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
This action is in response to the papers filed on 08/10/2026. Claims 1-3 and 6-9 are currently pending as per claims filed on 08/10/2026. Claim 1 has been amended and claims 4-5 and 10-19 have been cancelled as per claims filed on 08/10/2026.
Applicant’s election without traverse of Group I, which include claims 1-9 (claims 4-5 now cancelled), drawn to a method of cell transduction, in the reply filed on 08/10/2026 is acknowledged. Claims 10-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected subject matter, there being no allowable generic or linking claim.
It is noted that Group II, which consists of claims 10-19, has been cancelled as per claims filed 08/10/2026. Therefore, claims 1-3 and 6-9 are subject to examination to which the following grounds of rejection are applicable.
Priority
The instant application is a 371 of PCT/KR2022/004358 filed on 03/28/2022, which claims foreign priority to KOREA, REPUBLIC OF 10-2021-0042401 filed on 03/31/2021. Filing of a certified untranslated copy of the Korean Application No. 10-2021-0042401, on September 29, 2023, is acknowledged.
Thus, the earliest possible priority for the instant application is 03/31/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/29/2023 was filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
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 1-3 and 6-9 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 recites at lines 3-4 “…wherein the contacting is performed while the virus particles pass through the hydrogel, wherein the passing is performed by microfluid flow.”. It is unclear what the applicant’s intended meaning is for the phrase, “wherein the passing is performed by microfluid flow.” It is unclear how one would determine the fluid flow, does this mean flow volume, flow rate, or some other characteristic that distinguishes microfluid flow from any other fluid flow. Therefore, the metes and bounds cannot be determined, and the claim is rendered indefinite. For the purpose of examination, any prior art reading on fluid flow will be considered.
Claim 1 is indefinite in the recitation of “…the viral particles pass through the hydrogel” at line 4. As written, it is unclear what the applicant intends to claim. Do the viral particles enter one region of the hydrogel and will transport completely through said hydrogel? Do the viral particles need only penetrate/enter the hydrogel and travel sufficiently to merely contact cells which are encapsulated, without emergence from the hydrogel being required? Thus, the metes and bounds cannot be determined, and the claim is rendered indefinite. For the purpose of examination, any prior art reading on viral particle entry into a hydrogel will be considered.
Claims 2-3 and 6-9 are rejected as they ultimately depend on and inherit the deficiencies of claim 1.
Claim 2 recites, “…wherein the target cells are single-encapsulated.” It is unclear what the applicant’s intended meaning is for “single-encapsulated”. The specification does not appear to provide a definition for “single-encapsulated”. Does “single-encapsulated” mean each individual cell is encapsulated separate in its own separate hydrogel volume? Do the cells as a whole undergo a single encapsulation event as opposed to multiple coatings? Thus, the metes and bounds cannot be determined, and the claim is rendered indefinite.
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) 1, 3, 6, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Ayuso et al. (Ayuso, Jose M et al., Scientific reports, 2016) in view of Moore et al. (Moore N et al., Scientific reports, 2019).
Regarding Claim 1, Ayuso et al. teaches the development of a microfluidic model of the tumour microenvironment (Abstract). Ayuso teaches a hydrogel encapsulation of target cells (Pg. 2, Microdevice operation and Visualization of cells; Fig. 1, especially 1d). Ayuso demonstrates within their model the capacity to generate fluid flow (“interstitial flow”) through a hydrogel (Pg. 2, Analysis of Fluid Flow) and a hydrogel with encapsulated cells made successful contact with refreshed media provided by the microfluidic device (Pg. 8, Figure 5). Ayuso teaches .2µM particles (fluorescent beads) successfully penetrating the hydrogel through use of microfluidics (Pg. 2, Analysis of Fluid Flow; Fig. 2a-b).
Ayuso does not teach contacting viral particles with the target cells in the hydrogel.
Moore teaches a microfluidic device used to enhance viral transduction, termed microfluidic transduction device or “MTD” (Title, Abstract). Moore teaches use of MTD enhances transfection efficiency, specifically “We next demonstrated that the MTD enhanced transduction efficiencies relative to standard static transduction protocols. When compared to both 90-minute time-matched controls and standard overnight transductions, the 2M-MTD demonstrated improved transduction efficiencies across MOIs ranging from 0.5 to 15 (Fig. 2b). At sub-saturating MOI, the 2M-MTD routinely transduced T cells 4 to 5 fold more efficiently than 90-minute time matched static controls. Moreover, a 90-minute transduction time in the 2M-MTD averaged a 2.4-fold greater transduction efficiency relative to static controls run overnight (Fig. 2b,c). Similar rates of transduction were found to be consistent across data collected using T cells derived from multiple donors (Fig. 2c), and also when we used a second commercially available lentiviral vector (Supplementary Fig. 1a). At higher MOI (~5), the 2M-MTD reached a saturation point in transduction efficiency using approximately half the amount of virus needed with overnight static conditions (MOI between 10 and 15) (Fig. 2b).” (Pg. 4 1st full paragraph). Moore teaches the MTD improves transduction efficiency by enhanced colocalization of viral vector and target cell (Pg. 7, 2nd full paragraph).
It would have been prima facie obvious to a person having ordinary skill in the art at the time of the instant application filing to modify the model of Ayuso, to further contain viral particles as taught by Moore, to produce an improved microfluid method for efficient transduction of cells cultured within a 3D-hydrogel, particularly because Moore’s teaching that microfluidic flow enhances the efficiency of viral transduction by improving the interaction between viral vectors and target cells..
There would be reasonable expectation of success in combining these teaches as Ayuso demonstrates interstitial transport of .2µm particles into its collagen hydrogel and Moore describes lentiviral particles on the ~100nm scale (Pg. 2, Design and use of the microfluidic transduction device, 2nd full paragraph) and successfully transports viral vectors using microfluidic flow. One would reasonably expect that viral particles could likewise be delivered to encapsulated cells for efficient transduction.
Regarding Claim 3, Ayuso teaches the hydrogel is mixed with a culture medium of the target cells (Pg. 14, 3D cell culture with the microdevices).
Regarding Claim 6, Ayuso teaches cells embedded in 3D collagen hydrogels within the microdevice (Figure 5. Of Ayuso)
Regarding Claim 8-9, Moore teaches lentiviral vectors used in the transduction of T-cells in the microfluidic device (Abstract of Moore).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ayuso et al. (Ayuso, Jose M et al., Scientific reports, 2016) in view of Moore et al. (Moore N et al., Scientific reports, 2019), as applied to claim 1 above, and further in view of Shin et al. (WO 2016/004068).
Regarding Claim 2, The combined teachings of Ayuso and Moore render obvious the method of claim 1 as described in the 103 rejection above, the content of which is incorporated herein in its entirety.
Ayuso and Moore do not specifically teach encapsulation single cells isolated separately withing a hydrogel.
Shin et al. teaches microfluid methods for individually encapsulating target cells in hydrogel, which includes single cell encapsulation (Pg. 2, Paragraph [08]). Shin further teaches that this individual cell encapsulation allows for more fine tuning of biological function in vitro and in vivo (Pg. 2, Paragraph [08]). Shin teaches this method allows for a thin hydrogel layer that facilitates diffusion of nutrients and signaling molecules to and from encapsulated cells (Pg.39, Paragraph [0215]) , high encapsulation efficiency, and long term viability of encapsulated cells (Pg. 34, Paragraph [0195]).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to incorporate the single-cell hydrogel encapsulation taught by Shin for preparation of the target cells in the combined method of Ayuso and Moore to produce a hydrogel environment. One would have been motivated to combine these teachings with a reasonable expectation of success as Ayuso, Moore, and Shin teach related fields of microfluidics and 3D culture, and moreover Shin et al. demonstrates cell prepared by their single cell encapsulation method and used in a 3D culture have multiple desirable characteristics, such as allowing for facilitation of nutrients and signaling molecules, the ability to more finely control the culture environment, and long term viability. This would expectantly produce an optimized method of 3D cell culture performed using microfluidics with reasonable success.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Ayuso et al. (Ayuso, Jose M et al., Scientific reports, 2016) in view of Moore et al. (Moore N et al., Scientific reports, 2019), as applied to claim 1 above, and further in view Plou et al. (Plou, J et al., Scientific reports, Aug. 2018).
Regarding Claim 7, The combined teachings of Ayuso and Moore render obvious the method of claim 1 as described in the 103 rejection above, the content of which is incorporated herein in its entirety. Moreover, Ayuso teaches the penetration of 0.2µm beads in the hydrogel. However, Ayuso and Moore do not specifically describe the existence of a pore size between 10nm to 20µM. Plou et al. teaches type I collagen hydrogels having pore sizes of ~1.91µM, 1.25µM, and 0.69 µM at respective collagen concentrations of 2.5, 4, and 6 mg/mL (Pg. 2, Table 1). Plou further demonstrates that collagen concentration affects pore size and porosity of a produced hydrogel (Pg. 2, Table 1). The end result being an in vitro hydrogel model that possessed similar characteristics (stiffness, pore size, and porosity) to ranges found within various living tissue (Pg. 2, 2nd paragraph of Results).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to incorporate the teachings of Plou, who demonstrates that control of pore architecture to be associated with collagen concentration, within the combined teachings of Ayuso and Moore to allow for selection of hydrogel structural properties appropriate for transport of particles/molecules/chemicals of interest through culture within the 3D collagen matrix. One would have been motivated to combine these teachings with a reasonable expectation of success as Ayuso, Moore, and Plou teach related fields of microfluidics and 3D culture and the combination would provide one seeking to facilitate controlled interstitial transport through a cell-containing collagen hydrogel the capacity to select appropriate collagen concentration to obtain a desired pore-size. This would expectantly produce an optimized method of 3D cell culture performed using microfluidics with reasonable success.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KODYE LEE ABBOTT/ Examiner, Art Unit 1634 /MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights