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 .
The first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ) apply to any application for patent, and to any patent issuing thereon, that contains or contained at any time—
(A) a claim to a claimed invention that has an effective filing date on or after March 16, 2013 wherein the effective filing date is:
(i) if subparagraph (ii) does not apply, the actual filing date of the patent or the application for the patent containing a claim to the invention; or
(ii) the filing date of the earliest application for which the patent or application is entitled, as to such invention, to a right of priority under 35 U.S.C. 119, 365(a), or 365(b) or to the benefit of an earlier filing date under 35 U.S.C. 120, 121, or 365(c); or
(B) a specific reference under 35 U.S.C. 120 , 121, or 365(c), to any patent or application that contains or contained at any time a claim as defined in paragraph (A), above.
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 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.
Status of the Claims
Claim(s) 1-2, 6, 8, 10-17, 19-20, and 22-23 is/are pending. Claim(s) 11-17 is/are withdrawn. Claim(s) 3-5, 7, 9, 18, and 21 is/are canceled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submission filed on 11/3/2025 has been entered.
Response to Arguments
Applicant’s arguments, filed 11/3/2025, with respect to the 35 USC 112(b) rejections have been fully considered and are persuasive. The 35 USC 112(b) rejections of claims 9 and 22 has/have been withdrawn due to the Applicant’s 11/3/2025.
Applicant’s arguments with respect to claims 1-2, 6, 8, 10, 19-20, and 22-23 have been considered but are moot in view of the new grounds of rejection. The Examiner notes the change in prior art was necessitated by the Applicants amendments.
As previously cited prior art is re-used herein, the following responses are to Applicant’s arguments that also apply to the prior art as used herein.
Applicant argues the following features are not taught by the prior art.
A continuous elongated polymeric electrospun fiber (claim 1)
A subcellular material in the intermediate layer (claim 1)
Intrascopic removal (claim 23)
Applicant does not include any additional arguments as to why/how any feature is not taught. Thus, the Examiner notes the teaching of each element is found below in the prior art rejection section.
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.
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 1-2, 6, 8, 10, 19, and 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Leong, et al (Leong) (US 2010/0093093 A1) in view of Zhu, et al (Zhu) (Circumferentially aligned fibers guided functional neoartery regeneration in vivo, Biomaterials, v61, pp 85-94 (2015)) and further in view of Ehrenreich, et al (Ehrenreich) (US 2011/0230948 A1).
Regarding Claim 1, Leong teaches a multilayer scaffold device (e.g. [0064]) comprising:
a luminal electrospun layer (radially innermost layer), the luminal electrospun layer configured to provide an epithelium formation inducing environment on the luminal electrospun layer of the multilayer scaffold device (e.g. [0064], [0099]), the luminal electrospun layer having an inwardly oriented surface (luminal layer) and a luminal layer region proximate to and inward of the inwardly oriented surface (abluminal surface of the luminal layer, inward into the thickness of the device), the inwardly oriented surface defining a hollow interior (e.g. [0019], the device is formed on a mandrel and thus has a hollow interior where the mandrel is located during manufacturing, creating a hollow, tubular structure) the luminal electrospun layer has a luminal electrospun layer thickness (the layer inherently has a (radial) thickness), wherein the luminal electrospun layer comprises a continuous elongated polymeric electrospun fiber (e.g. [0064], [0099], electrospun layers inherently have fibers; [0077], polymeric material; [0043]; continuous fiber seen in Figure 1, oriented with the label at the top, the top row, right had side), the continuous elongated polymeric electrospun fiber of the luminal electrospun layer having a first end, a second end opposed to the first end and an intermediate region located between the first end and the second end (the fiber inherently has these sections), wherein the continuous elongated polymeric electrospun fiber present in the luminal electrospun layer is oriented such that segments of the continuous elongated polymeric electrospun fiber of the intermediate region of the luminal electrospun layer are in overlaying relationship to one another (e.g. Figure 1, oriented with the label at the top, the top row, right had side; [0112] indicates the prior descriptions are on a non-rotating mandrel (i.e. a stationary mandrel); the section of Figure 1 shows a single fiber being deposited back and forth longitudinally, thus on a stationary mandrel different segments of the fiber overlay each other as deposited) and contact each other forming luminal electrospun layer points of contact such that between 1,000 and 100,000,000 points of contact per cubic millimeter are defined in the luminal electrospun layer (e.g. annotated Figure 3c below, there are a plurality of contact points between the electrospun fibers; since the scale bar represents 100 mm or 0.1 millimeter, the area of a square scale bar is 0.01 mm squared; therefore, a square millimeter would contain at least 1,000 contact points);
an exterior electrospun layer (radially outermost layer), the exterior electrospun layer located radially exterior to the luminal electrospun layer (e.g. [0064]), the exterior electrospun layer having an outwardly oriented surface (abluminal/radially outermost surface), the exterior electrospun layer configured to induce formation of non-epithelial tissue (e.g. [0064], [0094], configured for muscle cells), wherein the exterior electrospun layer comprises a continuous exterior electrospun layer elongated polymeric electrospun fiber (e.g. [0043]), the continuous exterior electrospun layer elongated polymeric electrospun fiber having an average pore size between 10.0 mm and 100.0 mm (e.g. [0094], 60 mm -150 mm for SMCs, which are on the exterior electrospun layer (see cell populations below)); and
at least one intermediate layer interposed between the luminal electrospun layer and the exterior electrospun layer (e.g. [0064]), the intermediate layer defining a region acting on the luminal electrospun layer and the exterior electrospun layer wherein formation of epithelial tissue and non-epithelial tissue on the luminal electrospun layer and exterior electrospun layer are organized (as broadly claimed, the intermediate layer acts on and organizes the tissue formation by being a physical partition between the luminal and exterior layers) and subcellular material is maintained and transit(s) therethrough (e.g. [0099], the pore structure allows for proliferation of cells through the layer; [0088]-[0089] discusses adding components of the extracellular matrix to the pores of the scaffold, thus these materials are moved into the intermediate layer at that time; further [0089] also discloses the extracellular matrix material recruiting other cells; thus, because cellular sized particles can pass through the region, so can subcellular material because subcellular is smaller than cellular), the intermediate layer having a plurality of pores defined therein (e.g. [0064], the openings through which cells infiltrate the layers), the plurality of pores having an average pore size between 1 mm and 5 mm (e.g. [0094]), the at least one intermediate layer that is interposed between the luminal electrospun layer and the exterior electrospun layer comprises at least one elongated polymeric electrospun fiber (e.g. [0064], [0099], electrospun layers inherently have fibers; [0077], polymeric material; [0043]), the at least one elongated polymeric fiber in the intermediate layer has a first end, a second end opposed to the first end and an intermediate region located between the first end and the second end (the fiber inherently has these sections), wherein the intermediate region of the elongated polymeric fiber of the intermediate layer is oriented such that segments of the intermediate region of the intermediate layer contact each other forming between 2,000 and 200,000,000 points of contact per cubic millimeter between different locations of the electrospun fiber in the intermediate electrospun layer (e.g. annotated Figure 3c below, there are a plurality of contact points between the electrospun fibers; since the scale bar represents 100 mm or 0.1 millimeter, the area of a square scale bar is 0.01 mm squared; therefore, a square millimeter would contain at least 2,000 contact points) and defines the plurality of pores in the intermediate electrospun layer (e.g. [0064], the openings through which cells infiltrate the layers), the pores have an average pore size that is at least 25% less than the average pore size of pores defined in the exterior electrospun layer (e.g. [0094], when the average pore size exterior electrospun layer is 150 mm and the intermediate layer average port size is 60 mm, the intermediate layer average pore size is 50% less than those of the exterior electrospun layer), at least a portion of the pores present in the luminal electrospun layer are through the plurality of pores within the luminal layer (e.g. Leong, Figures 3b-c, the through holes have a black background) communicating with pores defined in the intermediate electrospun layer (since the pores are through pores, they inherently go through to the immediately adjacent layer, which is the intermediate electrospun layer);
a first population of cells comprising a first cell type adhering to the inwardly oriented surface defined on the luminal electrospun layer (e.g. [0097], bone marrow stem cells are MSCs, which can be differentiated into the epithelial cells noted supra) the first population of cells comprising the first cell type further present as cell colonies (e.g. [0097], [0099], the cells that grow at this layer inherently grow in groups as they divide and thereby for colonies adhered to the inwardly oriented surface) in the luminal layer region that is located proximate to and inward of the inwardly oriented luminal surface (e.g. [0099], the cells are throughout each layer and therefore at the luminal layer region); and
a second population of cells, wherein the second populations of cells comprises a second cell type and adheres to the outwardly oriented surface of the exterior electrospun layer (e.g. [0099], [0094], SMCs) forming a cellular sheath (the layer is a tubular layer and the cells are placed on the layer and are thereby a sheath), wherein the second cell type is different from the first cell type (discussed supra, MSCs and SMCs);
wherein the intermediate layer and at least one of the luminal electrospun layer or the exterior electrospun layer are composed of a polycarbonate-based polyurethane polymeric material (e.g. [0077], combination of polycarbonate and polyurethane), and
wherein the at least one exterior electrospun layer elongated polymeric electrospun fiber present in the exterior electrospun layer is randomly oriented (e.g. [0021], the electrospinning process randomly lays down the fiber).
Leong discloses the invention substantially as claimed but fails to teach the continuous elongated polymeric electrospun fiber present in the luminal electrospun layer having a fiber diameter between 1.0 mm and 25.0 mm and the continuous exterior electrospun layer elongated polymeric electrospun fiber having a fiber diameter between 1.0 mm and 25.0 mm and the at least one elongated polymeric electrospun fiber of the intermediate layer having a fiber diameter between 1.0 mm and 25.0 mm.
Zhu teaches a fiber diameter between 1.0 mm and 25 mm (e.g. page 88, Results section 3.1, first paragraph, 18.26 ± 6.13 mm).
Zhu and Leong are concerned with the same field of endeavor as the claimed invention, namely electrospun, multi-layer grafts.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Leong such that the fiber diameter of each of the luminal electrospun layer, the exterior electrospun layer, and the intermediate layer is between 1.0 mm and 25.0 mm as taught by Zhu in order to enhance cellular adhesion due to modulating the pore size (e.g. Leong, [0061] and Zhu, page 88, Results section 3.1, first paragraph).
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Annotated Figure 3C, Leong
The combination of Leong and Zhu discloses the invention substantially as claimed but fails to teach the luminal electrospun layer has an average pore size between 10.0 mm and 100.0 mm.
Leong teaches the following pore size: [0064], [0094], epithelial cells are skin cells and layers supporting them have pore diameters of 20 mm to 125 mm.
Leong is concerned with the same field of endeavor as the claimed invention, namely electrospun, multi-layer scaffolds seeded with cells.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of Leong and Zhu such that the luminal electrospun layer has an average pore size between 10.0 mm and 100.0 mm for these cell types since it has been held that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
If not inherent that Leong in the combination of Leong and Zhu teaches between 1,000 and 100,000,000 points of contact per cubic millimeter are defined in the luminal electrospun layer and between 2,000 and 200,000,000 points of contact per cubic millimeter between different locations of the electrospun fiber in the intermediate electrospun layer, then it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of Leong and Zhu such that there are between 1,000 to 100,000,000 points of contact between different locations defined in the luminal electrospun layer and between 2,000 to 200,000,000 points of contact between different locations defined in the intermediate electrospun layer since it has been held that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
The combination of Leong and Zhu discloses the invention substantially as claimed but fails to teach the scaffold device is configured to be intrascopically removable.
Ehrenreich teaches a tubular implant made of electrospun layers (e.g. [0019], abstract), that is configured to be intrascopically removable (e.g. [0016]).
Ehrenreich and the combination of Leong and Zhu are concerned with the same field of endeavor as the claimed invention, namely tubular implants made of electrospun layers.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of Leong and Zhu such that the scaffold is configured to be intrascopically removable as taught by Ehrenreich as it is combining prior art elements according to known methods to yield predictable results (MPEP 2143(I)). Here, the results are predictable because each claimed element performs in the same manner in the combination as it does separately. Specifically, the scaffold functions as a replacement vessel having a lumen and the delivery expansion/collapsible configurations allow for minimally invasive delivery.
Regarding Claim 2, each of the luminal electrospun layer, the exterior electrospun layer, or the intermediate layer are composed of a polycarbonate-based polyurethane polymeric material (e.g. Leong, [0077], as discussed supra for claim 1).
Regarding Claim 6, the at least one exterior electrospun layer elongated polymeric electrospun fiber having a first end, a second end opposed to the first end and an intermediate region located between the first end and the second end (the fiber inherently has these sections), wherein the at least one elongated polymeric electrospun fiber present in the exterior electrospun layer is oriented such that segments of the intermediate region of the at least one elongated polymeric electrospun fiber contact each other forming between 1,000 and 1,000,000 points of contact between different locations defined in the exterior electrospun layer (e.g. Leong, annotated Figure 3c above, there are a plurality of contact points between the electrospun fibers; since the scale bar represents 100 mm or 0.1 millimeter, the area of a square scale bar is 0.01 mm squared; therefore, a square millimeter would contain at least 1,000 contact points).
If not inherent that Leong in the combination of Leong, Zhu, and Ehrenreich teaches the number of contact points being 1,000 to 1,000,000, then it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of Leong, Zhu, and Ehrenreich such that there are between 1,000 to 1,000,000 points of contact between different locations defined in the exterior electrospun layer since it has been held that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Regarding Claim 8, the pores present in the exterior electrospun layer have an average pore size between 10.0 mm and 50.0 mm (e.g. Leong, [0094]).
Regarding Claim 10, the plurality of pores in the intermediate electrospun layer (discussed supra for claim 1) communicates between the luminal electrospun layer and the exterior electrospun layer (discussed supra for claim 4), the plurality of pores present in the intermediate electrospun layer have an average pore size less than 10 mm (discussed supra for claim 1).
Regarding Claim 19, the first population of cells is located in the thickness of the luminal electrospun layer (claim 1 requires the first population be at the surface, which is also the surface of the thickness) and is present in between 50% and 100% of the thickness of the luminal electrospun layer (e.g. [0064], [0094], during infiltration there is a configuration where the cells are located as claimed) and wherein the first population of cells comprises mesenchymal stem cells (MSCs) (e.g. Leong, [0097], bone marrow stem cells are MSCs) present in a percentage greater than 40% of total cells in the first cell population (100% of the population is MSCs), wherein the MSCs organize to produce esophageal tissue in a subject (e.g. Leong, [0099]; the organization would happen when the device is placed in a subject as the cells will continue to grow).
Regarding Claim 22, the points of contact between different locations in the intermediate layer is between 750,000 and 1,000,000 per cubic millimeter (discussed supra for claim 1).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the thickness of the intermediate layer (and thereby increase the number of contact points) such that there are between 750,000 and 1,000,000 contact points per millimeter as such a modification would have been an obvious matter of design choice involving a change in the size/proportions (here, thickness) of a component. A change in size is generally recognized as being within the level of ordinary skill in the art (see MPEP 2144.04 IV).
Regarding Claim 23, the limitations of claim 23 are discussed supra for claims 1-2 and 6, except that as follows.
If not inherent that Leong in the combination of Leong, Zhu, and Ehrenreich teaches between 1,000 and 1,000,000 points of contact per cubic millimeter between different locations of the electrospun fiber in the intermediate electrospun layer, then it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of Leong, Zhu, and Ehrenreich such that there are between 1,000 to 1,000,000 points of contact between different locations defined in the intermediate electrospun layer since it has been held that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Claim 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Leong, et al (Leong) (US 2010/0093093 A1) in view of Zhu, et al (Zhu) (Circumferentially aligned fibers guided functional neoartery regeneration in vivo, Biomaterials, v61, pp 85-94 (2015)) in view of and further in view of Ehrenreich, et al (Ehrenreich) (US 2011/0230948 A1) and as evidenced by Sexton (US 2017/0049627).
Regarding Claim 20, the second population of cells is present in between 50% and 100% of the exterior electrospun layer and wherein the second population of cells comprises smooth muscle cells (SMCs) (e.g. Leong, [0099], [0094]) present in a percentage greater than 40% of the total cells in the second cell population (100% of the cells in this population are SMCs) and are derived from cells seeded on the multilayer scaffold device during an incubation process (since the cells are present, they were inherently incubated in order to be present) and is configured as a cellular sheath connected to the outwardly oriented surface of the exterior electrospun layer (the layer is a tubular layer and the cells are placed on the layer and are thereby a sheath), wherein the cellular sheath has a cell thickness between 10 and 100 cells (Sexton teaches the size of vascular smooth muscle cells ranges from 0.1 mm to 100 mm (e.g. [0057]). Leong teaches the thickness of the exterior layer is 50 mm (e.g. [0140]) and this layer degrades (e.g. [0064]). When the layer degrades the cells seeded therein remain. Therefore the SMC layer is at least 50 mm thick and is 50-1 mm cells thick.)
Conclusion
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/LESLIE A LOPEZ/Primary Examiner, Art Unit 3774 11/11/2025