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
The amendments and arguments filed 5 September 2025 are acknowledged and have been fully considered. Claims 1-2, 5, 7-9, 11, 19, 24-26, 30-31, 40-42, 45-46, 54, 66, and 81 are currently pending. Claims 1 and 5 are amended; claims 3-4, 6, 10, 12-18, 20-23, 27-29, 32-39, 43-44, 47-53, 55-65, and 67-80 are cancelled; claims 7, 9, 26, 31, 40-42, 45-46, 54, and 66 are withdrawn; claim 81 is new.
Claims 1-2, 5, 8, 11, 19, 24-25, 30, and 81 are examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. In particular, the rejection of claims under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendment to the claim. Further, the rejection of claims under 35 U.S.C. 102(a)(1) has been withdrawn in view of Applicant’s amendment to claim 1. Additionally, the double patenting rejection over copending Application No. 17/611,035 has been withdrawn in view of Applicant’s amendment to claim 1. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
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.
Claims 1-2, 5, 8, 11, 19, 24-25, and 81 are rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. (ACS Biomater. Sci. Eng., 1 January 2018, Vol. 4, 3726-3736; of record) in view of Zhao et al. (Bone, 2009, Vol. 45, 517-527; of record).
Claim 1 is drawn to a scaffold biomaterial comprising:
a decellularized plant tissue from which cellular materials and nucleic acids of the tissue are removed, the decellularized plant tissue comprising a 3-dimensional porous structure; and
a protein-based hydrogel;
wherein pore walls of the decellularized plant tissue are mineralized.
Claim 2 is drawn to the scaffold biomaterial of claim 1, wherein the protein-based hydrogel comprises collagen (Applicant’s elected species).
Claim 11 is drawn to the scaffold biomaterial of claim 1, wherein the decellularized plant tissue is mineralized with apatite (Applicant’s elected species).
Claim 24 is drawn to the scaffold biomaterial of claim 1, wherein the decellularized plant is cellulose based.
Claim 25 is drawn to the scaffold biomaterial of claim 1, wherein the plant tissue comprises a tissue from apple hypanthium (Applicant’s elected species).
Hickey et al. teach plant derived cellulose scaffolds combined with hydrogels (Abstract). Hickey et al. further teach “Decellularization with the surfactant sodium dodecyl sulfate was used to obtain 3D cellulose scaffolds void of any native apple cells or nucleic acids” (Pg. 3727 right column second paragraph), wherein the plant tissue comprises apple hypanthium tissue (Pg. 3727 right column third paragraph) and the hydrogel comprising collagen (Pg. 3729 left column second paragraph).
As such, Hickey et al. teach a scaffold biomaterial comprising: a decellularized plant tissue from which cellular materials and nucleic acids of the tissue are removed, the decellularized plant tissue comprising a 3-dimensional porous structure; and a protein-based hydrogel, wherein the protein-based hydrogel comprises collagen, the decellularized plant tissue is cellulose based, and the plant tissue comprises tissue from apple hypanthium.
The scaffold biomaterial of Hickey et al. differs from the instantly claimed scaffold biomaterial in the following ways:
the pore walls of the decellularized plant of Hickey et al. are not mineralized.
Yet, as to 1: Hickey et al. further teach the cellulose scaffolds being useful for numerous applications in tissue engineering (Abstract), are versatile, easy to use, and display high biocompatibility with cell invasion occurring rapidly and more completely (Pg. 3727 left column third paragraph).
Zhao et al. also teach biomaterial-based scaffolds for tissue regrowth (Abstract), further teaching the mineralization of the scaffolds with apatite (Title). Zhao et al. further teach “the mineralization of silk scaffolds provides increased osteoconductive environment for bMSCs to construct tissue engineered bone to repair mandible defects in large animals” (Pg. 526 right column third paragraph), additionally teaching on pg. 525 (left column first paragraph):
“Natural bone, which contains inorganic as well as organic phases, are formed by a series of complex events involving mineralization with calcium phosphate in the form of hydroxyapatite (HAP) on extracellular matrix proteins. Besides, being a natural component of human bone, apatites have been shown to mediate and promote bone regeneration around wounds. Biomaterial scaffolds with apatite coatings have been shown to promote bone ingrowth in defects in dog and goat femurs, enhance direct bone contact in rat femoral medullary implants, and stimulate bone marrow stromal cells and adipose- derived stem cells to regenerate critical size defects.”
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have combined the versatile cellulose tissue scaffold of Hickey et al. with the teaching of apatite coated biomaterial scaffolds of Zhao et al. It would have been obvious to combine the known scaffold with the known apatite coating to yield the predictable result of a scaffold with increased osteoconductive environment for bone growth, with a reasonable expectation of success.
Based on all of the foregoing, claims 1-2, 11, and 24-25 are rejected as prima facie obvious.
Claim 5 is drawn to the scaffold biomaterial of claim 1, wherein the decellularized plant tissue comprises a pore size of about 100 to about 200 µm.
Claim 81 is drawn to the scaffold biomaterial of claim 1, wherein the decellularized plant tissue comprises a pore size of about 150 to about 200 µm.
Hickey et al. further teach the pore size of the decellularized plant tissue between about 100 and 200 µm (Fig. 1), overlapping with the instantly claimed ranges.
As such, claims 5 and 81 are rejected as prima facie obvious.
Claim 8 is drawn to the scaffold biomaterial of claim 1, having a Young’s moduli between about 20 kPa and about 1 MPa.
Hickey et al. further teach the scaffold biomaterial having a Young’s moduli of 2.3 x 101 ±1.7 kPa (Pg. 3729 left column last paragraph), corresponding to a range of 21.3 kPa to 24.7 kPa, overlapping with the instantly claimed range.
As such, claim 8 is rejected as prima facie obvious.
Claim 19 is drawn to the scaffold biomaterial of claim 1, wherein the decellularized plant tissue is mineralized with apatite by alternating exposure to solutions of calcium chloride and disodium phosphate.
Zhao et al. further teach the alternating exposure of a scaffold to calcium chloride and disodium phosphate solutions to result in the mineralization of the scaffold with apatite (Pg. 518 right column fifth paragraph).
As such, claim 19 is rejected as prima facie obvious.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al. and Zhao et al. as applied to claims 1-2, 5, 8, 11, 19, 24-25, and 81 above, and further in view of Alberti et al. (WO 2014/074134; of record) and Papenburg et al. (Biomaterials, 2009, Vol. 30, 6228-6239; of record).
The teachings of Hickey et al. and Zhao et al. have been set forth above.
Claim 30 is drawn to the scaffold of claim 1, comprising two or more subunits which are glued, cross-linked, or interlocked together.
Hickey et al. and Zhao et al. do not teach the scaffolding comprising two or more subunits.
Alberti et al. teach multilayer scaffolds (i.e., scaffolds comprising multiple subunits) for tissue engineering (Abstract), including for bone growth (Pg. 6 lines 1-3). Alberti et al. further teach the layers being held together by applying a binder such as fibrin glue or crosslinking the layers together (Pg. 4 line 32 – pg. 5 line 9).
And as taught by Papenburg et al., multilayer tissue scaffolds allow for space for nutrient supply by culture medium perfusion, leading to more even spreading of cells, as well as facilitation of cell alignment and support for tissue layers (Pg. 6229 left to right column bridging paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the scaffold of Hickey et al. and Zhao et al. to include multipole subunits glued or crosslinked together as taught by Alberti et al. It would have been obvious to use the known multi-unit scaffold technique to improve the scaffold of Hickey et al. and Zhao et al. in the same way, by improving the nutrient supply and facilitating cell alignment and layers, with a reasonable expectation of success.
As such, claim 30 is rejected as prima facie obvious.
Response to Arguments
Applicant's arguments filed 5 September 2025 have been fully considered but they are not persuasive.
Applicant’s arguments regarding Hickey et al. not teaching all feature of amended claim 1 are moot in view of the new grounds of rejection set forth above, necessitated by amendment.
Applicant argues on pg. 10 of the remarks that there is no teaching or suggestion present in Zhao et al. to motivate one of ordinary skill in the art to combine the apatite coating of Zhao et al. with the cellulose scaffold of Hickey et al., further arguing that the combination is an improper hindsight combination.
This argument is not persuasive. Zhao et al. teaches that apatite coated biomaterial scaffolds have been shown to facilitate bone growth in many mammals (Pg. 525 left column first paragraph), suggesting that the specific biomaterial the scaffold is formed of is not critical. As such, one of ordinary skill in the art would reasonably expect the known apatite coating of biomaterials to be effective when applied to the biomaterial plant-based cellulose scaffold of Hickey et al.
Further, 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). As both the biomaterial scaffolds of Hickey et al. and the apatite coating of biomaterial scaffolds taught by Zhao et al. were known in the art before the effective filing date of the claimed invention, the reconstruction is proper.
Applicant argues on pg. 11 of the remarks that there is no teaching or suggestion that the teachings of Alberti et al. or Papenburg et al. would apply to the decellularized plant scaffolds with mineralized pore walls, further arguing that the combination of Hickey et al. with Alberti et al. and Papenburg et al. is an impermissible hindsight combination.
This argument is not persuasive. Alberti et al. teach that the multilayer scaffolds are suitable for bone growth (Pg. 6 lines 1-3), aligning with the use of the scaffold of Hickey et al. and Zhao et al. Further, Papenburg et al. teach that the improved nutrient supply is due to the space between layers (Pg. 6229 left to right column bridging paragraph), suggesting that the makeup of the layers is not as important as the space between them. As such, one of ordinary skill in the art would reasonably expect the multilayer scaffold teachings of Alberti et al. and Papenburg et al. to be suitable for use in bone growth and improve the nutrient supply to the growing tissues.
Further, 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). As the biomaterial scaffolds of Hickey et al., multi-unit scaffolds held together by glue or crosslinking taught by Alberti et al., and improvement of nutrient flow in multi-unit scaffolds taught by Papenburg et al. were known in the art before the effective filing date of the claimed invention, the reconstruction is proper.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611