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
This Office Action is in response to the Applicant’s reply received 3/30/26. Claims 63-74 and 100-103 are pending and considered on the merits.
Election/Restriction Requirement
Applicant’s election of Group II, claims 63-74 and new claims 100-103, without traverse in the reply filed on 3/30/26 is acknowledged.
Priority Date
This case is not afforded the priority date of its CIPs (17/838284, and 17,882693) since these do not disclose the limitation of “providing a membrane with a region having a pattern with a spacing in the range of 0.01-500 microns”. The Effectively Filed Date of this Application is considered 5/29/23 since US Priority Document 63/504,774 is the earliest instance we see this limitation.
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 69, 70, 101, 104, and 107 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.
Regarding claims 69, 70, 104, and 107, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 101 is rejected because it depends from itself.
Claim 106 is indefinite because of the limitation of “reconstituting to a gel from solubilized or dried ECM”. The parent claim does not include an option for “dried ECM”.
Claim Rejections - 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.
Claim(s) 63-65, 68, 71, 72, and 102-107 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324).
Huh et al. teach a method of seeding a layer of tissue-specific human cells on a pre-fabricated membrane (Huh, Fig. 24). These cells are cultured to produce an ECM layer sandwiched between the cell layer and the membrane (Huh, Fig. 24) to produce a layer of cells attached to the ECM layer (Huh, pg. 32, lines 5-10). Huh teaches that these cells can be seeded and cultured to confluent monolayers (Huh, pg. 14, lines 20-25 and Figs 1J, 4, and 7A). The ECM layer can be peeled from the membrane (Huh, Fig. 2A). They also teach the ECM layer can be decellularized with a detergent to remove cells and DNA residue (Huh, Fig. 24). Alternatively, Fig. 23 shows the ECM sheet cultured by the cells can be decellularized with a detergent and the solubilized into an ECM solution. This solution can be used to make a membrane or hydrogel after the ECM solution is dried (Huh, Fig. 23, and pg. 11, lines 10-30). This ECM membrane can be used to culture seeded cells (Huh, pg. 12, lines 5-10) including human umbilical vein endothelial cells (Huh, pg. 13, line 35).
Huh et al. teach the cells can be seeded at high density or low density to make their confluent cell sheets (Huh, pg. 24, line 15, and pg. pg. 27, line 20). They do not teach adding cells to 60-90% confluence. However this would be a matter of routine optimization between adding cells at a high density and low density to obtain confluent cell sheets. One of ordinary skill would think it obvious to add sufficient cells to obtain the goal of a confluent cells sheet without using too little or too many cells and make the method economical by not wasting cells.
What Huh et al. does not teach is the membrane has a pattern with a spacing of 0.01-500 μm. However this would be obvious in view of Leung et al. who teach seeding cells on textured substrates to make single and multilayer cell sheets (Leung, [0001 and 0003]). The substrate surface can be textured by channels of a depth of 0.1 to 300 μm and a separation of 5-500 μm (Leung, [0139]). The channels can be arranged in several patterns including circumferential, parallel, or radial lines (Leung, 0141). They teach these textured substrates increase adhesion and retention of the cells (Leung, 0083]. They teach the cells layers cultured on these sheets can be removed with a scraper (Leung, 0096). Also Leung et al. teach the cell sheets can be multilayer and attached either by ECM or cell-to-cell binding proteins to form a continuous unit (e.g. fused) (Leung, 0055).
It would be obvious to use the textured substrate of Leung et al. in the to culture the cell layers of Huh et al. since this will increase the adhesion and retention of the cells. One of ordinary skill would recognize this as simply applying a known technique to improve cell adhesion when making cell sheets (MPEP 2141 III (C)).
Claim(s) 66 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324) as applied to claims 63-65, 68, 71, 72, and 102-107 above, and further in view of Iuliano et al. (Adv. Mater. Technol, 2020).
Huh et al. and Leung et al. teach culturing cells on a substrate textured with channels with a spacing of 5-500 μm to produce a cell sheet including ECM. They do not teach the mold to make the substrate is produced by FDM 3-D printing. However this would be obvious in view of Iuliano who teach several methods of producing molds to make patterned cell culture substrates (see Abstract). These include two methods using FDM 3-D printing comprising a) a direct peeling method and b) ESCARGOT method (Iuliano, Section 2.1 and 2.2 and Fig. 1). Both of these methods produce a negative ABS mold where the pattern is replicated on the substrate (Iulian, See Fig. 1 i) and ii).
It would be obvious to use the FDM 3-D printing to make the molds for the substates used by Huh et al. and Leung et al. since Iuliano et al. teach this is a suitable method to make textured cell culture substrates. One of ordinary skill would recognize this as simply applying a known technique to make the substrates required by Huh et al. and Leung et al. (MPEP 2141 III (C)).
Claim(s) 69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324) as applied to claims 63-65, 68, 71, 72, and 102-107 above, and further in view of Wu et al. (J. Tissue Eng Regen 2017).
Huh et al. and Leung et al. teach culturing cells on a substrate textured with channels with a spacing of 5-500 μm to produce a cell sheet with ECM. They do not teach adding ascorbic acid to the media. However this would be obvious in view of Wu et al. who teach culturing cells with ascorbic acid increases ECM deposition (Wu, Abstract) Since Huh et al. and Leung et al. are drawn to producing a cell layer with ECM, then it would be obvious to add ascorbic acid to the culture medium to increase ECM production and improve the overall method. One of ordinary skill would recognize this as simply applying a known technique to make produce more ECM for the cell layers required by Huh et al. and Leung et al. (MPEP 2141 III (C)).
Claim(s) 70 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324) as applied to claims 63-65, 68, 71, 72, and 102-107 above, and further in view of Baldwin et al. (J. Biomaterials app, 2022).
Huh et al. and Leung et al. teach culturing cells on a substrate textured with channels with a spacing of 5-500 μm to produce a cell sheet including ECM. However they do not teach cross-linking the ECM with tannic acid. However this would be obvious in view of Baldwin et al. who teach crosslinking ECM with tannic acid (TA) to improve its mechanical properties (Baldwin, pg. 1510, col 2, last lines) and inhibit enzymatic degradation in vivo (Baldwin, pg. 1511, col 2, end of 1st paragraph).
It would be obvious to crosslink the ECM layer of Huh et al. and Leung et al. since Baldwin et al. teach this is a suitable method to increase the mechanical properties of this layer and inhibit enzymatic degradation. One of ordinary skill would recognize this as simply applying a known technique to make the substrates required by Huh et al. and Leung et al. (MPEP 2141 III (C)).
Claim(s) 73 and 74 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324) as applied to claims 63-65, 68, 71, 72, and 102-107 above, and further in view of Murphy et al. (WO 2013/040087).
Huh et al. and Leung et al. teach culturing cells on a substrate textured with channels with a spacing of 5-500 μm to produce a cell sheets including ECM. However they do not teach rolling the sheets into a cell fiber or stacking the cell sheets. However this would be obvious in view of Murphy et al. who also teach culturing cells into a layer on decellularized ECM scaffolds (Murphy, [00106]). They teach these cell layers on scaffolds can be rolled into a tube (Murphy, [00143] and Fig 8 and 11) and stacked into multiple layers to make a tissue engineered organ (Murphy, [0054] and Fig 10). Therefore it would be obvious to roll the cell layers made by Huh et al. and Leung et al. into tubes to make cell fibers and to either stack these layers or tubes to make tissue engineered organs as taught by Murphy et al. One of ordinary skill would recognize this as simply applying a known technique to improve the method of Huh et al. and Leung et al. to produce tissue engineered organs (MPEP 2141 III (C)).
Claim(s) 100 and 101 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huh et al. (WO 2019/033096) in view of Leung et al. (WO2020/243324) as applied to claims 63-65, 68, 71, 72, and 102-107 above, and further in view of Lv et al. (New J Chem, 2020).
Huh et al. and Leung et al. teach culturing cells on a substrate textured with channels with a spacing of 5-500 μm to produce a cell sheet including ECM. Huh et al. teach ECM can be deposited on a PDMS (polydimethylsiloxane), an elastomeric material (Huh, pg. 11 lines 10-35). However they do not teach attaching tannic acid (e.g. a polyphenol) to the surface of PDMS. This is taught by Lv et al. who teach a surface coating of tannic acid improves adhesion and proliferation of the cells (Lv, Abstract).
It would be obvious to coat the PDMS substrate of Huh et al. and Leung et al. with tannic acid since Baldwin et al. teach this is a suitable method to increase the cell adhesion and proliferation. One of ordinary skill would recognize this as simply applying a known technique to improve the substrates required by Huh et al. and Leung et al. (MPEP 2141 III (C)).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 63-74 and 100-103 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11718830. Although the claims at issue are not identical, they are not patentably distinct from each other because both claims are to a method of growing cells sheets on a membrane with a parallel, circular, or concentric pattern produced by FDM 3-D printing. The cells produce ECM on the surface of the membrane with ascorbate in the media. The ECM produced is crosslinked with tannic acid. US’830 teach their patterns can be up to a few hundred microns (col 8, lines 30-40) which appears to fall into the range of 0.01-500 microns since “up to a few hundred microns” includes 1-200+ microns.
Claims 63-74 and 100-103 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20-of copending Application No. 18207165. Although the claims at issue are not identical, they are not patentably distinct from each other because are to a method of growing cells sheets on an elastomeric membrane with a parallel, circular, or concentric pattern produced by FDM 3-D printing. The patterns are separated by 0.01-500 microns. The cells produce ECM on the surface of the membrane with ascorbate in the media. The surface of the membrane is coated with a hydrophilic substance tannic acid..
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
In response to this office action the applicant should specifically point out the support for any amendments made to the disclosure, including the claims (MPEP 714.02 and 2163.06).
CONTACT INFORMATION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THANE E UNDERDAHL whose telephone number is (303) 297-4299. The examiner can normally be reached Monday through Thursday, M-F 8-5 MST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
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