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 .
A copy of the full document, Ruvolo et al. (Skin Pharmacol Physiol 20(6):313-21) for which the abstract only had been available previously, has been attached with this action.
Status of the Claims
Pursuant to the amendment dated 07/01/2026, claim 2 has been cancelled. Claims 1, 3, 9, 10, 12, 14, 17, 22, 23, 24, 27, 28, 30, 32, 38-41 and 42 are pending. Claims 23, 24, 27, 28, 30, 32, and 38-41 stand withdrawn without traverse.
Claims 1, 3, 9, 10, 12, 14, 17, 22, and 42 are under current examination in view of the species elections (a) tissue: skin; (b) polymer: PGA; and (c) cell: stem cells
All rejections not reiterated have been withdrawn.
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 1, 3, 9, 10, 12, 14, 17, 22, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Hansbrough et al. (US5460939; issue date: 10/24/1995); in view of Da Silva Ferreria (US20140147420; publication date: 05/29/2014), Doersam et al. (Advanced Materials Technol Vol 7, pages 1-28; published 11/2022), and further in view of Ruvolo et al. (Skin Pharmacol Physiol 20(6):313-21; publication year: 2007).
The claims are examined in view of the following species elections:
(a) tissue: skin;
(b) polymer: PGA; and
(c) cell: stem cells
With regard to claim 1, Hansbrough discloses a living skin replacement (abstract; elected species of tissue) formed from human neonatal fibroblasts cultured on three-dimensional knitted mesh [nylon in examples] (col 3, lines 35-40) that is preferably comprised of polyglycolic acid (PGA; elected species of biocompatible fiber) for in vivo use (col 7, lines 20-23). With regard to the limitation requiring the scaffold to have a microscopic and macroscopic porosity, the macroscopic porosity is described in the instant specification as follows: “The macroscopic porosity refers to the larger spaces in between knitted structures (typically 100 micrometers-2 millimeters) and varies with stretching.” As Hansbrough discloses a knit structure, Hansbrough’s scaffold also possesses macroscopic porosity. Microscopic porosity is described in the instant specification as follows: “For microscopic porosity, the materials have sufficient space or texture to house cells and/or other biological materials.” As Hansbrough’s scaffold also has structure sufficient to house cells, this limitation is also considered inherent in Hansbrough’s scaffold. Moreover, Hansbrough discloses that “Certain materials, such as nylon, polystyrene, etc., are poor substrates for cellular attachment. When these materials are used as the three-dimensional support matrix, it is advisable to pre-treat the framework prior to inoculation of stromal cells in order to enhance the attachment of stromal cells to the framework.” (col 7, lines 7-10) Thus, Hansbrough teaches creating microporous structures if they are not present in the scaffold material initially, i.e. fibers with surface sufficient for cellular attachment as the term is used in the instant application, if they are not initially present.
Hansbrough does not disclose the elected species of cell, stem cells.
Da Silva Ferreria teaches that inclusion of stem cells in compositions for wound healing improves outcome (abstract, 0003).
It would have been prima facie obvious to include stem cells in Hansbrough’s skin replacement. The skilled artisan would have been motivated to do so in order to improve healing of the skin and had reasonable expectation of success because Hansbrough demonstrates cellular infiltration and growth on the scaffold and discloses that additional cells may be added (col 9, lines 14-25).
Hansbrough does not discuss matching elasticity value and anisotropy value to a target tissue (elected species: skin).
Doersam describes many benefits of knitted scaffolds for tissue engineering (title, pages 6 and 7). Doersam teaches that knit structures can exhibit different mechanical properties between axial and transverse directions emphasizing their anisotropic properties, which makes them a good choice for applications that emulate the intrinsic anisotropy of tissues (page 6, left col).
Ruvolo teaches that skin has anisotropic elasticity (abstract).
It would have been prima facie obvious to design Hansbrough’s knit PGA scaffold to match the anisotropic elasticity of skin. The skilled artisan would have been motivated to do so in order to align the elasticity of the replacement skin with the surrounding natural skin to improve compatibility and would have had reasonable expectation of success because Doersam discloses this had been achievable by selecting the knitting parameters (page 6, right col) as of the instant effective filing date.
With regard to claim 1, the instant specification states: “The ability of the knit scaffolds to mimic the natural ‘uncrimping’ effect of tissue through inherent self-pleating rather than stretching provides unique advantages to the cells growing within the scaffold and avoiding the local stretching of cells at the micro level.” Thus, the features of claim 2 appear to be inherent qualities of any knit structure, which when under strain will open the spaces between stitches (uncrimping) before the fibers themselves stretch elastically.
With regard to claim 3, the examiner considers it a matter of routine, following the guidance provided in the cited prior art to optimize the elasticity and anisotropy of Hansbrough’s skin replacement to match that of a particular patient’s skin. See MPEP 2144.05.
With regard to claim 9, as noted above, Hansbrough’s scaffold contains neonatal foreskin fibroblasts, and it would have been prima facie obvious to also include stem cells within the scaffold.
With regard to claim 10, the neonatal foreskin fibroblasts deposit collagen over the scaffold (col 9, lines 38-67).
With regard to claim 12, Doersam teaches adjusting various parameters including yarn characteristics and stitch design (page 6, right col) and teaches that loop configuration defines the porosity, pore size, and pore distribution as well as mechanical properties (page 7, left col). For example, stitch density (i.e. number of stitches per length) affects mechanical properties with increasing density corresponding to increased strength (page 7, left col). Also fineness, linear density, twist and morphology of the yarn and their cross-sectional shape (yarn size) also affect micro-level properties (page 7, left col).
With regard to claim 14, as noted above, Hansbrough teaches PGA for in vivo application.
With regard to claim 17, Doersam discusses wale density and course density as some of the factors that can be optimized to adjust the mechanical properties of a knit tissue engineering scaffold (page 6, right col). As stitch length determines wale density and course density (see instant specification “knit type may be further altered by varying the stitch length, which effectively modifies the number of wales, and/or number of courses in a local region of the knit”) the examiner considers Doersam to teach optimization of stitch length to control the mechanical properties of the scaffold. For this reason, the limitation “the three-dimensional knit scaffold has a stitch length of between 1mm to 25 mm” to be a parameter that one having ordinary skill would have optimized as a matter of routine. See MPEP 2144.05.
With regard to claim 22, the examiner considers it obvious to shape the skin replacement to fit the area that it is needed (i.e. it comprises a shape or pattern that matches an area of the body where the scaffold is implemented). Moreover, the language recited in claim 22 does not place any specific limitation on the size or shape of the scaffold.
With regard to claim 42, the instant specification defines “primed” as follows: “As used herein, the term “primed” refers to an initial disturbance of the knit scaffold such that following the disturbance, the knit scaffold exhibits repeatable parameters (e.g., repeatable measurements of a stress/strain curve).” Claim 42 recites product by process language: “the … scaffold is primed for use”. According to MPEP 2113: product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. “The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art” therefore claim 42 is interpreted to limit the scaffold to one that repeatably stretches and elastically returns to it’s original shape. As knit scaffolds of the prior art are thus characterized, the examiner does not consider claim 42 to patentably define over the scaffold rendered obvious by Hansbrough, Da Silva Ferreria, Doersam, and Ruvolo.
Response to Arguments
Applicant's arguments filed 07/01/2026 have been fully considered but they are not persuasive.
On page 9, Applicant argues that claim 1 was not obvious over the cited prior art because the combination would not produce the claimed invention, specifically that the three dimensional knit scaffold has three characteristic regions of a stress/strain curve which mimic the target tissue and correspond to (i) uncrimping of the knit; (ii) transitioning to stretch; and (iii) stretching of the fibers which compose the knit. Applicant argues that Hansbrough simply teaches a knit mesh sized to enable cell stretching attached to a rubber backing as a temporary wound backing; Doersam describes textiles and how they can be used to mimic tissue. Applicant argues that neither Doersam et al. nor Hansbrough et al. disclose or suggest that a knit scaffold should include multiple parameters based on a stress/strain curve to actually mimic the tissue. The invention is based, at least in part, on the understanding of the stress/strain properties of tissue and accounting for those properties in the knit structure, which was not disclosed in the prior art. The knit material is based upon the desired stretchability (i.e., elasticity), ultimate strength, size, degradation rate, porosity, and/or level of uncrimp before stretching of the knit scaffold, in order to match the properties of the host tissue. Applicant describes the behavior of natural tissue has having three regions of stretch that are replicated by the instant invention. Applicant asserts that the prior art does not recognize these properties. On page 10, Applicant argues that, contrary to the examiner’s position that the three regions of a stress/strain curve are inherent properties of a knit scaffold, the instant invention obtains a previously unappreciated matching of scaffold to tissue by tuning knit structure, knit type, stitch length, filament denier, number of filaments, number of ends together in a single yarn and type of biocompatible material to produce a scaffold having a particular or a range of elasticity. Applicant argues that these features are not explicitly or inherently in Doersam or any of the other art.
The examiner respectfully disagrees with Applicant’s position that the prior art does not direct the artisan of ordinary skill towards the functional limitations recited in the claim. Firstly, Hansbrough’s objective is generally mimicking natural tissue, see e.g. col 6, lines 7-11 “… bear remarkable structural and functional similarity to living skin grafts…”. Moreover, the relationship between the variables like knit structure, knit type, stitch length, filament denier, number of filaments, number of ends together in a single yarn and type of biocompatible material were recognized at the time the instant invention was filed to affect the mechanical properties of knit scaffolds in a manner that could be adjusted to best suit the tissue being replaced. This is taught by Doersam, and discussed in detail in the rejection of the dependent claims above, in particular instant claims 12 and 17. For clarity, the examiner’s position is that knit scaffolds inherently possess the three distinct regions on a stress/strain curve due to the knit structure itself that the instant specification describes as imparting these three characteristic regions. The prior art teaches matching the scaffold’s mechanical properties/elastic stretching to natural tissue by optimizing variables including yarn characteristics, stitch design, loop configuration, porosity, pore size, pore distribution, stitch density, fineness, linear density, twist morphology of the yarn, cross-sectional shape of the fibers, wale density, and course density, all taught Doersam as factors to optimize the mechanical properties of the scaffold. Particularly in combination with Hansbrough, who teaches the premise of skin replacement with knit structure, and Ruvolo teaches that skin has anisotropic elasticity (abstract), one having ordinary skill would have found the necessary guidance in Doersam to match the properties of a knit scaffold to any tissue, including skin.
On page 9, Applicant argues that Da Silva Ferreria and Ruvolo do not make up for the deficiencies in Hansbrough and Doersam.
In response to applicant's arguments against the references 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).
On page 10, Applicant argues that absent the teachings of the instant specification the artisan of ordinary skill would not have arrived at the claimed invention.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
On page 10, Applicant argues that Doersam is related to designing textile-based scaffolds for long term implants and Hansbrough is designed to serve as a temporary wound dressing for serious skin wounds. Applicant argues that the two materials have different purposes and absent further teachings one would not expect their teachings to be compatible.
In response to applicant's argument that Hansbrough and Doersam are nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, both references are directed to knit scaffolds for tissue mimetic implants. The examiner notes that Hansbrough discusses various durations of use and the disclosure is not limited to short term use (see e.g. col 3, lines 13-15, which discuss long term persistence of the tissue replacement; col 3, lines 50-52, which discusses “permanent” skin coverage); and the foregoing notwithstanding, the structural benefits of knit would have been relevant to both long and short term use tissue replacements. The examiner maintains the opinion that Hansbrough and Doersam are sufficiently related to each other and to the instant invention to have been within the purview of the artisan of ordinary skill.
On page 11, Applicant argues that the rubber backing of Hansbrough distorts the knit properties and that even if the artisan of ordinary skill were motivated to modify the knit based on the teachings of Doersam, there would have been no reasonable expectation of success in modifying the properties of the knit to achieve any of the properties based on the teachings of Doersam.
The examiner respectfully disagrees. The artisan of ordinary skill, e.g. an individual with a Ph.D. in bioengineering, would have the background understanding that the backing layer in Hansbrough could be selected, as needed, to accommodate any stretching of the material underneath. Hansbrough even describes one application where the non-perforated upper layer is eventually removed as the graft becomes incorporated with living tissue, which would suggest to the artisan of ordinary skill, a highly intelligent and well-educated individual, that the attachment between the knit mesh and the non-perforated covering could be variable in strength, as needed.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617
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