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 .
Status of Claims
Receipt of Applicant’s Preliminary/Remarks and Amendments filed on 03/26/2024 is acknowledged. Claims 1-20 are pending and under examination in this application.
Claim Dependency (post-amendment):
Independent claims: 1 (bone repair device), 9 (surgical kit).
Claim 2: depends from claim 1 — adds cell adhesion method step + shape difference limitation.
Claims 3, 4, 5, 6, 7, 8: each depend solely from claim 1.
Claim 10: depends from claim 9 — adds cell adhesion method step + shape difference limitation.
Claims 11, 12, 14, 17: depend from claim 2.
Claims 13, 15, 18: depend from claim 3.
Claims 16, 19: depend from claim 4.
Claim 20: depends from claim 5.
Priority
The current application filed on 03/26/2024 is a National Phase application, under 35 U.S.C. §371 of International Application No. PCT/JP2022/034909 filed 09/20/2022, which in turn claims priority to patent application JP2021-156438 filed on 09/27/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/18/2026, 09/02/2025 and 05/15/2024 are in compliance with the provisions of 37 CFR 1.98. Accordingly, the information disclosure statements has been considered by the examiner. Signed copies have been attached to this office action.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of (JP 2023047494) (hereinafter “Fujita”).
Fujita discloses a bone repair device comprising: an intervertebral cage having a space inside into which body fluid can flow from outside; and a nonwoven fabric accommodated in the space, to which stem cells or osteoblast stem cells formed by being differentiated from stem cells are adhered (abstract). The following embodiments of Fujita maps directly to limitations of the instant claims. Fujita expressly discloses: (a) the stem cells are mesenchymal stem cells (¶ 0007); (b) the nonwoven fabric may be formed of a material containing at least one of polylactic acid, polyglycolic acid, silk fibroin, poly-epsilon-caprolactone, chitin, and chitosan (¶ 0010); (c) fiber diameter in the range of 0.1 µm to 30 µm (¶ 0008); and (d) fiber density in the range of 0.2 g/m2 to 150 g/m2 (¶ 0009); and (e) Surgical Kit (¶ 0005; ¶ 0014). The instant independent claims 1 and 9, and all dependent claims are therefore not patentably distinct from the claims of Fujita as set forth below.
Regarding claims 1 and 9, wherein recites “implant with fluid space + nonwoven with MSCs on intertwined fibers”: Fujita discloses an intervertebral cage with an interior space into which body fluid flows from outside, and a nonwoven fabric accommodated in the space to which mesenchymal stem cells are adhered to the intertwined fibers of the nonwoven fabric, wherein a surgical kit is included that promote bone repair (Abstract; ¶¶ 0002-0017; ¶0034).
Regarding claims 2 and 10, Fujita discloses that adhesion of mesenchymal stem cells to the nonwoven fabric is performed by interposing the nonwoven fabric between a pair of holders and flowing a cell suspension from one holder to the other, and that the shape of the nonwoven fabric when the mesenchymal stem cells are adhered differs from the shape of the implant space. (¶¶ 0029-0031; claims 1 and 8).
Regarding claims 3 and 11, as noted above, Fujita expressly discloses that the fiber diameter of the nonwoven fabric is within a range from 0.1 µm to 30 µm.
Regarding claims 5 and 14-16, as noted above, Fujita discloses that the nonwoven fabric is formed of at least one of polylactic acid, polyglycolic acid, silk fibroin, poly-epsilon-caprolactone, chitin, and chitosan.
Regarding claims 6 and 17-20, Fujita discloses accommodation of a bone fragment in the space of the implant together with the nonwoven fabric (¶ 0044).
Regarding claim 7, Fujita discloses a main body having an interior space and a through-hole penetrating from the outer surface to the space, configured to allow body fluid to flow into the space (¶ 0002, ¶ 0012 and claim 6).
Regarding claim 8, Fujita discloses that the implant is an intervertebral cage configured for insertion between a pair of vertebral bodies, the area resulting from dissection of an intervertebral disk (¶ 0013; (¶ 0016; (¶ 0018; (¶ 0020; (¶ 0023).
Regarding claim 9, Fujita discloses a surgical kit comprising an implant and a nonwoven fabric package, wherein mesenchymal stem cells are adhered to the intertwined fibers of the nonwoven fabric, and the nonwoven fabric is packed (¶ 0034).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 2, 10, 11, 12, 14 and 17 are 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.
Claim 2 recites, in pertinent part: "wherein adhesion of mesenchymal stem cells to the nonwoven fabric is performed by interposing the nonwoven fabric between a pair of holders and flowing a cell suspension containing the mesenchymal stem cells from one holder to the other holder, wherein a shape of the nonwoven fabric when the mesenchymal stem cells are adhered is different from a shape of the space of the implant." This language is indefinite for two independent reasons:
First, claim 2 is directed to a bone repair device (a product) but incorporates a method step ("adhesion... is performed by interposing... and flowing"). A product claim that recites a method of making the product is a product-by-process claim and must structurally distinguish the product per se from the prior art. See MPEP § 2173.05(p); Vanguard Prods. Corp. v. Parker Hannifin Corp., 234 F.3d 1370, 1372 (Fed. Cir. 2000). The method step of "interposing... and flowing" does not define any structural feature of the finished device that distinguishes it from a device made by any other cell-loading technique. It is therefore unclear what structural characteristic of the finished bone repair device is defined by this process limitation.
Second, the limitation "a shape of the nonwoven fabric when the mesenchymal stem cells are adhered is different from a shape of the space of the implant" fails to define the device with reasonable certainty. It is unclear: (a) whether "the shape of the nonwoven fabric when the mesenchymal stem cells are adhered" refers to the fabric shape during cell loading, before insertion into the implant, or after insertion; (b) how such a shape difference is measured or quantified in the assembled device; and (c) what specific structural relationship this limitation imposes on the final product as claimed. The metes and bounds of this limitation cannot be determined with reasonable certainty. See Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 901 (2014).
Claim 10 depends from claim 9 (surgical kit) and recites substantially the same cell adhesion method step and shape difference limitation. Claim 10 is indefinite for the same reasons set forth above with respect to claim 2.
Claims 11, 12, 14, and 17 depend from indefinite claim 2 and are each rejected under 35 U.S.C. § 112(b) by incorporation of the indefiniteness of claim 2. Claims 13, 15, 16, 18, 19, and 20 do not depend from claim 2 and are not rejected under § 112(b).
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.
Claim(s) 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Okimura (US 2013/0338790 A1) in view of Gilbride (US 20190201212 A1), Arinzeh (US 20110300626 A1) and further in view of Kalpakci (US 20190021862 A1).
Okimura teaches a bone regeneration material comprising a nonwoven fabric in which a bone prosthetic material is included between the biocompatible fibers constituting the nonwoven fabric (Abstract). The nonwoven fabric ensures significantly high cell — particularly osteoblast — proliferation efficiency (¶¶ 0011-0014). The biocompatible polymer fibers may be formed from polylactic acid, polyglycolic acid, PLA-PGA copolymer, polycaprolactone, or chitin (¶ 0015). The nonwoven fabric can be used as a scaffold for the culture of osteoblasts and provides an increase in bone regeneration efficiency; it enables quick bone regeneration by being implanted into or attached to the affected part (¶ 0030). Incorporation of osteoblasts may be performed by cell culture using the nonwoven fabric as a scaffold material (¶ 0078). Okimura discloses orthopedic applications (¶ 0083), including spinal applications (¶ 0084).
Gilbride discloses an intervertebral fusion implant for insertion between vertebral bodies following discectomy, comprising a spacer body (implant) having an interior space into which body fluid can flow from the surrounding environment, and through-holes or fenestrations extending from the outer surface of the main body to the interior space, configured to allow body fluid to flow into the space (abstract; ¶¶ 0005-0007; ¶¶ 0031-0032).
Arinzeh teaches electrospun nonwoven polymer scaffolds for bone and tissue repair applications (abstract) and discloses microscale fiber or micronized fiber are used interchangeably to refer to fibers whose diameter ranges from about 1 micrometer (10-6 m) to about 1000 micrometers. The terms "nanoscale fiber" or "nano sized fiber" are used interchangeably to refer to fibers whose diameter ranges from about 1 nanometer (10-9 m) to about 1000 nanometers (¶ 0033), and identifies fiber diameter in the range of 0.1 um to 30 um as a result-effective variable controlling cell attachment, proliferation, and osteogenic differentiation.
Kalpakci teaches A bone implant for enclosing bone material is provided. The
bone implant comprises a mesh having an inner surface and an outer surface opposing the inner surface. The inner surface is configured to receive a bone material when the
inner surface of the mesh is in an open configuration. A plurality of projections are disposed on or in at least a portion of the inner surface of the mesh. The plurality of
projections extend from at least the portion of the inner surface of the mesh and are configured to engage a section of the inner surface of the mesh or a section of the outer
surface of the mesh or both sections of the inner and outer surfaces of the mesh in a closed configuration so as to enclose the bone material. A tray, a kit and a method of
making the bone implant are also provided (abstract).
Regarding claim 1, Gilbride discloses an intervertebral cage (implant) having an interior space into which body fluid flows from outside through the cage structure (¶ 0003; ¶ 0006; ¶¶ 0053-0063). Okimura discloses a nonwoven fabric comprising intertwined biocompatible fibers to which osteoblasts are adhered, the fabric being configured for implantation into a bone repair site (¶¶ 0011-0014, 0030, 0078). To the extent Okimura does not expressly recite "mesenchymal stem cells" by name, it would have been obvious to a POSITA to seed Okimura's nonwoven scaffold with mesenchymal stem cells, as MSCs are the recognized osteogenic precursors to osteoblasts and their use in nonwoven scaffolds for bone repair was well-established in the art before September 27, 2021. It would have been obvious to a POSITA to accommodate Okimura's MSC-seeded nonwoven fabric within the interior space of Gilbride's cage implant, as the two components serve complementary purposes in bone repair.
Regarding claims 5, 15 and 16, Okimura discloses that the biocompatible fibers are formed from polylactic acid, polyglycolic acid, PLA-PGA copolymer, polycaprolactone, or chitin (¶ 0015). Claim 5 requires "at least any one of" these materials — Okimura's PLA, PGA, and PCL disclosures fully satisfy this open Markush element.
Regarding claims 6, and 18-20, It would have been obvious to a POSITA to include autologous bone fragments in the implant space of the Okimura/Gilbride combination to supplement cell-mediated bone repair with an osteoconductive matrix, a standard and well-established surgical technique yielding predictable benefit (¶¶ 0032-0041).
Regarding claim 7, Gilbride discloses a main body with through-holes penetrating from the outer surface to the interior space, configured to allow body fluid to flow into the space (Fig 1-5 and Fig 14; ¶¶ 0032-0038; ¶¶ 0061-0062).
Regarding claim 8, Gilbride is expressly directed to an intervertebral fusion cage for insertion between a pair of vertebral bodies following discectomy (¶ 0069; claim16).
Regarding claim 9, the combination of Okimura's cell-seeded nonwoven scaffold and Gilbride's intervertebral cage constitutes the components of the claimed surgical kit. A POSITA would have found it obvious to provide these components together as a pre-packaged sterile surgical kit, because packaging sterile implant components and pre-seeded scaffolds together for intraoperative delivery was a standard and well-established practice in the medical device and orthopedic surgery arts before the effective filing date. The act of packaging and sterilizing a cell-seeded scaffold for surgical delivery requires no inventive step and is a routine manufacturing and logistics consideration. See KSR, 550 U.S. at 421. The "nonwoven fabric being packed" limitation is met by the inherent requirement that medical scaffolds be packaged in sterile form prior to surgical use.
Motivation to Combine Okimura and Gilbride: A POSITA would have been motivated to combine the teachings of Okimura and Gilbride. Okimura provides a cell-seeded nonwoven scaffold optimized for bone regeneration, while Gilbride provides an intervertebral cage implant with an interior space designed to receive bone repair materials and permit body fluid ingress to promote integration. Both references are directed to the same field — bone repair and spinal fusion — and address the same objective: delivering osteogenic materials into a bone defect site in a form that promotes osseointegration. A POSITA would have had a clear reason to place Okimura's cell-seeded nonwoven scaffold into Gilbride's implant space, with a reasonable expectation that the combination would promote bone fusion more effectively than either component alone. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416, 421 (2007); Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966).
Okimura and Gilbride fails to specifically teach fiber diameter.
Regarding claims 3 and 11, Okimura discloses fiber density distributions and an interfiber distance of approximately 5 to 40 µm in the dense fiber portion (¶ 0063), which is consistent with fiber diameters in the submicron-to-micron range. To the extent the specific diameter range of 0.1-30 µm is not expressly disclosed by Okimura, Arinzeh expressly identifies fiber diameter in the range from nanoscale (sub-micron) to microscale (1-1000 µm) as a result-effective variable controlling cell attachment, proliferation, and osteogenic differentiation (¶ 0033; ¶¶ 0072-0081). A POSITA would have recognized the 0.1-30 µm range as a routine, result-effective design parameter and would have optimized it within this range with no more than ordinary skill. Optimization of a known result-effective variable is prima facie obvious. See In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Regarding claims 4, 12 and 13, the claims recite “a fiber density range of 0.2 g/m² to 150 g/m²”. Claim 13 depends from claim 3 and adds this fiber density limitation in the context of the claim 3 device (fiber diameter 0.1-30 µm). Arinzeh discloses basis weights within and encompassing the claimed range (¶¶ 0099-0100) and identifies fiber areal density as a result-effective variable affecting porosity, cell infiltration, and nutrient transport (¶¶ 0057-0059, 0074). A POSITA would have had reason to optimize fiber density within this range with a reasonable expectation of improved performance.
Regarding claims 2, 10 and 17, the claims recite the limitation of cell adhesion by perfusion; shape difference) and if the claims are found definite, the cell adhesion method step and shape difference limitation are rendered obvious by Okimura in view of Gilbride. Perfusion-based cell loading — flowing a cell suspension through a porous scaffold interposed between holders — was a well-established, routine technique in the bone tissue engineering art for achieving uniform cell seeding of nonwoven scaffolds before the effective filing date of September 27, 2021. A POSITA would have had clear reason and ability to apply this standard technique to seed Okimura's nonwoven scaffold with MSCs, with a reasonable expectation of achieving uniform cell adhesion throughout the fiber matrix. Kalpakci expressly discloses perfusion cell loading (¶¶ 0002-0004; ¶¶ 0111-0113). Okimura's nonwoven fabric, when cells are adhered under flat perfusion conditions, will have a planar or pre-formed shape that geometrically differs from the three-dimensional interior space of Gilbride's intervertebral cage. No inventive step is required to arrive at this shape difference — it is a predictable consequence of inserting a deformable scaffold into a rigid implant space of different geometry.
Regarding claims 14, 15 and 16, the claims requires silk fibroin and chitosan. Okimura expressly discloses polylactic acid, polyglycolic acid, PLA-PGA copolymer, polycaprolactone, and chitin as biocompatible fiber materials (¶ 0015), fully satisfying the material limitations of claims 5, 15, and 16 to the extent those materials are recited. To the extent silk fibroin and chitosan are not expressly taught by Okimura, Kalpakci discloses biodegradable polymer scaffolds for bone repair applications including silk fibroin and chitosan as biocompatible scaffold materials (¶ 0107; ¶ 0109; ¶ 0117). It would have been obvious to a POSITA to form the nonwoven scaffold from silk fibroin or chitosan, as both were recognized in the art before the effective filing date as biocompatible, biodegradable, and osteogenic scaffold materials with established cell adhesion properties.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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