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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Action is in response to the papers filed on March 30, 2026 for a Request for Continued Examination. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submission filed on March 30, 2026 has been entered.
Claims 1 and 17 have been amended, claims 10-16, 18-19 have been cancelled, and claims 20-28 are newly filed in Applicant’s amendment filed on March 30, 2026. Claims 1 and 17 are independent claims.
Therefore, claims 1-4, 9, 17, 20-28 are currently under examination to which the following grounds of rejection are applicable.
Priority
This application is a continuation of 17/725,222 filed on 04/20/2022, and claims the benefit under 35 U.S.C. 119(e) of prior-filed to U.S. provisional application 63/182,590, filed on April 30, 2021. Thus, the earliest possible priority for the instant application is April 30, 2021.
Response to Arguments
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments:
Claim Rejections - 35 USC § 112(a)
In view of Applicants’ amendment to the claims dated March 30, 2025, of which claims 1 and 17 have been amended, claims 10-16, 18-19 have been cancelled, the rejection to claims 1-4, 9 and 17 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement have been rendered moot. The rejection to now cancelled claims 10-16, 18-19 have been rendered moot.
The Applicant has accurately provided support that the Specification describes silver nanoparticles, and has amended the claims to overcome the other new matter situations that were described previously. The Specification cites silver nanoparticles as “Ag nanoparticles”, and therefore it was not identified previously. Furthermore, Ag nanoparticles was spelled incorrectly in an earlier filed Specification, but has been amended properly in the Specification filed 08/20/2025.
Claim Rejections - 35 USC § 103
In view of Applicants’ amendment to the claims dated March 30, 2025, of which claims 1 and 17 have been amended, claims 10-16, 18-19 have been cancelled, the rejection to claims 1-4, 9-14, and 17 rejected under 35 U.S.C. 103 as being unpatentable over Wood et al. in view of Broeckx et al. and Wood et al, and further evidenced by RECELL Procedure Guide (of record) and Quick et al., have been withdrawn.
The withdrawn rejections are in view of the amendments to claims 1 and 17. Applicants' arguments are moot in view of the withdrawn rejection. A response to any argument pertaining to a new or maintained rejection can be found below.
Double Patenting
In view of Applicants’ amendment to the claims dated March 30, 2025, of which claims 1 and 17 have been amended, claims 10-16, 18-19 have been cancelled, the double patenting rejection to now cancelled claims 18 and 19 have been rendered moot.
New Grounds of Objection/Rejection
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 1-4, 9, 17, 20-28 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.
Claims 1 and 17 recite “a selection process having predetermined thresholds configured to identify cells with sufficient therapeutic potential for skin regeneration”, yet there is no mention of these “predetermined thresholds”. It is unclear in the claim if these thresholds are the characteristics recited in relation to total cell count, cell viability, total viable cell count, and median live cell diameter of the viable cells, or rather include other characteristics, or rather pertain to entirely different thresholds not recited in the claims.
Claim Rejections - 35 USC § 103
Claims 1-4, 9 , 17, 20-28 are newly rejected under 35 U.S.C. 103 as being unpatentable over Wood et al (Burns 38.1 (2012): 44-51; hereinafter ‘Wood’; of record) in view of Zieger et al. (Military Medicine, Volume 182, Issue suppl_1, March 2017, Pages 376–382) and Wood et al. (Burns 33.6 (2007): 693-700; hereinafter ‘Wood-2’; of record), and further evidenced by Sun et al. (Cell 9.4 (1976): 511-521), Gereli et al. (Knee Surgery, Sports Traumatology, Arthroscopy 26.8 (2018): 2498-2504), RECELL Procedure Guide (of record) and Quick et al. (U.S. Pub. US-2015/0079153-A1; of record (respective patent to RECELL)).
Claim 1 is directed to a cell suspension therapeutic, comprising: a population of cells isolated from freshly disaggregated tissue, the population of cells identified via a selection process having predetermined thresholds configured to identify cells with sufficient therapeutic potential for skin regeneration, wherein the population of cells comprises at least 550,000 total cells per milliliter, wherein the population of cells has at least 30% viability, wherein at least 300,000 cells per milliliter are viable, and wherein the median live cell diameter of the viable cells is greater than or equal to 9 micrometers, wherein the population of cells comprises dermal and epidermal cells, wherein the selection process is configured such that cell populations meeting the predetermined thresholds are identified, and wherein the population of cells is configured to be applied to a full thickness recipient region on a patient within two hours after the selection process; an effective amount of buffer; a synthetic polymer microfibrous construct comprising silver nanoparticles; and an animal-derived acellular xenograft scaffold, wherein the cell suspension therapeutic is configured to be administered to the full-thickness recipient region on a patient.
Claim 17 is similar to claim 1, but does not require an animal-derived acellular xenograft scaffold, and is not limited to the microfibrous construct comprising silver nanoparticle as being synthetic.
M.P.E.P. § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 111 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Claims 1 and 17 are directed to a composition, however, it contains various product-by-process limitations such as the following:
“the population of cells identified via a selection process having predetermined thresholds configured to identify cells with sufficient therapeutic potential for skin regeneration”
“wherein the selection process is configured such that cell populations meeting the predetermined thresholds are identified”
It is not clear how these limitations impart differences in the structure of the claimed composition, and are therefore not being considered herein. However, the characteristics pertaining to structure of the composition such as total cell count, cell viability, total viable cell count, and median live cell diameter of the viable cells that are recited in the claim are being considered.
Regarding claims 1 and 17, Wood teaches a cell suspension therapeutic, comprising: a population of cells isolated from freshly disaggregated tissue (“The RECELL® device was used to harvest cells from a 2 cm2 piece of split-thickness skin isolated using a dermatome. The resulting cell suspension was analysed for cell yield, cell type, viability over time, proliferative potential and reproducibility.” (Abstract: Methods)), wherein the population of cells comprises at least 550,000 total cells per milliliter, wherein the population of cells has at least 30% viability, wherein at least 300,000 cells per milliliter are viable (“Average viable cell yield was 1.7 × 106/cm2 of tissue, with 75.5% of the total cell isolate viable.” (Abstract: Results); “Average viable cell yield at time of harvest (pre-spray) was 3.4 × 106 ± 0.76 × 106 (data presented as mean ± standard deviation, Fig. 1A) (Sec. 3.1)), wherein the population of cells comprises dermal and epidermal cells (“cells isolated from the dermal epidermal junction which are capable of adhering to a wound surface and proliferating to augment healing.” (p 45, par 3)) and an effective amount of buffer (“suspended in 10 ml of compound sodium lactate irrigation solution” (Sec. 2.1)).
In reference to the limitation “wherein the population of cells is configured to be applied to a full-thickness recipient region on a patient within two hours after the selection process”, Wood teaches that faster wound coverage reduces the incidence of infection and can lead to better aesthetic outcomes for patients, and that traditional approaches require “ex vivo cell culture and consequently a prolonged wait between cell harvesting and application. In addition, many methods of cell harvesting require many hours or even overnight incubations for cell separation, which reduces the possibility of use in an immediate clinical procedure.” (Discussion, par 1). The method taught by Wood uses the ReCell® device allows for immediate clinical use of harvested cells and thereby promote faster wound healing led to the use of autologous, un-cultured cells immediately post-harvesting from the donor site (Discussion, par 1).
As evidenced by the RECELL manual, on page 5 it describes the therapeutic suspension as being ready in around 30 minutes, and with four samples in around 1 hour. Therefore, Wood teaches the population of cells is configured to be applied in less than two hours.
Wood does not teach wherein the median live cell diameter of the viable cells is greater than or equal to 9 micrometers, a synthetic polymer microfibrous construct comprising silver nanoparticles; and an animal-derived acellular xenograft scaffold.
In reference to the synthetic polymer microfibrous construct comprising silver nanoparticles, Zieger teaches addition of silver nanoparticles to dermal substrates, i.e. Integra® wound matrix (in relation to the claimed synthetic polymer microfibrous construct), suppressed bacterial growth in a concentration dependent manner while not significantly impacting cell proliferation, and therefore wound healing outcomes (abstract).
In reference to the median live cell diameter of the viable cells being greater than or equal to 9 micrometers, it is noted that Wood teaches the disaggregated tissue pre-spray as comprising 64.3 + 28.8 % keratinocytes, and 30.3 + 14.0 % fibroblasts as listed in Table 1. As evidenced by Sun et al., keratinocytes are described as having an average diameter of around 14 µm in size or greater (Summary; Fig. 4), and as evidenced by Gereli et al., fibroblast are described as having average diameters greater than 20 µm in size (Fig. 4c). Therefore, it can be expected that the composition taught by Wood comprises a median live cell diameter of the viable cells being greater than or equal to 9 µm based on the majority of cells in the composition being keratinocytes and fibroblasts.
In reference to an animal-derived acellular xenograft scaffold, Wood-2 teaches a non-cultured autologous cell suspension prepared similarly to as Wood described above, and furthermore wherein the cell suspension is combined with the Integra® dermal regeneration template to repair full-thickness skin wounds (which is also employed by Zieger). Integra® is described as “comprises a layer of cross-linked bovine collagen and shark glycosaminoglycans that facilitates the formation of a reticular dermis [10–12]. A secondary layer is composed of a synthetic polysilicoxane polymer (silicone) layer that acts as a temporary pseudo-epidermis.” (p 694, col 1). Additionally, all sites were covered with Xeroform® dressings (Tyco Healthcare, USA) which is a fine mesh gauze occlusive dressing impregnated with petrolatum and 3% Xeroform (Bismuth Tribromophenate) (p 695, col 2). The methods describe “Surgical sites were cleaned with chlorhexidine diacetate and isopropyl alcohol and both animals received a single dose of Cefazolin 22 mg/kg IV as a prophylactic antibiotic.” (p 694, col 2). Lastly, the outcomes of using Integra® with a cell suspension “demonstrate that cells remain viable, migrate through the Integra® template and self-organize into differentiated epidermis. The results indicate that combining Integra® with autologous cells facilitates one-step skin reconstruction of a full-thickness skin wound.” (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cell suspension therapeutic taught by Wood to incorporate a synthetic polymer microfibrous construct comprising silver nanoparticles (as taught by Zieger) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. The inclusion of silver nanoparticles comprised in a synthetic polymer microfibrous construct taught by Zieger would have led to the predictable results with a reasonable expectation of success of the cell suspension therapeutic taught by Wood as having reduced bacterial contamination without impacting the cellular proliferation as this is the main finding described by Zieger when silver nanoparticles were employed.
Secondly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have clarified the composition as comprising a median live cell diameter of the viable cells as greater than or equal to 9 micrometers based on the teaching of Wood wherein the majority of the composition comprises keratinocytes and fibroblasts, and as evidenced by Gereli and Sun, these cells types are expected to have larger cell sizes than the claimed 9 µm. Therefore, the median cell diameter taught by Wood is expected to be larger than then claimed 9 µm.
Lastly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Wood’s cell suspension therapeutic by combining it with an animal-derived acellular xenograft scaffold based on Wood-2 teaching such combination as seen with a cell suspension prepared by Wood-2’s RECELL with Integra®, which has a layer of cross-linked bovine collagen and shark glycosaminoglycans and a layer of synthetic polysilicoxane polymer (silicone). The modification would have been obvious based on the improved outcomes described by Wood-2 in repairing full-thickness skin wounds.
Regarding claim 2, dependent on claim 1, and claim 20, dependent on claim 17, Wood teaches wherein the tissue comprises skin tissue as described above in the claim 1 rejection.
Regarding claim 3, dependent on claim 2, and claim 21 dependent on claim 20, Wood teaches wherein the population of cells comprises keratinocytes, melanocytes, and fibroblasts (Table 1, Sec. 3.3); pan-cytokeratin identified keratinocytes, Collagen I FACS identified fibroblasts, and S100/MelanA double-labelling identified melanocytes (Fig. 3).
Regarding claim 4, dependent on claim 1, and claim 22, dependent on claim 17, the claims are directed to product-by-process limitations by reciting the process of obtaining the composition recited in claims 1 and 17. As described above, the determination of patentability is based on the product itself and is not dependent on its method of production.
Regardless, Wood teaches wherein the population of cells is obtained by a process comprising: harvesting a split-thickness skin sample using a dermatome (“a piece of split thickness skin (split skin graft, SSG) obtained using a 0.006 in. gauge and Zimmer Micro 100 Dermatome.” (Sec. 2.1)); in which the sample were then processed using a RECELL device, following the manufacturer’s instructions. After processing, the isolated cells were suspended in a sodium lactate irrigation solution (Sec. 2.1).
As evidenced by the RECELL Instruction Manual, creation date of September 18, 2018 and latest modification date of September 28, 2018, it describes the following step for processing a harvested skin sample: Stage A employs enzymatic processing wherein a skin sample is incubated in a well with a heated enzyme (step 1), followed by a test scrape to determine aggregation status (step 2), and depending on the status of the previous step, rinsing the skin sample in a well comprising a prepared buffer (step 3). Stage B employs mechanical processing in which a buffer is prepared (step 4), the skin sample is mechanically separated via scalpel and some buffer (step 5), buffer is added to form cell suspension and aspirated into a syringe, and then the suspension is filtered through a filter (p 3, Stages A, B).
In reference to the filter size, as evidenced by Quick et al. in the related Patent Application for this specific RECELL device as described in US-2015/0079153-A1, it states: “the filter size can be between 50 μm and 200 μm, between 75 μm and 150 μm, or at about 100 μm.” (par 0056).
Based on the RECELL device instruction manual and US-2015/0079153-A1, Wood teaches these steps by stating to use the manufacturer’s instructions.
Regarding claim 9, dependent on claim 1, and claim 23, dependent on claim 17, Wood teaches wherein the cell suspension therapeutic is administered to the recipient region at point-of-care, as evidenced by the RECELL device instruction manual, it describes the device is to be used “by an appropriately-licensed healthcare professional at the patient’s point-of-care.” (p 4).
Regarding claims 24-26, the rejection above describes how Zieger uses silver nanoparticles with the Integra wound matrix which is made of type I collagen and chondroitin 6-sulphate in a 92:8 ratio (p 377, col 1; p 378, col 2). Furthermore, Wood-2 describes “Integra® comprises a layer of cross-linked bovine collagen and shark glycosaminoglycans that facilitates the formation of a reticular dermis [10–12]. A secondary layer is composed of a synthetic polysilicoxane polymer (silicone) layer that acts as a temporary pseudo-epidermis.” (p 694, col 1). Therefore, it can be seen that the references teach wherein the microfibrous construct is a synthetic polymer microfibrous construct (claim 24), a biological microfibrous construct (claim 25), and an animal-derived acellular xenograft scaffold (claim 26) since the Integra scaffold comprises all these elements. Moreover, Wood-2 employs test Group A wherein cells were adhered to a biological collagen side, and Group B that were adhered to a synthetic silicone side of a scaffold (Table 1).
Regarding claims 27 and 28, Wood teaches wherein the cells were stained as seen in using Trypan Blue solution to assess yield and viability, and a different solution was used with FACS for cell type identification (Sec. 2.3, 2.4).
Response to Applicants' Arguments as they apply to rejection of claims 1-4, 9-14, and 17 rejected under 35 USC § 103
Starting on page 6 of the remarks filed on March 30, 2026, Applicants essentially argue the following in relation to claims 1 and 17:
Applicants' state none of the prior art references teach “silver nanoparticles.”
Applicant acknowledges in the previous Office Action it is described that: “the claim is directed to a composition and not a method, and therefore there is no weight given to the steps of derivation unless it impacts the structure of the composition that is different than the prior art teachings. This is not the case for the instant application as the prior art teachings teach the claimed composition.; and Applicant disagrees based on Broeckx not adequately teaching a median live cell diameter of the viable cells greater than or equal to 9 micrometers, and why it would have been obvious to a person of ordinary skill to achieve a certain median cell diameter value in addition to the other thresholds, or how a person of ordinary skilled in the art would have gone about achieving that median cell diameter value in addition to the other thresholds with a reasonable expectation of success.”
In response to the argument it has been fully considered but is not persuasive due to the following reasons:
Regarding the first presented argument, wherein the Applicant states that none of the references teach silver nanoparticles, the Examiner agrees, and therefore the rejection has been withdrawn in addition to the 112(a) rejection regarding this element as support has been adequately provided in the amended Specification that now states “Ag nanoparticles”. However, a new rejection has been made wherein Zieger et al. provides this teaching as described above, wherein silver nanoparticles are taught as preventing bacterial contamination, and therefore the inclusion of silver nanoparticles would be an obvious choice to improve the composition taught by Wood.
Regarding the second presented argument, the new grounds of rejection no longer employ Broeckx to teach the median cell diameter, and now is supported by Sun and Gereli that teach the sizes of keratinocytes and fibroblasts as being larger than the claimed 9 µm. Wood teaches the cell suspension therapeutic as being comprised of largely keratinocytes and fibroblasts, and a small amount being melanocytes. Therefore, it is expected that this composition has a median live cell diameter of the viable cells as greater than or equal to 9 micrometers based on it described by Sun and Gereli that these viable cell types have cell diameters larger than this range. Furthermore, it would be obvious to not have cells smaller than this range based on the expectation that they would largely constitute cell debris for which Wood tries to limit as it may be potentially toxic cell debris (p 49, col 1). Altogether, these references provide evidence that Wood teaches this limitation despite not explicitly stating the median cell diameters.
Conclusion
Claims 1-4, 9, 17, and 20-28 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634