DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/13/2026 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 Any previously presented objections or rejections that are not presented in this Office Action are withdrawn.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 1-20 are pending.
Claim 16 is amended.
Claims 1-15 are withdrawn.
Claims 16-20 have been examined on the merits.
Priority
This application, U.S. Application No. 17769626, is a national stage entry of International Application Number PCT/US2020/056327 filed on 10/19/2020, which claims for domestic priority under 35 U.S.C. 119(e) to provisional application No. 62/973,695 filed on 10/18/2019.
Objections - Withdrawn
Objection to the claim 16 is withdrawn due to the amendment to the claim filed on 04/13/2026.
Rejections - Withdrawn
The rejection of Claims 16-20 under 35 U.S.C. 112(a), as failing to comply with the written description requirement, is withdrawn due to the amendment to the claims filed on 04/13/2026.
The rejection of Claims 16, 17, 19, and 20 on the ground of nonstatutory obviousness-type double patenting over claims 1-17 of US patent No. 12441981 in view of Simko et al. is withdrawn due to the Terminal Disclaimer filed by Applicant on 04/13/2026.
The rejection of Claims 16-20 on the ground of nonstatutory obviousness-type double patenting over claims 1-17 of US patent No. 12441981 in view of Simko et al. and Chien et al. is withdrawn due to the Terminal Disclaimer filed by Applicant on 04/13/2026.
Claim Rejections - 35 USC § 112, Second Paragraph
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 16-20 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.
Claims 16 and 18 are indefinite due to the recitation of “micro-tissue structure”. The term is not defined in the specification. It is unclear at which specific size a tissue structure can be considered as a micro-tissue structure, and whether the “micro” stands for “micron-sized” (in micrometer) or “any small size”.
The remaining claims are rejected for depending on an indefinite claim.
Claim Rejections - 35 USC § 102
Claims 16, 17, 19 and 20 are rejected 35 U.S.C. 102(a)(1) as being anticipated by Simko et al. (US 2017/0342374, 2017, cited in IDS).
Regarding Claims 16 and 17, Simko et al. teach a system for therapeutic cell devilry via injection and a method of generating the system through micro-tissue encapsulation by seeding cells to a tissue scaffold coated with extracellular matrix, the system comprising: a cell patch comprising cells/a cell monolayer as well as a micro-tissue structure comprising an extracellular matrix (ECM), which is folded (wrapped) around the cell patch (abstract; Claims 1 and 14-15; Figs. 1 & 7; paras 0004, 0006, 0012/last 2 lines, 0013, 0022, 0024/last 5 lines, 0025, 0070/lines 8-13, 0071, and 0064-65); wherein the ECM comprises one or more proteins selected from collagen IV, laminin, a fibroblast growth factor protein, and a vascular endothelial growth factor protein (paras 0010, Claim 7); and wherein the micro-tissue structure and cell patch are injectable into a tissue (0064-65, 0070, 0073, and Claim 2). Furthermore, Simko et al. teach that the system of cell patch comprising a cell monolayer is administered for repairing damaged tissue after delivery to a desired site for repair (para 0004), such as injecting a system comprising a cell patch of a corneal endothelium cell (CEC) monolayer through a small gauge needle into eyes of a subject for repairing corneal (paras 0012, 0022/last 7 lines, and 0065/lines 4-10).
Regarding the limitation “provide a physical barrier between the cell patch and an external environment” recited in Claim 16, Simko et al. teach that the micro-tissue structure comprising the ECM provides a physical protection to the cell patch so as to avoid damages caused by an external environment (Claim 3, para 0004/lines 7-10, 0024/last 5 lines, 0025/last 5 lines). Regarding the limitation “cell monolayer … maintains expressions for cell-cell junctions and cytoskeletons for cells …” recited in Claim 16, Simko et al. expressively teach that the cell patch comprising the cell monolayer maintains expression of Z0-1 tight-junction protein and F-actin cytoskeleton protein for maintaining cell-cell junctions and cytoskeletons for cells (para 0071, Fig. 8).
Regarding the limitation “the cell patch configured to release … and integrate into tissue forming an … monolayer having a cell density between 1250 cells per square millimeter …” recited at the end of claim 16, this limitation is directed to the outcome, i.e. what the cell patch does after the claimed system being delivered to a target tissue. Although Simko et al. are silent about a specific cell density of integrated tissue monolayer formed after delivering the system to a target tissue, the system, cell patch, and micro-tissue structure taught by Simko et al. have the same structure as those defined in the claim 16. In the absence of evidence to the contrary, it is presumed that a system/cell patch having substantially the same structure is capable of performing substantially the same function and generating the same outcome. Therefore, the teachings of Simko et al. meet the claimed limitation.
Regarding Claim 19, this claim requires the monolayer comprises 10-100 cells. Simko et al. further teach administering the system comprising micro-tissue structure and cell patch to a subject as a therapeutic agent (paras 0064-65, Claim 1), wherein a number of cells (in cell patches) administered varies with specific application (para 0065). Simko et al. expressively teach that 10,000 cells administered are present in around 200 – 250 cell patches (para 0065: page 7, right col, lines 3-5), which can be converted to a number of cells per cell patch/monolayer (10,000/200-250), i.e. about 40 – 50 cells per cell patch/monolayer. Thus, the teachings of Simko et al. meet the limitation of the claim 19.
Regarding Claim 20, Simko et al. teach the ECM is added with a vascular endothelial growth factor protein, as indicated above. Simko et al. further teach a muscle cell, i.e. murine skeletal myoblast cell, as a cell type used for forming the cell patch (para 0028, lines 2-4). The cell patch comprising a muscle cell monolayer taught by Simko et al. meets the limitation of “muscle tissue” recited in the claim.
Therefore, in view of the teachings of Simko et al., the system of Claims 16, 17, 19, and 20 is anticipated by the system of Simko et al.
Claim Rejections - 35 USC § 103
Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Simko et al. (US 2017/0342374, 2017, cited in IDS) in view of Chien et al. (US 2012/0027807, 2012, cited in IDS).
The teachings of Simko et al. are described above.
Regarding Claim 18, Simko et al. do not teach the micro-tissue structure forms a tube configuration. However, Simko et al. teach the geometries/shapes of the ECM/micro-tissue structure are readily adjustable (paras. 0022/lines 1-8, 0062/last 7 lines).
It would have been obvious to modify the system of Simko et al. through seeding cells onto a cylinder-shaped scaffold (precoated with ECM) in the method of Simko et al. for forming a micro-tissue structure having a tube configuration, so as to obtain the modified system comprising the micro-tissue structure having a tube configuration. This is because it is an obvious design choice to form the micro-tissue structure with a specific tube configuration. Furthermore, it is well known in the art to form an in vivo engineered tissue having a tube configuration by seeding cells onto a scaffold shaped as a cylinder, and such a tube-shaped engineered tissue is suitable for treating diseases such as cardiovascular disorders. In support, Chien et al. teach a tissue engineered myocardium having functional properties of cardiac muscle as well as a method of generating the tissue to be used for treating cardiovascular disorders (abstract, claims 21-22), wherein the tissue engineered myocardium is formed by seeding CVP cells onto a biopolymer scaffold that has any geometric shape, such as a spiral or V-shaped, or O-shaped scaffold, and the CVP cells form the tissue that conforms and remains the same shape of scaffold after removal of the scaffold; and wherein a hollow tube of the tissue engineered myocardium is formed by seeding the cells onto a scaffold shaped as a cylinder (para 0334).
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 claim objection as well as the rejection of claims 16-17 and 19-20 under 35 USC 112(a) in the response filed on 04/13/2026 (page 6) have been fully considered but they are moot because they have been withdrawn as indicated above.
Applicant's arguments about the double patenting rejections in the 04/13/2026 response (page 9) have been fully considered but they are moot because they have been withdrawn as indicated above.
Applicant's arguments about the rejection of claims 16-17 and 19-20 under 35 USC 103 in the response filed on 04/13/2026 (pages 7-8) have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s arguments based on the limitation about the cell density of an integrated monolayer formed in a target tissue in the 04/13/2026 response (pages 7-8), the Examiner reminds Applicant that the instant claims do not recite any limitation to define a specific cell density of the cell monolayer in the cell patch of the claimed system. The cell density “between 1250 cells per square millimeter and 2000 cells per square millimeter” recited in the amended claim 16 is not the cell density of the cell monolayer comprised in the cell patch of the claimed system, rather this cell density is directed to the outcome after the claimed system comprising the cell patch and micro-tissue structure is delivered to a target tissue. Although Simko et al. are silent about a specific cell density of an integrated tissue monolayer formed after their system is delivered to a target tissue, Simko et al. teach a system, a cell patch, and a micro-tissue structure having the same structure as those defined in the base claim 16; and it is presumed that a system having substantially the same structure is capable of performing substantially the same function and generating the same outcome, as indicated above. Thus, the teachings of Simko et al. meet the claimed limitation about the cell density “between 1250 cells per square millimeter and 2000 cells per square millimeter”.
In response to Applicant’s arguments based on treating corneal disease by using corneal endothelium cell monolayers in the 04/13/2026 response (page 8, 2nd half of para 1), it is noted that these arguments are based on features not recited in the instant claims. Furthermore, Simko et al. teach a system comprising a cell patch of a corneal endothelium cell (CEC) monolayer wrapped by a micro-tissue structure of ECM, and injecting the system through a small gauge needle into eyes of patients for repairing corneal (see paras 0012, 0022/last 7 lines, and 0065/lines 4-10). Given that CEC monolayers in cell patch of Simko et al. are composed of CECs, it would be expected that delivering the system/cell patch of Simko et al. into corneal/eyes increases a cell density of CECs in corneal/eyes. Thus, the claimed system is not superior to the system of Simko et al.
Overall, the system in claims 16-20 has no novelty in view of the cited prior art for all the reasons indicated above.
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