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 without traverse of Group I (claims 1-13 and 24) in the reply filed on April 1, 2026 is acknowledged.
Claims 14-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The claim set dated April 1, 2026 is the most recent claim set. Claim 24 has been newly added. Elected claims 1-13 and 24 are examined below.
Priority
The present application claims the benefit of a prior-filed parent provisional application 63/424,198, filed Nov. 10, 2022, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is Nov. 10, 2022.
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)(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, 2,4, and 5 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rubinsky et al. (U.S. Patent No. 11,130,277).
The claims are directed to methods of making a 3D-printed structure that including depositing a hydrogel and cell composition and a cryoprotectant from a 3D printer on to a freezing plate to form a frozen hydrogel filament, repeating this process, thereby forming a 3D-printed biomaterial and then removing the 3D-printed biomaterial from the freezing plate.
With respect to independent claim 1, Rubinsky et al. teach methods for creation of biomaterials for tissue engineering that include cryogenic 3D printing with controllable macro and micro structures with controlled morphology. (Abstract). More specifically, Rubinsky et al. teach depositing a hydrogel with cells from a 3D printer onto a platform 24 (“freezing plate”) to form a frozen hydrogel filament. (col. 4, ll. 1-8; col. 5, ll. 26-44; col. 12, ll. 9-13; col. 14, ll. 12-31; cols. 17-18, Ex. 4; col. 18, Ex. 5). While Rubinsky et al. does not explicitly teach that the cryoprotectant is part of the hydrogel, this limitation is inherently met, as Rubinsky et al. teach that “an important aspect of the technology is to immerse the entire region of the printed object, from the initial printing surface to the printing interface 18, in a liquid 20 with controlled temperature (below or equal to the phase transition temperature of the printed object material). The cryogenic liquid 20 preferably has a composition that is optimized for preserving the printed object (col. 8, ll. 3-12; Fig. 1, 18 & 20 touching). It is therefore asserted that for at least the area where the printing head interface 18 and the cryogenic liquid 20 meet, the printing fluid 14 will be a mixture of hydrogel, cells and cryoprotectant. Rubinsky et al. teach that successive layers of material are printed on top of one another until the desired shape and morphology is achieved. (col. 7, ll. 45-51; col. 11, ll. 41-51; col. 16, ll. 40-45). Rubinsky et al. implicitly teach that the 3D-printed material is removed from the freezing plate, as they teach that, for example, that immediately following the procedure, the scaffold was placed into a Styrofoam box containing liquid nitrogen. (col. 18, Ex. 4; also Ex. 3, “transferred to the drying process”).
With respect to claim 2, Rubinsky et al. teach the gel can be crosslinked. (col. 17-18, Ex. 4)
With respect to claim 4, Rubinsky et al. teach the hydrogel is extruded. (col. 6, ll. 55-63).
With respect to claim 5, Rubinsky et al. teach that the product is stored below 0 C. (Fig. 4).
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) 3, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Rubinsky et al. (U.S. Patent No. 11,130,277) as applied to claims 1, 2, 4 and 5 above, and further in view of Kim et al. (J Mat Chem, 2009).
Rubinsky et al. does not teach the biomaterial is crosslinked after being stored (claim 3); that the hydrogel is chilled to between 0 and 10 C before being deposited (claim 6); or that the freezing plate has a temperature between 5-30 C.
Kim et al. teach cryogenic 3D direct-plotting to fabricate collage scaffolds for tissue engineering. (Title). More specifically, Kim et al. teach the biomaterial is crosslinked after being stored; that the hydrogel is chilled to between 0 and 10 C before being deposited; and that the freezing plate has a temperature between 5-30 C. (pg. 8818, “Fabrication of collagen 3D scaffolds”)
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Rubinsky et al. to incorporate crosslinking after storage;, chilling the hydrogel to between 0 and 10 C before depositing it, and the freezing plate having a temperature of between 5-30 C (as taught by Kim et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating these modifications would have led to predictable results with a reasonable expectation of success because both references are directed to cryogenic 3D printing techniques that can aid in tissue engineering applications.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Rubinsky et al. (U.S. Patent No. 11,130,277) as applied to claims 1, 2, 4 and 5 above, and further in view of Liu et al. (Materials and Design, 2019).
Rubinsky et al. does not teach the hydrogel includes gelatin methacryoyl (GelMA).
Liu et al. teach 3D printing of muti-layered GelMA/nHA scaffolds for tissue engineering applications. (Title, Introduction).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Rubinsky et al. to incorporate using a hydrogel including gelatin methacryoyl (GelMA). (as taught by Liu et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because both references are directed to 3D printing techniques that can aid in tissue engineering applications and Liu et al. demonstrate that hydrogels including GelMA can be made using 3D extrusion printing and are appropriate for certain types of tissue engineering, such as repairing cartilage defects. (pg. 8, “Conclusions”).
Claim(s) 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Rubinsky et al. (U.S. Patent No. 11,130,277) as applied to claims 1, 2, 4 and 5 above, and further in view of Behera & Balaji.
Rubinsky et al. does not teach using melezitose as a cryoprotectant.
Behera & Balaji teach melezitose is a superior cryoprotectant, as it is a trisaccharide, and trisaccharides provide the highest survival rate for cells. (pg. 5, “5.3 ‘L’-lyoprotectant (and cryoprotectant)”).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Rubinsky et al. to incorporate using melezitose as the cryoprotectant (as taught by Behera & Balaji) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because Behera & Balaji specifically teach that melezitose is a superior cryoprotectant, enabling the greatest survival of cells when used
Claim(s) 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Rubinsky et al. (U.S. Patent No. 11,130,277) as applied to claims 1, 2, 4 and 5 above, and further in view of Ukpai (UC Berkeley, 2020).
Rubinsky et al. does not teach that the cells are myoblasts, fibroblasts, endothelial cells or stem cells; that the frozen hydrogel filaments are formed in the vertical direction; or that a plurality of 3D-printed material is prepared and combined.
Ukpai teaches that cells for 3D bioprinting at subfreezing temperatures can be done with stem cells; that hydrogel filament direction can be controlled and that 3D printing can be used to form complex structures, which need multiple printed material combined. (“Introduction”; “2.3.5 Prediction of cell survivability”; “4. Microstructure and mechanical properties of cryoprinted constructs”)
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Rubinsky et al. to incorporate stem cells; orienting the frozen hydrogel filaments in the vertical direction, and preparing and combining multiple 3D-printed material (as taught by Ukpai) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating these modifications would have led to predictable results with a reasonable expectation of success because both references are directed to cryogenic 3D printing techniques that can aid in tissue engineering applications.
Claim(s) 24 is rejected under 35 U.S.C. 103 as being unpatentable over Rubinsky et al. (U.S. Patent No. 11,130,277) as applied to claims 1, 2, 4 and 5 above, and further in view of Tan et al. (Sci Rep, 2017).
Rubinsky et al. does not teach the printed cells are neurons.
Tan et al. teach that cryogenic 3D printing can be extended to neurons. (pg. 7, “Discussion”)
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Rubinsky et al. to incorporate using neurons as the cell (as taught by Tan et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because both references are directed to cryogenic 3D printing techniques that can aid in tissue engineering applications.
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
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