DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 22 December 2025 have been entered. Claims 18-32 were previously pending in the application. Claim 19 has been cancelled by Applicant. Claims 18 and 20-32 are currently pending in the application. Claims 18, 24, 28, 30, 31, and 32 are independent claims.
The election of Group I, drawn to a method to obtain mesenchymal stem cells (MSC) with enhanced activity for the treatment of osteoarticular disease or trauma, remains in effect in the instant application. The following election of species remains in effect in the instant application:
ATP-synthase inhibitors: a. Oligomycin.
Claims 24-32 remain withdrawn from consideration as being directed to a nonelected invention, there being no allowable generic or linking claim.
Claims 18 and 20-23 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/IB2020/061190, filed 26 November 2020, which claims priority to EPO 19211428.8, filed 26 November 2019. Filing of a certified copy of the EPO 19211428.8, filed 26 November 2019 is acknowledged.
Thus, the earliest possible priority for the instant application is 26 November 2019.
Claim Objections
The objection to amended and cancelled claims 18-23 for reciting abbreviations (claim 18) and for referring to a method without the use of an indefinite article (claims 18-23) is withdrawn in view of the cancellation of claim 19 and Applicant’s amendment to claim 18 removing the abbreviations and to claims 18-23 adding in indefinite articles preceding “method”.
Claim Rejections - 35 USC § 112(b)
The rejection of amended and cancelled claims 18-23 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is withdrawn in view of Applicant’s amendments to the claims such that the issues of indefiniteness have been addressed.
Claim Rejections - 35 USC § 102
The rejection of amended and cancelled claims 18-20 and 23 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. 2008, Stem Cells, 26, 960-968, is withdrawn over cancelled claim 19 and maintained over amended claims 18, 20, and 23. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claim 18 to recite culturing the MSC in an induction media supplemented with 0.1 to 1 µg/ml of an ATP-synthase inhibitor, wherein the ATP-synthase inhibitor is oligomycin.
Chen teaches culturing the bone marrow-derived MSC in an induction media supplemented with 0.63 µg/ml oligomycin, wherein incubation with oligomycin decreased ALP activity in the MSCs and decreased Cbfa-1 mRNA expression in MSCs compared to cells not treated with oligomycin, thereby indicating that that decreased mitochondrial oxidative phosphorylation could hamper the osteogenic differentiation of hMSCs [column 12 ¶ 2, Figure 7B].
Applicant additionally amended independent claim 18 to recite functional limitations attributable to the improved MSCs produced by the claimed method. Note that the method steps recited by Chen are identical to the method steps recited in the instant claims. As such, the product generated thereby will necessarily and inherently have the same structural and functional properties, absent evidence to the contrary. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Therefore, by teaching all the limitations of amended claims 18, 20, and 23, Chen anticipates the instant invention as claimed.
Applicant argues that Chen does not teach culturing MSC in an induction media supplemented with 0.01 to 1 µg/ml of an ATP-synthase inhibitor.
However, this is not agreed.
As discussed above, Chen teaches to culture MSC in an induction media supplemented with 0.63 µg/ml of oligomycin (Figure 7B].
Therefore, Applicant’s amendments and arguments do not overcome a finding of anticipation under 35 U.S.C. 102(a)(1), and the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejection of amended and cancelled claims 18-23 under 35 U.S.C. 103 as being unpatentable over Chen et al. [2008, Stem Cells, 26, 960-968], is withdrawn over cancelled claim 19 and maintained over amended claims 18 and 20-23. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claim 18 to recite culturing the MSC in an induction media supplemented with 0.1 to 1 µg/ml of an ATP-synthase inhibitor, wherein the ATP-synthase inhibitor is oligomycin.
Chen teaches culturing the MSC in an induction media supplemented with 0.63 µg/ml oligomycin, wherein incubation with oligomycin decreased ALP activity in the MSCs and decreased Cbfa-1 mRNA expression in MSCs compared to cells not treated with oligomycin, thereby indicating that that decreased mitochondrial oxidative phosphorylation could hamper the osteogenic differentiation of hMSCs [column 12 ¶ 2, Figure 7B].
Applicant additionally amended independent claim 18 to recite functional limitations attributable to the improved MSCs produced by the claimed method. Note that the method steps recited by Chen are identical to the method steps recited in the instant claims. As such, the product generated thereby will necessarily and inherently have the same structural and functional properties, absent evidence to the contrary. Reliance upon inherency is not improper even though rejection is based on Section 103 instead of Section 102. In re Skoner, et al. 186 USPQ 80 (CCPA). As stated in MPEP 2112, The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995). See also In re Grasselli, 713 F.2d 731,739, 218 USPQ 769, 775 (Fed. Cir. 1983). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Applicant argues that:
there is no motivation to modify the methods of Chen to lower the amount of ATP-synthase inhibitor;
the method of the instant invention utilizes a glucose-enriched medium and does not require the addition of growth factors or exogenous cytokines to induce differentiation, unlike the method of Chen which requires exogenous factors such as ascorbic acid and dexamethasone, thereby simplifying the experimental system and allowing for the direct assessment of the effects of metabolic modulation;
the protocol of Chen does not provide MSCs with the same improved properties as that of the present claims and so does not render the present claims obvious.
However, that is not agreed.
In response to Applicant’s arguments, it is noted that the test for obviousness is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the reference would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Further, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Specifically, regarding Applicant’s argument 1), note that, as discussed above, Chen teaches to use 0.63 µg/ml of oligomycin, and so no motivation to modify is necessary [Figure 7B].
Regarding Applicant’s argument 2), note that the broadest reasonable interpretation of Applicant’s independent claim 18 as written encompasses any induction media and does not require the absence of growth factors or exogenous cytokines. Therefore, the claims as written encompass the induction media of Chen.
Regarding Applicant’s argument 3), note that the broadest reasonable interpretation of Applicant’s independent claim 18 as written encompasses any induction media comprising any components, to which the oligomycin is added as a supplement. As such, the claimed method encompasses the method taught by Chen. Given that the MSCs produced by the method of Chen were produced by the same method as claimed, the structural and functional properties of the cells produced by the method of Chen are expected to be identical to the cells produced by the instantly claimed method, absent evidence to the contrary.
Therefore, Applicant’s amendments and arguments do not overcome a finding of obviousness under 35 U.S.C. 103, and the rejection is maintained.
Conclusion
No claim is 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 Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634