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
Claims 1-18 are pending.
Priority
Claims 1-18 are a 371 of PCT/CN2022/072409 filed on January 17, 2022, which has priority to CHINA 202110075631.X filed on January 20, 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on July 10, 2023 and on February 26, 2024 were filed before the mailing of the First Office Action on December 13, 2025. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 2, 5, 6, and 7 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 7, 8, and 15 of copending Application No. 18/262,232 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Applicant is advised that should claim 1 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 8 recites that chondrocytes are either autologous or xenogenous. However, the limitation does not impose any structural limitation on the claimed complex. Autologous or xenogenous chondrocytes are a recipient dependent characteristic and not a property of the construct itself. Thus, despite the difference in wording, these claims have substantially the same scope.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 14, and are rejected under 35 U.S.C. §101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because:
Step 1: Is the claim to a process, machine, manufacture, or composition of matter? (I.e., a statutory category). No, claim 14 is directed to a “use” and does not recite a process, a machine, manufacture, or composition of matter. The claim is merely directed to the intended use or purpose.
Because claim 14 fails Step 1, no further analysis is needed, and Claim 14 is rejected under 35 U.S.C. §101 as being directed to non-statutory subject matter by not reciting a machine, process, manufacture, or composition of matter.
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 3, 4, 6, 10, and 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “2.5-5.5 days”, and the claim also recites “3-5 days” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation “≥ 90%”, and the claim also recites “≥ 95%” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation “6-30 days”, and the claim also recites “7-20 days, and most preferably 10-15 days” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 8 recites “preferably autologous ear chondrocytes”. However, the term “preferably” is unclear. The specification does not identify any embodiments or criteria in which autologous chondrocytes are preferred over other cell sources. Additionally, the specification does not provide guidance as to how this preference affects the structure or boundaries of the claimed complex. Based on this, it is unclear whether the claim requires chondrocytes to be autologous or is merely a suggestion.
Claim 8 recites “autologous ear chondrocytes or xenogenous ear chondrocytes”. The terms “autologous” and “xenogenous” describe a relationship between the cells and a specific recipient and is not a property inherent in the claimed complex itself. Because of this, these terms cannot be evaluated without reference to an unspecified organism. Therefore, it is unclear whether Applicant is intending to limit the claim to complexes that exist only within or in relation to a particular organism.
Claim 10 recites the limitation "ear cartilage gel ear cartilage sheet pieces-frame structure complex" in Lines 1 and 2. There is insufficient antecedent basis for this limitation in the claim. Applicant is advised to amend the claim to read “ear cartilage gel or ear cartilage sheet pieces-frame structure complex”.
Claim 14 recites “use” and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 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 14 is directed to nonstatutory subject matter. The claim(s) does not fall within at least one of the four categories of patent eligible subject matter because the term “use” is merely describing an intended application or purpose of a claimed invention rather than defining the invention itself as a statutory product. Therefore, a “use” limitation does not confer patent eligibility.
Claim 15 recites “…engineering complex of claim 1 is used to be transplanted into the defect joint of a patient”. However, “is used to be transplanted” is not clear. What is being used versus transplanted? Is the complex being transplanted? As written, a person of ordinary skill would not understand what is meant by the claim language.
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 1-18 are rejected under 35 U.S.C. §103 as being unpatentable over Masuda et al. [US 2003 229400 A1, 2003], in view of Vunjak-Novakovic (Hereinafter Vunjak) [US 2005 064042 A1, 2005], 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 chodrogenesis 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], in view of Gomes et al. [US 2004 0230303, 2004].
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 [¶ 0010].
Regarding claim 2 where the ear cartilage gel comprises a cell population of chondrocytes and extracellular matrix secreted by chondrocytes, Smeriglio, discussing the use of hydrogel scaffolds for culturing articular chondrocytes, discloses the use of hydrogels given these hydrogel scaffolding provides a physiologically relevant microenvironment for in vitro culture of chondrocytes [Abstract]. However, Smeriglio et al. or Masuda et al. do 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 Smeriglio et al. where the authors used hydrogels for culturing articular cartilage due to the benefits it provided in the microenvironment 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. with Smeriglio 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.
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 5 where the ear cartilage sheet pieces are minced with the similar density as claim 2, Vunjak, where the inventors disclose a cartilage implant plug with fibrin glue, teaches that the cartilage mixture can be minced. Given this, it would have prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to recognize the teachings of Vanjak et al. where minced cartilage would be an effective method of culturing elastic, i.e. ear, cartilage. Additionally, 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]. Therefore, there is a reasonable expectation of success that an artisan would combine the teachings of Masuda et al. that included the use of elastic cartilage, i.e. ear cartilage, as a source that could be used for an engineered tissue complex with the additional teachings of Vanjak et al. that taught the articular cartilage could be minced with the Gomes et al. that disclosed the ideal cell concentration range of chondrocytes for cartilage repair.
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 these 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 7 where gelation culture is in vitro with the gelation medium consisting of certain claimed components, Smeriglio et al. teaches the use of DMEM, 10% Fetal Bovine Serum, with 100 U/ml penicillin/streptomycin [Articular chondrocyte isolation No. 5].
For claim 8 where the ear chondrocytes are derived from autologous ear chondrocytes or xenogenic ear chondrocytes, Vanjak et al. discloses the use of autologous chondrocytes [¶ 0010].
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].
Here, 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. with the further teachings of Smeriglio where it is taught a gelation medium for culturing chondrocytes with the additional teachings of Vanjak that discloses the use of autologous chondrocytes. Given this, there is a reasonable expectation of success that an artisan would combine the teachings of Masuda et la. with the additional teachings of both Smeriglio et al. and Vanjak et al. where the artist would choose a gelation medium known for culturing chondrocytes and that the chondrocytes cultured could be autologous, allogenic, or xenogenic in nature.
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].
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.
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].
For claim 16 where the complex of claim 6 contains a gelation culture in vitro with a medium containing DMEM, 10% FBS, and 100U/ml penicillin-streptomycin, Smeriglio et al. teaches the use of DMEM, 10% Fetal Bovine Serum, with 100 U/ml penicillin/streptomycin [Articular chondrocyte isolation No. 5].
For claim 17 where the method of claim 11 where the ear cartilage gel comprises a cell population of chondrocytes and extracellular matrix secreted by chondrocytes, Smeriglio, discussing the use of hydrogel scaffolds for culturing articular chondrocytes, discloses the use of hydrogels given these hydrogel scaffolding provides a physiologically relevant microenvironment for in vitro culture of chondrocytes [Abstract]. However, Smeriglio et al. or Masuda et al. do 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 Smeriglio et al. where the authors used hydrogels for culturing articular cartilage due to the benefits it provided in the microenvironment 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. with Smeriglio 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.
For claim 18 where the method of claim 11 contains the ear cartilage sheet pieces are minced with the similar density as claim 2, Vunjak, where the inventors disclose a cartilage implant plug with fibrin glue, teaches that the cartilage mixture can be minced. Given this, it would have prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to recognize the teachings of Vanjak et al. where minced cartilage would be an effective method of culturing elastic, i.e. ear cartilage. Additionally, Gomes et al. teaches that in cartilage repair art the cellular density of the cells is preferably a range from 1.0 x 108 cells/ml to 5.0 x 108 [Abstract, Figures 1-9]. Therefore, there is a reasonable expectation of success that an artisan would combine the teachings of Masuda et al. that included the use of elastic cartilage, i.e. ear cartilage, as a source that could be used for an engineered tissue complex with the additional teachings of Vanjak et al. that taught the articular cartilage could be minced with the Gomes et al. that disclosed the ideal cell concentration range of chondrocytes for cartilage repair.
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.
Conclusion
No claims allowed.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638