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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s response filed February 6, 2026 has been received and entered into the application file. All arguments have been fully considered. Claims 17-22 and 24-29 are currently pending. Claims 19, 24-25 and 27 are withdrawn.
REJECTION(S) WITHDRAWN
Claim Rejections - 35 USC § 103
RE: Rejection of Claim(s) 17-18, 20-23 and 28 under 35 U.S.C. 103 as being unpatentable over Tongnetti, in view of Germain and Rooney;
Rejection of Claim 26 under 35 U.S.C. 103 as being unpatentable over Tongnetti, in view of Germain and Rooney, and further in view of Ge:
The rejections have been withdrawn in view of an updated prior art search. New grounds of rejection are set forth below.
NEW GROUND(S) OF REJECTION
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.
Claim(s) 17-18, 20-22 and 28-29, are rejected under 35 U.S.C. 103 as being unpatentable over Tongnetti et al., (IDS 11/5/2024), in view of Tian et al., (Cell Tissue Bank (2019) 20:109-115; see PTO-892) (“Tian”), Germain et al., (BURNS 47 (2021) 387-396; previously cited) (“Germain”), and Rooney et al., (BURNS 34 (2008) 664-673; previously cited) (“Rooney”).
Tongnetti is directed to skin banking methods to provide viable human cutaneous allografts for transplant to deep burns and hard-to-heal wounds (Abstract).
Regarding claim 17, Tongnetti discloses a method for the elaboration of a live patch which allows the supply of tissues for skin transplants, of whole skin which includes the dermis (a method for procuring and preserving viable human skin allografts from living donors for transplanting; abstract; page 43, column 2, third paragraph; page 44, first column, second paragraph). Tognetti teaches obtaining skin having thicknesses ranging from 400-800 µm (0.4-0.8 mm) (page 43, right col, fifth paragraph) and Tognetti’s Table 4 illustrates that full-thickness skin grafts have a thickness ranging from 0.45 mm to >0.6 mm. Tognetti’s Figure 5 further illustrates a skin allograft after 15 days of cryopreserved storage, wherein the full dermis appears to be present and dermal fibroblasts are clearly present in the dermis (page 47, left col, last paragraph).
Although Tognetti does not explicitly refer to the 400-800 µm skin samples and the Figure 5 sample as “full-thickness” (i.e., whole skin) allografts, it is further noted that Tian is directed to the use of cryopreserved autologous full-thickness skin in the treatment of large-area circumferential multi-plane traumas (Abstract). Tian’s Case 1 treatment (pages 110-111) sets forth the cryopreservation method employed for medium-thickness skin grafts that included immersion in the cryoprotectant for 30 minutes prior to transfer to liquid nitrogen storage in order to preserve the samples for future use while the patient’s traumatic injuries were stabilized (page 110, right col, first full paragraph). Tian further teaches the Case 2 treatment employed cryopreserved full-thickness skin graft, subjected to the same preservation method as used for the Case 1 preservation and treatment (page 111, left col., Case 2).
Thus, Tian has established it was well-known in the art that full-thickness (i.e., whole skin) allografts could be cryopreserved for future use in wound healing.
Accordingly, taking into hand the teachings of Tognetti and Tian, it would have been obvious to one of ordinary skill in the art at the time the invention was made to include preparing full-thickness allografts for whole skin transplant and subjecting the samples to cryopreservation in order to preserve the samples for future use with a reasonable expectation of success. Further regarding claim 17, Tognetti teaches the method comprises 3 mainstages, namely:
i. procuring whole skin tissue from a living donor undergoing abdominoplasty (i.e., body contouring) surgical procedure (full-thickness skin grafts are obtained from a living donor, comprise epidermis and a dermis) by cutting out the 400-800 µm skin patch from the donor’s posterior trunk (i.e., resected tissue) (Figures 3 and 7; page 43, column 2, third-fifth paragraphs; page44, first column, second paragraph; page 50, second column, second and third paragraphs), which reads on claim 17, step (i);
ii. treatment and preservation of the tissue (the skin grafts are treated and preserved; page 44, second column; page 51, Table 5), obtaining a live patch (a viable skin graft is obtained; page 45, second column, last paragraph; page 46, first column); and finally
iii. tissue graft in the final patient (the skin grafts are used in patients for wound management; page 51, column 1, last paragraph; page 51, column two; page 52, column 1).
As to claim 17, step (ii)(a), Tongnetti teaches procuring the whole skin allograft by harvesting a sample of at least 5-10 cm2 (i.e., measuring and cutting the skin live patch according to requisition to obtain segments of the live skin patch, reviewing the segments) (page 44, second col, Processing of skin samples). Subjecting the skin sample to washing in sterile saline or culture media (i.e., decrease microbial load), subjecting to microbiological testing (i.e., collecting samples for culturing), thereafter the skin is cryopreserved by incubating (i.e., immersing) in cryoprotectants (page 47, first col, Cryopreservation and freezing). Although Tongnetti does not further comment on incubating in the cryopreservation solution for a time period of 30 minutes to 3 hours, it is noted that Tian exemplifies immersion of the full-thickness skin graft in the cryoprotectant solution for 30 minutes and Germain is directed to methods for preparing cutaneous allografts, including cryopreservation of the donor skin samples and specifically teaches the obtained skin segments are incubated in the cryopreservative and cryoprotectant (glycerol) for 45 minutes to 2 hours prior to cryopreservation for up to 2 years until surgery (Fig. 1).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Tongnetti by incubating the skin sample in the cryopreservative and cryoprotectant (e.g., glycerol) for a time period ranging from 30 minutes to 2 hours, as taught by Germain, with a reasonable expectation of successfully preserving the obtained skin samples for up to 2 years, thus meeting the limitation of claim 17.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tongnetti with Tian and Germain because each of these teachings are directed at methods for preparing a skin graft for transplantation.
As to claim 17, step (ii)(b), it is noted that Tongnetti teaches preparation and processing of the tissue samples using standardized procedures to ensure sample traceability (i.e., labeling) (Abstract), preparation in an operating theater, cutting/trimming fragments to sizes ranging from 5-10 cm2 (i.e., measurement), samples are collected for incubation in culture media for microbiological testing, samples are subsequently packaged and frozen (i.e., banking), postprocessing samples are collected and sent for bacteriological and mycological testing (pages 44-45, Processing of skin samples), thus meeting the limitations of claim 17 step (ii)(b).
As to claim 17, step (ii)(c): Tongnetti further teaches cryopreservation and freezing of skin allografts, wherein skin samples are contacted with cryoprotectants, cooled gradually, stored at -60°C to -80°C or at -130°C, or in the vapor-phase of nitrogen at -196°C, thereafter thawed rapidly when needed (Cryopreservation and freezing, left col, page 47; Table 3), and further teaches sterilizing tissue grafts using gamma irradiation (Gamma-irradiation, page 49), thus meeting the limitations of claim 17, step (c).
As to claim 17, step (ii)(d): Tongnetti teaches sterilizing tissue grafts is advantageous for graft safety. Tongetti teaches gamma irradiation at a dose of 25 kGy in the presence of a radio-protectant agent (Gamma-irradiation, page 49). Tongnetti does not further teach irradiation in dry ice. However, Rooney is directed to sterilization of skin allografts using gamma irradiation, wherein skin samples immersed in the cryoprotectant glycerol were irradiated whilst frozen in dry ice (-79°C) in order to maintain native histological and physical properties (Abstract and page 665: 2.1.2 Group B, 2.1.3 Group C, 2.1.4 Group D, 2.1.5 Group E).
Thus, Rooney has established it was well known in the art to conduct gamma-irradiation of skin samples in dry ice for cold chain maintenance.
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Tongnetti by including irradiating whilst frozen in dry ice with a reasonable expectation of successfully producing a sterilized skin graft without altering the samples’ native histological or physical properties. The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tongnetti and Rooney because each of these teachings are directed at are directed at methods for preparing a skin graft for transplantation.
As to 17, step (ii)(e): Tongnetti teaches tissue banks should regulate all activities, including data recording and the tissue banking processes and protocols should be detailed in written procedures and validated (page 44, Donor screening and selection and Processing of skin samples), which reads on claim 17, step (ii)(e).
Regarding claim 18, it is noted that Tognetti teaches the donor skin patch is cut out (resecting) from the skin tissue of the donor at thicknesses ranging from 400-800 µm, such as cut from the posterior trunk and lower limbs by a battery-operated dermatome (page 43, Skin procurement, second col, fifth paragraph), and as illustrated at Tognetti’s Figure 3, said thickness would release fat tissue from the dermis. Tognetti further teaches the procured skin patch is submerged in 0.9% saline solution (i.e., physiological saline) comprising 100 IU/mL penicillin and 100 µg/mL streptomycin (i.e., antibiotic). Thus, Tognetti meets the limitation of at least claim 18, step (a).
Regarding claim 20, Tongnetti teaches the tissue is obtained in an operating theater (page 44, Processing of skin samples). Figure 1 illustrates donor tissue being obtained on an operating room table (suitable surface), and Tongnetti teaches the full-thickness skin grafts consist of the epidermis and all of the dermis (i.e., releasing the fat from the deeper dermis), thus meeting the limitations of claim 20.
Regarding claim 21, Tongnetti teaches postprocessing bacteriological (aerobic and anerobic) and mycological cultures (i.e., testing for one or more aerobic microorganism) are conducted on samples taken from the donors for quality testing (page 45, first col, Quality testing, Microbiological testing, Bacteria, Yeast and fungi), thus meeting the limitation of claim 21.
Regarding claims 22, Tongnetti teaches that, after resection (i.e., release of fat from the dermis) the skin allografts are placed in sealed sterile containers filled with medium supplemented with antibiotics, specifically 0.9% saline (physiological serum) is supplemented with penicillin and streptomycin (page 43, Skin procurement, second col, last paragraph), thus meeting the limitations of claim 22.
Regarding claim 28 and the limitation directed to grafting the CAWS in a final patient, it is noted Tongnetti discloses grafting of cryopreserved skin allografts at Figures 8 and 9, thus meeting the limitation of 28.
Regarding claim 29, Tognetti teaches the body contouring procedure is an abdominoplasty procedure (page 43, right col, third paragraph), thus meeting the limitation of claim 29.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Tongnetti, in view of Tian, Germain and Rooney, as applied to claims 17-18, 20-22 and 28-29 above, and further in view of Ge et al., (Skin Graft Preservation, Chapter 13, 2011, pages 159-174; previously cited) (“Ge”).
The teaching of Tongnetti, in view of Tian, Germain and Rooney, is set forth above.
Regarding claim 26, Tongnetti teaches using 15% glycerol as the cryopreservative and cryoprotectant solution (page 44, Processing of skin samples). Tongnetti does not further teach the glycerol concentration is 10% as recited in claim 26. However, Ge et al is directed to skin graft preservation (1. Introduction, page 159). Ge teaches frozen storage using various cryoprotectants, including 10% glycerin (i.e., glycerol) to avoid ice formation when the skin is stored frozen (4.2 Storage in -20°C, page 164).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention to substitute 10% glycerol, as taught by Ge, for the 15% glycerol of Tongnetti, since both concentrations of glycerol are known to have cryoprotectant capability. Therefore, one of ordinary skill in the art would recognize this as simply substituting one type of glycerol cryoprotectant for another useful for the same purpose ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
The skilled artisan would have had a reasonable expectation of success in substituting the teachings of Tongnetti with the teaching of Ge because each of these teachings are directed at using glycerol cryoprotectants for skin tissue preservation.
Response to Remarks:
As to Applicant’s remarks that Tognetti’s depiction of FTSG is solely to illustrate the classification of graft thickness, and thus Tognetti is silent with respect to a method for procuring FTSGs, as discussed at Applicant’s remarks (page 2), it is noted that Applicant’s remarks have been carefully considered, but are not found persuasive in view of the new grounds of rejection set forth above.
As set forth above, the teachings of Tognetti and Tian further address limitations directed to procuring FTSGs, which are subjected to cryopreservation.
Further in response to Applicant’s argument that Tognetti does not teach or suggest cryopreservation at -80°C, as discussed at Applicant’s remarks (page 3), it is noted that Tognetti’s Figure 5 clearly shows a skin allograft sample, comprising both epidermis and full dermis, that has been subjected to cryopreservation at -80°C.
Further, as to Applicant’s remarks that the cited references to Germain and Rooney do not provide any disclosure that would have motivated a person of ordinary skill in the art to cryopreserve CAWS at -80°C, as discussed at Applicant’s remarks (page 3), Applicant’s remarks are not found persuasive since Germain and Rooney need not teach the features already disclosed in Tognetti. Germain and Rooney are not relied upon for teaching cryopreservation at -80°C as this limitation is taught by Tognetti, as discussed immediately above. In response to applicant's arguments against Germain and Rooney individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Germain is relied upon for addressing the time period the obtained skin segments are incubated in the cryopreservative and cryoprotectant (glycerol), i.e., for 45 minutes to 2 hours prior to cryopreservation for up to 2 years until surgery (Fig. 1).
Rooney is relied upon for addressing it was well known in the art to conduct gamma-irradiation of skin samples in dry ice for cold chain maintenance (Abstract and page 665: 2.1.2 Group B, 2.1.3 Group C, 2.1.4 Group D, 2.1.5 Group E).
Conclusion
No claim is allowed. No claim is free of the prior art.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633