5/20/25, using a machine translation.
Regarding claim 1, Ichiro discloses monodisperse (uniform size, para [0002]) superparamagnetic beads (para [0027], particles), having a core-shell structure (base particle with multiple coating layers, para [0016]), said bead comprising:
a core portion formed from a polystyrene polymeric matrix material (polymerized styrene, para [0006]) with superparamagnetic nanoparticles adsorbed to the surface (para [0015]) and coated with an additional polymer layer (para [0016], multiple coating layers), which provides a polystyrene polymeric matrix material that encapsulates a first batch of superparamagnetic Fe₃O₄ nanoparticles (para [0009]).
The reference discloses that the beads comprise multiple coating layers that may contain the same or different magnetic particles and polymers (para [0016]) and therefore teaches first and second shells comprising multiple layers.
The shells and layers include a first shell portion located directly on top of the core portion and formed from a crosslinked polymeric matrix material that is formed from a styrene monomer (para [0017]-[0018]), a crosslinking monomer and a first functional monomer that has functional groups (para [0017]-[0018]), where the copolymeric matrix material encapsulates a second batch of superparamagnetic Fe₃O₄ (magnetic) nanoparticles between nonmagnetic polymer layers (para [0016]-[0017]) and a second shell on top of the first shell that comprises multiple layers (para [0016]).
The shell/coating layers comprise superparamagnetic Fe₃O₄ nanoparticles (para [0009]) and polymers selected from a group comprising conjugating monomers, bulk monomers (para [0019]), and functional monomers with functional groups (para [0017]) wherein the superparamagnetic Fe₃O₄ nanoparticles in the first layer are directly bound to the functional groups present on an outer surface of the first shell portion (via adsorption, para [0015]);
the first layer polymeric matrix material surrounds the superparamagnetic Fe₃O₄
nanoparticles in the first layer; and
the second layer polymeric matrix material extends from the first layer polymeric matrix material and forms an outer surface of each monodisperse superparamagnetic bead (in the formation of multilayered particle, para [0016]).
As discussed above, the bead may comprise multiple layers, which overlaps and encompasses a first shell and a second shell comprising a first, second and third layer in the instantly claimed configuration where the layers comprise magnetic nanoparticles, monomers and polymers selected from overlapping groups.
The reference is silent regarding the particular composition of the first, second and third layers of the second shell, particularly wherein,
the first layer comprises a first layer polymeric matrix material that comprises a conjugating monomer and a bulk monomer;
a second layer is formed from a second layer polymeric material that comprises a bulk monomer; and
a third layer is formed from a third layer polymeric material that comprises a bulk monomer and a second functional monomer that has functional groups.
However, as discussed above, the multiple layers can be the same or different (para [0016]) and the polymers are selected from overlapping groups comprising conjugated monomers, bulk monomers and monomers with functional groups (para [0016]-[0019]). It would therefore be obvious to one of ordinary skill in the art to select the particular monomer/polymer composition for each layer in each shell to facilitate formation of a multilayered composite bead/particle (para [0016]) with the desired combination of properties for use in diagnostic applications (para [0005] and [0026]).
Regarding claim 2, Ichiro discloses the beads according to Claim 1, wherein the second and third layer polymeric matrix materials function to prevent the superparamagnetic Fe₃O₄ nanoparticles from leaching out (para [0026]) and are therefore deemed capable of preventing the superparamagnetic Fe₃O₄ nanoparticles from leaching out when the beads are placed into a solvent, absent evidence to the contrary.
Regarding claim 3, Ichiro discloses the beads according to Claim 1, wherein the functional groups on the functional monomer in the first shell portion and the third layer of the second shell portion are independently selected from one or more of amino, epoxy (para [0013]), carboxyl (para [0018]), and hydroxy (para [0019]) groups.
Regarding claim 4, Ichiro discloses the beads according to Claim 1, wherein the beads have a coefficient of variation based on their diameter of less than 20% (para [0005]), which overlaps the instantly claimed range of less than 15%. See MPEP 2144.05(I), which states that ‘In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists’.
Regarding claim 6, Ichiro discloses the beads according to Claim 1, wherein the beads have an average diameter of 0.4 to 200 µm (para [0005]), which overlaps the instantly claimed range of from 0.2 to 5.0 µm. See MPEP 2144.05(I), cited above.
Regarding claim 7, Ichiro discloses the beads according to Claim 1, wherein the polystyrene polymeric matrix material is formed from one or more of the group consisting of styrene, a styrene derivative (para [0018]), and copolymers thereof (para [0019]).
Regarding claim 8, Ichiro discloses the beads according to Claim 1,
wherein all of the superparamagnetic Fe₃O₄ nanoparticles (20g) in a bead account for about 67 wt% (20/30, para [0028]), which falls within the instantly claimed range of 10 to 80 wt% of the entire weight of each bead (30 g, para [0028]).
Regarding claim 9, Ichiro discloses the beads according to Claim 8, wherein
(c) the superparamagnetic Fe₃O₄ nanoparticles in the first layer of the second shell portion represent 67 wt% (20/30, para [0028]), which falls within the instantly claimed range of 9.4 to 79.4 wt% of the entire weight of each bead.
This rejection is based on the interpretation set forth in para #4, above.
Regarding claim 10, Ichiro discloses the beads according to 1, wherein the crosslinking monomer is selected from one or more of the group consisting of
divinylbenzene, ethylene glycol dimethylacrylate, glycol diacrylate, poly(ethylene glycol) diacrylate, and combinations thereof (para [0018]).
Regarding claim 11, Ichiro discloses the beads according to Claim 1,
wherein the first functional monomer is selected from one or more of the group consisting of acrylic acid, methacrylic acid, 2-carboxyethyl acrylate, acrylamide, methacrylamide, (hydroxyethyl)methacrylate, 4-hydroxybutyl acrylate, glycidyl methacrylate, 2-hydroxyethyl methacrylate, 2-carboxyethyl acrylate oligomers, and combinations thereof (para [0019]).
Regarding claim 12, Ichiro discloses the beads according to 1, wherein the styrene monomer is selected from one or more of the group consisting of styrene, and a styrene derivative (para [0018]).
Regarding claim 13, Ichiro discloses the beads according to Claim 1, wherein the first shell may further comprise multiple layers comprising a first layer of a first polymeric matrix composition and
a second layer of a second polymeric matrix composition (para [0016], multiple layers that can be the same or different), where:
the first and second layers are formed from combinations of a copolymer of a styrene monomer, a crosslinking monomer; and a functional monomer (para [0017]-[0019]).
It would be obvious to one of ordinary skill in the art to select the particular polymer composition for each layer of the first shell to provide the desired adherence (para [0016]) without compromising magnetic properties (para [0005]).
Regarding claim 14, Ichiro discloses the beads according to Claim 1, wherein the superparamagnetic Fe₃O₄ nanoparticles have an average diameter of 10 nm (0.01 µm, para [0027]), which falls within the instantly claimed range of 5 to 15 nm.
Regarding claim 16, Ichiro discloses the beads according to Claim 1, wherein the Fe₃O₄ nanoparticles may further comprise oxide based substances comprising cobalt (Co) (para [0009]) but fails to expressly disclose Co in the form of Co₃O₄ nanoparticles. However, it would be obvious to one of ordinary skill in the art to employ Co₃O₄ nanoparticles to facilitate formation of a magnetic material with the desired saturation magnetization and residual magnetization (para [0009]).
Regarding claim 21, Ichiro discloses the beads according to Claim 1, but fails to expressly disclose wherein the combined weight of the second and third layer of the second shell accounts for from 1-30 wt% of the entire weight of each bead.
However, it would be obvious to one of ordinary skill in the art to optimize each layer of each shell to optimize the magnetic (para [0009]) and chemical properties of the beads (para [0026]).
Regarding claim 22, Ichiro discloses a method of preparing monodisperse (uniform) superparamagnetic beads, having a core-shell structure (as discussed above and para [0016]), the method comprising:
(a) providing monodisperse superparamagnetic precursor beads (para [0016]), which comprise
a core portion formed from a polystyrene polymeric matrix material, where the
polystyrene polymeric matrix material encapsulates a first batch of superparamagnetic
Fe₃O₄ nanoparticles;
a first shell portion located directly on top of the core portion and formed from a
crosslinked polymeric matrix material that is formed from a styrene monomer, a
crosslinking monomer and a first functional monomer that has functional groups (methacrylic acid) where the copolymeric matrix material encapsulates a second batch of superparamagnetic Fe₃O₄ nanoparticles; and
a second shell portion located directly on top of the first shell portion, which
comprises superparamagnetic Fe₃O₄ nanoparticles and polymeric precursor anchor points, both which are bound to the functional groups on a surface of the first shell portion (as discussed above, para [0016]); and
(b) forming a functional coating layer on the monodisperse superparamagnetic precursor beads by a one-pot (flask, para [0027]) free radical polymerization (via initiator, para [0017] and [0021]), which employs bulk monomers and functional monomers to form the beads (para [0016]-[0017]) wherein the functional coating layer is bound to the first shell portion by way of the polymeric precursor anchor points (adsorption, para [0016]).
The reference does not expressly recite the process steps as written wherein
(i) in a first step uses a bulk monomer; and
(ii) in a second step uses a second functional monomer that has functional groups to form the monodisperse superparamagnetic beads.
However, the reference does teach multiple steps wherein multiple polymers selected from conjugated, bulk, and functional monomers are mixed with magnetic nanoparticles to form multilayered superparamagnetic composite beads (para [0016]).
It would be obvious to one of ordinary skill in the art to provide the desired polymer combinations in the optimal order during processing to provide the desired composition in each layer and ultimately provide stable superparamagnetic beads with the desired combination of properties for use in diagnostic applications (para [0005] and [0026]).
Regarding claim 29, Ichiro discloses a process according to Claim 22,
wherein the monodisperse superparamagnetic precursor beads are formed by a process that comprises:
(i) providing naked monodisperse superparamagnetic beads (para [0027]), which comprise
a core portion formed from a polystyrene polymeric matrix material, where the
polystyrene polymeric matrix material encapsulates a first batch of superparamagnetic
Fe₃O₄ nanoparticles;
a first shell portion located directly on top of the core portion and formed from a
crosslinked polymeric matrix material that is formed from a styrene monomer, a
crosslinking monomer and a first functional monomer that has functional groups, where
the copolymeric matrix material encapsulates a second batch of superparamagnetic Fe₃O₄ nanoparticles (para [0027]-[0028]); and
a second shell portion located directly on top of the first shell portion, which
comprises superparamagnetic Fe₃O₄ nanoparticles which is bound to the functional groups on a surface of the first shell portion (step (i) repeated for multishell bead, para [0016]); and
(ii) forming the monodisperse superparamagnetic precursor beads by forming polymeric precursor anchor points on the first shell portion by reacting the naked monodisperse superparamagnetic beads with an anchoring material selected from a group comprising glycidyl methacrylate (para [0019]).
Regarding claim 41, Ichiro discloses the superparamagnetic beads according to Claim 1, wherein these beads are applied in IVD assays (diagnostic reagents, para [0026]).
Claims 30 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Ichiro in view of “Facile one-pot synthesis of multi-armed Fe3O4 nanocrystals” by Gu et al. (hereinafter Gu).
Regarding claim 30, Ichiro discloses the process according to Claim 29, wherein the naked monodisperse superparamagnetic beads are formed by a process that comprises:
(ai) providing monodisperse beads (para [0027]), which comprise:
a core portion formed from a polystyrene polymeric matrix material; and
a first shell portion located directly on top of the core portion and formed from a
crosslinked polymeric matrix material that is formed from a styrene monomer, a
crosslinking monomer and a first functional monomer that has functional groups, as discussed above; and
(aii) forming the naked monodisperse superparamagnetic beads by placing the monodisperse beads into a solution that comprises the superparamagnetic material in solution via a precipitation process (para [0027]).
The reference does not further disclose the precipitation process, particularly employment of a solution that comprises a Fe(III) salt and a Fe(II) salt and a step of adding a base.
However, Gu does teach a one-pot method of making Fe3O4 by combining a Fe(III) salt and a Fe(II) salt in a solution and adding a base (NaOH) to precipitate Fe3O4 nanoparticles (abstract and page 51, para 2).
It would be obvious to one of ordinary skill in the art to employ a conventional precipitation process to form the composite superparamagnetic beads in a simple and efficient manner (Ichiro, para [0003]).
Regarding claim 32, Ichiro in view of Gu, discloses the process according to Claim 30. Ichiro further discloses wherein the monodisperse beads are formed by a continuous one-pot (flask) three-stage process (para [0027]-[0028]) comprising:
(a) in a first stage, generating a polystyrene core by dispersion polymerization of a styrene monomer with an initiator and optional small amount of polymer stabilizer (para [0007]) in a mixture of alcohol (para [0023]) with water (emulsion) to form nucleated polystyrene cores (para [0027]);
(b) in a second stage, adding a crosslinking monomer (para [0018]) to mixture comprising nucleated polystyrene cores (crosslinking agent, para [0017]); and
(c) in a third stage adding a first functional monomer (para [0019]) to the material obtained from the second stage to provide the monodisperse beads (introducing functional groups, para [0017]).
Conclusion
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/L.E./Examiner, Art Unit 1734
/Matthew E. Hoban/Primary Examiner, Art Unit 1734