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
Applicant’s submission filed 04/03/2026 has been received and entered. Claims 98 and 99 have been cancelled. Claims 91-97 have been amended. Claims 100-110 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 91-97 are pending and under current examination.
Status of Prior Rejections/Response to Arguments
The objection to specification is withdrawn:
Applicant’s amendment to specification is effective to obviate the objection on record. The objection is withdrawn.
The rejection to claims 91-99 under 35 U.S.C. § 112(b) is withdrawn:
The cancellation of claims 98-99 renders the rejection thereto moot.
Applicant’s amendment to claims 91-94 and 96 replace “substantially” with “at least four-fold” and “at least two-fold” is effective to obviate the rejection on record. The rejection is withdrawn.
The rejection to claims 91-94 and 98-99 under 35 U.S.C. § 102 over Williams et al. is withdrawn:
The cancellation of claims 98-99 renders the rejection thereto moot.
Applicant’s amendment to claim 91 limits “the engineered extracellular vesicles are exosomes derived from cardiosphere-derived cells (CDCs) and the non-engineered vesicles are exosomes derived from CDCs”. Williams et al. do not teach this limitation. Therefore Applicant’s amendment is effective to obviate the current rejection on record. The rejection is withdrawn.
The rejection to claims 91-95 and 98-99 under 35 U.S.C. § 103 over Williams et al. is withdrawn:
The rejection to claims 91-99 are rejected under 35 U.S.C. § 103 over Williams et al. in view of Kim et al. is withdrawn:
The cancellation of claims 98-99 renders the rejection thereto moot.
Applicant’s amendment to claim 91 limits “the engineered extracellular vesicles are exosomes derived from cardiosphere-derived cells (CDCs) and the non-engineered vesicles are exosomes derived from CDCs”. Neither Williams et al. or Kim et al. teach this limitation. Therefore Applicant’s amendment overcome the obviousness rejection on record. The rejection is withdrawn.
New grounds of rejection are set forth as necessitated by Applicant’s amendment.
New 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.
Claims 91-95 are newly rejected under 35 U.S.C. 103 as being unpatentable over Marban et al. (WO 2014/028493 A2, published in 2014) in view of Oh et al. (J Cell Mol Med. 2020 Jul;24(13):7214-7227, published 06/02/2020). The rejection is necessitated by Applicant’s amendment.
Marban et al. teach methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in turn result in improved cell or tissue viability and/or function (Abstract).
Regarding claim 91, Marban et al. teach methods for regenerating tissue in an individual having damaged tissue, comprising, identifying an individual having damaged tissue and administering a plurality of exosomes to the individual, wherein the exosomes are secreted from regenerative cells, wherein the exosomes comprise one or more microRNA fragments, and wherein after administration of the plurality of exosomes, the one or more microRNA fragments alter gene expression in the damaged tissue, improve the viability of the damaged tissue, and/or facilitate the formation of new tissue in the
individual (prag 0006). In several embodiments, the regenerative cells comprise cardiosphere-derived cells (CDCs, parag 0009). In several embodiments, the microRNA fragments are selected from the
group consisting of miR-23a, miR-23b, miR-24, miR-26a, miR27-a, miR-30c, let-7e, mir-19b, miR-125b, mir-27b, let-7a, miR-19a, let-7c, miR-140-3p, miR-125a-5p, miR-132, miR-150, miR-155, mir-210, let-7b, miR-24, miR-423-Sp, miR-22, let-7f, miR-146a, and combinations thereof (parag 0017). This teaching reads on exosomes derived from cardiosphere-derived cells (CDCs) and said exosomes derived from CDCs are engineered to express various microRNA fragments.
Marban et al. do not teach engineering the exosomes derived from CDC to comprises miR-345, and expressing at least four-fold higher than an amount of miR-345 in non-engineered extracellular vesicles. However, miR-345 can be engineered in exosomes derived from CDC as for treatment of tissue damage is taught by Oh et al. at the time of instant invention.
Oh et al. established the miR expression profiles in EVs from murine normal and failing hearts and consecutively identified substantially altered miRs (Abstract).
Regarding claim 1, Oh et al. identified seven up-regulated and three down-regulated miRs in failing hearts compared to controls. Briefly, miR-757, miR-328, miR-92b, miR-139, miR-665, miR-378a and miR-345 were up-regulated (p7223, right column). miR-345 is ~ 4 folds higher in transverse
aortic constriction (TAC) than the control group. Oh et al. teach the up-regulated miRs are likely involved in the cardioprotective function (p7223, right column).
Given that Marban et al. teach CDCs provide exosomes that may be particularly beneficial in the context of tissue repair and/or regeneration, based on their ability to reduce cell death and increase proliferative activity (parag 0084), therefore is benefit for repairing or regeneration of the damaged cardiac cells or tissue (see parag 0084), and Oh et al. teach up-regulated miRs (i.e., miR-345) are likely involved in the cardioprotective function (p7223, right column), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include (engineer) miR-345 in CDC-derived exosomes to increase the effect of treating diseases such as heart failure. The combined effect would have been expected to be greater than the effect of either CDC-derived exosomes or miR-345 individually because the CDC-derived exosomes and miR-345 work in different manners (i.e., CDC-derived exosomes result in an increased proliferative activity, see parag 0084, and miR-345 involved in the cardioprotective function by regulating protein expression, see p7220, Table 1). The reason to combine the CDC-derived exosomes and miR-345 in the exosomes would be to improve overall effect of treating diseases such as heart failure. See MPEP 2143(I)(A).
Marban et al. in view of Oh et al. teach the combination of exosomes derived from CDC and engineer said exosomes to express miR-345, but do not teach the amount of miR-345 in the engineered extracellular vesicles is at least four-fold higher than an amount of miR-345 in non-engineered extracellular vesicles. However, it is not inventive to find optimal workable ranges by routine experimentation. It is considered that adjusting the level of overexpressing miRNAs will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such adjust level is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claims 92-94, following the discussion above, Marban et al. teach in several embodiments, the microRNA fragments are selected from the group consisting of miR-23a, miR-23b, miR-24, miR-26a, miR27-a, miR-30c, let-7e, mir-19b, miR-125b, mir-27b, let-7a, miR-19a, let-7c, miR-140-3p, miR-125a-5p, miR-132, miR-150, miR-155, mir-210, let-7b, miR-24, miR-423-Sp, miR-22, let-7f, miR-146a, and combinations thereof (parag 0017). Regarding the expression level of miRs in the exosomes derived from CDCs (at least two-fold), it is not inventive to find optimal workable ranges by routine experimentation. See Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 95, as discussed above, it is not inventive to find optimal workable ranges by routine experimentation. It is considered that adjusting the level of overexpressing miRNAs will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such adjust level is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 91-97 are newly rejected under 35 U.S.C. 103 as being unpatentable over Marban et al. (WO 2014/028493 A2, published in 2014) in view of Oh et al. (J Cell Mol Med. 2020 Jul;24(13):7214-7227, published 06/02/2020), as applied to claims 91-95 above, and further in view of Wang et al. (Pediatr Cardiol. 2014 Aug;35(6):1072-9). The rejection is necessitated by Applicant’s amendment.
The teaching of Marban et al. and Oh et al. is set forth above.
Regarding claims 96 and 97, Marban et al. and Oh et al. do not teach the amount of miR-10b in the engineered extracellular vesicles is at least two-fold lower than the amount of miR-10b in non-engineered extracellular vesicles derived from the cells. However, such was disclosed by Wang et al. at the time of instant invention.
Wang et al. identify microRNAs that modulate TBX5 expression, TBX5 is involved in embryonic cardiac development (Abstract).
Regarding claims 96 and 97, Wang et al. teach miR-10a and miR-10b inhibit TBX5 expression at the level of translation. Higher levels of miR-10a and miR-10b expression are associated with a higher risk of congenital heart defects (Abstract). Wang et al. teach the expressions of miR-10a and miR-10b were respectively 2.77 and 3.51 times higher in the CHD subjects than in the control heart tissues (p1075, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Marban et al. in view of Oh et al.’s exosomes derived from CDCs expressing higher level of miR-345, and decrease the level of miR-10b in the exosomes derived from CDCs. The skilled artisan would have been motivated to decrease the level of miR-10b in the exosomes derived from CDCs since Wang et al. teach higher levels of miR-10a and miR-10b expression are associated with a higher risk of congenital heart defects (Abstract). There would be a reasonable expectation of success of decreasing the level of miR-10b in the exosomes derived from CDCs since the method of decreasing the level of miR-10b in the exosomes is known in the art, such as transfection (an miR inhibitor). Moreover, the expression level (at least two-fold lower) is considered is not inventive to find optimal workable ranges by routine experimentation. See Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
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.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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