DETAILED ACTION
Applicant’s response filed October 16, 2025 has been received and entered into the application file. Applicant’s arguments and amendments to the claims have been fully considered.
Claims 1-2, 4-10, 18-22, 27-28, and 30 from the claim set filed October 16, 2025 are pending. Claims 3, 11-17, 23-26, and 29 are canceled. Claims 8-9, 18-22, 27-28, and 30 are withdrawn. Claims 1-2, 4-7, and 10 are being examined on the merits herein.
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 .
OBJECTION(S)/REJECTION(S) WITHDRAWN
Drawings
RE: The drawings are objected to because the character of the letters is poor in many of the figures. Examiner notes the character of the letters is especially poor in Figures 1, 5, 6, and 12.
Re: The drawings are objected to because the drawings are indicated by “Figure” rather than “FIG.” as required by 37 C.F.R § 1.84 (u)(1) (see also MPEP § 608.02 (V)).
Applicant submitted new drawings with improved resolution and replaced labels reciting “Figure” with “FIG.” As such, the previously filed objections are withdrawn.
Claim Rejections - 35 USC § 112(b)
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.
RE: Claims 1-7 and 10 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
RE: In regards to claim 1, the metes and bounds of the claim cannot be determined with the language of the claim as currently written. The issue at hand is the use of the term “providing”. The term “providing” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Applicant amendment replaced “providing” with “administering to a subject in need thereof, in a unit dosage injectable form, a therapeutically effective amount of cells…”. As such, the previously filed rejections are withdrawn. Examiner notes claim 3 is cancelled, thus making the rejection of said claim moot.
RE: Claim 2 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
RE: In regards to claim 2, the metes and bounds of the claim cannot be determined with the language of the claim as currently written. The issue at hand is the use of the term “substantially”.
Applicant amended claim 2 to delete “substantially”. As such, the previously filed rejection is withdrawn.
RE: Claim 6 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
RE: In regards to claim 6, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention or are optional.
Applicant amended claim 6 to delete “(such as torn meniscus)” and “(such as torn ligament)”. As such, the previously filed rejection is withdrawn.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
RE: Claims 1, 2, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chapman (Chapman et al., Stem Cells International (2017) (2905104; IDS filed 3/17/2022) as evidenced by Ghaneialvar (Ghaneialvar et al., Ind J Clin Biochem (2018) 33(1): 46-52; PTO 892).
Applicant amended claim 1 to incorporate the limitation of claim 3, i.e., “a method for promoting tissue repair in a subject in need thereof…”. Chapman does not teach this limitation. As such, the previously filed rejections are withdrawn. However, Applicant amendment has necessitated new grounds of rejection, as set forth below.
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.
RE: Claims 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Chapman, as evidenced by Ghaneialvar, in view of Estes (Estes, et al., Journal of Cellular Physiology (2006) 209:987-995; PTO 892) as evidenced by Tsuji (Tsuji, et al., World J Stem Cells (2014) 6(3): 312-321; PTO 892) and Bacenkova (Bacenkova, et al., International Journal of Molecular Sciences (2023) 23 (17096); PTO 892). Claim 7 is rejected under 35 USC 103 as being unpatentable over Chapman, as evidenced by Ghaneialvar, in view of Estes as evidenced by Tsuji and Bacenkova, and as further evidenced by Wang (Wang et al., Journal of Orthopedic Research (2013); IDS filed 3/17/2022).
For the reasons discussed above, the anticipation rejection over Chapman is withdrawn, and thus the obviousness rejections that are based on the same basis are likewise withdrawn. However, Applicant’s amendment has necessitated new grounds of rejection, as set forth below.
Claim 3 has been cancelled via Applicant amendment, thus making the rejection of said claim moot.
OBJECTION(S)/REJECTION(S) MAINTAINED
Claim Rejections - 35 USC § 112(b)
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.
RE: Claim 1 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
RE: In regards to claim 1, it is unclear what (“TIMP-1 secretion high”) and (“MMP13 gene expression low”) is meant to entail.
Applicant amendment removed the phrases in parenthesis and further amended to define the terms “TIMP-1 secretion+” and “MMP13 gene expression- “. As such, Applicant’s amendment clarified the previous rejection under 35 U.S.C. 112(b). However, in view of the newly added limitations in regards to defining TIMP-1 secretion+ and MMP13 gene expression-, the rejection under 35 U.S.C. 112(b) is maintained due to the new limitations being unclear.
In regards to TIMP-1 secretion+ “having an average of 100ng/ml or more of TIMP-1 from cells initially plated at a density of 2.25 million cells/well in a 24 hour period”, it is unclear if the method is now claiming an active step of plating cells at 2.25 million cells/well and culturing for 24 hours in order to have an average secretion of 100 ng/ml or more of TIMP-1.
Additionally, Examiner notes the amendment that MMP13 gene expression- “defined by an average level of MMP13 expression relative to a housekeeping gene that is half or less than half of said relative expression by freshly isolated MSCs”, further renders the claim unclear. “Freshly isolated MSCs” is a relative term which renders the claim indefinite. This reads on MSCs from all species and age ranges. There is not a definition for MMP13 expression from freshly isolated MSCs provided by the claims, nor does the specification provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The metes and bounds of the claim are unclear and thus renders the claim indefinite. Examiner notes gene expression is ever changing and thus no definitive range has been provided by the claim. Freshly isolated cells from a healthy individual would most likely have a different MMP13 expression level/housekeeping gene expression level than isolated cells from someone with osteoarthritis, for example. Thus, the claim is unclear and is properly rejected.
New Grounds of Rejection, Necessitated by Amendment
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.
Claims 1-2, 4-7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Chapman, as evidenced by Ghaneialvar, in view of Estes as evidenced by Tsuji and Bacenkova. Claim 7 is rejected under 35 USC 103 as being unpatentable over Chapman, as evidenced by Ghaneialvar, in view of Estes as evidenced by Tsuji and Bacenkova, and as further evidenced by Wang.
In regards to claim 1, Chapman teaches of the therapeutic benefit for late, but not early, passage MSCs on pain behavior in an animal model of osteoarthritis (OA) (Title). Chapman teaches the use of passage 10 (P10) murine bone marrow derived MSCs (p2, 2.4). Chapman teaches of intra-articular injection of late passage MSCs (P10) (p3, 2.6.1) and the effect of said injection on pain behavior (p4, 2nd column, 1st paragraph). Chapman teaches the passage number of MSCs markedly influences the effects of these cells on pain behavior following their injection into the knee joint in a surgical model of OA pain. Chapman teaches late passage MSCs significantly reduced weight-bearing difference, a surrogate index of pain on loading, whereas early passage MSCs exacerbated weight-bearing difference postinjection (p5, Discussion). Chapman teaches that higher passage cells may have an increased potential for therapeutic application (p9, 1st column, 1st paragraph). Thus, Chapman teaches a method of treatment comprising administering to the subject, in a unit injectable form, a therapeutically effective amount of cells.
Chapman does not teach per se of cells that are CD90+, CD105+ and CD45-. However, as is evidenced by Ghaneialvar, human and mouse MSCs express CD105 and CD90 and are negative for CD45 (Abstract). Thus, it is inherent that the murine MSCs of Chapman are CD90+, CD105+ and CD45-.
Chapman does not per se teach of TIMP-1 secretion+ and MMP13 gene expression-.
The instant application teaches that in usual culture conditions (p28, Results 1st paragraph; p37 Isolation and expansion of human marrow derived MSCs for in vitro studies) MSCs keep their TIMP-1 high expression over many passages (Fig 7C) but gradually lose their MMP13 expression (Fig 7A-B). Specifically, the instant application teaches the MMP13 gene is a marker of early passage cells which is lost with ageing of MSCs in vitro and further teaches secretion of the TIMP-1 protein is a marker of MSCs that is independent of in vitro ageing (Fig 7, p6). The instant application teaches MMP13 data from transcriptomics analysis shows decreasing gene expression with increasing passage number, with low MMP13 gene expression by passage 5 (Fig 7A-B). Additionally, the instant application teaches TIMP-1 data from proteomics analysis shows continuous protein secretion with increasing passage number (Fig 7C-D). The instant application further teaches a population of cells of the invention may comprise cells that have been subject to at least 5 passages (i.e., the cells will have low MMP13 gene expression and high TIMP-1 secretion) (p16, cell culture).
Importantly, the authors did not purify the cell population but simply analyzed the expression profile of the cell populations at different time points (p37 last paragraph-p38 first paragraph). Since these changes are inherent to any MSC population that is passaged several times, the MSC population disclosed by Chapman will also be “enriched” in cells expressing high TIMP-1 levels and low MMP13 levels compared to a fresh MSC population.
Further, in regards to the newly added limitation “TIMP-1 secretion+ having an average secretion of 100ng/ml or more of TIMP-1 from cells initially plated at a density of 2.25 million cells/well in a 24-hour period” and the newly added limitation of MMP13 gene expression- defined by an average level of MMP13 expression relative to a housekeeping gene that is half of less than half of said relative expression by freshly isolated MSCs”, Examiner notes, in view of Fig 7D of the instant application, that it appears that P2-P13 MSCs secrete an average of 100ng/ml or more of TIMP-1. Fig 7D shows P2 though P13 has overlapping data in regards to TIMP-1 secretion and thus the prior art of the same passages (i.e., P10 as taught by Chapman) would inherently have the same TIMP-1 secretion and thus would fulfill the TIMP-1 newly added limitation in regards to TIMP-1 secretion.
In regards to the MMP13 gene expression, Examiner notes that Fig 7A and B teaches by P10 there is virtually no MMP13 gene expression. Thus, the cells of Chapman, i.e., P10 cells, would meet the MMP13 gene expression limitation of claim 1.
Thus, Chapman teaches of the cell population of claim 1, i.e., Chapman teaches of cells that are CD90+; CD105+; CD45-; TIMP-1 secretion +; and MMP13 gene expression-.
While Chapman teaches a method of treating pain in an animal model of osteoarthritis, utilizing the required cells of claim 1, Chapman does not per se teach a method for the promotion of tissue repair but rather teaches there are varied results in regards to the use of late passage MSCs and their therapeutic benefit for promoting tissue repair.
Examiner acknowledges Chapman examined the effects of late versus early passage MSCs not only on pain behavior but also on structural changes to the knee joint (i.e., tissue repair) and circulating levels of tumor necrosis factor alpha and interleukin 10 (i.e., inflammation) in a surgical model of OA in the rat (p2, 2nd paragraph, 1st column). Chapman teaches late passage MSCs did not alter structural damage or synovial inflammation (p6, 1st column) and summarizes that the progression of MNX-induced joint pathology was not halted by intra-articular injection of late passage MSCs, suggesting that at least in this model the effects of MSC treatment on pain behavior are not associated with increased joint repair (p6, 2nd column). Chapman teaches that nevertheless, a peripheral site of action of the MSCs was supported by the demonstration that SiMAG-labelled MSCs were detected within the synovial cavity at 29 days postinjection (i.e., a possible method of promoting tissue repair) (p5, 2nd column, Discussion).
Chapman further notes, there is evidence of other phenotypic shifts in MSCs with prolonged culture which may provide insight. Chapman teaches earlier studies examining passage-dependent differences to chondrogenic potential (i.e., tissue repair potential) of MSCs have produced varied results with some studies reporting a maintenance of the chondrogenic potential of the cells up to passage 20 (i.e., thus teaching MSCs up to P20 can promote tissue repair) or an increase in COL2A1 and AGC1 expression (i.e., both of which are involved in the formation and maintenance of healthy cartilage and thus promote tissue repair) from P4 to P9 in human adipose derived adult stem cells. Another study reported a reduction of chondrogenic capabilities of MSCs at late passage. A further study noted with an increasing passage number, MSCs isolated from synovium shows migratory behavior similar to chondrocytes (i.e., and thus promoting tissue repair), whilst at low passage, a reduced ability to undergo chondrogenesis was observed.
Chapman summarizes the varied results in regards to phenotypic shifts of late passaged MSCs by stating, “What is clear is that selection of populations of cells for therapy will depend on the level of preculture with significant changes in phenotype and potential therapeutic activity as a result of prolonged culture.” (p9, 1st column, 1st full paragraph).
Thus, Chapman teaches there are wide-ranging results in regards to a method for promoting tissue repair via the administration of late passage MSCs and further study is needed.
Estes teaches extended passaging increases the chondrogenic potential of human adipose derived adult stem cells h(ADAS). Estes teaches COL2A1 expression (i.e., known to be involved in tissue repair) in P9 cells increased fivefold compared to P4 cells (Abstract).
As a POSITA will appreciate, and as is evidenced by Tsuji, adipose derived stem cells are MSCs (Abstract). Tsuji additionally teaches adipose derived stem cells (i.e., MSCs) express the typical mesenchymal markers such as CD90+, CD105+ and CD45- (p313, 2nd column, last paragraph).
Estes does not per se teach of TIMP-1 secretion and MMP13 gene expression, but as discussed supra, it is inherent Estes teaches of cells that are CD90+; CD105+; CD45-; TIMP-1 secretion +; and MMP13 gene expression- as Estes teaches the use of passage 9 cells (p988, 2nd column, 1st full paragraph).
Further as a POSITA will appreciate, and as is evidenced by Bacenkova, osteoarthritis (OA) is a very common joint disease that begins with the degeneration of joint cartilage and in the case of pathological processes, the production of collagen by chondrocytes changes (4.1). Chondrocytes are a differentiated cell type in a resting state that ensure the maintenance of the physiological state of the ECM of the articular cartilage. Chondrocyte dedifferentiation in an organism causes degeneration and is associated with OA, i.e., which is associated with cartilage damage (5.2). Thus, the teachings of Estes, i.e., that extended passaging increases the chondrogenic potential of hADAS, would motivate a POSITA to combine the teachings of Estes and Chapman in order to have a method of treating tissue regeneration (i.e., tissue repair) in osteoarthritis. A POSITA would be further motivated to combine the teachings of Estes and Chapman due to Chapman teaching varied results in regards to the use of late passage MSCs but specifically noting that several experiments have utilized late passage MSCs and noted a therapeutic benefit in regards to the promotion of tissue repair.
Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to do a simple substitution of one known element for another to obtain predictable results. It would have been obvious to substitute the late passage MSCs taught by Chapman for the late passage adipose derived MSCs taught by Estes in order to have a method of treating osteoarthritis via the promotion of tissue repair.
The skilled artisan would have had a reasonable expectation of successfully substituting the cells of Chapman for the cells of Estes for treating osteoarthritis via the promotion of tissue repair due to all working in the field of MSC therapy. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Thus, the claim is obvious and is properly rejected.
In regards to claim 2, the above cited references teach the method of claim 1. Further, Examiner notes the limitation “wherein the cells have substantially no multipotent potential” is a wherein statement that is directed to an intended result. It is noted that as indicated in MPEP § 2111.04, a wherein clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
As discussed above in regards to claim 1, both Chapman and Estes teach the same cells that are required by the limitations of claim 1. As discussed supra, it is inherent that the cells of Chapman and Estes express the same cell surface markers and have the same TIMP-1 secretion and MMP13 gene expression as required by the limitations of claim 1. As no other steps have been provided in the method of claim 1 in regards to said cells, it is thus inherent that the cells of Chapman, Estes, and the instant application are one and the same. Thus, because the cells are one and the same, it therefore stands to reason that said cells would inherently have substantially no multipotency potential.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process and produce the identical or substantially identical product. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). MPEP 2112.01
Therefore, the claim is obvious and is properly rejected.
In regards to claims 4 and 5, the above cited references teach the method of claim 1. Further, and as discussed supra, Estes and Chapman teach a method for promoting the tissue repair of cartilage.
Thus, the claims are obvious and are properly rejected.
In regards to claim 6, the above cited references teach the method of claim 1. Further and as discussed supra, Chapman and Estes teach a method of treating osteoarthritis.
Thus, the claim is obvious and is properly rejected.
In regards to claim 7, the above cited references teach the method of claim 1. Further and as discussed supra, Chapman and Estes teach a method for the promotion of tissue repair. As both Chapman and Estes teach the cells required by claim 1, i.e., cells that are CD90+; CD105+; CD45-; TIMP-1 secretion +; and MMP13 gene expression-, it is inherent that said cells would promote tissue repair through the stimulation of trophic repair.
Further, and as is evidenced by Wang, late passage MSCs (i.e., the cells required by claim 1 and taught by Chapman and Estes) are known to cause trophic stimulation of articular chondrocytes (Abstract).
Thus, it is inherent the cells of Chapman and Estes promote tissue repair by the stimulation of trophic repair.
Thus, the claim is obvious and is properly rejected.
In regards to claim 10, the above cited references teach the method of claim 1. As no other steps have been provided in the method of claim 1 in regards to said cells and the manner in which they are cultured, treated, etc., it is thus inherent that the cells of Chapman, Estes, and the instant application are one and the same. Thus, because the cells and the method of Chapman and Estes are one and the same as the instant application, it therefore stands to reason that said cells would inherently comprise a population comprising at least 15% of said cells.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process and produce the identical or substantially identical product. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). MPEP 2112.01
Therefore, the claim is obvious and is properly rejected.
Response to Remarks/Amendment
RE: Rejections under 35 USC 102/35 USC 103
In response to Applicant remarks stating a POSITA, reading Chapman, would not understand that they should select the cells in Chapman for tissue repair, Examiner respectfully points Applicant to the new rejection of claim 1 in which Examiner explains why a POSITA would combine the teachings of Chapman and Estes in order to have a method for promoting tissue repair.
In response to Applicants remarks stating the cells disclosed in Chapman do not inherently possess the presently claimed phenotypic characteristics (i.e., CD90+, CD105+, CD45-, and with particular TIMP-1 secretion and MMP13 gene expression characteristics), Examiner notes Applicant states the cells of Chapman have undergone fewer passages than those described in the present application and thus cannot be assumed to have the same phenotypic characteristics. Applicant states the cells in Chapman are passaged 3 or 10 times, in comparison to 13-17 times in the present application (Fig7).
Examiner respectfully notes, the claim language of claim 1, as currently written, does not require cells to be passaged a set amount of times.
Additionally, Examiner notes that Fig 7 shows virtually no MMP13 expression by P10 (i.e., the passage number taught by Chapman) (Fig 7a and 7B) and shows TIMP-1 expression is maintained regardless of passage number. This was noted in the previously filed OA: “The instant application teaches that in usual culture conditions (p28, Results 1st paragraph; p37 Isolation and expansion of human marrow derived MSCs for in vitro studies) MSCs keep their TIMP-1 high expression over many passages (Fig 7C) but gradually lose their MMP13 expression (Fig 7A-B). Specifically, the instant application teaches the MMP13 gene is a marker of early passage cells which is lost with ageing of MSCs in vitro and further teaches secretion of the TIMP-1 protein is a marker of MSCs that is independent of in vitro ageing (Fig 7, p6). The instant application teaches MMP13 data from transcriptomics analysis shows decreasing gene expression with increasing passage number, with low MMP13 gene expression by passage 5 (Fig 7A-B). Additionally, the instant application teaches TIMP-1 data from proteomics analysis shows continuous protein secretion with increasing passage number (Fig 7C-D). The instant application further teaches a population of cells of the invention may comprise cells that have been subject to at least 5 passages (i.e., the cells will have low MMP13 gene expression and high TIMP-1 secretion) (p16, cell culture).”
Thus, the cells of Chapman, which are passaged 10 times, read on the cells of the instant application, regardless that the cells of the instant application are passaged 13-17 times.
Examiner further respectfully notes the cells of Estes read on the cells of the instant application for the same reasons as applied to Chapman and as are discussed above in regards to the rejection of claim 1.
Examiner notes Applicant remarks state that a prima facie case of obviousness has not been established, and further states a POSITA would not have been motivated to modify Chapman in view of Estes. Applicants state Estes concludes that chondrogenic potential of MSCs increases with increasing passage, which is inconsistent with the data of the present application and the broader literature, which shows declining multipotency with extended culture. Applicant states, as such, a POSITA would conclude Estes contains outlier data inconsistent with the state of the art.
As stated in the previously filed OA, Chapman teaches earlier studies examining passage-dependent differences to chondrogenic potential (i.e., tissue repair potential) of MSCs have produced varied results with some studies reporting a maintenance of the chondrogenic potential of the cells up to passage 20 or increase in COL2A1 and AGC1 expression from P4 to P9 in human adipose derived adult stem cells. Another study reported a reduction of chondrogenic capabilities of MSCs at late passage. With an increasing passage number, MSCs isolated from synovium shows migratory behavior similar to chondrocytes, whilst at low passage, a reduced ability to undergo chondrogenesis was observed. Thus, Chapman teaches at least 2 studies which teach of the chondrogenic potential of late passage MSCs either being maintained or increasing. Thus, Examiner respectfully notes, Applicant remarks in regards to the teachings of Estes being considered outlier data and that the broader literature teaches declining multipotency with extended culture, have not been found persuasive.
Additionally, Examiner respectfully wishes to direct Applicant to the new 103 rejection of claim 1 in wish Examiner believes the reasons to combine Chapman and Estes, and the motivation in doing so, has been clearly explained.
In regards to Applicants remarks discussing the teachings of Wang and the trophic effects of late passage MSCs, Examiner respectfully notes the claim language as currently written does not require a certain passage number for the MSCs but rather requires a certain phenotype. As discussed supra in regards to claim 1, Fig 7 of the instant application teaches by P5, MSCs cells would have the MMP13 and TIMP-1 required limitations. Thus, the P6 cells of Wang would have the required MMP13 and TIMP-1 phenotype.
Conclusion
No claims are allowable.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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, Chris Babic, can be reached (571) 272-8507. 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.
/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
Prosecution Insights