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 .
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.
Claim Interpretation
With respect to claims 1, 12-14, claim scope is not limited by language that does not limit the claim to a particular structure. That is, intended use of an apparatus or composition is insufficient to distinguish the structure of the apparatus or composition from the prior art. See MPEP §§ 2111.02 and 2111.04. Therefore, only language that clearly defines structural limitations is considered with respect to patentability analysis. For example, “for treating trauma” does not clearly define a structural limitation of the apparatus or composition. Consequently, this limitation is not considered in analyzing the patentability of the apparatus or composition. For examination purposes claim 1 is interpreted as a composition comprising isolated mesenchymal stem cells (MSCs) wherein the MSCs are tenogenic induced (“activation of cell type specific genes or molecules in a multipotent or pluripotent stem cell, thereby driving such cell towards a more defined, specialized or differentiated cell lineage or cell type” or Specification p7 ln 30-32) and a cell culture media.
Election/Restrictions
Newly amended claims 12-14 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons. The newly amended claims are related as process of use for the originally claimed product. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case the originally claimed product may be used in a materially different process than that of the newly amended claims. For example, the originally claimed product may be used for drug screening applications.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 12-14 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Status
Applicant’s arguments and amendments dated 8/11/26 have been received and entered in the application.
Claims 1-10, 12-19 are currently pending.
Claims 15-17, 19 are withdrawn as directed to non-elected species in the response dated 1/5/26.
Claims 12-14 are withdrawn as directed to a non-elected invention by original presentation.
Claims 1-10, 18 are elected and examined on the merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections rejections not specifically reiterated are hereby withdrawn.
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.
Claim 5 is 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 5 contains the limitation “wherein said MSCs are allogenic MSCs when placed in a subject”. It is unclear if being in vivo is a required limitation of the claim.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-4, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lovati et al., (2012) Tenogenic differentiation of equine mesenchymal progenitor cells under indirect co-culture. Int J Artif Organs, 35(11): 996-1005 (hereinafter Lovati) in view of Mienaltowski, M.J., Birk, D.E. (2014). Mouse Models in Tendon and Ligament Research. In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 802. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7893-1_13 (hereinafter Mienaltowski).
Regarding claim 1, 4, and 18, Lovati discloses methods of tenogenic inducing equine MSCs (Abstract, Introduction). Lovati discloses co-culturing equine MSCs with tendon fragments in DMEM supplemented with 10 ng/ml of bFGF (BM-MSC culture, Co-culture conditions). Lovati discloses that the equine MSCs demonstrate upregulation of tenogenic markers indicating tenogenic commitment (Gene expression after tenogenic differentiation, Fig. 3).
Lovati does not disclose that the culture media comprises a certain FGF.
Mienaltowski examines mouse models for tendon and ligament research (Introduction). Mienaltowski explains that growth factors provide essential stimuli for tendon and ligament development and repair (13.9). In particular, Mienaltowski discloses that FGF-4 maintains expression of Scx and Tnc, which are critical for tendon development, during tendon development (13.9, 13.13). Additionally, Mienaltowski discloses that Egr1 and Egr2, transcription factors essential in early tendon development, expression is stimulated with FGF-4 supplementation (13.15). Therefore, there is a suggestion present in Mienaltowski that supplementation with FGF-4 may significantly enhance tenogenesis. A skilled artisan would be motivated to further supplement the culture media of Lovati with FGF-4 to support tenogenesis in the MSCs.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lovati and Mientalowski as applied to claims 1-4, 18 above, and in further view of Koerner et al., (2006) Equine peripheral blood-derived progenitors in comparison to bone marrow-derive mesenchymal stem cells. Stem Cells, 24(6): 1613-1619 (hereinafter Koerner).
Regarding claims 2-3, the combination does not disclose that the MSCs are peripheral blood derived MSCs.
Koerner compares characteristics of peripheral blood-derived and bone marrow-derived equine MSCs (Abstract). Koerner explains that peripheral blood-derived MSCs are easy to obtain from equine subjects, are safer to obtain, and demonstrate multilineage differentiation potential (though at a lesser degree than bone marrow-derived MSCs) (Discussion). Koerner concludes that peripheral blood-derived MSCs may be useful for clinical applications in bone, tendon, and ligament repair (Discussion, Conclusion). Therefore, there is a suggestion present in Koerner that peripheral blood-derived MSCs could be substituted for bone marrow-derived MSCs for bone, tendon, and ligament applications. A skilled artisan would be motivated to use the peripheral blood-derived MSCs of Koerner in the methods of the combination as an easy and safe substitute for bone marrow-derived MSCs.
Claim(s) 1, 6, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loo, T.S., (2013) Investigating GDF5-induced tenogenesis in mesenchymal stem cells for the potential improvement of tendon repair. University of Malaya, Thesis (hereinafter Loo) in view of Ker et al., (2011) Engineering spatial control of multiple differentiation fates within a stem cell population. Biomaterials, 32(13): https://doi.org/10.1016/j.biomaterials.2011.01.036 (hereinafter Ker).
Regarding claims 1, 18, Loo discloses compositions comprising GDF5-induced MSCs for tendon repair (Abstract). Loo discloses that MSCs cultured in low-glucose Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with GDF5 demonstrate significant upregulation of tenogenic markers and lineage commitment in the cells as compared to controls (2.5.1.1, 3.3.4, 3.4.2, Figs. 3.10-3.11, Tables 2.2, 3.3).
Regarding claim 6, Loo discloses treating an infraspinous tendon lesion with 1 to 2 x 106 cells (4.2, Table 4.1).
Loo does not disclose that the culture media is supplemented with an FGF.
Ker discloses methods of promoting muscle derived stem cells towards tenogenic differentiation (Abstract, Introduction). Ker discloses culturing MDSCs in DMEM supplemented with various growth factors such as FGF-2 and FGF-4 at concentrations between 0 ng/mL and 50 ng/mL (2.1-2.2, Supp Fig. 1-5). Ker discloses that FGF-2 causes an upregulation of the tendon marker Scx and myogenin in a dose dependent manner (3.2-3.3, Fig. 1, Supp Fig 3, 5). Ker concludes that supplementation with FGF-2 drives MDSCs towards a tenocyte fate (3.2-3.3, 4.3,Conclusions). Ker further discloses that FGF-4 similarly directs MDSCs to a tendon lineage (4.3, Supp Fig. 2). Therefore, there is a disclosure in Ker that the addition of FGF-2 and/or FGF-4 may be added to culture media to encourage differentiation to a tendon lineage. As both Loo and Ker are directed to methods of inducing tenogenic differentiation, a skilled artisan would understand that the references could be combined. A skilled artisan would be motivated to combine the teachings of Loo and Ker for improved tenogenic differentiation.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loo in view of Ker as applied to claims 1, 6, 18 above, and in further view of Zhang et al., (2010) Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. The American Journal of Sports Medicine, 38(10): 2477-2486 (hereinafter Zhang).
Regarding claim 7, the combination does not disclose that the composition further comprises platelet rich plasma (PRP).
Zhang examines the effect of PRP on tendon stem cells (TSCs) for tendon repair (Abstract, Introduction). Zhang discloses culturing TSCs in the presence of PRP clot releasate (Cell culture experiment). PRP clot releasate specifically induces differentiation into tenocytes (and not other cell types), increases proliferation, and increases collagen production (Results, Discussion, Figs. 2-4, 8). Zhang concludes that treating stem cells with PRP may be highly effective for treating injured tendons in vivo (Discussion).
As the references are all directed to cellular based treatment methods for tendons it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to incorporate the PRP of Zhang into the composition of Loo to improve tendon healing as disclosed by Zhang.
Claim(s) 1, 6, 8-10, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loo in view of Ker as applied to claims 1, 6, 18 above, and in further view of R. Ian Freshney, “Cryopreservation.” In: Culture of Animal Cell: A Manual of Basic Technique and Specialized Applications. (Hoboken, NJ, John Wiley & Sons, Inc., 2010), pp. 317-334. QH585.2.F74 2010 (hereinafter Freshney).
Regarding claims 8-10, the combination does not disclose that the MSCs are suspended in a media containing dimethyl sulfoxide (DMSO).
Freshney explains that it is essential to protect cells through cryopreservation for a multitude of reasons, including distribution to others (e.g., for therapeutic administration) (19.1). Freshney explains that DMSO is a well-understood, routine, and conventional cryopreservative (19.3.3, Protocol 19.1). Typically DMSO is added to the cell growth media at a concentration of between 5% and 15% (19.3.3, Protocol 19.1). As cryopreservation with DMSO is a well-understood, routine, and conventional means for preserving cells, it would be obvious to one of ordinary skill in the art that the cells of Loo could be cryopreserved accordingly. A skilled artisan would be motivated to cryopreserve the cells of Loo for distribution to others for therapeutic administration as disclosed by Freshney.
Response to Arguments
Applicant’s arguments and amendments dated 8/11/25 have been fully considered but are moot due to the new grounds of rejection necessitated by applicant’s amendments.
Conclusion
No claims are 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 KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
