DETAILED ACTION
This action is in reply to papers filed 4/28/2026. Claims 1-3 and 6-12 are pending and examined herein.
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/28/2026 has been entered.
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240325599A1, Published 10/3/2024.
Withdrawn Claim Rejections
The 112 (b) rejection of claim 5 is withdrawn in view of amendments made to claim 5.
The 103 (a) rejection of claims 1-4, 6 and 9-11 as being unpatentable over McKay, W.F. (PgPub US20110182965A1, Published 7/28/2011) in view of Khoshzaban et al. (Clin Cosmet Investig Dent. 2011 Sep 29:3:69-78.) is withdrawn in view of amendments made to claim 1.
The rejection of claim 12 as being unpatentable over McKay, W.F. (PgPub US20110182965A1, Published 7/28/2011) in view of Khoshzaban et al. (Clin Cosmet Investig Dent. 2011 Sep 29:3:69-78.) as applied to claims 1-4, 6 and 9-11 above, and further in view of Kobayashi et al. (PgPub US20130109836A1, Published 5/2/2013), Yamanaka et al. (PgPub US20130259838A1, Published 10/3/2013), Zhou et al. (CN104606717A, Published 5/13/2015) and Deng et al. (PgPub US20160175487A1, Published 6/23/2016) is withdrawn in view of amendments made to claim 12.
The 103 (a) rejection of claims 5, 7-8 and 12 as being unpatentable over McKay, W.F. (PgPub US20110182965A1, Published 7/28/2011) in view of Khoshzaban et al. (Clin Cosmet Investig Dent. 2011 Sep 29:3:69-78.) as applied to claims 1-4, 6 and 9-11 above, and further in view of Kobayashi et al. (PgPub US20130109836A1, Published 5/2/2013), Yamanaka et al. (PgPub US20130259838A1, Published 10/3/2013), Zhou et al. (CN104606717A, Published 5/13/2015) and Deng et al. (PgPub US20160175487A1, Published 6/23/2016) is withdrawn.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.
Prior Art Rejection 1
Claim(s) 1-3 and 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over McKay, W.F. (PgPub US20110182965A1, Published 7/28/2011; previously cited) in view of Khoshzaban et al. (Clin Cosmet Investig Dent. 2011 Sep 29:3:69-78.; previously cited), Yamanaka et al. (PgPub US20130259838A1, Published 10/3/2013; previously cited), Zhou et al. (CN104606717A, Published 5/13/2015; previously cited) and Deng et al. (PgPub US20160175487A1, Published 6/23/2016; previously cited).
McKay teaches a compression resistant (i.e. hard) matrix (as in claim 1a) for implantation at or near a target tissue site beneath the skin, the matrix comprising a porous ceramic skeleton disposed throughout the matrix in its interior and a polymer disposed throughout the matrix in its interior and extending to its exterior such that the matrix is porous (as in claim 1b) and compression resistant (Pg. 1, para. 9). McKay teaches the ceramic skeleton comprises a calcium phosphate ceramic material, such as tricalcium phosphate or hydroxyapatite (Pg. 3, para. 32). McKay teaches the polymer is collagen (as in claim 2) and is cross-linked (as in claim 1, in-part) (Pg. 3,para. 35; Pg. 3,para. 37). McKay teaches the ceramic skeleton pores may be in the range of about 1 mm (which is reasonably considered to include 800 µm) to about 10 mm in diameter and have a total porosity of about 50-90% (as in claim 1) (Pg. 4,para. 44). McKay teaches freeze drying the matrix for implantation (see Mckay at claim 16) (as further in claim 1). McKay teaches the matrix may be seeded with harvested cartilage cells (~ chondrocytes) (as in claim 6 and claim 9) (Pg. 4,para. 51). McKay teaches the matrix can be used to repair maxillofacial defects (as in claim 10) (Pg. 1, para. 7). McKay teaches there may be about 0.2-2% collagen and about 98-99.8% ceramic, wherein the percentages are based on weight (as in claim 11) (Pg. 4, para. 47).
Mckay fails to teach the hard matrix is comprised of decalcified bone (as further in claim 1 and as in claim 3).
Before the effective filing date of the claimed invention, Khoshzaban investigated the effectiveness of Iranian Tissue Bank-produced demineralized (~ decalcified) bone matrix (ITB-DBM) (as further in claim 1 and as in claim 3), beta-tricalcium phosphate (βTCP), and Bio-Oss were evaluated and compared with double controls. Khoshzaban teaches the main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control) defects (Pg. 69). Overall, Khoshzaban teaches the ITB-DBM group showed the best results. The authors conclude that human DBM (ITB-DBM) should be offered as an alternative for bone regeneration in animals, such as horses, as well as in humans, especially for jaw reconstruction (Pg. 69).
And although McKay teaches seeding the scaffold with cartilage cells, none of Mckay, Khoshzaban et al. and Kobayashi et al. teach the scaffolds are seeded with chondrocytes at a concentration of 1×107 to 1×109 cells/cm3 (as in claim 7).
Before the effective filing date of the claimed invention, Yamanaka taught a cultured cartilage tissue material which enables formation of cartilage tissue being substantially the same as the cartilage tissue actually in the living body (Abstract). Yamanaka teaches the cultured cartilage tissue material is to be used for knee joint (hard tissue) cartilage (Pg. 7, para. 90) regeneration and comprises chondrocytes, and is a mixed body of chondrocytes in a concentration of 1×107 to 1×109 cells/cm3 (as in claim 7), and a bioabsorbable polymer (Abstract).
And while McKay teaches a method of deriving the scaffold, none of the aforementioned references teach the process comprises the method steps of claim 8.
Before the effective filing date of the claimed invention, Zhou et al. teach a gelatin aqueous solution was poured into a porous β-TCP scaffold (as in claim 8 (i (in-part)) and (claim 8 ii(in-part)) at a temperature of 45 ° C and a vacuum of 0.08 MPa, and dried in a vacuum drying oven for 30 min (Pg. 1, para. 4). The scaffold was taken out and placed in a medical cryostat for 12 h at a temperature of -20 ° C (as in claim 8 iii(in-part))). The scaffold was quickly removed from the medical cryostat and placed in a vacuum freeze dryer for lyophilization for 24 h (as in claim 8 (iii (in-part)-iv)). The specific conditions were a pressure of 6.7 Pa and a temperature of -54 ° C. The freeze-dried scaffold was cross-linked with glutaraldehyde (as further in claim 1 and as in claim 8 (v)) for 12 h, then washed with distilled water for 3 times, and the sodium borohydride aqueous solution (5%) was soaked in dialdehyde and deionized water to fully soak, pre-freeze and freeze-dry twice (conditions as before) (as in claim 8 (vi)) (Pg. 1, para. 4).
And although none of the aforementioned references teach placing the crosslinker and the matrix material in a centrifuge tube, this is remedied by Deng et al. who teach PCL and gelatin were dissolved in trifluoroethanol in a mass ratio of 10:1 to form a solution. The solution entered into a centrifugal spinning (as further in claim 8vii) machine via a propel pump. The propelling rate of the propel pump was 150 g/min; the velocity of centrifugal coiling was 6000 m/min. The solution was rapidly spun into fibers at a spinning temperature of 50°C. Once the procedure was completed, the membrane was taken from the receiver, and the solvent was removed by vacuum drying, so that a composite fiber membrane (having a porous three-dimensional mesh (Abstract)) structure was obtained (Pg. 6, para. 83).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A, B and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of McKay, wherein McKay teaches a compression resistant matrix for implantation in treating a maxillofacial defect, the matrix comprising a porous tricalcium phosphate disposed throughout the matrix in its interior and a collagen polymer disposed throughout the matrix in its interior and extending to its exterior such that the matrix is porous, with the teachings of Khoshzaban et al, wherein in a comparison between demineralized bone matrix (DBM) and beta-tricalcium phosphate (βTCP), Khoshzaban teaches DBM should be offered as an alternative for bone regeneration in animals, especially for jaw reconstruction. That is, one of ordinary skill in the art would have found it prima facie obvious to substitute the tricalcium phosphate of McKay for the DBM of Khoshzaban because Khoshzaban teaches DBM showed best results in bone regeneration rat model.
Moreover, the skilled artisan would have found it prima facie obvious to seed chondrocytes at a concentration of 1×107 to 1×109 cells/cm3 because Yamanaka teaches this concentration is suitable for regeneration of cartilage/bone. Moreover, one of ordinary skill in the art would have found it prima facie obvious to mix the gelatin and DBM using the centrifugal spinning process of Zhou et al. and Deng et al. in order to obtain a homogenous solution.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Applicant’s Arguments/Response to Arguments
In order to practice compact prosecution, Applicant’s arguments are addressed below.
Applicant argues: As recorded in the disclosure of McKay (see paragraph [0044]), the ceramic skeleton pores may be in the range of about 1 to about 10 mm in diameter, or about 4 to about 6 mm in diameter, e.g., about 5 mm and have a total porosity of about 50-90% or about 60-80%, e.g., about 70% (before polymer addition); The collagen matrix inside the ceramic skeleton may have pores in the range of 0.01-1 mm diameter or 0.03-0.08 mm in diameter, e.g., about 0.05 mm and have a porosity of about 80-99% or about 93-97%, e.g., about 95% (after polymer addition). It can be seen that the porosity of the collagen matrix is increased compared to the ceramic skeleton. However, those skilled in the art should acknowledge that the addition of filler material (such as the collagen polymer used in McKay) to a porous scaffold can reduce the pore size of the original scaffold, but does not increase the porosity of the scaffold.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Per MPEP 716.01 (c), arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding inoperability of the prior art.
Applicant argues: In the present application, the claimed tissue engineering scaffold has significantly reduced pore size compared to the original hard large aperture frame structure (see Figure 1 and Figure 3 of the present application). Furthermore, the present application also identified that the porosity of the claimed tissue engineering scaffold is not increased compared to the original hard large aperture frame structure, see Figure S1 in the supplementary materials. On the contrary, the porosity of the claimed tissue engineering scaffold is decreased. If an artisan of ordinary skill combines the teachings of McKay with the teachings of Khoshzaban, he/she should obtain a tissue engineering scaffold with reduced pore size and increased porosity, rather than a tissue engineering scaffold with reduced pore size and decreased porosity as claimed in the present application.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Note that the claims do not require the tissue engineering scaffold to have a reduced pore size and decreased porosity as compared to the original hard aperture. Indeed, the only porosity and/or pore size claimed is drawn to the original hard aperture.
Applicant argues: In addition, the tissue engineering scaffold as claimed in the present application further has the following distinguish features over McKay: (1) The hard large aperture frame structure may be a decalcified bone matrix or a PCL framework; (2) The bio-gel is crosslinked with the hard large aperture frame structure using a chemical crosslinking agent selected from the group consisting of EDC, genipin, glutaraldehyde, and a combination thereof. McKay does not teach the hard large aperture frame structure is comprised of a decalcified bone matrix or a PCL framework. The crosslinking in McKay is achieved by laccase induced peptide cross-linking and suitable bridging molecules (see paragraph [0037]). Therefore, Applicant deems that an artisan of ordinary skill cannot readily obtain the claimed tissue engineering scaffold of the present application by combining the teachings of McKay with the teachings of Khoshzaban.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. As acknowledged by Applicant, McKay does not teach the chemical crosslinking agent selected from the group consisting of EDC, genipin, glutaraldehyde, and a combination thereof. However, this is remedied by Zhou who teach a freeze-dried scaffold that is cross-linked with glutaraldehyde.
Applicant argues: More importantly, the claimed tissue engineering scaffold of the present application has surprisingly technical effects. Experiments have shown that the bio-gel frame complex scaffold can effectively load inoculated cells and has good mechanical strength that can meet the mechanical strength requirements for immediate repair. The bio-gel frame complex scaffold cannot only be used for repairing bone defects, but also for repairing cartilage defects.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Prior Art Rejection 2
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over McKay, W.F. (PgPub US20110182965A1, Published 7/28/2011; previously cited) in view of Khoshzaban et al. (Clin Cosmet Investig Dent. 2011 Sep 29:3:69-78.; previously cited), Yamanaka et al. (PgPub US20130259838A1, Published 10/3/2013; previously cited), Zhou et al. (CN104606717A, Published 5/13/2015; previously cited) and Deng et al. (PgPub US20160175487A1, Published 6/23/2016; previously cited) as applied to claims 1-3 and 6-11 above, and further in view of Okamoto et al. (PgPub US20120237586A1, Published 9/20/2012).
The teachings of McKay, Khoshzaban et al., Zhou et al. and Deng et al. are relied upon as detailed above. However, none of the aforementioned references teach the cross-linking agent is EDC (as in claim 12).
Before the effective filing date of the claimed invention, Okamoto et al. teach a material for induction of hard tissue regeneration, comprising platelet-rich plasma and gelatin β-TCP sponge, which promotes angiogenesis, osteogenesis, chondrogenesis and the like (Abstract). Okamoto teaches a composition containing β-TCP and gelatin is subject to crosslinking and freeze-drying (Pg. 2,para. 22). Okamoto teaches the crosslinking agent to be used is not particularly limited and, for example, glutaraldehyde, water-soluble carbodiimide such as EDC (as in claim 12) (Pg. 3, para. 51).
When taken with the teachings of McKay, Khoshzaban et al., Zhou et al. and Deng et al., wherein the combination teaches a tissue engineering scaffold comprising decalcified bone matrix wherein said scaffold is formed by, inter alia, crosslinking decalcified bone matrix with glutaraldehyde, one of ordinary skill in the art would have found it prima facie obvious to substitute glutaraldehyde for EDC, as set forth in Okamoto. The skilled artisan would have been motivated to make such a substitution because Okamoto teaches an equivalence in their use as cross-linking agents. Thus, one of ordinary skill in the art seeking to an alternative to the cytotoxic glutaraldehyde would have found the substitution prima facie obvious.
Thus, the combination would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
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