DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-12 are pending.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claim(s) 1-8 and 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Varanasi et al (US20170143831A1) in view of Huang et al (US20230405187A1) and further in view of Gaharwar et al (US20200071550A1).
Regarding claim 1, Varanasi teaches a method for preparing a skull flap by photo-curing 3D (three dimensions) printing, comprising the following steps:
(1) constructing a 3D printing model: generating a corresponding 3D model based on a cranial scan data of a patient;
(Varanasi, "recording the surface profilometry in 3 dimensions to record the defect shape; programming the defect into the CAD program", [0149]; "computed tomography scanning", [0150]; "in-situ printing into calvarial bone defects of live rats", [0201]; Varanasi teaches a method for preparing a skull flap (calvarial scaffold) by generating a corresponding 3D printing model in a CAD program based on cranial scan data, such as computed tomography, of the patient's defect)
(2) preparing a 3D printing ink: weighing a photo-crosslinking hydrogel, mixing the photo-crosslinking hydrogel and a nanoclay solution to obtain a mixed system, and then adding a photoinitiator and a photoresist into the mixed system to obtain the 3D printing ink; and
(Varanasi, "combining an amount of the lyophilized MAG powder with a quantity of silicate-based nanoparticles (such as hydrous sodium lithium magnesium silicate (Laponite™) nanoparticles)", [0019]; "The slurry may also include a cross-linking agent, such as a photo-initiator component", [0024]; Huang, "mixing the HA-Glu/Col mixed solution prepared in step (1), the gelatin methacryloyl solution prepared in step (3) and the sodium carboxymethyl cellulose solution prepared in step (4), respectively, then adding a tartrazine with light-blocking property", [0013]; Varanasi teaches preparing a 3D printing bio-ink by mixing a photo-crosslinkable hydrogel (MAG/methacrylated gelatin), a nanoclay (Laponite) solution, and adding a photoinitiator. Varanasi lacks a photoresist. Huang teaches adding a light-blocking agent (tartrazine, acting as a photoresist) to a GelMA-based composite hydrogel ink)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to incorporate the teachings of Huang into the system or method of Varanasi in order to inhibit lateral photopolymerization and improve 3D printing precision. The combination of Varanasi and Huang also teaches other enhanced capabilities.
(3) conducting photo-curing 3D printing: subjecting the 3D printing ink to ultrasonic mixing, then filling into an ink tank of a photo-curing 3D printer, transferring the corresponding 3D model into the photo-curing 3D printer, and subjecting the corresponding 3D model to printing to obtain the skull flap;
(Varanasi, "The bio-ink filled dispenser tube was installed on the 3D printer", [0228]; "create a 3-D scaffold model of the tissue site... The 3-D scaffold model is then used to direct the extrusion and/or injection of the bio-Ink", [0191]; Gaharwar, "The solution was manually mixed then sonicated using a Fisher Scientific Model 120 Sonic Dismembrator for 2 minutes at 30% amplitude in order to ensure homogenous dispersion of components", [0063]; Varanasi teaches filling the 3D printing ink into an ink tank (dispenser tube), transferring the 3D model to direct the printer, and printing the skull scaffold. Varanasi lacks ultrasonic mixing. Gaharwar teaches subjecting a hydrogel-nanoclay bioink to ultrasonic mixing (sonication))
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to incorporate the teachings of Gaharwar into the system or method of Varanasi and Huang in order to ensure homogeneous dispersion of the bioink components before 3D printing. The combination of Varanasi, Huang and Gaharwar also teaches other enhanced capabilities.
wherein the nanoclay solution comprises an extracellular matrix component.
(Varanasi, "The bio-Ink may in some embodiments, also contain a variety of ingredients such as, but not limited to, demineralized allograft bone matrix (DMB)", [0034]; the bio-ink mixture, which includes the nanoclay, also comprises an extracellular matrix component such as demineralized bone matrix)
Regarding claim 2, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 1, wherein the cranial scan data of the patient in step (1) is obtained through computed tomography (CT) scanning or magnetic resonance imaging (MRI).
(Varanasi, "computed tomography scanning", [0150]; obtaining patient defect scan data utilizing computed tomography (CT) scanning to accurately resolve the dimensions for the 3D printed scaffold)
Regarding claim 3, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 1, wherein the 3D printing ink in step (2) is prepared by weighing 5 wt % to 20 wt % of the photo-crosslinking hydrogel, mixing the 5 wt % to 20 wt % of the photo-crosslinking hydrogel and 1 wt % to 4 wt % of the nanoclay solution to obtain the mixed system, and then adding 0.5 wt % to 5 wt % of the photoinitiator and 0.001 wt % to 3 wt % of the photoresist into the mixed system.
(Varanasi, "about 1% to about 20% wt. MAG", "between 2% and about 4% wt. LP", [0031]; "0.5% w/w(MAG) I2959", [0219]; Huang, "a concentration of the tartrazine with light-blocking property in the composite solution is 0.05% (w/v)", [0026]; Varanasi teaches preparing a bio-ink mixed system comprising 1-20 wt% photo-crosslinking hydrogel (MAG), 2-4 wt% nanoclay (LP), and 0.5 wt% photoinitiator (I2959). Varanasi does not explicitly disclose the addition of a photoresist. Huang teaches adding 0.05 wt% of tartrazine, which functions as a light-blocking property (photoresist). Incorporating Huang into Varanasi would precisely control the photo-curing penetration depth and improve the 3D printing resolution of the resulting hydrogel ink)
Regarding claims 4 and 11, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to any one of claim 1, wherein the photo-crosslinking hydrogel is at least one selected from the group consisting of methacrylated gelatin (GelMA), methacryloyl sodium alginate (AlgMA), and methacrylated hyaluronic acid (HAMA).
(Varanasi, "methacrylated gelatin (MAG)", [0028]; Huang, "gelatin methacryloyl (GelMA)", [0053]; Varanasi and Huang teach that the photo-crosslinking hydrogel comprises methacrylated gelatin)
Regarding claims 5 and 12, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to any one of claim 1, wherein a nanoclay in the nanoclay solution is at least one selected from the group consisting of hydroxyapatite, tricalcium phosphate, and lithium magnesium silicate.
(Varanasi, "hydrous sodium lithium magnesium silicate (Laponite™) nanoparticles", [0019]; using Laponite, which is a lithium magnesium silicate, as the nanoclay solution component)
Regarding claim 6, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 1, wherein the extracellular matrix component comprises at least one selected from the group consisting of a calcium phospholipid component, collagen protein, and glycosaminoglycan.
(Huang, "collagen is one of the main components of the extracellular matrix", [0037]; the incorporation of collagen protein as the extracellular matrix component promotes cell adhesion and biocompatibility)
Regarding claim 7, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 1, wherein the nanoclay solution further comprises a chemokine.
(Varanasi, "Bone Morphogenetic Protein", [0052]; incorporating biological factors, such as bone morphogenetic protein, which act as chemokines stimulates cell migration and tissue regeneration into the bio-ink/nanoclay system)
Regarding claim 8, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 7, wherein the chemokine is at least one selected from the group consisting of a ciliary neurotrophic factor (CNTF) neural factor, a vascular endothelial growth factor (VEGF) vascular factor, and a bone morphogenetic protein 2 (BMP-2) bone repair factor.
(Varanasi, "Vascular Endothelial Growth Factor", [0112]; "Bone Morphogenetic Protein", [0052]; the composition includes VEGF and BMP, satisfying the selection of vascular factors and bone repair factors as the claimed chemokines)
9. The method according to claim 1, wherein the ultrasonic mixing in step (3) is conducted at a power of 1,000 W to 1,300 W for 0.5 seconds to 1.5 seconds.
Regarding claim 10, the combination of Varanasi, Huang and Gaharwar teaches its base claim(s).
The combination further teaches the method according to claim 1, wherein the corresponding 3D model in step (3) is cut into multiple two-dimensional layers through model slicing, and then the multiple two-dimensional layers are transferred into the photo-curing 3D printer and subjected to the printing.
(Gaharwar, "Printed shapes were designed in Solidworks and exported as STL files. STL files were loaded into Slic3r to customize printing options and converted into G-code printer instructions.", [0084]; converting a 3D model into multiple 2D layers via model slicing software (Slic3r) and transferring these sliced instructions directly into a 3D printer to perform layer-by-layer printing)
Allowable Subject Matter
Claim(s) 9 is/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 Claim(s).
The following is a statement of reasons for the indication of allowable subject matter:
Claim(s) 9 recite(s) limitation(s) related to specifying the specific power and time duration parameters for the ultrasonic mixing step. There are no explicit teachings to the above limitation(s) found in the prior art cited in this office action and from the prior art search.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANXUN YANG whose telephone number is (571)272-9874. The examiner can normally be reached on MON-FRI: 8AM-5PM Pacific Time.
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/JIANXUN YANG/
Primary Examiner, Art Unit 2662 7/9/2026
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