Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined pursuant to the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
Applicants filed claims 1 – 70 with the instant application on 22 September 2023. In a Preliminary Amendment filed on 18 January 2024, Applicants amended claims 5, 7, 8, 10, 18, 25, 28, 31, 34, 38, 41, 49, 51, 54, 57, and 61, and canceled claims 2, 4, 9, 11 – 17, 19 – 24, 27, 29, 30, 32, 33, 35 – 37, 39, 40, 42 – 48, 50, 52, 53, 55, 56, 58 – 60, and 62 – 70. Consequently, claims 1, 3, 5 – 8, 10, 18, 25, 26, 28, 31, 34, 38, 41, 49, 51, 54, 57, and 61 remain available for substantive examination.
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statements (IDS’s) filed 22 September 2023, 18 January 2024, and 1 April 2024, which are now of record in the file.
Objections to the Specification
Use of the term “Solplus D560,” which is a trade name, or a mark, used in commerce, has been noted in this application (see ¶¶[0008], [0011], and [0026]). The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears and/or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 10 and 18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Rejections Pursuant to 35 U.S.C. § 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.
Claims 7, 26, 31, and 38 are rejected pursuant to 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the Applicant regards as the invention.
Claims 7 and 26 recite limitations directed to a dispersant identified as “Solplus D560.” The identification is a trademark currently owned by Lubrizol Advanced Materials, Inc. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. § 112(b). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain because the trademark or trade name is used to identify the source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name with the specificity necessary to satisfy 35 U.S.C. § 112. See MPEP § 2173.05(u). In the present case, the trademark/trade name is used to identify/describe a component characterized as a “dispersant," but does not disclose the chemical makeup or composition of the component. Accordingly, the identification/description is indefinite.
Claim 31 recites a dependency to claim 30. However, Applicants canceled claim 30 in the Amendment filed 18 January 2024. Appropriate correction or cancelation is necessary. In the interests of compact prosecution, the Examiner will treat the claim as dependent from claim 28.
Claim 38 recites a dependency to claim 37. However, Applicants canceled claim 37 in the Amendment filed 18 January 2024. Appropriate correction or cancelation is necessary. In the interests of compact prosecution, the Examiner will treat the claim as dependent from claim 34.
Rejections Pursuant to 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 that 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 absent any evidence to the contrary. Applicants are advised of the obligation pursuant to 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.
Claims 1, 3, 5, 6, 8, 25, 49, 51, 54, 57, and 61 are rejected pursuant to 35 U.S.C. § 103, as being obvious over KR 2013/0037324 A, published 16 April 2013, identified on the Information Disclosure Statement (IDS) filed 22 September 2023, cite no. 1 (FOR) (“KR ‘324”), in view of US 2021/0017319 A1 to Hong, Y., et al., published 21 January 2021 from an application claiming priority to 4 April 2018, identified on the IDS filed 22 September 2023, cite no. 3 (USPATAPP) (“Hong ‘319”), Li, C.-C., et al., Journal of Colloid and Interface Science 506: 180 – 187 (2017) (“Li (2017)”), and US 2022/0168474 A1 to Prawel, D., et al., claiming priority to 2 December 2021 (“Prawel ‘474”).
The Invention As Claimed
Applicants claim a method for fabricating a bone-regeneration scaffold comprising the steps of providing a printing material comprising a biologically-derived bone powder, and fabricating, via a 3D printer, the bone-regeneration scaffold using the printing material, wherein the printing material is a slurry, further comprising a photoinitiator, a dispersant, and a monomer, wherein the photoinitiator comprises diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide, wherein the monomer comprises ethylene glycol dimethacrylate, wherein the method further comprises the step of preparing the slurry by mixing a photoinitiator, a dispersant, and a monomer to form a first mixture, and mixing the first mixture and the biologically-derived bone powder to form the slurry, wherein the bone regeneration scaffold comprises a plurality of perfusion channels, and wherein the bone-regeneration scaffold further comprises an input port and an output port each in fluid communication with the perfusion channels, wherein the method comprises the further step of treating the perfusion channels with living autogenic cells capable of accelerating tissue growth, inhibiting infection, enhancing vascular tissue development, or reducing thrombogenic potential, one or more bioactive agents capable of accelerating tissue growth, inhibiting infection, enhancing vascular tissue development, or reducing thrombogenic potential, wherein the method comprises the further step of treating the bone-regeneration scaffold with one or more osteogenic agents capable of enhancing bone development, wherein the one or more osteogenic agents comprises recombinant bone morphogenic protein (rBMP)and/or vascular endothelial growth factor (VEGF), wherein the method further comprises the step of treating the bone-regeneration scaffold with patient cellular material comprising stem cells and/or platelet rich plasma, and wherein the method further comprises the steps of obtaining computed tomography scans of a patient, wherein the bone-regeneration scaffold is fabricated based at least in part on the computed tomography scans, obtaining clinician annotations to the computed tomography scans, wherein the bone regeneration scaffold is fabricated based at least in part on the computed tomography scans and the clinician annotations, wherein a shape of the bone-regeneration scaffold is based at least in part on a shape of a bone segment to be removed from the patient.
The Teachings of the Cited Art
KR ‘324 discloses a composition and method for 3D printing of a scaffold for tissue regeneration (see p. 2, 1st para.), wherein the composition comprises a bone powder coated with a coating agent as an active ingredient (see p. 2, 2nd para.), wherein the scaffold is a temporary matrix that provides structure and a specific environment for bone growth and tissue development (see p. 2, 5th para.), wherein RP (Rapid Prototype) technologies, such as powder based three-dimensional printing, have been attracting attention in order to manufacture such scaffolds, wherein RP technology produces an actual three-dimensional model in a short time by systematically stacking materials one by one through two-dimensional sectioning of three-dimensional image data (see p. 2, 6th para.), wherein, in the field of bone tissue engineering for regeneration, customized scaffolds for lesions have been manufactured based on CT imaging data of patients using powder samples, such as calcium based polymers, including hydroxyapatite and tri-calcium phosphate (TCP), or complexes of phosphate and trisulfate (see p. 2, 7th para.), wherein the bone powder may be selected from the group consisting of bone powder derived from human corpse, bone powder derived from animals other than human, synthetic bone powder, preferably derived from animals other than the human (see p. 3, 5th para.), wherein the bone regeneration scaffold is prepared by applying a binder/coating agent, capable of cross-linking, to the bone powder (see p. 3, 6th para.), wherein the binding/coating agent comprises bone marrow-derived stem cells, osteoblasts, bone formation promoters, anticancer agents, immunological diseases treatment agents, and antibiotics (see p. 3, 7th para.), and wherein scaffolds prepared by 3D printing technology have porosity and are suitable for cell attachment and growth and, thus, can provide an effective scaffold for bone regeneration in tissue engineering and regenerative medicine (see p. 3, 19th para.). The reference does not disclose a method for fabricating a bone-regeneration scaffold using a printing material/ink that is a slurry, or that comprises diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide as a photoinitiator, a dispersant, and ethylene glycol dimethacrylate as a monomer. The teachings of Hong ‘319, Li (2017), and Prawel ‘474 remedy those deficiencies.
Hong ‘319 discloses hydrogel compositions comprising a triblock copolymer having a formula A-B-A, wherein A is a polycaprolactone (PCL) block, or a polyvalerolactone (PVL) block, and B is a polyethylene glycol (PEG) block prepared by providing a photoinitiator with the triblock copolymer and photocrosslinking the polymer to form the hydrogel composition, which composition is used for printing a three-dimensional (3D) article by extruding the composition from a deposition nozzle moving relative to a substrate, depositing one or more layers comprising the composition on a substrate to form the printed 3D article (see Abstract), wherein the photocrosslinking occurs by exposure to a wavelength of light from about 380 to about 700 nm (see ¶[0009]), wherein the photoinitiator can be any photoinitiator capable of catalyzing a reaction which cross-links/gelates the triblock copolymer, such as a visible light-activated photoinitiator (see ¶[0076]), wherein the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (DAROCUR TPO) (see ¶[0078]), wherein the hydrogel printing materials can incorporate biomimetic peptides, proteins, growth factors, or other bioactive molecules (see ¶[0042]), wherein the compositions can further comprise additives useful for 3D printing, such as diluent synthetic polymers (e.g., PEG, polypropylene glycol, poly(vinyl alcohol), poly(methacrylic acid)), therapeutics (e.g., antibiotics such as penicillin and streptomycin), cell nutrients (e.g., proteins, peptides, amino acids, vitamins, carbohydrates (e.g., starches, celluloses, glycogen), and minerals (e.g., calcium, magnesium, iron), synthetic or naturally occurring peptides, nucleic acids, surfactants, plasticizers, salts (e.g., sodium chloride, potassium chloride, phosphate salts, acetate salts), viable/living cells, and cell components (e.g., elastin, fibrin, proteoglycans ) (see ¶[0080]), wherein the printing composition further comprises one or more viable cells, and the printed 3D article is a scaffold for depositing and/or growing cellular tissue (see ¶[0089]), and wherein the cells comprise stem cells, embryonic stem cells, amniotic fluid stem cells, cartilage cells, bone cells, muscle cells, skin cells, pancreatic cells, kidney cells, nerve cells, liver cells, and the like (see ¶[0092]).
Li (2017) discloses a newly designed dispersant for water-based suspensions, ammonium poly(methacrylate)-block-poly(2-phenoxyethyl acrylate) (PMA-b-PBEA), wherein the dispersion efficiency of this dispersant is superior to that of the commercially available ammonium polyacrylate (PAA-NH4), wherein the di-block structure of PMA-b-PBEA, which simultaneously contains a low-polar anchoring head group and a water-dissociable stabilizing moiety, is the main cause for its extremely high efficiency for powder dispersion (see Abstract), wherein, to obtain ceramic products with high mechanical strength and the required physicochemistry, ceramic powders in green bodies should be densely packed and able to be ultimately densified after sintering, such that the powder has to be de-agglomerated and well dispersed during initial slurry preparation, which process consists of mixing the ceramic powder in a solvent with a variety of organic and inorganic additives (see p. 180), wherein, when water is used as the slurry fluid, the aqueous process has the tendency to cause ceramic powders to form severe agglomerates, while powder agglomeration is less severe in non-aqueous based slurries (see p. 181, 1st col., 1st para.), wherein the newly-designed PMA-b-PBEA dispersant comprises two structures: polyelectrolytic PMA and non-polyelectrolytic PBEA, which is a low-polar undissociable segment, designed to act as an anchoring head for adsorption onto powder surfaces, while the polyelectrolytic PMA is dissociable in water and can extend itself into the dispersion medium to act as a stabilizing moiety (see p. 181, 1st col., 2nd para.), wherein, in general, a powder will be better stabilized if the added dispersant exhibits a larger amount of adsorption; this is because higher adsorption of a dispersant can result in the powder having greater electrostatic or steric repulsion for stabilization (see p. 183, 1st col., 2nd para.), and wherein the PMA-b-PBEA exhibited higher electrostatic energy and better dispersion efficiency than PAA-NH4 for the dispersion of TiO2 as a model powder (see p. 186, 2nd col., 1st para.).
Prawel ‘474 discloses methods for treating bone defects (see Abstract), wherein 3D printing (3DP) has emerged as a popular method to fabricate complex shaped structures with high precision, enabling creation of patient-specific, biodegradable osteogenic scaffolds directly from CT scans, ensuring that the scaffolds precisely fit the defect site, improving outcomes because the morphology of each bone and the percentage of bone removed varies between patients, depending on the size of the tumor (see ¶[0006]), wherein the method also includes obtaining computed tomography scans of the patient, and fabricating a biodegradable osteogenic scaffold based at least in part on the computed tomography scans (see ¶[0010]), wherein the scaffold may be treated with rhBMP-2 to enhance bone healing (see ¶[0029]), wherein the biodegradable osteogenic scaffolds are 3D printed with a printing material/ink slurry comprising hydroxyapatite particles mixed with a photopolymer comprising ethylene glycol dimethacrylate (EDGMA) using a planetary ball mill, wherein photopolymerization is initiated by continuous exposure of the deposited rods to a near-UV light source (405nm wavelength), resulting in polymerization and hardening of the continuous phase, layer-by-layer, wherein the printed biodegradable osteogenic scaffolds undergo a two-step sintering process to eliminate the polymeric content and consolidate the hydroxyapatite particle, the sintering process comprising heating the scaffold at 5° C/min up to 500° C, holding for one hour, and then heating further at a heating rate of 15° C/min up to 1150° C, and then held for 5 hours before cooling to room temperature (see ¶[0039]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a composition for 3D printing of a scaffold for tissue regeneration, wherein the composition comprises a bone powder coated with a coating agent as an active ingredient, wherein RP (Rapid Prototype) technologies, such as powder based three-dimensional printing, produces an actual three-dimensional model in a short time by systematically stacking materials one by one through two-dimensional sectioning of three-dimensional image data, wherein, in the field of bone tissue engineering for regeneration, customized scaffolds for lesions have been manufactured based on CT imaging data of patients using powder samples, wherein the bone powder may be bone powder derived from human corpse, bone powder derived from animals other than human, synthetic bone powder, wherein the coating agent comprises bone marrow-derived stem cells, osteoblasts, bone formation promoters, anticancer agents, immunological diseases treatment agents, and antibiotics, and wherein scaffolds prepared by 3D printing technology have sufficient porosity to be suitable for cell attachment and growth, as taught by KR ‘324, wherein the compositions comprise a triblock copolymer having a formula A-B-A prepared by providing a photoinitiator with the copolymer and photocrosslinking the polymer to form a hydrogel composition, which composition is used for printing a three-dimensional (3D) article, wherein the photocrosslinking occurs by exposure to a wavelength of light from about 380 to about 700 nm, wherein the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (DAROCUR TPO), wherein the compositions can further comprise viable/living cells, and cell components (e.g., elastin, fibrin, proteoglycans), and wherein the cells comprise stem cells, embryonic stem cells, amniotic fluid stem cells, cartilage cells, bone cells, muscle cells, skin cells, pancreatic cells, kidney cells, nerve cells, liver cells, and the like, as taught by Hong ‘319, wherein the compositions comprise a dispersant, such as ammonium poly(methacrylate)-block-poly(2-phenoxyethyl acrylate) (PMA-b-PBEA), wherein the dispersion efficiency of this dispersant is superior to that of the commercially available ammonium polyacrylate (PAA-NH4), wherein PMA-b-PBEA comprises two structures: polyelectrolytic PMA and non-polyelectrolytic PBEA (a low-polar undissociable segment), designed to act as an anchoring head for adsorption onto powder surfaces, while the polyelectrolytic PMA is dissociable in water and can extend itself into the dispersion medium to act as a stabilizing moiety, and wherein the PMA-b-PBEA exhibited higher electrostatic energy and better dispersion efficiency than PAA-NH4 for the dispersion of TiO2 as a model powder (see p. 186, 2nd col., 1st para.), as taught by Li (2017), and wherein 3D printing can be used to fabricate complex shaped structures with high precision, enabling creation of patient-specific, biodegradable osteogenic scaffolds directly from CT scans, ensuring that the scaffolds precisely fit the defect site, improving outcomes because the morphology of each bone and the percentage of bone removed varies between patients, depending on the size of the tumor (see ¶[0006]), wherein the method includes obtaining computed tomography scans of the patient, and fabricating a biodegradable osteogenic scaffold based at least in part on the computed tomography scans, wherein the biodegradable osteogenic scaffolds are 3D printed with a printing material/ink slurry comprising osteogenic ceramic particles mixed with a photopolymer comprising ethylene glycol dimethacrylate (EDGMA) using a planetary ball mill, wherein photopolymerization is initiated by continuous exposure of deposited rods/fibers to a near-UV light source (405 nm wavelength), and wherein the scaffolds are treated with rhBMP-2 to enhance bone healing, as taught by Prawell ‘474. One of ordinary skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the teachings of Hong ‘319 to the effect that diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide is an effective photoinitiator for the cross-linking/gelation of the polymer component of the composition, by the teachings of Li (2017) to the effect that PMA-b-PBEA exhibited higher electrostatic energy and better dispersion efficiency than PAA-NH4 for the dispersion of TiO2 as a model powder (see p. 186, 2nd col., 1st para.), and by the teachings of Prawell ‘474 to the effect that 3D printing scaffolds directly from CT scans ensures that the scaffolds precisely fit the defect site, improving outcomes because the morphology of each bone and the percentage of bone removed varies between patients, depending on the size of the tumor (see ¶[0006]).
With respect to claim 25, which claim recites limitations directed to preparation of the slurry comprising bone powder, a photoinitiator, a dispersant, and a monomer, the Examiner notes that the cited references do not explicitly disclose first preparing a mixture of photoinitiator, dispersant, and monomer, and then adding the bone powder to the mixture to create a slurry. However, it is the Examiner’s position that Applicants’ specification is silent on any particularly results obtained from the specifically claimed sequence of steps and that, as a consequence, it would have been prima facie obvious to mix together the particular components of the printing material slurry in any order, including those taught by the cited art. See, for example, Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.); see also, In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
With respect to claim 49, which claim recites limitations relating to “perfusion channels” in the 3D-printed scaffold, the Examiner notes that the cited references are silent on the presence of such channels in the printed scaffolds. However, the Examiner further notes that the references are replete with teachings directed to the extensive capabilities of 3D printing to achieve custom design of bone repair scaffolds. In light of these specific teachings, it is the Examiner’s position that it would have been prima facie obvious for one of ordinary skill in the art to prepare bone repair scaffolds by 3D printing processes with almost any desired degree of complexity, subject only to the inherent resolution of the chosen printing method, including scaffolds with perfusion channels connected to input and output ports.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 1, 3, 5, 6, 8, 25, 49, 51, 54, 57, and 61 would have been obvious within the meaning of 35 USC § 103.
Claims 28, 31, 34, 38 and 41 are rejected pursuant to 35 U.S.C. § 103, as being obvious over KR ‘324 A, Hong ‘319, Li (2017), and Prawel ‘474, as applied in the above rejection of claims 1, 3, 5, 6, 8, 25, 49, 51, 57, and 61, and further in view of US 2011/0089382 A1 to Zhang, K., et al., published 21 April 2011 (“Zhang ‘382”).
The Invention As Claimed
The invention with respect to claim 1 is described above. In addition, Applicants claim a method for fabricating a bone-regeneration scaffold using 3D printing with a material comprising a biologically-derived bone powder, wherein the photoinitiator, the dispersant, and the monomer are mixed within a milling jar containing a plurality of milling balls and the milling jar is an yttrium-stabilized zirconium planetary ball milling jar, and the milling balls are yttrium-stabilized zirconium milling balls, and the milling balls comprises a plurality of first milling balls each having a first diameter, and a plurality of second milling balls each having a second diameter that is greater than the first diameter, wherein the first diameter is 5 mm, wherein the second diameter is 10 mm, wherein a ratio of the first milling balls to the second milling balls is 3:2 by wgt %, wherein a ratio of the milling balls to the biologically-derived bone powder is 2:1 by weight, wherein the step of mixing the first mixture and the biologically-derived bone powder to form the slurry comprises mixing the first mixture and the biologically-derived bone powder using a planetary ball mill, wherein the first mixture and the biologically-derived bone powder are mixed within a milling jar containing a plurality of milling balls, wherein the milling jar is a yttrium-stabilized zirconium planetary ball milling jar, and wherein the milling balls are yttrium-stabilized zirconium milling balls, and wherein the plurality of milling balls comprises a plurality of first milling balls each having a first diameter, and a plurality of second milling balls each having a second diameter that is greater than the first diameter, wherein the first diameter is 5 mm, wherein the second diameter is 10 mm, wherein a ratio of the first milling balls to the second milling balls is 3:2 by wgt %, and wherein a ratio of the milling balls to the biologically-derived bone powder is 2:1 by wgt %, wherein mixing the first mixture and the biologically-derived bone powder to form the slurry comprises the steps of mixing the first mixture and a first amount of the biologically-derived bone powder using a planetary ball mill to form a second mixture, mixing the second mixture and a second amount of the biologically-derived bone powder using the planetary ball mill to form a third mixture, mixing the third mixture and a third amount of the biologically-derived bone powder using the planetary ball mill to form the slurry, wherein the first amount is greater than the second amount, and wherein the second amount is greater than the third amount.
The Teachings of the Cited References
The disclosures of KR ‘324 A, Hong ‘319, Li (2017), and Prawel ‘474, are relied upon as set forth in the above rejection of claims 1, 3, 5, 6, 8, 25, 49, 51, 57, and 61. The references do not disclose the use of planetary ball mixing in the preparation of printing material. These related deficiencies are remedied by the teachings of Zhang ‘382.
Zhang ‘382 discloses methods and systems for precisely controlling the surfactant concentration and character of nanoparticles (size and distribution) in a liquid dispersion (see Abstract), wherein the properties of the nanoparticles are extremely sensitive to their preparation techniques and conditions, particularly the techniques used in grinding the materials to nanoparticle sizes (see ¶[0004]), wherein a planetary ball mill as illustrated in FIG. 14 is used as the grinding system to achieve a nanometer-sized particle distribution (see ¶[0020]), wherein, with starting materials with sizes of about 3 µm, particles of different sizes are produced by a high-energy milling process, such as one using a planetary ball mill, such as a two-station PM200 planetary ball mill that provides a planet-like movement of a plurality of jars arranged on a rotating support disk with special drive mechanism that causes them to rotate around their own axes as shown in FIG. 14, with both the disk and the jar rotation speeds being independently controlled to obtain desired results (see ¶[0036]), wherein, in the use of a milling system, variables such as type of mill (i.e., planetary ball mill, shaker mill, two roll mill, jet milling, etc.); milling container; milling speed; milling time; type; size and size distribution of the grinding medium; ball-to-powder weight ratio; extent of filling the jar; process control agent; temperature of milling, and other parameters, may be controlled to achieve the desired size or narrow size range of nanoparticles, with the times needed to reach a certain size varying depending on the intensity of milling, the ball-to-powder ratio, and the temperature of milling, wherein a large size (and high density) of the grinding medium is useful since the larger weight of the balls will transfer more impact energy to the powder particles, such as, for example, balls of 1 mm in diameter, and formed of the same material as the jars, with a ratio of the weight of the balls to the powder being from a value as low as 1:1 to as high as 300:1 (see ¶[0037]), and wherein jars formed of partially stabilized zirconia+yttria may be used, as such material has a sufficiently high hardness to reduce contamination of the resulting mixture from particle fragments of the milling medium and jars (see ¶[0039]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a composition for 3D printing of a scaffold for tissue regeneration, wherein the composition comprises a bone powder, according to the teachings of KR ‘324 A, Hong ‘319, Li (2017), and Prawel ‘474, wherein the components of the printing material are mixed/size reduced with a ball mill as the grinding system, such as a two-station PM200 planetary ball mill that provides a planet-like movement of a plurality of jars arranged on a rotating support disk with special drive mechanism that causes them to rotate around their own axes, with both the disk and the jar rotation speeds being independently controlled to obtain desired results, wherein variables such as type of mill (i.e., planetary ball mill, shaker mill, two roll mill, jet milling, etc.); milling container; milling speed; milling time; type; size and size distribution of the grinding medium; ball-to-powder weight ratio; extent of filling the jar; process control agent; temperature of milling, and other parameters, are controlled to achieve the desired size, or narrow size range, of nanoparticles, with the times needed to reach a certain size result varying depending on the intensity of milling, the ball-to-powder ratio, and the temperature of milling, wherein a large size (and high density) of the grinding medium is useful since the larger weight of the balls will transfer more impact energy to the powder particles, and formed of the same material as the jars, with a ratio of the weight of the balls to the powder being from a value as low as 1:1 to as high as 300:1, and wherein the jars and milling balls are formed of partially stabilized zirconia+yttria, as such material has a sufficiently high hardness to reduce contamination of the resulting mixture from particle fragments of the milling medium and jars, as taught by Zhang ‘382. One of ordinary skill in the art would be motivated to do so, with a reasonable expectation of success in so doing by the express teachings of Zhang ‘382 to the effect that planetary ball milling systems using zirconia+yttria jars and milling media provide many advantages in terms of reduced contamination from the jars and balls, as well as a great deal of flexibility in obtained desired/optimal mixing and/or comminution results (see ¶¶[0037] – [0039]).
With respect to claims 28, 31, 34, and 38 directed to processes for mixing of the components of the printing material slurry, the Examiner notes that the claim recites limitations directed to the milling balls used in the mixing process. As recited, the claims enumerate the use of two populations of milling balls with different diameters (claims 28, 34), such as 5 mm and 10 mm (claims 31, 38). In this regard, the Examiner notes that Zhang ‘382 explicitly discloses only the use of a single population of milling balls with diameters of 1 cm. However, the Examiner notes that the reference is clear that the specifics of the disclosed processes, including those relating to the number, size, and composition of the milling balls, are among the numerous factors that need to be optimized for specific combinations of process types and mixture components. Consequently, in light of these teachings, it is the Examiner’s position that selection of the number, size, and proportion of milling balls used in the disclosed processes amount to nothing more than an optimization of a result-effective variable, the exercise of which is well with the expertise of one of ordinary skill in the appropriate art. Consequently, in the absence of evidence as to the criticality of such parameter, this limitation cannot support patentability. See MPEP § 2144.05 II. A.
With respect to claim 41, which claim recites limitations directed to preparation of the slurry comprising bone powder, a photoinitiator, a dispersant, and a monomer according to a sequence process steps, the Examiner notes that the cited references do not explicitly disclose first preparing a plurality of volumes of the mixture of the photoinitiator, dispersant, and monomer, and then adding separate amounts of the bone powder to each volume of the mixture to create the slurry. However, it is the Examiner’s position that Applicants’ specification is silent on any particularly results obtained from the specifically claimed sequence of steps and that, as a consequence, it would have been prima facie obvious to mix together the particular components of the printing material slurry in multiple aliquots, in any order, including those taught by the cited art. See Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959); see also, In re Burhans.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 28, 31, 34, 38, and 41 would have been obvious within the meaning of 35 USC § 103.
NO CLAIM IS ALLOWED.
CONCLUSION
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/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619