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 .
Applicant’s amendments and arguments of August 9, 2026, are entered.
Claim 1 has been amended.
Claims 8, 17, and 18 have been canceled.
No new claims have been added.
Status of Claims
Claims 1, 3-4, 6, and 9-15 are pending.
Double Patenting
The previous statutory double patenting rejection recited in the Office action dated May 8, 2026, is withdrawn.
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 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 7 of copending Application No. 18/262,232 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of copending Application No. 18/262,232 is generically directed to a cartilage tissue engineering complex, whereas claim 1 of the instant application is directed to the specific species of an ear cartilage tissue engineering complex. Both claims recite the same or substantially similar structural and compositional limitations concerning the carrier and cartilage-derived cellular material. The primary distinction is that the instant claim specifies ear cartilage. However, ear cartilage would have been an obvious choice to a person of ordinary skill over the copending applications generic limitation where obtaining an ear cartilage tissue engineering complex while retaining the same or substantially the same structural and compositional features. The same rational is applied to claim 6 of the instant application as it relates to claim 7 of the copending application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-4, 6, 9, 10-15 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 1 recites “…a more closely integrated structure with the carrier” as it relates to loading ear chondrocytes on a carrier and is a relative term that fails to identify referenced structures or conditions against which integration is compared. Additionally, the specification merely reiterates this language without providing an objective standard for determining how the more closely integration is formed or what degree of integration is required to meet the claimed limitation. Given this, a person of ordinary skill would not understand the metes and bounds of the claimed limitation.
Claims 3-4, 6, 9, 10-15 are also rejected given these claims inherit the same indefiniteness of claim 1.
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.
Claims 1, 3-4, 6, and 9-15 are rejected under 35 U.S.C. §103 as being unpatentable over Masuda et al. [US 2003 229400 A1, 2003], in view of in view of Gomes et al. [US 2004 0230303, 2004], in view of Mizuno et al. [Brief report: reconstruction of hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage, Stem Cells, 2014], in view of Yao et al. [Evaluation of insulin medium or chondrogenic medium or proliferation and chondrogenesis of ATDC5 cells, Biomed Research International, 2014], in view of Way et al. [Cytocentrifugation: a convenient and efficient method for seeding tendon-derived cells into a monolayer culture or 3-D tissue engineering scaffolds, Cytotechnology, 2011], in view of Smeriglio et al. [3D hydrogel scaffolds for articular chondrocyte culture and cartilage generation, J Vis Exp, 2015].
Regarding claim 1, Masuda et al. teaches a transplantable osteochondral implant comprised of engineered cartilage tissue that is attached to a biocompatible support scaffold that contains a plurality of pores [¶ 0008]. Masuda further teaches this osteochondral implant can be derived from a variety of sources that include auricular cartilage [¶ 0010]. Masuda et al. further teaches a cartilage tissue engineering complex that comprises a porous frame structure where the cartilage tissue is derived from chondrogenic cells cultured in vitro, and the cells have a cell associated matrix that implicitly encapsulates the cell population and that the scaffold is selected from natural cancellous bone, demineralized natural cancellous bone, collagen, and bone substitute material [Claims 1-2, 6; ¶ 0068]. Masuda et al. further teaches a gel and having 1 or 2 more layers of cartilage tissue or cells that can be cultured as a monolayer [¶ 0066]. Here, Masuda et al. teaches the structural arrangement presently claimed. For example, Masuda et al. teaches ear cartilage-derived chondrocytes associated with chondrocyte-secreted extracellular matrix and loaded onto or associated with a porous biocompatible carrier followed by further culture to produce an integrated cartilage tissue-engineering construct. Masuda et al. also teaches a chondrocyte culture media that uses DMEM-based medium, serum, and antibiotic components [¶ 0063]. However, Masuda et al. does not expressly teach a cell density of at least 1.0 x 108 cells/ml or 1.0 x 108 cells/g. However, Gomes et al. teaches that in cartilage repair art the cellular density of the cells is preferably range from 1.0 x 108 cells/ml to 5.0 x 108 [Abstract, Figures 1-9].
Based on this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Masuda et al. where it was disclosed an engineered cartilage tissue that is attached to a biocompatible support scaffold that contains a plurality of pores with the additional teachings of Gomes et al. that disclosed a preferred cellular concentration of chondrocytes to be used in cartilage repair. Therefore, there is a reasonable expectation of success that an artisan combining the teachings of Masuda et al. and Gomes et al. would develop ear cartilage tissue engineered complex cultured in a gel state where the extracellular matrix excreted by the chondrocytes would encapsulate the chondrocyte cell population with a preferred cell concentration range as disclosed by Gomes et al. given that is the preferred range for cartilage repair given the modification employs a known cell-inoculation concentration being used for its disclosed purpose in a compatible cartilage tissue engineering system where there would be a reasonable expectation of obtaining a complex containing viable chondrocytes capable of producing an engineered cartilage complex as taught by Masuda et al.
With respect to the recited language that the ear cartilage gel is “obtained by gelation culture for 2.5-5.5 days,” the ear cartilage sheet is “obtained by gelation culture for 6-30 days,” the cartilage sheet pieces are “prepared by mincing”, and the complex is “formed by inoculating”” the cartilage gel or sheet pieces on the carrier followed by chondrogenic culture, claim 1 is directed to the resulting ear cartilage tissue-engineering complex and therefore contains product-by-process limitations. Under §2113 states “[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).”
With respect to applicant’s amendment of claim 1 from “comprising” to “consists of”, the closed transitional phrase has been given its appropriate limiting effect consistent with MPEP § 2111.03. However, Masuda et al. continues to teach the recited chondrocyte/extracellular matrix components relied upon as stated above, and because claim 1 is directed to the resulting cartilage tissue-engineering complex, limitations concerning the manner in which the cartilage gel or sheet pieces are prepared constitute product-by-process limitations and are considered according to the structure imparted to the resulting product rather than the particular process steps used during preparation [See MPEP §2113]. Because of this, Masuda et al.’s use of agarose, sodium alginate, or other materials during preparation does not, without evidence that such processing produces a structurally distinguishable cartilage product overcome the teachings of Masuda et al. where chondrocytes associated with chondrocyte-produced extracellular matrix and their incorporation with a porous biocompatible support structure. Additionally, the specification does not identify the presently relied upon culture conditions or parameters as critical to obtaining the claimed tissue- engineering complex. The specification also does not show unexpected or superior results relative to the prior art teachings for cartilage tissue-engineering systems.
For claim 3 where the cartilage gel is obtained by gelation culture for about 10-15 days, preferably 3-5 days, Masuda et al. teaches that crosslinks exhibit a large increase in concentration after two weeks of culture [¶ 0052].
For claim 4 where the complex of claim 2 exhibits an adhesion rate of the ear cartilage gel greater than or equal to 90%, Masuda only states that a known method for chondrocyte isolation includes differential adhesion to plastic tissue culture vessels and that antibodies that bind to chondrocyte cell surface marker can be coated on tissue culture plates and then used selectively to bind chondrocytes from a heterogenous cell population [¶ 0038]. Based on this disclosure, an ordinary artisan would desire the highest adhesion rate possible such as 100% and thus achieving an adhesion rate of the cartilage gel of greater than or equal to 90% would have been obvious to an ordinary artisan.
For claim 6 where the ear cartilage sheet is obtained by gelation culture for 10-15 days, Smeriglio et al. discloses the use of hydrogels given that this hydrogel scaffolding provides a physiologically relevant microenvironment for in vitro culture of chondrocytes [Abstract]. Masuda et al. teaches that crosslinks exhibit a large increase in concentration after two weeks of culture [¶ 0052].
For claim 9 where the porous frame structure is made of a biodegradable material selected from and including decalcified bone matrix, Masuda et al. discloses the use of demineralized natural cancellous bone or bone substitute material [¶ 0007].
For claim 10 where the elastic ear cartilage frame structure complex is converted into articular cartilage under the joint microenvironment, Mizuno et al., discussing hyaline cartilage being derived from ear elastic cartilage, teaches that auricular, i.e. ear elastic cartilage, can undergo phenotypic modulation and produce hyaline-like cartilage matrix under appropriate environmental conditions that include exposure to TGF-Beta, compression, and/or joint-like biochemical and mechanical cues [Abstract]. Here, a person of ordinary skill in the art would have had a reasonable expectation of success to combine the teachings of Masuda et al. with the additional teachings of Mizuno et al. because Mizuno et al. demonstrated that ear-derived cartilage progenitor cells can produce cartilage having characteristics comparable to hyaline joint cartilage which establishes the ear-derived cartilage progenitor cells as suitable for cartilage tissue engineering. Therefore, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Masuda et al. that discloses a method for preparing a engineered cartilage complex with the additional teachings of Mizuno et al. where Mizuno et al. specifically taught that ear-derived cartilage progenitor cells are capable of producing hyaline like cartilage that is suitable for joint repair because the combination represents the use of known elements according to established methods yielding predictable results, i.e. an engineered cartilage complex capable of producing cartilage matrix.
For claim 11 where the ear cartilage gel or ear cartilage sheets are inoculated into a porous scaffolding frame, Way et al., discussing seeding methods for seeding tendon-derived cells, discloses the use of cytocentrifugation as a method for seeding chondrocytes onto a 3-D tissue engineered scaffold [Abstract, Introduction ¶ 4].
For claim 12 where the chondrogenic culture in vivo culture contains high-glucose DMEM, serum substitute, proline, vitamin C, TGF-Beta, insulin growth factor, and dexamethasone, Yao et al., discussing an insulin medium for proliferation and chondrogenesis, describes a medium that contains DMEM, ITS+, proline, ascorbic acid (vitamin C), TGF-Beta. However, Yao et al. does not disclose the use of an insulin growth factor, but it would have obvious to a person skilled in the art to substitute insulin with insulin growth factor since both are peptide hormones that activate similar downstream pathways, e.g. PI3K. Additionally, a person of ordinary skill would reasonably expect insulin growth factor to provide similar or superior results to insulin in a culture containing chondrocytes. It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Masuda et al. that teaches a method for engineering a cartilage complex with the teachings of Yao et la. that discloses an insulin culture medium designed for proliferation, chondrogenesis, and cartilage matrix production. A person of ordinary skill would have had a reasonable expectation of success based on the known chondrogenic activities of these factors as taught by Yao et al. where the combination represents the use of a known technique to improve a similar method in the same way.
For claim 13 where no liquid is added to the centrifugal system where the ear cartilage sheet pieces are loaded into a porous frame, Way discloses the use of cytocentrifugation as a means of seeding tendon-derived cells into a 3-D engineered scaffold without the addition of more liquid other than what is present in the cell cultures [Abstract].
For claim 14 where the ear cartilage tissue engineered complex is used for repairing defective joints, Masuda et al. discloses the use of an engineered chondrocyte complex to repair or replace articular cartilage and underlying bone [¶ 0005].
For claim 15 where the engineered complex is transplanted into the defective joint of a patient where the joint needs to be replaced, Masuda et al. discloses a transplantable osteochondral implant for the purpose of repairing or replacing articular cartilage and/or underlying bone [¶ 0005].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to modify the systems and methods of Masuda et al. in combination with the above cited references using known cartilage-forming materials, culture conditions, and biocompatible carrier techniques taught in the art to produce the presently claimed tissue-engineering complex where the combination involved known elements according to their established functions. Here, a person of ordinary skill in the art would have had a reasonable expectation of success in combining the above cited references to arrive at an ear cartilage tissue engineered construct capable of functioning as a transplantable osteochondral implant for repairing and/or replacing articular cartilage and/or underlying bone since the above cited references demonstrate the successful use of chondrocyte-containing cartilage constructs and biocompatible supporting materials for cartilage and osteochondral tissue engineering. Furthermore, combining the teachings of Masuda et al., Mizuno et al., and Yao et al., along with Way and Smeriglio et la., to arrive at the claimed cartilage tissue engineered complex employing known ear-derived cartilage cells and established chondrogenic culture conditions being used for their intended purpose would yield predictable results.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the 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 references, especially in the absence of evidence to the contrary.
Response to Argument
Applicant argues that the claimed invention adopts a technical system completely distinct from that disclosed in Masuda et al. for preparation of the ear cartilage gel. More specifically, Applicant argues that Masuda et al. employs conventional “cells + material carrier” system utilizing materials such as agarose or sodium alginate, whereas the present claimed invention establishes a carrier-free, pure, high-density culture system. Applicant further argues that the engineered cartilage tissue of Masuda et al. contains residual carrier material, while the engineered complex of the present application consists solely of cells and cell-secreted extracellular matrix resulting in a product that is fundamentally different.
Applicant’s argument has been considered but is not persuasive given it is not commensurate with the scope of claim 1. Furthermore, it is inconsistent with the express language of the claim. Although Applicant characterizes the claimed invention as employing a “carrier-free” system, claim 1 expressly does not claim a “carrier-free” product. Secondly, claim 1 does not require that the engineered cartilage be produced by the specific carrier-free, high density culture process that Applicant argues. Additionally, as explained in the §103 rejection, MPEP § 2113 requires patentability of a product based upon the product itself rather than the process by which it is made. The difference in the process of preparing the respective cartilage products does not, by itself, establish a patentable distinction where the claimed product is otherwise taught or rendered obvious by prior art. Applicant has not identified a claimed structural limitation resulting from the process that distinguishes the claimed product from the combined teachings of the cited references.
Likewise, Applicant reliance upon different culture density, culture conditions, culture duration, culture recovery, and the use or absence of agarose, sodium alginate, or other materials during the preparation is directed to the difference in the manufacturing or culture process rather than limitations actually required by claim 1. Furthermore, as explained by MPEP § 2113, patentability of a product is based upon the product itself and not the process by which the product is produced unless there is some cited unexpected result.
Applicant also argues that the origin of the cartilage material is similarly unpersuasive. Applicant emphasizes that the milled or minced cartilage pieces of Masuda et al. originate from natural cartilage tissue isolated from a subject, whereas Applicant’s cartilage gel or cartilage sheet pieces are obtained through in vitro culture. However, Applicant’s own specification states that autologous chondrocytes are taken from a subject having joint defects and subsequently cultured in vitro to prepare the ear cartilage gel or cartilage sheet pieces [See Specification pg. 12 Line 23-24]. Applicant’s disclosed process also begins with naturally derived cartilage obtained from a subject. Given this, the distinction claimed by Applicant concerns the subsequent processing and in vitro culture conditions of the naturally derived chondrocytes rather than a fundamentally different biological origin of the cartilage material or other biomimetic process for synthetic cartilage. Additionally, Applicant’s reliance upon the submitted comparative evidence is also insufficient given that Applicant’s comparative analysis is with demineralized bone [See Fig. 9] and not the engineered cartilage complex taught in Masuda et al. MPEP § 716.(e) explains that evidence relied upon to establish unexpected results must provide an appropriate comparison between the claimed invention and the closest prior art. Demineralized bone does not provide a comparison with the engineered cartilage tissue.
Based on this, Applicant’s arguments concerning a fundamentally different technical system, carrier-free culture, differences in culture density and conditions, the natural origin of Masuda et al.’s cartilage pieces, and the submitted comparative evidence do not overcome the case for prima facie obviousness. The asserted differences are either directed to unclaimed preparation conditions that cannot by imported into the claims, are inconsistent with or broader than the actual language, or are unsupported by comparative evidence demonstrating unexpected results relative to the closest prior art. Because of this, claims 1, 3-4, 6, and 9-15 are rejected under §103.
Conclusion
No claims allowed.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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