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 .
Claim Status:
Claims 3, 6, 8, 13 and 16 are cancelled.
Claims 1, 2, 4, 5, 7, 9-12, 14, 15 and 17-20 are pending.
Claims 11, 12, 15 and 17-201 are withdrawn.
Claims 1, 2, 4, 5, 7, 9, 10 and 14 are under examination.
Priority
The translation of the foreign priority document filed 2/3/26 is acknowledged.
Withdrawn rejections
Applicant's amendments and arguments filed 1/30/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
Claims 1, 2, 4, 5, 7-10 and 14 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claim 10 was rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Applicant’s amendments are persuasive. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 2, 4, 5, 7-10 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Masuda et al. (US20030229400) and Gomes et al. (US20040230303) and Vunjak-Novakovic et al. (US20050064042).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a tissue engineering research scientist, as is the case here, then one can assume comfortably that such an educated artisan will have knowledge of and draw conventional ideas from biology, biomaterials science, and tissue engineering for regenerative medicine, with practical skills in areas like cell culture, biomaterial design, and 3D tissue handling— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1 and 14, Masuda et al. teach a transplantable osteochondral implant comprising engineered cartilage tissue attached to a biocompatible support scaffold comprising a plurality of pores, hence a cartilage tissue engineering complex that comprises a carrier comprising a porous frame structure, wherein the cartilage tissue is derived from chondrogenic cells cultured in vitro, the cells having a cell associated matrix (CM) that implicitly encapsulates the cell population, and wherein the scaffold is selected from the group consisting of at least one of natural cancellous bone, demineralized natural cancellous bone, collagen, and bone substitute material (Claims 1-2 and 6; [0068]). It is the Examiner’s position that the associated matrix of the cartilage cells in the cartilage tissue reads on at least a gel in a gel state that encapsulates the cell population such that the chondrocytes are loaded on the carrier and form a more closely integrated structure with the carrier. See [0047-0051]. Furthermore, the “plurality of pores” of the biocompatible support scaffold implicitly is a porous frame structure that is a carrier made of a biocompatible material having a certain number of pores on its surface and interior to facilitate the attachment of cartilage gel or cartilage sheet inoculated thereon. Alternatively, Masuda et al. also teach adding a gel (Claim 19) and having 1 or 2 or more layers of cartilage tissue or cells can be cultured as a monolayer [0066], which would appear to read on sheets of cartilage.
Regarding the product-by-process limitations (“formed by”; “undergoing”; “obtained by”; “prepared by”) of claim 1 and claims dependent therefrom, please note that in product-by-process claims, “once a product appearing to be substantially identical is found and a 35 U.S.C. 102/103 rejection [is] made, the burden shifts to the applicant to show an unobvious difference.” See MPEP 2113 Product-by-Process Claims [R-08.2017] I. PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Regarding claims 1-2, Masuda et al. teach: “The chondrogenic cells can
be isolated directly from pre-existing cartilage tissue, for example, hyaline cartilage, elastic cartilage, or fibrocartilage.” ([0034]; see also [0053]). Thus, the chondrogenic cells can comprise elastic cartilage cells, fibrocartilage cells and hyaline cartilage cells. It is the Examiners position that the artisan can obtain the pre-existing tissue in the form of shavings/sheets and then mince those sheets into pieces for culture/extraction of chondrogenic cells.
Regarding claims 9-10, Masuda et al. teach that the scaffold can be selected from the group consisting of at least one of natural cancellous bone, demineralized natural cancellous bone, collagen, and bone substitute material (Claim 1) where that the bone substitute material has a thickness of at least about 2 mm or at least about 10 mm or even greater depending upon the anatomy of the joint into which the implant will be surgically inserted (Claim 5; [0008, 0024, 0058]). The limitation of “at least about 10 mm” is reasonably interpreted to be “at least 10 mm” or “about 10 mm” and “at least 10 mm is open ended and includes greater values such as 0.3-0.8 cm. The term “demineralized natural cancellous bone” is reasonably interpreted to read upon a “decalcified bone matrix”.
Regarding claim 1, Vunjak-Novakovic et al. teaches that it is common to have milled/minced cartilage pieces in a carrier repair assembly with chondrocytes (Claims 1-8; 12-13).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Masuda et al. is that Masuda et al. do not expressly teach minced cartilage sheet pieces, a cell density of chondrocytes of at least 1.0 X 108 cells/ml or 1.0 X 108 cells/g with a cell adhesion rate of ≥ 90% or ≥ 95%.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to make the implant of Masuda et al. with minced cartilage sheet pieces, a cell density of chondrocytes of at least 1.0 X 108 cells/ml or 1.0 X 108 cells/g with a cell adhesion rate of ≥ 90% or ≥ 95% and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. Masuda et al. teach: “cells with a reestablished CM are further cultured in medium on the biocompatible support scaffold for a length of time effective for allowing formation of a cohesive cartilage matrix. An effective time of culture is typically at least about 3 days under standard culture conditions.” [0064] While Masuda et al. is silent on the adhesion rate, the ordinary artisan would desire the highest adhesion rate possible such as 100% and thus achieving an adhesion rate of the cartilage gel of ≥ 90% or ≥ 95% is obvious to the ordinary artisan. While Masuda et al. is silent on the cell density, Gomes et al. teach that in the cartilage repair art (Abstract; claims 1-48; Figures 1-9 and accompanying text) and that: “cells include allogenic or autologous, bone marrow cells, stem cells and chondrocyte cells. The cellular density of the cells preferably ranges from 1.0 x l08 to 5.0 x l08 or from about 100 million to about 500 million cells per cc of putty or gel mixture.” Consequently, having at least 1.0 x 108 cells/ml or 1.0 x 108 cells/g in the implant of Masuda et al. is obvious in view of the combined references. With regard to the limitation of mincing a cartilage sheet to provide cartilage pieces, it is the Examiner’s position that Masuda et al. render obvious a cartilage sheet, as explained above, and the time to culture such as sheet is at the discretion of the ordinary artisan with no change to the structure of the implant. Cutting/mincing the sheet into pieces, thus it is no longer a sheet but just a bunch of particulate pieces of cartilage chondrocytes to provide the chondrocytes for the scaffold/carrier of Masuda et al. appears to be a routine and conventional in this art, as taught by Vunjak-Novakovic et al., which will provide chondrocytes for application to the carrier/scaffold with a reasonable expectation of success.
The difference between the instant application and Masuda et al. is that Masuda et al. do not expressly teach obtaining a cartilage gel obtained by gelation culture for 3-5 days or a cartilage sheet by gelation culture for 10-15 days or wherein the gelation medium contains the following components: high-glucose DMEM medium containing 4 to 5 wt% glucose, 10% PBS (v/v) and 100 U/ml penicillin-streptomycin. However, the instantly claimed sheet is ultimately minced into pieces and is no longer a sheet and Masuda et al. teach and suggest obtaining chondrogenic cells from any tissue that contains the cell [0034] and isolating by any suitable method [0037], which would include mincing a shaving/sheet of the tissue and exposing to a culture medium. A culture time of 3-5 days for a gel and 10-15 days for a sheet is at the discretion of the ordinary artisan to obtain the desired chondrogenic cells. Indeed, Masuda et al. teach: “crosslinks in particular show a large increase in concentration after two weeks of culture” [0052], which would provide a reasonable starting point for culture periods for gels and sheets within that time frame. Selection of a gelation medium as claimed is part of the product-by-process limitation and at the discretion of the ordinary artisan.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s arguments filed 1/30/26 have been carefully considered but are not persuasive.
On pages 8-9 of remarks, Applicant asserts that the cartilage gel disclosed by Masuda et al. is significantly different from the cartilage gel of the cartilage tissue engineering complex claimed. Applicant’s argument is based upon how the cartilage tissue has been cultured in a particular gelation medium resulting in density of chondrocytes, high fluidity, and an adhesion rate of ≥ 90% that can be inoculated into the porous frame structure directly. Applicant provided a comparative table. However, the table is misleading because the density of 2-6 X 104 cells/ml stated by Applicant is actually broader because Masuda et al. teach “at least about 104 cells/ml” [0042], which is open ended. Furthermore, the cells were cultured for 5 days to form a cell-associated matrix (CM) [0042], which means the actual density is larger due to proliferation of the cells in the cell culture medium. The table points out a 3 day culture for the instant application and 5 days for Masuda et al. However, the claim 5 recite: “wherein the cartilage gel is obtained by gelation culture for 3-5 days.” So, Masuda et al. is within the claimed limitation. What conditions and how the culture is recovered is not material to the examination of a composition of matter claim. Especially when Masuda et al. suggest that the chondrocytic cells are cultured in a suitable growth medium [0063].
On page 10 of remarks, Applicant asserts: “It can be seen that the preparation of the cartilage gel of the present application is more simple, and the cartilage gel is more pure. The preparation of the cartilage gel of the present application does not involve the use of agarose and sodium alginate in culture and their removal.” However, “more simple” and “The preparation” speak to the method of producing the cartilage gel and not the product obtained. A composition of matter claim is under examination; not a process claim. Independent claim 1 uses the transitional language “comprises” which is open to the inclusion of other components. Claim 1 does not exclude other components such as agarose or sodium alginate.
On page 10 of remarks, Applicant argues that Masuda et al. is silent on cartilage sheet pieces. However, claim 1 recites: “cartilage gel or cartilage sheet pieces”. The components are in the alternative. Furthermore, the cartilage sheet is just a waypoint in the method to prepare the final product and is destroyed in the mincing process to produce cartilage pieces, which is a common thing to do where Vunjak-Novakovic et al. teaches that it is common to have milled/minced cartilage pieces in a carrier repair assembly with chondrocytes. See MPEP 2113(I): PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
On pages 10-13, Applicant asserts that “the claimed cartilage tissue engineering complex showed unexpected advantage in animal transplantation experiment for repairing articular cartilage.” However as shown in Figure 9, the comparative example is demineralized bone alone and not the closest prior art engineered cartilage tissue of Masuda et al. To be effective to rebut a prima facie case of obviousness, the data must compare the claimed subject matter with the closest prior art. See MPEP 716.02(e). Applicant’s comparison with demineralized bone matrix is significantly different from the engineered cartilage chondrogenic cell associated matrix scaffold implant of Masuda et al. which comprises at least one of aggrecan, collagen types II, IX and XI, and hyaluronan and “closely resembles naturally occurring articular cartilage in its physicochemical properties” (Claim 6 and [0068] of Masuda et al.). Additionally, Applicant comments: “The wound at the defect B is rough and has only physical support, which cannot be repaired immediately.” However, this would appear to be an expected result as demineralized bone alone lacks cell associated matrix and at least one of aggrecan, collagen types II, IX and XI, and hyaluronan, as taught by Masuda et al., that would assist with immediate repair.
On page 13 of remarks, Applicant asserts that the results are unexpected. However, the Examiner had previously reviewed the specification for results characterized as unexpected by the inventors. See pages 7-8 of the non-FINAL: “A text search of the specification for “surprising” “surprisingly” “synergistic” or “unexpectedly” only had 1 hit. The specification states: “the inventors surprisingly discovered and developed a cartilage tissue engineering complex for the first time.” However, as shown below, cartilage tissue engineering complexes are already well- known in the art. Consequently, there does not appear to be anything surprising about it at all.” Therefore, the characterization of these results as "unexpected" is unsupported attorney argument. See In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997). While the data provided by Applicant has been considered, it is not persuasive. Respectfully, Applicant’s arguments are not persuasive.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 Claims 19 and 20 are improperly indicated as “Previously Presented” and not as Withdrawn. In the interest of stakeholder interaction and compact prosecution, the Examiner is not sending a Notice of Non-Compliant Claim Amendment. Rather, the Examiner is alerting Applicant to the issue for future correspondence.