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 .
Detailed Action
Pursuant to a preliminary amendment filed on May 23, 2024, claims 1 - 16 are currently pending in the instant application. Claims 1, 8 and 15 are independent claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 23, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed May 23, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/KR2022/018714, filed November 24, 2022, which claims the benefit of KR10-2021-0163531, filed November 24, 2021.
Receipt is acknowledged of untranslated certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Therefore, the earliest priority date is November 24, 2021.
Claim Rejection - 35 USC § 112(b)
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.
Claims 1- 7, 12, and 13 are 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.
Claim 1 is indefinite for the recitation of “the living body” in line 4. There is a lack of antecedent basis for the term “the living body.” It is also unclear what is the source of the “living body,” as this term has not been defined in the as-Filed Specification. Thus, the metes and bounds of the claim cannot be determined.
Claim 2 is indefinite for the recitation of “poly(poly(ethylene oxide)….” In line 6. There is a missing parenthesis in the claim, and it is unclear what is the biocompatible polymer. Further, it is unclear what is “poly(poly(“ as this term has not been used in the as-Filed Specification. Thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of “the tumor tissue has a length, width, and height of less than 1 mm” in lines 1 – 2. It is unclear whether the length, width, and height are all less than 1 mm together, or individually each component is less than 1 mm. Thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite for the recitation of “the microchannel” in line 1. There is a lack of antecedent basis for the term “the microchannel” because claim 1 teaches “ a plurality of microchannels.”
Claim 12 is indefinite for the recitation of “in methanol at a concentration of 34% to 36% and then spinning the solution” in lines 2 – 3. It is unclear what the concentration is referring to, whether it is referring to the concentration of methanol or the poly(N-isopropyl acrylamide). Further, it is unclear what “the solution” is referring to. It is unclear if it referring to the hydrogel solution taught in claim 8, or the solution made by dissolving the poly(N-isopropyl acrylamide) in methanol. Thus, the metes and bounds of the claim cannot be determined.
Claim 13 is indefinite for the recitation of “converting the three-dimensional fiber into a sol” in lines 1 – 2. It is unclear what a “sol” is, as this term has not been defined in the as-Filed Specification. Thus, the metes and bounds of the claim cannot be determined.
Claims 4 and 5 are indefinite insofar as they ultimately depend on claim 1.
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 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.
Claims 1 – 5, 14, and - 16 are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Berry et al. (hereinafter referred to as “Berry”) (US 9034571 B2, published May 19, 2015),
Regarding claim 1, Berry teaches that 3D vascularized constructs to make tissue models (Paragraph [85]). Berry teaches a 3D tissue construct of the cancer model includes a biocompatible scaffold material; comprising a 3D network of living cells within the scaffold material, where the network of cells includes cancer cells or a combination of cancer cells and non-cancerous cells; a plurality of channels extending through the construct, such that a substantial portion of the channels have an inlet at one surface of the construct and an outlet at an opposing surface of the construct (Paragraph [08]) (interpreted as a structure for tissue culture made of a biocompatible polymer and a 3D network formed by connecting a plurality of microchannels therein, and the tumor tissue is encapsulated in the structure for tissue culture, instant claim 1). Berry teaches that the 3D network of cells forms a (breast cancer) tumor (claim 16) (interpreted as tumor tissue isolated from the living body, instant claim 1).
Regarding claim 2, Berry teaches that the 3D biocompatible scaffold comprises a gel matrix comprised of alginate (Paragraph [7]).
Regarding claim 3 and 4, Berry teaches the 3D vascularized constructs to make tissue models, wherein the cancers can include glioblastomas (Paragraph [41]).
Regarding claim 5, Berry teaches that a substantial portion of the channels have an inlet at one surface of the construct and an outlet at an opposing surface of the construct, where the channels form a lumen for allowing passage of fluid media through the construct (Paragraph [8]).
Regarding claims 14, Berry teaches that the methods further include perfusing the scaffold with cell culture media, and incubating the seeded scaffold, such that a 3D network of cells of the at least one tissue type grows within the scaffold (Paragraph [10]) (interpreted as supplying a cell culture medium to the tumor tissue model, and culturing the tumor tissue model).
Regarding claim 16, Berry teaches the 3D vascularized constructs to make tissue models, wherein the cancers can include glioblastomas (Paragraph [41]).
Berry does not specifically exemplify the length, width, and height of the tissue (claim 6), the diameter of the microchannel (claim 7), and rate at which the cell culture medium is supplied (claim 15).
Claim Rejection - 35 USC § 103
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.
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.
Claims 1, 6, 7, 8 – 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Berry et al. (hereinafter referred to as “Berry”) (US 9034571 B2, published May 19, 2015; IDS filed May 23, 2024), and further in view of Lee et al. (hereinafter referred to as “Lee”) (Lee JB. Et al. Adv Healthy Mater. 2016 Apr 6;5(7):781-5.), as evidenced by Allen et al. (Allen ACB. Et al. Biomater Sci. 2017 Jul 25;5(8):1661-1669. doi: 10.1039/c7bm00324b. PMID: 28675203; PMCID: PMC5870125.), Machielak et al. (Macielak RJ. Et al. J Neurosurg. 2021 Oct 15;136(5):1289-1297. doi: 10.3171/2021.4.JNS21465. PMID: 34653971.), Sigma Aldric Product Specification (2015), and Korin et al. (Korin N. et al. Lab Chip. 2007 May;7(5):611-7. doi: 10.1039/b702392h. Epub 2007 Mar 21. PMID: 17476380).
With regard to instant claim 1, Berry teaches that 3D vascularized constructs to make tissue models (Paragraph [85]). Berry teaches a 3D tissue construct of the cancer model includes a biocompatible scaffold material; comprising a 3D network of living cells within the scaffold material, where the network of cells includes cancer cells or a combination of cancer cells and non-cancerous cells; a plurality of channels extending through the construct, such that a substantial portion of the channels have an inlet at one surface of the construct and an outlet at an opposing surface of the construct (Paragraph [08]) (interpreted as a structure for tissue culture made of a biocompatible polymer and a 3D network formed by connecting a plurality of microchannels therein, and the tumor tissue is encapsulated in the structure for tissue culture, instant claim 1). Berry teaches that the 3D network of cells forms a (breast cancer) tumor (claim 16) (interpreted as tumor tissue isolated from the living body, instant claim 1).
Berry does not specifically exemplify the length, width, and height of the tissue (claim 6), the diameter of the microchannel (claim 7), and rate at which the cell culture medium is supplied (claim 15).
Regarding claims 6, although Berry does not teach the specific size of the tumor, Berry does teach that the physical properties (size, shape, density) of the 3D vascularized tissue construct can be configured (Paragraph [84]). Further, it was known that preoperative tumor size cutpoints were defined in 1-mm increments and used to identify optimal size thresholds, as evidenced by Macielak et al. (Abstract). Thus, one of ordinary skill in the art would be able to determine the appropriate size of the tumor to use in the tissue model.
Regarding claim 15, Berry does not specifically teach the rate the cell culture medium is supplied. However, it was known in the art that at high flow rates (>0.3 ml h(-1)), the cells did not grow in the microchannel for more than a few days, and for low flow rates (<0.2 ml h(-1)), the cells grew well and a confluent layer was obtained, as evidenced by Korin et al. (Abstract). Thus, one of ordinary skill in the art would know the optimal rate the cell culture medium is supplied.
Regarding claim 8, Berry teaches that 3D vascularized constructs to make tissue models (Paragraph [85]). Berry teaches a 3D tissue construct of the cancer model includes a biocompatible scaffold material; comprising a 3D network of living cells within the scaffold material (Paragraph [8]) Berry teaches that biocompatible scaffold material includes a gel matrix and one or more crosslinking agents (Paragraph [67]).
Berry does not specifically exemplify supplying a hydrogel solution to a mold containing a 3D fiber bundle, cross-linking the hydrogel solution, and removing the 3D fiber bundle from the crosslinked hydrogel (claim 8).
Berry also does not specifically exemplify the diameter of the microchannel (claim 7).
Regarding claim 7 – 10, Lee teaches a 3D microvascularized gelatin hydrogel is produced using thermoresponsive sacrificial poly(N-isopropylacrylamide) (PNIPAM) microfibers (Abstract). Lee teaches that this hydrogel significantly improves the viability of human neonatal dermal fibroblasts encapsulated within the gel at a high density (Abstract). Lee teaches that high speed spinning of PNIPAM solution at room temperature yielded microfibers with smooth surfaces and diameters ranging from 3 to 55 µm (pg. 3, third paragraph) (referring to instant 7 and claim 10). Lee teaches that the assembly of the microfluidic hydrogels is achieved by embedding microfibers within an enzyme (microbial transglutaminase: mTGase) -mediated crosslinkable gelatin hydrogel with microchannels serving as inlet and outlet conduits for the perfusion setup (pg. 3, third paragraph) (interpreted as supplying a hydrogel solution to a mold containing a 3D fiber bundle, and cross-linking the hydrogel solution, instant claim 8). Lee teaches that upon complete gelation, the PNIPAM structure was removed by immersing the entire construct in cell culture media at room temperature (pg. 3, third paragraph) (interpreted as removing the 3D fiber bundle from the crosslinked hydrogel, instant claim 8).
Therefore, in view of the benefits of significantly improving the viability of human neonatal dermal fibroblasts encapsulated within the gel at a high density as taught by Lee, it would have been prima facia obvious for one of ordinary skill in the art to make the 3D vascularized constructs to make tissue models, as taught by Berry, using the PNIPAM microfibers to generate the microfibers, and crosslink to the hydrogel, as taught by Lee, with a reasonable expectation of success in physically making the 3D vascularized constructs. It would have been prima facia obvious to combine the cited references because Berry teaches 3D vascularized constructs that can be used for fibroblasts, but does not teach how to generate the hydrogels and actually crosslink the microfiber bundles, and Lee teaches the method of generating the microfibers, crosslinking to the hydrogels, and the advantage of improving the viability of human neonatal dermal fibroblasts encapsulated within the gel.
Regarding claim 11, Lee does not specifically teach that the PNIPAM has an average molecular weight of 85,000, however, the molecular weight of any molecule, including the molecular weight of PNIPAM is well known in the art as evidenced by the Sigma Aldrich product specification
Regarding claim 12, Lee does not specifically exemplify that 3D bundle is prepared by dissolving the PNIPAM in methanol. Lee does teach that the highspeed spinning of PNIPAM solution at room temperature yielded microfibers with smooth surfaces and diameters ranging from 3 to 55 µm (pg. 3, third paragraph). Further, it is well known in the art that PNIPAAm was dissolved 20% (wt/v) in methanol to generate polymer poly(N-isopropyl acrylamide) only fibers, as evidenced by Allen et al. (Allen ACB. Et al. Electrospun poly(N-isopropyl acrylamide)/poly(caprolactone) fibers for the generation of anisotropic cell sheets. Biomater Sci. 2017 Jul 25;5(8):1661-1669. doi: 10.1039/c7bm00324b. PMID: 28675203; PMCID: PMC5870125.) (pg. 2, last paragraph).
Regarding claim 13, Lee teaches that upon complete gelation, the PNIPAM structure was removed by immersing the entire construct in cell culture media at room temperature (pg. 3, third paragraph) (interpreted as converting the 3D fiber bundle into a sol).
Conclusion
Claims 1 – 16 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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