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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found
in a prior Office action.
This Action is in response to the papers filed on May 8, 2026. Pursuant to the amendment filed on May 8, 2026, claims 1, 3 and 5 are currently pending of which claims 1 and 5 have been amended and claims 4 and 6 have been cancelled.
The Declaration filed under 37 C.F.R. § 1.132 by Dr. Sung Won Kim on August 22, 2025 (“Kim Decl. ”), and filed on August 22, 2025 has been previously acknowledged.
Therefore, claims 1, and 3, and 5 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to Republic of Korea applications 10-2018-0095658 filed on August 16, 2018 and 10-2019-0099786 filed on August 14, 2019, both filed prior to PCT/KR2019/010438 filed on August 16, 2019. Receipt is acknowledged of untranslated certified copies of papers required by 37 CFR 1.55.
Thus, the earliest possible priority for the instant application is August 16, 2018.
Response to Arguments
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments:
Claim Rejections - 35 USC § 112(b)
In view of Applicants' amendment to the claims dated May 8, 2026, wherein claim 5 has been amended, the rejection to claim 5 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
Claim Rejections - 35 USC § 103
In view of Applicants' amendment to the claims dated May 8, 2026, wherein claims 1 and 5 have been amended, the rejection to claims 1 and 3 rejected under 35 U.S.C. 103 as being unpatentable over Stuart et al. in view of Funayama et al. and Chen et al. are withdrawn. The rejection to now cancelled claim 4 has been rendered moot.
In view of Applicants' amendment to the claims dated May 8, 2026, wherein claims 1 and 5 have been amended, the rejection to claims 5 rejected under 35 U.S.C. 103 as being unpatentable over Stuart et al. in view of Funayama et al. and Chen et al. further in view Shafiee et al. and Schmal et al. are withdrawn. The rejection to now cancelled claim 6 has been rendered moot.
The reasoning behind the withdrawn rejections is in view of the amended claims 1 and 5, and in view of the Remarks filed on May 8, 2026. In particular, the amended claim 1 has incorporated portions of now cancelled claim 4, yet some limitations were not incorporated, e.g. cell culture container containing BSA. Applicants' arguments are moot in view of the withdrawn rejection. A response to any argument pertaining to a new or maintained rejection can be found below.
New Grounds of Rejection
Claim Rejections - 35 USC § 103
Claims 1 and 3 are newly rejected under 35 U.S.C. 103 as being unpatentable over Shikani et al. (American journal of rhinology 18.2 (2004): 105-112) in view of Funayama et al. (J Orthop Sci (2008) 13:225–232; hereinafter ‘Funayama’; of record). This is a new rejection necessitated by Applicants' amendments to the claims in the response filed on May 8, 2026.
Regarding claim 1, Shikani teaches a method of isolating nasal septum chondrocytes from a nasal septum tissue of patients then culturing the isolated NSCs in a cell culture container that can culture cells in a spheroidal pellet via microcarrier spinner culture (Fig. 1; p 106, col 2- p 107, col 1). The chondrocytes are seeded on collagen microcarrier beads (reading on collagen support) wherein the chondrocytes form spheroids around day 15 and the ECM was observed to be rich in type II collagen (Fig 6, p 109, col 2). Shikani teaches the mean viability was >95% at each cell harvesting with no decrease in proliferative ability being observed, and in conclusion, “These studies support the feasibility of engineering cartilage tissue using chondrocytes harvested from the nasal septum. Injectable and solid formulations based on this technology are being evaluated for applications in craniomaxillofacial reconstructive surgery and for plastic and orthopedic surgery practices.” (p 108, col 2; abstract).
Shikani does not teach a method of treating articular cartilage damage, but rather states the findings can be used in such applications. Shikani does not teach wherein the recovered NSCs in a spheroidal pellet form are mixed with the collagen, yet Shikani does teach the NSC are seeded onto collagen beads and further express collagen type II after culturing.
Funayama teaches the repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes (title; “Chondrocyte/type II collagen solution mixed with PTE-TSG was injected via an 18-gauge needle into the right knee of each rabbit in the transplanted group until the defect was filled.” (p 226, col 2, par 3)). Funayama teaches that the results indicate that type II collagen gel is suitable for injection into cartilage defects without any covering of a graft and offers a useful scaffold during chondrocyte transplantation (p 225, col 2 , par 1)). Funayama further elucidates collagen as being the principal component of a natural matrix in articular cartilage wherein using collagen in scaffolds has advantageous properties (p 230, col 2, par 1). Lastly, the reference describes “Chondrocyte transplantation with type I collagen gels reportedly induces synthesis of type II collagen and proteoglycans in gels in vitro,8,16 and favorable results have been reported in vivo.” (p 229, col 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the chondrocytes of Funayama that are delivered in combination with injectable grade collagen with the spheroidal NSC taught by Shikani to obtain the predictable outcome of treating articular cartilage damage as shown by Funayama. This substitution is obvious in view of Shikani’s NSC spheroids being shown to retain fusion capacity, having high cell viability, and described as having a purpose in treating articular cartilage damage. Additionally, it would be obvious for the spheroids to be delivered with collagen based on Funayama teachings that collagen is suitable for injection into cartilage defects without any covering of a graft, is a principle component of articular cartilage, and it being shown that chondrocyte transplantation with collagen gels induces the synthesis of collagen and proteoglycans. Furthermore, the addition would be an obvious design steps based on Shikani teaching the spheroids as having some levels of collagen based on the microcarrier beads comprising collagen and the cultured spheroids expressing collagen. Altogether, it would be obvious to inject spheroidal nasal chondrocytes with collagen to treat articular cartilage damage based on the combined teachings of Shikani and Funayama collectively using chondrocytes with collagen in view of treating articular cartilage damage.
Regarding claim 3, dependent on claim 1, Shikani teaches wherein the NSCs express collagen type 2 (collagen: Fig. 7).
Claim 5 is newly rejected under 35 U.S.C. 103 as being unpatentable over Shikani et al. (American journal of rhinology 18.2 (2004): 105-112) in view of Funayama et al. (J Orthop Sci (2008) 13:225–232; hereinafter ‘Funayama’; of record) as applied to claims 1 and 3, and further in view of Schmal et al. (Tissue Engineering, Vol 12, No. 4, 2006; hereinafter ‘Schmal’; of record). This is a new rejection necessitated by Applicants' amendments to the claims in the response filed on May 8, 2026.
Regarding claims 5, the teachings of Shikani in view of Funayama are discussed supra.
Shikani teaches the individual chondrocytes were separated from undigested cartilage and cartilage debris using the Cellector tissue sieve (VWR International West Chester, PA) (p 106, col 2)
Funayama teaches the method step of using a filter after collagenase treatment to remove undigested fragments; however, Funayama does not teach the claimed filter size of a 40 to 50-nm filter, but rather a 100-mm filter (p 226, col 1, par 3).
Shikani in view of Funayama do not teach wherein, in Step (a), the NSCs are harvested by filtration using a 40 to 50-nm filter.
Schmal teaches that P0 and P2 chondrocytes were estimated to be in a range of 9 to 30 µm (average sizes of 12.99 + 0.22 and 12.64 + 0.31 µm, respectively (p 747, par 1)), which is larger than the pore size of the claimed filter.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught by Shikani in view of Funayama by utilizing a filter after dissociating a tissue/cell cluster prior to culturing wherein cellular debris is passed through and the chondrocytes are captured on the surface of the filter. In particular, by using a 40-50-nm filter chondrocytes would be collected/harvested based on their size being larger than the filter pore size, and cellular debris would pass through based on the inherent size of chondrocytes as discussed by Schmal. Altogether, this method step is well-known in the field of cell culturing where tissues are dissociated by chemical or physical means then captured/purified by filtration and/or centrifugation. The particular size of the filter is understood as optimization based on the target cell, as previously described in view of Schmal teachings Therefore, these teaching would have led one of ordinary skill in the art to combine the prior art reference teachings to arrive at the claimed invention.
Response to Applicants’ Arguments as they apply to rejection of claims 1, 3-6 under 35 USC § 103 over Stuart in view of Funayama and Chen.
Starting on page 4 of the remarks filed on May 8, 2026, Applicants essentially argue the following:
The CPC cells of Stuart and the NSCs of the instant claims as being different, and not substitutable, stating, “the two cannot be cytologically identified as the same.” The Applicant then further describes the use of NSCs as being unique in that unexpected results were observed when used in the spheroidal form, especially when combined with collagen.
Regarding all the arguments presented, the new grounds of rejection no longer employ the reference of Stuart or Chen for which the majority of the arguments are dependent. The rejections were withdrawn in view of the amended claims 1 and 5. The new rejection maintains that Funayama teaching the combination of chondrocytes with collagen for injections to treat articular cartilage damage, and providing in vivo teachings. The new rejection now employs Shikani that teaches the NSCs are cultured into spheroidal shape for use in treating articular cartilage damage all of which the instant claims are directed to. Altogether, these new rejections make obvious the limitations listed in claims 1 and 3, and claim 5 with Schmal et al..
Conclusion
Claims 1, 3, and 5 are rejected. No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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