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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Remarks
The amendments and remarks filed on 06/08/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn.
Claims 1-10 are pending.
Claim 1 is amended.
Claims 8-10 are withdrawn.
Claims 1-7 have been examined on the merits.
Priority
This application, U.S. Application number 17/763936 is a national stage entry of International Application Number PCT/KR2020/012585, filed on 09/17/2020, which claims for foreign priority under 35 U.S.C. 119(a)-(d) to foreign application KR10-2019-0119617 filed on 09/27/2019.
Rejections - Withdrawn
The rejection of Claims 1-7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, is withdrawn due to the amendment to the claims filed on 06/08/2026.
The rejection of claims 1-7 under 35 U.S.C. 112(b) in the previous office action is withdrawn due to the amendment to the claim 1.
The rejections of claims 1-7 under 35 U.S.C. 103 over Chang et al., either alone or in the combination with Chen et al. are withdrawn in favor of the rejections listed below.
Claim Rejections - 35 USC § 112, Second Paragraph
Claims 1-7 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 pre-AIA the applicant regards as the invention.
Claim 1 recites the limitation “the method does not comprise adding a separate scaffold to the cell culture other than that comprised in the … ECM powder”. The metes and bounds of the term “a separate scaffold” in this limitation cannot be determined because Applicant provides two conflict interpretations in the response filed 06/08/2026. Specifically, Applicant states in page 9, para 2 of the response that extracellular matrix components such as fibronectin, vitronectin and collagen in FBS in the culture medium disclosed in the specification of the instant application are not considered as a separate scaffold because these ECM components are dissolved in the medium and assist cell attachment by adsorption. In the contrast, Applicant states in page 8, para 4 of the response that a collagen solution used in the method of Chang et al. is considered as a separate scaffold, although the collagen is also dissolved in the solution/medium and it also assists cell attachment through mechanisms such as adsorption. It is unclear what specific material can be considered as “a separate scaffold”.
Claim 5 is indefinite due to the recitation of “added at a concentration of 0.1 to 3 mg/ml”. It is unclear whether the recited concentration refers to a concentration of decellularized ECM powders in a solution before being added to the cells, or refers to a final concentration of the decellularized ECM powder in the mixed culture solution after the ECM powder is added to the cells.
The remaining claims are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 102/103
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.
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 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.
Claims 1-4 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yin et al. (Acta Biomaterialia 33:96–109, 2016).
Yin et al. teach a method for fabricating functional cartilage microtissue aggregations by using an acellular matrix (ACM) powder comprising the steps: collecting articular cartilage from animals, wherein the cartilage comprises extracellular matrix (ECM) (Note: the cartilage reads on the “tissue-derived extracellular matrix” and/or “cartilage” recited in the claims 1 and 2); pulverizing the cartilage to obtain cartilage ECM-derived particles (CEDPs) (Note: CEDP reads on the “ECM powder” in the claim 1) and decellularizing the ECM-derived particles (CEDPs) to obtain decellularized ECM-derived particles (CEDPs) (i.e. decellularized ECM powders); transfer/adding the decellularized CEDPs/ECM powders to a culture vessel containing a cell suspension of BMSCs and a DMEM culture medium (Note: reading on the “a cell culture comprising cells to be cultured” in the claim 1); and culturing the cells to form functional cartilage microtissue aggregations of BMSC-laden CEDPs, wherein the formation of the aggregations occurs as culturing time increases (abstract; and the section of Materials and methods: paras 2.2, 2.2.1., 2.2.2., and 2.4.2.). Yin et al. further teach the BMSC cells proliferate rapidly on the surface of CEDPs, and they are differentiated into mature chondrocytes (abstract, lines 5-7). Yin et al. further teach implanting the cartilage microtissue aggregations into trochlear cartilage defects leads to better and more rapid joint function recovery and superior cartilage repair compared to control groups (abstract, lines 8-12).
Regarding the limitation “induce spontaneous fusion … form a cell-ECM powder self-assembly” recited in the step (b) of the claim 1, the cartilage microtissue aggregates of Yin et al. are self-assemblies of cells and decellularized ECM powders through spontaneous fusion, because these aggregates are assembled and formed spontaneously after BMSC stem cells contact/fuse with the decellularized ECM powders. Thus, the teachings of Yin et al. meet the claimed limitation.
Regarding the limitation that a size of the self-assembly is 1 cm or more as recited in the claim 1, it is noted that this limitation does not require all the self-assembles produced by the claimed method have a size of 1 cm or more, rather it only requires one or some of the self-assemblies has/have a size of 1 cm or more. Yin et al. are silent about whether any of cartilage microtissue aggregations (i.e. cell-ECM powder self-assemblies) generated by their method has a size of 1 cm or more. However, generating a cell-ECM powder self-assembly with a size of 1 cm or more is directed to the outcome of the claimed method. The method taught by Yin et al. consists of all the steps recited in the instant claim 1. It is presumed that methods having substantially the same steps are capable of generating substantially the same outcomes. Thus, the method of Yin et al. meets the claimed limitation, and anticipates the method of the claim 1. Alternatively, in the case that the method of Yin et al. generates a cartilage cell-ECM powder self-assembly has a different size, the reference Yin et al. is considered to render the claim obvious because a size of the cartilage self-assembly generated by the method of Yin et al. can be increased through optimization of operation conditions such as extending a time length of culturing, changing cell concentrations and their relative ratios to decellularized ECM powers. It is well settled that routine optimization is not patentable, even though it results in significant improvement over the prior art (see MPEP 2144.05).
Regarding the claims 3 and 4, the BMSC cells (bone marrow stromal cells) of Yin et al. are referred as mesenchymal stem cells (MSCs) (see title; page 97/left col: para 2/line 1 and last para/lines 7 and 11-13; page 98/para 2.4.2.), thus meeting the claimed limitations.
Regarding Claim 6, the tissue aggregates of Yin et al. is formed under in vitro conditions in the method of Yin et al., thus meeting the claimed limitation.
Regarding Claim 7, Yin et al. teach the BMSC cells in the aggregates proliferate and differentiate into mature chondrocytes.
Therefore, in view of the teachings of Yin et al., the method of claims 1-4 and 6-7 is either anticipated by or, in the alternative, prima facie obvious over Yin et al. to a person of ordinary skill in the art before the effective filing date of the claimed invention
Claim Rejections - 35 USC § 103
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Yin et al. (Acta Biomaterialia 33:96–109, 2016).
The teachings of Yin et al. are described above.
Regarding Claim 5, Yin et al. teach adding 100 mg of the decellularized CEDP/ECM powers to a cell suspension of 2 x 106 SMSC cells (page 98/para 2.4.2). Yin et al. are silent about a total volume of the resulted culture solution and a specific concentration of the powders in the culture solution. However, it is deemed merely a matter of routine optimization to adjust a total volume of the culture solution in the method of Yin et al. for facilitating downstream processes, thus obtaining a desired concentration of the powers in the claimed range. For example, if a total volume is adjusted to be in a range of 33-100 ml, the concentration of the ACM power would be in a range from 1 mg/ml to 3 mg/ml, which reads on the claimed range of “0.1 to 3 mg/ml”. It is noted that a concentration generally does not support the patentability of the claimed subject matter unless there is evidence indicating such concentration is critical. Thus, the teachings of Yin et al. render the claim to be obvious.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Yin et al. (Acta Biomaterialia 33:96–109, 2016), further in view of Chen et al. (Cell Tissue Res., 2017, 370:41-52, of record).
Examiner notes that this rejection further renders the “meniscus”, a species of tissue-derived extracellular matrix, recited in Claim 2 to be obvious in view of Yin et al. in combination with Chen et al.
The teachings of Yin et al. are described above.
Regarding Claim 2, Chang et al. do not teach the tissue-derived extracellular matrix is meniscus. However, Yin et al. teach using a cartilage tissue (articular cartilage) as the tissue-derived extracellular matrix.
Chen et al. teach that the meniscus is a fibrocartilage (a type of cartilage tissue) of the knee, which consists of 72% water, 22% collagen, and 0.8% GAGs (page 41, Introduction, para 1) (Note: collagen and GAGs are extracellular matrix (ECM) components, as evidenced by the specification of the instant application, see paras 0062-63). Chen et al. also teach that there is an increasing rate of injuries to the meniscus and about 50% of arthroscopic knee surgeries in the united states are related to the meniscus; and there is an urgent need to develop effective repair strategies (abstract/lines 1-2, page 41/right col/last para/lines 3-6). In addition, Chen et al. teach that decellularized ECM scaffolds are increasingly investigated as a natural replacement of injured meniscus for facilitating its regeneration, and it is believed that decellularized ECM scaffolds are the future biomaterials for successful meniscus replacement (page 42: left col/para 3/lines 1-3, abstract/last 3 lines). Chen et al. further teach that a general procedure of meniscus regeneration using the ECM scaffolds includes: decellularization of meniscus tissue, recellularization/repopulation of decellularized meniscus ECM scaffolds with appropriate cells, and implantation (page 42: right col/lines 2-7, Fig. 3), wherein mesenchymal stem cells (MSCs) are sources of cells suitable for recellularization of the decellularized ECM scaffolds (page 46, right col/para 2/lines 1-3; Fig. 3). Chen et al. further teach seeding and culturing bone marrow-derived MSCs on the meniscus ECM scaffolds under in vitro condition, and the MSCs showed the benefits of chondroprotective effect and expression of ECM (Fig. 5: Reseeding and Results in the row of Yamasaki et al., 2008; page 46/right col/para 2/lines 4-6).
It would have been obvious to a person of ordinary skill in the art to modify the method suggested by Yin et al. by replacing the articular cartilage tissue with meniscus cartilage tissue for preparing decellularized meniscus ECM-derived particles (i.e. decellularized ECM powders) to be used as scaffolds for culturing BMSC stem cells for forming and developing an artificial cartilage/meniscus tissue for repairing damaged meniscus, as taught by Chen et al. One of ordinary skill in the art would have been motivated to do so, because Chen et al. teach a rate of injuries to the meniscus is increasing and there is an urgent need to develop effective repair strategies, and the artificial meniscus tissues derived from decellularized ECM scaffolds is a promising natural replacement of injured meniscus for facilitating its regeneration of menisci. Furthermore, Chen et al. teach that the meniscus is a cartilage tissue of the knee, which is rich in extracellular matrix (ECM) components (including collagen and GAGs). Application of a meniscus-derived ECM particles/scaffolds rich in ECM components would facilitate the process of culturing mesenchymal stem cells for forming an artificial meniscus tissue. One of ordinary skill in the art has a reasonable expectation of success at forming a meniscus construct by practicing the method of Yin et al. through replacing the articular cartilage tissue with the meniscus cartilage tissue, because mesenchymal stem cells (e.g. BMSCs) of Yin et al. are cells suitable for culturing on meniscus-derived ECM particles/scaffolds, and the mesenchymal stem cells are successfully seeded and cultured with the scaffolds/powders for delivering benefits of chondroprotective effect for forming the artificial cartilage/meniscus tissue, as taught by Chen et al. Furthermore, both articular cartilage and meniscus are cartilage tissues of the knee, and both are rich in ECM components. Decellularized meniscus-derived ECM particles/powders are therefore art-recognized equivalents for the same purpose. Replacement of one source of ECM powders rich in ECM components with another and the results of the replacement would have been predictable.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments about the rejection of claims 1-7 under 35 USC 112(a) in the response filed on 06/08/2026 (page 4) have been fully considered but they are moot because the rejection has been withdrawn, as indicated above.
Applicant's arguments about the rejection of claims 1-7 under 35 USC 112(b) in the response filed on 06/08/2026 (page 5) have been fully considered but they are moot because the rejection in the previous office action has been withdrawn, as indicated above. However, Applicant’s newly amendment to the claim 1 raised new issues. Thus, the claims 1-7 are rejected under 35 USC 112(b) (please see details in page 4).
Applicant's arguments about the rejections of claims 1-7 under 35 USC 103 over Chang et al. either alone or in combination with Chen et al. in the 06/08/2026 response (pages 6-12) have been fully considered have been fully considered, but they are moot because the rejections have been withdrawn and the ground of rejections in this office action is different from that in the prior office action.
It is noted that Applicant’s arguments based on “cell-to-cell interactions” for inducing “a spontaneous self-assembly process” in the response (pages 9-10) are not persuasive. The cell-to-cell interactions and the spontaneous self-assembly are directed to an outcome of the claimed method. The method taught by the cited prior art comprises the same steps as the claimed method, thus being expected to generate the same outcome, i.e. inducing the spontaneous self-assembly between the cells and decellularized ECM powders, through cell-to-cell interactions. Furthermore, Examiner reminds Applicant that the instant claim 1 as currently written has an extremely broad scope, comprising: adding any amount of any tissue-derived decellularized ECM powders with any particle sizes to any cell culture comprising any amount of any type of cells and any kind of culture medium with any components; and culturing the cells under any culture conditions for any time period. The claimed method does not comprise steps distinct from those taught by the prior art, thus having no novelty.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656
Prosecution Insights