DETAILED ACTION
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
Receipt is acknowledged of the preliminary amendment submitted on 15 August 2024. Claims 3, 5, 8, 10-11, 13-14, 17-18, 22-26, and 31 are amended. Claims 4, 9, 12, and 15-16 are canceled.
Claims 1-3, 5-8, 10-11, 13-14, and 17-31 are pending.
Applicant’s election without traverse of the invention of group III (claims 6-8, and 10-11) drawn to a three-dimensional culture system for selecting an agent in the reply filed on 10 August 2026 is acknowledged.
Claims 1-3, 5, 13-14, and 17-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 6-8, and 10-11 are pending and under examination in the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2023/062656, filed 15 February 2023, which claims priority to United States provisional Application No. 63/310,299, filed 15 February 2022. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copies of papers required by 37 CFR 1.55 have been filed in this application on 15 August 2024.
The earliest possible priority for the instant application is 15 February 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 15 August 2024, 26 March 2025, and 12 December 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 15 August 2024 are accepted by the Examiner.
Claim Objections
Claims 6 and 10 are objected to because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims (for example: “PRG4”, “COL2A1”, “ACAN”, “IL-1β”, and “TGF-β”). Appropriate correction is required.
Claim 11 is objected to because of the following informalities: the claim is missing a definite article between “wherein” and “agent”. The claim should read -----wherein the agent----. Appropriate correction is required.
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.
Claims 6-8, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over US2016/0038544 (Of Record) (hereinafter “Keller”) in view of Dennis et al., Frontiers in bioengineering and biotechnology 8 (2020): 590743, of record, hereinafter “Dennis”.
Regarding claim 6, Keller teaches methods for generating chondrocytes and cartilage (Keller, Abstract). Keller teaches that the culturing may be in a three-dimensional system and that the methods use a scaffold (Keller, [0048], [0076]). Keller teaches that the chondrocytes can be modified to stably express a reporter protein operably linked to a lubricin (PRG4) promoter (Keller, [0261], [0070]). Keller specifically refers to a chondrocyte reporter system with a reporter protein linked to a chondrocyte specific promoter like lubricin (PRG4) (Keller, [0286]). Keller also teaches that reporter assays can be used to screen numerous candidate substances in a high-throughput drug-screening program (Keller, [0261]).
Keller does not teach to have the system at about 2% to 8% oxygen.
Dennis teaches oxygen percentages for the culture of chondrocytes in tissue-engineering contexts (Dennis, Title, Abstract). Dennis teaches that culturing chondrocytes at 5% oxygen (physiologic oxygen) increases the mechanical properties of engineered cartilage by increasing extracellular matrix component deposition by the chondrocytes (Dennis, Title, Abstract). Dennis specifically teaches that 5% oxygen results in a higher percentage of handleable tissue-engineered cartilage sheets than atmospheric oxygen (Dennis, page 4, last partial paragraph) and that these sheets are significantly thicker than those grown at atmospheric oxygen (Dennis, page 6, first paragraph). Thus, a person having ordinary skill in the art before the effective filing date of the claimed invention would have known from Dennis that culturing chondrocytes at physiologic oxygen levels provides distinct advantages over higher oxygen levels not in the least of which being the ability to produce engineered cartilage with better mechanical properties.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have used the 5% oxygen level taught by Dennis in the system of Keller and to have arrived at the invention claimed in instant claim 6 with a reasonable expectation of success because they would have been motivated to do so to increase the mechanical properties of the cartilage produced via the system or at least to have maintained the chondrocytes under conditions that more effectively recapitulate the physiologic environment they are naturally found in. There would have been a reasonable expectation of success in using the physiologic oxygen level of 5% of Dennis in the system of Keller insofar as both references are concerned with the culture of chondrocytes for tissue-engineering applications and a person having ordinary skill in the art would need to determine a concentration of oxygen to use for the system of Keller considering Keller’s silence on the issue and they would have reasonably expected the 5% oxygen level of Dennis to have similar advantageous effects on chondrocyte culture in the system of Keller.
Regarding claim 7, Dennis teaches 5% oxygen.
Regarding claim 8, Keller teaches that the reporter protein can be a fluorescent protein such as GFP, RFP, dsRed etc., or luciferase (Keller, [0261]). Luciferase is a bioluminescent protein.
Regarding claim 10, Keller teaches to treat the chondrocytes with TGFβ and/or IL-1β (Keller, Figure 6- 9; [0067]-[0070]).
Regarding claim 11, Keller teaches to screen a test substance using the chondrocytes wherein the test substance can be a disease mediator or a component with protective activity or can affect the biologic activity of the chondrocytes (Keller, [0263]-[0268]). Thus, Keller teaches the limitations of claim 11.
Additional Comments
The following is a list of other relevant pieces of prior art for the instant invention.
Malda, Jos, Travis J. Klein, and Zee Upton. "The roles of hypoxia in the in vitro engineering of tissues." Tissue engineering 13.9 (2007): 2153-2162, teaches the role of physiologic oxygen in the culture of cells other than chondrocytes for tissue-engineering applications.
Fathollahipour, Shahrzad, Pritam S. Patil, and Nic D. Leipzig. "Oxygen regulation in development: lessons from embryogenesis towards tissue engineering." Cells Tissues Organs 205.5-6 (2019): 350-371 teaches the importance of physiologic oxygen levels for specific cell types with a particular focus on embryonic stem cells in hypoxic conditions in early development.
Shang, Jin, et al. "Roles of hypoxia during the chondrogenic differentiation of mesenchymal stem cells." Current stem cell research & therapy 9.2 (2014): 141-147 teaches a physiologic oxygen range for the bone marrow of 1-7% oxygen and focuses on the effects of these oxygen concentrations on the differentiation of mesenchymal stem cells into chondrocytes. Provides a table which shows at least 9 other research groups have used 5% oxygen to culture MSCs with enhanced extracellular matrix deposition (Table 1).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA G LEAVITT can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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