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 .
Status of Claims
Claims 1 and 5 are cancelled. Claims 2-4 are pending and under examination.
Priority
This application filed on 05/29/2024 claims priority from Korean application KR10-2023-0070622 filed on 6/1/2023. Applicant has filed a certified copy of a foreign translation for KR10-2023-0070622.
However, it is noted that KR10-2023-0070622 does not support hyaluronic acid and does not support the new “wherein” clause. Therefore, the claims still have priority to the application’s filing date of 5/29/2024.
Rejections Withdrawn
The rejection under USC 112(b) over claim 1 is withdrawn per cancellation of claim 1.
The rejection under USC 102 over Kim WO2022025559A1 is withdrawn per applicant’s cancellation of claim 1.
The rejection under USC 102 over KR20220079315A is withdrawn per applicant’s amendment to include hyaluronic acid as the pretreatment.
The rejection under USC 102 over Zhang et al is withdrawn per applicant’s amendment to include hyaluronic acid as the pretreatment.
The rejection under non-statutory double patenting over copending 17/925450 is withdrawn per applicant’s cancelling claim 1.
As these rejections are withdrawn, applicant’s arguments toward these rejections are moot.
New Objection – As Necessitated by Amendment
Claim 2 is objected to for the phrasing of “at least one of ……and ….” which is more correct as “at least one of…. and/or….” Or “at least one of ….. or combinations thereof” for this group of options. Appropriate correction is required.
New Rejection – As Necessitated by Amendment
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.
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.
Claims 2-4 are 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 2 is indefinite for the recitation of “requires increasing expression of at least one of EGF, IGF1, ELN, FN1, and COL1A1” as the claim does not provide what type of expression is being referred to (e.g. mRNA or protein) or how the expression is determined. Since mRNA expression does not necessarily correlate to protein expression in all situations, this would make unclear whether all expression levels have to be in need of increasing or if only one of mRNA or protein is required. The claim also does not indicate if the area for required increase is the wound or can be other parts of the body. For the purpose of compact prosecution, if the prior art provides for any type of expression of one or more of these molecules at any site in the subject, it will read on the claim.
Claims 3-4 are rejected as being dependent on an indefinite claim.
Maintained Rejections – Modified with Evidentiary Reference to Address New Claim Limitation (“wherein” clause)
Claim Rejections - 35 USC § 102
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 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.
Claims 2 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jung et al (“Anti-senescence effects of extracellular vesicle from hyaluronic acid primed iMSC on human dermal fibroblast”, Brexogen, 1 page, May 10, 2023, in applicant IDS) as evidenced by Genc et al (Turkish Journal of Nature and Science, 12-2022, volume 11, pages 63-69).
Note that the foreign priority document (English translation) does not provide of use of hyaluronic acid or the subject being in need of increased expression of at least one of the given items. Therefore, the date of when the claimed invention is described is applicant’s filing date of 5/29/2024. Jung remains over one year from this date as it was published on 5/10/2023 and applicant’s described invention of claim 2 is from 5/29/2024.
Jung describes a method of using exosomes isolated from a hyaluronic acid primed (pre-treated) iMSC cell culture to administer to subjects with skin lesions of burn wounds and have healing (abstract and results). The methods provide for using human cells (stem cells are derived from human dermal fibroblasts). Genc teaches wound healing after skin injury and that production of FN1 and Col1a1 are important targets since their increasing is associated with wound healing (abstract, also introduction). Thus, subjects with wounded skin are in need of increased expression of FN1 and Col1a1 as evidenced by Genc.
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.
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.
Claims 2-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (J Transl Med, 2015, DOI 10.1186/s12967-015-0417-0, pages 1-14) and Kim WO2022025559A1 as evidenced by Genc et al (Turkish Journal of Nature and Science, 12-2022, volume 11, pages 63-69).
Zhang teaches that mesenchymal stem cell exosomes can facilitate wound healing after transplanting the exosomes at wound sites (abstract). Zhang provides for hiPSC-MSCs which were used to collect the exosomes (pages 2-3). Zhang teaches a skin wound model on rats (page 3). Genc teaches wound healing after skin injury and that production of FN1 and Col1a1 are important targets since their increasing is associated with wound healing (abstract, also introduction). Thus, subjects with wounded skin are in need of increased expression of FN1 and Col1a1 as evidenced by Genc.
Zhang does not teach exosomes prepared from a process with SSEA-4 negative cells or pretreatment with hyaluronic acid before obtaining exosomes.
Kim teaches “A composition according to the present invention has excellent effects in terms of anti-inflammatory effects, fibrosis inhibition, vascular endothelial cell proliferation, blood vessel formation, survival rate improvement, and protective regeneration of cardiomyocytes, and thus can be used as an agent for preventing or treating heart disease, inflammatory disease, immune disease, fibrotic disease, or vascular disease.” (abstract). Kim teaches culturing induced pluripotent stem cell-derived mesenchymal cell culture and isolation of the SSEA-4(-) cells that are then cultured to form BxC stem cells and then further cultured to differentiate into mesenchymal stem cells (example 1). Kim teaches isolating the exosomes and their characterization (examples 2-1, 2-2). Kim teaches the use of hyaluronic acid pretreatment of BxC stem cells (section 3-1) and then carrying out the process to collect the exosomes. Kim teaches the stem cell are animals including human (English translation). Therefore, it is anticipated that human stem cells had intention of being used. Kim provides for different administrations including topical administration of the pharmaceutical composition. Kim provides that its pretreatment molecules including hyaluronic acid increase the proliferation and stemness of stem cells (English translation). Additionally, Kim notes that with hyaluronic acid pretreatment “Compared to the mesenchymal stem cells that were not pretreated with any substance, the BxC-R11 stem cells increased the cell proliferation rate by about 360%, the exosome production efficiency increased by about 5 times, and the amount of exosome-derived proteins was increased by 5 times or more. is increased” (English translation).
One of ordinary skill in the art before the time of filing would have utilized exosomes prepared in teachings of Kim for treating wounds in Zhang as they would be seen as having higher amounts of exosomes and higher amounts of exosomal proteins than those that are not prepared in this manner. Zhang recognizes the ability of human induced pluripotent stem cells-derived MSCs to produce exosomes that are effective at treating wounds by administering the exosomes to the subject in need thereof. Therefore, there was a reasonable expectation of success in practicing the methods of Zhang with the exosomes produced in Kim and getting better treatment due to more exosomes. Additionally, Kim recognizes anti-inflammatory effects, vascular endothelial cell proliferation effects, and blood vessel growth effects which would be seen as effects beneficial for healing by one of ordinary skill in the art. Zhang notes that there are proliferation and migration of vein endothelial cells with such mesenchymal stem cell exosomes (see abstract of Zhang).
Response to Applicant’s Arguments
Applicant argues that the rule 130 affidavit along with certified English translation of the foreign priority document overcomes the rejection over Jung et al. However, the foreign priority document does not disclose using hyaluronic acid or the added “wherein” clause regarding need for expression of certain genes. As applicant does not have full benefit to the filing date of the foreign priority document for these claims, Jung et al remains more than one year from the filing date of 5/29/2024. This rejection is maintained. It is noted that this rejection does not cover the limitation of claim 3 and applicant may import the limitation of claim 3 into claim 2 in order to overcome the rejection over Jung et al.
Applicant argues that there would be no motivation to use hyaluronic acid pretreated cells in Zhang’s process with the expectation of results that applicant has found for wound healing. Zhang is to wound healing with exosomes from hiPSC-MSCs while Kim also involves using exosomes from such cells for anti-inflammatory and vessel formation effects in tissue repair/healing. It was further noted that “Kim provides that its pretreatment molecules including hyaluronic acid increase the proliferation and stemness of stem cells (English translation).”, which motivates the use of the hyaluronic acid pretreatment in making exosomes. The use of the hyaluronic acid pretreatment would offer the same benefits to production of the stem cell exosomes as recognized by applicant (see MPEP 2112 – a composition and its properties are inseparable (in this case, exosomes collected from iPSC-MSC stem cells similar to what applicant is using)).
Applicant argues that the teachings of the references do not provide for the enhanced activity. It remains that Kim provides for such pretreated stem cell derived exosomes and there is a motivation from Zhang to use iPSC-MSC derived exosomes for wound healing. Further Kim provides the advantages of obtaining exosomes with the hyaluronic acid pretreatment. The activities on the wound will occur when applying the teachings of exosomes in Kim to the method of treating wounds with exosomes in Zhang. Applicant has not provided the exact effect/activity with quantification that would be seen as unexpected in view of the teachings of the prior art. As there is a reasonable expectation of success in combining the teachings of the prior art to arrive at applicant’s claimed invention, there will be an expectation of successful wound treatment with the effects that exosomes of Kim would offer.
In regards to the limitation regarding “wherein the subject requires increasing expression of at least one of EGF, IGF1, ELN, FN1, and COL1A1”, an evidentiary reference is applied to show that a skin was recognized to benefit from increases in FN1 and COL1A1 expression. Thus, these listed items are construed to be genes that would need increased expression in context of a skin wound in need of healing. Zhang provides for a method to heal skin wounds. Note the claim also does not say these have to be increased after the administering, but only that the subject requires increasing expression, which is just a characteristic of the subject.
Thus, the rejection over Zhang and Kim 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 MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613
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