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
Claims 1-8 and 10 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statements do not include Certificate Statement and Privacy Act Statement (MPEP 609), and/or do not have a signature of the applicant or representative that is required in accordance with CFR 1.33.
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 1-8 and 10 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 1 recites the limitation “treating the extracellular vesicles…to a subject in need thereof”, which renders the claims indefinite because it is unclear what the term “treating” encompasses in the context of the claims and how the vesicles are treated to a subject without an active step, e.g., administration of the vesicles to a subject. For the purposes of examination and advancing prosecution, the “treating” of step (c) in instant Claim 1 is being treated as “administering”. Appropriate correction is required.
Claim 5 recites the limitation “highly express,” which is a relative term and is indefinite because it is not clear which values are included or excluded by “highly express.” For example, does “highly” include any level of expression of the claimed molecules greater than that of the 3D dynamic culture and/or 2Dc culture? Or does it only include expression values above a certain amount? Or is some other interpretation intended? Clarification is necessary.
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under 35 U.S.C. § 112(b) for the reasons set forth above.
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.
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.
Claims 1, 2, 4, 8, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cho et al. (WO 2021/221471 A1, translation US 2023/0220348 A1 (effective filing date 28 April 2020) as evidenced by StemCellTM Technologies (AggreWellTM400 6-well plate, 2026, 2 pages).
The instant claims are as of record, drawn to a method for wound healing or wound recovery in a subject in need thereof, comprising administering to said subject extracellular vesicles derived from three-dimensional spheroid-type cell aggregates prepared by three-dimensional culture of stem cells in a 200-800 μm diameter by 100-1000 μm depth microwell and isolation of extracellular vesicles.
Cho et al., however, anticipate the claims by teaching 3D-culture of 300-500 mesenchymal stem cells per well in microwells with a 400 μm diameter and 280 μm depth (see e.g., StemCellTM technologies product sheet for AggreWellTM400 6-well plate, product #34421 and #34425; Cho et al., [0072] & Claims 1-5; as required for instant Claims 1(a), 2, 4, and 10(a)). The extracellular vesicles are then isolated from the culture medium comprising a three-dimensional cell aggregate, which may be a spheroid in shape (Cho et al., [0022], [0072] & Claims 1-5, 9, and 11; as required for instant Claims 1(a), 1(b), 9(a), and 9(b)). When applied to keratinocytes which were scratched, those treated with exosomes showed faster wound closure and a composition comprising the exosomes can be administered to a subject in need thereof in the form of a pharmaceutical composition (e.g., method for wound healing or wound recovery; Cho et al., [0038], [0042], [0078], Fig. 6a and 6b; as required for instant Claims 1(c), 8, and 10).
Please note, since the Office does not have the facilities for examining and comparing
Applicants’ composition with the composition of the prior art, the burden is on applicant to show
a novel or unobvious difference between the claimed methods and the methods of the prior art.
See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67,
205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to
manufacture products by the myriad of processes put before it and then obtain prior art products
and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685,
688 (CCPA 1972).
Claims 1, 2, 4-8 and 10 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Cho et al. (WO 2021/221471 A1, translation US 2023/0220348 A1 (effective filing date 28 April 2020) as evidenced by StemCellTM Technologies (AggreWellTM400 6-well plate, 2026, 2 pages).
MPEP § 2112 provides guidance as to the Examiner' s burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property.
The instant claims are as of record, drawn to a method for wound healing or wound recovery in a subject in need thereof, comprising administering to said subject extracellular vesicles derived from three-dimensional spheroid-type cell aggregates prepared by three-dimensional culture of stem cells in a 200-800 μm diameter by 100-1000 μm depth microwell and isolation of extracellular vesicles.
Cho et al. teach 3D-culture of 300-500 mesenchymal stem cells per well in microwells with a 400 μm diameter and 280 μm depth (see e.g., StemCellTM technologies product sheet for AggreWellTM400 6-well plate, product #34421 and #34425; Cho et al., [0072] & Claims 1-5; as required for instant Claims 1(a), 2, 4, and 10(a)). The extracellular vesicles are then isolated from the culture medium comprising a three-dimensional cell aggregate, which may be a spheroid in shape (Cho et al., [0022], [0072] & Claims 1-5, 9, and 11; as required for instant Claims 1(a), 1(b), 9(a), and 9(b)). When applied to keratinocytes which were scratched, those treated with exosomes showed faster wound closure and a composition comprising the exosomes can be administered to a subject in need thereof in the form of a pharmaceutical composition (e.g., method for wound healing or wound recovery; Cho et al., [0038], [0042], [0078], Fig. 6a and 6b; as required for instant Claims 1(c), 8, and 10).
Although Cho et al. in view of StemCellTM Technologies teach each of the active steps in the claimed method, they are silent regarding the intended use of the method recited in dependent Claims 5-7, i.e., increased expression of miR-27a, miR-146a, or miR-146b relative to extracellular vesicles derived from 2D-cultured mesenchymal stem cells; promotion of mobility of fibroblasts or keratinocytes at the wound area; and promotion of angiogenesis. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not the 3D-cultured mesenchymal stem cell-derived extracellular vesicles of the prior art and the instant claims are the same. The single-step method of administration to a subject are the same, and the preparation methods are the same, and thus the properties of increased expression of miR-27a, miR-146a, or miR-146b relative to extracellular vesicles derived from 2D-cultured mesenchymal stem cells; promotion of mobility of fibroblasts or keratinocytes at the wound area; and promotion of angiogenesis are inherent, especially in the absence of evidence to the contrary. See MPEP §§ 2112-2112.02.
The cited art taken as a whole demonstrates a reasonable probability that the 3D-cultured mesenchymal stem cell-derived extracellular vesicles of the prior art are either identical or sufficiently similar to the claimed method that whatever differences exist, they are not patentably significant.
The cited reference discloses a method for preparing 3D-cultured mesenchymal stem cell-derived extracellular vesicles which appears to be identical to the presently claimed method for preparing 3D-cultured mesenchymal stem cell-derived extracellular vesicles since it is formulated and/or obtained from the same component materials and is administrable to a subject. Consequently, the claimed process (and compositions provided therein) appears to be anticipated by the reference. In the alternative, even if the process (and compositions therein (with respect to an intended therapeutic effect against wound healing or recovery) is not identical to the referenced process, with regard to some unidentified characteristics, the differences between that which is claimed and that which is disclosed, is so slight that the referenced composition is likely to inherently possess the same characteristics of in the claimed process, particularly in view of the similar characteristics which they have been shown to share (e.g. the similar component materials/formulations and the same broad administration). Thus, the claimed process (and administered-composition effects intrinsic thereto) would have at least been obvious to those of ordinary skill in the art within the meaning of 35 USC § 103(a).
Accordingly, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the reference, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Claims 1-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (WO 2021/221471 A1, translation US 2023/0220348 A1 (effective filing date 28 April 2020) as evidenced by StemCellTM Technologies (AggreWellTM400 6-well plate, 2026, 2 pages) as applied to Claims 1, 2, 4-8 and 10 above, and further in view of Bang et al. (KR 20200047330 A, machine translation, 12 pages).
The instant claims and teachings of Cho et al. in view of StemCellTM Technologies are as of record.
Cho et al. in view of StemCellTM Technologies do not teach wherein the 3D culture in step (a) is a static culture.
Bang et al. teach 3D-culture of 400 mesenchymal stem cells per microwell in a microwell plate with a microwell diameter of 200 μm, as well as a 2D culture method and static 3D culture without stirring (Bang et al., 1-2., pg. 4-5; as required for instant Claim 3). The static 3D culture formed mesenchymal stem cell spheroids which propagated to the surrounding area when cultured in a petri dish, doubling the number of cells within five days (Bang et al., 1-2., pg. 5). Microvesicles (extracellular vesicles) were then isolated from mesenchymal stem cells cultured by static 2D culture, dynamic 2D culture, static 3D culture, and dynamic 3D culture (Bang et al., 3-2., pg. 6). It was determined that 3D-cultured mesenchymal stem cell-derived microvesicles contain high levels of therapeutic microRNAs and are able to stimulate angiogenesis (Bang et al., 5-3., pg. 9; as required for instant Claim 7).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to use the static culture of Bang et al. in the method of Cho et al. in view of StemCellTM Technologies because static 3D culture resulted in greater cell proliferation during culture and skilled artisan would therefore be motivated to use static culture to obtain a larger number of cells in the culture system. A skilled artisan would therefore have a reasonable expectation of success at using the static culture method because it was already shown by Bang et al. to be a viable method which produces a larger number of microvesicles (see e.g., original version of Cho et al., Fig. 4b on pg. 20).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ composition with the composition of the prior art (including compositions within the processes thereof), the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-11 of copending Application No. 18/289,530 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because while the intended uses are different between instant Claims 1 and 10 and ‘530 Claims 1 and 11 (e.g., method for wound healing or wound recovery versus promoting angiogenesis), respectively, the methods of preparing the composition and single-step method of treating to a subject are identical. Additionally, instant Claim 7 recites promotion of angiogenesis and ‘530 Claim 7 recites prevention or treatment of burns and ulcers (e.g., wounds). It would therefore be obvious to a skilled artisan, without evidence to the contrary, that the identical methods of use and preparation methods of the instant claims and ‘530 claims would have the same effects, including those of instant Claim 6 and ’530 Claim 6.
Instant Claims 2 and 3 are identical to ‘530 Claims 2 and 3.
Instant Claims 4, 5, 7, and 8 have overlapping ranges or limitations with ‘530 Claims 4, 5, 7 & 8, and 9, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1, 2, 4-8, 10, and 11 of copending Application No. 18/289,532 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because, while the intended uses are different between the combination of instant Claims 1. 3 (e.g., incorporating static culture), and 10 and ‘532 Claims 1 and 11 (e.g., method for wound healing or wound recovery versus promoting neurogenesis), the methods of preparing the composition and single-step method of treating/administration to a subject are the same. It would therefore be obvious to a skilled artisan, without evidence to the contrary, that the same methods of use and preparation methods of the instant claims and ‘532 claims would have the same effects, including those of instant Claims 6 and 7 and ’532 Claims 6-8. Additionally, instant Claim 2 is identical to ‘532 Claim; and instant Claims 4, 5, and 8 have overlapping ranges or limitations with ‘530 Claims 4, 5, and 10, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowed.
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/J.L.C./Examiner, Art Unit 1655
/AARON J KOSAR/Primary Examiner, Art Unit 1655
Prosecution Insights