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 .
Examiner Note
The Examiner would like to note that the handling of prosecution has switched from Examiner Rosanne Kosson to Examiner Alyssa Weston.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 16-24, and the species of a recovered three-dimensional cultured skin from a culture vessel, 10-300 mg/mL of trehalose, and a collagen gel in the reply filed on 21 November 2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. It is of note that Applicant has cancelled claims 25-33, which were drawn to non-elected Group II, and have added new claims 34-35. New claims 34-35 are directed to the elected invention.
Therefore, claims 16-24 and 34-35, of record 21 November 2025, are pending. Claim 20 is withdrawn from reading on an unelected species. Prosecution on the merits commences for claims 16-19, 21-24, and 34-35.
Status of Prior Rejections/Response to Arguments
RE: Objection to claim 15
The cancellation of claim 15 renders the objection of record moot. Therefore, the objection is withdrawn.
RE: Rejection of claims 1-4, 11, and 15 under 35 USC 112(b)
The cancellation of claims 1-4, 11, and 15 renders the rejection of record moot. Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-4 under 35 USC 103 over Hashimoto et al
The cancellation of claims 1-4 renders the rejection of record moot. Therefore, the rejection is withdrawn.
RE: Rejection of claim 15 under 35 USC 103 over Hashimoto et al in view of Boquest et al
The cancellation of claim 15 renders the rejection of record moot. Therefore, the rejection is withdrawn.
It is of note that Applicant did not specifically traverse the disclosure of Boquest et al within the Remarks filed 11 September 2025.
New Grounds of Rejection
Drawings
The replacement drawing sheets filed 11 September 2025 are acknowledged and entered into the application file.
Specification
The preliminary amendments to the Specification filed 25 February 2022 are acknowledged and entered into the application file.
However, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in Paragraph [0033]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claims 16-19, 21-23, and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Hashimoto et al (US 2008/0039940 A1, of record on IDS filed 25 February 2022) in view of Tanabe et al (US 2007/0003502 A1, of record on IDS filed 20 July 2023).
Hashimoto et al and Tanabe et al are each considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 16, 19, and 22: Hashimoto et al disclose a biological tissue sheet which is expected as exerting a favorable therapeutic effect and a high safety in transplantation (Abstract).
As such, Hashimoto et al disclose a method of forming a three-dimensional cultured skin sheet, wherein keratinocytes are placed and cultured upon on a collagen gel containing fibroblasts (Paragraphs [0043], [0046], [0070]-[0073], [0106], [0145]-[0147]; Figure 4).
Hashimoto et al do not disclose that the collagen gel containing fibroblast further comprises trehalose, as required by instant claim 16.
Tanabe et al, however, disclose the administration of 6% w/v (60 mg/mL) trehalose to fibroblasts, wherein the trehalose promotes the proliferation of fibroblasts (Paragraphs [0083]-[0086]).
Therefore, it would have been prima facie obvious to have modified the method of Hashimoto et al such that the fibroblasts within the collagen gel are contacted with trehalose, as suggested in Tanabe et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to enhance the proliferation of the fibroblasts, as the cells comprised within the three-dimensional cell sheet were not well proliferated (Hashimoto et al: Paragraph [0147] – control group 2), and would have had a reasonable expectation of success since Tanabe et al disclose that trehalose can be combined with collagen (Paragraph [0023]). See MPEP § 2143(I)(G).
Consequently, Hashimoto et al as modified by Tanabe et al render obvious a method of forming a three-dimensional cultured skin sheet, wherein keratinocytes are placed and cultured upon on a collagen gel (claim 22) containing fibroblasts and 60 mg/mL trehalose (claim 19). As the collagen gel will necessarily be present within the interstices of the fibroblasts, this therefore renders obvious the method of instant claim 16.
Regarding claim 17: Following the discussion of claim 16, Hashimoto et al further disclose that the outermost surface layer of the three-dimensional cultured skin sheet is brought into contact with air (Paragraphs [0038], [0077]-[0079], [0085], [0107], [0109]-[0111], [0116]-[0117], [0139], [0142], [0145]). This therefore reads on the method of the instant claim.
Regarding claim 18: Following the discussion of claim 16, Hashimoto et al further disclose that the three-dimensional cultured skin sheet is removed from a culture dish (Paragraphs [0108], [0113]). This therefore reads on the method of the instant claim.
Regarding claim 21: Following the discussion of claim 16, Hashimoto et al further disclose that the collagen gel is seeded with 5×105 cells/mL fibroblasts (Paragraph [0104]). As that roughly computes to 5×105 cells/cm3 fibroblasts, this therefore reads on the method of the instant claim. See MPEP § 2131.03.
Regarding claim 23: Following the discussion of claim 16, Hashimoto et al further disclose an embodiment of the invention wherein an epidermal sheet is put into contact with the collagen gel composition (Paragraphs [0046], [0145]-[0147]). As the epidermal sheet inherently comprises keratinocytes (Paragraph [0052]) and there is no subculture prior to placing it on the collagen gel composition, this therefore reads on the method of the instant claim.
Regarding claims 34-35: Following the discussion of claim 18, Hashimoto et al further disclose that the multilayer keratinocyte section and collagen gel composition can be separated from the resulting three-dimensional cultured skin sheet and utilized as a transplantation material (Paragraphs [0009], [0069], [0108], [0113]). Therefore, the ordinary artisan would have understood that the recovered three-dimensional cultured skin sheet can be stripped of the multilayer keratinocyte section (claim 34) or the collagen gel composition (claim 35). This therefore reads on the method of the instant claims.
Claims 16-19, 21-24, and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Hashimoto et al (US 2008/0039940 A1, of record on IDS filed 25 February 2022) in view of Tanabe et al (US 2007/0003502 A1, of record on IDS filed 20 July 2023), and further in view of Boquest et al (Biology of Reproduction, 1999, of record).
The discussion of Hashimoto et al as modified by Tanabe et al regarding claim 16 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Hashimoto et al as modified by Tanabe et al render obvious claims 16-19, 21-23, and 34-35. Boquest et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 24: Following the discussion of claim 16, Hashimoto et al further disclose that the collagen gel composition comprises a mixture of type I collagen and human fibroblasts in a logarithmic growth phase, which are then gelled and static cultured (Paragraph [0073]).
The combination of Hashimoto et al and Tanabe et al fail to teach that 1 to 50% of the fibroblasts within the collagen gel composition are in the G2 phase of the cell cycle, as required by instant claim 24.
Boquest et al, however, teach that fetal fibroblasts in a proliferative state – referred to as “cycling” – and those that are stationary in confluent culture have different percentages of fibroblasts within the cell cycle phases (Abstract, Page 1013). As such, Boquest et al disclose that the G2 phase fibroblasts in proliferating culture are present at a level of 18.2%, while the G2 fibroblasts in stationary/confluent culture are present at a level of 8.8% (Page 1016, Tables 1-2).
Therefore, it would have been prima facie obvious to have modified the method of Hashimoto et al in view of Tanabe et al such that about 9% to about 18% of the fibroblasts in the collagen gel composition are in the G2 phase, as taught by Boquest et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to have the percentage of fibroblasts in the G2 phase, as that indicates that the fibroblasts are proliferating, and would have had a reasonable expectation of success given that Hashimoto et al teach that proliferating fibroblasts are mixed with type I collagen to form the collagen gel composition. See MPEP § 2143(I)(G).
Consequently, Hashimoto et al as modified by Tanabe et al and Boquest et al render obvious a method of forming a three-dimensional cultured skin sheet, wherein 1 to 50% of fibroblasts within the collagen gel composition are in the G2 phase. This therefore renders obvious the method of the instant claim. See MPEP § 2131.03 and 2144.05.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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