DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 30 October 2025 have been entered. Claims19-36 were previously pending in the application. Claims 19-36 are currently pending in the application. Claims 19 and 36 are independent claims. The following election of species remains in effect in the instant application:
Cartilage-related disease: h. degeneration of cartilage and/or subchondral bone,
Additional treatments: a. repairing cartilage tissue and/or subchondral bone,
Claims 19-36 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/JP2021/001162, filed 15 January 2021, which claims priority to JP 2020-005679, filed 17 January 2020. Filing of a certified copy of the JP 2020-005679, filed 17 January 2020 is acknowledged.
Thus, the earliest possible priority for the instant application is 17 January 2020.
Specification
The objection to the specification of the disclosure for the Brief Description of the Drawings not including a description of each panel individually and for reciting trade names and/or marks used in commerce without corresponding generic terms and/or symbols, is withdrawn in view of the amendment to the specification.
Drawings
Applicant’s Drawings containing Replacement Sheets for Figures 2-6 received on 30 October 2025 have been entered.
Claim Objections
The objection to amended claim 27 for reciting the abbreviation “GPC-MALS” without first writing out the term for which it is an abbreviation, is withdrawn in view of the amendment to claim 27.
Claim Rejections - 35 USC § 112(b)
The rejection of amended claims 26-27 and 30 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claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is withdrawn in view of Applicant’s amendments to claims 26-27 and 30 clarifying the claims.
Claim Rejections - 35 USC § 103
The rejection of amended and previously presented claims 19-36 under 35 U.S.C. 103 as being unpatentable over Iwasaki [US20130189231A1, published 25 July 2013], in view of Gianakos et al. [2017, World Journal of Orthopedics, 8(6), 491-506]; Gobbi et al. [2011, Cartilage, 2(3), 286-299, IDS]; Sudo et al. [JP2019088900A, published 13 June 2019]; and Vitello et al. [2015, Journal of Veterinary Medicine, 152730, 1-4], is maintained. 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 the claims to address issues of indefiniteness and informalities. No amendments were introduced which altered the scope of the claims sufficiently to overcome the obviousness rejection of record.
Applicant argues that:
1) Gianakos does not remedy Iwasaki’s deficiencies because Gianakos teaches that concentrated bone marrow aspirate (cBMA) only demonstrated positive results with improved pain and clinical scores initially but had no significant deference after a year;
2) Gobbi does not teach or suggest a method comprising a cBMA in the absence of a collagen I/III matrix nor provide a reasonable expectation of success in replacing bone marrow mesenchymal stem cells with cBMA;
3) the instant application provides unexpected results of using the claimed method to treat cartilage injury, in that Example 1 provides that the overall macroscopic scores in the UPA+BMAC group were significantly higher than the scores in the UPAL+MSC group or the control groups.
However, this is not agreed.
In response to applicant’s arguments against the references individually, it is noted that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it 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 references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). 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 although Gianakos teaches that “after one-year follow-up, there was no significant difference between groups receiving cBMA and those that did not” specifically for knee osteoarthritis [column 13 ¶ 1], initial improvements alone is sufficient motivation for an ordinarily skilled artisan to use the cBMA, in that any pain relief or improvement in clinical scores is better for a patient than no pain relief or clinical improvement.
Further, Gianakos teaches substantial motivation for using cBMA for treating cartilage injuries, including improvements with durations beyond a year (e.g., up to 5 years):
“The current literature demonstrates the potential benefits of utilizing cBMA for the repair of cartilage injury in the clinical setting. Significant clinical improvement in functional scores was demonstrated with the use of cBMA in the treatment of full thickness cartilage injury, post-traumatic osteoarthritis, and osteochondral lesions. Improved clinical and histologic results were reported when cBMA was used as an adjunctive procedure with either microfracture or MACI in the treatment of full thickness chondral lesions[4,6,7]. On MRI, groups treated with cBMA demonstrated superior cartilage ingrowth with T2 values closer to that of superficial hyaline cartilage when compared to either a control scaffold or MACI alone[7,10]. These positive results were also demonstrated when utilizing cBMA in the treatment of OCLs. Gobbi et al[18] compared with microfracture with cBMA in the treatment of OCLs and found that microfracture resulted in 65% normal IKDC at 2 years with decline to 27% at 5 years vs 100% normal at 2 years and no decline at 5 years for patients treated with cBMA. Buda et al[11] reported a higher presence of hyaline like values and lower incidence of fibrocartilage on T2 mapping in patients who received cBMA when compared to those who received ACI. Hannon et al[19] also demonstrated better T2 relaxation values with higher measurements of adjacent cartilage in patients treated with bone marrow stimulation (BMS) with cBMA than those treated with BMS alone. Surprisingly, these positive results were not translated as effectively when evaluating cBMA in the treatment of knee OA.” [column 12 ¶ 2- column 13 ¶ 1].
Note also that Applicant has not claimed any level or duration of treatment efficacy which would require pain relief and/or clinical improvements beyond a year. Further, Gianakos provides motivation for using cBMA for treating cartilage injury lesions as well as providing a reasonable expectation of success for achieving at least some amount of pain relief and/or clinical improvements.
Regarding Applicant’s argument 2), note that the instant claims as written do not require an absence of collagen I/III matrix. As described above, Gianakos provides the reasonable expectation of success for replacing bone marrow mesenchymal stem cells with cBMA, whereas Gobbi was cited for teaching cartilage injury lesion sizes for treatment.
Regarding Applicant’s argument 3), note that, as discussed above, the combination of Iwasaki and Gianakos provide both teachings and motivation for the limitations recited in instant independent claims 19 and 36, wherein improvements were observed for at least 5 years. Additionally, Applicant’s arguments of unexpected results reference Example 1 of the specification, specifically [0141-0142] and Figures 2-3 referenced therein. The experiment recited in [0141] discusses improvements observed 4 weeks following administration of the cBMA to a cartilage injury lesion. The experiment recited in [0142] discusses improvements observed 16 weeks following administration of the cBMA to a cartilage injury lesion. As such, the improvements presented in Example 1 do not represent a longer duration of improvement compared to that taught by the cited references.
Additionally, note that statistically significant improvement or a successful treatment does not necessarily indicate that such improvement or success were unexpected. As discussed above, the treatment of cartilage injury lesions with cBMA would have been expected by an ordinarily skilled artisan at the time of filing to produce a treatment efficacy in a patient at the time of filing the instant application.
It is also noted that any evidence of unexpected results must be commensurate in scope with the claimed invention, and that a greater, or greater than additive, effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected MPEP 716.02 (a) and (d). Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
Specifically, note that the data presented in [0141-0142] and Figures 2-3 present results for repair of a single cartilage injury lesion type (e.g., the application of sodium alginate solution and cBMA to a rabbit osteochondral defect model wherein a n electric drill was used to produce a osteochondral defect in the center of the trochlea of rabbit knees [0114]), with a single preparation of UPAL+BMAC, and does not present sufficient examples to encompass all cartilage injury lesions and all monovalent metal salt of alginic acid + cBMA preparations having fluidity as recited in independent claim 19.
Therefore, Applicant’s amendments and arguments do not overcome a finding of obviousness over Iwasaki, Gianakos, Gobbi, Sudo, and Vitell under 35 U.S.C. 103, and the rejection is maintained.
Double Patenting
The rejection of amended and previously presented claims 19-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9,216,201, hereafter referred to as the ‘201 patent in view of Gianakos et al. [2017, World Journal of Orthopedics, 8(6), 491-506], is maintained 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 the claims to address issues of indefiniteness and informalities. No amendments were introduced which altered the scope of the claims sufficiently to overcome the nonstatutory double patenting rejection of record.
Applicant argues that the ‘201 patent claims recite “applying a composition comprising… at least one type of cell selected from the group consisting of bone marrow mesenchymal stem cells and bone marrow mesenchymal stromal cells to a cartilage injury lesion” [‘201 patent claim 1], and as such does not require applying a concentrated bone marrow aspirate (cBMA) to a site of a cartilage injury lesion.
However, this is not agreed.
Note that cBMA is a composition which comprises bone marrow mesenchymal stem cells and/or bone marrow mesenchymal stromal cells, as taught by Gianakos [column 1 ¶ 1]. Additionally, as described above for the obviousness rejection under 35 U.S.C. 103, Gianakos further provides teachings and motivation for using cBMA for treating cartilage injury lesions [column 12 ¶ 2- column 13 ¶ 1], such that it would have been obvious to an ordinarily skilled artisan at the time of filing the instant application to use cBMA as a source of bone marrow mesenchymal stem cells and/or bone marrow mesenchymal stromal cells.
Additionally, as discussed in more detail above for the obviousness rejection under 35 U.S.C. 103, the results and data presented in the disclosure for Example 1 [0141-0142, Figures 2-3] would not have been unexpected given the teachings of Gianakos [e.g., see Gianakos column 12 ¶ 2- column 13 ¶ 1]. Statistical significance and/or success are insufficient to indicate that the method is non-obvious given that teachings in the prior art already provide expectations of success for the claimed method.
Therefore, Applicant’s amendments and arguments do not overcome the nonstatutory double patenting rejection over the ‘201 patent claims, 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